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题名: Probing the structural requirements of A-type Aurora kinase inhibitors using 3D-QSAR and molecular docking analysis
作者: Zhang, Hui-xiao1;  Li, Yan2, 3;  Wang, Xia1;  Wang, Yong-hua1
关键词: Aurora-A ;  Inhibitor ;  3D-QSAR ;  CoMFA ;  CoMSIA ;  Molecular docking
刊名: JOURNAL OF MOLECULAR MODELING
发表日期: 2012-03-01
DOI: 10.1007/s00894-011-1042-3
卷: 18, 期:3, 页:1107-1122
收录类别: SCI
文章类型: Article
类目[WOS]: Biochemistry & Molecular Biology ;  Biophysics ;  Chemistry, Multidisciplinary ;  Computer Science, Interdisciplinary Applications
研究领域[WOS]: Biochemistry & Molecular Biology ;  Biophysics ;  Chemistry ;  Computer Science
英文摘要: Aurora-A, the most widely studied isoform of Aurora kinase overexpressed aberrantly in a wide variety of tumors, has been implicated in early mitotic entry, degradation of natural tumor suppressor p53 and centrosome maturation and separation; hence, potent inhibitors of Aurora-A may be therapeutically useful drugs in the treatment of various forms of cancer. Here, we report an in silico study on a group of 220 reported Aurora-A inhibitors with six different substructures. Three-dimensional quantitative structure-activity relationship (3D-QSAR) studies were carried out using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) techniques on this series of molecules. The resultant optimum 3D-QSAR models exhibited an r(cv)(2) value of 0.404-0.582 and their predictive ability was validated using an independent test set, ending in r(pred)(2) 0.512-0.985. In addition, docking studies were employed to explore these protein-inhibitor interactions at the molecular level. The results of 3D-QSAR and docking analyses validated each other, and the key structural requirements affecting Aurora-A inhibitory activities, and the influential amino acids involved were identified. To the best of our knowledge, this is the first report on 3D-QSAR modeling of Aurora-A inhibitors, and the results can be used to accurately predict the binding affinity of related analogues and also facilitate the rational design of novel inhibitors with more potent biological activities.
关键词[WOS]: HUMAN COLORECTAL CANCERS ;  IN-VIVO ;  ANTITUMOR-ACTIVITY ;  ANTICANCER AGENTS ;  P-GLYCOPROTEIN ;  B KINASE ;  DISCOVERY ;  POTENT ;  OVEREXPRESSION ;  BINDING
语种: 英语
WOS记录号: WOS:000303539500027
Citation statistics: 
内容类型: 期刊论文
URI标识: http://cas-ir.dicp.ac.cn/handle/321008/142900
Appears in Collections:中国科学院大连化学物理研究所_期刊论文

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作者单位: 1.NW A&F Univ, Ctr Bioinformat, Yangling 712100, Shaanxi, Peoples R China
2.Dalian Univ Technol, Sch Chem Engn, Dalian 116012, Liaoning, Peoples R China
3.Chinese Acad Sci, Dalian Inst Chem Phys, Lab Pharmaceut Resource Discovery, Grad Sch, Dalian 116023, Liaoning, Peoples R China

Recommended Citation:
Zhang, Hui-xiao,Li, Yan,Wang, Xia,et al. Probing the structural requirements of A-type Aurora kinase inhibitors using 3D-QSAR and molecular docking analysis[J]. JOURNAL OF MOLECULAR MODELING,2012,18(3):1107-1122.
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