Insights into the Mechanism of Thiol-Triggered COS/HS Release from -Dithiasuccinoyl Amines.

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.