title: Structure-based design, synthesis, and antifungal activity of new triazole derivatives.
abstract: A series of new antifungal triazole derivatives with phenylacetamide side chain were rational designed and synthesized on the basis of the structural information of lanosterol 14-demethylase (CYP51). In vitro antifungal activity assay indicated that several compounds showed higher activity than fluconazole. Especially, compound 8h showed excellent inhibitory activity against Candida albicans and Cryptococcus neoformans (MIC=0.0156 μg/mL), suggesting that it is a promising lead for the development of novel antifungal agents. The binding mode of compound 8h was investigated by flexible molecular docking. It interacted with CACYP51 through hydrophobic and van der Waals interactions.
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China.
authors.forename: Chunquan
authors.initials: C
authors.lastname: Sheng
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Che
authors.forename: Wenya
authors.initials: W
authors.lastname: Wang
authors.forename: Shengzheng
authors.initials: S
authors.lastname: Wang
authors.forename: Yongbing
authors.initials: Y
authors.lastname: Cao
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Yao
authors.forename: Zhenyuan
authors.initials: Z
authors.lastname: Miao
authors.forename: Wannian
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000083:Acetanilides / Q000737:chemistry; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001393:Azoles / Q000737:chemistry; D015195:Drug Design; D005658:Fungi / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000083:Acetanilides; D000935:Antifungal Agents; D001393:Azoles; D014230:Triazoles