A Structure–Activity Relationship Study of Imidazole-5-Carboxylic Acid 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 acid analogs and their angiotensin II \(\hbox {AT}_{1}\) receptor antagonist 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 were used in conjunction with simulated annealing (SA), genetic algorithm and stepwise 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 \(r^{2} = 0.8040\) and \(\hbox {pred}\_r^{2} = 0.7764\) was developed by SA-partial least square with the descriptors like \(\hbox {SsCH}_{3}\) count, 5Chain count, SdsCHE-index, and H-acceptor count, showing that increase in the values of these descriptors is beneficial to the activity. The 3D-QSAR studies were performed using the SA-PLS. A leave-one-out cross...
Source: Interdisciplinary Sciences, Computational Life Sciences - Category: Bioinformatics Source Type: research