In vitro Antifungal Activity of Dihydropyrimidinones/Thiones Against Candida albicans and Cryptococcus neoformans

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.Fil: De Azambuja, Gabriel Oliveira. Universidade Federal do Rio Grande do Sul; BrasilFil: Svetaz, Laura Andrea. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Área Farmacognosia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; ArgentinaFil: Goncalves, Itamar Luis. Universidade Federal do Rio Grande do Sul; BrasilFil: Corbelini, Patricia Frasson. Universidade Federal do Rio Grande do Sul; BrasilFil: von Poser, Gilsane Lino. Universidade Federal do Rio Grande do Sul; BrasilFil: Kawano, Daniel Fabio. Universidade Estadual Do Campinas. Instituto de Química.; BrasilFil: Zacchino, Susana Alicia Stella. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Área Farmacognosia; ArgentinaFil: Eifler Lima, Vera Lucia. Universidade Federal do Rio Grande do Sul; Brasi