Insights into the Mechanism of Thiol-Triggered COS/H2S Release from N‑Dithiasuccinoyl Amines

The hydrolysis of carbonyl sulfide (COS) to form H2S by carbonic anhydrase has been demonstrated to be a viable strategy to deliver H2S in a biological system. Herein, we describe N-dithiasuccinoyl amines as thiol-triggered COS/H2S donors. Notably, thiol species especially GSH and homocysteine can t...

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Bibliographic Details
Published in:Journal of organic chemistry 2020-07, Vol.85 (13), p.8352-8359
Main Authors: Zhou, Shengchao, Mou, Yujie, Liu, Miao, Du, Qian, Ali, Basharat, Ramprasad, Jurupula, Qiao, Chunhua, Hu, Li-Fang, Ji, Xingyue
Format: Article
Language:English
Online Access:Get full text
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Summary:The hydrolysis of carbonyl sulfide (COS) to form H2S by carbonic anhydrase has been demonstrated to be a viable strategy to deliver H2S in a 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-1 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 biological studies or H2S-based therapeutics development.
ISSN:0022-3263
1520-6904
DOI:10.1021/acs.joc.0c00559