American Journal of Phytomedicine and Clinical Therapeutics www.ajpct.org Original Article Comprehensive Structure Activity Relationship Studies for Angiotensin II Receptor Antagonists as Antihypertensive Agents

Angiotensin II receptor antagonists (ATIIRA) has become an attractive molecular target for drugs that aim to treat hypertension triggered by renin angiotensin system. To study the relationship between the structure of several ATIIRA we have performed a two dimensional and three-dimensional quantitative structure–activity relationship (QSAR) study of benzimidazole based derivatives. A series of 40 compounds containing 4, 5, 6, 7 substituted benzimidazoles were subjected to comprehensive 2D and 3D advanced kNN-MFA QSAR analysis employing multiple linear regression, partial least square, principle component analysis, advanced kNN molecular field analysis, stepwise forward back method, simulated annealing and genetic algorithm method. The model allowed the identification of relevant structural features required for the interaction with the AT1 receptor, enabling the prediction of activity of molecules. Some highly predictive 2D and 3D-QSAR models, with significant models with r2 = 0.84 and r2 = 0.83 were obtained in 2D analysis and with q2 = 0.77 and q2 = 0.67 by advanced kNN MFA method in 3D analysis. These models are in good agreement with the structural characteristics of the potential angiotensin II receptor antagonists and provide some structural insights for the improvement of bioactivities