Thiol-Activated 1,2,4-Thiadiazolidin-3,5-diones Release Hydrogen Sulfide through a Carbonyl-Sulfide-Dependent Pathway.

Recent efforts have expanded the development of small molecule donors that release the important biological signaling molecule hydrogen sulfide (HS). Previous work on 1,2,4-thiadiazolidin-3,5-diones (TDZNs) reported that these compounds release HS directly, albeit inefficiently. However, TDZNs showed promising efficacy in HS-mediated relaxation in ex vivo aortic ring relaxation models. Here, we show that TDZNs release carbonyl sulfide (COS) efficiently, which can be converted to HS by the enzyme carbonic anhydrase (CA) rather than releasing HS directly as previously reported.