Zhu Li-Ping, Ye De-Yong, Tang Yun
Department of Medicinal Chemistry, School of Pharmacy, Fudan University, 138 Yixueyuan Road, Shanghai, 200032, China.
J Mol Model. 2007 Jan;13(1):121-31. doi: 10.1007/s00894-006-0131-1. Epub 2006 Sep 5.
Structure-based 3D-QSAR studies were performed on 20 thiazoles against their binding affinities to the 5-HT(3) receptor with comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). The thiazoles were initially docked into the binding pocket of a human 5-HT(3A) receptor homology model, constructed on the basis of the crystal structure of the snail acetylcholine binding protein (AChBP), using the GOLD program. The docked conformations were then extracted and used to build the 3D-QSAR models, with cross-validated r2omega values 0.785 and 0.744 for CoMFA and CoMSIA, respectively. An additional five molecules were used to validate the models further, giving satisfactory predictive r2 values of 0.582 and 0.804 for CoMFA and CoMSIA, respectively. The results would be helpful for the discovery of new potent and selective 5-HT(3) receptor antagonists.
采用比较分子场分析（CoMFA）和比较分子相似性指数分析（CoMSIA）方法，对20种噻唑类化合物与5-羟色胺（5-HT(3)）受体的结合亲和力进行了基于结构的三维定量构效关系（3D-QSAR）研究。首先，使用GOLD程序将噻唑类化合物对接至基于蜗牛乙酰胆碱结合蛋白（AChBP）晶体结构构建的人5-HT(3A)受体同源模型的结合口袋中。然后提取对接构象并用于构建3D-QSAR模型，CoMFA和CoMSIA的交叉验证r2omega值分别为0.785和0.744。另外使用五个分子进一步验证模型，CoMFA和CoMSIA的预测r2值分别为0.582和0.804，结果令人满意。这些结果将有助于发现新的强效和选择性5-HT(3)受体拮抗剂。
