Anti-fungal composition and method of treatment

Abstract

The invention provides an antifungal compound, in which the compound is 1-(phenylsulfonyl)-1H-indol-2-ylmethanone or a derivative thereof. Also provided are combinations and compositions comprising the compound and other known antifungal agents and pharmaceutically acceptable carriers. The invention further relates to the therapeutic use of an antifungal compound in the prevention or treatment of fungal diseases, and provides that the antifungal compound may be administered to a subject orally or topically.

Description

ANTIFUNGAL COMPOSITION AND TREATMENT METHOD TECHNICAL FIELD [1] The present disclosure relates to a pharmaceutical composition containing an active compound for use in the treatment of fungal diseases, including onychomycosis. Specifically, this disclosure covers the chemical structure of the active compound and the treatment of fungal diseases with the composition by oral and / or topical administration. CROSS-REFERENCE TO RELATED APPLICATIONS [2] This application claims the benefit of U.S. Provisional Patent Application No. 63 / 620,290, filed January 12, 2024, which is incorporated by reference in its entirety herein. INTRODUCTION [3] Onychomycosis, a fungal infection of the nails, is a pressing global health problem affecting millions of people. It occurs in approximately 10% of the general population and is about five times more common among older adults. Onychomycosis is characterized by yellowish-white discoloration, thickening, scaling, and separation of the nail from the surrounding skin. Cases of onychomycosis are typically caused by three types of fungi: dermatophytes, yeasts, and molds. Dermatophytes are the predominant cause, accounting for over 90% of nail infections. The most common dermatophytes causing nail infections in the Americas and Europe are known as Trichophyton rubrum and Trichophyton mentagrophytes, with T rubrum being the main cause of onychomycosis. [4] Over the past five decades, numerous medications have been developed for the treatment of onychomycosis, both for oral and topical use. However, most oral medications must be taken consistently for extended periods, and many have been shown to cause liver damage. Because of these predominant side effects, typical oral treatments for onychomycosis are often accompanied by frequent blood testing, allowing healthcare professionals to monitor and manage the detrimental effects of such treatment. The additional step of monitoring the patient's condition through blood testing places an additional burden on both the patient and the physician. [5] Although many topical medications are not subject to the same side effects, they also require significant commitment and discipline on the part of the patient in their use. The most commonly used topical compositions to treat onychomycosis today are terbinafine and ciclopirox olamine. Some topical solutions require multiple applications per day for the entire course of treatment, which typically spans 12 weeks, but can be longer. Because T. rubrum and T. mentagrophytes evolve, these fungi tend to become resistant to traditional treatments, especially in cases where patients do not complete the full course of treatment. Since topical treatments commonly require multiple daily doses for 12 or more weeks, there is a significant risk that a patient will not comply with the treatment plan.One of the advantages of this active compound is that it represents a new molecule not previously reported in the literature, which could be considered part of a novel class of pharmaceutical compositions for the treatment of fungal infections of nails and skin. For this reason, the active compound of the present disclosure is unlikely to face the challenges of adaptive resistance that arise when using known methods to treat infections caused by the most common dermatophytes responsible for onychomycosis. [6] Accelerated symptom clearance is desirable for several reasons. Onychomycosis affects self-image, makes walking uncomfortable or painful, and may contribute to the development of other diseases. Efficient clearance or reduction of these symptoms is clinically desirable, and is also important because it will encourage patients to maintain a consistent standard of care throughout the treatment period.[7] Onychomycosis is notoriously easy to contract and difficult to eradicate. Most treatments for onychomycosis require consistent administration of a topical or oral treatment over an extended period to combat the infection. Additionally, most topical treatments must be applied to the affected area daily. Even if a patient is able to adhere to a consistent treatment schedule, commonly used treatments for onychomycosis may not provide results in a timeframe that aligns with the patient's expectations. Therefore, it is not uncommon for patients to opt for a faster, but more invasive, treatment option. These options include surgical removal of the affected nails or laser treatment to thermally eradicate the fungus. These treatments are typically reserved for severe cases where onychomycosis poses a significant threat to the patient's overall health. [8] It would also be desirable to treat onychomycosis with a composition containing an active compound that limits the development of fungal resistance to treatment. It would be even more desirable to treat onychomycosis with a composition containing an active compound that demonstrates rapid fungicidal activity. SUMMARY [9] In some aspects, the present disclosure relates to a pharmaceutical composition for the treatment of onychomycosis; wherein the composition comprises an active compound and at least one carrier. The active compound has the following Formula (I):

[0010] For the active compound of Formula (I), R1 may be selected from hydrogen, SO2CH3 (methylsulfonyl), SO2Ph (benzylsulfonyl), and any other arylsulfonyl group. R2, R3, R4, and R5 may be independently selected from hydrogen, halogen, methyl, hydroxyl, carboxylic acid, and derivatives thereof, including but not limited to carboxylate, ester, amide, thioester, and acyl phosphate groups. R6 and R7 may be independently selected from sulfur, nitrogen, and / or a methine group, while R8 may be selected from sulfur, oxygen, an amine group, and a methylene group. Separately, R9 may be selected from a methine group, nitrogen, and sulfur.

[0011] The composition may be formulated for topical administration, oral administration, or any combination thereof. Alternatively, the composition may be formulated for delivery by any method known in the art. In one embodiment, the composition may be incorporated into a cream, oil, lotion, gel, serum, nail polish, spray, aerosol, or any combination thereof for topical application to a patient.

[0012] This disclosure also teaches a method of treating a fungal infection in a subject, which may comprise administering the aforementioned composition to the subject topically, orally, or by any method known in the art. The composition may be administered to treat infections caused by fungi, including but not limited to the following: T. rubriim, T. mentagrophytes, Candida albicans, Epidermophyton floccosum, Scopulariposis brevicaulis, Cryptococcus neoformans, or fungi of the Microsporum, Fusarium, or Aspergillus species. DETAILED DESCRIPTION

[0013] The following detailed description provides antifungal compositions and may refer to one or more figures. These figures should not be construed in a limiting manner, and are included only as illustrative examples of possible embodiments of the active compound of this disclosure. These figures describe the structure of the active compound of the present disclosure in sufficient detail to enable those skilled in the art to carry out the disclosure. It should be understood that other implementations may be utilized, and that structural changes and / or substitutions of various functional groups may be made without departing from the scope and spirit of this disclosure.

[0014] The terms “formulation” and “composition” are used interchangeably herein to refer to a product of the disclosed invention comprising all active and inactive ingredients. The term “active” refers to the ingredient, component, or constituent of the compositions of the disclosed invention responsible for the desired therapeutic effect. The terms “pharmaceutical formulation” or “pharmaceutical composition” as used herein refer to a formulation or composition that is employed to prevent, reduce the intensity of, cure, or otherwise treat a targeted condition or disease.

[0015] The terms “administer” or “administration” as used herein are used interchangeably to mean the delivery or application of a substance and include in vivo administration as well as administration directly to tissue ex vivo. The term “carrier” as used herein describes a material that does not cause significant irritation to an organism and that does not abrogate the biological activity or properties of the compound in the composition of the invention described. Carriers should be of sufficient purity and sufficiently low toxicity to be suitable for administration to the mammal being treated. The carrier may be inert, or it may possess pharmaceutical benefits.

[0016] The terms “substantially or essentially free” are used to refer to a material that is at least 80%, i.e., at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95% free from components that normally accompany or interact with it, as found in its natural environment.

[0017] The terms “disease” or “disorder” as used herein refer to a deterioration in health or a condition of abnormal functioning. The term “symptom” as used herein refers to a sign or indication of a disorder or disease, especially when experienced by an individual as a change in normal functioning, sensation, or appearance.

[0018] The term “topical” refers to the administration of the composition at or immediately below the site of application. The phrase “topical application” describes application to one or more surfaces, including epithelial surfaces, by transdermal patches, ointments, creams, gels, polishes, balms, liquids, pastes, or foams, or by other topical methods known in the art. The term “oral” refers to the administration of the composition through the mouth of a mammalian subject. “Oral” administrations may take the form of tablets, capsules, suspensions, powders, lozenges, sachets, oral solutions or syrups, oral emulsions, oral gels, oral films, oral liquids, powder, e.g., for suspension, or any other method known in the art.

[0019] The term “treat” or “treating” as used herein refers to achieving one or more of the following: (a) reducing the severity of a disorder; (b) limiting the development of symptoms characteristic of the disorder or disorders being treated; (c) limiting the worsening of symptoms characteristic of the disorder or disorders being treated; (d) limiting the recurrence of the disorder or disorders in patients who previously had the disorder or disorders; and (e) limiting the recurrence of symptoms in patients who were previously symptomatic for the disorder or disorders.

[0020] The composition of the present disclosure may be useful for treating fungal diseases, including onychomycosis. It may be administered orally and / or topically, and may include an active compound and at least one carrier. The active compound may have the following general structure, Formula (I): wherein R1 is selected from any suitable combination of hydrogen, methylsulfonyl (SO2CH3, also abbreviated in the art as “Ms”), phenylsulfonyl (SO2Ph or SO2C6H5, also abbreviated in the art as “PhS”), and any arylsulfonyl group; R2, R3, R4, and R5 are independently selected from hydrogen, halogen, methyl, hydroxyl, or carboxylic acid and derivatives thereof, including but not limited to carboxylate, ester, amide, thioester, and phosphate acyl groups; R6 and R7 are independently selected from nitrogen, sulfur, and a methine group; R8 is selected from sulfur, oxygen, an amine group, and a methylene group; and R9 is selected from a methine group, nitrogen, and sulfur.

[0021] Methylsulfonyl means a sulfonyl group substituted with an alkyl group Cl, having the formula SO2CH3, also abbreviated in the art as “Ms”. Phenylsulfonyl means a sulfonyl group substituted with an aryl group, which may have the formulas SO2Ph or SO2C6H5, also abbreviated in the art as “PhS”. An aryl group is defined as an optionally substituted cyclic group of C6 to C12, with conjugated electrons TI [4n+2], where n is 1, 2 or 3. Non-limiting examples of aryl groups include heteroaryls, benzene and naphthalene. Aryls may be unsubstituted or substituted. A substituted aryl may be optionally substituted with 1, 2, 3, 4, 5 or 6 substituents located at any position on the ring.

[0022] Heteroaryl means a monocyclic or heterocyclic aryl group containing 1, 2, 3 or 4 substituted heteroatoms in the carbon chain. Examples of heteroaryls include, but are not limited to, pyridine, pyrimidine, pyrazine, pyridazine, imidazole, pyrazole, triazole, quinoline, indole, purine, furan, benzofuran, thiophene, thiazole, benzothiazole, oxazole, isoxazole, dithiadiazole, thiazolidiazole, carbazole, pyrrolidine and pyrrole.

[0023] More specifically, heteroaryls may include 1,2,3-thiazolidadiazole, 1.2.4-thiazolidadiazole, 1,2,5-thiazolidadiazole, 1,2,3-dithiadiazole, 1,3,2-dithiadiazole, 1.3.4-thiazolidadiazol and 1,2, 3, 5 -dithiadiazole.

[0024] “Halo” or “halogen” means fluorine, chlorine, bromine, or iodine. Methyl, methines, and methylene refer to hydrocarbon groups with one carbon atom. In some implementations, alkyl groups may be substituted for methyl groups. The term “alkyl groups” refers to hydrocarbon chains of between 2 and 6 carbon atoms, which may be straight, branched, or cyclic. Examples of alkyl groups include, but are not limited to, ethyl, n-propyl, n-pentyl, n-butyl, isoamyl, isopropyl, t-butyl, cycloalkyl, cyclohexyl, or cyclopentyl. Alkyl groups may be substituted or unsubstituted. Substituted alkyl groups may be optionally substituted with 1, 2, 3, 4, 5, or 6 substituents on any carbon of the alkyl group. Substituents refer to any atom or group of atoms other than hydrogen.

[0025] Hydroxyl refers to a group having the formula -OH, including alcohols, phenols, and carboxylic acids. A carboxylic group or carboxylic acid indicates a group having the structure -COOH. Carboxylate refers to the conjugate base of a carboxylic acid with the formula -COO-. Ester refers to a group with the formula -COO- interposed within a carbon chain, where one carbon atom is double bonded to an oxygen atom and single bonded to another oxygen atom. Thioesters have the general formula -C(=O)-S- interposed within a carbon chain. Amide refers to a group containing a carbonyl group (a carbon doubly bonded to an oxygen atom) that is directly bonded to a nitrogen atom, with the general formula -CO-N-, and interposed within a carbon chain.Amine refers to a formula characterized by a group with the formula -NH2 connected to a hydrocarbon group, such as an alkyl, aryl, or other substituent group. Acyl phosphate refers to a group characterized by the presence of a phosphorylated acyl group, with a phosphoryl group attached to the acyl group through an ester bond, having the general formula -C(=O)-O-[PO3]— , interposed within a carbon chain.

[0026] This disclosure is not intended to limit the structure of the active compound to a particular stereoisomeric isomer, and all shallow stereoisomers are contemplated by this disclosure. The term shallow stereoisomer refers to diastereomers, epimers, and enantiomers of any formula. Chiral centers in any formula may have either an S configuration or an R configuration, unless specifically indicated otherwise.

[0027] The region of the composition containing R6, R7, and R8 can be optimized according to the desired processing properties of the composition. In one embodiment featuring a nitrogen-based five-membered heterocycle, the ring can be characterized as pyrrolidine, pyrrole, imidazole, pyrazole, or triazole. These structures are illustrative and do not limit the character of the compound. Several examples of embodiments featuring nitrogen-substituted heterocycles of Formula (I) include, but are not limited to, Formula (II): and Formula (III):

[0028] In addition to nitrogen as a substituent, this five-membered heterocyclic region may be substituted with sulfur. In a preferred implementation, this five-membered heterocycle may be a thiazole. This five-membered heterocycle may be 1,2,3-thiadiazole, 1,2,4-thiadiazole, 1,2,5-thiadiazole, 1,2,3-dithiazole, 1,3,2-dithiazole, 1,3,4-thiadiazole, 1,2,3,5-dithiadiazole, or any other structure calibrated to impart the desired antifungal effect. Various non-limiting examples of structures featuring sulfur- and nitrogen-substituted heterocycles may include, but are not limited to, the following Formulas (IV-VII). Formula (IV) is: Formula (V): Formula (VI): and Formula (VII):

[0029] In an implementation where R1 is PhS (as in Formula VI mentioned above), the nitrogen adjacent to R1 may present a localized positive charge. In such an implementation, the active compound of the present disclosure may be accompanied by a stabilizing molecule. The stabilizing molecule may be any negatively charged organic or inorganic molecule known in the art. In a preferred implementation, the stabilizing molecule (i.e., the anion) may be a halogen. In an alternative implementation, the stabilizing molecule may be any suitable molecule known in the art that neutralizes the positive charge present on the nitrogen adjacent to R1 of an implementation of the compound of the present disclosure. In another alternative implementation, the positive charge may be stabilized by the aromaticity of one or more ardo groups present in the active compound of the present disclosure.

[0030] The specific structure of this region and of the active compound in general can be optimized to best inhibit a fungal infection. In an alternative embodiment, the structure of this region can be optimized to achieve the best fungicidal effect by any mechanism known in the art.

[0031] R2, R3, R4, and R5 may be independently selected from hydrogen, halo, methyl, hydroxyl, carboxylic acid, and derivatives thereof, including but not limited to carboxylate, ester, amide, thioester, and acyl phosphate groups. A selection of halo may allow for the inclusion of fluorine, chlorine, bromine, or iodine in the composition of the present disclosure. In a preferred halo-substituted embodiment, R2, R3, R4, and / or R5 may be chlorine.

[0032] R9 may be selected from a methine, nitrogen, or sulfur group. In one embodiment, sulfur may be selected to enhance the antifungal properties of the active compound.

[0033] In a preferred embodiment, the active compound of the present disclosure may have the following Formula (VIII):

[0034] This specific embodiment of the active compound may be l-(phenylsulfonyl)-lH-indol-2-ylmethanone (designated as JC-XX-109) and may have the following chemical structure: C18H12N2S2O3. It is contemplated that other groups may exist functional groups that confer the antifungal benefits of the active compound of the present disclosure. This specific embodiment may be preferable because it balances the challenges that accompany the synthesis of the active compound of the present disclosure with the functional advantages that its structure provides (i.e., advanced antifungal properties). However, any of the various embodiments contemplated herein can be used to address any challenge known to one of ordinary skill in the art regarding optimizing antifungal properties for a given scenario.

[0035] When used to treat onychomycosis, the compounds of the present disclosure, including the compounds of Formulas (I-VIII), may induce an antifungal effect by inhibiting the synthesis of one or more transmitters, molecules, proteins, or other compounds in the cell, including ergosterol; by altering or interfering with cell wall function, including transport sites, for example, by blocking nucleic acid synthesis, by inhibiting microtubule function, or by any other mechanism of action known in the art. Furthermore, the active compound of the present disclosure may have improved efficacy in eradicating onychomycosis infections compared to traditional methods known in the art. For example, in vitro testing has shown that the active compound of the present disclosure is thousands of times more effective in eliminating T. rubrum and T. infections.mentagrophytes compared to terbinafine. As another example, in vitro testing has shown that the active compound of the present disclosure is thousands of times more effective at eliminating T. rubrum and T. mentagrophytes infections compared to ciclopirox. The specific findings of these tests are discussed in more detail below.

[0036] As a result of this increased efficacy, patients suffering from onychomycosis may need to exercise less discipline in maintaining their treatment regimen. A composition containing a therapeutically effective amount of the active compound of the present disclosure is expected to require topical application or oral administration less frequently or in smaller doses than terbinafine and / or ciclopirox. As another result of the efficacy of the active compound of the present disclosure in treating onychomycosis, the treatment period may be shorter than other treatments known in the art, namely terbinafine and ciclopirox. This shorter exposure period may allow patients suffering from onychomycosis to experience relief from their symptoms sooner than patients who choose to use other treatments known in the art. Furthermore, the shorter treatment period and the lower Required doses may reduce the likelihood of complications associated with onychomycosis, which is especially high in patients with other chronic conditions. The increased likelihood that patients will complete the full course of treatment may also provide other benefits, such as a reduction in the likelihood of recurrent infections or long-term relief from the symptoms of onychomycosis. In summary, the composition of the present disclosure may reduce the burden of onychomycosis treatment in terms of duration, dosage, and frequency, which is expected to lead to higher recovery rates and lower recurrence rates among patients.

[0037] When used to treat infections caused by T. rubrum and T. mentagrophytes, the composition of the present disclosure may avoid the common problem of resistance that develops over time. Test results indicate that common causes of onychomycosis have not developed resistance to the active compound of the present disclosure. In contrast, antifungal treatments commonly used in the art, such as terbinafine and ciclopirox, become less effective over time. It is also not uncommon for an individual who has successfully completed treatment with a conventional antifungal to relapse and subsequently need to restart the treatment process. By using the composition of the present disclosure to treat a fungal disease, a patient may be able to more quickly reduce the symptoms of onychomycosis, eradicate the underlying fungal infection, and reduce the possibility of relapse or recurrence.

[0038] In another aspect, the composition or active compound of the present disclosure may be combined with other compositions to enhance the desired effects of a topical or oral treatment. Any other treatment method known in the art may be used. As a non-limiting example, a topical treatment application containing the active compound of the present disclosure may include any number of inactive ingredients to facilitate application of the treatment. As another non-limiting example, a topical treatment application containing the active compound of the present disclosure may include any number of inactive ingredients and may also include any number of active ingredients calibrated to enhance the fungicidal properties of the treatment. Additional active ingredients may include dispersing agents, other fungicidal compounds, or any other suitable compound or carrier known in the art.Furthermore, it is contemplated that the active compound of the present disclosure may be diluted or combined with other compounds to limit the effectiveness of the resulting composition, which may be particularly applicable in a stepped treatment plan.

[0039] Furthermore, the active compound and composition of the present disclosure may have other medical benefits that have not yet been explored. Currently available test results indicate that the active compound of the present disclosure may be effective in treating infections caused by T. rubrum and T. mentagrophytes. It is contemplated that one of ordinary skill in the art would understand that the active compound of the present disclosure may be applicable to other species, through the same or similar mechanisms of action. To that end, it is contemplated that the composition of the present disclosure will have a similar effect when used to treat infections caused by Candida albicans, Epidermophyton floccosum, Scopulariposis brevicaulis, Cryptococcus neoformans, or fungi of the Microsporum, Fusarium, or Aspergillus species.Furthermore, it is contemplated in this disclosure that there may be other applications in which this composition or active compound is useful, including antibacterial, antimicrobial, antiviral or anticancer treatments. Although specific configurations are disclosed in this document, it is contemplated that other configurations may be achieved with different formations and structures. Furthermore, it is contemplated that slight variations to the aforementioned configurations may be implemented to achieve similar results, and such configurations are considered within the scope of this disclosure. EXAMPLE ACTIVITY: Measuring Minimum Inhibitory Concentrations

[0040] A total of 24 strains of Trichophyton rubrum were tested, including 23 clinical isolates of dermatophytes from different origins and strain ATCC 28188. All microorganisms are part of the dermatophyte collection of the Medical Mycology Laboratory, University of Costa Rica.

[0041] To prepare the fungal samples, T. rubrum isolates were grown for 7 days at 35°C in test tubes containing oatmeal agar. Spores were collected by flooding the test tubes with 85% sterile saline (1 mL) and lightly scraping the agar surface with a cotton swab. Spores were then counted in a Bürker hemocytometer and diluted in RPMI 1640 medium (Gibco™) to a concentration of 1.5 x 10 A 7 spores / mL for minimum inhibitory concentration determination tests.

[0042] Sterile microtiter plates were inoculated with 100 µL of RPMI 1640 medium, 100 µL of T. rubrum spores, and 100 µL of drug dilution stock containing a predetermined concentration of the active compound of this disclosure, either terbinafine (obtained from Royal Pharma) or ciclopirox (obtained from Jinlan Pharm-Drugs). Standard solutions of terbinafine and ciclopirox were prepared at a concentration of 5 mg / mL by methods known to those skilled in the art.

[0043] Two-fold serial dilutions of each variable material were prepared on microtiter plates. Growth and sterility controls were included for each test. Growth controls consisted of spores, DMSO, and RPMI 1640 medium. Sterility controls consisted of RPMI 1640 medium and DMSO, without spores. Each test was repeated twice. After preparing the samples and control plates, all plates were incubated at 28°C for 4 days. Growth was assessed using the Biotek Synergy HT multidetection reader to measure the optical density at 450 nm for each sample.The optical density of the growth control wells was assumed to correspond to 100% growth, according to the CLSI (Clinical Laboratory Standards Institute) microdilution reference method M38-A2, as well as other analytical methods known in the art, including broth dilution antifungal susceptibility testing methods for filamentous fungi. (Approved Standard M38-A2. 2. a Wayne, PA: Clinical and Laboratory Standards Institute, 2008).

[0044] The minimum inhibitory concentration (MIC) of a compound can be defined as the lowest concentration of the drug that inhibits the growth of an organism by more than 80% compared to a drug-free control. Therefore, the MIC for each compound was calculated as the concentration of treatment material in the last well where the optical density was 20% lower than the optical density of the growth control.

[0045] As shown in Table 1 above, in 90% of the cases tested (samples 1-18), the active compound of the present disclosure (JC-XX-109) exhibited a lower MIC against T. rubrum than Terbinafine; and in 100% of the cases (samples 1-20), the active compound of the present disclosure (JC-XX-109) was more effective (i.e., had a lower MIC) than Ciclopirox. Based on the data in Table 1, the active compound of the present disclosure (JC-XX-109) was up to 2932 times more active than Terbinafine (samples 2, 4, 5, 6). Similarly, the active compound of the present disclosure (JC-XX-109) was up to 3109 times more effective against T. rubrum than Ciclopirox (samples 4, 5, 6, 7, 14, 15, 16, 18, 20). Therefore, the MIC of the active compound has been shown to be of the present disclosure is consistently lower than the MICs for Ciclopirox and Terbinafine.

[0046] Analogous MIC experiments, detailed above, showed that the active compound of the present disclosure (JC-XX-109) also displayed significant antifungal activity on samples inoculated with Trichophyton mentagrophytes. These experiments were carried out identically to those described above, except that the plates were inoculated with Trichophyton mentagrophytes spores instead of the Trichophyton rubrum spores used previously.

[0047] In 100% of the samples tested, the active compound of the present disclosure (JC-XX-109) showed similar inhibitory efficacy at significantly lower concentrations than Terbinafine and Ciclopirox against T. mentagrophytes. The active compound of the present disclosure (JC-XX-109) was up to 2932 times more effective than Terbinafine (isolate 21), and up to 3109 times more active than Ciclopirox (isolate 24) against T. mentagrophytes.

[0048] Other fungi may be used in the above assay, including, but not limited to, T. rubrum, T. mentagrophytes, Candida albicans, Epidermophyton floccosum, Scopulariposis brevicaulis, Cryptococcus neoformans, or fungi of the Microsporum, Fusarium, or Aspergillus species. Fungi are grown by standard methods known to those skilled in the art, and minimum inhibitory concentrations (MICs) are measured as detailed above. EXAMPLE OF IN VIVO TOXICITY

[0049] To determine potential dermal irritation and toxicity of the active compound of the present disclosure (JC-XX-109), a series of laboratory tests were conducted on animals. The results of these tests are summarized in Table 3 below.

[0050] *Tested on New Zealand rabbits

[0051] * *Tested on Sprague-Dawley rats

[0052] The aforementioned tests show that the active compound of the present disclosure (JC-XX-109) could be very safe for use in a topical composition for mammalian subjects. It does not produce significant skin or eye irritation (based on rabbit testing) and does not pose a significant risk of acute toxicity when administered orally to rats. Examples

[0053] The following non-limiting examples are illustrative of the present invention.

[0054] Example 1: A composition for the treatment of fungal diseases in a subject; wherein the composition includes a carrier and an active compound, where the active compound has the following formula: where R1 is selected from hydrogen, SO2CH3 and an arylsulfonyl group; where R2, R3, R4 and R5 are independently selected from hydrogen, halo, methyl, hydroxyl, carboxylic acid, carboxylate and ester groups; where R6 and R7 are independently selected from sulfur, nitrogen, and a methylene group; where R8 is selected from a methylene group, an amine group, oxygen, and sulfur; and where R9 is selected from a methylene group, nitrogen, and sulfur.

[0055] Example 2: The composition of Example 1, wherein the composition is formulated for topical administration, oral administration, or a combination of both.

[0056] Example 3: The composition of Example 1, wherein the composition is formulated into a cream, oil, lotion, gel, serum, nail polish, spray, aerosol, or a combination thereof.

[0057] Example 4: A method for treating a fungal disease in a subject, comprising administering a therapeutically effective amount of the composition of Example 1 to a subject.

[0058] The method of treating a fungal disease in a subject of Example 4, wherein the fungal disease is caused by T. rubrum, T. Mentagrophytes, Candida albicans, Epidermophyton floccosum, Scopulariposis brevicaulis, Cryptococcus neoformans, or fungi of the Microsporum, Fusarium, or Aspergillus species.

[0059] Various elements, described herein in the context of one or more embodiments, may be provided separately or in any suitable subcombination. Furthermore, the processes described herein are not limited to the specific embodiments described. For example, the processes described herein are not limited to the specific processing order described herein, and instead, process blocks may be reordered, combined, eliminated, or performed in parallel or in series, as needed, to achieve the results set forth herein.

[0060] It will further be understood that various modifications in the details, materials and arrangements of parts described and illustrated herein may be made by persons skilled in the art without departing from the scope of the following claims.

[0061] All references, patents, patent applications, and publications cited or referenced in this application are incorporated herein by reference in their entirety. Finally, other implementations of the disclosure will become apparent to those skilled in the art upon consideration of the specification and practice of the disclosure set forth herein. The specification and examples are intended to be considered exemplary only, and the true scope and spirit of the disclosure are indicated by the claims.

Claims

CLAIMS 1. A composition for the treatment of fungal diseases in a subject; the composition includes a carrier and an active compound, the active compound having the following formula: where R1 is selected from hydrogen, SO2CH3 and an arylsulfonyl group; where R2, R3, R4 and R5 are independently selected from hydrogen, halo, methyl, hydroxyl, carboxylic acid, carboxylate and ester groups; where R6 and R7 are independently selected from sulfur, nitrogen and a methine group; where R8 is selected from a methylene group, an amine group, oxygen and sulfur; and where R9 is selected from a methine group, nitrogen and sulfur.

2. The composition of claim 1, wherein the composition is formulated for topical administration, oral administration, or a combination of both.

3. The composition of claim 1, wherein the composition is formulated into a cream, oil, lotion, gel, serum, nail polish, aerosol, spray, or a combination thereof.

4. A method for treating a fungal disease in a subject, comprising administering a therapeutically effective amount of the composition of claim 1 to a subject.

5. The method of treating a fungal disease in a subject of claim 4, wherein the fungal disease is caused by T. rubrum, T. Mentagrophytes, Candida albicans, Epidermophyton floccosum, Scopulariposis brevicaulis, Cryptococcus neoformans, or fungi of the Microsporum, Fusarium or Aspergillus species.

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