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Synthesis, Molecular Docking, and Biological Evaluation of Novel Triazole Derivatives as Antifungal Agents
Author(s) -
Guan Zhongjun,
Chai Xiaoyun,
Yu Shichong,
Hu Honggang,
Jiang Yuanying,
Meng Qingguo,
Wu Qiuye
Publication year - 2010
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2010.01038.x
Subject(s) - antifungal , docking (animal) , combinatorial chemistry , chemistry , triazole , computational biology , pharmacology , stereochemistry , biology , organic chemistry , medicine , microbiology and biotechnology , nursing
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 1 H NMR, 13 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.