Photoprotective compositions containing malassezia-derived compounds and / or chemical analogs thereof - Patent Application 20070122999

Abstract

To provide a method for treating a disease.SOLUTION: The present invention relates to compounds, compositions, and methods for modulating skin pigmentation and treating or preventing UV-induced skin damage, erythema, aging of the skin, sunburn, and hyperpigmentation in a subject. The compounds, compositions, and methods of the present invention generally involve Malassezia-derived compounds, including malassezin and indirubin, and / or chemical analogs thereof. Other applications of the compounds and compositions disclosed herein include, but are not limited to, improving hyperpigmentation caused by a hyperpigmentation disorder, inducing melanocyte apoptosis, and modulating arylhydrocarbon receptor (AhR) activity, melanogenesis, melanin production, melanosome biogenesis, melanosome transfer, melanocyte activity, and melanin concentration.SELECTED DRAWING: Figure 1A

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Application No. 62 / 656,769, filed April 12, 2018, U.S. Provisional Application No. 62 / 668,007, filed May 7, 2018, U.S. Provisional Application No. 62 / 685,800, filed June 15, 2018, U.S. Provisional Application No. 62 / 686,912, filed June 19, 2018, U.S. Provisional Application No. 62 / 722,412, filed August 24, 2018, and U.S. Provisional Application No. 62 / 742,657, filed October 8, 2018, the entire contents of which are incorporated herein by reference.

[0002] The present invention relates to compounds produced by or derived from Malassezia yeast, and their chemical analogs.The compounds of the present invention and compositions containing the compounds have, among other beneficial properties, photoprotective properties.Methods of using the compounds and compositions of the present invention are also contemplated. [Background technology]

[0003] Individuals worldwide use skin lightening agents to achieve several cosmetic goals, including producing anti-aging effects, repairing sun damage, and meeting certain cultural standards of beauty. Many commercially available skin lightening products, while offering varying degrees of effectiveness, contain harmful ingredients, some of which have been linked to cancer. Thus, there is a need for new skin lightening agents and formulations that exhibit a higher level of safety and / or efficacy than currently available agents.

[0004] Malassezia is a genus of lipophilic yeasts commonly found in the normal flora of human skin. Malassezia is involved in several skin disorders, including tinea versicolor (pityriasis versicolor), seborrheic dermatitis, and atopic dermatitis. This is the cause.

[0005] The natural habitat of M. furfur is the upper epidermis. However, exposure to ultraviolet light is destructive to the organism in its natural habitat. Therefore, UV filters may be necessary for the organism's survival. Two such UV-filtering indoles produced by the organism have been identified: pityriacitrine and pityrialactone. Pityriacitrine, first described in Mayser et al., 2002, is synthesized by M. furfur. Pityriacitrine is a stable, yellow, lipophilic compound that exhibits broad absorption across the UVA, UVB, and UVC spectrum. A similar compound from the genus Paracoccus has been isolated and patented as a UV protection agent (Zhang et al., 2018).

[0006] Gambichler et al. (2007) investigated the UV protective effects of pityriacitrin in humans using in vitro and in vivo test methods. Spectrophotometric measurements of pityriacitrin cream and vehicle were performed in the wavelength range of 290-400 nm. UV transmittance and sun protection factor ("SPF") for various cream formulations were evaluated. The authors used colorimetric analysis to evaluate erythema and pigmentation after irradiating protected and unprotected skin with the cream in healthy subjects. With increasing pityriacitrin concentration, UVB and UVA transmittance decreased. Increasing pityriacitrin concentrations to 1.25, 2.5, and 5% was associated with slight improvements in SPF of 1.4, 1.5, and 1.7, respectively. In vivo testing confirmed the effectiveness of pityriacitrin determined in vitro. The SPF efficacy of a 5% cream of pityriacitrin was confirmed. Overall, the UV protective effect of pityriacitrin was very weak, suggesting that pityriacitrin is probably only a recessive cofactor in the development of hypopigmentation in tinea versicolor lesions after sun exposure.

[0007] Further investigation of the UV-filtering effect of pityriacitrin was carried out on the human skin microflora (Machowinski et al., 2006). The authors concluded that pityriacitrin It was determined that pityrialactone has a UV-protective effect against non-virulent Candida albicans and staphylococci in the range of 100 μg / mL. The UV-protective properties of pityrialactone were also confirmed in a yeast model (Mayser et al., 2003). Pityrialactone appears to be responsible for the yellow fluorescence of pityriasis versicolor in the Wood's lamp test.

[0008] Tinea versicolor is a non-contagious skin disease caused by Malassezia overgrowth, which locally alters pigmentation levels. Malassezia yeast has two metabolic pathways for synthesizing melanin and indole pigments derived from tryptophan. Malassezin and indirubin are tryptophan metabolites of Malassezia that may contribute to the depigmentation characteristic of Malassezia overgrowth. Summary of the Invention [Problem to be solved by the invention]

[0009] The invention disclosed herein utilizes compounds produced by or derived from Malassezia yeast, including malassedins, indirubins, and their chemical analogs, as the basis for safe and effective skin lightening and skin pigmentation compositions.Also disclosed herein are photoprotective compositions comprising malassedins, indirubins, and their chemical analogs. [Means for solving the problem]

[0010] One embodiment of the present invention is a skin lightening compound that is a chemical analog of a compound produced by Malassezia yeast, or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0011] Another embodiment of the present invention is a compound that induces melanocyte apoptosis, which is a chemical analog of a compound produced by Malassezia yeast, or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0012] A further embodiment of the present invention is a compound that modulates melanocyte activity, which is a chemical analog of a compound produced by Malassezia yeast, or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0013] An additional embodiment of the present invention is a compound that agonizes the aromatic hydrocarbon receptor (AhR), which is a chemical analog of a compound produced by Malassezia yeast, or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0014] Another embodiment of the present invention is a compound that improves hyperpigmentation caused by hyperpigmentation disorders, the compound being a chemical analog of a compound produced by Malassezia yeast, or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0015] A further embodiment of the present invention is a compound that modulates melanin production. The compound may be a chemical analog of a compound produced by Malassezia yeast, or A crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt of

[0016] An additional embodiment of the present invention is a compound that modulates melanosome biogenesis, which is a chemical analog of a compound produced by Malassezia yeast, or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0017] Another embodiment of the present invention is a compound that modulates melanosome transport, the compound being a chemical analog of a compound produced by Malassezia yeast, or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0018] A further embodiment of the present invention is a composition comprising Malassezia yeast and a cosmetically or pharmaceutically acceptable vehicle, diluent, or carrier. An additional embodiment of the present invention is a composition comprising a compound isolated or isolatable from Malassezia yeast and a cosmetically or pharmaceutically acceptable vehicle, diluent, or carrier.

[0019] Another embodiment of the present invention is a composition comprising any of the compounds, including analogs, disclosed herein and a cosmetically or pharmaceutically acceptable vehicle, diluent, or carrier.

[0020] A further embodiment of the invention is a method of lightening skin in a subject, comprising the step of contacting the subject with any of the compounds or compositions disclosed herein.

[0021] An additional embodiment of the invention is a method of inducing melanocyte apoptosis in a subject, comprising contacting the subject with any of the compounds or compositions disclosed herein.

[0022] Another embodiment of the invention is a method of modulating melanocyte activity in a subject, comprising the step of contacting the subject with any of the compounds or compositions disclosed herein.

[0023] A further embodiment of the invention is a method of agonizing the aryl hydrocarbon receptor (AhR) in a subject, comprising contacting the subject with any of the compounds or compositions disclosed herein.

[0024] An additional embodiment of the invention is a method of improving hyperpigmentation caused by a hyperpigmentation disorder in a subject in need thereof, comprising the step of contacting the subject with any of the compounds or compositions disclosed herein.

[0025] Another embodiment of the invention is a method of modulating melanin production in a subject, comprising the step of contacting the subject with any of the compounds or compositions disclosed herein.

[0026] A further embodiment of the invention is a method of modulating melanosome biogenesis in a subject, comprising contacting the subject with any of the compounds or compositions disclosed herein.

[0027] An additional embodiment of the present invention is a method of modulating melanosome transport in a subject. The method includes the step of contacting a subject with any of the compounds or compositions disclosed herein.

[0028] Another embodiment of the present invention is a compound having the structure of formula (II): [ka] (In the formula, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10 and R11 are independently selected from the group consisting of hydrogen and methyl, and at least one of R1, R2, R3, R4, R5, R6, R7, R8, R9, R10 and R11 is methyl), or a crystalline form, hydrate, or a cosmetically or pharmaceutically acceptable salt thereof.

[0029] A further embodiment of the present invention is a compound having the structure of formula (III): [ka] wherein R1, R2, R3, R4, R5, R6, R7, R8, R9 and R10 are independently selected from the group consisting of hydrogen and methyl, and at least one of R1, R2, R3, R4, R5, R6, R7, R8, R9 and R10 is methyl, or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0030] An additional embodiment of the present invention is a skin lightening compound having the structure of formula (II): [ka] wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10 and R11 are independently selected from the group consisting of hydrogen and methyl, or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0031] Another embodiment of the present invention is a skin lightening compound having the structure of formula (III): [ka] wherein R1, R2, R3, R4, R5, R6, R7, R8, R9 and R10 are independently selected from the group consisting of hydrogen and methyl, or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0032] A further embodiment of the present invention is a compound that induces melanocyte apoptosis. The compound has the structure of formula (II): [ka] wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10 and R11 are independently selected from the group consisting of hydrogen and methyl, or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0033] An additional embodiment of the present invention is a compound that induces melanocyte apoptosis. The compound has the structure of formula (III): [ka] wherein R1, R2, R3, R4, R5, R6, R7, R8, R9 and R10 are independently selected from the group consisting of hydrogen and methyl, or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0034] Another embodiment of the present invention is a compound that agonizes the aromatic hydrocarbon receptor (AhR). The compound has the structure of formula (II): [ka] wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10 and R11 are independently selected from the group consisting of hydrogen and methyl, or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0035] A further embodiment of the present invention is a compound that agonizes the aromatic hydrocarbon receptor (AhR). The compound has the structure of formula (III): [ka] wherein R1, R2, R3, R4, R5, R6, R7, R8, R9 and R10 are independently selected from the group consisting of hydrogen and methyl, or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0036] An additional embodiment of the present invention is a composition comprising a compound having the structure of Formula (II): [ka] wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10 and R11 are independently selected from the group consisting of hydrogen and methyl, or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof, and a cosmetically or pharmaceutically acceptable vehicle, diluent or carrier.

[0037] Another embodiment of the present invention is a composition comprising a compound having the structure of formula (III): [ka] wherein R1, R2, R3, R4, R5, R6, R7, R8, R9 and R10 are independently selected from the group consisting of hydrogen and methyl, or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof, and a cosmetically or pharmaceutically acceptable vehicle, diluent or carrier.

[0038] A further embodiment of the present invention is a method of lightening the skin in a subject. The method comprises administering to the subject a compound having the structure of Formula (II): [ka] wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10 and R11 are independently selected from the group consisting of hydrogen and methyl, or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0039] An additional embodiment of the present invention is a method of lightening the skin in a subject. The method comprises administering to the subject a compound having the structure of Formula (III): [ka] wherein R1, R2, R3, R4, R5, R6, R7, R8, R9 and R10 are independently selected from the group consisting of hydrogen and methyl, or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0040] Another embodiment of the present invention is a method of inducing melanocyte apoptosis in a subject, the method comprising administering to the subject a compound having the structure of Formula (II): [ka] wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10 and R11 are independently selected from the group consisting of hydrogen and methyl, or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0041] A further embodiment of the present invention is a method of inducing melanocyte apoptosis in a subject, the method comprising administering to the subject a compound having the structure of formula (III): [ka] wherein R1, R2, R3, R4, R5, R6, R7, R8, R9 and R10 are independently selected from the group consisting of hydrogen and methyl, or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0042] Another embodiment of the present invention is a method of agonizing the aryl hydrocarbon receptor (AhR) in a subject. The method comprises administering to the subject a compound having the structure of Formula (II): [ka] wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10 and R11 are independently selected from the group consisting of hydrogen and methyl, or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0043] A further embodiment of the present invention is a method of agonizing the aromatic hydrocarbon receptor (AhR) in a subject, the method comprising administering to the subject a compound having the structure of Formula (III): [ka] wherein R1, R2, R3, R4, R5, R6, R7, R8, R9 and R10 are independently selected from the group consisting of hydrogen and methyl, or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0044] One embodiment of the present invention is a compound having the structure of the following formula: [ka] (Wherein, X is NR 14 and O, and Y is a covalent bond, CR5R6, O, or NR 15 and R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 is hydrogen, halogen, CN, hydroxyl, R 16 OR 16 and R is independently selected from the group consisting of 13 , R 14 and R 15 are independently hydrogen or R 16 and R5 and R6 are hydrogen, hydroxyl, OR 16 , R 16 and C 3~6 cycloalkyl, or R5 and R6 together represent an oxo (=O) group or C 3~6 Forming a cycloalkyl, R 12 is hydrogen, -COR a and R 16 and R 16 are each independently formyl, C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 alkynyl, and R a is hydrogen, hydroxyl and OR 16 and R a is hydrogen, Y is CR5R6, and R 13 and R14 are both hydrogen, R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 and R 11 At least one of the 16 or R5 is hydroxyl, OR 16 , R 16 and C 3~6 cycloalkyl, or R5 and R6 together represent an oxo (=O) group or C 3~6 cycloalkyl-forming), or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0045] Another embodiment of the present invention is a compound having the structure of the following formula: [ka] (Wherein R1, R4, R5, R6, R9 and R 10 is hydrogen, hydroxyl, halogen ,CN,R. 13 , OR 13 ,OCOR 13 and -CHO, and R2 and R3 are independently selected from the group consisting of hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, or R2 and R3 together form a 5- or 6-membered heterocyclyl, and R7 and R8 are independently selected from the group consisting of hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, or R7 and R8 together form a 5- or 6-membered heterocyclyl, and R 11 and R 12 are independently hydrogen or R 13 and R 13 are each independently, C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9alkynyl, and R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 wherein at least one of is not hydrogen), or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0046] An additional embodiment of the present invention is a skin lightening compound having the structure of the following formula: [ka] (Wherein, X is NR 14 and O, and Y is a covalent bond, CR5R6, O, or NR 15 and R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 is hydrogen, halogen, CN, hydroxyl, R 16 OR 16 and R is independently selected from the group consisting of 13 , R 14 and R 15 are independently hydrogen or R 16 and R5 and R6 are hydrogen, hydroxyl, OR 16 , R 16 and C 3~6 cycloalkyl, or R5 and R6 together represent an oxo (=O) group or C 3~6 Forming a cycloalkyl, R 12 is hydrogen, -COR a and R 16 and R 16 are each independently formyl, C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 alkynyl, and R a is hydrogen, hydroxyl and OR 16 or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0047] A further embodiment of the present invention is a skin lightening compound having the structure of the following formula: [ka] (Wherein R1, R4, R5, R6, R9 and R 10 is hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, and R2 and R3 are independently selected from the group consisting of hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, or R2 and R3 together form a 5- or 6-membered heterocyclyl, and R7 and R8 are independently selected from the group consisting of hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and the group consisting of -CHO or R7 and R8 together form a 5- or 6-membered heterocyclyl; R 11 and R 12 are independently hydrogen or R 13 and R 13 are each independently, C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 alkynyl), or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0048] Another embodiment of the present invention is a compound that lightens the skin. [ka] is selected from the group consisting of:

[0049] An additional embodiment of the present invention is a compound that induces melanocyte apoptosis. The compound has the structure of the following formula: [ka] (Wherein, X is NR 14 and O, and Y is a covalent bond, CR5R6, O, or NR 15 and R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 is hydrogen, halogen, CN, hydroxyl, R 16 OR 16 and R is independently selected from the group consisting of 13 , R 14 and R 15 are independently hydrogen or R 16 and R5 and R6 are hydrogen, hydroxyl, OR 16 , R 16 and C 3~6 cycloalkyl, or R5 and R6 together represent an oxo (=O) group or C 3~6 Forming a cycloalkyl, R 12 is hydrogen, -COR a and R 16 and R 16 are each independently formyl, C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 alkynyl, and R a is hydrogen, hydroxyl and OR 16 or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0050] A further embodiment of the present invention is a compound that induces melanocyte apoptosis. The compound has the structure of the following formula: [ka] (Wherein R1, R4, R5, R6, R9 and R 10 is hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13and -CHO, and R2 and R3 are independently selected from the group consisting of hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, or R2 and R3 together form a 5- or 6-membered heterocyclyl, and R7 and R8 are independently selected from the group consisting of hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, or R7 and R8 together form a 5- or 6-membered heterocyclyl, and R 11 and R 12 are independently hydrogen or R 13 and R 13 are each independently, C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 alkynyl), or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0051] Another embodiment of the present invention is a compound that induces melanocyte apoptosis. [ka] is selected from the group consisting of:

[0052] An additional embodiment of the present invention is a compound that modulates aryl hydrocarbon receptor (AhR) activity. The compound has the structure of the following formula: [ka] (Wherein, X is NR 14 and O, and Y is a covalent bond, CR5R6, O, or NR 15 and R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 is hydrogen, halogen, CN, hydroxyl, R 16 OR16 and R is independently selected from the group consisting of 13 , R 14 and R 15 are independently hydrogen or R 16 and R5 and R6 are hydrogen, hydroxyl, OR 16 , R 16 and C 3~6 cycloalkyl, or R5 and R6 together represent an oxo (=O) group or C 3~6 Forming a cycloalkyl, R 12 is hydrogen, -COR a and R 16 and R 16 are each independently formyl, C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 alkynyl, and R a is hydrogen, hydroxyl and OR 16 or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0053] A further embodiment of the present invention is a compound that modulates aryl hydrocarbon receptor (AhR) activity. The compound has the structure of the following formula: [ka] (Wherein R1, R4, R5, R6, R9 and R 10 is hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, and R2 and R3 are independently selected from the group consisting of hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, or R2 and R3 together form a 5- or 6-membered heterocyclyl, and R7 and R8 are independently selected from the group consisting of hydrogen, hydroxyl, halogen, CN, R 13 , OR 13,OCOR 13 and -CHO, or R7 and R8 together form a 5- or 6-membered heterocyclyl, and R 11 and R 12 are independently hydrogen or R 13 and R 13 are each independently, C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 alkynyl), or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0054] Another embodiment of the present invention is a compound that modulates aryl hydrocarbon receptor (AhR) activity. [ka] is selected from the group consisting of:

[0055] An additional embodiment of the present invention is a compound that modulates melanogenesis. The compound has the structure of the following formula: [ka] (Wherein, X is NR 14 and O, and Y is a covalent bond, CR5R6, O, or NR 15 and R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 is hydrogen, halogen, CN, hydroxyl, R 16 OR 16 and R is independently selected from the group consisting of 13 , R 14 and R 15 are independently hydrogen or R 16 and R5 and R6 are hydrogen, hydroxyl, OR 16 , R 16 and C 3~6 cycloalkyl, or R5 and R6 together represent an oxo (=O) group or C3~6 Forming a cycloalkyl, R 12 is hydrogen, -COR a and R 16 and R 16 are each independently formyl, C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 alkynyl, and R a is hydrogen, hydroxyl and OR 16 or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0056] A further embodiment of the present invention is a compound that modulates melanogenesis. The compound has the structure of the following formula: [ka] (Wherein R1, R4, R5, R6, R9 and R 10 is hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, and R2 and R3 are independently selected from the group consisting of hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, or R2 and R3 together form a 5- or 6-membered heterocyclyl, and R7 and R8 are independently selected from the group consisting of hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, or R7 and R8 together form a 5- or 6-membered heterocyclyl, and R 11 and R 12 are independently hydrogen or R 13 and R 13 are each independently, C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9alkynyl), or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0057] Another embodiment of the present invention is a compound that modulates melanogenesis. The compound comprises: [ka] is selected from the group consisting of:

[0058] An additional embodiment of the present invention is a compound that modulates melanin concentration. The compound has the structure of the following formula: [ka] (Wherein, X is NR 14 and O, and Y is a covalent bond, CR5R6, O, or NR 15 and R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 is hydrogen, halogen, CN, hydroxyl, R 16 OR 16 and R is independently selected from the group consisting of 13 , R 14 and R 15 are independently hydrogen or R 16 and R5 and R6 are hydrogen, hydroxyl, OR 16 , R 16 and C 3~6 cycloalkyl, or R5 and R6 together represent an oxo (=O) group or C 3~6 Forming a cycloalkyl, R 12 is hydrogen, -COR a and R 16 and R 16 are each independently formyl, C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 alkynyl, and R a is hydrogen, hydroxyl and OR 16or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0059] A further embodiment of the present invention is a compound that modulates melanin concentration. The compound has the structure of the following formula: [ka] (Wherein R1, R4, R5, R6, R9 and R 10 is hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, and R2 and R3 are independently selected from the group consisting of hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, or R2 and R3 together form a 5- or 6-membered heterocyclyl, and R7 and R8 are independently selected from the group consisting of hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, or R7 and R8 together form a 5- or 6-membered heterocyclyl, and R 11 and R 12 are independently hydrogen or R 13 and R 13 are each independently, C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 alkynyl), or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0060] Another embodiment of the present invention is a compound that modulates melanin concentration. The compound comprises: [ka] is selected from the group consisting of:

[0061] An additional embodiment of the present invention is a composition comprising a compound having the structure of the following formula: [ka] (Wherein, X is NR 14 and O, and Y is a covalent bond, CR5R6, O, or NR 15 and R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 is hydrogen, halogen, CN, hydroxyl, R 16 OR 16 and R is independently selected from the group consisting of 13 , R 14 and R 15 are independently hydrogen or R 16 and R5 and R6 are hydrogen, hydroxyl, OR 16 , R 16 and C 3~6 cycloalkyl, or R5 and R6 together represent an oxo (=O) group or C 3~6 Forming a cycloalkyl, R 12 is hydrogen, -COR a and R 16 and R 16 are each independently formyl, C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 alkynyl, and R a is hydrogen, hydroxyl and OR 16 or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0062] A further embodiment of the present invention is a composition comprising a compound having the structure of the following formula: [ka] (Wherein R1, R4, R5, R6, R9 and R 10 is hydrogen, hydroxyl, halogen, CN, R13 , OR 13 ,OCOR 13 and -CHO, and R2 and R3 are independently selected from the group consisting of hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, or R2 and R3 together form a 5- or 6-membered heterocyclyl, and R7 and R8 are independently selected from the group consisting of hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, or R7 and R8 together form a 5- or 6-membered heterocyclyl, and R 11 and R 12 are independently hydrogen or R 13 and R 13 are each independently, C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 alkynyl) or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0063] Another embodiment of the present invention is a composition comprising: [ka] The compound includes a compound selected from the group consisting of:

[0064] An additional embodiment of the present invention is a method of lightening the skin in a subject. The method comprises administering to the subject a compound having a structure of the following formula: [ka] (Wherein, X is NR 14 and O, and Y is a covalent bond, CR5R6, O, or NR 15 and R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 is hydrogen, halogen, CN, hydroxyl, R16 OR 16 and R is independently selected from the group consisting of 13 , R 14 and R 15 are independently hydrogen or R 16 and R5 and R6 are hydrogen, hydroxyl, OR 16 , R 16 and C 3~6 cycloalkyl, or R5 and R6 together represent an oxo (=O) group or C 3~6 Forming a cycloalkyl, R 12 is hydrogen, -COR a and R 16 and R 16 are each independently formyl, C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 alkynyl, and R a is hydrogen, hydroxyl and OR 16 or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0065] A further embodiment of the present invention is a method of lightening the skin in a subject, the method comprising administering to the subject a compound having a structure of the following formula: [ka] (Wherein R1, R4, R5, R6, R9 and R 10 is hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, and R2 and R3 are independently selected from the group consisting of hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, or R2 and R3 together form a 5- or 6-membered heterocyclyl, and R7 and R8 are independently selected from the group consisting of hydrogen, hydroxyl, halogen, CN, R 13, OR 13 ,OCOR 13 and -CHO, or R7 and R8 together form a 5- or 6-membered heterocyclyl, and R 11 and R 12 are independently hydrogen or R 13 and R 13 are each independently, C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 The method includes contacting a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof with a compound represented by the formula (I) above, which is a methyl group, a methyl group, or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0066] Another embodiment of the present invention is a method of lightening the skin in a subject. The method comprises administering to the subject a compound selected from the group consisting of: [ka] The method includes contacting the

[0067] An additional embodiment of the present invention is a method of inducing melanocyte apoptosis in a subject, the method comprising administering to the subject a compound having a structure of the following formula: [ka] (Wherein, X is NR 14 and O, and Y is a covalent bond, CR5R6, O, or NR 15 and R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 is hydrogen, halogen, CN, hydroxyl, R 16 OR 16 and R is independently selected from the group consisting of 13 , R 14 and R 15 are independently hydrogen or R 16 and R5 and R6 are hydrogen, hydroxyl, OR 16 , R 16 and C 3~6cycloalkyl, or R5 and R6 together represent an oxo (=O) group or C 3~6 Forming a cycloalkyl, R 12 is hydrogen, -COR a and R 16 and R 16 are each independently formyl, C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 alkynyl, and R a is hydrogen, hydroxyl and OR 16 or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0068] A further embodiment of the present invention is a method of inducing melanocyte apoptosis in a subject, the method comprising administering to the subject a compound having the structure of the following formula: [ka] (Wherein R1, R4, R5, R6, R9 and R 10 is hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, and R2 and R3 are independently selected from the group consisting of hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, or R2 and R3 together form a 5- or 6-membered heterocyclyl, and R7 and R8 are independently selected from the group consisting of hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, or R7 and R8 together form a 5- or 6-membered heterocyclyl, and R 11 and R 12 are independently hydrogen or R 13 and R 13are each independently, C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 The method includes contacting a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof with a compound represented by the formula (I) above, which is a methyl group, a methyl group, or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0069] Another embodiment of the present invention is a method of inducing melanocyte apoptosis in a subject, the method comprising administering to the subject a compound selected from the group consisting of: [ka] The method includes contacting the

[0070] An additional embodiment of the invention is a method of modulating aryl hydrocarbon receptor (AhR) activity in a subject, the method comprising administering to the subject a compound having the structure of the following formula: [ka] (Wherein, X is NR 14 and O, and Y is a covalent bond, CR5R6, O, or NR 15 and R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 is hydrogen, halogen, CN, hydroxyl, R 16 OR 16 and R is independently selected from the group consisting of 13 , R 14 and R 15 are independently hydrogen or R 16 and R5 and R6 are hydrogen, hydroxyl, OR 16 , R 16 and C 3~6 cycloalkyl, or R5 and R6 together represent an oxo (=O) group or C 3~6 Forming a cycloalkyl, R 12 is hydrogen, -COR a and R 16 and R 16are each independently formyl, C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 alkynyl, and R a is hydrogen, hydroxyl and OR 16 or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0071] A further embodiment of the present invention is a method of modulating aryl hydrocarbon receptor (AhR) activity in a subject, the method comprising administering to the subject a compound having the structure of the following formula: [ka] (Wherein R1, R4, R5, R6, R9 and R 10 is hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, and R2 and R3 are independently selected from the group consisting of hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, or R2 and R3 together form a 5- or 6-membered heterocyclyl, and R7 and R8 are independently selected from the group consisting of hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, or R7 and R8 together form a 5- or 6-membered heterocyclyl, and R 11 and R 12 are independently hydrogen or R 13 and R 13 are each independently, C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 The method includes contacting a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof with a compound represented by the formula (I) above, which is a methyl group, a methyl group, or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0072] Another embodiment of the present invention is a method of modulating aryl hydrocarbon receptor (AhR) activity in a subject, the method comprising administering to the subject a compound selected from the group consisting of: [ka] The method includes contacting the

[0073] An additional embodiment of the present invention is a method of modulating melanogenesis in a subject, the method comprising administering to the subject a compound having a structure of the following formula: [ka] (Wherein, X is NR 14 and O, and Y is a covalent bond, CR5R6, O, or NR 15 and R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 is hydrogen, halogen, CN, hydroxyl, R 16 OR 16 and R is independently selected from the group consisting of 13 , R 14 and R 15 are independently hydrogen or R 16 and R5 and R6 are hydrogen, hydroxyl, OR 16 , R 16 and C 3~6 cycloalkyl, or R5 and R6 together represent an oxo (=O) group or C 3~6 Forming a cycloalkyl, R 12 is hydrogen, -COR a and R 16 and R 16 are each independently formyl, C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 alkynyl, and R a is hydrogen, hydroxyl and OR 16or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0074] A further embodiment of the present invention is a method of modulating melanogenesis in a subject, the method comprising administering to the subject a compound having a structure of the following formula: [ka] (Wherein R1, R4, R5, R6, R9 and R 10 is hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, and R2 and R3 are independently selected from the group consisting of hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, or R2 and R3 together form a 5- or 6-membered heterocyclyl, and R7 and R8 are independently selected from the group consisting of hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, or R7 and R8 together form a 5- or 6-membered heterocyclyl, and R 11 and R 12 are independently hydrogen or R 13 and R 13 are each independently, C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 The method includes contacting a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof with a compound represented by the formula (I) above, which is a methyl group, a methyl group, or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0075] Another embodiment of the present invention is a method of modulating melanogenesis in a subject, the method comprising administering to the subject a compound selected from the group consisting of: [ka] The method includes contacting the

[0076] An additional embodiment of the present invention is a method of modulating melanin levels in a subject. The method comprises administering to the subject a compound having a structure of the following formula: [ka] (Wherein, X is NR 14 and O, and Y is a covalent bond, CR5R6, O, or NR 15 and R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 is hydrogen, halogen, CN, hydroxyl, R 16 OR 16 and R is independently selected from the group consisting of 13 , R 14 and R 15 are independently hydrogen or R 16 and R5 and R6 are hydrogen, hydroxyl, OR 16 , R 16 and C 3~6 cycloalkyl, or R5 and R6 together represent an oxo (=O) group or C 3~6 Forming a cycloalkyl, R 12 is hydrogen, -COR a and R 16 and R 16 are each independently formyl, C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 alkynyl, and R a is hydrogen, hydroxyl and OR 16 or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0077] A further embodiment of the present invention is a method of modulating melanin concentration in a subject, the method comprising administering to the subject a compound having a structure of the following formula: [ka] (Wherein R1, R4, R5, R6, R9 and R 10 is hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, and R2 and R3 are independently selected from the group consisting of hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, or R2 and R3 together form a 5- or 6-membered heterocyclyl, and R7 and R8 are independently selected from the group consisting of hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, or R7 and R8 together form a 5- or 6-membered heterocyclyl, and R 11 and R 12 are independently hydrogen or R 13 and R 13 are each independently, C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 The method includes contacting a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof with a compound represented by the formula (I) above, which is a methyl group, a methyl group, or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0078] Another embodiment of the present invention is a method of modulating melanin levels in a subject, the method comprising administering to the subject a compound selected from the group consisting of: [ka] The method includes contacting the

[0079] One embodiment of the present invention is a skin lightening compound having the structure of the following formula: [ka] or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0080] Another embodiment of the present invention is a compound that induces melanocyte apoptosis. The compound has the structure of the following formula: [ka] or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0081] An additional embodiment of the present invention is a compound that modulates aryl hydrocarbon receptor (AhR) activity. The compound has the structure of the following formula: [ka] or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0082] A further embodiment of the present invention is a compound that modulates melanogenesis. The compound has the structure of the following formula: [ka] or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0083] Another embodiment of the present invention is a compound that modulates melanin concentration. The compound has the structure of the following formula: [ka] or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0084] An additional embodiment of the present invention is a composition comprising a compound having the structure of the following formula: [ka] or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0085] A further embodiment of the present invention is a method of lightening the skin in a subject, comprising the step of contacting the subject with a compound, wherein the compound has a structure of the following formula: [ka] or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0086] Another embodiment of the present invention is a method of inducing melanocyte apoptosis in a subject, comprising the step of contacting the subject with a compound, wherein the compound has the structure of the following formula: [ka] or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0087] An additional embodiment of the invention is a method of modulating aryl hydrocarbon receptor (AhR) activity in a subject, the method comprising contacting the subject with a compound, wherein the compound has a structure of the following formula: [ka] or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0088] A further embodiment of the invention is a method of modulating melanogenesis in a subject, comprising the step of contacting the subject with a compound, wherein the compound has a structure of the following formula: [ka] or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0089] Another embodiment of the present invention is a method of modulating melanin concentration in a subject, the method comprising the step of contacting the subject with a compound, wherein the compound has a structure of the following formula: [ka] or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0090] An additional embodiment of the present invention is a composition comprising one or more of the compounds listed in Table 5 or Figure 130, or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0091] A further embodiment of the present invention is a method of whitening skin in a subject, comprising contacting the subject with one or more of the compounds listed in Table 5 or Figure 130, or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0092] Another embodiment of the invention is a method of inducing melanocyte apoptosis in a subject, comprising contacting the subject with one or more of the compounds listed in Table 5 or Figure 130, or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0093] An additional embodiment of the present invention is a method of modulating aryl hydrocarbon receptor (AhR) activity in a subject, comprising contacting the subject with one or more of the compounds listed in Table 5 or Figure 130, or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0094] A further embodiment of the invention is a method of modulating melanogenesis in a subject, comprising contacting the subject with one or more of the compounds listed in Table 5 or Figure 130, or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0095] Another embodiment of the invention is a method of modulating melanin concentration in a subject, comprising the step of contacting the subject with one or more of the compounds listed in Table 5 or Figure 130, or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0096] An additional embodiment of the present invention is a composition comprising one or more of the compounds listed in Table 5 or Figure 130, or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0097] A further embodiment of the present invention is a skin lightening composition comprising one or more of the compounds listed in Table 5 or Figure 130, or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0098] Another embodiment of the present invention is a composition for inducing melanocyte apoptosis, comprising one or more of the compounds listed in Table 5 or Figure 130, or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0099] An additional embodiment of the present invention is a composition for modulating aromatic hydrocarbon receptor (AhR) activity, comprising one or more of the compounds listed in Table 5 or Figure 130, or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0100] A further embodiment of the present invention is a composition for modulating melanogenesis, comprising one or more of the compounds listed in Table 5 or Figure 130, or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0101] Another embodiment of the present invention is a composition for modulating melanin concentration, comprising one or more of the compounds listed in Table 5 or Figure 130, or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0102] An additional embodiment of the present invention is a method of lightening skin in a subject, comprising the step of contacting the subject with a composition comprising one or more of the compounds listed in Table 5 or Figure 130, or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0103] A further embodiment of the invention is a method of inducing melanocyte apoptosis in a subject, comprising contacting the subject with a composition comprising one or more of the compounds listed in Table 5 or Figure 130, or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0104] Another embodiment of the present invention is a method of modulating aromatic hydrocarbon receptor (AhR) activity in a subject, comprising contacting the subject with a composition comprising one or more of the compounds listed in Table 5 or Figure 130, or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0105] An additional embodiment of the invention is a method of modulating melanogenesis in a subject, comprising contacting the subject with a composition comprising one or more of the compounds listed in Table 5 or Figure 130, or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof. A further embodiment of the invention is a method of modulating melanin concentration in a subject, comprising contacting the subject with a composition comprising one or more of the compounds listed in Table 5 or Figure 130, or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0106] Another embodiment of the present invention is a composition comprising Malassezia yeast and a cosmetically or pharmaceutically acceptable vehicle, diluent, or carrier.

[0107] An additional embodiment of the present invention is a composition comprising a compound having the structure of the following formula: [ka] (In the formula, X is NR 14 and O, and Y is a covalent bond, CR5R6, O, or NR 15 and R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 is hydrogen, halogen, CN, hydroxyl, R 16 OR 16and R is independently selected from the group consisting of 13 , R 14 and R 15 are independently hydrogen or R 16 and R5 and R6 are hydrogen, hydroxyl, OR 16 , R 16 and C 3~6 cycloalkyl, or R5 and R6 together represent an oxo (=O) group or C 3~6 Forming a cycloalkyl, R 12 is hydrogen, -COR a and R 16 and R 16 are each independently formyl, C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 alkynyl, and R a is hydrogen, hydroxyl and OR 16 selected from the group consisting of or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof, and a cosmetically or pharmaceutically acceptable vehicle, diluent or carrier.

[0108] A further embodiment of the present invention is a composition comprising a compound having the structure of the formula: Compound: [ka] (In the formula, R1, R4, R5, R6, R9 and R 10 is hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, and R2 and R3 are independently selected from the group consisting of hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13and -CHO, or R2 and R3 together form a 5- or 6-membered heterocyclyl, and R7 and R8 are independently selected from the group consisting of hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, or R7 and R8 together form a 5- or 6-membered heterocyclyl, and R 11 and R 12 are independently hydrogen or R 13 and R 13 are each independently, C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 alkynyl) or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof, and a cosmetically or pharmaceutically acceptable vehicle, diluent or carrier.

[0109] Another embodiment of the present invention is a composition comprising a compound listed in Table 5 or Figure 130, or a chemical analog, crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof, and a cosmetically or pharmaceutically acceptable vehicle, diluent or carrier.

[0110] An additional embodiment of the invention is a method of treating or preventing UV-induced skin damage in a subject, comprising contacting the subject with any of the compositions disclosed herein.

[0111] A further embodiment of the invention is a method of treating or preventing UV-induced erythema in a subject, comprising contacting the subject with any of the compositions disclosed herein.

[0112] Another embodiment of the present invention is a method of treating or preventing UV-induced aging of the skin in a subject, comprising contacting the subject with any of the compositions disclosed herein.

[0113] An additional embodiment of the invention is a method of treating or preventing sunburn in a subject, comprising the step of contacting the subject with any of the compositions disclosed herein.

[0114] A further embodiment of the invention is a method of treating or preventing UV-induced hyperpigmentation in a subject, comprising contacting the subject with any of the compositions disclosed herein.

[0115] Another embodiment of the present invention is a method of lightening the skin in a subject. , comprising contacting any of the compositions disclosed herein.

[0116] An additional embodiment of the invention is a method of inducing melanocyte apoptosis in a subject, comprising contacting the subject with any of the compositions disclosed herein.

[0117] A further embodiment of the invention is a method of modulating aryl hydrocarbon receptor (AhR) activity in a subject, comprising contacting the subject with any of the compositions disclosed herein.

[0118] Another embodiment of the invention is a method of modulating melanogenesis in a subject, comprising the step of contacting the subject with any of the compositions disclosed herein.

[0119] An additional embodiment of the present invention is a method of modulating melanin concentration in a subject, comprising contacting the subject with any of the compositions disclosed herein.

[0120] The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee. [Brief explanation of the drawings]

[0121] [Figure 1A] Figure 1A is a schematic diagram of the component layers of skin. The inset shows the cellular organization of the epidermis and dermis. Figure 1B is a schematic diagram illustrating the potential mechanism of action of hypopigmentation inducers. [Figure 1B] Figure 1A is a schematic diagram of the component layers of skin. The inset shows the cellular organization of the epidermis and dermis. Figure 1B is a schematic diagram illustrating the potential mechanism of action of hypopigmentation inducers.

[0122] [Figure 2A] Figure 2 shows a series of synthetic schemes for malasedin and malasedin derivatives: Figure 2A: malasedin and indolo[3,2-b]carbazole; Figure 2B: compounds I and IV; Figure 2C: compound II. [Figure 2B] Figure 2 shows a series of synthetic schemes for malasedin and malasedin derivatives: Figure 2A: malasedin and indolo[3,2-b]carbazole; Figure 2B: compounds I and IV; Figure 2C: compound II. [Figure 2C] Figure 2 shows a series of synthetic schemes for malasedin and malasedin derivatives: Figure 2A: malasedin and indolo[3,2-b]carbazole; Figure 2B: compounds I and IV; Figure 2C: compound II.

[0123] [Figure 3-1]Figure 3A is a summary chart showing EC50 values ​​for Annexin V induction in MeWo and WM115 cells for certain compounds of the invention. Figures 3B-3M are line graphs showing the percentage of MeWo (Figures 3B-3G) or WM115 (Figures 3H-3M) cells labeled with Annexin V after exposure to various concentrations of the listed compounds. [Figure 3-2] Figure 3A is a summary chart showing EC50 values ​​for Annexin V induction in MeWo and WM115 cells for certain compounds of the invention. Figures 3B-3M are line graphs showing the percentage of MeWo (Figures 3B-3G) or WM115 (Figures 3H-3M) cells labeled with Annexin V after exposure to various concentrations of the listed compounds. [Figure 3-3] Figure 3A is a summary chart showing EC50 values ​​for Annexin V induction in MeWo and WM115 cells for certain compounds of the invention. Figures 3B-3M are line graphs showing the percentage of MeWo (Figures 3B-3G) or WM115 (Figures 3H-3M) cells labeled with Annexin V after exposure to various concentrations of the listed compounds. [Figure 3-4] Figure 3A is a summary chart showing EC50 values ​​for Annexin V induction in MeWo and WM115 cells for certain compounds of the invention. Figures 3B-3M are line graphs showing the percentage of MeWo (Figures 3B-3G) or WM115 (Figures 3H-3M) cells labeled with Annexin V after exposure to various concentrations of the listed compounds. [Figure 3-5] Figure 3A is a summary chart showing EC50 values ​​for Annexin V induction in MeWo and WM115 cells for certain compounds of the invention. Figures 3B-3M are line graphs showing the percentage of MeWo (Figures 3B-3G) or WM115 (Figures 3H-3M) cells labeled with Annexin V after exposure to various concentrations of the listed compounds.

[0124] [Figure 4-1]Figures 4A-4D are charts showing relative annexin V levels (%) in MeWo and WM115 cells after exposure to various concentrations of the listed compounds for 6, 24, 48, and 72 hours. Figures 4E-4J are histograms showing the results from Figures 4A-4D. Figures 4K and 4L are histograms showing the percentage of MeWo (Figure 4K) and WM115 (Figure 4L) cells labeled with annexin V after 6 hours of exposure to the listed compounds at the indicated concentrations. [Figure 4-2] Figures 4A-4D are charts showing relative annexin V levels (%) in MeWo and WM115 cells after exposure to various concentrations of the listed compounds for 6, 24, 48, and 72 hours. Figures 4E-4J are histograms showing the results from Figures 4A-4D. Figures 4K and 4L are histograms showing the percentage of MeWo (Figure 4K) and WM115 (Figure 4L) cells labeled with annexin V after 6 hours of exposure to the listed compounds at the indicated concentrations. [Figure 4-3] Figures 4A-4D are charts showing relative annexin V levels (%) in MeWo and WM115 cells after exposure to various concentrations of the listed compounds for 6, 24, 48, and 72 hours. Figures 4E-4J are histograms showing the results from Figures 4A-4D. Figures 4K and 4L are histograms showing the percentage of MeWo (Figure 4K) and WM115 (Figure 4L) cells labeled with annexin V after 6 hours of exposure to the listed compounds at the indicated concentrations. [Figure 4-4] Figures 4A-4D are charts showing relative annexin V levels (%) in MeWo and WM115 cells after exposure to various concentrations of the listed compounds for 6, 24, 48, and 72 hours. Figures 4E-4J are histograms showing the results from Figures 4A-4D. Figures 4K and 4L are histograms showing the percentage of MeWo (Figure 4K) and WM115 (Figure 4L) cells labeled with annexin V after 6 hours of exposure to the listed compounds at the indicated concentrations. [Figure 4-5]Figures 4A-4D are charts showing relative annexin V levels (%) in MeWo and WM115 cells after exposure to various concentrations of the listed compounds for 6, 24, 48, and 72 hours. Figures 4E-4J are histograms showing the results from Figures 4A-4D. Figures 4K and 4L are histograms showing the percentage of MeWo (Figure 4K) and WM115 (Figure 4L) cells labeled with annexin V after 6 hours of exposure to the listed compounds at the indicated concentrations. [Figure 4-6] Figures 4A-4D are charts showing relative annexin V levels (%) in MeWo and WM115 cells after exposure to various concentrations of the listed compounds for 6, 24, 48, and 72 hours. Figures 4E-4J are histograms showing the results from Figures 4A-4D. Figures 4K and 4L are histograms showing the percentage of MeWo (Figure 4K) and WM115 (Figure 4L) cells labeled with annexin V after 6 hours of exposure to the listed compounds at the indicated concentrations. [Figure 4-7] Figures 4A-4D are charts showing relative annexin V levels (%) in MeWo and WM115 cells after exposure to various concentrations of the listed compounds for 6, 24, 48, and 72 hours. Figures 4E-4J are histograms showing the results from Figures 4A-4D. Figures 4K and 4L are histograms showing the percentage of MeWo (Figure 4K) and WM115 (Figure 4L) cells labeled with annexin V after 6 hours of exposure to the listed compounds at the indicated concentrations. [Figure 4-8] Figures 4A-4D are charts showing relative annexin V levels (%) in MeWo and WM115 cells after exposure to various concentrations of the listed compounds for 6, 24, 48, and 72 hours. Figures 4E-4J are histograms showing the results from Figures 4A-4D. Figures 4K and 4L are histograms showing the percentage of MeWo (Figure 4K) and WM115 (Figure 4L) cells labeled with annexin V after 6 hours of exposure to the listed compounds at the indicated concentrations.

[0125] [Figure 5]5A-5K are photomicrographs showing the morphology of MeWo cells after treatment with various concentrations of CV-8684, CV-8685, CV-8688, DMSO, and staurosporine for 6 hours.

[0126] [Figure 6] 6A-6K are photomicrographs showing the morphology of MeWo cells after treatment with various concentrations of CV-8684, CV-8685, CV-8688, DMSO, and staurosporine for 24 hours.

[0127] [Figure 7] 7A-7K are photomicrographs showing the morphology of MeWo cells after treatment with various concentrations of CV-8684, CV-8685, CV-8688, DMSO, and staurosporine for 48 hours.

[0128] [Figure 8] 8A-8K are photomicrographs showing the morphology of MeWo cells after treatment with various concentrations of CV-8684, CV-8685, CV-8688, DMSO, and staurosporine for 72 hours.

[0129] [Figure 9] 9A-9K are photomicrographs showing the morphology of WM115 cells after treatment with various concentrations of CV-8684, CV-8685, CV-8688, DMSO, and staurosporine for 6 hours.

[0130] [Figure 10] 10A-10K are photomicrographs showing the morphology of WM115 cells after treatment with various concentrations of CV-8684, CV-8685, CV-8688, DMSO, and staurosporine for 24 hours.

[0131] [Figure 11]11A-11K are photomicrographs showing the morphology of WM115 cells after treatment with various concentrations of CV-8684, CV-8685, CV-8688, DMSO, and staurosporine for 48 hours.

[0132] [Figure 12] 12A-12K are photomicrographs showing the morphology of WM115 cells after treatment with various concentrations of CV-8684, CV-8685, CV-8688, DMSO, and staurosporine for 72 hours.

[0133] [Figure 13-1] Figures 13A-13D are charts showing the percentage of viable MeWo and WM115 cells remaining after treatment with various concentrations of CV-8684 (Figure 13A), CV-8685 (Figure 13B), CV-8688 (Figure 13C), or staurosporine (Figure 13D) for 6, 24, 48, and 72 hours. Cell viability was assayed using CellTiter-Glo®. Figures 13E-13J are histograms showing the results from Figures 13A-13D. Figure 13K is a summary chart comparing the percentage of viable MeWo and WM115 cells after exposure to the listed concentrations of malasedin, indolocarbazole, Compound II, and staurosporine for 24, 48, and 72 hours. [Figure 13-2] Figures 13A-13D are charts showing the percentage of viable MeWo and WM115 cells remaining after treatment with various concentrations of CV-8684 (Figure 13A), CV-8685 (Figure 13B), CV-8688 (Figure 13C), or staurosporine (Figure 13D) for 6, 24, 48, and 72 hours. Cell viability was assayed using CellTiter-Glo®. Figures 13E-13J are histograms showing the results from Figures 13A-13D. Figure 13K is a summary chart comparing the percentage of viable MeWo and WM115 cells after exposure to the listed concentrations of malasedin, indolocarbazole, Compound II, and staurosporine for 24, 48, and 72 hours. [Figure 13-3]Figures 13A-13D are charts showing the percentage of viable MeWo and WM115 cells remaining after treatment with various concentrations of CV-8684 (Figure 13A), CV-8685 (Figure 13B), CV-8688 (Figure 13C), or staurosporine (Figure 13D) for 6, 24, 48, and 72 hours. Cell viability was assayed using CellTiter-Glo®. Figures 13E-13J are histograms showing the results from Figures 13A-13D. Figure 13K is a summary chart comparing the percentage of viable MeWo and WM115 cells after exposure to the listed concentrations of malasedin, indolocarbazole, Compound II, and staurosporine for 24, 48, and 72 hours. [Figure 13-4] Figures 13A-13D are charts showing the percentage of viable MeWo and WM115 cells remaining after treatment with various concentrations of CV-8684 (Figure 13A), CV-8685 (Figure 13B), CV-8688 (Figure 13C), or staurosporine (Figure 13D) for 6, 24, 48, and 72 hours. Cell viability was assayed using CellTiter-Glo®. Figures 13E-13J are histograms showing the results from Figures 13A-13D. Figure 13K is a summary chart comparing the percentage of viable MeWo and WM115 cells after exposure to the listed concentrations of malasedin, indolocarbazole, Compound II, and staurosporine for 24, 48, and 72 hours. [Figure 13-5] Figures 13A-13D are charts showing the percentage of viable MeWo and WM115 cells remaining after treatment with various concentrations of CV-8684 (Figure 13A), CV-8685 (Figure 13B), CV-8688 (Figure 13C), or staurosporine (Figure 13D) for 6, 24, 48, and 72 hours. Cell viability was assayed using CellTiter-Glo®. Figures 13E-13J are histograms showing the results from Figures 13A-13D. Figure 13K is a summary chart comparing the percentage of viable MeWo and WM115 cells after exposure to the listed concentrations of malasedin, indolocarbazole, Compound II, and staurosporine for 24, 48, and 72 hours. [Figure 13-6] Figures 13A-13D are charts showing the percentage of viable MeWo and WM115 cells remaining after treatment with various concentrations of CV-8684 (Figure 13A), CV-8685 (Figure 13B), CV-8688 (Figure 13C), or staurosporine (Figure 13D) for 6, 24, 48, and 72 hours. Cell viability was assayed using CellTiter-Glo®. Figures 13E-13J are histograms showing the results from Figures 13A-13D. Figure 13K is a summary chart comparing the percentage of viable MeWo and WM115 cells after exposure to the listed concentrations of malasedin, indolocarbazole, Compound II, and staurosporine for 24, 48, and 72 hours. [Figure 13-7] Figures 13A-13D are charts showing the percentage of viable MeWo and WM115 cells remaining after treatment with various concentrations of CV-8684 (Figure 13A), CV-8685 (Figure 13B), CV-8688 (Figure 13C), or staurosporine (Figure 13D) for 6, 24, 48, and 72 hours. Cell viability was assayed using CellTiter-Glo®. Figures 13E-13J are histograms showing the results from Figures 13A-13D. Figure 13K is a summary chart comparing the percentage of viable MeWo and WM115 cells after exposure to the listed concentrations of malasedin, indolocarbazole, Compound II, and staurosporine for 24, 48, and 72 hours.

[0134] [Figure 14-1]Figures 14A-14D are charts showing lactate dehydrogenase ("LDH") release levels from MeWo and WM115 cells after treatment with various concentrations of CV-8684 (Figure 14A), CV-8685 (Figure 14B), CV-8688 (Figure 14C), or staurosporine (Figure 14D) for 6, 24, 48, and 72 hours. Figures 14E-14J are histograms showing the results from Figures 14A-14D. Figures 14K and 14L are histograms showing lactate dehydrogenase levels after 24 hours of exposure of MeWo (Figure 14K) and WM115 (Figure 14L) cells to the listed concentrations of malasedin, carbazole, Compound II, and staurosporine. [Figure 14-2] Figures 14A-14D are charts showing lactate dehydrogenase ("LDH") release levels from MeWo and WM115 cells after treatment with various concentrations of CV-8684 (Figure 14A), CV-8685 (Figure 14B), CV-8688 (Figure 14C), or staurosporine (Figure 14D) for 6, 24, 48, and 72 hours. Figures 14E-14J are histograms showing the results from Figures 14A-14D. Figures 14K and 14L are histograms showing lactate dehydrogenase levels after 24 hours of exposure of MeWo (Figure 14K) and WM115 (Figure 14L) cells to the listed concentrations of malasedin, carbazole, Compound II, and staurosporine. [Figure 14-3] Figures 14A-14D are charts showing lactate dehydrogenase ("LDH") release levels from MeWo and WM115 cells after treatment with various concentrations of CV-8684 (Figure 14A), CV-8685 (Figure 14B), CV-8688 (Figure 14C), or staurosporine (Figure 14D) for 6, 24, 48, and 72 hours. Figures 14E-14J are histograms showing the results from Figures 14A-14D. Figures 14K and 14L are histograms showing lactate dehydrogenase levels after 24 hours of exposure of MeWo (Figure 14K) and WM115 (Figure 14L) cells to the listed concentrations of malasedin, carbazole, Compound II, and staurosporine. [Figure 14-4]Figures 14A-14D are charts showing lactate dehydrogenase ("LDH") release levels from MeWo and WM115 cells after treatment with various concentrations of CV-8684 (Figure 14A), CV-8685 (Figure 14B), CV-8688 (Figure 14C), or staurosporine (Figure 14D) for 6, 24, 48, and 72 hours. Figures 14E-14J are histograms showing the results from Figures 14A-14D. Figures 14K and 14L are histograms showing lactate dehydrogenase levels after 24 hours of exposure of MeWo (Figure 14K) and WM115 (Figure 14L) cells to the listed concentrations of malasedin, carbazole, Compound II, and staurosporine. [Figure 14-5] Figures 14A-14D are charts showing lactate dehydrogenase ("LDH") release levels from MeWo and WM115 cells after treatment with various concentrations of CV-8684 (Figure 14A), CV-8685 (Figure 14B), CV-8688 (Figure 14C), or staurosporine (Figure 14D) for 6, 24, 48, and 72 hours. Figures 14E-14J are histograms showing the results from Figures 14A-14D. Figures 14K and 14L are histograms showing lactate dehydrogenase levels after 24 hours of exposure of MeWo (Figure 14K) and WM115 (Figure 14L) cells to the listed concentrations of malasedin, carbazole, Compound II, and staurosporine. [Figure 14-6] Figures 14A-14D are charts showing lactate dehydrogenase ("LDH") release levels from MeWo and WM115 cells after treatment with various concentrations of CV-8684 (Figure 14A), CV-8685 (Figure 14B), CV-8688 (Figure 14C), or staurosporine (Figure 14D) for 6, 24, 48, and 72 hours. Figures 14E-14J are histograms showing the results from Figures 14A-14D. Figures 14K and 14L are histograms showing lactate dehydrogenase levels after 24 hours of exposure of MeWo (Figure 14K) and WM115 (Figure 14L) cells to the listed concentrations of malasedin, carbazole, Compound II, and staurosporine. [Figure 14-7]Figures 14A-14D are charts showing lactate dehydrogenase ("LDH") release levels from MeWo and WM115 cells after treatment with various concentrations of CV-8684 (Figure 14A), CV-8685 (Figure 14B), CV-8688 (Figure 14C), or staurosporine (Figure 14D) for 6, 24, 48, and 72 hours. Figures 14E-14J are histograms showing the results from Figures 14A-14D. Figures 14K and 14L are histograms showing lactate dehydrogenase levels after 24 hours of exposure of MeWo (Figure 14K) and WM115 (Figure 14L) cells to the listed concentrations of malasedin, carbazole, Compound II, and staurosporine. [Figure 14-8] Figures 14A-14D are charts showing lactate dehydrogenase ("LDH") release levels from MeWo and WM115 cells after treatment with various concentrations of CV-8684 (Figure 14A), CV-8685 (Figure 14B), CV-8688 (Figure 14C), or staurosporine (Figure 14D) for 6, 24, 48, and 72 hours. Figures 14E-14J are histograms showing the results from Figures 14A-14D. Figures 14K and 14L are histograms showing lactate dehydrogenase levels after 24 hours of exposure of MeWo (Figure 14K) and WM115 (Figure 14L) cells to the listed concentrations of malasedin, carbazole, Compound II, and staurosporine.

[0135] [Figure 15A] Figures 15A-15E show raw data and line graphs of aryl hydrocarbon receptor ("AhR") activation in HepG2 cells stably transfected with an AhR-responsive luciferase reporter gene plasmid upon exposure to various concentrations of omeprazole (Figure 15A), CV-8684 (Figure 15B), CV-8685 (Figure 15C), CV-8686 (Figure 15D), and CV-8688 (Figure 15E). Figure 15F shows the EC50 values ​​for each compound tested. [Figure 15B]Figures 15A-15E show raw data and line graphs of aryl hydrocarbon receptor ("AhR") activation in HepG2 cells stably transfected with an AhR-responsive luciferase reporter gene plasmid upon exposure to various concentrations of omeprazole (Figure 15A), CV-8684 (Figure 15B), CV-8685 (Figure 15C), CV-8686 (Figure 15D), and CV-8688 (Figure 15E). Figure 15F shows the EC50 values ​​for each compound tested. [Figure 15C] Figures 15A-15E show raw data and line graphs of aryl hydrocarbon receptor ("AhR") activation in HepG2 cells stably transfected with an AhR-responsive luciferase reporter gene plasmid upon exposure to various concentrations of omeprazole (Figure 15A), CV-8684 (Figure 15B), CV-8685 (Figure 15C), CV-8686 (Figure 15D), and CV-8688 (Figure 15E). Figure 15F shows the EC50 values ​​for each compound tested. [Figure 15D] Figures 15A-15E show raw data and line graphs of aryl hydrocarbon receptor ("AhR") activation in HepG2 cells stably transfected with an AhR-responsive luciferase reporter gene plasmid upon exposure to various concentrations of omeprazole (Figure 15A), CV-8684 (Figure 15B), CV-8685 (Figure 15C), CV-8686 (Figure 15D), and CV-8688 (Figure 15E). Figure 15F shows the EC50 values ​​for each compound tested. [Figure 15E] Figures 15A-15E show raw data and line graphs of aryl hydrocarbon receptor ("AhR") activation in HepG2 cells stably transfected with an AhR-responsive luciferase reporter gene plasmid upon exposure to various concentrations of omeprazole (Figure 15A), CV-8684 (Figure 15B), CV-8685 (Figure 15C), CV-8686 (Figure 15D), and CV-8688 (Figure 15E). Figure 15F shows the EC50 values ​​for each compound tested. [Figure 15F]Figures 15A-15E show raw data and line graphs of aryl hydrocarbon receptor ("AhR") activation in HepG2 cells stably transfected with an AhR-responsive luciferase reporter gene plasmid upon exposure to various concentrations of omeprazole (Figure 15A), CV-8684 (Figure 15B), CV-8685 (Figure 15C), CV-8686 (Figure 15D), and CV-8688 (Figure 15E). Figure 15F shows the EC50 values ​​for each compound tested.

[0136] [Figure 16-1] 16A-16K are photographs of MelanoDerm™ matrix on either day 0 or day 7 after exposure to untreated (FIG. 16A), sterile deionized water (FIG. 16B), 1% kojic acid (FIG. 16C), 0.2% DMSO (FIG. 16D), 0.05% DMSO (FIG. 16E), 200 μM CV-8684 (FIG. 16F), 50 μM CV-8684 (FIG. 16G), 200 μM CV-8686 (FIG. 16H), 50 μM CV-8686 (FIG. 16I), 200 μM CV-8688 (FIG. 16J), and 50 μM CV-8688 (FIG. 16K). [Figure 16-2] 16A-16K are photographs of MelanoDerm™ matrix on either day 0 or day 7 after exposure to untreated (FIG. 16A), sterile deionized water (FIG. 16B), 1% kojic acid (FIG. 16C), 0.2% DMSO (FIG. 16D), 0.05% DMSO (FIG. 16E), 200 μM CV-8684 (FIG. 16F), 50 μM CV-8684 (FIG. 16G), 200 μM CV-8686 (FIG. 16H), 50 μM CV-8686 (FIG. 16I), 200 μM CV-8688 (FIG. 16J), and 50 μM CV-8688 (FIG. 16K).

[0137] [Figure 17-1]17A-17K are 15x photomicrographs of MelanoDerm™ matrix at either day 0 or day 7 after exposure to untreated (FIG. 17A), sterile deionized water (FIG. 17B), 1% kojic acid (FIG. 17C), 0.2% DMSO (FIG. 17D), 0.05% DMSO (FIG. 17E), 200 μM CV-8684 (FIG. 17F), 50 μM CV-8684 (FIG. 17G), 200 μM CV-8686 (FIG. 17H), 50 μM CV-8686 (FIG. 17I), 200 μM CV-8688 (FIG. 17J), and 50 μM CV-8688 (FIG. 17K). [Figure 17-2] 17A-17K are 15x photomicrographs of MelanoDerm™ matrix at either day 0 or day 7 after exposure to untreated (FIG. 17A), sterile deionized water (FIG. 17B), 1% kojic acid (FIG. 17C), 0.2% DMSO (FIG. 17D), 0.05% DMSO (FIG. 17E), 200 μM CV-8684 (FIG. 17F), 50 μM CV-8684 (FIG. 17G), 200 μM CV-8686 (FIG. 17H), 50 μM CV-8686 (FIG. 17I), 200 μM CV-8688 (FIG. 17J), and 50 μM CV-8688 (FIG. 17K).

[0138] [Figure 18] Figures 18A-18F show photographs of zebrafish exposed to untreated (Figure 18A), DMSO (Figure 18B), phenylthiourea ("PTU") (Figure 18C), and 2.5 μM (Figure 18D), 5 μM (Figure 18E), and 10 μM (Figure 18F) Compound II. Red arrows indicate normal melanocytes.

[0139] [Figure 19] Figures 19A-19F are photographs of zebrafish exposed to untreated (Figure 19A), DMSO (Figure 19B), phenylthiourea ("PTU") (Figure 19C), and 0.3 μM (Figure 19D), 1 μM (Figure 19E), and 3 μM (Figure 19F) Compound II. Red arrows indicate normal melanocytes. Yellow arrows indicate abnormally small melanocytes.

[0140] [Figure 20] Figure 20 is a summary chart showing the number and percentage of zebrafish with reduced skin pigmentation after exposure to the listed conditions. The last six columns show the effects of various concentrations of Compound II. [Figure 21] 21A-21E are photographs of zebrafish untreated (FIG. 21A), treated with DMSO (FIG. 21B), PTU (FIG. 21C), 0.5 μM (FIG. 21D), and 1.5 μM (FIG. 21E). The bottom panel contains the reversed region of the color scheme.

[0141] [Figure 22A] 22A and 22B are histograms showing pigmentation density, as measured by colored pixels / mm3 (FIG. 22A) and total pixels (FIG. 22B), from photographs of zebrafish embryos illustrated in FIGS. 21A-21E. [Figure 22B] 22A and 22B are histograms showing pigmentation density, as measured by colored pixels / mm3 (FIG. 22A) and total pixels (FIG. 22B), from photographs of zebrafish embryos illustrated in FIGS. 21A-21E.

[0142] [Figure 23A] Figures 23A-23C are mass spectra of CV-8684 in DMSO (Figure 23A), RPMI medium (Figure 23B), and DMEM (Figure 23C). Figures 23D-23F are mass spectra of CV-8686 in DMSO (Figure 23D), RPMI medium (Figure 23E), and DMEM (Figure 23F). Figures 23G-23I are mass spectra of CV-8688 in DMSO (Figure 23G), RPMI medium (Figure 23H), and DMEM (Figure 23I). Figure 23J is a summary chart showing the percentage of test compound remaining in the listed solvent after 2 hours of incubation. [Figure 23B]Figures 23A-23C are mass spectra of CV-8684 in DMSO (Figure 23A), RPMI medium (Figure 23B), and DMEM (Figure 23C). Figures 23D-23F are mass spectra of CV-8686 in DMSO (Figure 23D), RPMI medium (Figure 23E), and DMEM (Figure 23F). Figures 23G-23I are mass spectra of CV-8688 in DMSO (Figure 23G), RPMI medium (Figure 23H), and DMEM (Figure 23I). Figure 23J is a summary chart showing the percentage of test compound remaining in the listed solvent after 2 hours of incubation. [Figure 23C] Figures 23A-23C are mass spectra of CV-8684 in DMSO (Figure 23A), RPMI medium (Figure 23B), and DMEM (Figure 23C). Figures 23D-23F are mass spectra of CV-8686 in DMSO (Figure 23D), RPMI medium (Figure 23E), and DMEM (Figure 23F). Figures 23G-23I are mass spectra of CV-8688 in DMSO (Figure 23G), RPMI medium (Figure 23H), and DMEM (Figure 23I). Figure 23J is a summary chart showing the percentage of test compound remaining in the listed solvent after 2 hours of incubation. [Figure 23D] Figures 23A-23C are mass spectra of CV-8684 in DMSO (Figure 23A), RPMI medium (Figure 23B), and DMEM (Figure 23C). Figures 23D-23F are mass spectra of CV-8686 in DMSO (Figure 23D), RPMI medium (Figure 23E), and DMEM (Figure 23F). Figures 23G-23I are mass spectra of CV-8688 in DMSO (Figure 23G), RPMI medium (Figure 23H), and DMEM (Figure 23I). Figure 23J is a summary chart showing the percentage of test compound remaining in the listed solvent after 2 hours of incubation. [Figure 23E]Figures 23A-23C are mass spectra of CV-8684 in DMSO (Figure 23A), RPMI medium (Figure 23B), and DMEM (Figure 23C). Figures 23D-23F are mass spectra of CV-8686 in DMSO (Figure 23D), RPMI medium (Figure 23E), and DMEM (Figure 23F). Figures 23G-23I are mass spectra of CV-8688 in DMSO (Figure 23G), RPMI medium (Figure 23H), and DMEM (Figure 23I). Figure 23J is a summary chart showing the percentage of test compound remaining in the listed solvent after 2 hours of incubation. [Figure 23F] Figures 23A-23C are mass spectra of CV-8684 in DMSO (Figure 23A), RPMI medium (Figure 23B), and DMEM (Figure 23C). Figures 23D-23F are mass spectra of CV-8686 in DMSO (Figure 23D), RPMI medium (Figure 23E), and DMEM (Figure 23F). Figures 23G-23I are mass spectra of CV-8688 in DMSO (Figure 23G), RPMI medium (Figure 23H), and DMEM (Figure 23I). Figure 23J is a summary chart showing the percentage of test compound remaining in the listed solvent after 2 hours of incubation. [Figure 23G] Figures 23A-23C are mass spectra of CV-8684 in DMSO (Figure 23A), RPMI medium (Figure 23B), and DMEM (Figure 23C). Figures 23D-23F are mass spectra of CV-8686 in DMSO (Figure 23D), RPMI medium (Figure 23E), and DMEM (Figure 23F). Figures 23G-23I are mass spectra of CV-8688 in DMSO (Figure 23G), RPMI medium (Figure 23H), and DMEM (Figure 23I). Figure 23J is a summary chart showing the percentage of test compound remaining in the listed solvent after 2 hours of incubation. [Figure 23H]Figures 23A-23C are mass spectra of CV-8684 in DMSO (Figure 23A), RPMI medium (Figure 23B), and DMEM (Figure 23C). Figures 23D-23F are mass spectra of CV-8686 in DMSO (Figure 23D), RPMI medium (Figure 23E), and DMEM (Figure 23F). Figures 23G-23I are mass spectra of CV-8688 in DMSO (Figure 23G), RPMI medium (Figure 23H), and DMEM (Figure 23I). Figure 23J is a summary chart showing the percentage of test compound remaining in the listed solvent after 2 hours of incubation. [Figure 23I] Figures 23A-23C are mass spectra of CV-8684 in DMSO (Figure 23A), RPMI medium (Figure 23B), and DMEM (Figure 23C). Figures 23D-23F are mass spectra of CV-8686 in DMSO (Figure 23D), RPMI medium (Figure 23E), and DMEM (Figure 23F). Figures 23G-23I are mass spectra of CV-8688 in DMSO (Figure 23G), RPMI medium (Figure 23H), and DMEM (Figure 23I). Figure 23J is a summary chart showing the percentage of test compound remaining in the listed solvent after 2 hours of incubation. [Figure 23J] Figures 23A-23C are mass spectra of CV-8684 in DMSO (Figure 23A), RPMI medium (Figure 23B), and DMEM (Figure 23C). Figures 23D-23F are mass spectra of CV-8686 in DMSO (Figure 23D), RPMI medium (Figure 23E), and DMEM (Figure 23F). Figures 23G-23I are mass spectra of CV-8688 in DMSO (Figure 23G), RPMI medium (Figure 23H), and DMEM (Figure 23I). Figure 23J is a summary chart showing the percentage of test compound remaining in the listed solvent after 2 hours of incubation.

[0143] [Figure 24-1]Figures 24A-24S show the synthesis schemes of the malasedin derivatives of the present invention. Figure 24A: Compound C (CV-8802); Figure 24B: Compound K (CV-8803); Figure 24C: Compound A (CV-8804); Figure 24D: Compound E (AB12508); Figure 24E: Compound A5 (CV-8819); Figure 24F: Compound H (AB12509); Figure 24G: Compound B (CV-8877); Figure 24H: Compound B10; Figure 24I: Compound AB11644; Figure 24J: O52 (AB12976); Figure 24K : Malassezia indole A (AB17011); Figure 24L: Pityriacitrine (AB17014); Figure 24M: AB17151; Figure 24N: Compound VI (AB17225); Figure 24O: Malassezia lactic acid (AB17227); Figure 24P: AB12507; Figure 24Q: Compound V (AB17219); Figure 24R: Compound VIII (AB17220) and Figure 24S: Compound VII (AB17221). [Figure 24-2] Figures 24A-24S show the synthesis schemes of the malasedin derivatives of the present invention. Figure 24A: Compound C (CV-8802); Figure 24B: Compound K (CV-8803); Figure 24C: Compound A (CV-8804); Figure 24D: Compound E (AB12508); Figure 24E: Compound A5 (CV-8819); Figure 24F: Compound H (AB12509); Figure 24G: Compound B (CV-8877); Figure 24H: Compound B10; Figure 24I: Compound AB11644; Figure 24J: O52 (AB12976); Figure 24K : Malassezia indole A (AB17011); Figure 24L: Pityriacitrine (AB17014); Figure 24M: AB17151; Figure 24N: Compound VI (AB17225); Figure 24O: Malassezia lactic acid (AB17227); Figure 24P: AB12507; Figure 24Q: Compound V (AB17219); Figure 24R: Compound VIII (AB17220) and Figure 24S: Compound VII (AB17221). [Figure 24-3]Figures 24A-24S show the synthesis schemes of the malasedin derivatives of the present invention. Figure 24A: Compound C (CV-8802); Figure 24B: Compound K (CV-8803); Figure 24C: Compound A (CV-8804); Figure 24D: Compound E (AB12508); Figure 24E: Compound A5 (CV-8819); Figure 24F: Compound H (AB12509); Figure 24G: Compound B (CV-8877); Figure 24H: Compound B10; Figure 24I: Compound AB11644; Figure 24J: O52 (AB12976); Figure 24K : Malassezia indole A (AB17011); Figure 24L: Pityriacitrine (AB17014); Figure 24M: AB17151; Figure 24N: Compound VI (AB17225); Figure 24O: Malassezia lactic acid (AB17227); Figure 24P: AB12507; Figure 24Q: Compound V (AB17219); Figure 24R: Compound VIII (AB17220) and Figure 24S: Compound VII (AB17221). [Figure 24-4] Figures 24A-24S show the synthesis schemes of the malasedin derivatives of the present invention. Figure 24A: Compound C (CV-8802); Figure 24B: Compound K (CV-8803); Figure 24C: Compound A (CV-8804); Figure 24D: Compound E (AB12508); Figure 24E: Compound A5 (CV-8819); Figure 24F: Compound H (AB12509); Figure 24G: Compound B (CV-8877); Figure 24H: Compound B10; Figure 24I: Compound AB11644; Figure 24J: O52 (AB12976); Figure 24K : Malassezia indole A (AB17011); Figure 24L: Pityriacitrine (AB17014); Figure 24M: AB17151; Figure 24N: Compound VI (AB17225); Figure 24O: Malassezia lactic acid (AB17227); Figure 24P: AB12507; Figure 24Q: Compound V (AB17219); Figure 24R: Compound VIII (AB17220) and Figure 24S: Compound VII (AB17221). [Figure 24-5]Figures 24A-24S show the synthesis schemes of the malasedin derivatives of the present invention. Figure 24A: Compound C (CV-8802); Figure 24B: Compound K (CV-8803); Figure 24C: Compound A (CV-8804); Figure 24D: Compound E (AB12508); Figure 24E: Compound A5 (CV-8819); Figure 24F: Compound H (AB12509); Figure 24G: Compound B (CV-8877); Figure 24H: Compound B10; Figure 24I: Compound AB11644; Figure 24J: O52 (AB12976); Figure 24K : Malassezia indole A (AB17011); Figure 24L: Pityriacitrine (AB17014); Figure 24M: AB17151; Figure 24N: Compound VI (AB17225); Figure 24O: Malassezia lactic acid (AB17227); Figure 24P: AB12507; Figure 24Q: Compound V (AB17219); Figure 24R: Compound VIII (AB17220) and Figure 24S: Compound VII (AB17221). [Figure 24-6] Figures 24A-24S show the synthesis schemes of the malasedin derivatives of the present invention. Figure 24A: Compound C (CV-8802); Figure 24B: Compound K (CV-8803); Figure 24C: Compound A (CV-8804); Figure 24D: Compound E (AB12508); Figure 24E: Compound A5 (CV-8819); Figure 24F: Compound H (AB12509); Figure 24G: Compound B (CV-8877); Figure 24H: Compound B10; Figure 24I: Compound AB11644; Figure 24J: O52 (AB12976); Figure 24K : Malassezia indole A (AB17011); Figure 24L: Pityriacitrine (AB17014); Figure 24M: AB17151; Figure 24N: Compound VI (AB17225); Figure 24O: Malassezia lactic acid (AB17227); Figure 24P: AB12507; Figure 24Q: Compound V (AB17219); Figure 24R: Compound VIII (AB17220) and Figure 24S: Compound VII (AB17221). [Figure 24-7]Figures 24A-24S show the synthesis schemes of the malasedin derivatives of the present invention. Figure 24A: Compound C (CV-8802); Figure 24B: Compound K (CV-8803); Figure 24C: Compound A (CV-8804); Figure 24D: Compound E (AB12508); Figure 24E: Compound A5 (CV-8819); Figure 24F: Compound H (AB12509); Figure 24G: Compound B (CV-8877); Figure 24H: Compound B10; Figure 24I: Compound AB11644; Figure 24J: O52 (AB12976); Figure 24K : Malassezia indole A (AB17011); Figure 24L: Pityriacitrine (AB17014); Figure 24M: AB17151; Figure 24N: Compound VI (AB17225); Figure 24O: Malassezia lactic acid (AB17227); Figure 24P: AB12507; Figure 24Q: Compound V (AB17219); Figure 24R: Compound VIII (AB17220) and Figure 24S: Compound VII (AB17221). [Figure 24-8] Figures 24A-24S show the synthesis schemes of the malasedin derivatives of the present invention. Figure 24A: Compound C (CV-8802); Figure 24B: Compound K (CV-8803); Figure 24C: Compound A (CV-8804); Figure 24D: Compound E (AB12508); Figure 24E: Compound A5 (CV-8819); Figure 24F: Compound H (AB12509); Figure 24G: Compound B (CV-8877); Figure 24H: Compound B10; Figure 24I: Compound AB11644; Figure 24J: O52 (AB12976); Figure 24K : Malassezia indole A (AB17011); Figure 24L: Pityriacitrine (AB17014); Figure 24M: AB17151; Figure 24N: Compound VI (AB17225); Figure 24O: Malassezia lactic acid (AB17227); Figure 24P: AB12507; Figure 24Q: Compound V (AB17219); Figure 24R: Compound VIII (AB17220) and Figure 24S: Compound VII (AB17221). [Figure 24-9]Figures 24A-24S show the synthesis schemes of the malasedin derivatives of the present invention. Figure 24A: Compound C (CV-8802); Figure 24B: Compound K (CV-8803); Figure 24C: Compound A (CV-8804); Figure 24D: Compound E (AB12508); Figure 24E: Compound A5 (CV-8819); Figure 24F: Compound H (AB12509); Figure 24G: Compound B (CV-8877); Figure 24H: Compound B10; Figure 24I: Compound AB11644; Figure 24J: O52 (AB12976); Figure 24K : Malassezia indole A (AB17011); Figure 24L: Pityriacitrine (AB17014); Figure 24M: AB17151; Figure 24N: Compound VI (AB17225); Figure 24O: Malassezia lactic acid (AB17227); Figure 24P: AB12507; Figure 24Q: Compound V (AB17219); Figure 24R: Compound VIII (AB17220) and Figure 24S: Compound VII (AB17221). [Figure 24-10] Figures 24A-24S show the synthesis schemes of the malasedin derivatives of the present invention. Figure 24A: Compound C (CV-8802); Figure 24B: Compound K (CV-8803); Figure 24C: Compound A (CV-8804); Figure 24D: Compound E (AB12508); Figure 24E: Compound A5 (CV-8819); Figure 24F: Compound H (AB12509); Figure 24G: Compound B (CV-8877); Figure 24H: Compound B10; Figure 24I: Compound AB11644; Figure 24J: O52 (AB12976); Figure 24K : Malassezia indole A (AB17011); Figure 24L: Pityriacitrine (AB17014); Figure 24M: AB17151; Figure 24N: Compound VI (AB17225); Figure 24O: Malassezia lactic acid (AB17227); Figure 24P: AB12507; Figure 24Q: Compound V (AB17219); Figure 24R: Compound VIII (AB17220) and Figure 24S: Compound VII (AB17221). [Figure 24-11]Figures 24A-24S show the synthesis schemes of the malasedin derivatives of the present invention. Figure 24A: Compound C (CV-8802); Figure 24B: Compound K (CV-8803); Figure 24C: Compound A (CV-8804); Figure 24D: Compound E (AB12508); Figure 24E: Compound A5 (CV-8819); Figure 24F: Compound H (AB12509); Figure 24G: Compound B (CV-8877); Figure 24H: Compound B10; Figure 24I: Compound AB11644; Figure 24J: O52 (AB12976); Figure 24K : Malassezia indole A (AB17011); Figure 24L: Pityriacitrine (AB17014); Figure 24M: AB17151; Figure 24N: Compound VI (AB17225); Figure 24O: Malassezia lactic acid (AB17227); Figure 24P: AB12507; Figure 24Q: Compound V (AB17219); Figure 24R: Compound VIII (AB17220) and Figure 24S: Compound VII (AB17221). [Figure 24-12] Figures 24A-24S show the synthesis schemes of the malasedin derivatives of the present invention. Figure 24A: Compound C (CV-8802); Figure 24B: Compound K (CV-8803); Figure 24C: Compound A (CV-8804); Figure 24D: Compound E (AB12508); Figure 24E: Compound A5 (CV-8819); Figure 24F: Compound H (AB12509); Figure 24G: Compound B (CV-8877); Figure 24H: Compound B10; Figure 24I: Compound AB11644; Figure 24J: O52 (AB12976); Figure 24K : Malassezia indole A (AB17011); Figure 24L: Pityriacitrine (AB17014); Figure 24M: AB17151; Figure 24N: Compound VI (AB17225); Figure 24O: Malassezia lactic acid (AB17227); Figure 24P: AB12507; Figure 24Q: Compound V (AB17219); Figure 24R: Compound VIII (AB17220) and Figure 24S: Compound VII (AB17221).

[0144] [Figure 25A] 25A-25D show data tables containing the percentage of Annexin V-positive cells at 6 hours (FIG. 25A), 24 hours (FIG. 25B), 48 hours (FIG. 25C), and 72 hours (FIG. 25D) after exposure to the indicated treatments. [Figure 25B] 25A-25D show data tables containing the percentage of Annexin V-positive cells at 6 hours (FIG. 25A), 24 hours (FIG. 25B), 48 hours (FIG. 25C), and 72 hours (FIG. 25D) after exposure to the indicated treatments. [Figure 25C] 25A-25D show data tables containing the percentage of Annexin V-positive cells at 6 hours (FIG. 25A), 24 hours (FIG. 25B), 48 hours (FIG. 25C), and 72 hours (FIG. 25D) after exposure to the indicated treatments. [Figure 25D] 25A-25D show data tables containing the percentage of Annexin V-positive cells at 6 hours (FIG. 25A), 24 hours (FIG. 25B), 48 hours (FIG. 25C), and 72 hours (FIG. 25D) after exposure to the indicated treatments.

[0145] [Figure 26A] 26A-26D show data tables containing fold caspase 3 / 7 induction at 6 hours (FIG. 26A), 24 hours (FIG. 26B), 48 hours (FIG. 26C), and 72 hours (FIG. 26D) after exposure to the indicated treatments. [Figure 26B] 26A-26D show data tables containing fold caspase 3 / 7 induction at 6 hours (FIG. 26A), 24 hours (FIG. 26B), 48 hours (FIG. 26C), and 72 hours (FIG. 26D) after exposure to the indicated treatments. [Figure 26C] 26A-26D show data tables containing fold caspase 3 / 7 induction at 6 hours (FIG. 26A), 24 hours (FIG. 26B), 48 hours (FIG. 26C), and 72 hours (FIG. 26D) after exposure to the indicated treatments. [Figure 26D] 26A-26D show data tables containing fold caspase 3 / 7 induction at 6 hours (FIG. 26A), 24 hours (FIG. 26B), 48 hours (FIG. 26C), and 72 hours (FIG. 26D) after exposure to the indicated treatments.

[0146] [Figure 27]27A-27B show the percentage of residual cell viability for MeWo (FIG. 27A) and WM115 (FIG. 27B) cells after exposure to AB12508 (Compound E).

[0147] [Figure 28] 28A-28B show the percentage of remaining cell viability for MeWo (FIG. 28A) and WM115 (FIG. 28B) cells after exposure to unknown compositions.

[0148] [Figure 29] 29A-29B show the percentage of remaining cell viability for MeWo (FIG. 29A) and WM115 (FIG. 29B) cells after exposure to CV-8803 (Compound K).

[0149] [Figure 30] 30A-30B show the percentage of residual cell viability for MeWo (FIG. 30A) and WM115 (FIG. 30B) cells after exposure to CV-8804 (Compound A).

[0150] [Figure 31] 31A-31B show the percentage of remaining cell viability for MeWo (FIG. 31A) and WM115 (FIG. 31B) cells after exposure to CV-8684 (malasedin).

[0151] [Figure 32] 32A-32B show the percentage of remaining cell viability for MeWo (FIG. 32A) and WM115 (FIG. 32B) cells after exposure to CV-8685 (indolo[3,2-b]carbazole).

[0152] [Figure 33] 33A-33B show the percentage of residual cell viability for MeWo (FIG. 33A) and WM115 (FIG. 33B) cells after exposure to CV-8686 (Compound I).

[0153] [Figure 34] 34A-34B show the percentage of remaining cell viability for MeWo (FIG. 34A) and WM115 (FIG. 34B) cells after exposure to CV-8688 (Compound II).

[0154] [Figure 35] 35A-35B show the percentage of remaining cell viability for MeWo (FIG. 35A) and WM115 (FIG. 35B) cells after exposure to staurosporine.

[0155] [Figure 36] Figure 36A shows AhR activity readouts from a HepG2-AhR-luciferase assay upon exposure to various concentrations of omeprazole. Figure 36B shows a line graph of the data from Figure 36A, while the inset shows the measured EC50.

[0156] [Figure 37] Figure 37A shows AhR activity readouts from a HepG2-AhR-luciferase assay upon exposure to various concentrations of CV-8684 (malasedin). Figure 37B shows a line graph of the data from Figure 37A, while the inset shows the measured EC50.

[0157] [Figure 38] Figure 38A shows AhR activity readouts from a HepG2-AhR-luciferase assay upon exposure to various concentrations of CV-8685 (indolo[3,2-b]carbazole). Figure 38B shows a line graph of the data from Figure 38A, while the inset shows the measured EC50.

[0158] [Figure 39] Figure 39A shows AhR activity readouts from a HepG2-AhR-luciferase assay upon exposure to various concentrations of CV-8686 (Compound I). Figure 39B shows a line graph of the data from Figure 39A, while the inset shows the measured EC50.

[0159] [Figure 40] Figure 40A shows AhR activity readouts from a HepG2-AhR-luciferase assay upon exposure to various concentrations of unknown compositions. Figure 40B shows a line graph of the data from Figure 40A, while the inset shows the measured EC50.

[0160] [Figure 41] Figure 41A shows AhR activity readouts from a HepG2-AhR-luciferase assay upon exposure to various concentrations of CV-8803 (Compound K). Figure 41B shows a line graph of the data from Figure 41A, while the inset shows the measured EC50.

[0161] [Figure 42] Figure 42A shows AhR activity readouts from a HepG2-AhR-luciferase assay upon exposure to various concentrations of CV-8804 (Compound A). Figure 42B shows a line graph of the data from Figure 42A, while the inset shows the measured EC50.

[0162] [Figure 43] Figure 43A shows AhR activity readouts from a HepG2-AhR-luciferase assay upon exposure to various concentrations of AB12508 (Compound E). Figure 43B shows a line graph of the data from Figure 43A, while the inset shows the measured EC50.

[0163] [Figure 44] Figure 44A shows AhR activity readouts from a HepG2-AhR-luciferase assay upon exposure to various concentrations of CV-8688 (Compound II). Figure 44B shows a line graph of the data from Figure 44A, while the inset shows the measured EC50.

[0164] [Figure 45]Figure 45A shows AhR activity readouts from a HepG2-AhR-luciferase assay upon exposure to various concentrations of omeprazole. Figure 45B shows a line graph of the data from Figure 45A.

[0165] [Figure 46] Figure 46A shows AhR activity readouts from a HepG2-AhR-luciferase assay upon exposure to various concentrations of unknown compositions. Figure 46B shows a line graph of the data from Figure 46A.

[0166] [Figure 47] Figure 47A shows AhR activity readouts from a HepG2-AhR-luciferase assay upon exposure to various concentrations of 2,3,7,8-tetrachlorodibenzodioxin (TCDD). Figure 47B shows a line graph of the data from Figure 47A.

[0167] [Figure 48] Figure 48A shows AhR activity readouts from a HepG2-AhR-luciferase assay upon exposure to various concentrations of CV-8819 (compound A5). Figure 48B shows a line graph of the data from Figure 48A.

[0168] [Figure 49] Figure 49A shows AhR activity readouts from a HepG2-AhR-luciferase assay upon exposure to various concentrations of CV-8684 (malasedin). Figure 49B shows a line graph of the data from Figure 49A.

[0169] [Figure 50] Figure 50A shows AhR activity readouts from a HepG2-AhR-luciferase assay upon exposure to various concentrations of AB12508 (Compound E). Figure 50B shows a line graph of the data from Figure 50A.

[0170] [Figure 51]Figure 51A shows AhR activity readouts from a HepG2-AhR-luciferase assay upon exposure to various concentrations of CV-8686 (Compound I). Figure 51B shows a line graph of the data from Figure 51A.

[0171] [Figure 52] Figure 52A shows AhR activity readouts from a HepG2-AhR-luciferase assay upon exposure to various concentrations of AB12509 (Compound H). Figure 52B shows a line graph of the data from Figure 52A.

[0172] [Figure 53] Figure 53A shows AhR activity readouts from a HepG2-AhR-luciferase assay upon exposure to various concentrations of CV-8688 (Compound II). Figure 53B shows a line graph of the data from Figure 53A.

[0173] [Figure 54] Figure 54A shows AhR activity readouts from a HepG2-AhR-luciferase assay upon exposure to various concentrations of CV-8877 (Compound B). Figure 54B shows a line graph of the data from Figure 54A.

[0174] [Figure 55] Figure 55A shows AhR activity readouts from a HepG2-AhR-luciferase assay upon exposure to various concentrations of CV-8685 (indolo[3,2-b]carbazole). Figure 55B shows a line graph of the data from Figure 55A.

[0175] [Figure 56] Figure 56A shows AhR activity readouts from a HepG2-AhR-luciferase assay upon exposure to various concentrations of Compound B10. Figure 56B shows a line graph of the data from Figure 56A.

[0176] [Figure 57]Figure 57A shows AhR activity readouts from a HepG2-AhR-luciferase assay upon exposure to various concentrations of CV-8687 (Compound IV). Figure 57B shows a line graph of the data from Figure 57A.

[0177] [Figure 58] Figure 58A shows AhR activity readouts from a HepG2-AhR-luciferase assay upon exposure to various concentrations of omeprazole. Figure 58B shows a line graph of the data from Figure 58A.

[0178] [Figure 59] Figure 59A shows AhR activity readouts from a HepG2-AhR-luciferase assay upon exposure to various concentrations of TCDD. Figure 59B shows a line graph of the data from Figure 59A.

[0179] [Figure 60] Figure 60A shows AhR activity readouts from a HepG2-AhR-luciferase assay upon exposure to various concentrations of malasedin precursors. Figure 60B shows a line graph of the data from Figure 60A.

[0180] [Figure 61] Figure 61A shows AhR activity readouts from a HepG2-AhR-luciferase assay upon exposure to various concentrations of ABl 1644. Figure 61B shows a line graph of the data from Figure 61A.

[0181] [Figure 62] Figure 62A shows AhR activity readouts from a HepG2-AhR-luciferase assay upon exposure to various concentrations of 3-methylcholanthrene (3-MC). Figure 62B shows a line graph of the data from Figure 62A.

[0182] [Figure 63]Figure 63A shows AhR activity readouts from a HepG2-AhR-luciferase assay upon exposure to various concentrations of AB12976(O52). Figure 63B shows a line graph of the data from Figure 63A.

[0183] [Figure 64] Figure 64A shows AhR activity readouts from a HepG2-AhR-luciferase assay upon exposure to various concentrations of AB17011 (Malassezia indole A). Figure 64B shows a line graph of the data from Figure 64A.

[0184] [Figure 65] Figure 65A shows AhR activity readouts from a HepG2-AhR-luciferase assay upon exposure to various concentrations of AB17014 (pityriacitrine). Figure 65B shows a line graph of the data from Figure 65A.

[0185] [Figure 66] Figure 66A shows AhR activity readouts from a HepG2-AhR-luciferase assay upon exposure to various concentrations of AB17151. Figure 66B shows a line graph of the data from Figure 66A.

[0186] [Figure 67] Figure 67A shows AhR activity readouts from a HepG2-AhR-luciferase assay upon exposure to various concentrations of AB17225. Figure 67B shows a line graph of the data from Figure 67A.

[0187] [Figure 68] FIG. 68 is a table showing MTT viability data resolved from MelanoDerm™ substrates treated with various concentrations of the indicated compounds.

[0188] [Figure 69]FIG. 69 is a table showing melanin concentration data resolved from MelanoDerm™ substrates treated with various concentrations of the indicated compounds.

[0189] [Figure 70] Figure 70 shows representative macroscopic photographic images of MelanoDerm™ samples exposed to CV-8686 (Compound I) and AB11644, taken on the indicated days, where the samples were exposed to the indicated treatments.

[0190] [Figure 71] Figure 71 shows representative microscopic (15x) photographic images of MelanoDerm™ samples exposed to CV-8686 (Compound I) and AB11644, taken on the indicated days, where the samples were exposed to the indicated treatments.

[0191] [Figure 72] FIG. 72 shows representative microscopic (15×) photographic images of MelanoDerm™ samples exposed to CV-8686 (Compound I) and kojic acid, taken on the indicated days, where the samples were exposed to the indicated treatments.

[0192] [Figure 73] FIG. 73 shows representative macroscopic photographic images of MelanoDerm™ samples exposed to CV-8686 (Compound I) and kojic acid, taken on the indicated days, where the samples were exposed to the indicated treatments.

[0193] [Figure 74] FIG. 74 shows representative macroscopic photographic images of MelanoDerm™ samples exposed to CV-8686 (Compound I) and kojic acid, taken on the indicated days, where the samples were exposed to the indicated treatments.

[0194] [Figure 75]Figure 75 is a table showing the mean tissue viability and melanin concentration data resolved from MelanoDerm™ substrates treated with various concentrations of the indicated compounds. Where the sponsor's designation is blank, the sample was of unknown composition.

[0195] [Figure 76] FIG. 76 shows representative macroscopic photographic images of MelanoDerm™ samples exposed to the indicated treatments, taken on the indicated days.

[0196] [Figure 77] Figure 77 shows representative macroscopic photographic images of MelanoDerm™ samples exposed to the indicated treatments, taken 7 days after treatment. Where the compound name is blank, the sample was of unknown composition.

[0197] [Figure 78] FIG. 78 shows representative microscopic (15×) photographic images of MelanoDerm™ samples exposed to the indicated treatments, taken on the indicated days.

[0198] [Figure 79] Figure 79 shows representative microscopic (15x) photographic images of MelanoDerm™ samples exposed to the indicated treatments, taken on the indicated days. Where the compound name is blank, the sample was of unknown composition.

[0199] [Figure 80] Figures 80-87 show representative macroscopic photographic images of MelanoDerm™ samples exposed to the indicated treatments taken on day 7. In Figure 85, where the compound name is blank, the sample was of unknown composition. [Figure 81] Figures 80-87 show representative macroscopic photographic images of MelanoDerm™ samples exposed to the indicated treatments taken on day 7. In Figure 85, where the compound name is blank, the sample was of unknown composition. [Figure 82] Figures 80-87 show representative macroscopic photographic images of MelanoDerm™ samples exposed to the indicated treatments taken on day 7. In Figure 85, where the compound name is blank, the sample was of unknown composition. [Figure 83] Figures 80-87 show representative macroscopic photographic images of MelanoDerm™ samples exposed to the indicated treatments taken on day 7. In Figure 85, where the compound name is blank, the sample was of unknown composition. [Figure 84] Figures 80-87 show representative macroscopic photographic images of MelanoDerm™ samples exposed to the indicated treatments taken on day 7. In Figure 85, where the compound name is blank, the sample was of unknown composition. [Figure 85] Figures 80-87 show representative macroscopic photographic images of MelanoDerm™ samples exposed to the indicated treatments taken on day 7. In Figure 85, where the compound name is blank, the sample was of unknown composition. [Figure 86] Figures 80-87 show representative macroscopic photographic images of MelanoDerm™ samples exposed to the indicated treatments taken on day 7. In Figure 85, where the compound name is blank, the sample was of unknown composition. [Figure 87] Figures 80-87 show representative macroscopic photographic images of MelanoDerm™ samples exposed to the indicated treatments taken on day 7. In Figure 85, where the compound name is blank, the sample was of unknown composition.

[0200] [Figure 88] FIG. 88 is a table showing mean tissue viability and melanin concentration data resolved from MelanoDerm™ matrices treated with various concentrations of the indicated compounds.

[0201] [Figure 89-1]Figures 89A-89X show histograms of B16 melanocyte viability and percent melanin change after the indicated treatments. In Figures 89M-89N, where the compound name is blank, the sample was of unknown composition. [Figure 89-2] Figures 89A-89X show histograms of B16 melanocyte viability and percent melanin change after the indicated treatments. In Figures 89M-89N, where the compound name is blank, the sample was of unknown composition. [Figure 89-3] Figures 89A-89X show histograms of B16 melanocyte viability and percent melanin change after the indicated treatments. In Figures 89M-89N, where the compound name is blank, the sample was of unknown composition. [Figure 89-4] Figures 89A-89X show histograms of B16 melanocyte viability and percent melanin change after the indicated treatments. In Figures 89M-89N, where the compound name is blank, the sample was of unknown composition. [Figure 89-5] Figures 89A-89X show histograms of B16 melanocyte viability and percent melanin change after the indicated treatments. In Figures 89M-89N, where the compound name is blank, the sample was of unknown composition. [Figure 89-6] Figures 89A-89X show histograms of B16 melanocyte viability and percent melanin change after the indicated treatments. In Figures 89M-89N, where the compound name is blank, the sample was of unknown composition. [Figure 89-7] Figures 89A-89X show histograms of B16 melanocyte viability and percent melanin change after the indicated treatments. In Figures 89M-89N, where the compound name is blank, the sample was of unknown composition. [Figure 89-8] Figures 89A-89X show histograms of B16 melanocyte viability and percent melanin change after the indicated treatments. In Figures 89M-89N, where the compound name is blank, the sample was of unknown composition. [Figure 89-9]Figures 89A-89X show histograms of B16 melanocyte viability and percent melanin change after the indicated treatments. In Figures 89M-89N, where the compound name is blank, the sample was of unknown composition. [Figure 89-10] Figures 89A-89X show histograms of B16 melanocyte viability and percent melanin change after the indicated treatments. In Figures 89M-89N, where the compound name is blank, the sample was of unknown composition. [Figure 89-11] Figures 89A-89X show histograms of B16 melanocyte viability and percent melanin change after the indicated treatments. In Figures 89M-89N, where the compound name is blank, the sample was of unknown composition. [Figure 89-12] Figures 89A-89X show histograms of B16 melanocyte viability and percent melanin change after the indicated treatments. In Figures 89M-89N, where the compound name is blank, the sample was of unknown composition.

[0202] [Figure 90-1] Figures 90A, 90C, and 90E show tables of data including the percentage of Annexin V-positive B16F1 cells (Figure 90A), MeWo cells (Figure 90C), and WM115 cells (Figure 90E) at 6, 24, 48, and 72 hours after exposure to staurosporine. Figures 90B, 90D, and 90F show tables of data including the percentage of propidium iodide (PI)-positive B16F1 cells (Figure 90B), MeWo cells (Figure 90D), and WM115 cells (Figure 90F) at 6, 24, 48, and 72 hours after exposure to staurosporine. [Figure 90-2]Figures 90A, 90C, and 90E show tables of data including the percentage of Annexin V-positive B16F1 cells (Figure 90A), MeWo cells (Figure 90C), and WM115 cells (Figure 90E) at 6, 24, 48, and 72 hours after exposure to staurosporine. Figures 90B, 90D, and 90F show tables of data including the percentage of propidium iodide (PI)-positive B16F1 cells (Figure 90B), MeWo cells (Figure 90D), and WM115 cells (Figure 90F) at 6, 24, 48, and 72 hours after exposure to staurosporine.

[0203] [Figure 91-1] Figures 91A, 91C, and 91E show tables of data including the percentage of Annexin V-positive B16F1 cells (Figure 91A), MeWo cells (Figure 91C), and WM115 cells (Figure 91E) at 6, 24, 48, and 72 hours after exposure to Compound H (AB12509). Figures 91B, 91D, and 91F show tables of data including the percentage of propidium iodide (PI)-positive B16F1 cells (Figure 91B), MeWo cells (Figure 91D), and WM115 cells (Figure 91F) at 6, 24, 48, and 72 hours after exposure to Compound H (AB12509). [Figure 91-2] Figures 91A, 91C, and 91E show tables of data including the percentage of Annexin V-positive B16F1 cells (Figure 91A), MeWo cells (Figure 91C), and WM115 cells (Figure 91E) at 6, 24, 48, and 72 hours after exposure to Compound H (AB12509). Figures 91B, 91D, and 91F show tables of data including the percentage of propidium iodide (PI)-positive B16F1 cells (Figure 91B), MeWo cells (Figure 91D), and WM115 cells (Figure 91F) at 6, 24, 48, and 72 hours after exposure to Compound H (AB12509).

[0204] [Figure 92-1]Figures 92A, 92C, and 92E show tables of data including the percentage of Annexin V-positive B16F1 cells (Figure 92A), MeWo cells (Figure 92C), and WM115 cells (Figure 92E) at 6, 24, 48, and 72 hours after exposure to malasedin (CV-8684). Figures 92B, 92D, and 92F show tables of data including the percentage of propidium iodide (PI)-positive B16F1 cells (Figure 92B), MeWo cells (Figure 92D), and WM115 cells (Figure 92F) at 6, 24, 48, and 72 hours after exposure to malasedin (CV-8684). [Figure 92-2] Figures 92A, 92C, and 92E show tables of data including the percentage of Annexin V-positive B16F1 cells (Figure 92A), MeWo cells (Figure 92C), and WM115 cells (Figure 92E) at 6, 24, 48, and 72 hours after exposure to malasedin (CV-8684). Figures 92B, 92D, and 92F show tables of data including the percentage of propidium iodide (PI)-positive B16F1 cells (Figure 92B), MeWo cells (Figure 92D), and WM115 cells (Figure 92F) at 6, 24, 48, and 72 hours after exposure to malasedin (CV-8684).

[0205] [Figure 93-1] Figures 93A, 93C, and 93E show tables of data including the percentage of Annexin V-positive B16F1 cells (Figure 93A), MeWo cells (Figure 93C), and WM115 cells (Figure 93E) at 6, 24, 48, and 72 hours after exposure to Compound B (CV-8877). Figures 93B, 93D, and 93F show tables of data including the percentage of propidium iodide (PI)-positive B16F1 cells (Figure 93B), MeWo cells (Figure 93D), and WM115 cells (Figure 93F) at 6, 24, 48, and 72 hours after exposure to Compound B (CV-8877). [Figure 93-2]Figures 93A, 93C, and 93E show tables of data including the percentage of Annexin V-positive B16F1 cells (Figure 93A), MeWo cells (Figure 93C), and WM115 cells (Figure 93E) at 6, 24, 48, and 72 hours after exposure to Compound B (CV-8877). Figures 93B, 93D, and 93F show tables of data including the percentage of propidium iodide (PI)-positive B16F1 cells (Figure 93B), MeWo cells (Figure 93D), and WM115 cells (Figure 93F) at 6, 24, 48, and 72 hours after exposure to Compound B (CV-8877).

[0206] [Figure 94-1] Figures 94A, 94C, and 94E show tables of data including the percentage of Annexin V-positive B16F1 cells (Figure 94A), MeWo cells (Figure 94C), and WM115 cells (Figure 94E) at 6, 24, 48, and 72 hours after exposure to Compound I (CV-8686). Figures 94B, 94D, and 94F show tables of data including the percentage of propidium iodide (PI)-positive B16F1 cells (Figure 94B), MeWo cells (Figure 94D), and WM115 cells (Figure 94F) at 6, 24, 48, and 72 hours after exposure to Compound I (CV-8686). [Figure 94-2] Figures 94A, 94C, and 94E show tables of data including the percentage of Annexin V-positive B16F1 cells (Figure 94A), MeWo cells (Figure 94C), and WM115 cells (Figure 94E) at 6, 24, 48, and 72 hours after exposure to Compound I (CV-8686). Figures 94B, 94D, and 94F show tables of data including the percentage of propidium iodide (PI)-positive B16F1 cells (Figure 94B), MeWo cells (Figure 94D), and WM115 cells (Figure 94F) at 6, 24, 48, and 72 hours after exposure to Compound I (CV-8686).

[0207] [Figure 95-1]Figures 95A, 95C, and 95E show tables of data including the percentage of Annexin V-positive B16F1 cells (Figure 95A), MeWo cells (Figure 95C), and WM115 cells (Figure 95E) at 6, 24, 48, and 72 hours after exposure to Compound B10. Figures 95B, 95D, and 95F show tables of data including the percentage of propidium iodide (PI)-positive B16F1 cells (Figure 95B), MeWo cells (Figure 95D), and WM115 cells (Figure 95F) at 6, 24, 48, and 72 hours after exposure to Compound B10. [Figure 95-2] Figures 95A, 95C, and 95E show tables of data including the percentage of Annexin V-positive B16F1 cells (Figure 95A), MeWo cells (Figure 95C), and WM115 cells (Figure 95E) at 6, 24, 48, and 72 hours after exposure to Compound B10. Figures 95B, 95D, and 95F show tables of data including the percentage of propidium iodide (PI)-positive B16F1 cells (Figure 95B), MeWo cells (Figure 95D), and WM115 cells (Figure 95F) at 6, 24, 48, and 72 hours after exposure to Compound B10.

[0208] [Figure 96-1] Figures 96A, 96C, and 96E show tables of data including the percentage of Annexin V-positive B16F1 cells (Figure 96A), MeWo cells (Figure 96C), and WM115 cells (Figure 96E) at 6, 24, 48, and 72 hours after exposure to Compound II (CV-8688). Figures 96B, 96D, and 96F show tables of data including the percentage of propidium iodide (PI)-positive B16F1 cells (Figure 96B), MeWo cells (Figure 96D), and WM115 cells (Figure 96F) at 6, 24, 48, and 72 hours after exposure to Compound II (CV-8688). [Figure 96-2]Figures 96A, 96C, and 96E show tables of data including the percentage of Annexin V-positive B16F1 cells (Figure 96A), MeWo cells (Figure 96C), and WM115 cells (Figure 96E) at 6, 24, 48, and 72 hours after exposure to Compound II (CV-8688). Figures 96B, 96D, and 96F show tables of data including the percentage of propidium iodide (PI)-positive B16F1 cells (Figure 96B), MeWo cells (Figure 96D), and WM115 cells (Figure 96F) at 6, 24, 48, and 72 hours after exposure to Compound II (CV-8688).

[0209] [Figure 97-1] Figures 97A, 97C, and 97E show tables of data including the percentage of Annexin V-positive B16F1 cells (Figure 97A), MeWo cells (Figure 97C), and WM115 cells (Figure 97E) at 6, 24, 48, and 72 hours after exposure to malassedin precursors. Figures 97B, 97D, and 97F show tables of data including the percentage of propidium iodide (PI)-positive B16F1 cells (Figure 97B), MeWo cells (Figure 97D), and WM115 cells (Figure 97F) at 6, 24, 48, and 72 hours after exposure to malassedin precursors. [Figure 97-2] Figures 97A, 97C, and 97E show tables of data including the percentage of Annexin V-positive B16F1 cells (Figure 97A), MeWo cells (Figure 97C), and WM115 cells (Figure 97E) at 6, 24, 48, and 72 hours after exposure to malassedin precursors. Figures 97B, 97D, and 97F show tables of data including the percentage of propidium iodide (PI)-positive B16F1 cells (Figure 97B), MeWo cells (Figure 97D), and WM115 cells (Figure 97F) at 6, 24, 48, and 72 hours after exposure to malassedin precursors.

[0210] [Figure 98-1]Figures 98A, 98C, and 98E show tables of data including the percentage of Annexin V-positive B16F1 cells (Figure 98A), MeWo cells (Figure 98C), and WM115 cells (Figure 98E) at 6, 24, 48, and 72 hours after exposure to indolo[3,2-b]carbazole (CV-8685). Figures 98B, 98D, and 98F show tables of data including the percentage of propidium iodide (PI)-positive B16F1 cells (Figure 98B), MeWo cells (Figure 98D), and WM115 cells (Figure 98F) at 6, 24, 48, and 72 hours after exposure to indolo[3,2-b]carbazole (CV-8685). [Figure 98-2] Figures 98A, 98C, and 98E show tables of data including the percentage of Annexin V-positive B16F1 cells (Figure 98A), MeWo cells (Figure 98C), and WM115 cells (Figure 98E) at 6, 24, 48, and 72 hours after exposure to indolo[3,2-b]carbazole (CV-8685). Figures 98B, 98D, and 98F show tables of data including the percentage of propidium iodide (PI)-positive B16F1 cells (Figure 98B), MeWo cells (Figure 98D), and WM115 cells (Figure 98F) at 6, 24, 48, and 72 hours after exposure to indolo[3,2-b]carbazole (CV-8685).

[0211] [Figure 99-1] Figures 99A, 99C, and 99E show tables of data including the percentage of Annexin V-positive B16F1 cells (Figure 99A), MeWo cells (Figure 99C), and WM115 cells (Figure 99E) at 6, 24, 48, and 72 hours after exposure to AB17151. Figures 99B, 99D, and 99F show tables of data including the percentage of propidium iodide (PI)-positive B16F1 cells (Figure 99B), MeWo cells (Figure 99D), and WM115 cells (Figure 99F) at 6, 24, 48, and 72 hours after exposure to AB17151. [Figure 99-2]Figures 99A, 99C, and 99E show tables of data including the percentage of Annexin V-positive B16F1 cells (Figure 99A), MeWo cells (Figure 99C), and WM115 cells (Figure 99E) at 6, 24, 48, and 72 hours after exposure to AB17151. Figures 99B, 99D, and 99F show tables of data including the percentage of propidium iodide (PI)-positive B16F1 cells (Figure 99B), MeWo cells (Figure 99D), and WM115 cells (Figure 99F) at 6, 24, 48, and 72 hours after exposure to AB17151.

[0212] [Figure 100-1] Figures 100A, 100C, and 100E show tables of data including the percentage of Annexin V-positive B16F1 cells (Figure 100A), MeWo cells (Figure 100C), and WM115 cells (Figure 100E) at 6, 24, 48, and 72 hours after exposure to Compound IV (CV-8687). Figures 100B, 100D, and 100F show tables of data including the percentage of propidium iodide (PI)-positive B16F1 cells (Figure 100B), MeWo cells (Figure 100D), and WM115 cells (Figure 100F) at 6, 24, 48, and 72 hours after exposure to Compound IV (CV-8687). [Figure 100-2] Figures 100A, 100C, and 100E show tables of data including the percentage of Annexin V-positive B16F1 cells (Figure 100A), MeWo cells (Figure 100C), and WM115 cells (Figure 100E) at 6, 24, 48, and 72 hours after exposure to Compound IV (CV-8687). Figures 100B, 100D, and 100F show tables of data including the percentage of propidium iodide (PI)-positive B16F1 cells (Figure 100B), MeWo cells (Figure 100D), and WM115 cells (Figure 100F) at 6, 24, 48, and 72 hours after exposure to Compound IV (CV-8687).

[0213] [Figure 101-1]Figures 101A, 101C, and 101E show tables of data including the percentage of Annexin V-positive B16F1 cells (Figure 101A), MeWo cells (Figure 101C), and WM115 cells (Figure 101E) at 6, 24, 48, and 72 hours after exposure to AB17011. Figures 101B, 101D, and 101F show tables of data including the percentage of propidium iodide (PI)-positive B16F1 cells (Figure 101B), MeWo cells (Figure 101D), and WM115 cells (Figure 101F) at 6, 24, 48, and 72 hours after exposure to AB17011. [Figure 101-2] Figures 101A, 101C, and 101E show tables of data including the percentage of Annexin V-positive B16F1 cells (Figure 101A), MeWo cells (Figure 101C), and WM115 cells (Figure 101E) at 6, 24, 48, and 72 hours after exposure to AB17011. Figures 101B, 101D, and 101F show tables of data including the percentage of propidium iodide (PI)-positive B16F1 cells (Figure 101B), MeWo cells (Figure 101D), and WM115 cells (Figure 101F) at 6, 24, 48, and 72 hours after exposure to AB17011.

[0214] [Figure 102-1] Figures 102A, 102C, and 102E show tables of data including the percentage of Annexin V-positive B16F1 cells (Figure 102A), MeWo cells (Figure 102C), and WM115 cells (Figure 102E) at 6, 24, 48, and 72 hours after exposure to ABl 1644. Figures 102B, 102D, and 102F show tables of data including the percentage of propidium iodide (PI)-positive B16F1 cells (Figure 102B), MeWo cells (Figure 102D), and WM115 cells (Figure 102F) at 6, 24, 48, and 72 hours after exposure to ABl 1644. [Figure 102-2]Figures 102A, 102C, and 102E show tables of data including the percentage of Annexin V-positive B16F1 cells (Figure 102A), MeWo cells (Figure 102C), and WM115 cells (Figure 102E) at 6, 24, 48, and 72 hours after exposure to ABl 1644. Figures 102B, 102D, and 102F show tables of data including the percentage of propidium iodide (PI)-positive B16F1 cells (Figure 102B), MeWo cells (Figure 102D), and WM115 cells (Figure 102F) at 6, 24, 48, and 72 hours after exposure to ABl 1644.

[0215] [Figure 103-1] Figures 103A, 103C, and 103E show tables of data including the percentage of Annexin V-positive B16F1 cells (Figure 103A), MeWo cells (Figure 103C), and WM115 cells (Figure 103E) at 6, 24, 48, and 72 hours after exposure to AB17014. Figures 103B, 103D, and 103F show tables of data including the percentage of propidium iodide (PI)-positive B16F1 cells (Figure 103B), MeWo cells (Figure 103D), and WM115 cells (Figure 103F) at 6, 24, 48, and 72 hours after exposure to AB17014. [Figure 103-2] Figures 103A, 103C, and 103E show tables of data including the percentage of Annexin V-positive B16F1 cells (Figure 103A), MeWo cells (Figure 103C), and WM115 cells (Figure 103E) at 6, 24, 48, and 72 hours after exposure to AB17014. Figures 103B, 103D, and 103F show tables of data including the percentage of propidium iodide (PI)-positive B16F1 cells (Figure 103B), MeWo cells (Figure 103D), and WM115 cells (Figure 103F) at 6, 24, 48, and 72 hours after exposure to AB17014.

[0216] [Figure 104-1]Figures 104A, 104C, and 104E show tables of data including the percentage of Annexin V-positive B16F1 cells (Figure 104A), MeWo cells (Figure 104C), and WM115 cells (Figure 104E) at 6, 24, 48, and 72 hours after exposure to an unknown composition. Figures 104B, 104D, and 104F show tables of data including the percentage of propidium iodide (PI)-positive B16F1 cells (Figure 104B), MeWo cells (Figure 104D), and WM115 cells (Figure 104F) at 6, 24, 48, and 72 hours after exposure to an unknown composition. [Figure 104-2] Figures 104A, 104C, and 104E show tables of data including the percentage of Annexin V-positive B16F1 cells (Figure 104A), MeWo cells (Figure 104C), and WM115 cells (Figure 104E) at 6, 24, 48, and 72 hours after exposure to an unknown composition. Figures 104B, 104D, and 104F show tables of data including the percentage of propidium iodide (PI)-positive B16F1 cells (Figure 104B), MeWo cells (Figure 104D), and WM115 cells (Figure 104F) at 6, 24, 48, and 72 hours after exposure to an unknown composition.

[0217] [Figure 105-1] Figures 105A, 105C, and 105E show tables of data including the percentage of Annexin V-positive B16F1 cells (Figure 105A), MeWo cells (Figure 105C), and WM115 cells (Figure 105E) at 6, 24, 48, and 72 hours after exposure to AB17225. Figures 105B, 105D, and 105F show tables of data including the percentage of propidium iodide (PI)-positive B16F1 cells (Figure 105B), MeWo cells (Figure 105D), and WM115 cells (Figure 105F) at 6, 24, 48, and 72 hours after exposure to AB17225. [Figure 105-2]Figures 105A, 105C, and 105E show tables of data including the percentage of Annexin V-positive B16F1 cells (Figure 105A), MeWo cells (Figure 105C), and WM115 cells (Figure 105E) at 6, 24, 48, and 72 hours after exposure to AB17225. Figures 105B, 105D, and 105F show tables of data including the percentage of propidium iodide (PI)-positive B16F1 cells (Figure 105B), MeWo cells (Figure 105D), and WM115 cells (Figure 105F) at 6, 24, 48, and 72 hours after exposure to AB17225.

[0218] [Figure 106-1] Figures 106A, 106C, and 106E show tables of data including the percentage of Annexin V-positive B16F1 cells (Figure 106A), MeWo cells (Figure 106C), and WM115 cells (Figure 106E) at 6, 24, 48, and 72 hours after exposure to Compound A5 (CV-8819). Figures 106B, 106D, and 106F show tables of data including the percentage of propidium iodide (PI)-positive B16F1 cells (Figure 106B), MeWo cells (Figure 106D), and WM115 cells (Figure 106F) at 6, 24, 48, and 72 hours after exposure to Compound A5 (CV-8819). [Figure 106-2] Figures 106A, 106C, and 106E show tables of data including the percentage of Annexin V-positive B16F1 cells (Figure 106A), MeWo cells (Figure 106C), and WM115 cells (Figure 106E) at 6, 24, 48, and 72 hours after exposure to Compound A5 (CV-8819). Figures 106B, 106D, and 106F show tables of data including the percentage of propidium iodide (PI)-positive B16F1 cells (Figure 106B), MeWo cells (Figure 106D), and WM115 cells (Figure 106F) at 6, 24, 48, and 72 hours after exposure to Compound A5 (CV-8819).

[0219] [Figure 107-1]Figures 107A, 107C, and 107E show tables of data including the percentage of Annexin V-positive B16F1 cells (Figure 107A), MeWo cells (Figure 107C), and WM115 cells (Figure 107E) at 6, 24, 48, and 72 hours after exposure to AB12976. Figures 107B, 107D, and 107F show tables of data including the percentage of propidium iodide (PI)-positive B16F1 cells (Figure 107B), MeWo cells (Figure 107D), and WM115 cells (Figure 107F) at 6, 24, 48, and 72 hours after exposure to AB12976. [Figure 107-2] Figures 107A, 107C, and 107E show tables of data including the percentage of Annexin V-positive B16F1 cells (Figure 107A), MeWo cells (Figure 107C), and WM115 cells (Figure 107E) at 6, 24, 48, and 72 hours after exposure to AB12976. Figures 107B, 107D, and 107F show tables of data including the percentage of propidium iodide (PI)-positive B16F1 cells (Figure 107B), MeWo cells (Figure 107D), and WM115 cells (Figure 107F) at 6, 24, 48, and 72 hours after exposure to AB12976.

[0220] [Figure 108-1] Figures 108A, 108C, and 108E show tables of data including the percentage of Annexin V-positive B16F1 cells (Figure 108A), MeWo cells (Figure 108C), and WM115 cells (Figure 108E) at 6, 24, 48, and 72 hours after exposure to Compound E (AB12508). Figures 108B, 108D, and 108F show tables of data including the percentage of propidium iodide (PI)-positive B16F1 cells (Figure 108B), MeWo cells (Figure 108D), and WM115 cells (Figure 108F) at 6, 24, 48, and 72 hours after exposure to Compound E (AB12508). [Figure 108-2]Figures 108A, 108C, and 108E show tables of data including the percentage of Annexin V-positive B16F1 cells (Figure 108A), MeWo cells (Figure 108C), and WM115 cells (Figure 108E) at 6, 24, 48, and 72 hours after exposure to Compound E (AB12508). Figures 108B, 108D, and 108F show tables of data including the percentage of propidium iodide (PI)-positive B16F1 cells (Figure 108B), MeWo cells (Figure 108D), and WM115 cells (Figure 108F) at 6, 24, 48, and 72 hours after exposure to Compound E (AB12508).

[0221] [Figure 109] 109A, 109B, and 109C show tables of data containing the caspase 3 / 7 induction rate in B16F1, MeWo, and WM115 cells compared to vehicle control at 6, 24, 48, and 72 hours, respectively, after exposure to staurosporine.

[0222] [Figure 110] Figures 110A, 110B and 110C show tables of data including the caspase 3 / 7 induction rate in B16F1 cells, MeWo cells and WM115 cells compared to vehicle control at 6, 24, 48 and 72 hours, respectively, after exposure to malasedin (CV-8684).

[0223] [Figure 111] Figures 111A, 111B, and 111C show tables of data including caspase 3 / 7 induction rates in B16F1 cells, MeWo cells, and WM115 cells compared to vehicle controls at 6, 24, 48, and 72 hours after exposure to Compound I (CV-8686), respectively.

[0224] [Figure 112]Figures 112A, 112B, and 112C show tables of data including caspase 3 / 7 induction rates in B16F1 cells, MeWo cells, and WM115 cells compared to vehicle controls at 6, 24, 48, and 72 hours after exposure to Compound II (CV-8688), respectively.

[0225] [Figure 113] Figures 113A, 113B, and 113C show tables of data containing caspase 3 / 7 induction rates in B16F1, MeWo, and WM115 cells, respectively, after exposure to indolo[3,2-b]carbazole (CV-8685) compared to vehicle control at 6, 24, 48, and 72 hours.

[0226] [Figure 114] Figures 114A, 114B, and 114C show tables of data including caspase 3 / 7 induction rates in B16F1, MeWo, and WM115 cells compared to vehicle controls at 6, 24, 48, and 72 hours, respectively, after exposure to Compound IV (CV-8687).

[0227] [Figure 115] 115A, 115B, and 115C show tables of data containing the caspase 3 / 7 induction rate in B16F1, MeWo, and WM115 cells compared to vehicle control at 6, 24, 48, and 72 hours, respectively, after exposure to ABl 1644.

[0228] [Figure 116] Figures 116A, 116B, and 116C show tables of data including caspase 3 / 7 induction rates in B16F1, MeWo, and WM115 cells compared to vehicle controls at 6, 24, 48, and 72 hours, respectively, after exposure to an unknown composition.

[0229] [Figure 117]Figures 117A, 117B, and 117C show tables of data containing the caspase 3 / 7 induction rate in B16F1, MeWo, and WM115 cells compared to vehicle control at 6, 24, 48, and 72 hours, respectively, after exposure to Compound A5 (CV-8819).

[0230] [Figure 118] Figures 118A, 118B, and 118C show tables of data containing the caspase 3 / 7 induction rate in B16F1 cells, MeWo cells, and WM115 cells compared to vehicle control at 6, 24, 48, and 72 hours, respectively, after exposure to Compound E (AB12508).

[0231] [Figure 119] Figures 119A, 119B, and 119C show tables of data containing caspase 3 / 7 induction rates in B16F1, MeWo, and WM115 cells compared to vehicle controls at 6, 24, 48, and 72 hours, respectively, after exposure to Compound H (AB12509).

[0232] [Figure 120] Figures 120A, 120B, and 120C show tables of data containing the caspase 3 / 7 induction rate in B16F1, MeWo, and WM115 cells compared to vehicle control at 6, 24, 48, and 72 hours, respectively, after exposure to Compound B (CV-8877).

[0233] [Figure 121] 121A, 121B, and 121C show tables of data containing the caspase 3 / 7 induction rate in B16F1, MeWo, and WM115 cells compared to vehicle control at 6, 24, 48, and 72 hours, respectively, after exposure to compound B10.

[0234] [Figure 122]Figures 122A, 122B and 122C show tables of data containing the caspase 3 / 7 induction rate in B16F1, MeWo and WM115 cells compared to vehicle control at 6, 24, 48 and 72 hours, respectively, after exposure to malasedin precursors.

[0235] [Figure 123] 123A, 123B, and 123C show tables of data containing the caspase 3 / 7 induction rate in B16F1, MeWo, and WM115 cells compared to vehicle control at 6, 24, 48, and 72 hours, respectively, after exposure to AB17151.

[0236] [Figure 124] 124A, 124B, and 124C show tables of data containing the caspase 3 / 7 induction rate in B16F1, MeWo, and WM115 cells compared to vehicle control at 6, 24, 48, and 72 hours, respectively, after exposure to AB17011.

[0237] [Figure 125] 125A, 125B, and 125C show tables of data containing the caspase 3 / 7 induction rate in B16F1, MeWo, and WM115 cells compared to vehicle control at 6, 24, 48, and 72 hours, respectively, after exposure to AB17014.

[0238] [Figure 126] 126A, 126B, and 126C show tables of data containing the percent caspase 3 / 7 induction in B16F1, MeWo, and WM115 cells compared to vehicle control at 6, 24, 48, and 72 hours, respectively, after exposure to AB17225.

[0239] [Figure 127]127A, 127B, and 127C show tables of data containing the percentage of caspase 3 / 7 induction in B16F1, MeWo, and WM115 cells compared to vehicle control at 6, 24, 48, and 72 hours, respectively, after exposure to ABl2976.

[0240] [Figure 128-1] 128-129 are tables showing mean tissue viability and melanin concentration data resolved from separate experiments using MelanoDerm™ substrates treated with various concentrations of the indicated test articles. [Figure 128-2] 128-129 are tables showing mean tissue viability and melanin concentration data resolved from separate experiments using MelanoDerm™ substrates treated with various concentrations of the indicated test articles. [Figure 129-1] 128-129 are tables showing mean tissue viability and melanin concentration data resolved from separate experiments using MelanoDerm™ substrates treated with various concentrations of the indicated test articles. [Figure 129-2] 128-129 are tables showing mean tissue viability and melanin concentration data resolved from separate experiments using MelanoDerm™ substrates treated with various concentrations of the indicated test articles.

[0241] [Figure 130-1] FIG. 130 shows compounds produced by Malassezia. [Figure 130-2] FIG. 130 shows compounds produced by Malassezia. [Figure 130-3] FIG. 130 shows compounds produced by Malassezia. [Figure 130-4] FIG. 130 shows compounds produced by Malassezia.

[0242] [Figure 131]FIG. 131 is a table showing mean tissue viability and melanin concentration data resolved from separate experiments using MelanoDerm™ substrates treated with various concentrations of the indicated test article / composition. [Figure 132] FIG. 132 is a table showing mean tissue viability and melanin concentration data resolved from separate experiments using MelanoDerm™ substrates treated with various concentrations of the indicated test article / composition.

[0243] [Figure 133A] Figures 133A-133B show synthetic schemes for AB17590 (Figure 133A) and AB17653, AB17654, AB17655, AB17656, AB17657 and AB17658 (Figure 133B). [Figure 133B] Figures 133A-133B show synthetic schemes for AB17590 (Figure 133A) and AB17653, AB17654, AB17655, AB17656, AB17657 and AB17658 (Figure 133B).

[0244] [Figure 134] Figure 134 is a schematic diagram showing the type of skin treatment for a patient with skin type IV. Values ​​indicate UV dose of any area in mJ / cm2.

[0245] [Figure 135] FIG. 135 is a table showing the Dualight scale for skin types I-VI.

[0246] [Figure 136] FIG. 136 is a table showing the Mexameter MX16 measurements of melanin and erythema on the eighth day after irradiation on the seventh day.

[0247] [Figure 137-1] FIG. 137 is a table showing the Mexameter MX16 measurements of melanin and erythema on the 15th day after the 14th day of irradiation. [Figure 137-2] FIG. 137 is a table showing the Mexameter MX16 measurements of melanin and erythema on the 15th day after the 14th day of irradiation.

[0248] [Figure 138] Figure 138 is a table showing the erythema scale, which is a numerical value associated with various degrees of erythema.

[0249] [Figure 139] Figure 139 is a photograph showing the skin of a subject 24 hours after irradiation with various levels of UV according to the type of skin treatment shown in Figure 7. The minimal erythema dose ("MED") 24 hours after irradiation was 120 mJ UVB.

[0250] [Figure 140] FIG. 140 is a photograph showing the test site on the subject's skin on day 7.

[0251] [Figure 141] Figure 141 is a photograph showing the test site on the subject's skin on day 8, 24 hours after irradiation with 120 mJ UVB.

[0252] [Figure 142] Figure 142 is a photograph showing the test site on the subject's skin on day 14, after an additional week of malasedin treatment. The treatment area was administered 120 mJ UVB.

[0253] [Figure 143] Figure 143 is a photograph showing the test site on the subject's skin on day 15, 24 hours after irradiation with 120 mJ UVB. Note the presence of erythema at the vehicle site on days 7 and 9. Also note the presence of minimal to mild erythema at the Malasedin 1% treatment site on days 14, 10, and 8, with slight erythema on days 1 and 3. DETAILED DESCRIPTION OF THE INVENTION

[0254] One embodiment of the present invention is a skin lightening compound that is a chemical analog of a compound produced by Malassezia yeast, or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0255] In one aspect of this embodiment, the compound produced by Malassezia yeast has the structure of formula (I): [ka] It has.

[0256] In another aspect of this embodiment, the compound is a chemical analog of malasedin.

[0257] Another embodiment of the present invention is a compound that induces melanocyte apoptosis, which is a chemical analog of a compound produced by Malassezia yeast, or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0258] In one aspect of this embodiment, the compound produced by Malassezia yeast has the structure of formula (I): [ka] It has.

[0259] In another aspect of this embodiment, the compound is a chemical analog of malasedin.

[0260] A further embodiment of the present invention is a compound that modulates melanocyte activity, which is a chemical analog of a compound produced by Malassezia yeast, or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0261] In one aspect of this embodiment, the compound produced by Malassezia yeast has the structure of formula (I): [ka] It has.

[0262] In another aspect of this embodiment, the compound is a chemical analog of malasedin.

[0263] An additional embodiment of the present invention is a compound that agonizes the aromatic hydrocarbon receptor (AhR), which is a chemical analog of a compound produced by Malassezia yeast, or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0264] In one aspect of this embodiment, the compound produced by Malassezia yeast has the structure of formula (I): [ka] It has.

[0265] In another aspect of this embodiment, the compound is a chemical analog of malasedin.

[0266] Another embodiment of the present invention is a compound that improves hyperpigmentation caused by hyperpigmentation disorders, the compound being a chemical analog of a compound produced by Malassezia yeast, or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0267] In one aspect of this embodiment, the compound produced by Malassezia yeast has the structure of formula (I): [ka] It has.

[0268] In another aspect of this embodiment, the compound is a chemical analog of malasedin.

[0269] A further embodiment of the present invention is a compound that modulates melanin production, which is a chemical analog of a compound produced by Malassezia yeast, or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0270] In one aspect of this embodiment, the compound produced by Malassezia yeast has the structure of formula (I): [ka] It has.

[0271] In another aspect of this embodiment, the compound is a chemical analog of malasedin.

[0272] An additional embodiment of the present invention is a compound that modulates melanosome biogenesis. The compound may be a chemical analog of a compound produced by Malassezia yeast, or or its crystalline form, hydrate, or a cosmetically or pharmaceutically acceptable salt thereof.

[0273] In one aspect of this embodiment, the compound produced by Malassezia yeast has the structure of formula (I): [ka] It has.

[0274] In another aspect of this embodiment, the compound is a chemical analog of malasedin.

[0275] Another embodiment of the present invention is a compound that modulates melanosome transport, the compound being a chemical analog of a compound produced by Malassezia yeast, or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0276] In one aspect of this embodiment, the compound produced by Malassezia yeast has the structure of formula (I): [ka] It has.

[0277] In another aspect of this embodiment, the compound is a chemical analog of malasedin.

[0278] A further embodiment of the present invention is a composition comprising Malassezia yeast and a cosmetically or pharmaceutically acceptable vehicle, diluent or carrier.

[0279] An additional embodiment of the present invention is a composition comprising a compound isolated or isolatable from Malassezia yeast and a cosmetically or pharmaceutically acceptable vehicle, diluent, or carrier.

[0280] Another embodiment of the present invention is a composition comprising any of the compounds disclosed herein, including analogs, and a cosmetically or pharmaceutically acceptable vehicle, diluent, or carrier.

[0281] A further embodiment of the invention is a method of lightening skin in a subject, comprising the step of contacting the subject with any of the compounds or compositions disclosed herein.

[0282] An additional embodiment of the invention is a method of inducing melanocyte apoptosis in a subject, comprising contacting the subject with any of the compounds or compositions disclosed herein.

[0283] Another embodiment of the invention is a method of modulating melanocyte activity in a subject, comprising the step of contacting the subject with any of the compounds or compositions disclosed herein.

[0284] A further embodiment of the invention is a method of agonizing the aryl hydrocarbon receptor (AhR), comprising contacting a subject with any of the compounds or compositions disclosed herein.

[0285] An additional embodiment of the invention is a method of improving hyperpigmentation caused by a hyperpigmentation disorder in a subject in need thereof, comprising contacting the subject with any of the compounds or compositions disclosed herein.

[0286] Another embodiment of the invention is a method of modulating melanin production in a subject, comprising the step of contacting the subject with any of the compounds or compositions disclosed herein.

[0287] A further embodiment of the invention is a method of modulating melanosome biogenesis in a subject, comprising contacting the subject with any of the compounds or compositions disclosed herein.

[0288] An additional embodiment of the invention is a method of modulating melanosome transport in a subject, comprising contacting the subject with any of the compounds or compositions disclosed herein.

[0289] Another embodiment of the present invention is a compound having the structure of formula (II): [ka] wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10 and R11 are independently selected from the group consisting of hydrogen and methyl, and at least one of R1, R2, R3, R4, R5, R6, R7, R8, R9, R10 and R11 is methyl, or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0290] In one aspect of this embodiment, the compound is [ka] is selected from the group consisting of:

[0291] A further embodiment of the present invention is a compound having the structure of formula (III): [ka] wherein R1, R2, R3, R4, R5, R6, R7, R8, R9 and R10 are independently selected from the group consisting of hydrogen and methyl, and at least one of R1, R2, R3, R4, R5, R6, R7, R8, R9 and R10 is methyl, or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0292] In one aspect of this embodiment, the compound is [ka] is.

[0293] An additional embodiment of the present invention is a skin lightening compound having the structure of formula (II): [ka] wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10 and R11 are independently selected from the group consisting of hydrogen and methyl, or crystalline forms, hydrates, or cosmetically or pharmaceutically acceptable salts.

[0294] In one aspect of this embodiment, the compound is [ka] is selected from the group consisting of:

[0295] Another embodiment of the present invention is a skin lightening compound having the structure of formula (III): [ka] wherein R1, R2, R3, R4, R5, R6, R7, R8, R9 and R10 are independently selected from the group consisting of hydrogen and methyl, or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0296] In one aspect of this embodiment, the compound is [ka] is selected from the group consisting of:

[0297] A further embodiment of the present invention is a compound that induces melanocyte apoptosis. The compound has the structure of formula (II): [ka] wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10 and R11 are independently selected from the group consisting of hydrogen and methyl, or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0298] In one aspect of this embodiment, the compound is [ka] is selected from the group consisting of:

[0299] An additional embodiment of the present invention is a compound that induces melanocyte apoptosis. The compound has the structure of formula (III): [ka] wherein R1, R2, R3, R4, R5, R6, R7, R8, R9 and R10 are independently selected from the group consisting of hydrogen and methyl, or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0300] In one aspect of this embodiment, the compound is [ka] is selected from the group consisting of:

[0301] Another embodiment of the present invention is a compound that agonizes the aromatic hydrocarbon receptor (AhR). The compound has the structure of formula (II): [ka] wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10 and R11 are independently selected from the group consisting of hydrogen and methyl, or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0302] In one aspect of this embodiment, the compound is [ka] is selected from the group consisting of:

[0303] A further embodiment of the present invention is a compound that agonizes the aromatic hydrocarbon receptor (AhR). The compound has the structure of formula (III): [ka] wherein R1, R2, R3, R4, R5, R6, R7, R8, R9 and R10 are independently selected from the group consisting of hydrogen and methyl, or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0304] In one aspect of this embodiment, the compound is [ka] is selected from the group consisting of:

[0305] An additional embodiment of the present invention is a composition comprising a compound having the structure of Formula (II): [ka] wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10 and R11 are independently selected from the group consisting of hydrogen and methyl, or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof, and a cosmetically or pharmaceutically acceptable vehicle, diluent or carrier.

[0306] In one aspect of this embodiment, the compound is [ka] is selected from the group consisting of:

[0307] Another embodiment of the present invention is a composition comprising a compound having the structure of formula (III): [ka] wherein R1, R2, R3, R4, R5, R6, R7, R8, R9 and R10 are independently selected from the group consisting of hydrogen and methyl, or a crystalline form, hydrate, or a cosmetically or pharmaceutically acceptable salt and a cosmetically or pharmaceutically acceptable vehicle, diluent or carrier thereof.

[0308] In one aspect of this embodiment, the compound is [ka] is selected from the group consisting of:

[0309] A further embodiment of the present invention is a method of lightening the skin in a subject. The method comprises administering to the subject a compound having the structure of Formula (II): [ka] wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10 and R11 are independently selected from the group consisting of hydrogen and methyl, or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0310] In one aspect of this embodiment, the compound is [ka] is selected from the group consisting of:

[0311] An additional embodiment of the present invention is a method of lightening the skin in a subject. The method comprises administering to the subject a compound having the structure of Formula (III): [ka] wherein R1, R2, R3, R4, R5, R6, R7, R8, R9 and R10 are independently selected from the group consisting of hydrogen and methyl, or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0312] In one aspect of this embodiment, the compound is [ka] is selected from the group consisting of:

[0313] Another embodiment of the present invention is a method of inducing melanocyte apoptosis in a subject, the method comprising administering to the subject a compound having the structure of Formula (II): [ka] wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10 and R11 are independently selected from the group consisting of hydrogen and methyl, or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0314] In one aspect of this embodiment, the compound is [ka] is selected from the group consisting of:

[0315] A further embodiment of the present invention is a method of inducing melanocyte apoptosis in a subject, the method comprising administering to the subject a compound having the structure of formula (III): [ka] wherein R1, R2, R3, R4, R5, R6, R7, R8, R9 and R10 are independently selected from the group consisting of hydrogen and methyl, or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0316] In one aspect of this embodiment, the compound is [ka] is selected from the group consisting of:

[0317] An additional embodiment of the present invention is a method of agonizing the aryl hydrocarbon receptor (AhR) in a subject, the method comprising administering to the subject a compound having the structure of Formula (II): [ka] wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10 and R11 are independently selected from the group consisting of hydrogen and methyl, or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0318] In one aspect of this embodiment, the compound is [ka] is selected from the group consisting of:

[0319] Another embodiment of the present invention is a method of agonizing the aromatic hydrocarbon receptor (AhR) in a subject. The method comprises administering to the subject a compound having the structure of Formula (III): [ka] wherein R1, R2, R3, R4, R5, R6, R7, R8, R9 and R10 are independently selected from the group consisting of hydrogen and methyl, or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0320] In one aspect of this embodiment, the compound is [ka] is selected from the group consisting of:

[0321] One embodiment of the present invention is a compound having the structure of the following formula: [ka] (Wherein, X is NR 14 and O, and Y is a covalent bond, CR5R6, O, or NR 15 and R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 is hydrogen, halogen, CN, hydroxyl, R 16 OR 16 and R is independently selected from the group consisting of 13 , R 14 and R 15 are independently hydrogen or R 16 and R5 and R6 are hydrogen, hydroxyl, OR 16, R 16 and C 3~6 cycloalkyl, or R5 and R6 together represent an oxo (=O) group or C 3~6 Forming a cycloalkyl, R 12 is hydrogen, -COR a and R 16 and R 16 are each independently formyl, C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 alkynyl, and R a is hydrogen, hydroxyl and OR 16 and R a is hydrogen, Y is CR5R6, and R 13 and R 14 are both hydrogen, R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 and R 11 At least one of the 16 or R5 is hydroxyl, OR 16 , R 16 and C 3~6 cycloalkyl, or R5 and R6 together represent an oxo (=O) group or C 3~6 cycloalkyl-forming), or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0322] In one aspect of this embodiment, the compound has the following structure: [ka] or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0323] In another aspect of this embodiment, X is NH.

[0324] In an additional aspect of this embodiment, Y is CR5R6, R5 is hydrogen, and R6 is hydrogen, C 1~4 Alkyl, C 3~6 Cycloalkyl or O-(C 1~4 alkyl), or R5 and R6 together form an oxo (=O) group.

[0325] Preferably, CR5R6 is CH2, CHCH3, CHOCH3, C=O or CH(C3H5).

[0326] In a further aspect of this embodiment, R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 At least one of the 1~4 It is alkyl.

[0327] Preferably, R2 is C 1~4 It is alkyl.

[0328] More preferably, R2 is methyl.

[0329] In another aspect of this embodiment, R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 are hydrogen atoms.

[0330] In an additional aspect of this embodiment, R 12 -COR a or C 1~4 hydroxyalkyl, and R a is hydrogen or C 1~4 It is alkyl.

[0331] Preferably, R 12 is CHO, CH2OH or C(=O)-O-(C 1~4 alkyl).

[0332] More preferably, R 12 is CHO, CH2OH or CO2CH3.

[0333] In a further aspect of this embodiment, X is NH, Y is CR5R6, and R1, R3, R4, R7, R8, R9, R 10 , R 11 and R 13 are each hydrogen, and R2 is hydrogen or C 1~4 alkyl, R5 is hydrogen, R6 is hydrogen, C 1~4 Alkyl, C 3~6 Cycloalkyl or O-(C 1~4 alkyl), or R5 and R6 together form an oxo (=O) group, and R 12 -COR a or C 1~4 hydroxyalkyl, and R a is hydrogen or C 1~4 It is alkyl.

[0334] In another aspect of this embodiment, the compound is [ka] [ka] is selected from the group consisting of:

[0335] Another embodiment of the present invention is a compound having the following structure: [ka] (Wherein R1, R4, R5, R6, R9 and R 10 is hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, and R2 and R3 are independently selected from the group consisting of hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13and -CHO, or R2 and R3 together form a 5- or 6-membered heterocyclyl, and R7 and R8 are independently selected from the group consisting of hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, or R7 and R8 together form a 5- or 6-membered heterocyclyl, and R 11 and R 12 are independently hydrogen or R 13 and R 13 are each independently, C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 alkynyl, and R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 wherein at least one of is not hydrogen), or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0336] In one aspect of this embodiment, the compound has a structure according to formula (II): [ka] or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0337] In another aspect of this embodiment, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 is hydrogen and C 1~4 alkyl.

[0338] Preferably, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 One or two of the 1~4 alkyl, and the remaining groups are hydrogen.

[0339] In a further aspect of this embodiment, R5 and R 10 One of them is C1~4 The other is alkyl and the other is hydrogen.

[0340] In a further aspect of this embodiment, one of R1, R2, R3, R4, R6, R7, R8 and R9 is C 1~4 alkyl, and the remaining groups are hydrogen.

[0341] Preferably, R 11 and R 12 are each hydrogen, and R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 One, two, three or four of the groups are methyl and the remaining groups are hydrogen.

[0342] In another aspect of this embodiment, the compound is [ka] is selected from the group consisting of:

[0343] An additional embodiment of the present invention is a skin lightening compound having the structure of the following formula: [ka] (Wherein, X is NR 14 and O, and Y is a covalent bond, CR5R6, O, or NR 15 and R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 is hydrogen, halogen, CN, hydroxyl, R 16 OR 16 and R is independently selected from the group consisting of 13 , R 14 and R 15 are independently hydrogen or R 16 and R5 and R6 are hydrogen, hydroxyl, OR 16 , R 16 and C 3~6 cycloalkyl, or R5 and R6 together represent an oxo (=O) group or C3~6 Forming a cycloalkyl, R 12 is hydrogen, -COR a and R 16 and R 16 are each independently formyl, C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 alkynyl, and R a is hydrogen, hydroxyl and OR 16 or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0344] In one aspect of this embodiment, the compound has the following structure: [ka] or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0345] In another aspect of this embodiment, X is NH.

[0346] In an additional aspect of this embodiment, Y is CR5R6, R5 is hydrogen, and R6 is hydrogen, C 1~4 Alkyl, C 3~6 Cycloalkyl or O-(C 1~4 alkyl), or R5 and R6 together form an oxo (=O) group.

[0347] Preferably, CR5R6 is CH2, CHCH3, CHOCH3, C=O or CH(C3H5).

[0348] In a further aspect of this embodiment, R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 At least one of the 1~4 It is alkyl.

[0349] Preferably, R2 is C1~4 It is alkyl.

[0350] More preferably, R2 is methyl.

[0351] In another aspect of this embodiment, R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 are hydrogen atoms.

[0352] In an additional aspect of this embodiment, R 12 -COR a or C 1~4 hydroxyalkyl, and R a is hydrogen or C 1~4 It is alkyl.

[0353] Preferably, R 12 is CHO, CH2OH or C(=O)-O-(C 1~4 alkyl).

[0354] More preferably, R 12 is CHO, CH2OH or CO2CH3.

[0355] In a further aspect of this embodiment, X is NH, Y is CR5R6, and R1, R3, R4, R7, R8, R9, R 10 , R 11 and R 13 are each hydrogen, and R2 is hydrogen or C 1~4 alkyl, R5 is hydrogen, R6 is hydrogen, C 1~4 Alkyl, C 3~6 Cycloalkyl or O-(C 1~4 alkyl), or R5 and R6 together form an oxo (=O) group, and R 12 -COR a or C 1~4 hydroxyalkyl, and R a is hydrogen or C 1~4 It is alkyl.

[0356] In another aspect of this embodiment, the compound is [ka] is selected from the group consisting of:

[0357] In an additional aspect of this embodiment, R a is hydrogen, Y is CR5R6, and R 13 and R 14 are both hydrogen, then R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 and R 11 At least one of the 16 or R5 is hydroxyl, OR 16 , R 16 and C 3~ or R5 and R6 together form an oxo (=O) group or a C3-6 cycloalkyl.

[0358] A further embodiment of the present invention is a skin lightening compound having the following formula: [ka] (Wherein R1, R4, R5, R6, R9 and R 10 is hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, and R2 and R3 are independently selected from the group consisting of hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, or R2 and R3 together form a 5- or 6-membered heterocyclyl, and R7 and R8 are independently selected from the group consisting of hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, or R7 and R8 together form a 5- or 6-membered heterocyclyl, and R11 and R 12 are independently hydrogen or R 13 and R 13 are each independently, C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 alkynyl), or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0359] In one aspect of this embodiment, the compound has a structure according to formula (II): [ka] or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0360] In another aspect of this embodiment, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 is hydrogen and C 1~4 alkyl.

[0361] Preferably, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 One or two of the 1~4 alkyl, and the remaining groups are hydrogen.

[0362] In a further aspect of this embodiment, R5 and R 10 One of them is C 1~4 The other is alkyl and the other is hydrogen.

[0363] In a further aspect of this embodiment, one of R1, R2, R3, R4, R6, R7, R8 and R9 is C 1~4 alkyl, and the remaining groups are hydrogen.

[0364] In another aspect of this embodiment, R 11 and R 12are each hydrogen, and R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 One, two, three or four of the groups are methyl and the remaining groups are hydrogen.

[0365] In a further aspect of this embodiment, the compound is [ka] is selected from the group consisting of:

[0366] In a further aspect of this embodiment, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 At least one of the is not hydrogen.

[0367] Another embodiment of the present invention is a compound that lightens the skin. [ka] is selected from the group consisting of:

[0368] An additional embodiment of the present invention is a compound that induces melanocyte apoptosis. The compound has the structure of the following formula: [ka] (Wherein, X is NR 14 and O, and Y is a covalent bond, CR5R6, O, or NR 15 and R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 is hydrogen, halogen, CN, hydroxyl, R 16 OR 16 and R is independently selected from the group consisting of 13 , R 14 and R 15 are independently hydrogen or R 16 and R5 and R6 are hydrogen, hydroxyl, OR 16 , R 16 and C 3~6cycloalkyl, or R5 and R6 together represent an oxo (=O) group or C 3~6 Forming a cycloalkyl, R 12 is hydrogen, -COR a and R 16 and R 16 are each independently formyl, C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 alkynyl, and R a is hydrogen, hydroxyl and OR 16 or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0369] In one aspect of this embodiment, the compound has the following structure: [ka] or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0370] In another aspect of this embodiment, X is NH.

[0371] In an additional aspect of this embodiment, Y is CR5R6, R5 is hydrogen, and R6 is hydrogen, C 1~4 Alkyl, C 3~6 Cycloalkyl or O-(C 1~4 alkyl), or R5 and R6 together form an oxo (=O) group.

[0372] Preferably, CR5R6 is CH2, CHCH3, CHOCH3, C=O or CH(C3H5).

[0373] In a further aspect of this embodiment, R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 At least one of the 1~4 It is alkyl.

[0374] Preferably, R2 is C 1~4 It is alkyl.

[0375] More preferably, R2 is methyl.

[0376] In another aspect of this embodiment, R1, R2, R3, R4, R7, R8, R9, R 10 oh Yobi R 11 are hydrogen atoms.

[0377] In an additional aspect of this embodiment, R 12 -COR a or C 1~4 hydroxyalkyl, and R a is hydrogen or C 1~4 It is alkyl.

[0378] Preferably, R 12 is CHO, CH2OH or C(=O)-O-(C 1~4 alkyl).

[0379] More preferably, R 12 is CHO, CH2OH or CO2CH3.

[0380] In a further aspect of this embodiment, X is NH, Y is CR5R6, and R1, R3, R4, R7, R8, R9, R 10 , R 11 and R 13 are each hydrogen, and R2 is hydrogen or C 1~4 alkyl, R5 is hydrogen, R6 is hydrogen, C 1~4 Alkyl, C 3~6 Cycloalkyl or O-(C 1~4 alkyl), or R5 and R6 together form an oxo (=O) group, and R 12 -COR a or C 1~4 hydroxyalkyl, and R a is hydrogen or C1~4 It is alkyl.

[0381] In another aspect of this embodiment, the compound is [ka] [ka] is selected from the group consisting of:

[0382] In an additional aspect of this embodiment, R a is hydrogen, Y is CR5R6, and R 13 and R 14 are both hydrogen, then R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 and R 11 At least one of the 16 or R5 is hydroxyl, OR 16 , R 16 and C 3~6 cycloalkyl, or R5 and R6 together represent an oxo (=O) group or C 3~6 Forms a cycloalkyl.

[0383] A further embodiment of the present invention is a compound that induces melanocyte apoptosis, the compound having the following formula: [ka] (Wherein R1, R4, R5, R6, R9 and R 10 is hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, and R2 and R3 are independently selected from the group consisting of hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13and -CHO, or R2 and R3 together form a 5- or 6-membered heterocyclyl, and R7 and R8 are independently selected from the group consisting of hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, or R7 and R8 together form a 5- or 6-membered heterocyclyl, and R 11 and R 12 are independently hydrogen or R 13 and R 13 are each independently, C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 alkynyl), or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0384] In one aspect of this embodiment, the compound has a structure according to formula (II): [ka] or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0385] In another aspect of this embodiment, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 is hydrogen and C 1~4 alkyl.

[0386] Preferably, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 One or two of the 1~4 alkyl, and the remaining groups are hydrogen.

[0387] In a further aspect of this embodiment, R5 and R 10 One of them is C 1~4 The other is alkyl and the other is hydrogen.

[0388] In a further aspect of this embodiment, one of R1, R2, R3, R4, R6, R7, R8 and R9 is C 1~4 alkyl, and the remaining groups are hydrogen.

[0389] In another aspect of this embodiment, R 11 and R 12 are each hydrogen, and R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 One, two, three or four of the groups are methyl and the remaining groups are hydrogen.

[0390] In a further aspect of this embodiment, the compound is [ka] [ka] is selected from the group consisting of:

[0391] In a further aspect of this embodiment, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 At least one of the is not hydrogen.

[0392] Another embodiment of the present invention is a compound that induces melanocyte apoptosis. [ka] is selected from the group consisting of:

[0393] An additional embodiment of the present invention is a compound that modulates aryl hydrocarbon receptor (AhR) activity. The compound has the structure of the following formula: [ka] (Wherein, X is NR 14 and O, and Y is a covalent bond, CR5R6, O, or NR 15and R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 is hydrogen, halogen, CN, hydroxyl, R 16 OR 16 and R is independently selected from the group consisting of 13 , R 14 and R 15 are independently hydrogen or R 16 and R5 and R6 are hydrogen, hydroxyl, OR 16 , R 16 and C 3~6 cycloalkyl, or R5 and R6 together represent an oxo (=O) group or C 3~6 Forming a cycloalkyl, R 12 is hydrogen, -COR a and R 16 and R 16 are each independently formyl, C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 alkynyl, and R a is hydrogen, hydroxyl and OR 16 or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0394] In one aspect of this embodiment, the compound has the following structure: [ka] or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0395] In another aspect of this embodiment, X is NH.

[0396] In an additional aspect of this embodiment, Y is CR5R6, R5 is hydrogen, and R6 is hydrogen, C 1~4 Alkyl, C 3~6 Cycloalkyl or O-(C 1~4alkyl), or R5 and R6 together form an oxo (=O) group.

[0397] Preferably, CR5R6 is CH2, CHCH3, CHOCH3, C=O or CH(C3H5).

[0398] In a further aspect of this embodiment, R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 At least one of the 1~4 It is alkyl.

[0399] Preferably, R2 is C 1~4 It is alkyl.

[0400] More preferably, R2 is methyl.

[0401] In another aspect of this embodiment, R1, R2, R3, R4, R7, R8, R9, R 10 oh Yobi R 11 are hydrogen atoms.

[0402] In an additional aspect of this embodiment, R 12 -COR a or C 1~4 hydroxyalkyl, and R a is hydrogen or C 1~4 It is alkyl.

[0403] Preferably, R 12 is CHO, CH2OH or C(=O)-O-(C 1~4 alkyl).

[0404] More preferably, R 12 is CHO, CH2OH or CO2CH3.

[0405] In a further aspect of this embodiment, X is NH, Y is CR5R6, and R1, R3, R4, R7, R8, R9, R 10 , R 11and R 13 are each hydrogen, and R2 is hydrogen or C 1~4 alkyl, R5 is hydrogen, R6 is hydrogen, C 1~4 Alkyl, C 3~6 Cycloalkyl or O-(C 1~4 alkyl), or R5 and R6 together form an oxo (=O) group, and R 12 -COR a or C 1~4 hydroxyalkyl, and R a is hydrogen or C 1~4 It is alkyl.

[0406] In another aspect of this embodiment, the compound is [ka] [ka] is selected from the group consisting of:

[0407] In an additional aspect of this embodiment, R a is hydrogen, Y is CR5R6, and R 13 and R 14 are both hydrogen, then R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 and R 11 At least one of the 16 or R5 is hydroxyl, OR 16 , R 16 and C 3~6 cycloalkyl, or R5 and R6 together represent an oxo (=O) group or C 3~6 Forms a cycloalkyl.

[0408] A further embodiment of the present invention is a compound that modulates aryl hydrocarbon receptor (AhR) activity. The compound has the following formula: [ka] (Wherein R1, R4, R5, R6, R9 and R 10 is hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, and R2 and R3 are independently selected from the group consisting of hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, or R2 and R3 together form a 5- or 6-membered heterocyclyl, and R7 and R8 are independently selected from the group consisting of hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, or R7 and R8 together form a 5- or 6-membered heterocyclyl, and R 11 and R 12 are independently hydrogen or R 13 and R 13 are each independently, C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 alkynyl), or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0409] In one aspect of this embodiment, the compound has a structure according to formula (II): [ka] or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0410] In another aspect of this embodiment, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 is hydrogen and C 1~4 alkyl.

[0411] Preferably, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 One or two of the 1~4 alkyl, and the remaining groups are hydrogen.

[0412] In a further aspect of this embodiment, R5 and R 10 One of them is C 1~4 The other is alkyl and the other is hydrogen.

[0413] In a further aspect of this embodiment, one of R1, R2, R3, R4, R6, R7, R8 and R9 is C 1~4 alkyl, and the remaining groups are hydrogen.

[0414] In another aspect of this embodiment, R 11 and R 12 are each hydrogen, and R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 One, two, three or four of the groups are methyl and the remaining groups are hydrogen.

[0415] In a further aspect of this embodiment, the compound is [ka] [ka] is selected from the group consisting of:

[0416] In a further aspect of this embodiment, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 At least one of the is not hydrogen.

[0417] Another embodiment of the present invention is a compound that modulates aryl hydrocarbon receptor (AhR) activity. [ka] is selected from the group consisting of:

[0418] An additional embodiment of the present invention is a compound that modulates melanogenesis. The compound has the structure of the following formula: [ka] (Wherein, X is NR 14 and O, and Y is a covalent bond, CR5R6, O, or NR 15 and R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 is hydrogen, halogen, CN, hydroxyl, R 16 OR 16 and R is independently selected from the group consisting of 13 , R 14 and R 15 are independently hydrogen or R 16 and R5 and R6 are hydrogen, hydroxyl, OR 16 , R 16 and C 3~6 cycloalkyl, or R5 and R6 together represent an oxo (=O) group or C 3~6 Forming a cycloalkyl, R 12 is hydrogen, -COR a and R 16 and R 16 are each independently formyl, C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 alkynyl, and R a is hydrogen, hydroxyl and OR 16 or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0419] In one aspect of this embodiment, the compound has the following structure: [ka] or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0420] In another aspect of this embodiment, X is NH.

[0421] In an additional aspect of this embodiment, Y is CR5R6, R5 is hydrogen, and R6 is hydrogen, C 1~4 Alkyl, C 3~6 Cycloalkyl or O-(C 1~4 alkyl), or R5 and R6 together form an oxo (=O) group.

[0422] Preferably, CR5R6 is CH2, CHCH3, CHOCH3, C=O or CH(C3H5).

[0423] In a further aspect of this embodiment, R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 At least one of the 1~4 It is alkyl.

[0424] Preferably, R2 is C 1~4 It is alkyl.

[0425] More preferably, R2 is methyl.

[0426] In another aspect of this embodiment, R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 are hydrogen atoms.

[0427] In an additional aspect of this embodiment, R 12 -COR a or C 1~4 hydroxyalkyl, and R a is hydrogen or C 1~4 It is alkyl.

[0428] Preferably, R 12is CHO, CH2OH or C(=O)-O-(C 1~4 alkyl).

[0429] More preferably, R 12 is CHO, CH2OH or CO2CH3.

[0430] In a further aspect of this embodiment, X is NH, Y is CR5R6, and R1, R3, R4, R7, R8, R9, R 10 , R 11 and R 13 are each hydrogen, and R2 is hydrogen or C 1~4 alkyl, R5 is hydrogen, R6 is hydrogen, C 1~4 Alkyl, C 3~6 Cycloalkyl or O-(C 1~4 alkyl), or R5 and R6 together form an oxo (=O) group, and R 12 -COR a or C 1~4 hydroxyalkyl, and R a is hydrogen or C 1~4 It is alkyl.

[0431] In another aspect of this embodiment, the compound is [ka] [ka] is selected from the group consisting of:

[0432] In an additional aspect of this embodiment, R a is hydrogen, Y is CR5R6, and R 13 and R 14 are both hydrogen, then R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 and R 11 At least one of the 16 or R5 is hydroxyl, OR 16 , R 16and C 3~6 cycloalkyl, or R5 and R6 together represent an oxo (=O) group or C 3~6 Forms a cycloalkyl.

[0433] A further embodiment of the present invention is a compound that modulates melanogenesis. The compound has the following formula: [ka] (Wherein R1, R4, R5, R6, R9 and R 10 is hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, and R2 and R3 are independently selected from the group consisting of hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, or R2 and R3 together form a 5- or 6-membered heterocyclyl, and R7 and R8 are independently selected from the group consisting of hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, or R7 and R8 together form a 5- or 6-membered heterocyclyl, and R 11 and R 12 are independently hydrogen or R 13 and R 13 are each independently, C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 alkynyl), or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0434] In one aspect of this embodiment, the compound has a structure according to formula (II): [ka] or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0435] In another aspect of this embodiment, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 is hydrogen and C 1~4 alkyl.

[0436] Preferably, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 One or two of the 1~4 alkyl, and the remaining groups are hydrogen.

[0437] In another aspect of this embodiment, R5 and R 10 One of them is C 1~4 The other is alkyl and the other is hydrogen.

[0438] In an additional aspect of this embodiment, one of R1, R2, R3, R4, R6, R7, R8 and R9 is C 1~4 alkyl, and the remaining groups are hydrogen.

[0439] In a further aspect of this embodiment, R 11 and R 12 are each hydrogen, and R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 One, two, three or four of the groups are methyl and the remaining groups are hydrogen.

[0440] In another aspect of this embodiment, the compound is [ka] [ka] is selected from the group consisting of:

[0441] In a further aspect of this embodiment, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 At least one of the is not hydrogen.

[0442] Another embodiment of the present invention is a compound that modulates melanogenesis. The compound comprises: [ka] is selected from the group consisting of:

[0443] An additional embodiment of the present invention is a compound that modulates melanin concentration. The compound has the structure of the following formula: [ka] (Wherein, X is NR 14 and O, and Y is a covalent bond, CR5R6, O, or NR 15 and R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 is hydrogen, halogen, CN, hydroxyl, R 16 OR 16 and R is independently selected from the group consisting of 13 , R 14 and R 15 are independently hydrogen or R 16 and R5 and R6 are hydrogen, hydroxyl, OR 16 , R 16 and C 3~6 cycloalkyl, or R5 and R6 together represent an oxo (=O) group or C 3~6 Forming a cycloalkyl, R 12 is hydrogen, -COR a and R 16 and R 16 are each independently formyl, C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 alkynyl, and R a is hydrogen, hydroxyl and OR16 or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0444] In one aspect of this embodiment, the compound has the following structure: [ka] or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0445] In another aspect of this embodiment, X is NH.

[0446] In an additional aspect of this embodiment, Y is CR5R6, R5 is hydrogen, and R6 is hydrogen, C 1~4 Alkyl, C 3~6 Cycloalkyl or O-(C 1~4 alkyl), or R5 and R6 together form an oxo (=O) group.

[0447] Preferably, CR5R6 is CH2, CHCH3, CHOCH3, C=O or CH(C3H5).

[0448] In a further aspect of this embodiment, R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 At least one of the 1~4 It is alkyl.

[0449] Preferably, R2 is C 1~4 It is alkyl.

[0450] More preferably, R2 is methyl.

[0451] In another aspect of this embodiment, R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 are hydrogen atoms.

[0452] In an additional aspect of this embodiment, R 12 -COR a or C 1~4 hydroxyalkyl, and R a is hydrogen or C 1~4 It is alkyl.

[0453] Preferably, R 12 is CHO, CH2OH or C(=O)-O-(C 1~4 alkyl).

[0454] More preferably, R 12 is CHO, CH2OH or CO2CH3.

[0455] In a further aspect of this embodiment, X is NH, Y is CR5R6, and R1, R3, R4, R7, R8, R9, R 10 , R 11 and R 13 are each hydrogen, and R2 is hydrogen or C 1~4 alkyl, R5 is hydrogen, R6 is hydrogen, C 1~4 Alkyl, C 3~6 Cycloalkyl or O-(C 1~4 alkyl), or R5 and R6 together form an oxo (=O) group, and R 12 -COR a or C 1~4 hydroxyalkyl, and R a is hydrogen or C 1~4 It is alkyl.

[0456] In another aspect of this embodiment, the compound is [ka] [ka] is selected from the group consisting of:

[0457] In an additional aspect of this embodiment, R ais hydrogen, Y is CR5R6, and R 13 and R 14 are both hydrogen, then R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 and R 11 At least one of the 16 or R5 is hydroxyl, OR 16 , R 16 and C 3~6 cycloalkyl, or R5 and R6 together represent an oxo (=O) group or C 3~6 Forms a cycloalkyl.

[0458] A further embodiment of the present invention is a compound that modulates melanin concentration. The compound has the following formula: [ka] (Wherein R1, R4, R5, R6, R9 and R 10 is hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, and R2 and R3 are independently selected from the group consisting of hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, or R2 and R3 together form a 5- or 6-membered heterocyclyl, and R7 and R8 are independently selected from the group consisting of hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, or R7 and R8 together form a 5- or 6-membered heterocyclyl, and R 11 and R 12 are independently hydrogen or R 13 and R 13 are each independently, C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9alkynyl), or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0459] In one aspect of this embodiment, the compound has a structure according to formula (II): [ka] or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0460] In another aspect of this embodiment, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 is hydrogen and C 1~4 alkyl.

[0461] Preferably, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 One or two of the 1~4 alkyl, and the remaining groups are hydrogen.

[0462] In a further aspect of this embodiment, R5 and R 10 One of them is C 1~4 The other is alkyl and the other is hydrogen.

[0463] In a further aspect of this embodiment, one of R1, R2, R3, R4, R6, R7, R8 and R9 is C 1~4 alkyl, and the remaining groups are hydrogen.

[0464] In another aspect of this embodiment, R 11 and R 12 are each hydrogen, and R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 One, two, three or four of the groups are methyl and the remaining groups are hydrogen.

[0465] In a further aspect of this embodiment, the compound is [ka] [ka] is selected from the group consisting of:

[0466] In a further aspect of this embodiment, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 At least one of the is not hydrogen.

[0467] Another embodiment of the present invention is a compound that modulates melanin concentration. The compound comprises: [ka] is selected from the group consisting of:

[0468] An additional embodiment of the present invention is a composition comprising a compound having the structure of the following formula: [ka] (Wherein, X is NR 14 and O, and Y is a covalent bond, CR5R6, O, or NR 15 and R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 is hydrogen, halogen, CN, hydroxyl, R 16 OR 16 and R is independently selected from the group consisting of 13 , R 14 and R 15 are independently hydrogen or R 16 and R5 and R6 are hydrogen, hydroxyl, OR 16 , R 16 and C 3~6 cycloalkyl, or R5 and R6 together represent an oxo (=O) group or C 3~6 Forming a cycloalkyl, R 12 is hydrogen, -COR aand R 16 and R 16 are each independently formyl, C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 alkynyl, and R a is hydrogen, hydroxyl and OR 16 or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0469] In one aspect of this embodiment, the compound has the following structure: [ka] or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0470] In another aspect of this embodiment, X is NH.

[0471] In an additional aspect of this embodiment, Y is CR5R6, R5 is hydrogen, and R6 is hydrogen, C 1~4 Alkyl, C 3~6 Cycloalkyl or O-(C 1~4 alkyl), or R5 and R6 together form an oxo (=O) group.

[0472] Preferably, CR5R6 is CH2, CHCH3, CHOCH3, C=O or CH(C3H5).

[0473] In a further aspect of this embodiment, R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 At least one of the 1~4 It is alkyl.

[0474] Preferably, R2 is C 1~4 It is alkyl.

[0475] More preferably, R2 is methyl.

[0476] In another aspect of this embodiment, R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 are hydrogen atoms.

[0477] In an additional aspect of this embodiment, R 12 -COR a or C 1~4 hydroxyalkyl, and R a is hydrogen or C 1~4 It is alkyl.

[0478] Preferably, R 12 is CHO, CH2OH or C(=O)-O-(C 1~4 alkyl).

[0479] More preferably, R 12 is CHO, CH2OH or CO2CH3.

[0480] In a further aspect of this embodiment, X is NH, Y is CR5R6, and R1, R3, R4, R7, R8, R9, R 10 , R 11 and R 13 are each hydrogen, and R2 is hydrogen or C 1~4 alkyl, R5 is hydrogen, R6 is hydrogen, C 1~4 Alkyl, C 3~6 Cycloalkyl or O-(C 1~4 alkyl), or R5 and R6 together form an oxo (=O) group, and R 12 -COR a or C 1~4 hydroxyalkyl, and R a is hydrogen or C 1~4 It is alkyl.

[0481] In another aspect of this embodiment, the compound is [ka] [ka] is selected from the group consisting of:

[0482] A further embodiment of the present invention is a composition comprising a compound having the following formula: [ka] (Wherein R1, R4, R5, R6, R9 and R 10 is hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, and R2 and R3 are independently selected from the group consisting of hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, or R2 and R3 together form a 5- or 6-membered heterocyclyl, and R7 and R8 are independently selected from the group consisting of hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, or R7 and R8 together form a 5- or 6-membered heterocyclyl, and R 11 and R 12 are independently hydrogen or R 13 and R 13 are each independently, C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 alkynyl), or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0483] In one aspect of this embodiment, the compound has a structure according to formula (II): [ka] or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0484] In another aspect of this embodiment, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 is hydrogen and C 1~4 alkyl.

[0485] Preferably, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 One or two of the 1~4 alkyl, and the remaining groups are hydrogen.

[0486] In a further aspect of this embodiment, R5 and R 10 One of them is C 1~4 The other is alkyl and the other is hydrogen.

[0487] In a further aspect of this embodiment, one of R1, R2, R3, R4, R6, R7, R8 and R9 is C 1~4 alkyl, and the remaining groups are hydrogen.

[0488] In another aspect of this embodiment, R 11 and R 12 are each hydrogen, and R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 One, two, three or four of the groups are methyl and the remaining groups are hydrogen.

[0489] In a further aspect of this embodiment, the compound is [ka] is selected from the group consisting of:

[0490] Another embodiment of the present invention is a composition comprising a compound: [ka] is selected from the group consisting of:

[0491] An additional embodiment of the present invention is a method of lightening skin in a subject, the method comprising the step of contacting the subject with a compound, wherein the compound has a structure of the following formula: [ka] (Wherein, X is NR 14 and O, and Y is a covalent bond, CR5R6, O, or NR 15 and R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 is hydrogen, halogen, CN, hydroxyl, R 16 OR 16 and R is independently selected from the group consisting of 13 , R 14 and R 15 are independently hydrogen or R 16 and R5 and R6 are hydrogen, hydroxyl, OR 16 , R 16 and C 3~6 cycloalkyl, or R5 and R6 together represent an oxo (=O) group or C 3~6 Forming a cycloalkyl, R 12 is hydrogen, -COR a and R 16 and R 16 are each independently formyl, C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 alkynyl, and R a is hydrogen, hydroxyl and OR 16 or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0492] In one aspect of this embodiment, the compound has the following structure: [ka] or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0493] In another aspect of this embodiment, X is NH.

[0494] In an additional aspect of this embodiment, Y is CR5R6, R5 is hydrogen, and R6 is hydrogen, C 1~4 Alkyl, C 3~6 Cycloalkyl or O-(C 1~4 alkyl), or R5 and R6 together form an oxo (=O) group.

[0495] Preferably, CR5R6 is CH2, CHCH3, CHOCH3, C=O or CH(C3H5).

[0496] In a further aspect of this embodiment, R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 At least one of the 1~4 It is alkyl.

[0497] Preferably, R2 is C 1~4 It is alkyl.

[0498] More preferably, R2 is methyl.

[0499] In another aspect of this embodiment, R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 are hydrogen atoms.

[0500] In an additional aspect of this embodiment, R 12 -COR a or C 1~4 hydroxyalkyl, and R a is hydrogen or C 1~4 It is alkyl.

[0501] Preferably, R12 is CHO, CH2OH or C(=O)-O-(C 1~4 alkyl).

[0502] More preferably, R 12 is CHO, CH2OH or CO2CH3.

[0503] In a further aspect of this embodiment, X is NH, Y is CR5R6, and R1, R3, R4, R7, R8, R9, R 10 , R 11 and R 13 are each hydrogen, and R2 is hydrogen or C 1~4 alkyl, R5 is hydrogen, R6 is hydrogen, C 1~4 Alkyl, C 3~6 Cycloalkyl or O-(C 1~4 alkyl), or R5 and R6 together form an oxo (=O) group, and R 12 -COR a or C 1~4 hydroxyalkyl, and R a is hydrogen or C 1~4 It is alkyl.

[0504] In another aspect of this embodiment, the compound is [ka] is selected from the group consisting of:

[0505] A further embodiment of the present invention is a method of lightening the skin in a subject, comprising the step of contacting the subject with a compound having the following formula: [ka] (Wherein R1, R4, R5, R6, R9 and R 10 is hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13and -CHO, and R2 and R3 are independently selected from the group consisting of hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, or R2 and R3 together form a 5- or 6-membered heterocyclyl, and R7 and R8 are independently selected from the group consisting of hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, or R7 and R8 together form a 5- or 6-membered heterocyclyl, and R 11 and R 12 are independently hydrogen or R 13 and R 13 are each independently, C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 alkynyl), or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0506] In one aspect of this embodiment, the compound has a structure according to formula (II): [ka] or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0507] In another aspect of this embodiment, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 is hydrogen and C 1~4 alkyl.

[0508] Preferably, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 One or two of the 1~4 alkyl, and the remaining groups are hydrogen.

[0509] In a further aspect of this embodiment, R5 and R 10 One of them is C 1~4 The other is alkyl and the other is hydrogen.

[0510] In a further aspect of this embodiment, one of R1, R2, R3, R4, R6, R7, R8 and R9 is C 1~4 alkyl, and the remaining groups are hydrogen.

[0511] In another aspect of this embodiment, R 11 and R 12 are each hydrogen, and R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 One, two, three or four of the groups are methyl and the remaining groups are hydrogen.

[0512] In a further aspect of this embodiment, the compound is [ka] is selected from the group consisting of:

[0513] Another embodiment of the present invention is a method of lightening skin in a subject, the method comprising the step of contacting the subject with a compound, the compound comprising: [ka] The method includes a step selected from the group consisting of:

[0514] An additional embodiment of the invention is a method of inducing melanocyte apoptosis in a subject, the method comprising contacting the subject with a compound, wherein the compound has the structure of the following formula: [ka] (Wherein, X is NR 14 and O, and Y is a covalent bond, CR5R6, O, or NR 15 and R1, R2, R3, R4, R7, R8, R9, R10 and R 11 is hydrogen, halogen, CN, hydroxyl, R 16 OR 16 and R is independently selected from the group consisting of 13 , R 14 and R 15 are independently hydrogen or R 16 and R5 and R6 are hydrogen, hydroxyl, OR 16 , R 16 and C 3~6 cycloalkyl, or R5 and R6 together represent an oxo (=O) group or C 3~6 Forming a cycloalkyl, R 12 is hydrogen, -COR a and R 16 and R 16 are each independently formyl, C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 alkynyl, and R a is hydrogen, hydroxyl and OR 16 or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0515] In one aspect of this embodiment, the compound has the following structure: [ka] or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0516] In another aspect of this embodiment, X is NH.

[0517] In an additional aspect of this embodiment, Y is CR5R6, R5 is hydrogen, and R6 is hydrogen, C 1~4 Alkyl, C 3~6 Cycloalkyl or O-(C 1~4alkyl), or R5 and R6 together form an oxo (=O) group.

[0518] Preferably, CR5R6 is CH2, CHCH3, CHOCH3, C=O or CH(C3H5).

[0519] In a further aspect of this embodiment, R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 At least one of the 1~4 It is alkyl.

[0520] Preferably, R2 is C 1~4 It is alkyl.

[0521] More preferably, R2 is methyl.

[0522] In another aspect of this embodiment, R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 are hydrogen atoms.

[0523] In an additional aspect of this embodiment, R 12 -COR a or C 1~4 hydroxyalkyl, and R a is hydrogen or C 1~4 It is alkyl.

[0524] Preferably, R 12 is CHO, CH2OH or C(=O)-O-(C 1~4 alkyl).

[0525] More preferably, R 12 is CHO, CH2OH or CO2CH3.

[0526] In a further aspect of this embodiment, X is NH, Y is CR5R6, and R1, R3, R4, R7, R8, R9, R 10 , R 11 and R13 are each hydrogen, and R2 is hydrogen or C 1~4 alkyl, R5 is hydrogen, R6 is hydrogen, C 1~4 Alkyl, C 3~6 Cycloalkyl or O-(C 1~4 alkyl), or R5 and R6 together form an oxo (=O) group, and R 12 -COR a or C 1~4 hydroxyalkyl, and R a is hydrogen or C 1~4 It is alkyl.

[0527] In another aspect of this embodiment, the compound is [ka] [ka] is selected from the group consisting of:

[0528] A further embodiment of the invention is a method of inducing melanocyte apoptosis in a subject, comprising the step of contacting the subject with a compound having the following formula: [ka] (Wherein R1, R4, R5, R6, R9 and R 10 is hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, and R2 and R3 are independently selected from the group consisting of hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, or R2 and R3 together form a 5- or 6-membered heterocyclyl, and R7 and R8 are independently selected from the group consisting of hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13and -CHO, or R7 and R8 together form a 5- or 6-membered heterocyclyl, and R 11 and R 12 are independently hydrogen or R 13 and R 13 are each independently, C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 alkynyl), or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0529] In one aspect of this embodiment, the compound has a structure according to formula (II): [ka] or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0530] In another aspect of this embodiment, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 is hydrogen and C 1~4 alkyl.

[0531] Preferably, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 One or two of the 1~4 alkyl, and the remaining groups are hydrogen.

[0532] In a further aspect of this embodiment, R5 and R 10 One of them is C 1~4 The other is alkyl and the other is hydrogen.

[0533] In a further aspect of this embodiment, one of R1, R2, R3, R4, R6, R7, R8 and R9 is C 1~4 alkyl, and the remaining groups are hydrogen.

[0534] In another aspect of this embodiment, R 11 and R 12 are each hydrogen, and R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 One, two, three of Or four are methyl and the remaining groups are hydrogen.

[0535] In a further aspect of this embodiment, the compound is [ka] is selected from the group consisting of:

[0536] Another embodiment of the invention is a method of inducing melanocyte apoptosis in a subject, the method comprising the step of contacting the subject with a compound, the compound comprising: [ka] The method includes a step selected from the group consisting of:

[0537] An additional embodiment of the invention is a method of modulating aryl hydrocarbon receptor (AhR) activity in a subject, the method comprising contacting the subject with a compound, wherein the compound has a structure of the following formula: [ka] (Wherein, X is NR 14 and O, and Y is a covalent bond, CR5R6, O, or NR 15 and R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 is hydrogen, halogen, CN, hydroxyl, R 16 OR 16 and R is independently selected from the group consisting of 13 , R 14 and R 15 are independently hydrogen or R 16 and R5 and R6 are hydrogen, hydroxyl, OR 16, R 16 and C 3~6 cycloalkyl, or R5 and R6 together represent an oxo (=O) group or C 3~6 Forming a cycloalkyl, R 12 is hydrogen, -COR a and R 16 and R 16 are each independently formyl, C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 alkynyl, and R a is hydrogen, hydroxyl and OR 16 or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0538] In one aspect of this embodiment, the compound has the following structure: [ka] or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0539] In another aspect of this embodiment, X is NH.

[0540] In an additional aspect of this embodiment, Y is CR5R6, R5 is hydrogen, and R6 is hydrogen, C 1~4 Alkyl, C 3~6 Cycloalkyl or O-(C 1~4 alkyl), or R5 and R6 together form an oxo (=O) group.

[0541] Preferably, CR5R6 is CH2, CHCH3, CHOCH3, C=O or CH(C3H5).

[0542] In a further aspect of this embodiment, R1, R2, R3, R4, R7, R8, R9, R 10 and R 11At least one of the 1~4 It is alkyl.

[0543] Preferably, R2 is C 1~4 It is alkyl.

[0544] More preferably, R2 is methyl.

[0545] In another aspect of this embodiment, R1, R2, R3, R4, R7, R8, R9, R 10 oh Yobi R 11 are hydrogen atoms.

[0546] In an additional aspect of this embodiment, R 12 -COR a or C 1~4 hydroxyalkyl, and R a is hydrogen or C 1~4 It is alkyl.

[0547] Preferably, R 12 is CHO, CH2OH or C(=O)-O-(C 1~4 alkyl).

[0548] More preferably, R 12 is CHO, CH2OH or CO2CH3.

[0549] In a further aspect of this embodiment, X is NH, Y is CR5R6, and R1, R3, R4, R7, R8, R9, R 10 , R 11 and R 13 are each hydrogen, and R2 is hydrogen or C 1~4 alkyl, R5 is hydrogen, R6 is hydrogen, C 1~4 Alkyl, C 3~6 Cycloalkyl or O-(C 1~4 alkyl), or R5 and R6 together form an oxo (=O) group, and R 12 -COR a or C 1~4hydroxyalkyl, and R a is hydrogen or C 1~4 It is alkyl.

[0550] In another aspect of this embodiment, the compound is [ka] is selected from the group consisting of:

[0551] A further embodiment of the invention is a method of modulating aryl hydrocarbon receptor (AhR) activity in a subject, the method comprising contacting the subject with a compound having the following formula: [ka] (Wherein R1, R4, R5, R6, R9 and R 10 is hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, and R2 and R3 are independently selected from the group consisting of hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, or R2 and R3 together form a 5- or 6-membered heterocyclyl, and R7 and R8 are independently selected from the group consisting of hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, or R7 and R8 together form a 5- or 6-membered heterocyclyl, and R 11 and R 12 are independently hydrogen or R 13 and R 13 are each independently, C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 alkynyl), or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0552] In one aspect of this embodiment, the compound has a structure according to formula (II): [ka] or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0553] In another aspect of this embodiment, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 is hydrogen and C 1~4 alkyl.

[0554] Preferably, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 One or two of the 1~4 alkyl, and the remaining groups are hydrogen.

[0555] In a further aspect of this embodiment, R5 and R 10 One of them is C 1~4 The other is alkyl and the other is hydrogen.

[0556] In a further aspect of this embodiment, one of R1, R2, R3, R4, R6, R7, R8 and R9 is C 1~4 alkyl, and the remaining groups are hydrogen.

[0557] In another aspect of this embodiment, R 11 and R 12 are each hydrogen, and R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 One, two, three or four of the groups are methyl and the remaining groups are hydrogen.

[0558] In a further aspect of this embodiment, the compound is [ka] is selected from the group consisting of:

[0559] Another embodiment of the invention is a method of modulating aryl hydrocarbon receptor (AhR) activity in a subject, the method comprising the step of contacting the subject with a compound, wherein the compound: [ka] The method includes a step selected from the group consisting of:

[0560] An additional embodiment of the invention is a method of modulating melanogenesis in a subject, the method comprising the step of contacting the subject with a compound, wherein the compound has a structure of the following formula: [ka] (Wherein, X is NR 14 and O, and Y is a covalent bond, CR5R6, O, or NR 15 and R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 is hydrogen, halogen, CN, hydroxyl, R 16 OR 16 and R is independently selected from the group consisting of 13 , R 14 and R 15 are independently hydrogen or R 16 and R5 and R6 are hydrogen, hydroxyl, OR 16 , R 16 and C 3~6 cycloalkyl, or R5 and R6 together represent an oxo (=O) group or C 3~6 Forming a cycloalkyl, R 12 is hydrogen, -COR a and R 16 and R 16 are each independently formyl, C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 alkynyl, and R ais hydrogen, hydroxyl and OR 16 or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0561] In one aspect of this embodiment, the compound has the following structure: [ka] or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0562] In another aspect of this embodiment, X is NH.

[0563] In an additional aspect of this embodiment, Y is CR5R6, R5 is hydrogen, and R6 is hydrogen, C 1~4 Alkyl, C 3~6 Cycloalkyl or O-(C 1~4 alkyl), or R5 and R6 together form an oxo (=O) group.

[0564] Preferably, CR5R6 is CH2, CHCH3, CHOCH3, C=O or CH(C3H5).

[0565] In a further aspect of this embodiment, R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 At least one of the 1~4 It is alkyl.

[0566] Preferably, R2 is C 1~4 It is alkyl.

[0567] More preferably, R2 is methyl.

[0568] In another aspect of this embodiment, R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 are hydrogen atoms.

[0569] In an additional aspect of this embodiment, R 12 -COR a or C 1~4 hydroxyalkyl, and R a is hydrogen or C 1~4 It is alkyl.

[0570] Preferably, R 12 is CHO, CH2OH or C(=O)-O-(C 1~4 alkyl).

[0571] More preferably, R 12 is CHO, CH2OH or CO2CH3.

[0572] In a further aspect of this embodiment, X is NH, Y is CR5R6, and R1, R3, R4, R7, R8, R9, R 10 , R 11 and R 13 are each hydrogen, and R2 is hydrogen or C 1~4 alkyl, R5 is hydrogen, R6 is hydrogen, C 1~4 Alkyl, C 3~6 Cycloalkyl or O-(C 1~4 alkyl), or R5 and R6 together form an oxo (=O) group, and R 12 -COR a or C 1~4 hydroxyalkyl, and R a is hydrogen or C 1~4 It is alkyl.

[0573] In another aspect of this embodiment, the compound is [ka] is selected from the group consisting of:

[0574] A further embodiment of the present invention is a method of modulating melanogenesis in a subject, comprising the step of contacting the subject with a compound having the following formula: [ka] (Wherein R1, R4, R5, R6, R9 and R 10 is hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, and R2 and R3 are independently selected from the group consisting of hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, or R2 and R3 together are independently selected from the group consisting of form a 5- or 6-membered heterocyclyl, and R7 and R8 are hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, or R7 and R8 together form a 5- or 6-membered heterocyclyl, and R 11 and R 12 are independently hydrogen or R 13 and R 13 are each independently, C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 alkynyl), or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0575] In one aspect of this embodiment, the compound has a structure according to formula (II): [ka] or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0576] In another aspect of this embodiment, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 is hydrogen and C 1~4 alkyl.

[0577] Preferably, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 One or two of the 1~4 alkyl, and the remaining groups are hydrogen.

[0578] In a further aspect of this embodiment, R5 and R 10 One of them is C 1~4 The other is alkyl and the other is hydrogen.

[0579] In a further aspect of this embodiment, one of R1, R2, R3, R4, R6, R7, R8 and R9 is C 1~4 alkyl, and the remaining groups are hydrogen.

[0580] In another aspect of this embodiment, R 11 and R 12 are each hydrogen, and R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 One, two, three or four of the groups are methyl and the remaining groups are hydrogen.

[0581] In a further aspect of this embodiment, the compound is [ka] is selected from the group consisting of:

[0582] Another embodiment of the invention is a method of modulating melanogenesis in a subject, the method comprising the step of contacting the subject with a compound, wherein the compound: [ka] The method includes a step selected from the group consisting of:

[0583] An additional embodiment of the present invention is a method of modulating melanin concentration in a subject, the method comprising the step of contacting the subject with a compound, wherein the compound has a structure of the following formula: [ka] (Wherein, X is NR 14 and O, and Y is a covalent bond, CR5R6, O, or NR 15 and R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 is hydrogen, halogen, CN, hydroxyl, R 16 OR 16 and R is independently selected from the group consisting of 13 , R 14 and R 15 are independently hydrogen or R 16 and R5 and R6 are hydrogen, hydroxyl, OR 16 , R 16 and C 3~6 cycloalkyl, or R5 and R6 together represent an oxo (=O) group or C 3~6 Forming a cycloalkyl, R 12 is hydrogen, -COR a and R 16 and R 16 are each independently formyl, C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 alkynyl, and R a is hydrogen, hydroxyl and OR 16 or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0584] In one aspect of this embodiment, the compound has the following structure: [ka] or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0585] In another aspect of this embodiment, X is NH.

[0586] In an additional aspect of this embodiment, Y is CR5R6, R5 is hydrogen, and R6 is hydrogen, C 1~4 Alkyl, C 3~6 Cycloalkyl or O-(C 1~4 alkyl), or R5 and R6 together form an oxo (=O) group.

[0587] Preferably, CR5R6 is CH2, CHCH3, CHOCH3, C=O or CH(C3H5).

[0588] In a further aspect of this embodiment, R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 At least one of the 1~4 It is alkyl.

[0589] Preferably, R2 is C 1~4 It is alkyl.

[0590] More preferably, R2 is methyl.

[0591] In another aspect of this embodiment, R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 are hydrogen atoms.

[0592] In an additional aspect of this embodiment, R 12 -COR a or C 1~4 hydroxyalkyl, and R a is hydrogen or C 1~4 It is alkyl.

[0593] Preferably, R 12is CHO, CH2OH or C(=O)-O-(C 1~4 alkyl).

[0594] More preferably, R 12 is CHO, CH2OH or CO2CH3.

[0595] In a further aspect of this embodiment, X is NH, Y is CR5R6, and R1, R3, R4, R7, R8, R9, R 10 , R 11 and R 13 are each hydrogen, and R2 is hydrogen or C 1~4 alkyl, R5 is hydrogen, R6 is hydrogen, C 1~4 Alkyl, C 3~6 Cycloalkyl or O-(C 1~4 alkyl), or R5 and R6 together form an oxo (=O) group, and R 12 -COR a or C 1~4 hydroxyalkyl, and R a is hydrogen or C 1~4 It is alkyl.

[0596] In another aspect of this embodiment, the compound is [ka] is selected from the group consisting of:

[0597] A further embodiment of the present invention is a method of modulating melanin concentration in a subject, comprising the step of contacting the subject with a compound having the following formula: [ka] (Wherein R1, R4, R5, R6, R9 and R 10 is hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13and -CHO, and R2 and R3 are independently selected from the group consisting of hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, or R2 and R3 together are independently selected from the group consisting of form a 5- or 6-membered heterocyclyl, and R7 and R8 are hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, or R7 and R8 together form a 5- or 6-membered heterocyclyl, and R 11 and R 12 are independently hydrogen or R 13 and R 13 are each independently, C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 alkynyl), or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0598] In one aspect of this embodiment, the compound has a structure according to formula (II): [ka] or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof.

[0599] In another aspect of this embodiment, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 is hydrogen and C 1~4 alkyl.

[0600] Preferably, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 One or two of the 1~4 alkyl, and the remaining groups are hydrogen.

[0601] In a further aspect of this embodiment, R5 and R 10 One of them is C 1~4 The other is alkyl and the other is hydrogen.

[0602] In a further aspect of this embodiment, one of R1, R2, R3, R4, R6, R7, R8 and R9 is C 1~4 alkyl, and the remaining groups are hydrogen.

[0603] In another aspect of this embodiment, R 11 and R 12 are each hydrogen, and R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 One, two, three or four of the groups are methyl and the remaining groups are hydrogen.

[0604] In a further aspect of this embodiment, the compound is [ka] is selected from the group consisting of:

[0605] Another embodiment of the present invention is a method of modulating melanin concentration in a subject, the method comprising the step of contacting the subject with a compound, the compound comprising: [ka] The method includes a step selected from the group consisting of:

[0606] One embodiment of the present invention is a skin lightening compound having the structure of the following formula: [ka] or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0607] Another embodiment of the present invention is a compound that induces melanocyte apoptosis, the compound having the structure of the following formula: [ka] or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0608] An additional embodiment of the present invention is a compound that modulates aryl hydrocarbon receptor (AhR) activity. The compound has the structure of the following formula: [ka] or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0609] A further embodiment of the present invention is a compound that modulates melanogenesis, the compound having the structure of the following formula: [ka] or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0610] Another embodiment of the present invention is a compound that modulates melanin concentration. The compound has the structure of the following formula: [ka] or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0611] An additional embodiment of the present invention is a composition comprising a compound having the structure of the following formula: [ka] or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0612] A further embodiment of the present invention is a method of lightening the skin in a subject, comprising the step of contacting the subject with a compound, wherein the compound has a structure of the following formula: [ka] or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0613] Another embodiment of the present invention is a method of inducing melanocyte apoptosis in a subject, comprising the step of contacting the subject with a compound, wherein the compound has the structure of the following formula: [ka] or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0614] An additional embodiment of the invention is a method of modulating aryl hydrocarbon receptor (AhR) activity in a subject, the method comprising contacting the subject with a compound, wherein the compound has a structure of the following formula: [ka] or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0615] A further embodiment of the invention is a method of modulating melanogenesis in a subject, comprising the step of contacting the subject with a compound, wherein the compound has a structure of the following formula: [ka] or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0616] Another embodiment of the present invention is a method of modulating melanin concentration in a subject, the method comprising the step of contacting the subject with a compound, wherein the compound has a structure of the following formula: [ka] or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0617] An additional embodiment of the present invention is a composition. The composition comprises one or more of the compounds listed in Table 5 or Figure 130, or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof. In one aspect of this embodiment, the composition comprises a first compound having the structure of the following formula: [ka] or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof; and a second compound having a structure of the following formula: [ka] or its chemical analogs, crystalline forms, hydrates, or pharmaceutically or cosmetically acceptable forms Contains acceptable salts.

[0618] A further embodiment of the present invention is a method of whitening skin in a subject, comprising contacting the subject with one or more of the compounds listed in Table 5 or Figure 130, or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0619] In one aspect of this embodiment, the subject receives a first compound having a structure of the following formula: [ka] or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof; and a second compound having a structure of the following formula: [ka] or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0620] Another embodiment of the invention is a method of inducing melanocyte apoptosis in a subject, comprising contacting the subject with one or more of the compounds listed in Table 5 or Figure 130, or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0621] In one aspect of this embodiment, the subject receives a first compound having a structure of the following formula: [ka] or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof; and a second compound having a structure of the following formula: [ka] or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0622] An additional embodiment of the present invention is a method of modulating aryl hydrocarbon receptor (AhR) activity in a subject, comprising contacting the subject with one or more of the compounds listed in Table 5 or Figure 130, or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0623] In one aspect of this embodiment, the subject receives a first compound having a structure of the following formula: [ka] or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof; and a second compound having a structure of the following formula: [ka] or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0624] A further embodiment of the invention is a method of modulating melanogenesis in a subject, comprising contacting the subject with one or more of the compounds listed in Table 5 or Figure 130, or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0625] In one aspect of this embodiment, the subject receives a first compound having a structure of the following formula: [ka] or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof; and a second compound having a structure of the following formula: [ka] or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0626] Another embodiment of the invention is a method of modulating melanin concentration in a subject, comprising the step of contacting the subject with one or more of the compounds listed in Table 5 or Figure 130, or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0627] In one aspect of this embodiment, the subject receives a first compound having a structure of the following formula: [ka] or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof; and a second compound having a structure of the following formula: [ka] or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0628] An additional embodiment of the present invention is a composition comprising one or more of the compounds listed in Table 5 or Figure 130, or a chemical analog, crystalline form, hydrate, or This includes pharmaceutically or cosmetically acceptable salts.

[0629] A further embodiment of the present invention is a skin lightening composition comprising one or more of the compounds listed in Table 5 or Figure 130, or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0630] Another embodiment of the present invention is a composition for inducing melanocyte apoptosis, comprising one or more of the compounds listed in Table 5 or Figure 130, or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0631] An additional embodiment of the present invention is a composition for modulating aromatic hydrocarbon receptor (AhR) activity, comprising one or more of the compounds listed in Table 5 or Figure 130, or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0632] A further embodiment of the present invention is a composition for modulating melanogenesis, comprising one or more of the compounds listed in Table 5 or Figure 130, or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0633] Another embodiment of the present invention is a composition for modulating melanin concentration, comprising one or more of the compounds listed in Table 5 or Figure 130, or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0634] An additional embodiment of the present invention is a method of lightening skin in a subject, comprising the step of contacting the subject with a composition comprising one or more of the compounds listed in Table 5 or Figure 130, or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0635] A further embodiment of the invention is a method of inducing melanocyte apoptosis in a subject, comprising contacting the subject with a composition comprising one or more of the compounds listed in Table 5 or Figure 130, or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0636] Another embodiment of the present invention is a method of modulating aromatic hydrocarbon receptor (AhR) activity in a subject, comprising contacting the subject with a composition comprising one or more of the compounds listed in Table 5 or Figure 130, or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0637] An additional embodiment of the invention is a method of modulating melanogenesis in a subject, comprising contacting the subject with a composition comprising one or more of the compounds listed in Table 5 or Figure 130, or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0638] A further embodiment of the invention is a method of modulating melanin concentration in a subject, comprising contacting the subject with a composition comprising one or more of the compounds listed in Table 5 or Figure 130, or a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0639] In a preferred embodiment, the compositions of the present invention comprise a compound listed in Table 7.

[0640] In other preferred embodiments, the compositions of the present invention comprise a compound listed in Table 8.

[0641] In additional preferred embodiments, the compositions of the invention comprise a compound listed in Table 9.

[0642] In a further preferred embodiment, the compositions of the present invention comprise a compound listed in Table 10.

[0643] In other preferred embodiments, the compositions of the present invention comprise a compound listed in Table 11.

[0644] In additional preferred embodiments, the methods of the invention comprise contacting a subject with a composition comprising a compound listed in Table 7.

[0645] In a further preferred embodiment, the methods of the invention comprise contacting a subject with a composition comprising a compound listed in Table 8.

[0646] In other preferred embodiments, the methods of the present invention comprise contacting a subject with a composition comprising a compound listed in Table 9.

[0647] In additional preferred embodiments, the methods of the invention comprise contacting a subject with a composition comprising a compound listed in Table 10.

[0648] In a further preferred embodiment, the methods of the invention comprise the step of contacting a subject with a composition comprising a compound listed in Table 11.

[0649] Another embodiment of the present invention is a composition comprising Malassezia yeast and a cosmetically or pharmaceutically acceptable vehicle, diluent, or carrier.

[0650] An additional embodiment of the present invention is a composition comprising a compound having the structure of the following formula: [ka] (In the formula, X is NR 14 and O, and Y is a covalent bond, CR5R6, O, or NR 15 and R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 is hydrogen, halogen, CN, hydroxyl, R 16 OR 16 and R is independently selected from the group consisting of 13 , R 14 and R 15 are independently hydrogen or R 16 and R5 and R6 are hydrogen, hydroxyl, OR 16 , R 16 and C 3~6 cycloalkyl, or R5 and R6 together represent an oxo (=O) group or C 3~6 Forming a cycloalkyl, R 12 is hydrogen, -COR a and R 16and R 16 are each independently formyl, C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 alkynyl, and R a is hydrogen, hydroxyl and OR 16 selected from the group consisting of or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof and a cosmetically or pharmaceutically acceptable vehicle, diluent or carrier.

[0651] A further embodiment of the present invention is a composition comprising a compound having the structure of the following formula: [ka] (In the formula, R1, R4, R5, R6, R9 and R 10 is hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, and R2 and R3 are independently selected from the group consisting of hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, or R2 and R3 together form a 5- or 6-membered heterocyclyl, and R7 and R8 are independently selected from the group consisting of hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 ,OCOR 13 and -CHO, or R7 and R8 together form a 5- or 6-membered heterocyclyl, and R 11 and R 12 are independently hydrogen or R 13 and R 13 are each independently, C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 alkynyl) or a crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof and a cosmetically or pharmaceutically acceptable vehicle, diluent or carrier.

[0652] Another embodiment of the present invention is a composition comprising a compound listed in Table 5 or Figure 130, or a chemical analog, crystalline form, hydrate, or cosmetically or pharmaceutically acceptable salt thereof. and a cosmetically or pharmaceutically acceptable vehicle, diluent or carrier.

[0653] In a preferred embodiment, any of the compositions of the present invention prevents UV-induced erythema in a subject.

[0654] In a preferred embodiment, any of the compositions of the present invention reduces epidermal melanin in a subject.

[0655] In a preferred embodiment, any of the compositions of the present invention provides a photoprotective or UV protective benefit in a subject.

[0656] In a preferred embodiment, any of the compositions of the present invention filters, absorbs or reflects UV radiation.

[0657] In preferred embodiments, any of the compositions of the present invention prevents hyperpigmentation and / or promotes hypopigmentation.

[0658] In a preferred embodiment, any of the compositions of the present invention is a sunscreen, photoprotectant and / or UV protectant.

[0659] Additional embodiments of the present invention provide a method for treating or preventing UV-induced skin damage in a subject. The method includes contacting a subject with any of the compositions disclosed herein.

[0660] A further embodiment of the invention is a method of treating or preventing UV-induced erythema in a subject, comprising contacting the subject with any of the compositions disclosed herein.

[0661] Another embodiment of the present invention is a method of treating or preventing UV-induced aging of the skin in a subject, comprising contacting the subject with any of the compositions disclosed herein.

[0662] An additional embodiment of the invention is a method of treating or preventing sunburn in a subject, comprising the step of contacting the subject with any of the compositions disclosed herein.

[0663] A further embodiment of the invention is a method of treating or preventing UV-induced hyperpigmentation in a subject, comprising contacting the subject with any of the compositions disclosed herein.

[0664] Another embodiment of the present invention is a method of lightening skin in a subject, comprising the step of contacting the subject with any of the compositions disclosed herein.

[0665] An additional embodiment of the invention is a method of inducing melanocyte apoptosis in a subject, comprising contacting the subject with any of the compositions disclosed herein.

[0666] A further embodiment of the invention is a method of modulating aryl hydrocarbon receptor (AhR) activity in a subject, comprising contacting the subject with any of the compositions disclosed herein.

[0667] Another embodiment of the invention is a method of modulating melanogenesis in a subject, comprising the step of contacting the subject with any of the compositions disclosed herein.

[0668] An additional embodiment of the present invention is a method of modulating melanin concentration in a subject, comprising contacting the subject with any of the compositions disclosed herein. definition

[0669] As used herein, the term "compound" refers to two or more atoms joined by one or more chemical bonds. In the present invention, chemical bonds include, but are not limited to, covalent bonds, ionic bonds, hydrogen bonds, and van der Waals interactions. Covalent bonds in the present invention include single bonds, double bonds, and triple bonds. Compounds of the present invention include, but are not limited to, organic molecules.

[0670] The organic compounds / molecules of the present invention include linear, branched and cyclic hydrocarbons, with or without functional groups. x~y " when used in conjunction with a chemical moiety such as alkyl, alkenyl, alkynyl, or alkoxy, is intended to include groups containing x to y carbons in the chain. For example, the term "C x~y "Alkyl" refers to groups having x to y alkyl groups in the chain, including haloalkyl groups such as trifluoromethyl and 2,2,2-trifluoroethyl. The term "C" refers to a substituted or unsubstituted saturated hydrocarbon group, including straight-chain alkyl and branched-chain alkyl groups, containing carbon atoms of 0 to 100 carbon atoms. x~y alkenyl" and "C x~y "Alkynyl" refers to substituted or unsubstituted unsaturated aliphatic groups similar in length and possibly with substitution to the alkyls described above, but which contain at least one double or triple bond respectively.

[0671] The term "aliphatic," as used herein, means a group consisting of carbon and hydrogen atoms that does not contain an aromatic ring. Thus, aliphatic groups include alkyl, alkenyl, alkynyl, and carbocyclyl groups.

[0672] As used herein, the term "alkyl" refers to linear and branched acyclic hydrocarbon groups, e.g., C1-C 20 "Alkyl" refers to an alkyl group having 1 to 20 carbons. The alkyl group may be linear or branched. Examples of alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, tert-pentylhexyl, isohexyl, and the like. Other alkyl groups will be readily apparent to those of ordinary skill in the art given the benefit of this disclosure. The alkyl group may be unsubstituted or substituted with one or more substituents described herein. For example, the alkyl group may be substituted with one or more (e.g., 1, 2, 3, 4, 5, or 6 independently selected) halogen, -COR', -COOH, -CN, -OH, -OR', -NH, -NHR', -N(R')2, -SR', or -SOR', where each instance of R' is independently a C1-C3 alkyl. In an embodiment, the alkyl is unsubstituted. In embodiments, the alkyl is substituted (e.g., with 1, 2, 3, 4, 5, or 6 substituents described herein). For example, the term "hydroxyalkyl" refers to an alkyl group, as described herein, that includes a hydroxyl (-OH) substituent, including groups such as -CHOH.

[0673] As used herein, "alkenyl" means any linear or branched hydrocarbon chain with one or more unsaturated carbon-carbon double bonds that may occur at any stable point along the chain, e.g., "C2-C 20"Alkenyl" refers to an alkenyl group having 2 to 20 carbons. For example, alkenyl groups include prop-2-enyl, but-2-enyl, but-3-enyl, 2-methylprop-2-enyl, hex-2-enyl, hex-5-enyl, 2,3-dimethylbut-2-enyl, and the like. In embodiments, an alkenyl contains one, two, or three carbon-carbon double bonds. In embodiments, an alkenyl contains one carbon-carbon double bond. In embodiments, multiple double bonds (e.g., two or three) are conjugated. An alkenyl group can be unsubstituted or substituted with one or more substituents described herein. For example, an alkenyl group can be substituted with one or more (e.g., 1, 2, 3, 4, 5, or 6 independently selected substituents) of halogen, -COR', -CN, -OH, -OR', -NH, -NHR', -N(R')2, -SR', or -SOR', where each instance of R' is independently C1-C3 alkyl. In embodiments, the alkenyl is unsubstituted. In embodiments, the alkenyl is substituted (e.g., with 1, 2, 3, 4, 5, or 6 substituents described herein).

[0674] As used herein, "alkynyl" means any hydrocarbon chain of either linear or branched configuration with one or more carbon-carbon triple bonds occurring at any stable point along the chain, e.g., "C2-C 20 "Alkynyl" refers to an alkynyl group having 2 to 20 carbons. Examples of alkynyl groups include prop-2-ynyl, but-2-ynyl, but-3-ynyl, pent-2-ynyl, and 3-methylpent-4-ynyl. , hex-2-ynyl, hex-5-ynyl, and the like. In embodiments, the alkynyl comprises one carbon-carbon triple bond. The alkynyl group can be unsubstituted or substituted with one or more substituents described herein. For example, the alkynyl group can be substituted with one or more (e.g., 1, 2, 3, 4, 5, or 6 independently selected) of halogen, —COR′, —CN, —OH, —OR′, —NH, —NHR′, —N(R′)2, —SR′, or —SOR′, where each instance of R′ is independently C1-C3 alkyl. In embodiments, the alkynyl is unsubstituted. In embodiments, the alkynyl is substituted (e.g., with 1, 2, 3, 4, 5, or 6 substituents described herein).

[0675] As used herein, the term "cycloalkyl" refers to a saturated non-aromatic cyclic group, such as "C3-C 10"cycloalkyl" means "cycloalkyl." In embodiments, a cycloalkyl is monocyclic. In embodiments, a cycloalkyl is polycyclic (e.g., bicyclic or tricyclic). In polycyclic cycloalkyl groups, the individual rings can be fused, bridged, or spirocyclic. Examples of cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, norbornanyl, bicyclo[3.2.1]octanyl, octahydro-pentalenyl, spiro[4.5]decanyl, and the like. The term "cycloalkyl" may be used interchangeably with the term "carbocycle." A cycloalkyl group can be unsubstituted or substituted with one or more substituents described herein. For example, a cycloalkyl group can be substituted with one or more (e.g., 1, 2, 3, 4, 5, or 6 independently selected substituents) of halogen, —COR′, —CN, —OH, —OR′, —NH, —NHR′, —N(R′)2, —SR′, or —SOR′, where each instance of R′ is independently C1-C3 alkyl. In embodiments, the cycloalkyl is unsubstituted. In embodiments, the cycloalkyl is substituted (e.g., with 1, 2, 3, 4, 5, or 6 substituents described herein).

[0676] As used herein, the term "halogen" means fluorine, chlorine, bromine or iodine.

[0677] As used herein, an "aromatic compound," "aromatic," or a compound containing an "aromatic ring" is an aryl or heteroaryl compound. The term "aryl," as used herein, includes substituted or unsubstituted monocyclic aromatic groups in which each atom of the ring is carbon. Preferably, the ring is a 3- to 8-membered ring, more preferably a 6-membered ring. The term "aryl" also includes polycyclic ring systems having two or more cyclic rings, in which two or more carbons are common to two adjacent rings, at least one of the rings is aromatic, and the other cyclic rings can be, for example, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, and / or heterocyclyl. Aryl groups include benzene, naphthalene, phenanthrene, phenol, aniline, and the like. The term "heteroaryl" includes substituted or unsubstituted aromatic monocyclic ring structures, preferably 3- to 8-membered rings, more preferably 5- to 7-membered rings, and even more preferably 5- to 6-membered rings, wherein the ring structure contains at least one heteroatom, preferably 1-4 heteroatoms, and more preferably 1 or 2 heteroatoms. The term "heteroaryl" also includes polycyclic ring systems having two or more cyclic rings, where two or more carbons are common to two adjacent rings, and at least one of the rings is heteroaromatic, e.g., the other cyclic rings can be cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, and / or heterocyclyl. Heteroaryl groups include, for example, pyrrole, furan, thiophene, indole, imidazole, oxazole, thiazole, pyrazole, pyridine, pyrazine, pyridazine, and pyridine. imidine, etc. Preferably, certain compounds of the present invention contain at least one, preferably two, indole groups and at least one aldehyde group.

[0678] The term "substituted" refers to a moiety having at least one substituent replacing a hydrogen atom on one or more carbons of the backbone. It is understood that "substituted" or "substituted by" includes the implicit assumption that such substitution is subject to the permissible valence of the atom and substituent being substituted, and that the substitution results in a stable compound that does not spontaneously undergo transformation, for example, by rearrangement, cyclization, elimination, and the like. Permissible substituents can be one or more and can be the same or different for appropriate organic compounds.

[0679] As used herein, the term "heterocycle" or "heterocyclic" refers to a monocyclic, bicyclic, or tricyclic ring system containing at least one heteroatom, including, but not limited to, oxygen, nitrogen, and sulfur.

[0680] Monocyclic heterocyclic rings consist of, for example, a 3-, 4-, 5-, 6-, 7-, 8-, 9-, or 10-membered ring containing at least one heteroatom. Representative examples of monocyclic heterocyclic rings include, but are not limited to, azetidinyl, azepanyl, aziridinyl, diazepanyl, 1,3-dioxanyl, 1,3-dioxolanyl, 1,3-dithiolanyl, 1,3-dithianyl, imidazolinyl, imidazolidinyl, isothiazolinyl, isothiazolidinyl, isoxazolinyl, isoxazolidinyl, morpholinyl, oxadiazolinyl, and oxadiazolidinyl. , oxazolinyl, oxazolidinyl, piperazinyl, piperidinyl, pyranyl, pyrazolinyl, pyrazolidinyl, pyrrolinyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothienyl, thiadiazolinyl, thiadiazolidinyl, thiazolinyl, thiazolidinyl, thiomorpholinyl, 1,1-dioxidethiomorpholinyl (thiomorpholinesulfone), thiopyranyl, and trithianyl.

[0681] Bicyclic heterocyclic rings are, by way of non-limiting example, monocyclic heterocyclic rings fused to a distal aryl ring, or monocyclic heterocyclic rings fused to a distal cycloalkyl ring, or monocyclic heterocyclic rings fused to a distal cycloalkenyl ring, or monocyclic heterocyclic rings fused to a distal monocyclic heterocyclic ring, or monocyclic heterocyclic rings fused to a distal monocyclic heteroaryl ring. Representative examples of bicyclic heterocyclic rings include, but are not limited to, 1,3-benzodioxolyl, 1,3-benzodithiolyl, 2,3-dihydro-1,4-benzodioxinyl, 2,3-dihydro-1-benzofuranyl, 2,3-dihydro-1-benzothienyl, 2,3-dihydro-1H-indolyl, and 1,2,3,4-tetrahydroquinolinyl.

[0682] A tricyclic heterocyclic ring is, by way of non-limiting example, a bicyclic heterocyclic ring fused to a phenyl group, or a bicyclic heterocyclic ring fused to a cycloalkyl group, or a bicyclic heterocyclic ring fused to a cycloalkenyl group, or a bicyclic heterocyclic ring fused to another monocyclic heterocyclic ring. Representative examples of tricyclic heterocyclic rings include, but are not limited to, 2,3,4,4a,9,9a-hexahydro-1H-carbazolyl, 5a,6,7,8,9,9a-hexahydrodibenzo[b,d]furanyl, and 5a,6,7,8,9,9a-hexahydrodibenzo[b,d]thienyl.

[0683] Heterocycles of the present invention include, by way of non-limiting example, alkenyl, alkoxy, alkoxyalkyl, alkoxyalkynyl, alkoxycarbonyl, alkoxycarbonylalkyl, alkoxy-NH=C(alkyl)-, alkyl, alkylcarbonyl, alkylcarbonylalkyl, alkylcarbonyloxy, alkylsulfonyl, alkylthio, alkynyl, aryl, arylalkoxy, arylalkyl, arylcarbonyl, aryl and phenyl.

[0684] As used herein, "modulating skin pigmentation" and grammatical variations thereof generally refer to the skin lightening and skin darkening effects of the compounds and compositions of the present invention.

[0685] As used herein, "skin whitening" and its grammatical variations generally refer to any actual or apparent reduction in skin pigmentation. Skin whitening methods are used to reduce pigmentation in hyperpigmented skin areas due to age, sun exposure, or hyperpigmentation disorders. For example, when the compounds and compositions of the present invention are applied to the skin of a subject, pigmentation can be reduced, resulting in the skin appearing lighter or whiter than before said application. Skin pigmentation can be measured by, for example, but not limited to, the von Luschan chromatic scale, the Fitzpatrick skin classification test (Fitzpatrick et al., 1988), and the Taylor hyperpigmentation scale. It can be assessed in several ways, including visual assessment using a filter (Taylor et al., 2005), as well as reflectance spectrophotometry (Zonios, et al., 2001). The Scottish Skin Classification System includes six skin types (I-VI), and as the term is used herein, Type VI skin, which is Type V or below, is "whitened." As discussed further below, skin lightening can occur through several phenomena, including, but not limited to, modulating melanocyte activity, inducing melanocyte apoptosis, or modulating aromatic hydrocarbon receptor (AhR) activity, melanogenesis, melanosome biogenesis, melanosome transport, or melanin concentration.

[0686] Similarly, as used herein, " skin darkening " and its grammatical variants generally refer to any actual or apparent increase in skin pigmentation.Skin darkening methods are used to increase the pigmentation of skin areas that have reduced pigmentation due to hypopigmentation disorders, for example.For example, when the compound and composition of the present invention are applied to the skin of a subject, pigmentation can be increased, and as a result, skin appears darker than before said application.

[0687] Certain compounds of the present invention are produced by, derived from, isolated from, or isolatable from Malassezia yeast. Malassezia yeasts are yeasts of the genus Malassezia, including, but not limited to, Malassezia globosa, Malassezia restricta, Malassezia furfur, Malassezia sympodialis, Malassezia slooffiae, Malassezia obtusa, Malassezia pachydermatis, Malassezia dermatis, Malassezia japonica, Malassezia nana, Malassezia yamatoensis, Malassezia equine, Malassezia caprae, and Malassezia cuniculi (Gueho, et al., 1996; Gaitanis, et al., 2013). Malassezia yeasts are normally Malassezia yeasts are a normal part of the human skin microbiota and do not normally produce pathogenic effects. However, Malassezia yeasts can cause several diseases, including but not limited to tinea versicolor (both tinea nigricans and tinea alba), seborrheic dermatitis, dandruff, atopic dermatitis, Malassezia folliculitis, psoriasis, and confluent reticular papillomatosis (Gaitanis, et al., 2013).

[0688] As used herein, the term "chemical analog" refers to a compound that is structurally related to a parent compound and contains different functional groups or substituents.For example, parent compounds of the present invention include malassezin and indirubin, and chemical analogs of malassezin and indirubin contain certain functional groups and substituents that are different from malassezin and indirubin, respectively.Chemical analogs of the present invention may have significant advantages over a given parent compound, including a pharmacokinetic profile that is suitable for cosmetic or pharmaceutical use.In some embodiments, chemical analogs are produced from parent molecules by one or more chemical reactions.In other embodiments, chemical analogs of the present invention can be produced using alternative synthetic schemes that do not originate from parent compounds.

[0689] The compounds of the present invention are produced by Malassezia yeast when, over the course of its life cycle and under appropriate growth conditions, the yeast synthesizes, secretes, accumulates, or otherwise produces the compounds. Malassezia yeast secretes different compounds depending on what is supplemented in its growth medium (Nazzaro-Porro, et al., 2001). al., 1978). While the present invention includes any compound produced by Malassezia yeast under any growth conditions, preferred compounds include, for example, malassedin, indirubin, and their chemical analogs.

[0690] The compounds of the present invention are derived from Malassezia yeast when the compounds are present on or within the yeast at any time during the yeast's life cycle.

[0691] Malassedin is an example of a compound produced by the Malassezia yeast of the present invention. Malassedin, also known as 2-(1H-indol-3-ylmethyl)-1H-indole-3-carbaldehyde, is a tryptophan metabolite originally isolated from Malassezia furfur. Malassedin is a known agonist of the aryl hydrocarbon receptor (AhR), a receptor involved in cell growth, differentiation, and gene expression (Wille et al., 2001). Malassedin also inhibits apoptosis in primary human melanocytes. Recently, certain chemical analogs of malassezins have been shown to induce A rhodopsin analog was synthesized by Winston-McPherson and coworkers, who tested the analog for AhR agonist activity (Winston-McPherson, et al., 2014).

[0692] Indirubin is another example of the compound produced by Malassezia yeast of the present invention.Indirubin is a metabolite isolated from Malassezia furfur.Indirubin is a known agonist of aromatic hydrocarbon receptor (AhR), which is a receptor involved in cell growth, differentiation and gene expression.

[0693] As used herein, the term "melanocyte" refers to a dendritic cell of the epidermis that normally synthesizes tyrosinase and the pigment melanin within melanosomes. The melanocytes of the present invention exhibit upregulation of certain genes, including, but not limited to, one or more of the following: tyrosinase (oculocutaneous albinism IA), microphthalmia-associated transcription factor, alpha-2-macroglobulin, tyrosinase-related protein 1, solute carrier family 16, GS3955 protein, v-kit Hardy-Zuckerman 4 feline sarcoma, ocular albinism 1, Rag D protein, glycogenin 2, G protein-coupled receptor, family C, oculocutaneous albinism II resected in esophageal cancer 1, melan-A, SRY-box 10, ATPase, class V, type 10C, matrix metalloproteinase 1, latent transforming growth factor beta b, ATP-binding cassette, subfamily C, hydroxyprostaglandin dehydrogenase 15, transmembrane 7 superfamily member 1, glutaminyl-peptide cyclotransferase, and other genes identified by Lee and colleagues (Lee, et al., 2013).

[0694] Melanocytes, like many other cell types, undergo programmed cell death, or apoptosis. The melanocyte apoptotic pathway is known to those skilled in the art (Wang, et al. al., 2014), and apoptotic pathways have been generally reviewed by Elmore (Elmore, 2007). The compounds or compositions of the present invention may be used to inhibit apoptosis in, for example, melanocytes. The compounds or compositions of the present invention "induce" melanocyte apoptosis by causing the activation of certain pro-apoptotic signaling pathways or the inhibition of certain anti-apoptotic pathways. It is envisioned that the compounds or compositions of the present invention can directly activate / inhibit apoptosis-related pathways by directly interacting with signaling molecules of the pathways or by indirectly interacting with molecules of the pathways through direct interaction with one or more intermediate molecules that do not normally function within the pathways.

[0695] Melanocyte activity can be modulated in several ways contemplated by the present invention, including, but not limited to, inducing melanocyte apoptosis or altering melanocyte gene expression, cell motility, cell growth, melanin production, melanosome biogenesis or melanosome transport.

[0696] As used herein, the terms "modulate," "modulating," and grammatical variations thereof refer to adjusting a biological activity or phenomenon to a desired level. "Modulate" in this invention is intended to include adjustments that increase or decrease the level of a biological activity or phenomenon.

[0697] As used herein, the terms "agonist," "agonize," and grammatical variations thereof refer to a molecule that triggers (e.g., initiates or promotes), partially or fully enhances, stimulates, or activates one or more biological activities. Agonists of the present invention can interact with and activate receptors, thereby initiating a physiological or pharmacological response characteristic of that receptor. Agonists of the present invention include natural and synthetic substances.

[0698] As used herein, the term "antagonist", "antagonize" and its grammatical variants refer to a molecule that partially or completely suppresses, inhibits or inactivates one or more biological activities.The antagonist of the present invention can competitively bind to receptor at the same site as agonist, but does not activate the intracellular response initiated by the active form of receptor.The antagonist of the present invention can inhibit the intracellular response of agonist or partial agonist.

[0699] The aryl hydrocarbon receptor (AhR) of the present invention is any naturally occurring aryl hydrocarbon receptor in the subject described herein. Aromatic hydrocarbon receptors are known to those skilled in the art (Noakes, 2015). Aromatic hydrocarbon receptor agonists include, but are not limited to: Although not commonly used, tryptophan-related compounds include kynurenine, kynurenic acid, cinnavalinic acid, and 6-formylindolo[3,2-b]carbazole (FICZ). Malasedin is also known as an aromatic hydrocarbon receptor agonist (Wille, et al., 2001).

[0700] As used herein, the compounds, compositions, and methods of the present invention can be used to improve hyperpigmentation caused by hyperpigmentation disorders, for example, by reducing the level of hyperpigmentation in areas affected by hyperpigmentation disorders, by slowing further hyperpigmentation, or by preventing further hyperpigmentation from occurring. However, it is possible that not all subjects will respond to a particular administration protocol, regimen, or method, and therefore, it is important to understand the scope of the invention. Amelioration of hyperpigmentation does not require achieving a desired physiological response or outcome in every subject or subject population. Thus, a given subject or subject population may not respond or may respond inadequately to administration, while other subjects or subject populations may respond and therefore experience improvement in their hyperpigmentation disorder.

[0701] As used herein, the term "hyperpigmentation" refers to a real or visually perceived skin disorder that is too dark.The skin damage can be real, for example, due to age, excessive sun exposure, or a disease or condition that causes the skin area to darken.The dark skin area can be in the form of a spot, a stain, or a relatively large black area.This skin damage can also be visually perceived, for example, the individual's perception that their skin tone is too dark.An individual may have a cosmetic desire to lighten their skin tone.

[0702] Hyperpigmentation disorders are disorders in which hyperpigmentation is a primary symptom and disorders in which hyperpigmentation occurs as a secondary symptom. Hyperpigmentation disorders of the present invention include, but are not limited to, congenital hyperpigmentation disorders and acquired hyperpigmentation disorders. Congenital hyperpigmentation disorders of the present invention include, but are not limited to, those involving epidermal hyperpigmentation (nevus cell nevi, Spitz nevi, and nevus spilus), dermal hyperpigmentation (blue nevi, nevus of Ota, cutaneous melanosis, nevus of Ito, and Mongolian spots), freckles, acropigmentation reticulata, acropigmentation / acropigmentation, and lentigines (generalized lentigines, leopard syndrome, hereditary patterned lentigines, Carney complex, Peutz-Jeghers syndrome, Laugier-Hunziker-Baran syndrome, and Cronkhite-Canada syndrome). (Yamaguchi, et al., 2014). Acquired hyperpigmentation disorders of the present invention include, but are not limited to, senile lentigo / lentigines, melasma / chloasma, Lille's melanosis, lip melanoma, penile / vulvovaginal melanosis, facial follicular erythematous melanosis (Kitamura), UV-induced pigmentation (sunburn and actinic petaloid pigmentation), post-inflammatory pigmentation (frictional melanosis and ashy dermatosis), chemical / drug-induced pigmentation (polychlorinated biphenyls, arsenic, 5-FU, bleomycin, cyclophosphamide, methotrexate, chlorpromazine, phenytoin, tetracycline, and chloroquine), pigmented borders, and foreign body deposits (such as carotene, silver, gold, mercury, bismuth, and tattoos). Hyperpigmentation associated with systemic disorders includes metabolic / enzymatic disorders (hemochromatosis, Wilson's disease, Gaucher's disease, Niemann-Pick disease, amyloidosis, histochromia nigricans, acanthosis nigricans, and porphyria cutanea tarda), endocrine disorders (Addison's disease, Cushing's syndrome, and hyperthyroidism), nutritional disorders (pellagra, vitamin B12 deficiency, folate deficiency, Vagabond's disease, and prurigo pigmentosa), mastocytosis, collagen diseases, and liver and kidney dysfunction. Hyperpigmentation can also be associated with infectious diseases (measles, syphilis, and Malassezia furfur) and syndromes (von Recklinghausen's disease, Sotos syndrome, POEMS syndrome, Naegeli syndrome, Cantu syndrome, McCune-Albright syndrome, Watson syndrome, and Bloom syndrome) (Yamaguchi, et al., 2014).

[0703] Melanin is a naturally occurring pigment that provides skin and hair with color. A schematic diagram of skin is shown in FIG. 1A. Melanin is produced by melanocytes in organelles known as melanosomes through a process known as melanogenesis. The compounds or compositions of the present invention modulate melanin production (also known as melanogenesis) in a subject, for example, by modulating melanosome biogenesis and directly or indirectly inhibiting melanin synthesis at the enzyme level.

[0704] Melanosome biogenesis occurs in four stages: Stage I is characterized by premelanosomes, which are essentially non-pigmented vacuoles; in Stage II, premelanosomes develop striations into which melanin is deposited in Stage III; and by Stage IV, mature melanin-rich melanosomes are formed. The compounds and compositions of the present invention modulate melanosome biogenesis by inhibiting or attenuating the biological processes that normally drive any or all of these steps (Wasmeier, et al., 2008).

[0705] Melanin synthesis primarily involves three enzymes: tyrosinase, tyrosinase-related protein-1, and dopachrome tautomerase. Additional factors that affect the intracellular trafficking of these enzymes include, but are not limited to, BLOC-1, OA1, and SLC45A2. The compounds and compositions of the present invention can modulate melanin production, for example, by inhibiting or attenuating the activity of any of these enzymes or factors (Yamaguchi, et al., 2014).

[0706] Once melanosomes are formed and melanin is synthesized, they must be transported from epidermal melanocytes to skin and hair keratinocytes. Melanosomes originate near the nucleus of melanocytes and are transported along microtubules and actin filaments to the periphery of melanocytes. The compounds and compositions of the present invention modulate melanosome transport by interfering with the biological processes that lead to the transport of melanosomes from the perinuclear region to the periphery of melanocytes and into adjacent keratinocytes. A schematic diagram of melanin synthesis, melanin transport, and melanocyte apoptosis is shown in Figure 1B.

[0707] Melanin concentration can be modulated, for example, in a subject by increasing or decreasing melanin formation, or by promoting melanin degradation, or by eliminating it from the subject.

[0708] The compounds isolated from the Malassezia yeast of the present invention are necessarily present in or produced by the Malassezia yeast prior to isolation. Thus, the compounds isolated from Malassezia yeast are derived from actual yeast cells. Standard protocols for extracting compounds from cellular material are known to those skilled in the art.

[0709] Compounds that can be isolated from Malassezia yeast do not necessarily have to be derived from actual yeast cells. Instead, synthetic reactions can be used to generate compounds produced in yeast without the involvement of actual yeast cells. Organic synthesis reactions are well known to those skilled in the art and can be used in this regard.

[0710] As used herein, the term "epidermal melanin" refers to melanin that is produced in, transported to, or otherwise found in the epidermis.

[0711] As used herein, the term "reduce" and its grammatical variants refer to causing a reduction in the level of a given biological phenomenon or species. For example, the compounds and compositions of the present invention reduce epidermal melanin in a subject, meaning that the compounds and compositions of the present invention induce a reduction in the level of epidermal melanin in a subject. The term "reduce" and its grammatical variants can refer to, for example, reducing the level of a given phenomenon or species by at least 5%, 10%, 25%, 50%, 75% or 100%.

[0712] As used herein, the term "contacting" and grammatical variations thereof refer to bringing two or more substances into sufficient proximity so that they can interact. Thus, for illustrative purposes only, a compound of the present invention can contact a melanocyte, for example, by interacting with a receptor on the surface of the melanocyte. Similarly, the compositions of the present invention can be contacted with a human subject, for example, by application directly to the subject's skin.

[0713] As used herein, "subject" refers to a mammalian cell, tissue, organism, or population thereof. Subjects of the present invention are preferably humans, including human cells, tissues, and organisms, but also include primates, livestock, farm animals, laboratory animals, and the like. Some examples of agricultural animals include cows, pigs, horses, goats, and the like. Some examples of farm animals include dogs, cats, and the like. Some examples of laboratory animals include primates, rats, mice, rabbits, guinea pigs, and the like.

[0714] As used herein, a subject "in need" of improvement in hyperpigmentation caused by a hyperpigmentation disorder includes a subject who has a real or apparent need for improvement.

[0715] As used herein, the terms "treat," "treating," "treatment," and their grammatical variants refer to administering a protocol, regimen, method, or therapy to an individual subject, and it is desired to obtain a physiological response or outcome in the subject, e.g., a patient. In particular, the methods and compositions of the present invention may be used to slow down the onset of disease symptoms, or to delay the onset of a disease or condition, or to stop the progression of disease development. However, treating does not necessarily achieve a desired physiological response or outcome in every subject or subject group, e.g., a patient group, because not all treated subjects may respond to a particular treatment protocol, regimen, method, or therapy. Thus, a given subject or subject group, e.g., a patient group, may not respond to treatment or may respond inappropriately.

[0716] As used herein, the terms "prevent," "preventing," "prevention," and grammatical variations thereof mean that the compounds of the invention are useful when administered to patients who have not been diagnosed as possibly having a disorder or disease at the time of administration, but who are normally expected to develop the disorder or disease or to be at increased risk of the disorder or disease. The compounds and compositions of the invention, for example, slow the onset of symptoms of the disorder or disease, delay the onset of the disorder or disease, or prevent the individual from developing the disorder or disease altogether. Prevention also includes administering a compound of the invention to such individuals believed to be susceptible to a disorder or disease due to age, family history, genetic or chromosomal abnormalities, and / or the presence of one or more biological markers for the disorder or disease.

[0717] As used herein, the term "facilitate" and grammatical variations thereof means to enable, enhance, permit, facilitate, encourage, encourage, induce, or otherwise help to cause.

[0718] As used herein, the term "produce" and grammatical variations thereof mean to cause, bring about, or produce a particular result. As a non-limiting example, the compounds and compositions of the present invention produce a photoprotective or UV protective effect in a subject.

[0719] As used herein, the term "erythema" refers to reddening of the skin. Erythema can be caused by the dilation and / or irritation of superficial capillaries. The term "UV-induced erythema" refers to reddening of the skin that develops as a result of UV exposure. As used herein, "sunburn" and its grammatical variants refer to UV-induced erythema caused by exposure to sunlight or artificial UV sources (e.g., tanning beds).

[0720] As used herein, the term "hyperpigmentation" generally refers to an area of ​​skin (e.g., pigmented spots, age spots, lentigines, etc.) in which the pigmentation is greater than that of adjacent areas of the skin. Hyperpigmentation of the present invention includes, but is not limited to, localized hyperpigmentation due to melanocyte hyperactivity, other localized hyperpigmentation due to benign melanocyte hyperactivity and proliferation, disease-related hyperpigmentation, as well as incidental hyperpigmentation such as that due to photosensitivity, genetic makeup, chemical ingestion or other exposure (e.g., UV exposure), age, and post-lesional scarring. As used herein, "UV-induced hyperpigmentation" refers to any hyperpigmentation caused by exposure to natural or artificial UV.

[0721] As used herein, the term "hypopigmentation" generally refers to an area of ​​skin that is less pigmented than adjacent areas of the skin. Hypopigmentation of the present invention includes, but is not limited to, vitiligo, depigmentation, pityriasis alba, focal hypopigmentation, post-inflammatory hypopigmentation, mottling, albinism, tinea versicolor, photosensitivity, congenital hypopigmentation, hypomelanosis, atopic dermatitis, psoriasis, etc.

[0722] As used herein, "UV-induced skin damage" refers to skin damage resulting from exposure to UV, including UVA, UVB, and UVC. The UV-induced skin damage of the present invention includes, but is not limited to, wrinkles, hyperpigmentation, dysplasia, actinic keratosis, and skin cancer.

[0723] As used herein, "UV-induced aging of skin" refers to aging of skin caused by exposure to UV, including UVA, UVB, and UVC. The UV-induced aging of skin in the present invention is manifested, for example, as wrinkles, fine lines, age spots, lentigines, dryness, thinning, or loss of skin elasticity, uneven skin tone, and other declines in skin radiance, texture, elasticity, firmness, sagging, and clarity, caused in whole or in part by UV exposure.

[0724] As used herein, the term "photoprotective" and grammatical variations thereof, when used to describe the effects of the compounds and compositions of the present invention, means that the compounds and compositions described herein prevent and / or mitigate damage caused by light, particularly sunlight. Similarly, "photoprotective agents" of the present invention are compounds and compositions described herein that prevent and / or mitigate damage caused by light, particularly sunlight.

[0725] As used herein, the term "UV protective" and its grammatical variations, when used to describe the effects of the compounds and compositions of the present invention, means that the compounds and compositions described herein prevent and / or mitigate damage caused by ultraviolet ("UV") light. Similarly, "UV protectants" of the present invention are compounds and compositions described herein that prevent and / or mitigate damage caused by UV light. Ultraviolet light of the present invention includes, for example, UVA (320-240 nm), UVB (290-320 nm), and UVC (200-290 nm).

[0726] As used herein, the term "filter" and grammatical variations thereof means to block, reflect, absorb, or scatter UV light. "Sunscreens" of the present invention include all compounds and compositions of the present invention that block, reflect, absorb, or scatter UV light.

[0727] As used herein, the term "absorb" and grammatical variations thereof means to capture UV or convert UV into heat energy. As a non-limiting example, the compounds and compositions of the present invention can absorb UV and thereby release heat energy into their surroundings. It can emit ghee.

[0728] As used herein, the term "reflect" and grammatical variations thereof, when used in the context of UV, means to transmit or bounce UV without absorbing it.

[0729] As used herein, the term "composition" refers to an entity comprising one or more compounds of the present invention, as well as any entity derived directly or indirectly from a combination of one or more compounds of the present invention with other ingredients. Compositions of the present invention can be used, for example, as research reagents in vitro or in vivo. Compositions of the present invention can also be applied directly to the skin of a human or non-human subject for cosmetic or pharmaceutical benefits. Additionally, compositions of the present invention comprise one or more of the compounds listed in Table 5 or Figure 130, or chemical analogs, crystalline forms, hydrates, or pharmaceutically or cosmetically acceptable salts thereof.

[0730] The compositions of the present invention may be administered in any desired and effective manner for both in vitro and in vivo use: orally or parenterally, or by any suitable method, such as intraperitoneally, subcutaneously, topically, intradermally, by inhalation, pulmonary, rectally, vaginally, sublingually, intramuscularly, intravenously, intraarterially, intrathecally, or intralymphatically. Additionally, the compositions of the present invention may be administered in conjunction with other compositions. The compositions of the present invention may be encapsulated or otherwise protected from gastric or other secretions, if desired.

[0731] The compositions of the present invention comprise one or more active ingredients mixed with one or more cosmetically or pharmaceutically acceptable carriers, and optionally one or more other compounds, ingredients and / or substances. Regardless of the route of administration selected, the compounds and compositions of the present invention are formulated into cosmetically or pharmaceutically acceptable dosage forms by conventional methods known to those skilled in the art.

[0732] Cosmetically or pharmaceutically acceptable vehicles, diluents, and carriers are well known in the art and include materials suitable for contact with human and non-human tissues without undue toxicity, incompatibility, instability, irritation, allergic reaction, etc. Cosmetically or pharmaceutically acceptable vehicles, diluents, and carriers include, for example, any substantially non-toxic material conventionally usable for topical, oral, intraperitoneal, or subcutaneous administration of cosmetics or pharmaceuticals, such that the compounds and compositions of the present invention remain stable and bioavailable when applied, ingested, injected, or otherwise administered to a human or non-human subject. Cosmetically or pharmaceutically acceptable carriers suitable for topical application are known to those skilled in the art and include cosmetically or pharmaceutically acceptable liquids, creams, oils, lotions, ointments, gels, or solids, such as conventional cosmetic night creams, foundation creams, suntan lotions, sunscreens, hand lotions, makeup and makeup bases, masks, etc. Carriers suitable for a selected dosage form and intended route of administration are well known in the art, and acceptable carriers for a selected dosage form and method of administration can be determined using ordinary skill in the art.

[0733] The compositions of the present invention may contain other ingredients conventional in cosmetics, including fragrances, estrogen, vitamins A, C, and E, alpha-hydroxy acids or alpha-keto acids such as pyruvic acid, lactic acid, or glycolic acid, lanolin, petrolatum, aloe, methyl or propyl paraben, pigments, etc. Non-limiting cosmetically or pharmaceutically acceptable vehicles, diluents, and carriers of the present invention include sugars (e.g., lactose, sucrose, mannitol, and sorbitol), starches, cellulose preparations, calcium phosphates (e.g., dicalcium phosphate, tricalcium phosphate, and calcium hydrogen phosphate), and the like. Examples of suitable carriers include cereals containing glutamic acid, glutamic acid, cereals containing glutamic acid, and cereals containing glutamic acid include glutamic acid, glutamic acid, glutamic acid esters ...

[0734] The composition of the present invention may optionally contain additional ingredients and / or materials that are commonly used in cosmetic compositions.These ingredients and materials are well known in the art, and include, for example, (1) fillers or extenders such as starch, lactose, sucrose, glucose, mannitol, and silicic acid; (2) binders such as carboxymethylcellulose, alginate, gelatin, polyvinylpyrrolidone, hydroxypropylmethylcellulose, sucrose, and acacia; (3) moisturizers such as glycerol; (4) agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates, sodium starch glycolate; (6) absorption enhancers such as quaternary ammonium compounds; (7) wetting agents such as cetyl alcohol and glycerol monostearate; (8) absorbents such as kaolin and bentonite clay; (9) lubricants such as talc, calcium stearate, magnesium stearate, solid polyethylene glycol, and sodium lauryl sulfate; (10) suspending agents such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar, and tragacanth; (11) buffering agents; (12) lactose, milk sugar, polyethylene glycol, animal and vegetable fats, oils, waxes, paraffin, cocoa butter, starch, tragacanth, cellulose derivatives, polyethylene glycol, silicones, bentonite, silicic acid, talc, salicylates, zinc oxide, aluminum hydroxide, calcium silicate, and polyamide powder. (13) inert diluents such as water or other solvents, (14) preservatives, (15) surfactants, (16) dispersing agents, (17) controlled-release or absorption-delaying agents such as hydroxypropyl methylcellulose, other polymer matrices, biodegradable polymers, liposomes, microspheres, aluminum monostearate, gelatin, and waxes, (18) opacifying agents, (19) adjuvants, (20) wetting agents, (21) emulsifying and suspending agents, (22) ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate,These include solubilizing and emulsifying agents such as benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, oils (especially cottonseed oil, peanut oil, corn oil, germ oil, olive oil, castor oil, and sesame oil), glycerol, tetrahydrofuryl alcohol, polyethylene glycol, and fatty acid esters of sorbitan, (23) propellants such as chlorofluorohydrocarbons and volatile unsubstituted hydrocarbons (such as butane and propane), (24) antioxidants, (25) agents that render the formulation isotonic with the blood of the intended recipient, such as sugars and sodium chloride, (26) thickening agents, (27) coating materials such as lecithin, and (28) sweetening agents, flavoring agents, coloring agents, perfumes, and preservatives. Each such ingredient or substance must be "acceptable" in the sense of being compatible with the other ingredients of the formulation and not injurious to the subject. Ingredients and materials suitable for a selected dosage form and intended route of administration are well known in the art, and acceptable ingredients and materials for a selected dosage form and method of administration can be determined using ordinary skill in the art.

[0735] Compositions of the present invention suitable for oral administration can be in the form of a capsule, cachet, pill, tablet, powder, granule, solution, or suspension in an aqueous or non-aqueous liquid, an oil-in-water or water-in-oil liquid emulsion, an elixir or syrup, pastille, bolus, electuary, or paste. These formulations can be prepared by methods known in the art, for example, by conventional pan-coating, mixing, granulating, or lyophilizing methods.

[0736] Solid dosage forms for oral administration (such as capsules, tablets, pills, dragees, powders, and granules) can be prepared, for example, by mixing the active ingredient with one or more cosmetically or pharmaceutically acceptable carriers, and, optionally, one or more fillers, extenders, binders, humectants, disintegrants, solution retarders, absorption accelerators, wetting agents, absorbents, lubricants, and / or colorants. Solid compositions of a similar type may also be used as fillers in soft and hard-filled gelatin capsules using suitable excipients. Tablets may be made by compression or molding, optionally with one or more accessory ingredients. Compressed tablets may be prepared using suitable binders, lubricants, inert diluents, preservatives, disintegrants, surfactants, or dispersing agents. Molded tablets may be made by molding in a suitable machine. Tablets, as well as other solid dosage forms such as capsules, pills, and granules, may be scored, or prepared with coatings and shells, such as enteric coatings and other coatings well known in the cosmetic formulation arts. They may also be formulated to achieve sustained or controlled release of the active ingredient therein. They may be sterilized, for example, by filtration through a bacteria-retaining filter. These compositions may also optionally contain opacifying agents, and may be formulated so as to release the active ingredient only, or preferentially, in a certain part of the gastrointestinal tract, optionally in a delayed manner. The active ingredient may also be in microencapsulated form.

[0737] The liquid dosage form for oral administration includes cosmetically or pharmaceutically acceptable emulsion, microemulsion, solution, suspension, syrup and elixir.Liquid dosage form can contain suitable inert diluent commonly used in the art.In addition to inert diluent, this oral composition can also contain adjuvants such as wetting agent, emulsifying and suspending agent, sweetener, flavoring agent, coloring agent, perfume and preservative.Suspension can also contain suspending agent.

[0738] The composition of the present invention for rectal or vaginal administration may be provided as a suppository, which can be prepared by mixing one or more active ingredients with one or more suitable non-irritating carriers, which are solid at room temperature but liquid at body temperature, and therefore melt in the rectum or vaginal cavity to release the active compound.The composition of the present invention suitable for vaginal administration also includes pessaries, tampons, creams, gels, pastes, foams or spray formulations containing such cosmetically or pharmaceutically acceptable carriers known to be suitable in the art.

[0739] Dosage forms for topical or transdermal administration include powders, sprays, ointments, pastes, creams, lotions, gels, solutions, patches, drops, emulsions, suspensions, aerosols, and inhalants. Any desired conventional vehicles, adjuvants, and, if necessary, additional active ingredients may be added to the formulation.

[0740] Preferred auxiliaries are from the group comprising preservatives, antioxidants, stabilizers, solubilizers, vitamins, colorants, odor improvers, film formers, thickeners and moisturizers.

[0741] Solutions and emulsions may be prepared using conventional vehicles such as solvents, solubilizers and emulsifiers. , for example, water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butyl glycol, oils, especially cottonseed oil, peanut oil, corn oil, olive oil, castor oil and sesame oil, glycerol fatty acid esters, polyethylene glycol, and fatty acid esters of sorbitan, or mixtures of these substances.

[0742] Emulsions may exist in various forms, and thus may be, for example, water-in-oil (W / O) or oil-in-water (O / W) emulsions or microemulsions, or may be multiple emulsions, such as water-in-oil-in-water (W / O / W) emulsions or microemulsions.

[0743] The compositions according to the invention may also be in the form of emulsifier-free dispersed preparations, for example aqueous dispersions or Pickering emulsions.

[0744] Suspensions may include conventional vehicles such as liquid diluents, for example, water, ethanol or propylene glycol, suspending media, for example, ethoxylated isostearyl alcohol, polyoxyethylene sorbitol esters and polyoxyethylene sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar and tragacanth, or mixtures of these substances.

[0745] The pastes, ointments, gels and creams may contain conventional vehicles such as animal and vegetable fats, waxes, paraffin, starch, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonite, silicic acid, talc and zinc oxide, or mixtures of these substances.

[0746] Face and body oils may contain conventional vehicles such as synthetic oils (such as fatty acid esters, fatty alcohols, silicone oils), natural oils (such as vegetable oils and oily plant extracts, paraffin oil, lanolin oil), or mixtures of these substances.

[0747] Sprays may contain customary propellants, such as chlorofluorocarbons, propane / butane or dimethyl ether.

[0748] The compositions of the present invention suitable for parenteral administration comprise one or more compounds in combination with one or more cosmetically or pharmaceutically acceptable sterile isotonic aqueous or non-aqueous solutions, dispersions, suspensions, or emulsions, or sterile powders that can be reconstituted immediately before use into sterile injectable solutions or dispersions, which may contain suitable antioxidants, buffers, solutes that render the formulation isotonic with the blood of the intended recipient, or suspending or thickening agents. Proper fluidity can be maintained, for example, by the use of coating materials, by maintaining the required particle size in the case of dispersions, and by the use of surfactants. These compositions may also contain suitable adjuvants such as wetting agents, emulsifying agents, and dispersing agents. It may also be desirable to include an isotonic agent. In addition, prolonged absorption of injectable cosmetic forms can be achieved by including an agent that delays absorption.

[0749] In some cases, in order to prolong the effect, it is desirable to slow the absorption from subcutaneous or intramuscular injection. This can be accomplished by the use of a liquid suspension of crystalline or amorphous material with poor water solubility.

[0750] The rate of absorption of the active agent / drug then depends on its rate of dissolution, which in turn may depend on crystal size and crystalline form. Alternatively, delayed absorption of a parenterally administered composition can be achieved by dissolving or suspending the active compound in an oil vehicle. Depot formulations can be prepared by forming microencapsulated matrices of active ingredients in biodegradable polymers.The release rate of active ingredients can be controlled depending on the ratio of active ingredients to polymer and the properties of the specific polymer used.Injectable depot formulations can also be prepared by entrapping drugs in liposomes or microemulsions that are compatible with body tissues.Injectable materials can be sterilized, for example, by filtration through a bacteria-retaining filter.

[0751] The compositions of the invention may be presented in unit-dose or multi-dose sealed containers, for example, ampoules and vials, and may be stored in a freeze-dried condition requiring only the addition of the sterile liquid carrier, for example, water for injections, immediately prior to use. Extemporaneous injection solutions and suspensions may be prepared from sterile powders, granules, and tablets of the type described above.

[0752] In the present invention, the term "crystalline form" refers to the crystalline structure of a compound. A compound may exist in one or more crystalline forms, which may have different structural, physical, pharmacological, or chemical properties. Differences in nucleation, growth rate, aggregation, and breakage can be used to obtain different crystalline forms. Nucleation occurs when the phase transition energy barrier is overcome, allowing particles to form from a supersaturated solution. Crystal growth is the expansion of crystalline particles caused by the deposition of chemical compounds on the existing surface of the crystal. The relative rates of nucleation and growth determine the size distribution of the formed crystals. The thermodynamic driving force for both nucleation and growth is supersaturation, which is defined as a deviation from thermodynamic equilibrium. Aggregation is the formation of larger particles by two or more particles (e.g., crystals) adhering to each other to form a larger crystalline structure.

[0753] The term "hydrate," as used herein, means a solid or semi-solid form of a chemical compound that contains water in a molecular complex. The water is generally in a stoichiometric amount relative to the chemical compound.

[0754] As used herein, "cosmetically or pharmaceutically acceptable salts" refers to derivatives of the compounds disclosed herein, in which the compound is modified by making its acid or base salt. Examples of cosmetically or pharmaceutically acceptable salts include, but are not limited to, inorganic or organic acid salts of basic residues such as amines, alkali or organic salts of acidic residues such as carboxylic acids, etc. For example, such salts include ammonia, L-arginine, betaine, benethamine, benzathine, calcium hydroxide, choline, deanol, diethanolamine (2,2'-iminobis(ethanol)), diethylamine, 2-(diethylamino)-ethanol, 2-aminoethanol, ethylenediamine, N-ethyl-glucamine, hydrabamine, 1H-imidazole, lysine, magnesium hydroxide, 4-(2-hydroxyethyl)-morpholine, piperazine, potassium hydroxide, 1-(2-hydroxyethyl)-pyrrolidine, sodium hydroxide, triethanolamine (2 ,2',2"-Nitrilotris(ethanol)), tromethamine, zinc hydroxide, acetic acid, 2,2-dichloro-acetic acid, adipic acid, alginic acid, ascorbic acid, L-aspartic acid, benzenesulfonic acid, benzoic acid, 2,5-dihydroxybenzoic acid, 4-acetamido-benzoic acid, (+)-camphoric acid, (+)-camphor-10-sulfonic acid, carbonic acid, cinnamic acid, citric acid, cyclamic acid, decanoic acid, dodecylsulfuric acid, ethane-1,2-disulfonic acid, ethanesulfonic acid, 2-hydroxy-ethanesulfonic acid, ethylenediaminotetraacetic acid, formic acid, fumaric acid, mucic acid (galacaric acid), gentisic acid, D-glucoheptonic acid, D- Gluconic acid, D-glucuronic acid, glutamic acid, glutantic acid, Glutaric acid, 2-oxoglutaric acid, glycerophosphate, glycine, glycolic acid, hexanoic acid, hippuric acid, hydrobromic acid, hydrochloric acid, isobutyric acid, DL-lactic acid, lactobionic acid, lauric acid, lysine, maleic acid, (-)-L-malic acid, malonic acid, DL-mandelic acid, meta Included are salts from benzoic acid, ...

[0755] The cosmetically or pharmaceutically acceptable salts of the present invention can be synthesized from the compounds disclosed herein that contain a basic or acidic moiety by conventional chemical methods. Generally, such salts can be prepared by reacting the free acid or base form of these compounds with a sufficient amount of the appropriate base or acid in water or an organic diluent such as ether, ethyl acetate, ethanol, isopropanol, or acetonitrile, or a mixture thereof.

[0756] It is envisioned that the compounds and compositions of the present invention may be included in cosmetic or pharmaceutical compositions for both in vitro and in vivo applications.

[0757] It is envisioned that compounds and compositions of the present invention, including one or more compounds listed in Table 5 or Figure 130, or chemical analogs, crystalline forms, hydrates, or pharmaceutically or cosmetically acceptable salts thereof, can be co-administered to a subject to achieve the objective of modulating skin pigmentation of the present invention.

[0758] It is also envisioned that the compositions of the present invention may contain one or more compounds listed in Table 5 or Figure 130, or chemical analogs, crystalline forms, hydrates, or pharmaceutically or cosmetically acceptable salts thereof. For example, the compositions of the present invention may contain indirubin or a chemical analog thereof in combination with malasedin or a chemical analog thereof.

[0759] Furthermore, it is contemplated that the compounds of the present invention include compounds produced by Malassezia, or their chemical analogs, crystalline forms, hydrates, or pharmaceutically or cosmetically acceptable salts. Furthermore, it is contemplated that the compositions and methods of the present invention may include one or more compounds produced by Malassezia, or their chemical analogs, crystalline forms, hydrates, or pharmaceutically or cosmetically acceptable salts. For example, compounds produced by or derived from Malassezia include, but are not limited to, the compounds shown in Figure 130.

[0760] It is further envisioned that the methods of the present invention may include the step of co-administering two or more compounds and / or compositions of the present invention to achieve the objective of modulating skin pigmentation described herein.

[0761] The co-administered compounds and compositions of the present invention may, for example, be contacted with the subject substantially simultaneously or sequentially.

[0762] Compositions of the invention containing one or more Malassezia-derived compounds or chemical analogs thereof may demonstrate synergistic effects over the component compounds alone on various efficacy criteria, including, but not limited to, average tissue viability, melanin concentration, skin lightening, skin darkening, induction of melanocyte apoptosis, and modulating aromatic hydrocarbon (AhR) activity, melanogenesis, or melanin concentration.

[0763] The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting. As used in this specification and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise.

[0764] With respect to the recitation of numerical ranges herein, each intervening value therebetween, to the same precision, is specifically contemplated. For example, in the range of 6 to 9, the values ​​7 and 8 are specifically contemplated in addition to 6 and 9, and in the range of 6.0 to 7.0, the values ​​6.0, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, and 7.0 are specifically contemplated.

[0765] The following examples are presented to further illustrate the method of the present invention. These examples are merely illustrative and are not intended to limit the scope of the invention in any way. [Example]

[0766] Example 1 Materials and Methods Isolation of compounds produced by Malassezia. Malasedins can be isolated using procedures outlined, for example, in Wille et al., 2001. The protocol is briefly outlined below. Culture medium

[0767] A medium consisting of Tween 80 (30 mL), cycloheximide (0.5 g), chloramphenicol (0.05 g), agar (20 g), and enough water to make a 1000 mL mixture is sterilized and mixed with 0.3% sterile-filtered L-tryptophan at a concentration of 0.3 g at 50° C. 10 mL aliquots are poured into 10 cm Petri dishes and the pH is adjusted to 5.5 using 0.1 M HCl. Cultivation of Malassezia furfur and isolation of compounds produced by M. furfur

[0768] Malassezia furfur is scraped onto the above medium and incubated at 30°C for 14 days. The contents of the Petri dish are pureed and extracted with ethyl acetate for 12 hours. The extract is filtered over glass wool, evaporated to dryness, and dissolved in methanol. The extract is then fractionated by chromatography on Sephadex LH-20 using methanol as the eluent. Further separation is performed using preparative thin-layer chromatography with toluene:ethyl formate:formic acid (10:5:3). The major area is partitioned between water and ethyl acetate. Fractions are analyzed for the desired activity. Compounds from the desired fractions are isolated by HPLC. Synthesis of Malasedin and Chemical Analogues of Malasedin

[0769] Malasedin was synthesized according to the protocol described in Wille et al., 2001. Chemical analogs of malasedin have been synthesized using Shinki synthesis protocols and Winston-McPherson, The synthesis is carried out in accordance with the synthesis protocol described in [End Page 130] et al., 2014. Screening Protocol

[0770] Effective skin lightening compounds are evaluated using both screening protocols known to those skilled in the art and novel screening methods. For example, malassezin and its chemical analogs are evaluated by the tyrosinase bioassay, as described above. The aryl hydrocarbon receptor (A Other screening protocols involving both in vitro cell and in vivo tissue models, including HIV-1 (human R) binding assays, are utilized. Tyrosinase bioassay

[0771] Tyrosinase bioassays are performed as described by Wille et al., 2001. Briefly, L-dopa is mixed with tyrosinase enzyme. The disappearance, indicating the formation of dopaquinone, is measured over 1 minute. For example, using the fractions discussed above, these fractions are dissolved in DMSO and added directly to the tyrosinase reaction, with pure DMSO as a control. Tyrosinase inhibitory activity is measured as a decrease in the increase in disappearance compared to the control. Aromatic hydrocarbon receptor binding assay

[0772] The AhR binding assay was carried out according to the protocol described, for example, in Song, et al., 2002. Briefly, human and mouse AhRs are expressed in vitro using, for example, the TnT Quick-coupled Reticulocyte Lysate Systems reaction (Promega, Madison, WI). Receptor ligand binding studies are performed using the scroll method described by Karchner, et al., 1999. Velocity sedimentation on a gradient is used. EROD assay

[0773] The compounds, compositions and formulations of the present invention are also evaluated using the ethoxyresorufin-O-deethylase (EROD) assay, which is known to those skilled in the art (Donato, et al., 1993; Whyte, et al., 2000; Wille et al., 2001). Assay of melanocyte apoptosis

[0774] Candidate compounds are evaluated for apoptosis-inducing activity in melanocytes. Human epidermal melanocytes are cultured in Medium 254 supplemented with Human Melanocyte Growth Supplement (HMGS) (Thermo-Fisher Scientific, Waltham, MA) or Keratocyte Basal Medium (ATCC, Manassas, VA). Additional components of human melanocyte growth medium may include, but are not limited to, insulin (5 μg / ml), ascorbic acid (50 μg / ml), L-glutamine (6 mM), epinephrine (1.0 μM), and calcium chloride (0.2 mM). Human melanocyte cultures are maintained at 37°C in 5% CO2.

[0775] Candidate compounds are diluted in DMSO and mixed directly with the melanocyte cultures. An equivalent volume of pure DMSO is used as a control. Cytotoxicity assays known to those skilled in the art are performed according to the manufacturer's instructions. Cytotoxicity assays used in the present invention include, but are not limited to, the CellTox™ Green cytotoxicity assay, the Apo-ONE fluorescent caspase assay, the ApoTox-Glo™ assay, and the Caspase-Glo® assay (Promega, Madison, WI). Fluorescence detection can be performed using standard FACS known to those skilled in the art, including those described in Kramer, et al., 2005. or using a microscopic assay.

[0776] Additional means of assessing apoptosis are used, including FACS analysis for Annexin V and Western blot for caspase-9 expression. Western blotting is performed according to methods known to those skilled in the art. Mouse xenograft assay

[0777] Mouse xenograft models of human skin are generated according to protocols known in the art (Black, et al., 1985; Manning et al., 1973; Reed, et al., 1973; Plen (Taylor, et al., 1992; Scott et al., 1998; Otulakowski, et al., 1994). Once the mouse xenograft model is established, it is exposed to the compounds of the present invention and changes in pigmentation are observed compared to controls. Changes in skin pigmentation are assessed using various pigmentation scal...

Claims

1. 1. A composition for use in a method of modulating aromatic hydrocarbon receptor (AhR) activity in a subject, wherein said composition comprises a compound of the following formula: 【Chemistry 1】 [In the formula, X is selected from the group consisting of NH and O; Y is CR ５ R ６ , O or NR １５ and R １ , R ２ , R ３ , R ４ , R ７ , R ８ , R ９ , R １０ and R １１ is hydrogen, halogen, CN, hydroxyl, R １６ and OR １６ are independently selected from the group consisting of: R １５ is hydrogen or R １６ and R ５ and R ６ is hydrogen, hydroxyl, OR １６ , R １６ and C ３～６ cycloalkyl, or R ５ and R ６ together form an oxo (=O) group or C ３～６ Forming a cycloalkyl; R １２ is COR ａ and R １６ are each independently formyl, C １～９ Alkyl, C ２～９ alkenyl or C ２～９ alkynyl; and R ａ represents hydrogen, hydroxyl and OR １６ selected from the group consisting of: where: R ａ is hydrogen and Y is CR ５ R ６ If R ５ is hydroxyl, OR １６ and C ３～６ cycloalkyl or R ５ and R ６ Together, C ３～６ forming a cycloalkyl] or a hydrate or a cosmetically or pharmaceutically acceptable salt thereof.

2. The composition has the following structure: 【Chemistry 2】 10. The composition of claim 1, comprising a compound having the formula: or a hydrate or a cosmetically or pharmaceutically acceptable salt thereof.

3. 1. A composition for use in a method of modulating aromatic hydrocarbon receptor (AhR) activity in a subject, wherein said composition comprises a compound of the following formula: 【Transformation 3】 [In the formula, X is NR １４ and O; R １ , R ２ , R ３ , R ４ , R ７ , R ８ , R ９ , R １０ and R １１ is hydrogen, halogen, CN, hydroxyl, R １６ and OR １６ are independently selected from the group consisting of R １４ is hydrogen or R １６ and R １２ is COR ａ and R １６ are each independently formyl, C １～９ Alkyl, C ２～９ alkenyl or C ２～９ is alkynyl; R ａ represents hydrogen, hydroxyl and OR １６ selected from the group consisting of: Y is CR ５ R ６ and R ５ is hydrogen, and R ６ is C ３～６ Cycloalkyl or O—(C １～４ alkyl)] or a hydrate or a cosmetically or pharmaceutically acceptable salt thereof.

4. R １ , R ２ , R ３ , R ４ , R ７ , R ８ , R ９ , R １０ and R １１ The composition of claim 1 , wherein each of is hydrogen.

5. 4. The composition of claim 3, Where: X is NH; R １ , R ３ , R ４ , R ７ , R ８ , R ９ , R １０ and R １１ each of is hydrogen; and R ２ is hydrogen or C １～４ is alkyl, composition.

6. 4. The composition of claim 3, wherein X is NH.

7. 5. The composition of claim 4, wherein X is NH.

8. R １２ is CO(-O-C １～４ The composition of claim 5 wherein the aryl group is alkyl.

9. R １２ is CO(-O-C １～４ The composition of claim 1 , wherein the aryl group is aryl, ...

10. R １２ is CO(-O-C １～４ The composition of claim 2 wherein the aryl group is alkyl.

11. R １２ is CO(-O-C １～４ The composition of claim 6, wherein the aryl group is alkyl.

12. R １２ is CO(-O-C １～４ The composition of claim 7, wherein the aryl group is alkyl.

13. Y is CH(C ３ H ５ 6. The composition of claim 5, wherein

14. Y is CH(C ３ H ５ 9. The composition of claim 8, wherein

15. Y is CH(C ３ H ５ 10. The composition of claim 9, wherein

16. Y is CH(C ３ H ５ 11. The composition of claim 10, wherein

17. Y is CH(C ３ H ５ 12. The composition of claim 11, wherein

18. Y is CH(C ３ H ５ 13. The composition of claim 12, wherein

19. The composition comprises: 【Chemistry 19】 2. The composition of claim 1, comprising a compound selected from the group consisting of: or a hydrate or a cosmetically or pharmaceutically acceptable salt thereof.

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