Binding interaction of quereetin-3-beta-galactoside and its synthetic derivatives with SARS-CoV 3CL(pro): Structure-activity relationship studies reveal salient pharmacophore features
文献类型：期刊论文
| 作者 | Chen, Lili ; Li, Jian; Luo, Cheng; Liu, Hong; Xu, Weijun; Chen, Gang; Liew, Oi Wah; Zhu, Weiliang; Puah, Chum Mok; Shen, Xu
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| 刊名 | BIOORGANIC & MEDICINAL CHEMISTRY
 |
| 出版日期 | 2006-12-15 |
| 卷号 | 14期号:24页码:8295-8306 |
| 关键词 | SARS-CoV 3CL(pro) virtual screening quercetin-3-beta-galactoside molecular modeling structure-activity relationships |
| ISSN号 | 0968-0896 |
| DOI | 10.1016/j.bmc.2006.09.014 |
| 文献子类 | Article |
| 英文摘要 | The 3C-like protease (3CL(pro)) of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is one of the most promising targets for discovery of drugs against SARS, because of its critical role in the viral life cycle. In this study, a natural compound called quercetin-3-beta-galacto side was identified as an inhibitor of the protease by molecular docking, SPR/FRET-based bioassays, and mutagenesis studies. Both molecular modeling and Q189A mutation revealed that Gln189 plays a key role in the binding. Furthermore, experimental evidence showed that the secondary structure and enzymatic activity of SARS-CoV 3CL(pro) were not affected by the Q189A mutation. With the help of molecular modeling, eight new derivatives of the natural product were designed and synthesized. Bioassay results reveal salient features of the structure-activity relationship of the new compounds: (1) removal of the 7-hydroxy group of the quercetin moiety decreases the bioactivity of the derivatives; (2) acetoxylation of the sugar moiety abolishes inhibitor action; (3) introduction of a large sugar substituent on 7-hydroxy of quercetin can be tolerated; (4) replacement of the galactose moiety with other sugars does not affect inhibitor potency. This study not only reveals a new class of compounds as potential drug leads against the SARS virus, but also provides a solid understanding of the mechanism of inhibition against the target enzyme. (c) 2006 Elsevier Ltd. All rights reserved. |
| WOS关键词 | ACUTE RESPIRATORY SYNDROME ; CORONAVIRUS MAIN PROTEINASE ; 3C-LIKE PROTEINASE ; 3CL PROTEASE ; IDENTIFIES INHIBITORS ; HONG-KONG ; DESIGN ; QUERCETIN ; MOLECULES ; MECHANISM |
| WOS研究方向 | Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000242454700013 |
| 出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/273424]  |
| 专题 | 药物发现与设计中心 药理学第三研究室 |
| 通讯作者 | Xu, Weijun |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China 2.Singapore Polytech, Technol Ctr Life Sci, Singapore 139651, Singapore |
| 推荐引用方式 GB/T 7714 | Chen, Lili,Li, Jian,Luo, Cheng,et al. Binding interaction of quereetin-3-beta-galactoside and its synthetic derivatives with SARS-CoV 3CL(pro): Structure-activity relationship studies reveal salient pharmacophore features[J]. BIOORGANIC & MEDICINAL CHEMISTRY,2006,14(24):8295-8306. |
| APA | Chen, Lili.,Li, Jian.,Luo, Cheng.,Liu, Hong.,Xu, Weijun.,...&Jiang, Hualiang.(2006).Binding interaction of quereetin-3-beta-galactoside and its synthetic derivatives with SARS-CoV 3CL(pro): Structure-activity relationship studies reveal salient pharmacophore features.BIOORGANIC & MEDICINAL CHEMISTRY,14(24),8295-8306. |
| MLA | Chen, Lili,et al."Binding interaction of quereetin-3-beta-galactoside and its synthetic derivatives with SARS-CoV 3CL(pro): Structure-activity relationship studies reveal salient pharmacophore features".BIOORGANIC & MEDICINAL CHEMISTRY 14.24(2006):8295-8306. |
入库方式： OAI收割
来源：上海药物研究所
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