Abstract: The present article is an attempt to formulate the three-dimensional quantitative structure–activity relationship (3D-QSAR) modeling of 2-alkylbenzimidazoles. Molecular field analysis was applied for the generation of steric, electrostatic and hydrophobic descriptors based on aligned structures. Partial least-squares (PLS) method was applied for QSAR model development considering training and test set approaches. The k-Nearest Neighbor Molecular Field Analysis (kNN-MFA), a three dimensional quantitative structure activity relationship (3D-QSAR) method has been used in the present case to study the correlation between the molecular properties and the angiotensin II receptor  activities on a series of 2-alkylbenzimidazoles derivatives. kNN-MFA calculations for both electrostatic, steric and hydrophobic field were carried out. Model - S_42, S_288, E_772, H_734, the template based alignment shows a q2 (cross validated r2) of 0.8165 with four descriptors. A non-cross-validated r2 of 0.8197, F values of 48.547 and number nearest neighbors k of 4 were observed with this model. i.e. all the values are proved statistically significant and exhibited good external prediction with r2 pred of 0.768.

 

Keywords: Ang II, molecular field analysis (MFA); partial least square (PLS).