Structural insights into styrylquinolines analogs as tubulin polymerization inhibitors: In silico Approach

Abstract

:<strong> </strong>Cancer is one of the fastest-growing epidemics that affect millions yearly. A handful of anticancer drugs are available on the market, but they produce undesirable side effects. Currently, tubulin inhibitors targeting the colchicine binding site are considered an important target due to their structural simplicity and favorable pharmacokinetics with fewer side effects. Different researchers conducted many studies to discover a novel tubulin inhibitor targeting the colchicine binding site with high safety and potency. In the present study, we performed computational analysis of 48 styrylquinolines analogs obtained from literature using different drug designing tools. The pharmacophore mapping study was conducted to identify the important pharmacophoric features essential for biological activity. Atom-based 3D-QSAR (3-dimensional quantitative structure-activity relationship) analysis was carried out to know the contribution of different atoms to model development. The generated model showed a statistically significant coefficient of determinations for the training and test sets. The best QSAR model was selected based on R<sup>2</sup> (0.8624) and Q<sup>2</sup> (0.6707) values. Contour plot analysis of the developed model unveiled the chemical features necessary for tubulin inhibition. A docking study was performed on potent styrylquinoline analog 9VII-f(46), which shows the highest SP docking scores (-5.494). ADME (Absorption, distribution, metabolism, and excretion) analysis provides valuable information about the drugability of newly designed compounds.