title: Structure-based rational design, synthesis and antifungal activity of oxime-containing azole derivatives.
abstract: In an attempt to find novel azole antifungal agents with improved activity and broader spectrum, computer modeling was used to design a series of new azoles with piperidin-4-one O-substituted oxime side chains. Molecular docking studies revealed that they formed hydrophobic and hydrogen-bonding interactions with lanosterol 14alpha-demethylase of Candida albicans (CACYP51). In vitro antifungal assay indicates that most of the synthesized compounds showed good activity against tested fungal pathogens. In comparison with fluconazole, itraconazole and voriconazole, several compounds (such as 10c, 10e, and 10i) show more potent antifungal activity and broader spectrum, suggesting that they are promising leads for the development of novel antifungal agents.
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China.
authors.forename: Yulan
authors.initials: Y
authors.lastname: Xu
authors.forename: Chunquan
authors.initials: C
authors.lastname: Sheng
authors.forename: Wenya
authors.initials: W
authors.lastname: Wang
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Che
authors.forename: Yongbing
authors.initials: Y
authors.lastname: Cao
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Dong
authors.forename: Shengzheng
authors.initials: S
authors.lastname: Wang
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
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001393:Azoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D020134:Catalytic Domain; D003198:Computer Simulation; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry; D015195:Drug Design; D008826:Microbial Sensitivity Tests; D010091:Oximes / Q000737:chemistry*; D058886:Sterol 14-Demethylase; D013329:Structure-Activity Relationship
chemical_list: D000935:Antifungal Agents; D001393:Azoles; D010091:Oximes; D003577:Cytochrome P-450 Enzyme System; D058886:Sterol 14-Demethylase