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论文类型：期刊论文

发表时间：2011-12-01

发表刊物：JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY

收录刊物：PubMed、Scopus、SCIE

卷号：26

期号：6

页面范围：792-804

ISSN号：1475-6366

关键字：FIXa; benzothiophene; docking; CoMFA; MD

摘要：Recently, benzothiophenes attract much attention of interest due to its possible inhibitory activity targeting FIXa, a blood coagulation factor that is essential for the amplification or consolidation phase of blood coagulation. To explore this inhibitory mechanism, three-dimensional quantitative structure-activity relationship (3D-QSAR), molecular docking and molecular dynamics (MD) studies on a series of 84 benzothiophene analogues, for the first time, were performed. As a result, a highly predictive CoMFA model was developed with the q(2) = 0.52, r(2) = 0.97 and r(pred)(2) = 0.81, respectively. The CoMFA contour maps, the docking analysis, as well as the MD simulation results are all in a good agreement, proving the reliability and robustness of the model. These models and the information, we hoped, would be helpful in screening and development of novel drugs against thrombosis prior to synthesis.