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Synthesis, Biological Evaluation and Molecular Docking of Certain Sulfones as Potential Nonazole Antifungal Agents.

ABSTRACT: We reported herein the synthesis, antifungal activity, docking and in silico ADME prediction studies of four novel series of sulfones 6a-f, 8a-c, 10a-f and 12a-c. All the newly synthesized sulfones were tested against four strains of Candida (including fluconazole-resistant Candida), two strains of Aspergillus, two dermatophytic fungi (Trichophytons mentagrophyte and Microsporum canis) and Syncephalastrum sp. with fluconazole as a reference drug. In general, compounds 8a and 10b showed selective and potent anticandidal activity (MIC: 0.19-0.81 µM) relative to fluconazole (MIC = 1.00 µM). Furthermore, 10e and 12a elicited a remarkable and selective antifungal activity against Aspergillus sp. and the dermatophytic fungi (MIC: 0.16-0.79 µM) relative to fluconazole (MIC: 2-2.6 µM). Moreover, the docking results of the sulfones 6a, 8a, 10a and 10b at the active site of CYT P450 14?-sterol demethylase showed a comparable binding interaction (interaction Energy = -34.87 to -42.43 kcal/mol) with that of fluconazole (IE = -40.37 kcal/mol).

SUBMITTER: Fares M

PROVIDER: S-EPMC6274496 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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