Iminothioethers as Hydrogen Sulfide Donors: From the Gasotransmitter Release to the Vascular Effects

The gasotransmitter hydrogen sulfide (H 2 S) is an important tuner of the cardiovascular homeostasis, and its deficiency is etiologically associated with a number of cardiovascular diseases. Therefore, the research of original moieties able to release H 2 S represents a timely issue for drug discovery. In this work, we developed a collection of iminothioethers (ITEs), exhibiting H 2 S-releasing properties and producing vasorelaxing effects on rat aortic rings. Derivatives 4 and 11, selected as representative of slow and fast rate H 2 S donors, respectively, produced a complete recovery of the basal coronary flow, reverting the AngII-induced effects in isolated rat hearts. In addition, studies on human aortic smooth muscle cells (HASMCs) demonstrated membrane hyperpolarizing effects, well related to the intracellular generation of H 2 S. Taken together, the results obtained support ITEs 4 and 11 as new pharmacological tools, as well as effective and innovative H 2 S donors for cardiovascular drug discovery.