A Structure-Activity Relationship Study of Imidazole-5-Carboxylic Acid Derivatives as Angiotensin II Receptor Antagonists Combining 2D and 3D QSAR Methods

作者：Sharma Mukesh C^*

来源：Interdisciplinary Sciences, Computational Life Sciences, 2016, 8(1): 1-10.

DOI：10.1007/s12539-015-0014-1

• Imidazole-5-carboxylic acids
• 2D and 3D-QSAR
• Angiotensin II AT(1) receptor
• Antihypertensive agents

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 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 pred_r(2) = 0.7764 was developed by SA-partial least square with the descriptors like 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-validated correlation coefficient q(2) = 0.7188 and predicate activity pred_r(2) = 0.7226 were obtained. The information rendered by QSAR models may lead to a better understanding of structural requirements of substituted imidazole-5-carboxylic acid derivatives and also aid in designing novel potent antihypertensive molecules.

• 出版日期2016-3