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 compo...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 q2=0.652 and r2=0.991. The contours analysis provides useful information about the structural requirements for 4-aminoquinazolines for inhib- iting Aurora B. Scaffold hopping method was used to generate new structures based on the maximum common sub- structure 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 in- hibitors for Aurora B kinase.展开更多
基金Project supported by the National Major Science and Technology Project of China （Nos. 2008ZX09401-001, 2009ZX09501-003）, the Specialized Research Fund for the Doctoral Program of Higher Education （No. 20090096110003）, the National Natural Science Foundation for the Youth （No. 30801437）.
文摘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 q2=0.652 and r2=0.991. The contours analysis provides useful information about the structural requirements for 4-aminoquinazolines for inhib- iting Aurora B. Scaffold hopping method was used to generate new structures based on the maximum common sub- structure 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 in- hibitors for Aurora B kinase.
