Organic Isothiocyanates as Hydrogen Sulfide Donors

Abstract

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.