Abstract

Background: Since the Monastrol discovery in 1999 as the first inhibitor of Eg5, functionalized dihydropyrimidinones/thiones (DHPMs) have emerged as prototypes for drug design in different targets. The present work aimed to evaluate the antifungal activity of a chemical library of DHPMs.

Methods: The compounds were obtained employing Biginelli reaction. Their antifungal activities were assessed against C. neoformans and C. albicans.

Results: The compounds 1-i and 1-k inhibited moderately the fungal growth of C. neoformans, with compound 2-k presenting MIC80 values of 62.5-125 µg·mL-1. Considering activity against C. albicans, the compounds 1-i and 1-n present an MIC50 value of 125-250 µg·mL-1.

Conclusion: The changes performed in DHPM scaffold appear to be valuable for generating compounds with potential antifungal effect.

Keywords: Biginelli reaction, Cryptococcus neoformans, Candida albicans, Antifungal activity, Structure activity relationship, Multicomponent reaction.