A series of fourteen novel synthesized arylazothiazole and arylhydrazothiazole derivatives were tested for their antifungal activity and structure-activity relationship. The activity of the compounds depends mainly on the side chains of the nucleus compound. The antifungal activity was more significant when both side chains are aromatic > one aromatic and one aliphatic and substituted aromatic with CH3 or OCH3 > non-substituted > substituted aromatic with chloro- or nitro-groups. Thiazole derivatives 7a, 7c, 7e, 7f, 7 g, 7i, 7 m, and 11a showed the most effective as antifungal compounds and were comparable with fluconazole as antifungal reference drug when investigated against Candida albicans, Microsporum gypseum and Trichophyton mentagrophytes. The minimum inhibitory concentration (MIC) reached 2 µg/mL in the case of C. albicans for compounds 7a, 7b, 7c and 11a and measured 4 µg/mL in the case of M. gypseum and T. mentagrophytes for the same compounds. The minimum fungicidal concentration (MFC) for the same compounds was 4 µg/mL for C. albicans and ranged from 8 to 32 µg/mL for the other two fungi. The results revealed that compounds 7c and 11a were the most antifungal compounds against the test fungi regarding keratinase activity and ergosterol biosynthesis. The in vivo efficacy of synthesized thiazoles 7c and 11a applied at their respective MFC was more effective in the treatment of skin infection of guinea pigs previously inoculated with the test fungi as compared with fluconazole. The Molecular Operating Environment (MOE) software was used to analyze the docking poses and binding energies of compound 11a and keratinase. The computational studies supported the biological activity results.
Keywords: Cutaneous fungi; Docking; Ergosterol; Keratinase; Thiazole.
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