Design, synthesis and evaluation of antifungal activity of novel triazole-3-thiol derivatives containing substituted phenyl moiety as inhibitors of enolase 1

Abstract

The emergence of azole resistant candida species is a significant clinical problem and indicates an urgent need for novel medications and treatment approaches. This research outlines the design, synthesis, and assessment of novel triazole-3-thiol derivatives that act as inhibitors of enolase 1 (Eno1). A total of seven triazole-3-thiol derivatives were designed to target Candida albicans by interfering with glycolysis through the inhibition of enolase 1 (Eno1). The molecular docking of these compounds into the active site of the crystal structure of Enolase1 from Candida albicans that is complexed with 2'-phosphoglyceric acid sodium (PDB ID: 7vrd) demonstrated similar binding modes and docking scores compared to those of Fluconazole. The compound (E)-4-(((3-mercapto-5-phenyl-4H-1,2,4-triazol-4-yl)imino)methyl)-2-methoxyphenol exhibits the greatest binding affinity to the target. Derivatives were synthesized by the reaction of thiocarbohydrazide, different carboxylic acid and vanillin. The structures of the newly created compounds were determined through their spectral data. The antifungal properties were assessed in vitro by determining the minimal inhibitory concentrations (MICs) using a microdilution assay. All synthesized derivatives exhibit notable antifungal efficacy against candida albicans.