Design, synthesis, and biological evaluation of novel boron-containing azoles as potential antifungal agents

A series of novel boron-containing azoles were designed, synthesized, and characterized via 1H NMR, 13C-NMR, and HRMS. Subsequent antifungal tests in vitro revealed that the target compounds possessed moderate to exceptional efficacy against the five fluconazole-sensitive Candida strains. Most interesting is that these target compounds showed superior activity against fluconazole-resistant strains compared to positive drug fluconazole. To complete with the study of antifungal mechanism, the effect of target compounds on the sterol composition of fungal was investigated. Meantime, the target compound N01 might cause direct harm to the fungal cell wall and cell membrane. Furthermore, compound N01 was nearly non-toxic to mammalian MRC-5 cell with IC50 >100 & mu;M. Molecular docking experiment revealed that compound N01 interacted with Candida albicans CYP51 in a similar to that of the eutectic small molecule VT-1161. These findings strongly suggested that compound N01 warrants further investigation as a potential azole CYP51 inhibitor.