Structure-based 3D-QSAR studies on thiazoles as 5-HT3 receptor antagonists

Abstract

Structure-based 3D-QSAR studies were performed on 20 thiazoles against their binding affinities to the 5-HT3 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-HT3A 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 rcv2 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-HT3 receptor antagonists. © Springer-Verlag 2006.