Synthesis of Sordaricin Analogues as Potent Antifungal Agents Against Candida albicans.

Sordaricin derivatives possessing a cyclohexane ring appendage attached via an ether, thioether, amine, oxime, ester or amide linkage were synthesized and their antifungal activity was evaluated in vitro. Compounds containing a thioether bond or an oxime bond as a linkage exhibited potent MICs (≤0.125 μg/mL) against four Candida albicans strains including azole-low-susceptible strains. They were also active (MIC ≤0.125 μg/mL) against Candida glabrata. Their in vivo efficacy was confirmed in a murine intravenous infection model with Candida albicans.