Isobavachalcone effectively inhibits the growth of Candida albicans

Candida albicans (C. albicans) is a commensal, drug-resistant opportunistic pathogen, and the eradication of invasive candidiasis represents a significant clinical challenge. This study investigated the inhibitory effect of isobavachalcone (IBC) on C. albicans growth and elucidated its mechanism. The antifungal activity of IBC was evaluated using minimum inhibitory concentration 90% (MIC₉₀) and minimum fungicidal concentration (MFC), combined with murine vaginitis and oral thrush models to assess in vivo efficacy. An MTT assay was used to assess drug safety. Mechanistic investigations included cell membrane/wall damage assessments, virulence factor inhibition, oxidative stress evaluation, ATP metabolism analysis, protein expression profiling, and target identification (including RT-qPCR, inhibitor intervention experiments, and related methodologies). The antifungal potency of IBC against C. albicans was demonstrated with a MIC₉₀ of 2 µg/mL and an MFC of 8 μg/mL. Against strain S393, IBC exhibited potent efficacy with median effective and effective concentrations of 1.301 µg/mL and 1.449 µg/mL, respectively. In vivo, IBC significantly alleviated vulvovaginal candidiasis and oropharyngeal thrush, outperforming fluconazole in therapeutic efficacy and mucosal protection. Mechanistic studies revealed that IBC prevented fungal invasion by inhibiting C. albicans adhesion and colonization on mucosal surfaces, mitigated inflammation through suppression of proinflammatory cytokine release, and downregulated the expression of ADE13, TPI1, and ADK1 genes, with ADK1 demonstrating the most significant suppression. Furthermore, IBC specifically bound to ADK1, inhibiting ATP synthesis and disrupting cellular energy metabolism in C. albicans. IBC represents a promising antifungal drug that acts by downregulating the ADE13, TPI1, and ADK1 genes. Its downregulation of ADK1 leads to impaired ATP synthesis, induced DNA damage, and suppressed fungal proliferation.