Design, synthesis and evaluation of benzotriazole derivatives as novel antifungal agents

Considering the need for discovery of new antifungal drugs with greater potency and broader spectrum of activity, a new series of 5-substituted benzotriazole derivatives were designed, through structure based design, as inhibitors of fungal cytochrome P450 lanosterol 14-alpha demethylase. These were further optimized by a combination of iterative medicinal chemistry principles and molecular docking. Based on the best docking scores, some benzotriazole derivatives were synthesized and characterized by IR, H-1 NMR and MS/MS. The molecules were evaluated for their antifungal action against Candida albicans by cup plate method and ergosterol quantification method by UV spectroscopy. Reasonably good correlation between docking scores and antifungal activity were observed. The computational predictions were in consensus with the experimental results. (C) 2015 Elsevier Ltd. All rights reserved.