Antidermatophytic activity of some newly synthesized azole derivatives / Ihab Abdalah Abdelsamed Sharawy ; Supervised Salama A. Ouf , Sobhy Mohamed Gomaa , Mohamed Eweis Mahmoud

Thesis (M.Sc.) - Cairo University - Faculty of Science - Department of Botany and Microbiology

A series of fourteen novel arylazothiazole derivatives were synthesized in a good yield via coupling of thiazole derivatives with arenediazonium chloride in ethanol in the presence of sodium acetate trihydrate at 0-5 {u00B0}C. The structure of the newly synthesized products was elucidated via elemental analysis, spectral data and alternative routes whenever possible. Moreover, the antifungal activity screening of the products was evaluated using the diameter of inhibition zone, minimum inhibitory concentration (MIC), minimum fungicidal concentration (MFC). The structure-activity relationship was evaluated. The activity of the synthesized compounds depends mainly of (R) and (Ar) side chains of the nucleus compound and the toxicity indicates that when both are aromatic > one aromatic and on aliphatic and substituted aromatic with CH3 or OCH3> non-substituted >substituted aromatic with chloro- or nitro-groups. Thiazole derivatives7a, 7c, 7e, 7f, 7g, 7i, 7m, and 11a and showed the most efficacious compound and were compatible with fluconazole as antifungal reference drug when investigated against Candida albicans, Microsporum gypseum and Trichophyton mentagrophytes. The MIC reached 2 æg/mL in the case of C. albicans for compounds 7a, 7b, 7c and 11a and measured 4 æg/mL in the case of M. gypseum and T. mentagrophytes for the same compounds. The MFCs for the same compounds were 4 æg/mL for C. albicans and ranged from 8-32 æg/mL for the other two fungi. The results revealed that compounds 7c and 11a were the most toxic compounds against the tested fungi regarding keratinase activity and ergosterol synthesis. The efficacy of synthesized thiazoles 3c and 11a applied at their respective MFC were effective in treatment of skin infection of guinea pigs due to inoculation with the tested fungi 48 days after inoculation as compared with fluconazole. The MOE 2014.010 package software was used to analyze all docking poses and binding energies between compound 11a and keratinase to evaluate the affinity of the compound according to its binding energy with the enzyme. The computational studies supported the biological activity results

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