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- Title
Synthesis, Molecular Docking, and Biological Evaluation of Novel Triazole Derivatives as Antifungal Agents.
- Authors
Guan, Zhongjun; Chai, Xiaoyun; Yu, Shichong; Hu, Honggang; Jiang, Yuanying; Meng, Qingguo; Wu, Qiuye
- Abstract
Twenty-eight novel triazole derivatives (compounds 1a-v, 2a-f) have been synthesized for structure-activity relationship studies as antifungal agents. The compounds were designed on the basis of the structure of fluconazole and molecular modeling of the active site of the cytochrome P450 14α-demethylase (CYP51). All of them are reported for the first time. Their chemical structures are characterized by H NMR, C NMR, LC-MS, and elemental analysis. The antifungal activities have been evaluated in vitro by measuring the minimal inhibitory concentrations (MICs). Compounds 1a-v exhibited higher activity against nearly all fungi tested except Aspergillus fumigatus (A. fum) than fluconazole (FCZ). The computational molecular docking experiments indicated that the inhibition of CYP51 involves a coordination bond with iron of the heme group, a hydrophilic H-bonding region, a hydrophobic region, and a narrow hydrophobic binding cleft.
- Subjects
TRIAZOLES; ANTIFUNGAL agents; MOLECULAR models; CYTOCHROME P-450; MICROBIAL sensitivity tests; HYDROGEN bonding
- Publication
Chemical Biology & Drug Design, 2010, Vol 76, Issue 6, p496
- ISSN
1747-0277
- Publication type
Article
- DOI
10.1111/j.1747-0285.2010.01038.x