In Silico Discovery and in vitro Evaluation of the Antifungal and Cytotoxicity Properties of Zeaxanthin and β-Carotene.

The increasing drug resistance in pathogenic fungi has highlighted the need to identify novel molecular targets and safer antifungal compounds. In this study, a target-based chemoinformatics approach was employed to identify mannosyltransferase 2 (MNT2), key components of fungal cell wall glycosylation. Virtual screening of FDA-approved drugs against these fungal enzymes identified two natural carotenoids, Zeaxanthin and β-carotene, as promising candidates. The interaction of these compounds with MNTs was evaluated by molecular docking and ADMET analyses. The antifungal activity of Zeaxanthin and β-carotene was investigated in vitro against selected yeast and mold species, including Candida spp. and Aspergillus spp., and the MIC and MFC values were determined. Additionally, the cytotoxicity of these compounds on the L929 cell line and their hemolytic activity on human erythrocytes were assessed. The results showed that both compounds had mild but detectable antifungal activity, while exhibiting negligible cytotoxicity and hemolysis, even at high concentrations. FE-SEM analysis indicated that both compounds compromised the cell envelope and membrane integrity of C. albicans, leading to cell wall damage. Taken together, these findings suggest that Zeaxanthin and β-carotene, identified through a target-based chemoinformatics approach, could be considered as low-toxicity natural compounds with potential for topical or complementary applications in novel antifungal strategies.