Organic Isothiocyanates as Hydrogen Sulfide Donors

Hydrogen sulfide (H₂S), the "new entry" in the series of endogenous gasotransmitters, plays a fundamental role in regulating the biological functions of various organs and systems. Consequently, the lack of adequate levels of H₂S may represent the etiopathogenetic factor of multiple pathological alterations. In these diseases, the use of H₂S donors represents a precious and innovative opportunity. Natural isothiocyanates (ITCs), sulfur compounds typical of some botanical species, have long been investigated because of their intriguing pharmacological profile. Recently, the ITC moiety has been proposed as a new H₂S-donor chemotype (with a l-cysteine-mediated reaction). Based on this recent discovery, we can clearly observe that almost all the effects of natural ITCs can be explained by the H₂S release. Consistently, the ITC function was also used as an original H₂S-releasing moiety for the design of synthetic H₂S donors and original "pharmacological hybrids." Very recently, the chemical mechanism of H₂S release, resulting from the reaction between l-cysteine and some ITCs, has been elucidated. Available literature gives convincing demonstration that H₂S is the real player in ITC pharmacology. Further, countless studies have been carried out on natural ITCs, but this versatile moiety has been used only rarely for the design of synthetic H₂S donors with optimal drug-like properties. The development of more ITC-based synthetic H₂S donors with optimal drug-like properties and selectivity toward specific tissues/pathologies seem to represent a stimulating and indispensable prospect of future experimental activities.