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 (H 2 S). Previous work on 1,2,4-thiadiazolidin-3,5-diones (TDZNs) reported that these compounds release H 2 S directly, albeit inefficiently. However, TDZNs showed promising efficacy in H 2 S-mediated relaxation in ex vivo aortic ring relaxation models. Here, we show that TDZNs release carbonyl sulfide (COS) efficiently, which can be converted to H 2 S by the enzyme carbonic anhydrase (CA) rather than releasing H 2 S directly as previously reported.