Studies of tricyclic piperazine/piperidine furnished molecules as novel integrin alpha(v)beta(3)/alpha(IIb)beta(3) dual antagonists using 3D-QSAR and molecular docking
文献类型：期刊论文
| 作者 | Yan, Yulian1; Li, Yan1; Zhang, Shuwei1; Ai, Chunzhi2 |
| 刊名 | journal of molecular graphics & modelling
 |
| 出版日期 | 2011-02-01 |
| 卷号 | 29期号:5页码:747-762 |
| 关键词 | 3D-QSAR Integrin alpha(v)beta(3) Integrin alpha(IIb)beta(3) Antagonist CoMFA CoMSIA |
| 英文摘要 | the development of injectable integrin alpha(v)beta(3)/alpha(iib)beta(3) dual antagonists attracts much attention of research for treating of acute ischemic diseases in recent years. in this work, based on a dataset composed of 102 tricyclic piperazine/piperidine furnished dual alpha(v)beta(3) and alpha(iib)beta(3) antagonists, a variety of in silico modeling approaches including the comparative molecular field analysis (comfa), comparative similarity indices analysis (comsia), and molecular docking were applied to reveal the requisite 3d structural features impacting the biological activities. our statistical results show that the ligand-based 3d-qsar models for both the alpha(v)beta(3) and alpha(iib)beta(3) studies exhibited satisfactory internal and external predictability, i.e., for the comfa models, results of q(2) = 0.48, r-ncv(2) = 0.87, r-pred(2) = 0.71 for alpha(v)beta(3) and q(2) = 0.50, r-ncv(2) = 0.85, r-pred(2) = 0.72 for alpha(iib)beta(3) analysis were obtained, and for the comsia ones, the outcomes of q(2) = 0.55, r-ncv(2) = 0.90, r-pred(2) = 0.72 for alpha(v)beta(3) and q(2) = 0.52, r-ncv(2) = 0.88, r-pred(2) = 0.74 for alpha(iib)beta(3) were achieved respectively. in addition, through a comparison between 3d-qsar contour maps and docking results, it is revealed that that the most crucial interactions occurring between the tricyclic piperazine/piperidine derivatives and alpha(v)beta(3)/alpha(iib)beta(3) receptor ligand binding pocket are h-bonding, and the key amino acids impacting the interactions are arg214, asn215, ser123, and lys253 for alpha(v)beta(3), but arg214, asn215, ser123 and tyr190 for alpha(iib)beta(3) receptors, respectively. halogen-containing groups at position 15 and 16, benzene sulfonamide substituent at position 23, and the replacement of piperazine with 4-aminopiperidine of ring b may increase the alpha(v)beta(3)/alpha(iib)beta(3) antagonistic activity. the potencies for antagonists to inhibit isolated alpha(v)beta(3) and alpha(iib)beta(3) are linear correlated, indicating that similar interaction mechanisms may exist for the series of molecules. to our best knowledge this is the first report on 3d-qsar modeling of these dual alpha(v)beta(3)/alpha(iib)beta(3) antagonists. the results obtained should provide information for better understanding of the mechanism of antagonism and thus be helpful in design of novel potent dual alpha(v)beta(3)/alpha(iib)beta(3) antagonists. (c) 2011 elsevier inc. all rights reserved. |
| WOS标题词 | science & technology ; life sciences & biomedicine ; technology ; physical sciences |
| 类目[WOS] | biochemical research methods ; biochemistry & molecular biology ; computer science, interdisciplinary applications ; crystallography ; mathematical & computational biology |
| 研究领域[WOS] | biochemistry & molecular biology ; computer science ; crystallography ; mathematical & computational biology |
| 关键词[WOS] | pharmacophore-based molecules ; glycoprotein-iib-iiia ; alpha(v)beta(3) integrin ; integrin-alpha(v)beta(3) antagonists ; vitronectin receptor ; potent antagonists ; glanzmann thrombasthenia ; binding-affinity ; beta 3 ; fibrinogen |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000288236400018 |
| 公开日期 | 2015-11-17 |
| 源URL | [http://159.226.238.44/handle/321008/142663]  |
| 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, Sch Chem Engn, Dalian 116012, Liaoning, Peoples R China 2.Chinese Acad Sci, Dalian Inst Chem Phys, Grad Sch, Lab Pharmaceut Resource Discovery, Dalian 116023, Liaoning, Peoples R China |
| 推荐引用方式 GB/T 7714 | Yan, Yulian,Li, Yan,Zhang, Shuwei,et al. Studies of tricyclic piperazine/piperidine furnished molecules as novel integrin alpha(v)beta(3)/alpha(IIb)beta(3) dual antagonists using 3D-QSAR and molecular docking[J]. journal of molecular graphics & modelling,2011,29(5):747-762. |
| APA | Yan, Yulian,Li, Yan,Zhang, Shuwei,&Ai, Chunzhi.(2011).Studies of tricyclic piperazine/piperidine furnished molecules as novel integrin alpha(v)beta(3)/alpha(IIb)beta(3) dual antagonists using 3D-QSAR and molecular docking.journal of molecular graphics & modelling,29(5),747-762. |
| MLA | Yan, Yulian,et al."Studies of tricyclic piperazine/piperidine furnished molecules as novel integrin alpha(v)beta(3)/alpha(IIb)beta(3) dual antagonists using 3D-QSAR and molecular docking".journal of molecular graphics & modelling 29.5(2011):747-762. |
入库方式： OAI收割
来源：大连化学物理研究所
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