title: Triazole derivatives with improved in vitro antifungal activity over azole drugs.
abstract: A series of triazole antifungal agents with piperidine side chains was designed and synthesized. The results of antifungal tests against eight human pathogenic fungi in vitro showed that all the compounds exhibited moderate-to-excellent activities. Molecular docking between 8d and the active site of Candida albicans CYP51 was provided based on the computational docking results. The triazole interacts with the iron of the heme group. The difluorophenyl group is located in the S3 subsite and its fluorine atom (2-F) can form H-bonds with Gly307. The side chain is oriented into the S4 subsite and formed hydrophobic and van der Waals interactions with the amino residues. Moreover, the phenyl group in the side chain interacts with the phenol group of Phe380 through the formation of π-π face-to-edge interactions.
authors.affiliation: Department of Organic Chemistry, School of Pharmacy, Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Shichong
authors.initials: S
authors.lastname: Yu
authors.affiliation: Department of Organic Chemistry, School of Pharmacy, Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Chai
authors.affiliation: Department of Organic Chemistry, School of Pharmacy, Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Yanwei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Drug Research Center, School of Pharmacy, Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Yongbing
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Overseas Education Faculty of the Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Organic Chemistry, School 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, School of Pharmacy, Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Dazhi
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Drug Research Center, School of Pharmacy, Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Yuanying
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Pharmacology, School of Pharmacy, China Pharmaceutical University, Nanjing, People's Republic of China.
authors.forename: Tianhua
authors.initials: T
authors.lastname: Yan
authors.affiliation: Department of Organic Chemistry, School of Pharmacy, Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Qingyan
authors.initials: Q
authors.lastname: Sun
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D062105:Molecular Docking Simulation; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D000935:Antifungal Agents; D014230:Triazoles
keywords: CYP51; azole agents; molecular docking; synthesis
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