Identification and synthesis of substituted pyrrolo[2,3-d]pyrimidines as novel firefly luciferase inhibitors
文献类型：期刊论文
| 作者 | Liu, Yang2; Fang, Jianping1; Cai, Haiyan3; Xiao, Fei1; Ding, Kan1 ; Hu, Youhong2
|
| 刊名 | BIOORGANIC & MEDICINAL CHEMISTRY
 |
| 出版日期 | 2012-09-15 |
| 卷号 | 20期号:18页码:5473-5482 |
| 关键词 | Luciferase Inhibitor Pyrrolo[2,3-d]pyrimidine High-throughput screening Molecular docking |
| ISSN号 | 0968-0896 |
| DOI | 10.1016/j.bmc.2012.07.035 |
| 文献子类 | Article |
| 英文摘要 | A novel firefly luciferase inhibitor (3a) with a pyrrolo[2,3-d] pyrimidine core was identified in a cell-based NF-kappa B luciferase reporter gene assay. It potently inhibited the firefly luciferase derived from Photinus pyralis with an IC50 value of 0.36 +/- 0.05 mu M. Kinetic analysis of 3a inhibition showed that it is predominantly competitive with respect to D-luciferin and uncompetitive with respect to ATP. Therefore, several pyrrolo[2,3-d] pyrimidine analogues were prepared to further investigate the structure-activity relationship (SAR) for luciferase inhibition. The most potent inhibitor of this series was 4c, which showed an IC50 value of 0.06 +/- 0.01 mu M. In addition, molecular docking studies suggested that both 3a and 4c could be accommodated in the D-luciferin binding pocket, which is expected for a predominantly competitive inhibitor with respect to D-luciferin. (C) 2012 Elsevier Ltd. All rights reserved. |
| WOS关键词 | LUMINESCENCE ; BINDING ; ANALOG ; ASSAYS |
| 资助项目 | State Key Laboratory of Drug Research[00000000] ; National Science Fund for Distinguished Young Scholars in China[81125025] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000308808700019 |
| 出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277943]  |
| 专题 | 药理学第三研究室 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 药物化学研究室 |
| 通讯作者 | Ding, Kan |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Glycochem & Glycobiol Lab, Shanghai 201203, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Liu, Yang,Fang, Jianping,Cai, Haiyan,et al. Identification and synthesis of substituted pyrrolo[2,3-d]pyrimidines as novel firefly luciferase inhibitors[J]. BIOORGANIC & MEDICINAL CHEMISTRY,2012,20(18):5473-5482. |
| APA | Liu, Yang,Fang, Jianping,Cai, Haiyan,Xiao, Fei,Ding, Kan,&Hu, Youhong.(2012).Identification and synthesis of substituted pyrrolo[2,3-d]pyrimidines as novel firefly luciferase inhibitors.BIOORGANIC & MEDICINAL CHEMISTRY,20(18),5473-5482. |
| MLA | Liu, Yang,et al."Identification and synthesis of substituted pyrrolo[2,3-d]pyrimidines as novel firefly luciferase inhibitors".BIOORGANIC & MEDICINAL CHEMISTRY 20.18(2012):5473-5482. |
入库方式： OAI收割
来源：上海药物研究所
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