Organic Isothiocyanates as Hydrogen Sulfide Donors.

Significance: 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. Recent Advances: 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. Critical Issues: 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. Future Directions: 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.