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 (H2S). Previous work on 1,2,4-thiadiazolidin-3,5-diones (TDZNs) reported that these compounds release H2S directly, albeit inefficiently. However, TDZNs showed promising efficacy in H2S-mediated relaxation in ex vivo aortic ring relaxation models. Here, we show that TDZNs release carbonyl sulfide (COS) efficiently, which can be converted to H2S by the enzyme carbonic anhydrase (CA) rather than releasing H2S directly as previously reported.

Automated summary

Recent efforts have focused on the development of small molecule donors that can release hydrogen sulfide (H2S), an important biological signaling molecule. In particular, 1,2,4-thiadiazolidin-3,5-diones (TDZNs) have shown promising efficacy in H2S-mediated relaxation. It has been discovered that TDZNs release carbonyl sulfide (COS) efficiently, which can be converted to H2S by the enzyme carbonic anhydrase (CA), rather than directly releasing H2S as previously thought.