Insight into the Structural Requirements of Benzimidazole Derivatives as Interleukin-2 Inducible T-cell Kinase Inhibitors by Computational Explorations
文献类型：期刊论文
| 作者 | Wang, Jinghui1; Li, Feng1,2; Li, Yan; Yang, Yinfeng1; Wang, Bin3; Zhang, Shuwei1; Yang, Ling4 |
| 刊名 | international journal of quantum chemistry
 |
| 出版日期 | 2013-11-05 |
| 卷号 | 113期号:21页码:2385-2396 |
| 关键词 | 3D-QSAR ITK inhibitors comparative molecular field analysis comparative molecular similarity indices analysis molecular dynamics docking |
| 英文摘要 | in the present work, a set of ligand- and receptor-based 3d-qsar models were developed to explore the structure-activity relationship of 109 benzimidazole-based interleukin-2-inducible t-cell kinase (itk) inhibitors. in order to reveal the requisite 3d structural features impacting the biological activities, a variety of in silico modeling approaches including the comparative molecular field analysis (comfa), comparative molecular similarity indices analysis (comsia), docking, and molecular dynamics were applied. the results showed that the ligand-based comfa model (q(2) = 0.552, r-ncv(2) = 0.908, r-pred(2) = 0.787, see = 0.252, sep = 0.558) and comsia model (q(2) = 0.579, r-ncv(2) = 0.914, r-pred(2) = 0.893, see = 0.240, sep = 0.538) were superior to other models with greater predictive power. in addition, a combined analysis between the 3d contour maps and docking results showed that: (1) compounds with bulky or hydrophobic substituents near ring d and electropositive or hydrogen acceptor groups around rings c and d could increase the activity. (2) the key amino acids impacting the receptor-ligand interactions in the binding pocket are met438, asp500, lys391, and glu439. the results obtained from this work may provide helpful guidelines in design of novel benzimidazole analogs as inhibitors of itk. (c) 2013 wiley periodicals, inc. |
| WOS标题词 | science & technology ; physical sciences |
| 类目[WOS] | chemistry, physical ; mathematics, interdisciplinary applications ; physics, atomic, molecular & chemical |
| 研究领域[WOS] | chemistry ; mathematics ; physics |
| 关键词[WOS] | molecular similarity indexes ; itk inhibitors ; drug design ; signal-transduction ; crystal-structures ; cross-validation ; tyrosine kinase ; analysis comsia ; field analysis ; 3d qsar |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000325078500008 |
| 公开日期 | 2015-11-10 |
| 源URL | [http://159.226.238.44/handle/321008/137901]  |
| 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.Dalian Univ Technol, Dept Mat Sci & Chem Engn, Dalian 116023, Liaoning, Peoples R China 2.Henan Inst Engn, Dept Civil Engn, Zhengzhou 451191, Henan, Peoples R China 3.Dalian Ocean Univ, Aquat Prod Life Acad, Dalian 116023, Liaoning, Peoples R China 4.Chinese Acad Sci, Lab Pharmaceut Resource Discovery, Dalian Inst Chem Phys, Grad Sch, Dalian 116023, Liaoning, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wang, Jinghui,Li, Feng,Li, Yan,et al. Insight into the Structural Requirements of Benzimidazole Derivatives as Interleukin-2 Inducible T-cell Kinase Inhibitors by Computational Explorations[J]. international journal of quantum chemistry,2013,113(21):2385-2396. |
| APA | Wang, Jinghui.,Li, Feng.,Li, Yan.,Yang, Yinfeng.,Wang, Bin.,...&Yang, Ling.(2013).Insight into the Structural Requirements of Benzimidazole Derivatives as Interleukin-2 Inducible T-cell Kinase Inhibitors by Computational Explorations.international journal of quantum chemistry,113(21),2385-2396. |
| MLA | Wang, Jinghui,et al."Insight into the Structural Requirements of Benzimidazole Derivatives as Interleukin-2 Inducible T-cell Kinase Inhibitors by Computational Explorations".international journal of quantum chemistry 113.21(2013):2385-2396. |
入库方式： OAI收割
来源：大连化学物理研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。