Bakuchiol derivative, preparation method therefor, and use thereof

Abstract

Disclosed in embodiments of the present disclosure are a bakuchiol derivative, a preparation method therefor, and a use thereof. The bakuchiol derivative comprises: a bakuchiol derivative having the structure of formula (I) or a bakuchiol derivative having the structure of formula (II).

Description

Bakeuchiol derivatives, methods of making and uses of bakeuchiol derivatives

[0001] Cross-reference to Related Applications

[0002] This application claims priority to the Chinese patent application with the application date of September 13, 2024, the application number of 2024112918639, and the invention title of “Bakeuchiol derivatives, methods of making and uses of bakeuchiol derivatives”, the entire content of which is incorporated herein by reference in its entirety. TECHNICAL FIELD

[0003] Embodiments of the present disclosure relate to the field of biotechnology, in particular to bakeuchiol derivatives, methods of making and uses of bakeuchiol derivatives. BACKGROUND

[0004] In recent years, drug development based on synergistic mechanisms of drug active molecules has gradually become one of the research hotspots in the field of biotechnology. This approach aims to act on multiple targets or signaling pathways in a combined manner to achieve synergistic effects, thereby achieving more effective effects than single drugs. At present, the drug development method based on the synergistic mechanism of drug active molecules is to connect two compounds through a chemical bond to construct a new drug active molecule. The drug obtained based on this drug development method is usually a synergistic drug. Specifically, a synergistic drug is a new molecule that connects two different drugs through a covalent bond to achieve the purpose of concentrated exertion of drug effects and enhancement of synergistic effects between drugs. For example, by combining the antibiotic ampicillin and the beta-lactamase inhibitor sulbactam, ampicillin exerts its antibacterial effect while not being hydrolyzed by drug-resistant bacteria, thereby effectively solving the problem of ampicillin resistance.

[0005] Bakeuchiol (BKU) is a monoterpene compound isolated from Psoralea corylifolia L. of Leguminosae. It can be used to treat sallow skin and post-inflammatory pigmentation; it can inhibit free radical-induced lipid peroxidation; it can prevent damage to the skin by ultraviolet light and delay cell apoptosis; it can reduce collagen degradation and promote collagen synthesis. In addition, bakeuchiol has high mildness, low skin irritation, and no photosensitivity.

[0006] However, based on bakeuchiol, the following technical problems often exist:

[0007] How to develop a new active molecule with lower cytotoxicity and multiple effects on the basis of bakeuchiol has become a problem to be solved.

[0008] The above information disclosed in this Background section is only for enhancing the understanding of the background of the present inventive concepts, and therefore it can include information that does not form the prior art that is already known in this field to a person of ordinary skill in the art. SUMMARY

[0009] The Summary part of the disclosure is provided to introduce briefly the concepts that will be described later in the detailed description section. The Summary part of the disclosure is not intended to identify key or essential features of the claimed technology nor is it intended to be used to limit the scope of the claimed technology.

[0010] Some embodiments of the present disclosure propose psoralen derivatives, methods for preparing psoralen derivatives and uses, to solve one or more of the technical problems mentioned in the Background section.

[0011] In a first aspect, some embodiments of the present disclosure provide a psoralen derivative, comprising: a psoralen derivative of formula (I) or a psoralen derivative of formula (II), wherein formula (I) is:

[0012] Formula (II) is:

[0013] In a second aspect, some embodiments of the present disclosure provide a method for preparing a psoralen derivative, comprising: mixing 3-(benzo[d][1,3]dioxol-5-yl)propenoic acid, psoralen, 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride, 4-dimethylaminopyridine, triethylamine and tetrahydrofuran, and stirring uniformly at room temperature to obtain a mixture; performing first vacuum concentration on the mixture to obtain a first concentrated substance; extracting a target phase of the first concentrated substance after water dissolution with ethyl acetate, and collecting an organic layer; performing second vacuum concentration on the dried organic layer to obtain a second concentrated substance; adding petroleum ether to the second concentrated substance and performing third vacuum concentration to obtain a first solid; mixing a mixed solution with the first solid, and then filtering by beating to obtain a filter cake, wherein the mixed solution comprises petroleum ether and ethyl acetate; and performing vacuum drying on the filter cake to obtain a psoralen derivative, wherein the psoralen derivative is the psoralen derivative of formula (I) described in the first aspect.

[0014] In a third aspect, some embodiments of the present disclosure provide a preparation method of bakuchiol derivative, comprising: mixing 2,4-dimethoxycinnamic acid, bakuchiol, 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride, 4-dimethylaminopyridine, triethanolamine and tetrahydrofuran, and stirring uniformly at room temperature to obtain a mixture; performing first vacuum concentration on the mixture to obtain a first concentrated product; extracting a target phase of the first concentrated product after dissolving in water by ethyl acetate, and collecting an organic layer; performing second vacuum concentration on the dried organic layer to obtain a second concentrated product; adding petroleum ether to the second concentrated product and performing third vacuum concentration to obtain a first solid; mixing a mixed solution with the first solid, and filtering by beating to obtain a filter cake, wherein the mixed solution comprises petroleum ether and ethyl acetate; and performing vacuum drying on the filter cake to obtain the bakuchiol derivative, wherein the bakuchiol derivative is the bakuchiol derivative of the structure of formula (II) in the first aspect.

[0015] In a fourth aspect, some embodiments of the present disclosure provide a skin care composition, comprising: a bakuchiol derivative, wherein the bakuchiol derivative is the bakuchiol derivative of the structure of formula (I) or the bakuchiol derivative of the structure of formula (II) in the first aspect; and a physiologically acceptable excipient or carrier.

[0016] Optionally, the bakuchiol derivative accounts for 0.01% to 5% by weight based on the total weight of the skin care composition.

[0017] Optionally, the bakuchiol derivative accounts for 0.01% to 0.1% by weight based on the total weight of the skin care composition.

[0018] Optionally, the bakuchiol derivative accounts for 0.01% to 0.05% by weight based on the total weight of the skin care composition.

[0019] Optionally, the bakuchiol derivative accounts for 0.05% to 0.1% by weight based on the total weight of the skin care composition.

[0020] Optionally, the bakuchiol derivative accounts for 0.1% to 0.2% by weight based on the total weight of the skin care composition.

[0021] Optionally, the bakuchiol derivative accounts for 0.2% to 0.3% by weight based on the total weight of the skin care composition.

[0022] Optionally, the bakuchiol derivative accounts for 0.3% to 0.4% by weight based on the total weight of the skin care composition.

[0023] Optionally, the above-mentioned bakuchiol derivative is 0.4% to 0.5% by weight, relative to the total weight of the above-mentioned skin care composition.

[0024] Optionally, the above-mentioned bakuchiol derivative is 0.5% to 0.6% by weight, relative to the total weight of the above-mentioned skin care composition.

[0025] Optionally, the above-mentioned bakuchiol derivative is 0.6% to 0.7% by weight, relative to the total weight of the above-mentioned skin care composition.

[0026] Optionally, the above-mentioned bakuchiol derivative is 0.7% to 0.8% by weight, relative to the total weight of the above-mentioned skin care composition.

[0027] Optionally, the above-mentioned bakuchiol derivative is 0.8% to 0.9% by weight, relative to the total weight of the above-mentioned skin care composition.

[0028] Optionally, the above-mentioned bakuchiol derivative is 0.9% to 1% by weight, relative to the total weight of the above-mentioned skin care composition.

[0029] Optionally, the above-mentioned bakuchiol derivative is 1% to 1.2% by weight, relative to the total weight of the above-mentioned skin care composition.

[0030] Optionally, the above-mentioned bakuchiol derivative is 1.2% to 1.4% by weight, relative to the total weight of the above-mentioned skin care composition.

[0031] Optionally, the above-mentioned bakuchiol derivative is 1.4% to 1.6% by weight, relative to the total weight of the above-mentioned skin care composition.

[0032] Optionally, the above-mentioned bakuchiol derivative is 1.6% to 1.8% by weight, relative to the total weight of the above-mentioned skin care composition.

[0033] Optionally, the above-mentioned bakuchiol derivative is 1.8% to 2% by weight, relative to the total weight of the above-mentioned skin care composition.

[0034] Optionally, the above-mentioned bakuchiol derivative is 2% to 2.5% by weight, relative to the total weight of the above-mentioned skin care composition.

[0035] Optionally, the above-mentioned bakuchiol derivative is 2.5% to 3% by weight, relative to the total weight of the above-mentioned skin care composition.

[0036] Optionally, the above-mentioned bakuchiol derivative is 3% to 3.5% by weight, relative to the total weight of the above-mentioned skin care composition.

[0037] Optionally, the above psoralen derivative is present in an amount of 3.5% to 4% by weight relative to the total weight of the above skin care composition.

[0038] Optionally, the above psoralen derivative is present in an amount of 4% to 5% by weight relative to the total weight of the above skin care composition.

[0039] Optionally, the above skin care composition further comprises one or more of an organic solvent, an oil, a wax, a pigment, a filler, a dye, a surfactant, an emulsifier, a cosmetic active, an organic or inorganic photoprotective agent, a polymer, a thickening agent, a preservative, a fragrance, a bactericide, an active, retinol, a retinol derivative, an odor absorber, an antioxidant, a rheology modifier.

[0040] Optionally, the above skin care composition is in a dosage form comprising one or more of a solution, an aqueous preparation, an emulsion, a cream, a cleanser, an ointment, a balm, a gel, a paste, a powder, a spray, an inhalant, a patch.

[0041] Optionally, the above aqueous preparation comprises one or more of a skin care water, a toner, an essence.

[0042] Optionally, the above cleanser can comprise one or more of a facial foam, a facial water, a facial liquid.

[0043] Optionally, the above active comprises one or more of a small molecule, a peptide, a protein, a carbohydrate, a monosaccharide, an oligosaccharide, a polysaccharide, a nucleoprotein, a mucoprotein, a synthetic polypeptide, a small molecule linked to a protein, a glycoprotein, a steroid, a nucleic acid, a deoxyribonucleic acid, a ribonucleic acid, a nucleoside, a nucleotide, an oligonucleotide, an antisense oligonucleotide, a lipid, a hormone, vitamin A, a vitamin A derivative, a cell.

[0044] In a fifth aspect, some embodiments of the present disclosure provide a use of a psoralen derivative, comprising any one of the following uses of the psoralen derivative of formula (I) or the psoralen derivative of formula (II) as described in the first aspect: anti-aging; inhibiting apoptosis; regulating cell cycle; inhibiting deoxyribonucleic acid damage; inhibiting tumor.

[0045] In a sixth aspect, some embodiments of the present disclosure provide a use of the skin care composition as described in the fourth aspect, comprising any one of the following uses: anti-aging; inhibiting apoptosis; regulating cell cycle; inhibiting deoxyribonucleic acid damage; inhibiting tumor. BRIEF DESCRIPTION OF DRAWINGS

[0046] The above described and other features, advantages and aspects of the embodiments of the present disclosure will become more apparent as various embodiments of the present disclosure are described in conjunction with the following detailed description by reference to the following drawings in which: like reference numerals in the figures represent like elements throughout. It should be understood that the drawings are schematic and elements are not necessarily drawn to scale.

[0047] Figure 1 is a schematic diagram of the synthesis process of the psoralen derivative of structure (I) according to some embodiments of the present disclosure;

[0048] Figure 2 is a mass spectrum of the psoralen derivative of structure (I) according to some embodiments of the present disclosure;

[0049] Figure 3 is a schematic diagram of the synthesis process of the psoralen derivative of structure (II) according to some embodiments of the present disclosure;

[0050] Figure 4 is a mass spectrum of the psoralen derivative of structure (II) according to some embodiments of the present disclosure;

[0051] Figure 5 is a comparison chart of cell survival rate corresponding to Experiment 2 according to some embodiments of the present disclosure;

[0052] Figure 6 is a comparison chart of Caspase3 relative expression amount corresponding to Experiment 3 according to some embodiments of the present disclosure;

[0053] Figure 7 is a comparison chart of Caspase3 relative expression amount corresponding to Experiment 3 according to some embodiments of the present disclosure;

[0054] Figure 8 is a comparison chart of WIP1 relative expression amount corresponding to Experiment 4 according to some embodiments of the present disclosure;

[0055] Figure 9 is a comparison chart of WIP1 relative expression amount corresponding to Experiment 4 according to some embodiments of the present disclosure;

[0056] Figure 10 is a comparison chart of Caspase3 relative expression amount corresponding to Experiment 5 according to some embodiments of the present disclosure;

[0057] Figure 11 is a comparison chart of WIP1 relative expression amount corresponding to Experiment 5 according to some embodiments of the present disclosure. DETAILED DESCRIPTION

[0058] Embodiments of the present disclosure will be described in more detail by referring to the drawings. Although certain embodiments of the present disclosure are shown in the drawings, it is understood that the present disclosure can be implemented in various forms and should not be construed as being limited to the embodiments set forth herein. Rather, these embodiments are provided so that the present disclosure can be more thoroughly and completely understood. It should be understood that the drawings and embodiments of the present disclosure are merely for exemplary purposes and are not intended to limit the scope of protection of the present disclosure.

[0059] It should also be noted that, for the sake of brevity, only parts of the drawings that are related to the present application are shown. The embodiments and features in the present disclosure can be combined with each other as long as there is no conflict.

[0060] It should be noted that the modification of "one", "a plurality of" mentioned in the present disclosure is illustrative but not restrictive, and those skilled in the art should understand that unless the context clearly indicates otherwise, it should be understood as "at least one".

[0061] It should be noted that the "about" mentioned in the present disclosure means ±5% of the specified numerical value when used to define the numerical value.

[0062] It should be noted that the term "%" mentioned in the present disclosure means mass% unless otherwise specified.

[0063] It should be noted that the "room temperature" mentioned in the present disclosure means the ambient temperature, that is, no special heating or cooling treatment is performed.

[0064] Explanation of terms

[0065] The term "psoralen" is a monoterpene compound isolated from the legume Psoralea corylifolia, with the chemical formula C 18 H 24 O, and the structure is as follows:

[0066] The term "ferulic acid" is a hydroxyphenylpropenoic acid, which is a rich phenolic phytochemical present in plant cell walls, and the structure is as follows:

[0067] The term "3-(benzo[d][1,3]dioxol-5-yl)acrylic acid" has the chemical formula C 10 H8O4, and the structure is as follows:

[0068] The term "2,4-dimethoxycinnamic acid" has the chemical formula C 11 H 12 O4, and the structure is as follows:

[0069] The term "compound of formula (III)", wherein the compound of formula (III) is a graft of ferulic acid and psoralen, and the structure is as follows:

[0070] The term "1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride" has the chemical formula C8H 18 ClN3, abbreviated as EDCI.

[0071] The term "4-dimethylaminopyridine" is a pyridine derivative, which is a colorless to pale yellow crystal, with the chemical formula C7H 10 N2, abbreviated as DMAP.

[0072] The term "triethylamine" is an amine organic compound, which is a colorless to pale yellow transparent liquid, has a pungent fishy smell, extremely bitter taste, slightly smokes in the air, and the chemical formula is C6H 15 N, abbreviated as ET3N.

[0073] The term "tetrahydrofuran" is also known as oxolane, which is a heterocyclic organic compound, a colorless transparent liquid, the chemical formula is C4H8O, abbreviated as THF.

[0074] The term "ethyl acetate" is a compound generated by replacing the hydroxyl group in acetic acid with an ethoxy group, and the chemical formula is C4H8O2.

[0075] The term "petroleum ether" is a light petroleum product mainly composed of pentane and hexane, which is a colorless extremely flammable transparent liquid with a kerosene odor.

[0076] The term "triethanolamine" is a pale yellow liquid, and the chemical formula is C6H 15 NO3.

[0077] The term "ampicillin" is also known as ampicillin, which is an organic compound, and the chemical formula is C 16 H 19 N3O4S.

[0078] The term "sulbactam" is an irreversible competitive β-lactamase inhibitor, which can inhibit the β-lactamase produced by Gram-positive and negative bacteria except Pseudomonas aeruginosa, and the chemical formula is C 14 H 21 NO7S.

[0079] The term "anhydrous sodium sulfate" is an ionic sulfate salt, which is a white or light yellow granular crystal or powder, and the chemical formula is Na2O4S.

[0080] The term "dimethyl sulfoxide" is also known as DMSO, which is a colorless polar aprotic solvent, and the chemical formula is (CH3)2SO.

[0081] The technical problem to be solved by the present disclosure is how to develop a new active molecule with lower cytotoxicity and multiple effects on the basis of bakuchiol.

[0082] In order to solve the above problems, some embodiments of the present disclosure propose a bakuchiol derivative, i.e. a bakuchiol derivative of formula (I) or a bakuchiol derivative of formula (II), which realizes the grafting of bakuchiol and ferulic acid, so that the obtained bakuchiol derivative has the effects of inhibiting cell apoptosis, regulating cell cycle, etc. and has low toxicity.

[0083] The present disclosure will be described in detail below with reference to the accompanying drawings and in combination with embodiments.

[0084] Preparation method

[0085] Preparation method A of the psoralenol derivative comprises:

[0086] In the first step, 3-(benzo[d][l,3]dioxol-5-yl) acrylic acid, psoralenol, 1-ethyl-(3- dimethylaminopropyl) carbodiimide hydrochloride, 4-dimethylaminopyridine, triethylamine and tetrahydrofuran are mixed and stirred at room temperature to obtain a mixture.

[0087] In practice, 3-(benzo[d][l,3]dioxol-5-yl) acrylic acid 4.5 g (22.6 mmol, 1.5 equiv), psoralenol 4.5 g (15 mmol, 1 equiv), 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride 5.76 g (30 mmol, 2 equiv), 4-dimethylaminopyridine 180 mg (1.5 mmol, 0.1 equiv), triethylamine 4.8 mL (37.6 mmol, 2.5 equiv) and tetrahydrofuran 80 mL are added into a 200 mL reaction kettle, and stirred at room temperature for 12 hours to obtain a mixture.

[0088] In the second step, the above mixture is subjected to first vacuum concentration to obtain a first concentrate.

[0089] In the second step, the above mixture is subjected to first vacuum concentration to obtain a first concentrate.

[0090] In the third step, the above first concentrate after water dissolution is extracted with ethyl acetate, and the organic layer is collected.

[0091] In practice, first, 200 mL of water is added to the first concentrate to dissolve the first concentrate in water. Then, the above first concentrate after water dissolution is extracted with ethyl acetate (200 mL x 3) to obtain the water layer. Wherein, the target times ≥ 1. Finally, the organic layers are combined.

[0092] In the fourth step, the above organic layer after drying is subjected to second vacuum concentration to obtain a second concentrate.

[0093] In practice, first, 10 g of anhydrous sodium sulfate is added to the organic layer to dry the above organic layer and obtain the above organic layer after drying. Then, the above organic layer after drying is subjected to vacuum concentration at a temperature of 40 ± 5 °C to obtain a second concentrate (crude oil product).

[0094] In the fifth step, petroleum ether is added to the above second concentrate and subjected to third vacuum concentration to obtain a first solid.

[0095] In practice, 60 mL of petroleum ether was added to the above-mentioned second concentrate, and vacuum concentration was performed at a temperature of 40±5°C to obtain a first solid (yellow solid).

[0096] In the sixth step, the mixed solution was mixed with the above-mentioned first solid, and then the mixture was beaten and filtered to obtain a filter cake.

[0097] The mixed solution includes petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate is 50:1.

[0098] In practice, the mixed solution of 200 mL of petroleum ether and ethyl acetate was mixed with the first solid and beaten for 30 minutes, and then filtered through a Buchner funnel to obtain a filter cake.

[0099] In the seventh step, vacuum drying was performed on the above-mentioned filter cake to obtain a psoralen derivative.

[0100] The psoralen derivative is a psoralen derivative of formula (I).

[0101] In practice, vacuum drying was performed on the above-mentioned filter cake at a temperature of 40±5°C to obtain a psoralen derivative (4 g, yield: 62%).

[0102] Specifically, the synthesis process of the psoralen derivative of formula (I) is shown in FIG. 1. The mass spectrum of the psoralen derivative of formula (I) is shown in FIG. 2.

[0103] Specifically, the NMR spectrum of the psoralen derivative of formula (I) is attributed as follows:

[0104] 1 H NMR (400 MHz, CDCl3): δ = 7.77 (d, J = 15.9 Hz, 1H), 7.39 (d, J = 8.6 Hz, 2H), 7.15-7.03 (m, 4H), 6.84 (d, J = 7.9 Hz, 1H), 6.44 (d, J = 15.8 Hz, 1H), 6.38-6.13 (m, 2H), 6.03 (s, 2H), 5.89 (dd, J = 17.5, 10.7 Hz, 1H), 5.16-4.99 (m, 3H), 1.97 (q, J = 7.5 Hz, 2H), 1.69 (s, 3H), 1.60 (s, 3H), 1.56-1.49 (m, 2H), 1.22 (s, 3H).

[0105] 13C NMR (101 MHz, CDC13): δ = 165.59, 149.95, 149.71, 148.42, 146.20, 145.65, 138.07, 135.56, 131.33, 128.60, 126.94, 126.32, 124.86, 124.68, 121.59, 115.09, 112.08, 108.60, 106.56, 101.62, 42.62, 41.19, 25.66, 23.27, 23.19, 17.62.

[0106] The nuclear magnetic data is measured by a nuclear magnetic resonance spectrometer (model: AVANCE III HD 400MHz, manufacturer: Bruker Corporation, Switzerland).

[0107] The preparation method B of the psoralenol derivative comprises:

[0108] In the first step, 2,4-dimethoxycinnamic acid, psoralenol, 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride, 4-dimethylaminopyridine, triethanolamine and tetrahydrofuran are mixed and stirred uniformly at room temperature to obtain a mixture.

[0109] In practice, 2,4-dimethoxycinnamic acid 468 mg (2.25 mmol, 1.5 equiv), psoralenol 384 mg (1.5 mmol, 1 equiv), 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride 465 mg (3 mmol, 2 equvi), 4-dimethylaminopyridine 18 mg (0.15 mmol, 0.1 equiv), triethanolamine 0.48 mL (3.75 mmol, 2.5 equiv) and tetrahydrofuran 1 mL are added into a 200 mL reaction kettle, and stirred at room temperature for 12 hours to obtain a mixture.

[0110] In the second step, the above mixture is subjected to first vacuum concentration to obtain a first concentrated product.

[0111] In practice, the mixture is subjected to first vacuum concentration under stable conditions at 40±5°C to obtain a first concentrated product.

[0112] In the third step, the above first concentrated product after water dissolution is extracted with ethyl acetate, and the organic layer is collected.

[0113] In practice, first, 200 mL of water is added to the first concentrated product to dissolve the first concentrated product in water. Then, the above first concentrated product after water dissolution is extracted with ethyl acetate (200 mL x 3) to obtain the water layer. The target extraction times are ≥1. Finally, the organic layers are combined.

[0114] Fourthly, the above organic layer is dried and filtered to obtain a dried organic layer.

[0115] In practice, first, 10 g of anhydrous sodium sulfate is added to the organic layer to dry the layer and obtain a dried organic layer. Then, the dried organic layer is concentrated under reduced pressure at a temperature of 40±5℃ to obtain a second concentrate (an oily crude product).

[0116] Fifthly, petroleum ether is added to the second concentrate and concentrated under reduced pressure to obtain a first solid.

[0117] In practice, 10 mL of petroleum ether is added to the second concentrate and concentrated under reduced pressure at a temperature of 40±5℃ to obtain a first solid (a yellow solid).

[0118] Sixthly, the mixture is mixed with the first solid and then filtered to obtain a filter cake.

[0119] The mixture includes petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate is 50:1.

[0120] In practice, the mixture of 20 mL of petroleum ether and ethyl acetate is mixed with the first solid for 30 minutes and then filtered through a Buchner funnel to obtain a filter cake.

[0121] Seventhly, the filter cake is vacuum dried to obtain a psoralen derivative.

[0122] The psoralen derivative is a psoralen derivative of formula (II).

[0123] In practice, the filter cake is vacuum dried at a temperature of 40±5℃ to obtain a psoralen derivative (442 mg, yield: 66%).

[0124] Specifically, the synthesis process of the psoralen derivative of formula (II) is shown in FIG. 3. In FIG. 3, “RT” represents room temperature. The mass spectrum of the psoralen derivative of formula (II) is shown in FIG. 4.

[0125] Specifically, the NMR spectrum of the psoralen derivative of formula (II) is attributed as follows:

[0126] 1H NMR (400 MHz, CDC13): δ = 8.09 (d, J = 16.1 Hz, 1H), 7.48 (d, J = 8.6 Hz, 1H), 7.39 (d, J = 8.7 Hz, 2H), 7.11 (d, J = 8.6 Hz, 2H), 6.63 (d, J = 16.0 Hz, 1H), 6.52 (dd, J = 8.6, 2.4 Hz, 1H), 6.46 (d, J = 2.3 Hz, 1H), 6.38 - 6.13 (m, 2H), 5.90 (dd, J = 17.4, 10.7 Hz, 1H), 5.19 - 5.01 (m, 3H), 3.87 (s, 3H), 3.83 (s, 3H), 1.98 (q, J = 7.6 Hz, 2H), 1.69 (s, 3H), 1.60 (s, 3H), 1.57 - 1.46 (m, 2H), 1.22 (s, 3H).

[0127] 13 C NMR (101 MHz, CDC13): δ = 166.19, 162.97, 159.99, 149.87, 145.56, 141.85, 137.76, 135.22, 131.13, 130.75, 126.77, 126.30, 124.62, 121.61, 116.20, 114.80, 111.96, 105.26, 98.26, 55.30, 55.29, 42.50, 41.10, 25.56, 23.16, 23.10, 17.51.

[0128] The nuclear magnetic data were measured by a nuclear magnetic resonance spectrometer (model: AVANCE III HD 400MHz, manufacturer: Bruker Corporation, Switzerland).

[0129] Experimental method

[0130] Experiment 1 (cytotoxicity experiment)

[0131] In the experiment 1, a control sample, sample 1, sample 2, sample 3 and sample 4 were used. The specific description of the samples is as follows:

[0132] The control sample was DMEM medium containing 10% FBS and 1% penicillin / streptomycin.

[0133] Sample 1: First, psoralen was taken and mixed in DMSO to form a mother liquor. Then, the mother liquor was diluted to the required concentration for the experiment by DMEM medium containing 10% FBS and 1% penicillin / streptomycin.

[0134] Sample 2: First, the compound of formula (III) was mixed into DMSO to form a mother liquor. Then, the mother liquor was diluted to the required concentration for the experiment by DMEM medium containing 10% FBS and 1% penicillin / streptomycin.

[0135] Sample 3: First, the compound of formula (I) was mixed into DMSO to form a mother liquor. Then, the mother liquor was diluted to the required concentration for the experiment by DMEM medium containing 10% FBS and 1% penicillin / streptomycin.

[0136] Sample 4: First, the compound of formula (II) was mixed into DMSO to form a mother liquor. Then, the mother liquor was diluted to the required concentration for the experiment by DMEM medium containing 10% FBS and 1% penicillin / streptomycin.

[0137] Process description of the experiment

[0138] Step 1: HDF (human dermal fibroblast) cell inoculation

[0139] In which, 2x10 4 cells / well were inoculated into a 96-well plate, specifically, 100 μL of DMEM medium containing 10% FBS and 1% penicillin / streptomycin (complete medium) was added to each well, and incubated in an incubator (incubation temperature: 37°C; incubation environment: 5% CO2) for 24 hours.

[0140] Step 2: When the cell plating rate in the 96-well plate reached 40%-50%, the drug was administered.

[0141] In which, 100 μL of sample was added to each well. Six replicates were set for each group, and after the drug administration was completed, the plate was placed in an incubator (incubation temperature: 37°C; incubation environment: 5% CO2) for 24 hours.

[0142] Step 3: After the cells were incubated for 24 hours, the supernatant was discarded, and 100 μL of CCK8 working solution (prepared by DMEM medium) was added, incubated at 37°C for 2 hours in the dark, and after the incubation was completed, the OD value (relative activity) was read at 450nm and 650nm, respectively.

[0143] Step 4: The proliferation rate was determined based on the blank control group.

[0144] In which, the proliferation rate = (relative activity of the experimental group - relative activity of the blank control group) / relative activity of the blank control group.

[0145] Explanation of experimental results

[0146] In which, the experimental results of Experiment 1 are shown in Table 1:

[0147] Table 1

[0148] The analysis found that, first, sample 1, sample 3 and sample 4 did not produce cytotoxicity to HDF cells in the concentration range of 12.5 μM to 50 μM. Second, the cell proliferation rate of sample 2 at a concentration of 50 μM was 72.71%, which had cytotoxicity.

[0149] Experiment 2 (phototoxicity experiment)

[0150] Among them, experiment 1 uses control sample (Control), UVA control sample (UVA), sample 1, sample 2, sample 3 and sample 4. Among them, the specific description of the sample is as follows:

[0151] Control sample: DMEM culture medium containing 10% FBS and 1% penicillin / streptomycin.

[0152] UVA control sample (UVA): DMEM culture medium containing 10% FBS and 1% penicillin / streptomycin.

[0153] Sample 1: First, psoralen phenol is taken into DMSO to form a mother liquor. Then, the mother liquor is diluted to the required concentration of the experiment by DMEM culture medium containing 10% FBS and 1% penicillin / streptomycin.

[0154] Sample 2: First, the compound of formula (III) is mixed into DMSO to form a mother liquor. Then, the mother liquor is diluted to the required concentration of the experiment by DMEM culture medium containing 10% FBS and 1% penicillin / streptomycin.

[0155] Sample 3: First, the psoralen phenol derivative of formula (I) structure is mixed into DMSO to form a mother liquor. Then, the mother liquor is diluted to the required concentration of the experiment by DMEM culture medium containing 10% FBS and 1% penicillin / streptomycin.

[0156] Sample 4: First, the psoralen phenol derivative of formula (II) structure is mixed into DMSO to form a mother liquor. Then, the mother liquor is diluted to the required concentration of the experiment by DMEM culture medium containing 10% FBS and 1% penicillin / streptomycin.

[0157] Process description of the experiment

[0158] First, HDF (human dermal fibroblast) cells are inoculated.

[0159] Among them, 2x10 4The cells were inoculated at a density of 1,000 cells / well into a 96-well plate, specifically, 100 μL of DMEM medium containing 10% FBS and 1% penicillin / streptomycin (complete medium) was added to each well, and the cells were incubated in an incubator (incubation temperature: 37°C; incubation environment: 5% CO2) for 24 hours.

[0160] In the second step, when the plating rate of the cells in the 96-well plate reached 40% to 50%, UVA irradiation and drug administration were performed.

[0161] Specifically, 100 μL of PBS was added to each well, and UVA irradiation was performed for 7 J. After the irradiation, 100 μL of the sample was added to each well. Six replicates were set for each group, and after the drug administration was completed, the samples were incubated in an incubator (incubation temperature: 37°C; incubation environment: 5% CO2) for 24 hours.

[0162] In the third step, after the cells were incubated for 24 hours, the supernatant was discarded, and 100 μL of CCK8 working solution (prepared by using DMEM medium) was added. The mixture was incubated at 37°C in the dark for 2 hours. After the incubation, the OD values (relative viability) were read at 450 nm and 650 nm, respectively.

[0163] In the fourth step, the proliferation rate was determined based on the blank control group.

[0164] Specifically, the proliferation rate = (relative viability of the experimental group - relative viability of the blank control group) / relative viability of the blank control group.

[0165] Experimental results

[0166] Specifically, the experimental results of Experiment 2 are shown in Table 2 and FIG. 5:

[0167] Table 2

[0168] It was found that, first, after UVA irradiation, the cell survival rate decreased. In addition, as the concentration increased, the cytotoxicity of Sample 1 gradually increased, and when the concentration was 50 μM, the cell survival rate was only 62.95%. Next, when the concentration of Sample 2 was 25 μM, the cell survival rate was only 60.45%, and when the concentration was 50 μM, the cell survival rate was only 5.57%. At the same time, when the concentration of Sample 3 and Sample 4 was 50 μM, the cell survival rates were 82.03% and 77.58%, respectively. Among them, Sample 3 and Sample 4 showed higher safety compared to Sample 1 and Sample 2.

[0169] Experiment 3 (Caspase 3 inhibition (cell) experiment)

[0170] Caspase 3 is a kind of protease, which plays a key role in the process of apoptosis. It is one of the executors of apoptosis, which induces cell death by cleaving specific intracellular proteins, therefore, the expression level of Caspase 3 is often used as an indicator of apoptosis.

[0171] In the experiment 3, control sample, sample 1, sample 2, sample 3 and sample 4 were used. The specific description of the samples is as follows:

[0172] Control sample: DMEM medium containing 10% FBS and 1% penicillin / streptomycin.

[0173] Sample 1: First, psoralen was mixed into DMSO to form a mother liquor. Then, the mother liquor was diluted to the required concentration by DMEM medium containing 10% FBS and 1% penicillin / streptomycin.

[0174] Sample 2: First, the compound of formula (III) was mixed into DMSO to form a mother liquor. Then, the mother liquor was diluted to the required concentration by DMEM medium containing 10% FBS and 1% penicillin / streptomycin.

[0175] Sample 3: First, the psoralen derivative of formula (I) structure was mixed into DMSO to form a mother liquor. Then, the mother liquor was diluted to the required concentration by DMEM medium containing 10% FBS and 1% penicillin / streptomycin.

[0176] Sample 4: First, the psoralen derivative of formula (II) structure was mixed into DMSO to form a mother liquor. Then, the mother liquor was diluted to the required concentration by DMEM medium containing 10% FBS and 1% penicillin / streptomycin.

[0177] Experimental process description

[0178] First step, HDF (human dermal fibroblast) cell inoculation.

[0179] In which, according to the inoculation density of 8x10 5 6 wells, specifically, 2000 μL of DMEM medium containing 10% FBS and 1% penicillin / streptomycin (complete medium) was added to each well, and cultured in an incubator (incubation temperature: 37℃; incubation environment: 5% CO2) for 24 hours.

[0180] Second step, when the cell plating rate in the 6-well plate reaches 70%-80%, grouping and dosing are carried out.

[0181] Wherein, add complete medium containing different concentrations of drugs, each group set 3 wells, and after the completion of the drug placed in the incubator (incubation temperature: 37℃; incubation environment: 5% CO2) for 24 hours.

[0182] Third step, RNA extraction.

[0183] Wherein, (1), pour out the culture solution, and rinse once with PBS. Specifically, first, every 10 cm 2 1 mL of TansZol TM Up reagent, horizontally placed for a while, and then evenly distributed on the cell surface using lysis solution for cell lysis. Then, use a pipette to blow the cells to make them fall off (wherein, for firmly adherent culture cells, a cell scraper can be used to peel off the cells). Next, transfer the cell lysate to a centrifuge tube, and add 0.2 mL of RNA Extraction Agent (total RNA extraction reagent), and after repeatedly blowing and sucking the lysate with a pipette without obvious precipitation, vortex at room temperature for 5 minutes. (2) Centrifuge the sample between 2℃ and 8℃ for 15 minutes, at which time the sample is divided into 3 layers, including: the upper layer (colorless aqueous phase), the middle layer, and the lower layer (pink organic phase). Wherein, the RNA is in the aqueous phase, and the volume of the aqueous phase is 50%-60% of the TansZol Up reagent used (in order to avoid DNA contamination caused by suction into the middle layer, a portion of the aqueous phase can be appropriately reserved). (3) Transfer the colorless aqueous phase to a new centrifuge tube, and add an equal volume of anhydrous ethanol (at which time precipitation may occur), and mix gently after adding. (4) Add the obtained solution and precipitate to a centrifugal column, and after centrifuging at room temperature for 30 seconds, discard the effluent. (5) Add 500 μL of CB9, centrifuge at room temperature for 30 seconds, discard the effluent, and repeat once. (6) Add 500 μL of WB9 (check whether anhydrous ethanol is added before use), centrifuge at room temperature for 30 seconds, discard the effluent, and repeat once. (7) Centrifuge at room temperature for 2 minutes to completely remove the residual ethanol. (8) Place the centrifugal column in an RNase-free Tube, and add 50-200 μL of Nase-free Water in the center of the centrifugal column, and stand at room temperature for 1 minute. (9) Centrifuge at room temperature for 1 minute to elute the RNA. (10) Measure the concentration of the RNA using a microspectrophotometer, and store the RNA at -80℃.

[0184] Fourth step, calculate the corresponding RNA volume with 2 ug of RNA sample of measured concentration, and add the corresponding volume of Rnase Free water and reverse transcriptase mix.

[0185] Wherein, the total volume of the system is 20 μL. Specifically, the RT-PCR reaction system and the RTPCR reaction program are shown in Table 3:

[0186] Table 3

[0187] After the reverse transcription procedure, 20 μL of the reverse transcription sample was diluted to 400 μL, in which the final concentration of the cDNA sample was 5 ng / μL (in which, each sample was tested in triplicate for each gene, and after adding, the QPCR reaction procedure was performed on the machine). Specifically, the QPCR reaction system and the QPCR reaction procedure are shown in Table 4:

[0188] Table 4

[0189] In which, the 2-△△Ct method was used to analyze the mRNA expression level of the related genes, and the data between groups was statistically analyzed by One-way ANOVA, P<0.05 indicating significant difference, with statistical significance.

[0190] The experimental results show that

[0191] In which, the experimental results of Experiment 3 are shown in Table 5, Figure 6 and Figure 7:

[0192] Table 5

[0193] It was found that, first, Sample 1 had an inhibitory effect on the expression of Caspase3 at a concentration of 25 μM, and enhanced the expression of Caspase3 at a concentration of 50 μM, which was about 2200% higher than that of the control sample. Second, Sample 2 increased the expression of Caspase3 at a concentration of 25 μM and 50 μM, which was about 100% higher than that of the control sample. Then, Sample 3 and Sample 4 showed an inhibitory effect on Caspase3 at a concentration of 25 μM and 50 μM, which was about 50% lower than that of the control sample. In summary, Sample 3, Sample 4 and Sample 2 have completely different biological activities.

[0194] Experiment 4 (WIP1 inhibition (cell) experiment)

[0195] In which, WIP1 (Wild-type p53-induced phosphatase 1) is a phosphatase belonging to the Ser / Thr protein phosphatase family. It is induced by the p53 gene and plays an important role in cell cycle regulation, DNA damage response and other processes. The expression level of WIP1 can be used as an indicator of DNA damage response, cell cycle regulation, and tumor occurrence and development process.

[0196] Experiment 4 uses a control sample, sample 1, sample 2, sample 3 and sample 4. The specific description of the samples is as follows:

[0197] Control sample: DMEM medium containing 10% FBS and 1% penicillin / streptomycin.

[0198] Sample 1: First, psoralen is mixed in DMSO to form a mother liquor. Then, the mother liquor is diluted to the required concentration by DMEM medium containing 10% FBS and 1% penicillin / streptomycin.

[0199] Sample 2: First, the compound of formula (III) is mixed in DMSO to form a mother liquor. Then, the mother liquor is diluted to the required concentration by DMEM medium containing 10% FBS and 1% penicillin / streptomycin.

[0200] Sample 3: First, the psoralen derivative of formula (I) structure is mixed in DMSO to form a mother liquor. Then, the mother liquor is diluted to the required concentration by DMEM medium containing 10% FBS and 1% penicillin / streptomycin.

[0201] Sample 4: First, the psoralen derivative of formula (II) structure is mixed in DMSO to form a mother liquor. Then, the mother liquor is diluted to the required concentration by DMEM medium containing 10% FBS and 1% penicillin / streptomycin.

[0202] Experimental process description

[0203] Step 1: HDF (human dermal fibroblast) cell inoculation.

[0204] In which, according to the inoculation density of 80×10 4 cells / well, inoculate into a 6-well plate. Specifically, add 2000 μL of DMEM medium containing 10% FBS and 1% penicillin / streptomycin (complete medium) to each well, and incubate in an incubator (incubation temperature: 37°C; incubation environment: 5% CO2) for 24 hours.

[0205] Step 2: When the cell plating rate in the 6-well plate reaches 70%-80%, group and administer the drug.

[0206] In which, add complete medium containing different concentrations of drugs to each group, set 3 replicate wells, and place in an incubator (incubation temperature: 37°C; incubation environment: 5% CO2) for 24 hours after drug administration is complete.

[0207] Step 3: RNA extraction.

[0208] In which, (1), pour out the culture solution and rinse once with PBS. Specifically, first, pour out the culture solution from each 10 cm2 1 mL of TansZol was added to the growing culture cells TM Up reagent, after a few minutes of horizontal placement, the lysis solution was evenly distributed on the cell surface for cell lysis. Then, the cells were blown off using a pipette (wherein, for the firmly adherent culture cells, a cell scraper can be used to peel off the cells). Next, the cell lysis solution was transferred to a centrifuge tube, 0.2 mL of RNA Extraction Agent (total RNA extraction reagent) was added, and after repeatedly blowing and sucking the lysis solution with a pipette until no obvious precipitate was observed, it was vortexed at room temperature for 5 minutes. (2) The sample was centrifuged at 2-8°C for 15 minutes, at which time the sample was divided into three layers, including: the upper layer (colorless aqueous phase), the middle layer, and the lower layer (pink organic phase). Among them, the RNA is located in the aqueous phase, and the volume of the aqueous phase is 50%-60% of the TansZol Up reagent used (in order to avoid DNA contamination caused by suction into the middle layer, a part of the aqueous phase can be appropriately reserved). (3) The colorless aqueous phase was transferred to a new centrifuge tube, and an equal volume of anhydrous ethanol was added (at which time a precipitate may appear), and after mixing gently. (4) The resulting solution and precipitate were added to a centrifugal column, and after centrifugation at room temperature for 30 seconds, the effluent was discarded. (5) 500 μL of CB9 was added, centrifuged at room temperature for 30 seconds, the effluent was discarded, and the process was repeated once. (6) 500 μL of WB9 (check whether anhydrous ethanol is added before use) was added, centrifuged at room temperature for 30 seconds, the effluent was discarded, and the process was repeated once. (7) Centrifugation at room temperature for 2 minutes to completely remove residual ethanol. (8) The centrifugal column was placed in an RNase-free Tube, and 50-200 μL of Nase-free Water was added to the center of the centrifugal column, and left to stand at room temperature for 1 minute. (9) Centrifugation at room temperature for 1 minute to elute the RNA. (10) The concentration of the RNA was measured using a microspectrophotometer, and the RNA was stored at -80°C.

[0209] Fourthly, the RNA sample with the measured concentration was calculated for the corresponding RNA volume at 2 ug, and the corresponding volume of Rnase Free water and reverse transcriptase mix was added.

[0210] The total volume of the system was 20 μL. Specifically, the RT-PCR reaction system and the RTPCR reaction program are shown in Table 6:

[0211] Table 6

[0212] After the reverse transcription procedure, 20 μL of the reverse transcription sample was diluted to 400 μL, in which the final concentration of the cDNA sample was 5 ng / μL (in which, each sample was tested in triplicate for each gene, and after adding, the QPCR reaction procedure was performed on the machine).

[0213] Table 7

[0214] In which, the 2-△△Ct method was used to analyze the mRNA expression level of the related genes, and the data between groups was statistically analyzed by One-way ANOVA, P<0.05 indicating significant difference, with statistical significance.

[0215] The experimental results show that

[0216] In which, the experimental results of experiment 4 are shown in Table 8, Figure 8 and Figure 9:

[0217] Table 8

[0218] It was found that first, sample 1 increased the expression level of WIP1 at concentrations of 25 μM and 50 μM, which was about 70% higher than that of the control sample. Second, sample 2 strongly promoted the expression of WIP1 at concentrations of 25 μM and 50 μM, which was about 800% and 1800% higher than that of the control sample, respectively. Third, sample 3 and sample 4 showed inhibition of WIP1 at concentrations of 25 μM and 50 μM, which was about 20-40% lower than that of the control sample. In summary, sample 3, sample 4 and sample 2 have completely different biological activities.

[0219] Experiment 5 (animal experiment)

[0220] In which, experiment 5 used 25g-30g C57BL / 6 male mice (age: 6-8 weeks, source: Guangdong Experimental Animal Center), and before the experiment, the mice were first used for 12 hours of light / dark cycle, the temperature was 22℃, and the adaptation period was 4 days. Specifically, experiment 5 used a control sample (Control, blank control group), sample 1 (experimental group 1), sample 2 (experimental group 2), sample 3 (experimental group 3) and sample 4 (experimental group 4), in which each group contained 5 mice, and the specific description of the samples is as follows:

[0221] Control sample: smear the same amount of normal saline every day.

[0222] Sample 1: smear 0.1% water solution of bakuchiol every day.

[0223] Sample 2: Compound (III) was applied daily as a 0.1% mass fraction aqueous solution.

[0224] Sample 3: Compound (I) was applied daily as a 0.1% mass fraction aqueous solution.

[0225] Sample 4: Compound (II) was applied daily as a 0.1% mass fraction aqueous solution.

[0226] Note: One day before the experiment, the experimental group mice were depilated on the back within an area of about 4 cm x 4 cm, except for the blank control group. Then, 200 μL of the solution was applied to the depilated area per day. After three days of continuous administration, the experiment was completed, and the mice were sacrificed by the dislocation of the spine. The back skin tissue was collected. Part of the back skin tissue was fixed in a 10% paraformaldehyde solution and stored in a refrigerator at 4°C. The rest of the back skin tissue was frozen in a -80°C refrigerator or liquid nitrogen for subsequent index analysis.

[0227] Explanation of the experimental process

[0228] The analysis includes Caspase3 content analysis and WIP1 content analysis. Specifically:

[0229] Caspase3 content analysis includes the following steps:

[0230] First, grind the skin tissue with liquid nitrogen to a fine state and collect it in an EP tube.

[0231] Second, add RIPA protein lysate at 10% (mg / mL) and use an automatic tissue homogenizer to break the skin tissue.

[0232] Third, after breaking, place the sample on ice for further lysis for 30 minutes, and vortex for 10 seconds every 10 minutes during this period.

[0233] The vortex conditions are: 4°C; 12000 x g centrifugation.

[0234] Fourth, after the end, collect the supernatant and use the Caspase3 ELISA detection kit to determine the content of Caspase3 in the skin tissue.

[0235] WIP1 content analysis includes the following steps:

[0236] First, grind the skin tissue with liquid nitrogen to a fine state and collect it in an EP tube.

[0237] Second, add RIPA protein lysate at 10% (mg / mL) and use an automatic tissue homogenizer to break the skin tissue.

[0238] Third step, after crushing, the sample is placed on ice for 30 min, and vortexed for 10 seconds every 10 minutes.

[0239] The vortex condition is 4℃; 12000xg centrifugation.

[0240] Fourth step, after the end, the supernatant is collected, and the WIP1 content in the supernatant is determined by using the WIP1 ELISA detection kit.

[0241] The data between groups are analyzed by One-way ANOVA, and P<0.05 indicates that the difference is significant and has statistical significance.

[0242] The experimental results show that

[0243] The experimental results of experiment 5 are shown in Tables 9, 10, 10 and 11.

[0244] Table 9

[0245] Table 10

[0246] First, the expression level of Caspase3 is observed, which is increased by nearly 10 times in the experimental group 1, and is increased by nearly 2 times in the experimental group 2, compared with the blank control group. The expression level of Caspase3 in the experimental group 3 and the experimental group 4 is decreased by more than 50%, indicating that the experimental group 3 and the experimental group 4 have obvious inhibition effect. Second, the expression level of Caspase3 is observed, which is increased by nearly 2 times in the experimental group 1, and is increased by 17 times in the experimental group 2, compared with the blank control group. The expression level of WIP1 in the experimental group 3 and the experimental group 4 is decreased by 30% and 10% respectively, indicating that the experimental group 3 and the experimental group 4 have obvious inhibition effect.

[0247] Application example

[0248] Application example 1

[0249] The emulsion prepared based on the psoralen derivative in application example 1 is shown in Table 11.

[0250] Table 11

[0251] Application example 2

[0252] The emulsion prepared based on the psoralen derivative in application example 2 is shown in Table 12.

[0253] Table 12

[0254] Application example 3

[0255] In application example 3, the cream is prepared based on the psoralen derivative, and the specific formula is shown in Table 13:

[0256] Table 13

[0257] Application example 4

[0258] In application example 4, the cream is prepared based on the psoralen derivative, and the specific formula is shown in Table 14:

[0259] Table 14

[0260] The above description is only some of the preferred embodiments of the present disclosure and the explanation of the applied technical principles. Those skilled in the art should understand that the scope of the application involved in the embodiments of the present disclosure is not limited to the technical solutions formed by the specific combinations of the above technical features, and should also cover other technical solutions formed by any combination of the above technical features or their equivalent features without departing from the above inventive concept. For example, the above features are replaced with the technical features disclosed in the embodiments of the present disclosure (but not limited to) having similar functions to form technical solutions.

[0261] All embodiments of the present disclosure can be executed independently or in combination with other embodiments, and are considered to be within the scope of protection required by the present disclosure.

Claims

1. A psoralen derivative, comprising: Psoralen derivatives of the structure of formula (I) or psoralen derivatives of the structure of formula (II), wherein formula (I) is: Formula (II) is: 2.A method for preparing a psoralen derivative, comprising: mixing 3-(benzo[d][l,3]dioxol-5-yl)propenoic acid, psoralen, l-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride, 4-dimethylaminopyridine, triethylamine and tetrahydrofuran, and stirring the mixture at room temperature to obtain a mixture; performing first vacuum concentration on the mixture to obtain a first concentrated product; extracting the first concentrated product dissolved in water with ethyl acetate, and collecting an organic layer; performing second vacuum concentration on the dried organic layer to obtain a second concentrated product; adding petroleum ether to the second concentrated product and performing third vacuum concentration to obtain a first solid; mixing a mixed solution with the first solid, and then beating and filtering to obtain a filter cake, wherein the mixed solution comprises petroleum ether and ethyl acetate; vacuum drying the filter cake to obtain a psoralen derivative, wherein the psoralen derivative is the psoralen derivative of the structure of formula (I) as claimed in claim 1. 3.A method for preparing a psoralen derivative, comprising: mixing 2,4-dimethoxycinnamic acid, psoralen, l-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride, 4-dimethylaminopyridine, triethylamine and tetrahydrofuran, and stirring the mixture at room temperature to obtain a mixture; performing first vacuum concentration on the mixture to obtain a first concentrated product; extracting the first concentrated product dissolved in water with ethyl acetate, and collecting an organic layer; performing second vacuum concentration on the dried organic layer to obtain a second concentrated product; adding petroleum ether to the second concentrated product and performing third vacuum concentration to obtain a first solid; mixing a mixed solution with the first solid, and then beating and filtering to obtain a filter cake, wherein the mixed solution comprises petroleum ether and ethyl acetate; vacuum drying the filter cake to obtain a psoralen derivative, wherein the psoralen derivative is the psoralen derivative of the structure of formula (II) as claimed in claim 1. 4.A skin care composition, comprising: a psoralen derivative, wherein the psoralen derivative is the psoralen derivative of the structure of formula (I) or the psoralen derivative of the structure of formula (II) as claimed in claim 1; and a physiologically acceptable excipient or carrier. The psoralen derivative accounts for 0.01%-5% by weight based on the total weight of the skin care composition.

5. The skin care composition of claim 4, wherein, The skin care composition further comprises one or more of an organic solvent, an oil, a wax, a pigment, a filler, a dye, a surfactant, an emulsifier, a cosmetic active agent, an organic or inorganic light protection agent, a polymer, a thickening agent, a preservative, a fragrance, a bactericide, an active, retinol, a retinol derivative, an odor absorber, an antioxidant, a rheology modifier.

6. The skin care composition of any of claims 4-5, wherein, The dosage form of the skin care composition comprises one or more of a solution, an aqueous agent, an emulsion, a cream, a cleanser, an ointment, a balm, a gel, a paste, a powder, a spray, an inhalant, a patch.

7. The skin care composition of any of claims 4-5, wherein, The active comprises:

8. The skin care composition of claim 6, wherein, ​ small molecules, peptides, proteins, carbohydrates, monosaccharides, oligosaccharides, polysaccharides, nucleoproteins, mucoproteins, synthetic polypeptides, small molecules attached to proteins, glycoproteins, steroids, nucleic acids, deoxyribonucleic acids, ribonucleic acids, nucleosides, nucleotides, oligonucleotides, antisense oligonucleotides, lipids, hormones, vitamin A, vitamin A derivatives, one or more of the foregoing in a cell.

9. A use of a bakuchiol derivative comprising either of a bakuchiol derivative of the structure of Formula (I) or a bakuchiol derivative of the structure of Formula (II) as claimed in claim 1 for: anti-aging; inhibition of apoptosis; modulation of cell cycle; inhibition of DNA damage; inhibition of tumors.

10. A use of a skin care composition comprising the skin care composition of any one of claims 4 to 8 for: anti-aging; inhibition of apoptosis; modulation of cell cycle; inhibition of DNA damage; inhibition of tumors.

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