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 kinaseinhibitors regarded as promising antitumor agents to complement the existing therapies, wassubjected to a three-dimensional quantitative activity relationship (3D QSAR). Different QSARmethods, comparative molecular field analysis (CoMFA), CoMFA region focusing, andcomparative molecular similarity indices analysis (CoMSIA), were compared. All these QSARbasedmodels 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, whichimplied 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 q2and r2 values. The results of 3D contour maps can be useful for the future development of CDKsinhibitors. The results of 3D QSAR models are in agreement with docking results, and thestatistical parameters of the models explain that the data are well fitted and have high predictiveability.