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

Hydrogen sulfide (HS) 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 HS 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 HS in vitro as well in vivo. Aiming to obtain novel HS 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 HS in controlled manner. All the synthesized compounds were evaluated for their HS 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 HS donor, THIA 3 (C 65.4 μM and EC 1.7 μM).