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-Candidaactivity of13was evaluated against fourCandidaspecies (C. albicans, C. krusei, C. parapsilosis, andC. glabrata). Compound13displayed 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.) againstC. albicans, C. krusei, C. parapsilosis, andC. glabrata, respectively. A molecular modeling of the newly synthesized compound13was 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 of13and fluconazole at the active site of CYT P450 14α-sterol demethylase. Furthermore, compound13showed no cytotoxicity against normal human breast cell line MCF10A.