Clopidogrel as a donor probe and thioenol derivatives as flexible promoieties for enabling H2S biomedicine
文献类型：期刊论文
| 作者 | Zhu, Yaoqiu5; Romero, Elkin L.5; Ren, Xiaodong5; Sanda, Angel J.5; Du, Congkuo4; Liu, Cai1; Karim, Zubair A.2; Alshbool, Fatima Z.2; Khasawneh, Fadi T.2; Zhou, Jiang3 |
| 刊名 | NATURE COMMUNICATIONS
 |
| 出版日期 | 2018-09-27 |
| 卷号 | 9 |
| ISSN号 | 2041-1723 |
| DOI | 10.1038/s41467-018-06373-0 |
| 文献子类 | Article |
| 英文摘要 | Hydrogen sulfide has emerged as a critical endogenous signaling transmitter and a potentially versatile therapeutic agent. The key challenges in this field include the lack of approved hydrogen sulfide-releasing probes for in human exploration and the lack of controllable hydrogen sulfide promoieties that can be flexibly installed for therapeutics development. Here we report the identification of the widely used antithrombotic drug clopidogrel as a clinical hydrogen sulfide donor. Clopidogrel is metabolized in patients to form a circulating metabolite that contains a thioenol substructure, which is found to undergo spontaneous degradation to release hydrogen sulfide. Model studies demonstrate that thioenol derivatives are a class of controllable promoieties that can be conveniently installed on a minimal structure of ketone with an alpha-hydrogen. These results can provide chemical tools for advancing hydrogen sulfide biomedical research as well as developing hydrogen sulfide-releasing drugs. |
| WOS关键词 | HYDROGEN-SULFIDE DONORS ; PLATELET-AGGREGATION ; ACTIVE METABOLITE ; HUMAN PLASMA ; IN-VITRO ; GASOTRANSMITTER ; BIOACTIVATION ; RESISTANCE ; CYP2C19 ; PARAOXONASE-1 |
| 资助项目 | Border Biomedical Research Center (National Institutes of Health)[5G12MD007592] ; University of Texas at El Paso[00000000] |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| 出版者 | NATURE PUBLISHING GROUP |
| WOS记录号 | WOS:000445819400003 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279570]  |
| 专题 | 上海药物代谢研究中心 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 | Zhu, Yaoqiu |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Materia Med, State Key Lab Drug Res, 501 Haike Rd, Shanghai 201203, Peoples R China; 2.Univ Texas El Paso, Sch Pharm, Dept Pharmaceut Sci, El Paso, TX 79902 USA; 3.Peking Univ, Coll Chem & Mol Engn, Analyt Instrumentat Ctr, Beijing 100871, Peoples R China 4.CAMS PUMC, Fuwai Hosp, Hypertens Ctr, State Key Lab Cardiovasc Dis, Beijing 102300, Peoples R China; 5.Univ Texas El Paso, Border Biomed Res Ctr, Dept Chem & Biochem, El Paso, TX 79968 USA; |
| 推荐引用方式 GB/T 7714 | Zhu, Yaoqiu,Romero, Elkin L.,Ren, Xiaodong,et al. Clopidogrel as a donor probe and thioenol derivatives as flexible promoieties for enabling H2S biomedicine[J]. NATURE COMMUNICATIONS,2018,9. |
| APA | Zhu, Yaoqiu.,Romero, Elkin L..,Ren, Xiaodong.,Sanda, Angel J..,Du, Congkuo.,...&Geng, Bing.(2018).Clopidogrel as a donor probe and thioenol derivatives as flexible promoieties for enabling H2S biomedicine.NATURE COMMUNICATIONS,9. |
| MLA | Zhu, Yaoqiu,et al."Clopidogrel as a donor probe and thioenol derivatives as flexible promoieties for enabling H2S biomedicine".NATURE COMMUNICATIONS 9(2018). |
入库方式： OAI收割
来源：上海药物研究所
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