Clopidogrel as a donor probe and thioenol derivatives as flexible promoieties for enabling H2S biomedicine

Yaoqiu Zhu, Elkin L. Romero, Xiaodong Ren, Angel J. Sanca, Congkuo Du, Cai Liu, Zubair A. Karim, Fatima Z. Alshbool, Fadi T. Khasawneh, Jiang Zhou, Dafang Zhong, Bing Geng

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

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 α-hydrogen. These results can provide chemical tools for advancing hydrogen sulfide biomedical research as well as developing hydrogen sulfide-releasing drugs.

Original languageEnglish (US)
Article number3952
JournalNature communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Fingerprint

Dive into the research topics of 'Clopidogrel as a donor probe and thioenol derivatives as flexible promoieties for enabling H2S biomedicine'. Together they form a unique fingerprint.

Cite this