3D-QSAR and docking analysis on a series of multi-cyclin-dependent kinase inhibitors using CoMFA, and CoMSIA

A series of 42 Pyrazolo[4,3-h]quinazoline-3-carboxamides as multi-cyclin-dependent kinase inhibitors regarded as promising antitumor agents to complement the existing therapies, was subjected to a three-dimensional quantitative activity relationship (3D QSAR). Different QSAR methods, comparative molecular field analysis (CoMFA), CoMFA region focusing, and comparative molecular similarity indices analysis (CoMSIA), were compared. All these QSARbased models had good statistical parameters and yielded q2 values of 0.717, 0.806, and 0.557, respectively. The CoMFA region focusing model provided the highest q2 and r2 values, which implied the significance of correlation of steric and electrostatic fields with biological activities. The quality of CoMSIA was slightly lower than that of CoMFA region focusing in terms of q2 and r2 values. The results of 3D contour maps can be useful for the future development of CDKs inhibitors. The results of 3D QSAR models are in agreement with docking results, and the statistical parameters of the models explain that the data are well fitted and have high predictive ability.