2D and 3D quantitative structure-activity relationship studies on a series of bis-pyridinium compounds as choline kinase inhibitors

Abstract

Two-dimensional (2D) and three-dimensional (3D) quantitative structure activity relationship (QSAR) studies have been carried out on a series of 55 bis-pyridinium compounds to find out the structural requirements of choline kinase (ChoK) inhibitors. The best predictions were obtained from the model where 44 compounds were considered in the training set and the remaining 11 in the test set. The heuristic and BMLR methods resulted with r² and q² values of 0.86, 0.83 and 0.87, 0.84 respectively. The obtained Fisher and S² values for both the methods are 49.02 and 54.05, 0.053 and 0.0397 respectively. The best model for 3D-QSAR has been obtained with r²=0.97, q² = 0.58 and r²_pred=0.68 when CoMFA fields were used. The r² of 0.85, q² of 0.55 and r²_pred=0.66 have been observed when CoMSIA fields were used. The results that are obtained from 2D and 3D-QSAR studies may provide useful insights into the roles of various substitution patterns on the bis-pyridinium skeleton and may also help to design more potent compounds.