Probing the structural requirements of A-type Aurora kinase inhibitors using 3D-QSAR and molecular docking analysis
文献类型：期刊论文
| 作者 | Zhang, Hui-xiao1; Li, Yan2,3; Wang, Xia1; Wang, Yong-hua1 |
| 刊名 | journal of molecular modeling
 |
| 出版日期 | 2012-03-01 |
| 卷号 | 18期号:3页码:1107-1122 |
| 关键词 | Aurora-A Inhibitor 3D-QSAR CoMFA CoMSIA Molecular docking |
| 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. |
| 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 |
| 关键词[WOS] | human colorectal cancers ; in-vivo ; antitumor-activity ; anticancer agents ; p-glycoprotein ; b kinase ; discovery ; potent ; overexpression ; binding |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000303539500027 |
| 公开日期 | 2015-11-17 |
| 源URL | [http://159.226.238.44/handle/321008/142900]  |
| 专题 | 大连化学物理研究所_中国科学院大连化学物理研究所 |
| 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 |
| 推荐引用方式 GB/T 7714 | 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. |
| APA | Zhang, Hui-xiao,Li, Yan,Wang, Xia,&Wang, Yong-hua.(2012).Probing the structural requirements of A-type Aurora kinase inhibitors using 3D-QSAR and molecular docking analysis.journal of molecular modeling,18(3),1107-1122. |
| MLA | Zhang, Hui-xiao,et al."Probing the structural requirements of A-type Aurora kinase inhibitors using 3D-QSAR and molecular docking analysis".journal of molecular modeling 18.3(2012):1107-1122. |
入库方式： OAI收割
来源：大连化学物理研究所
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