title: Synthesis and biological evaluation of triazole derivatives as potential antifungal agent.
abstract: A series of triazole antifungal agents with piperidine side chains were designed and synthesized. Results of preliminary antifungal tests against eight human pathogenic fungi in vitro showed that all the title compounds exhibited excellent activities with broad spectrum. Moreover, a molecular model for the binding between compound 12 and the active site of CACYP51 was provided based on the computational docking results. The side chain of the compound 12 is oriented into substrate access channel 2 (FG loop) and forms hydrophobic and van der waals interactions with surrounding hydrophobic residues. The phenyl group of the side chain can interact with the phenyl group of Phe380 through the formation of π-π face-to-edge interaction.
authors.affiliation: Department of Organic Chemistry, School of Pharmacy, Second Military Medical University, Shanghai, China.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Chai
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Shichong
authors.initials: S
authors.lastname: Yu
authors.forename: Yan
authors.initials: Y
authors.lastname: Zou
authors.forename: Qiuye
authors.initials: Q
authors.lastname: Wu
authors.forename: Dazhi
authors.initials: D
authors.lastname: Zhang
authors.forename: Yuanying
authors.initials: Y
authors.lastname: Jiang
authors.forename: Yongbing
authors.initials: Y
authors.lastname: Cao
authors.forename: Qingyan
authors.initials: Q
authors.lastname: Sun
mesh_terms: D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D020134:Catalytic Domain; D005658:Fungi / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D009181:Mycoses / Q000188:drug therapy; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D058886:Sterol 14-Demethylase / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000935:Antifungal Agents; D010880:Piperidines; D014230:Triazoles; C032727:piperidine; D058886:Sterol 14-Demethylase