2D and 3D Quantitative Structure‐Activity Relationship Studies on a Series of bis‐Pyridinium Compounds as Choline Kinase Inhibitors

Abstract

AbstractTwo‐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 r$\rm{ {_{pred}^{2}}}$=0.68 when CoMFA fields were used. The r2 of 0.85, q2 of 0.55 and r$\rm{ {_{pred}^{2}}}$=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.