Insights into the Mechanism of Thiol-Triggered COS/H2S Release from N-Dithiasuccinoyl Amines
- 4 June 2020
- journal article
- research article
- Published by American Chemical Society (ACS) in The Journal of Organic Chemistry
- Vol. 85 (13), 8352-8359
- https://doi.org/10.1021/acs.joc.0c00559
Abstract
The hydrolysis of COS to form H2S by carbonic anhydrase has been demonstrated to be a viable strategy to deliver H2S in biological system. Herein, we describe N-dithiasuccinoyl amines as thiol-triggered COS/H2S donors. Notably, thiol species especially GSH and homocysteine can trigger the release of both COS and H2S directly from several specific analogues via an unexpected mechanism. Importantly, two representative analogues Dts-1 and Dts-5 show intracellular H2S release, and Dts-5 imparts potent anti-inflammatory effects in LPS challenged microglia cells. In conclusion, N-dithiasuccinoyl amine could serve as promising COS/H2S donors for either H2S biology studies or H2S-based therapeutics development.Keywords
Funding Information
- Six Talent Peaks Project in Jiangsu Province (YY-050, YY-053)
- National Natural Science Foundation of China (81773608, 81870997)
- Priority Academic Program Development of Jiangsu Higher Education Institutions
- Suzhou Clinical Research Center of Neurological Disease, Second Affiliated Hospital of Soochow University (Szzx201503)
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