3D-QSAR study using CoMFA and CoMSIA methods for a series of histone H3 phosphorylation inhibitors

Three-dimensional quantitative structure-activity relationship (3D-QSAR) analysis of inhibitory activities for a series of pyrrolotriazine derivatives against histone H3 phosphorylation (pHH3) was performed using comparative of molecular field analysis (CoMFA) and comparative of molecular similarities indices analysis (CoMSIA) techniques. 62 derivatives were used to establish and validate two models by considering a high deviation in biological activities and structural variations. Optimum CoMFA and CoMSIA models obtained from the training set were statistically significant with cross-validated correlation coefficients q (2) of 0.551 and 0.621, and conventional correlation coefficients (r (2)) of 0.999 and 0.995, respectively. The predicted correlation coefficients of test set (R (2)) for CoMFA and CoMSIA were 0.835 and 0.918, respectively. Two models obtained provide guidelines to trace the features that really matter chiefly with respect to the design of novel pyrrolotriazine derivatives.