title: Design, synthesis and antifungal activities of novel 1,2,4-triazole derivatives.
abstract: A series of novel 1,2,4-triazole derivatives with a 4-(4-substitutedphenyl) piperazine side chain were designed and synthesized based on the structure of lanosterol 14α-demethylase (CYP51). Their antifungal activities against eight human pathogenic fungi were evaluated in vitro by measuring the minimal inhibitory concentrations. Nearly all tested compounds were found to be more potent against Candida albicans than control drug fluconazole. Noticeably, the MIC(80) value of compounds 6,7,9,14 and 29 is 16 times lower than that of voriconazole against C. albicans. The activities of compounds 7 and 21 against Cryptococcus neoformans in vitro are comparable to that of voriconazole with a MIC(80) value of 0.0156 μg/mL. Moreover, the molecular model for the binding between compound 7 and the active site of CACYP51 was provided based on the computational docking results.
authors.affiliation: Department of Organic Chemistry, Second Military Medical University, Guohe Road 325, Shanghai 200433, People's Republic of China.
authors.forename: Jianming
authors.initials: J
authors.lastname: Xu
authors.forename: Yongbing
authors.initials: Y
authors.lastname: Cao
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: Xiaoyun
authors.initials: X
authors.lastname: Chai
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: Qingyan
authors.initials: Q
authors.lastname: Sun
mesh_terms: D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects / Q000254:growth & development; D020134:Catalytic Domain; D003455:Cryptococcus neoformans / Q000187:drug effects / Q000254:growth & development; D065607:Cytochrome P-450 Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D015195:Drug Design; D015725:Fluconazole / Q000494:pharmacology; D005656:Fungal Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D062105:Molecular Docking Simulation; D010879:Piperazines / Q000737:chemistry; D058886:Sterol 14-Demethylase / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D065819:Voriconazole / Q000494:pharmacology
chemical_list: D000935:Antifungal Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D005656:Fungal Proteins; D010879:Piperazines; D014230:Triazoles; C045575:1,2,4-triazole; D015725:Fluconazole; D058886:Sterol 14-Demethylase; D065819:Voriconazole