title: Design, synthesis, and antifungal activity of novel conformationally restricted triazole derivatives.
abstract: A series of new triazole derivatives were designed and synthesized on the basis of the active site of lanosterol 14alpha-demethylase from Candida albicans (CACYP51). 2-(2,4-Difluorophenyl)-3-(methyl-(3-phenoxyalkyl)amino)-1-(1H-1,2,4-triazol-1-yl)propan-2-ols show excellent in-vitro activity against most of the tested pathogenic fungi. The MIC(80) value of compound 8a against Candida albicans is 0.01 microM, which provides a good starting template for further structural optimization. The binding modes of the designed compounds were investigated by flexible molecular docking. The compounds interacted with CACYP51 through hydrophobic, van-der-Waals, and hydrogen-bonding interactions.
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai, P.R. China.
authors.forename: Wenya
authors.initials: W
authors.lastname: Wang
authors.forename: Chunquan
authors.initials: C
authors.lastname: Sheng
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Che
authors.forename: Haitao
authors.initials: H
authors.lastname: Ji
authors.forename: Zhenyuan
authors.initials: Z
authors.lastname: Miao
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Yao
authors.forename: Wannian N
authors.initials: WN
authors.lastname: Zhang
mesh_terms: D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001665:Binding Sites / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects*; D015195:Drug Design; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D000935:Antifungal Agents; D014230:Triazoles