Molecular docking and ADMET study of quinoline-based derivatives for anti-cancer activity

Abstract

An In silico study was carried on a series of novel quinoline based inhibitors which were designed, synthesized and assessed for their in vitro activity versus the human colon cancer cell line HT29 and the human breast cancer cell line MDA-MB231 by Arafa RK et. al. We have designed these 22 inhibitors in ChemBioDraw ultra 12.0 and minimized using the LigPrep tool of Schrödinger 2011.  A docking study of these inhibitors into different cancer proteins active sites was performed in order to give a suggestion to the proposed invitro mechanism of action. Some prominent cancer proteins specifically causing breast and colon cancers are used as targets in this computational study to predict the most active quinoline based derivative. The proteins are minimized using the protein preparation wizard and Grid is generated by specifying the active site amino acids. The binding model of best scoring inhibitor with each protein was assessed from their G-scores and disclosed by docking analysis using the XP visualizer tool. Interestingly the result of docking was found to match with the previous invitro study where the most active derivative against both tested cell lines was the Schiff’s base 4e.  The pharmacokinetic parameters study was done using the QikProp 3.4 tool to display ADME and Toxicity properties of these inhibitors.