Cardio-green butyl acetate targets ergosterol to kill Candida albicans

The rising incidence of invasive Candida infections highlights the urgent need for distinct antifungal agents with improved safety and efficacy. Although several antifungal drugs are clinically available, their associated toxicity and the increasing emergence of drug-resistant Candida species often result in poor therapeutic outcomes. In this study, we report the antifungal potential of cardio-green butyl acetate (CaGA), a previously unknown synthesized compound, and investigate its activity and mechanism of action. CaGA exhibited strong fungicidal activity against Candida albicans, significantly reducing planktonic cell viability and biofilm biomass. Membrane disruption was demonstrated by protein leakage assays, Nile red and live/dead staining, and scanning electron microscopy. Isothermal titration calorimetry (ITC) confirmed direct interaction between CaGA and ergosterol, the major sterol component of the C. albicans membrane. Coarse-grained membrane simulations further revealed preferential interaction with ergosterol-rich domains and pore-like structure formation. Together, these findings identify CaGA as a promising next-generation antifungal candidate with a distinct membrane-targeting mechanism, offering therapeutic potential against drug-resistant Candida infections.