School of Chemical Engineering, Dalian University of Technology, Dalian, Liaoning, China.
J Enzyme Inhib Med Chem. 2011 Dec;26(6):792-804. doi: 10.3109/14756366.2011.554414. Epub 2011 Mar 7.
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(2)(pred) = 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.
最近，苯并噻吩因其可能对 FIXa 的抑制活性而引起了广泛的关注，FIXa 是一种血液凝固因子，对于血液凝固的放大或巩固阶段至关重要。为了探索这种抑制机制，首次对一系列 84 种苯并噻吩类似物进行了三维定量构效关系（3D-QSAR）、分子对接和分子动力学（MD）研究。结果，建立了一个高度可预测的 CoMFA 模型，其 q² = 0.52、r² = 0.97 和 r²（pred）= 0.81。CoMFA 等高线图、对接分析以及 MD 模拟结果均非常吻合，证明了模型的可靠性和稳健性。这些模型和信息，我们希望，在合成之前有助于筛选和开发针对血栓形成的新型药物。
