Metabolomic profiling and biological evaluation of botanical extracts reveal antifungal flavonoids against Candida species

Species of the genus Candida are considered opportunistic pathogenic yeasts capable of causing infections, especially in immunocompromised individuals. The increase in the incidence of candidiasis is partly associated with the development of resistance in these pathogens to conventional antifungal treatments. In this regard, plant extracts have been used and studied for centuries as antifungal therapies. The aim of this study was to analyze metabolomic profiles and to evaluate the antifungal activityof twelve botanical extracts against four candida species, to conduct a correlation study to identify candidate metabolites associated with antifungal activity. Initially, a preliminary phytochemical analysis was performed, followed by metabolomic profiling using HPTLC, UPLC-DAD, and LC-QTOF-MS. The antifungal activity of four strains of C. albicans, C. auris, C. glabrata, and C. tropicalis was evaluated. Correlation studies were performed using multivariate and univariate statistical analyses. The results of phytochemical analysis and metabolomic profiling allowed the annotation of several metabolites, predominantly lipids, peptides, flavonoids, fatty acids, steroids, terpenoids, phenolic acid derivatives, alcohols, and organic acids. Biological activity assays showedthat extracts of Bidens pilosa, Tillandsia usneoides, and Xanthosoma sagittifolium were the most active, with MIC80 values of 256 µg/mL, mainly against C. glabrata. Correlation analysis indicated that cyanidin-derived flavonoids are the main candidates responsible for the antifungal activity. These results demonstrate the chemical and biological potential of several underexplored plant species in Colombia and establishes a foundation for future research into compounds with potential applications as antifungal agents