Computer-aided molecular design, synthesis and evaluation of antifungal activity of heterocyclic compounds

Abstract

Outpatient complications for fungal infections in immunocompromised patients and the development of antimicrobial drug resistance mechanisms demonstrate the need to develop new antifungal agents. In this perspective, heterocyclic compounds namely thiazolylhydrazones, furan, tetrazole, triazole and thiadiazoline derivatives were synthesized and tested in vitro against seven clinical importance Cryptococcus and Candida species. In this study, virtual screening techniques were applied using a scaffold-hopping database, FDA approved drugs and a ZINC subset. Some of the compounds evaluated showed promising antifungal activity against C. albicans, C. glabrata, C. krusei, C. parapsilosis, C. tropicalis, C. neoformans and C. gatti, displaying minimal inhibitory concentration (MIC) values in the range of 0.12–250 µM.