3D-QSAR Study on dihydro-1,3,5-triazines and their spiro derivatives as DHFR inhibitors by comparative molecular field analysis (CoMFA)

Abstract

A 3D-QSAR/CoMFA was performed for a series of triazine and its spiro derivative based DHFR inhibitors displaying IC 50 values ranging from 0.002 to 58.8 μM. Analyses resulted in a reliable computational model with the parameters of n = 46, r 2 = 0.986, q 2 = 0.724, SE = 0.164, F = 275.889. It is shown that the steric and electrostatic properties predicted by CoMFA contours can be related to the DHFR inhibitory activity. The predictive ability of the resultant model was evaluated using a test set comprised of 18 molecules and the results show that the CoMFA model is able to correctly predict the poor inhibitory activities of the compounds in the testing set. This model is a significant guide to trace the features that really matter especially with respect to the design of novel compounds. © 2012 Elsevier Ltd. All rights reserved.