Novel mercapto conjugates of oleanolic acid as potential antifungal agents

The increasing incidence of antifungal resistance in Candida species underscores the urgent need for new agents that effectively inhibit fungal growth and virulence while exhibiting minimal host toxicity. In this study, DBE-7 was identified as a potent antifungal compound with strong activity against Candida albicans. DBE-7 inhibited fungal growth at low micromolar concentrations (MIC = 3.37 µM) and exhibited fungicidal rather than fungistatic activity. The compound markedly impaired key virulence attributes, including hyphal morphogenesis and biofilm formation. Quantitative image analysis demonstrated a concentration-dependent reduction in hyphal elongation and filamentous cell formation, with inhibitory effects comparable to those of fluconazole. DBE-7 also significantly reduced biofilm biomass, indicating its ability to disrupt biofilm architecture. DBE-7 effectively eradicated preformed mature biofilms in a concentration-dependent manner, indicating its ability not only to prevent biofilm development but also to disrupt established biofilm. Kill kinetics revealed rapid and sustained fungicidal activity in a time- and concentration-dependent manner. DBE-7 also displayed low cytotoxicity toward mammalian cell lines, maintaining high cell viability within its antifungal concentration range. Molecular docking revealed a strong binding affinity of DBE-7 toward lanosterol 14-α-demethylase (LDM), while the marked reduction in cellular ergosterol levels in DBE-7-treated C. albicans further supports disruption of the ergosterol biosynthetic pathway, suggesting potential targeting of LDM. Collectively, these findings highlight DBE-7 as a promising antifungal candidate that effectively targets C. albicans growth and virulence while exhibiting a favorable safety profile, supporting its further preclinical development.