Discovery of Novel Acetohydroxyacid Synthase Inhibitors as Active Agents against Mycobacterium tuberculosis by Virtual Screening and Bioassay
文献类型：期刊论文
| 作者 | Wang, Di2; Zhu, Xuelian3; Cui, Changjun1; Dong, Mei2; Jiang, Hualiang3 ; Li, Zhengming1; Liu, Zhen2; Zhu, Weiliang3; Wang, Jian-Guo1
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| 刊名 | JOURNAL OF CHEMICAL INFORMATION AND MODELING
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| 出版日期 | 2013-02 |
| 卷号 | 53期号:2页码:343-353 |
| ISSN号 | 1549-9596 |
| DOI | 10.1021/ci3004545 |
| 文献子类 | Article |
| 英文摘要 | Acetohydroxyacid synthase (AHAS) has been regarded as a promising drug target against Mycobacterium tuberculosis (MTB) as it catalyzes the biosynthesis of branched-chain amino acids. In this study, 23 novel AHAS inhibitors were identified through molecular docking followed by similarity search. The determined IC50 values range from 0.385 +/- 0.026 mu M to >200 mu M against bacterium AHAS. Five of the identified compounds show significant in vitro activity against H37Rv strains (MICs in the range of 2.5-80 mg/L) and clinical MTB strains, including MDR and XDR isolates. More impressively, compounds 5 and 7 can enhance the killing ability against macrophages infected pathogen remarkably. This study suggests our discovered inhibitors can be further developed as novel anti-MTB therapeutics targeting AHAS. |
| WOS关键词 | DRUG-RESISTANT TUBERCULOSIS ; ACETOLACTATE SYNTHASE ; MOLECULAR DOCKING ; ANTITUBERCULOSIS AGENTS ; SULFONYLUREA HERBICIDES ; DESIGN ; ACIDS ; DERIVATIVES ; IMIDAZOLINONES ; BIOSYNTHESIS |
| 资助项目 | National Natural Science Foundation of China[81271777] ; National Natural Science Foundation of China[30970419] ; National Natural Science Foundation of China[81273435] ; National Natural Science Foundation of China[81000001] ; National Basic Research Project of China[2013CB734004] ; National Basic Research Project of China[2010CB126103] ; National Key Technology Research and Development Program[2011BAE06B05-3] ; International Collaboration Project from the S&T Ministry of China on drug and diagnostics innovation of tropical diseases[2010DFA33970] |
| WOS研究方向 | Pharmacology & Pharmacy ; Chemistry ; Computer Science |
| 语种 | 英语 |
| WOS记录号 | WOS:000315478900005 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277742]  |
| 专题 | 药物发现与设计中心 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Liu, Zhen |
| 作者单位 | 1.Nankai Univ, State Key Lab & Inst Elementoorgan Chem, Tianjin 300071, Peoples R China 2.309 Hosp Chinese Peoples Liberat Army, Dept Clin Lab, Beijing 100091, Peoples R China; 3.Shanghai Inst Mat Med, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai 201203, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Wang, Di,Zhu, Xuelian,Cui, Changjun,et al. Discovery of Novel Acetohydroxyacid Synthase Inhibitors as Active Agents against Mycobacterium tuberculosis by Virtual Screening and Bioassay[J]. JOURNAL OF CHEMICAL INFORMATION AND MODELING,2013,53(2):343-353. |
| APA | Wang, Di.,Zhu, Xuelian.,Cui, Changjun.,Dong, Mei.,Jiang, Hualiang.,...&Wang, Jian-Guo.(2013).Discovery of Novel Acetohydroxyacid Synthase Inhibitors as Active Agents against Mycobacterium tuberculosis by Virtual Screening and Bioassay.JOURNAL OF CHEMICAL INFORMATION AND MODELING,53(2),343-353. |
| MLA | Wang, Di,et al."Discovery of Novel Acetohydroxyacid Synthase Inhibitors as Active Agents against Mycobacterium tuberculosis by Virtual Screening and Bioassay".JOURNAL OF CHEMICAL INFORMATION AND MODELING 53.2(2013):343-353. |
入库方式： OAI收割
来源：上海药物研究所
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