title: Synthesis, In Vitro Biological Evaluation, and Molecular Docking of New Triazoles as Potent Antifungal Agents.
abstract: Based on the structure of the active site of CYP51 and the structure-activity relationships of azole antifungal compounds that we designed in a previous study, a series of 1-{1-[2-(substitutedbenzyloxy)ethyl]-1H-1,2,3-triazol-4-yl}-2-(2,4-difluorophenyl)-3-(1H-1,2,4-triazol-1-yl)propan-2-ols (6a-n) were designed and synthesized utilizing copper-catalyzed azide-alkyne cycloaddition. Preliminary antifungal tests against eight human pathogenic fungi in vitro showed that all the title compounds exhibited excellent antifungal activities with a broad spectrum in vitro. Molecular docking results indicated that the interaction between the title compounds and CYP51 comprised π-π interactions, hydrophobic interactions, and the narrow hydrophobic cleft.
authors.affiliation: Department of Organic Chemistry, College of Pharmacy, Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Organic Chemistry, College of Pharmacy, Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Organic Chemistry, College of Pharmacy, Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Tang
authors.affiliation: Department of Organic Chemistry, College of Pharmacy, Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Qiuye
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Organic Chemistry, College of Pharmacy, Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Honggang
authors.initials: H
authors.lastname: Hu
authors.affiliation: Department of Organic Chemistry, College of Pharmacy, Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Qingjie
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Department of Organic Chemistry, College of Pharmacy, Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zou
mesh_terms: D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002175:Candida / Q000187:drug effects / Q000302:isolation & purification; D008826:Microbial Sensitivity Tests; D062105:Molecular Docking Simulation; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000935:Antifungal Agents; D014230:Triazoles
keywords: Antifungal activity; CYP51; Molecular docking; SAR; Triazoles