科研之友
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摘要
Tubulins, an alpha beta heterodimers, the major component of microtubules, are important molecular target of numerous small molecule ligands for anticancer therapy. In this study, the molecular modeling studies were performed to develop predictive 3D-QSAR models using set of 32 compounds of benzoyl urea derivatives as tubulin-binding agents for antiproliferative activity. A five-point common pharmacophore hypotheses with one hydrogen bond acceptor (A), two hydrogen bond donors (D), one hydrophobic (H), and one ring (R) vector features were selected for alignment of all compounds. The 3D-QSAR models generated using training set of 21 compounds and test set of 11 compounds showed good partial least squares statistical results. The developed CPHs and 3D-QSAR models were validated further externally by predicting the activity of database of compounds from literature and comparing it with actual activity. Docking studies were also carried out for all compounds on colchicine-binding site of beta-tubulin for studying of binding affinity of compounds for antiproliferative activity. The results of these molecular modeling studies are helpful to refine the pharmacophore for design of new potential compounds for antiproliferative activity.
- 出版日期2013-3
