College of Pharmaceutical Science, Soochow University, Suzhou, Jiangsu 215021, China.
Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou, Jiangsu 215123, China.
J Org Chem. 2020 Jul 2;85(13):8352-8359. doi: 10.1021/acs.joc.0c00559. Epub 2020 Jun 17.
The hydrolysis of carbonyl sulfide (COS) to form HS by carbonic anhydrase has been demonstrated to be a viable strategy to deliver HS in a biological system. Herein, we describe -dithiasuccinoyl amines as thiol-triggered COS/HS donors. Notably, thiol species especially GSH and homocysteine can trigger the release of both COS and HS directly from several specific analogues via an unexpected mechanism. Importantly, two representative analogues and show intracellular HS release, and imparts potent anti-inflammatory effects in LPS-challenged microglia cells. In conclusion, -dithiasuccinoyl amine could serve as promising COS/HS donors for either HS biological studies or HS-based therapeutics development.
碳酸酐酶将羰基硫（COS）水解生成 HS 已被证明是在生物体系中输送 HS 的一种可行策略。在此，我们将 -二硫代琥珀酰亚胺描述为硫醇触发的 COS/HS 供体。值得注意的是，硫醇物质，尤其是 GSH 和高半胱氨酸，可以通过一种意想不到的机制直接从几种特定的类似物中触发 COS 和 HS 的释放。重要的是，两种代表性的类似物 和 显示出细胞内 HS 的释放，并且 在 LPS 刺激的小神经胶质细胞中赋予了强大的抗炎作用。总之，-二硫代琥珀酰亚胺可用作有前途的 COS/HS 供体，用于 HS 的生物学研究或基于 HS 的治疗药物的开发。
