| Literature DB >> 16610794 |
Chunquan Sheng1, Wannian Zhang, Haitao Ji, Min Zhang, Yunlong Song, Hui Xu, Jie Zhu, Zhenyuan Miao, Qingfen Jiang, Jianzhong Yao, Youjun Zhou, Jü Zhu, Jiaguo Lü.
Abstract
In a continuing effort to develop highly potent azole antifungal agents, the three-dimensional quantitative structure-activity relationship methods, CoMFA and CoMSIA, were applied using a set of novel azole antifungal compounds. The binding mode of the compounds at the active site of lanosterol 14alpha-demethylase was further explored using the flexible docking method. Various hydrophobic, van der Waals, pi-pi stacking, and hydrogen bonding interactions were observed between the azoles and the enzyme. Based on results from the molecular modeling, a receptor-based pharmacophore model was established to guide the rational optimization of the azole antifungal agents. Thus, a total of 57 novel azoles were designed and synthesized by a three-step optimization process. In vitro antifungal assay revealed that the antifungal activities of these novel azoles were greatly improved, which confirmed the reliability of the model from molecular modeling.Entities:
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Year: 2006 PMID： 16610794 DOI： 10.1021/jm051211n
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446