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

The gasotransmitter hydrogen sulfide (HS) 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 HS represents a timely issue for drug discovery. In this work, we developed a collection of iminothioethers (ITEs), exhibiting HS-releasing properties and producing vasorelaxing effects on rat aortic rings. Derivatives 4 and 11, selected as representative of slow and fast rate HS 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 HS. Taken together, the results obtained support ITEs 4 and 11 as new pharmacological tools, as well as effective and innovative HS donors for cardiovascular drug discovery.