Design, synthesis, and molecular docking of 1-(1-(4-chlorophenyl)-2-(phenylsulfonyl)ethylidene)-2-phenylhydrazine as potent nonazole anticandidal agent

Abstract

1-(1-(4-Chlorophenyl)-2-(phenylsulfonyl)ethylidene)-2-phenylhydrazine (13) was designed and synthesized as potential nonazole anticandidal agent and precisely characterized by IR, 1H NMR, 13C NMR, and ESI-MS. The anti-Candida activity of 13 was evaluated against four Candida species (C. albicans, C. krusei, C. parapsilosis, and C. glabrata). Compound 13 displayed good anticandidal activities (MIC=0.39, 0.195, 0.39, and 1.56 μmol/mL, resp.) in comparison with that of the standard drug fluconazole (MIC=0.195, inactive, 1.56, and 1.56 μmol/mL, resp.) against C. albicans, C. krusei, C. parapsilosis, and C. glabrata, respectively. A molecular modeling of the newly synthesized compound 13 was built in order to investigate its mode of action towards the prospective target cytochrome P450-dependent enzyme lanosterol 14α-demethylase (PDB-code: 1EA1). The docking results showed a similar binding interaction of 13 and fluconazole at the active site of CYT P450 14α-sterol demethylase. Furthermore, compound 13 showed no cytotoxicity against normal human breast cell line MCF10A.