Identification of Trypanosoma brucei leucyl-tRNA synthetase inhibitors by pharmacophore- and docking-based virtual screening and synthesis
文献类型：期刊论文
| 作者 | Zhao, Yaxue2; Wang, Qing2; Meng, Qingqing2; Ding, Dazhong2; Yang, Huaiyu1; Gao, Guangwei2; Li, Dawei2; Zhu, Weiliang1 ; Zhou, Huchen2
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| 刊名 | BIOORGANIC & MEDICINAL CHEMISTRY
 |
| 出版日期 | 2012-02-01 |
| 卷号 | 20期号:3页码:1240-1250 |
| 关键词 | Human African trypanosomiasis Trypanosoma brucei Leucyl-tRNA synthetase Virtual screening Pharmacophore Docking |
| ISSN号 | 0968-0896 |
| DOI | 10.1016/j.bmc.2011.12.035 |
| 文献子类 | Article |
| 英文摘要 | Human African trypanosomiasis (HAT), caused by the protozoan parasite Trypanosoma brucei, is a neglected fatal disease. Leucyl-tRNA synthetase (LeuRS), which has been successfully applied in the development of antifungal agent, represents a potential antiprotozoal drug target. In this study, a 3D model of T. brucei LeuRS (TbLeuRS) synthetic active site was constructed and subjected to virtual screening using a combination of pharmacophore- and docking-based methods. A new 2-pyrrolinone scaffold was discovered and the structure-activity relationship (SAR) studies aided by the docking model and organic synthesis were carried out. Compounds with various substituents on R-1, R-2 and R-3 were synthesized and their SAR was discussed. (C) 2012 Elsevier Ltd. All rights reserved. |
| WOS关键词 | HUMAN AFRICAN TRYPANOSOMIASIS ; CCR2 RECEPTOR ANTAGONISTS ; CRYSTAL-STRUCTURE ; DRUG DISCOVERY ; SB-203207 ; LIGANDS ; ANALOGS ; DESIGN ; AGENTS ; LEAD |
| 资助项目 | National Science Foundation of China[20702031] ; Ministry of Science and Technology of China[2009CB918404] ; E-Institutes of Shanghai Universities (EISU) Chemical Biology Division[00000000] ; National Comprehensive Technology Platforms for Innovative Drug RD[2009ZX09301-007] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000299535400009 |
| 出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278207]  |
| 专题 | 药物发现与设计中心 |
| 通讯作者 | Zhou, Huchen |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China 2.Shanghai Jiao Tong Univ, Sch Pharm, Shanghai 200240, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Zhao, Yaxue,Wang, Qing,Meng, Qingqing,et al. Identification of Trypanosoma brucei leucyl-tRNA synthetase inhibitors by pharmacophore- and docking-based virtual screening and synthesis[J]. BIOORGANIC & MEDICINAL CHEMISTRY,2012,20(3):1240-1250. |
| APA | Zhao, Yaxue.,Wang, Qing.,Meng, Qingqing.,Ding, Dazhong.,Yang, Huaiyu.,...&Zhou, Huchen.(2012).Identification of Trypanosoma brucei leucyl-tRNA synthetase inhibitors by pharmacophore- and docking-based virtual screening and synthesis.BIOORGANIC & MEDICINAL CHEMISTRY,20(3),1240-1250. |
| MLA | Zhao, Yaxue,et al."Identification of Trypanosoma brucei leucyl-tRNA synthetase inhibitors by pharmacophore- and docking-based virtual screening and synthesis".BIOORGANIC & MEDICINAL CHEMISTRY 20.3(2012):1240-1250. |
入库方式： OAI收割
来源：上海药物研究所
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