title: 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-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.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Fudan University, 138 Yixueyuan Road, Shanghai, 200032, China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Zhu
authors.forename: De-Yong
authors.initials: DY
authors.lastname: Ye
authors.forename: Yun
authors.initials: Y
authors.lastname: Tang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D018360:Crystallography, X-Ray; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D021281:Quantitative Structure-Activity Relationship; D017386:Sequence Homology, Amino Acid; D058831:Serotonin 5-HT3 Receptor Antagonists; D012908:Snails; D013844:Thiazoles / Q000737:chemistry*
chemical_list: C428944:AChBP protein, Lymnaea; D002352:Carrier Proteins; D058831:Serotonin 5-HT3 Receptor Antagonists; D013844:Thiazoles