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

The gasotransmitter hydrogen sulfide
(H2S) 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 H2S represents
a timely issue for drug discovery. In this work, we developed a collection
of iminothioethers (ITEs), exhibiting H2S-releasing properties
and producing vasorelaxing effects on rat aortic rings. Derivatives 4 and 11, selected as representative of slow
and fast rate H2S 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 H2S. Taken
together, the results obtained support ITEs 4 and 11 as new pharmacological tools, as well as effective and
innovative H2S donors for cardiovascular drug discovery.