A structure-activity relationship study of imidazole-5-carboxylic acids derivatives as angiotensin II receptor antagonists combining 2D and 3D QSAR methods.

Abstract

Two Dimensional (2D) and Three Dimensional (3D) Quantitative Structure-Activity Relationship (QSAR) studies were performed for correlating the chemical composition of Imidazole-5-carboxylic Acids analogues and their Angiotensin II AT1 Receptor Antagonists activity using partial least squares and k Nearest Neighbor respectively. For Comparing the three different feature selection methods of 2D-QSAR, k Nearest Neighbor models was used in conjunction with simulated annealing (SA), genetic algorithm (GA) and stepwise (SW) coupled with Partial least square (PLS) showed variation in biological activity. The statistically significant best 2D-QSAR model having good predictive ability with statistical values of r2 = 0.8040, and pred_r2 = 0.7764, was developed by SA-Partial least square with the descriptors like SsCH3Count, 5Chain Count, SdsCHE-index and H-acceptor count showed that increase in the values of these descriptors are beneficial for the activity. The 3D-QSAR studies were performed using the SA-PLS a leave-one-out cross-validated correlation coefficient q2=0.7188 and predicate activity pred_r2 =0.7226 were obtained. The information rendered by QSAR models may lead to a better understanding of structural requirements of substituted Imidazole-5-carboxylic Acids derivatives and also aid in designing novel potent antihypertensive molecules.