location: Current position: Home >> Scientific Research >> Paper Publications

Investigation on the binding mode of benzothiophene analogues as potent factor IXa (FIXa) inhibitors in thrombosis by CoMFA, docking and molecular dynamic studies

Hits:

Indexed by:期刊论文

Date of Publication:2011-12-01

Journal:JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY

Included Journals:PubMed、Scopus、SCIE

Volume:26

Issue:6

Page Number:792-804

ISSN No.:1475-6366

Key Words:FIXa; benzothiophene; docking; CoMFA; MD

Abstract: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.

Pre One:Structural Requirements of N-Substituted Spiropiperidine Analogues as Agonists of Nociceptin/Orphanin FQ Receptor

Next One:Combined 3D-QSAR, Molecular Docking, and Molecular Dynamics Study on Piperazinyl-Glutamate-Pyridines/Pyrimidines as Potent P2Y(12) Antagonists for Inhibition of Platelet Aggregation (vol 51, pg 2560, 2011)