Abstract
Fungal infections caused by Candida species represent a significant and growing clinical challenge, exacerbated by the emergence of antifungal resistance and the limited availability of therapeutic options. In this study, we evaluated the antifungal activity of seven selected synthetic compounds against ten clinically relevant Candida species, including Candida albicans, Candida parapsilosis, Candida orthopsilosis, Candida metapsilosis, Candida tropicalis, Nakaseomyces glabratus, Candida dubliniensis, Pichia kudriavzevii, Meyerozyma guilliermondii, and Candidozyma auris. Antifungal susceptibility was determined by minimum inhibitory concentration assays, and the potential fungicidal or fungistatic nature of the compounds was predicted calculating the minimum fungicidal concentrations. Several compounds exhibited broad-spectrum antifungal activity, with variable susceptibility profiles among the tested species. A tendency toward higher antifungal activity was observed among compounds containing multiple nitrogen atoms, including those with hydroxamic acid functional groups, although the structural diversity of the library precludes the establishment of a definitive structure activity relationship. Furthermore, several of the active compounds were originally developed for antiparasitic or antihyperglycemic applications, suggesting that molecules designed for other therapeutic purposes display relevant antifungal properties. These results highlight the relevance of exploring structurally diverse synthetic molecules and repositioned drugs as complementary sources for the identification of new antifungal candidates against Candida species.