Combined 3D-QSAR, Pharmacophore and Docking Studies on Benzenesulfonamide Derivatives as Potent 12-Lipoxygenase Inhibitors

Abstract

Background: Lipoxygenases(LOXs) are a family of enzymes which catalyze the oxidation of unsaturated fatty acids. Objective: To quantitatively disclose the relationship between activity and structure of a series of 12- LOX inhibitors. Method: 3D-QSAR (three dimensions quantitative structure-activity relationship) studies based on COMFA(comparative molecular field analysis) and COMSIA(comparative molecular similarity indices analysis) and pharmacophore studies were performed. Results: 3D-QSAR results show that both CoMFA and CoMSIA models yielded well statistical significance respectively, with q2=0.708, r2=0.983, F=162.3, SEE=0.090 in CoMFA model and q2=0.735, r2=0.981, F=130.5, SEE=0.095 in CoMSIA model, four derivatives as potential 12-LOX inhibitors with high predicted bioactivities has been designed. Additionally, pharmacophore results suggested different group on the core parts of 12-LOX inhibitor might enhance the bioactivities. Keywords: 12-Lipoxygenase, 3D-QSAR, CoMFA, CoMSIA, pharmacophore, docking.