Molecular docking-based 3D-QSAR studies of pyrrolo[3,4-c]pyrazole derivatives as Aurora-A inhibitors

	Molecular docking-based 3D-QSAR studies of pyrrolo[3,4-c]pyrazole derivatives as Aurora-A inhibitors
	He, G. ; Qiu, M. H. ; Li, R. ; Song, X. R. ; Zheng, X. ; Shi, J. Y. ; Xu, G. B. ; Han, J. ; Yu, L. T. ; Yang, S. Y. ; Chen, L. J. ; Wei, Y. Q.
通讯作者	Li, R (reprint author), Sichuan Univ, State Key Lab Biotherapy, W China Hosp, Chengdu 610041, Peoples R China. li_rui@yahoo.cn
	2011
发表期刊	MOLECULAR SIMULATION
ISSN	0892-7022
卷号	37 期号:1 页码:31-42
摘要	In recent years, Aurora kinases have been highlighted as attractive targets for the development of novel anti-cancer agents. To find the correlation between Aurora-A and its inhibitors, structure-based 3D-quantitative structure-activity relationship (QSAR) models were performed on a series of pyrrolo[3,4-c] pyrazole derivatives with comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methods. Based on the docking results, predictive 3D-QSAR models were established, with cross-validated coefficient values (r(cv)(2)) up to 0.667 for CoMFA and 0.664 for CoMSIA, respectively. Furthermore, the CoMFA and CoMSIA models were mapped back to the binding sites of Aurora-A, which could get a better understanding of vital interactions between the inhibitors and the kinase. Ligands binding in the ATP pocket and the hydrogen bonds with Ala213 and Glu211 were found to be crucial for the potent ligand binding and kinases selectivity. Therefore, these results demonstrated the power of combining the docking/QSAR approach to explore the probable binding conformations of compounds at the active sites of the protein, and further provided useful information for designing new compounds that showed very low binding free energy against the Aurora-A kinase, and which had been shifted for further experimental assay studies.
关键词	Pyrrolo[3 4-c]Pyrazole Derivatives 3d-qsar Molecular Docking Comfa Comsia Kinase Inhibitors Protein-kinase Pharmacophore Model Similarity Indexes Analysis Comsia Potent Identification Binding Profile Comfa
学科领域	Chemistry, Physical ; Physics, Atomic, Molecular & Chemical
收录类别	sci
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kib.ac.cn/handle/151853/15372
专题	植物化学与西部植物资源持续利用国家重点实验室
推荐引用方式 GB/T 7714	He, G.,Qiu, M. H.,Li, R.,et al. Molecular docking-based 3D-QSAR studies of pyrrolo[3,4-c]pyrazole derivatives as Aurora-A inhibitors[J]. MOLECULAR SIMULATION,2011,37(1):31-42.
APA	He, G..,Qiu, M. H..,Li, R..,Song, X. R..,Zheng, X..,...&Wei, Y. Q..(2011).Molecular docking-based 3D-QSAR studies of pyrrolo[3,4-c]pyrazole derivatives as Aurora-A inhibitors.MOLECULAR SIMULATION,37(1),31-42.
MLA	He, G.,et al."Molecular docking-based 3D-QSAR studies of pyrrolo[3,4-c]pyrazole derivatives as Aurora-A inhibitors".MOLECULAR SIMULATION 37.1(2011):31-42.

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