Docking study and three-dimensional quantitative structure-activity relationship (3D-QSAR) analyses and novel molecular design of a series of 4-aminoquinazolines as inhibitors of aurora B kinase

The Aurora proteins are critical regulators of major mitotic events and attractive targets for anticancer therapy. 3D-QSAR studies based on molecular docking were performed on a dataset of 40 4-aminoquinazolines compounds. The CoMSIA model produced significantly better results than CoMFA model, with q(2) = 0.652 and r(2) = 0.991. The contours analysis provides useful information about the structural requirements for 4-aminoquinazolines for inhibiting Aurora B. Scaffold hopping method was used to generate new structures based on the maximum common substructure of the training and test set compounds. The ADMET property, binding affinity and inhibitory activity of the new designed compounds were predicted, respectively. Finally 16 compounds were identified as the novel inhibitors for Aurora B kinase.