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 |
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Authors: | Haopeng Sun Jia Zhu Yadong Chen Yuan Sun Huijing Zhi Hao Li YouQidong You Qin Xiao |
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Affiliation: | 1. Key Laboratory of Carcinogenesis and Intervention of Jiangsu Province, China Pharmaceutical University, Nanjing, Jiangsu 210009, China;2. Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing, Jiangsu 210009, China |
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Abstract: | 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 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. |
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Keywords: | 4‐aminoquinazolines 3D‐QSAR molecular modeling quantum chemistry CoMSIA aurora B inhibitors |
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