Insight into the structural requirement of substituted quinazolinone biphenyl acylsulfonamides derivatives as angiotensin II AT1 receptor antagonist : 2D and 3D QSAR approach

Abstract EN

A series of 19 molecules substituted quinazolinone biphenyl acylsulfonamides derivatives displaying variable inhibition of Angiotensin II receptor AT1 activity were selected to develop models for establishing 2D and 3D QSAR.

The compounds in the selected series were characterized by spatial, molecular and electro topological descriptors using QSAR module of Molecular Design Suite (V Life MDS 3.5.

The best 2D QSAR model was selected, having correlation coefficient r2 (0.8056) and cross validated squared correlation coefficient q2 (0.6742) with external predictive ability of pred_r2 0.7583 coefficient of correlation of predicted data set (pred_r2se) 0.2165.

The results obtained from QSAR studies could be used in designing better Ang II activity among the congeners in future.

The optimum QSAR model showed that the parameters Ssss CHE index, Sdd CE-index, T_2_Cl_4, and Sss NHE-index contributed in the model.

3D QSAR analysis by kNN-molecular field analysis approach developed based on principles of the k-nearest neighbor method combined with Genetic algorithms, stepwise forward variable selection approach ; a leave-one-out cross-validated correlation coefficient (q2) of 0.6516 and a non-cross-validated correlation coefficient (r2) of 0.8316 and pred_r2 0.6954 were obtained.

Contour maps using this approach showed that steric, electrostatic, and hydrophobic field effects dominantly determine binding affinities.

The information rendered by 3D QSAR models may lead to a better understanding of structural requirements of Angiotensin II receptor and can help in the design of novel potent antihypertensive molecules.