1,2,4-Thiadiazolidin-3,5-diones as novel hydrogen sulfide donors

Abstract Hydrogen sulfide (H 2 S) is an endogenous modulator that plays significant physio-pathological roles in several biological systems. In this research field there is a large interest in developing selective CBS and CSE inhibitors and H 2 S releasing moieties, that could be either used as therapeutic agents or linked to known drugs. One of the major problem is the limited availability of chemicals that ensure a controlled release of H 2 S in vitro as well in vivo. Aiming to obtain novel H 2 S donors, whose release properties could be appropriately modulated, we have synthesized a series of 1,2,4-thiadiazolidine-3,5-diones ( THIA 1–10 ) as innovative donors that could release H 2 S in controlled manner. All the synthesized compounds were evaluated for their H 2 S releasing properties by an amperometric approach and for their vasorelaxant ability on aorta rings. In order to rationalize the obtained results, a detailed study on the release mechanism has been performed using the most efficient H 2 S donor, THIA 3 (C max 65.4 μM and EC 50 1.7 μM).