Abstract
INTRODUCTION: Fungal infections represent a global health concern with significant implications for human well-being. Among them, refractory and sight-threatening fungal keratitis (FK) poses a serious threat to ocular health. This underscores an urgent need for developing novel antifungal agents to meet clinical demands. OBJECTIVE: This study aimed to screen boron-containing compounds for potent antifungal activity. The selected compounds were then subjected to in vitro and in vivo bioactivity evaluation, and their antifungal mechanisms were investigated. METHODS: The antifungal effects of boron-containing compounds were evaluated using minimum inhibitory concentration assays, resistance studies, time-kill curves, and hyphal and biofilm inhibition assays. The in vitro and in vivo drug-likeness of the candidate compounds was assessed. Transcriptome sequencing, SYTOX Green staining, DiSC3(5) staining, ergosterol binding assays, sorbitol rescue assays, transmission electron microscopy, intracellular reactive oxygen species and adenosine triphosphate (ATP) content assays, succinate dehydrogenase (SDH) activity assays, calcofluor white staining, and RT-qPCR were employed to investigate the antifungal mechanisms of the candidate compounds. RESULTS: In this study, we identified compound BD11 as a promising candidate with potent antifungal activity against various pathogenic fungi and low cytotoxicity. BD11 impaired mitochondrial function, reduced the activity of SDH, decreased intracellular ATP levels, and disrupted the integrity of the cell wall, thereby effectively inhibiting the growth and virulence of Candida albicans. Importantly, in a murine FK model, BD11 significantly attenuated corneal damage. CONCLUSION: These results highlight the excellent clinical potential of compound BD11 in combating fungal infections. This study provides new insights for the discovery and development of novel antifungal agents for the treatment of fungal diseases.