Synthesis, Molecular Docking, and Biological Evaluation of Novel Triazole Derivatives as Antifungal Agents

Abstract

Twenty-eight novel triazole derivatives (compounds 1a-v, 2a-f) have been synthesized for structure-activity relationship studies as antifungal agents. The compounds were designed on the basis of the structure of fluconazole and molecular modeling of the active site of the cytochrome P450 14α-demethylase (CYP51). All of them are reported for the first time. Their chemical structures are characterized by 1H NMR, 13C NMR, LC-MS, and elemental analysis. The antifungal activities have been evaluated in vitro by measuring the minimal inhibitory concentrations (MICs). Compounds 1a-v exhibited higher activity against nearly all fungi tested except Aspergillus fumigatus (A. fum) than fluconazole (FCZ). The computational molecular docking experiments indicated that the inhibition of CYP51 involves a coordination bond with iron of the heme group, a hydrophilic H-bonding region, a hydrophobic region, and a narrow hydrophobic binding cleft. © 2010 John Wiley & Sons A/S.