Abstract

Present work describes the atom based 3D QSAR analysis using pharmacophore based alignment to explore the essential three dimensional structural feature requirements of study molecules for better antagonism of P2X7 receptor. The best pharmacophore model (HPRRR.13) was developed and used to align study molecules for 3D QSAR analysis. The best QSAR model (HPRRR.134) generated with PLS factor 4 showed good values of statistical parameters i.e. R2 training, SD, F-value, q2 test, and Pearson-rtest. Moreover, the contours of different properties generated using best model were able to explain the variation in the activity of dataset with respect to these properties. The best pharmacophore model was subjected to screen in-house database where it picks some molecules that are reported as COX-2 inhibitors in the literature. Therefore, generated pharmacophore based 3D QSAR model may successfully be used to design new potent congener representatives.

Keywords: Atom based 3D QSAR, Pharmacophore, P2X7 receptor antagonists, Schrodinger, PHASE, Rheumatoid arthritis, P2X7 receptor, 3D QSAR model, Anti-Inflammatory Agents, macrophages, Alignment of Molecules, PHASE 3.2, MCMM, LMOD method, Pharmacophore Modeling, PLS Analysis