Exploring Long Arm Amide-Linked Side Chains in the Design of Antifungal Azole Inhibitors of Sterol 14α-Demethylase (CYP51).

ABSTRACT: The rise in fungal drug resistance has exacerbated the treatment of invasive fungal infections, most commonly caused by Candida. This research describes the synthesis of extended "long-arm" azole antifungals that were evaluated against wild-type and resistant fungal species. Biphenyl derivative 22 was the most effective derivative, displaying potent inhibitory activity against Saccharomyces, Candida, and Cryptococcus CYP51 enzymes, including in resistant strains, in comparison with posaconazole. The X-ray crystal structure of S-22 complexed with S. cerevisiae CYP51 showed a hydrogen bond between the oxygen of the trifluoromethoxy group of S-22 and the His381 side chain of S. cerevisiae CYP51, which i

SUBMITTER: Alsulaimany M 

PROVIDER: S-EPMC12169614 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature