PREDICTING POTENT ANTIHYPERTENSIVE COMPOUNDS OF PYRIDINE DERIVATIVES BY MOLECULAR MODELING APPROACH

Abstract

A quantitative structure activity relationship study was performed on a series of pyridine substituted compounds as angiotensin II receptors for establishing quantitative relationship between biological activity and their physicochemical structural properties. Partial least square (PLS) methodology coupled with stepwise forward backward method were applied to derive QSAR models, which were further validated for statistical significance and predictive ability by internal and external validation. A 2D QSAR model was generated with correlation coefficient (r2) of 0.8874, significant cross-validated correlation coefficient (q2) of 0.7498, r2 for external test set (pred_r2) 0.7869. A Zscore_r2 value of 3.9853, Zscore_q2 value of 2.8642 and Zscore_ pred_r2 value of 1.0583 statistically validates the significance of the obtained QSAR model. Molecular field analysis (MFA) was used to construct the best 3D-QSAR model showing good correlative and predictive capabilities in terms of q2= 0.7264 and pred_r2= 0.6988. The quantitative structure activity relationship study provides important structural insights in the designing of potent antihypertensive molecules.