Development of hydrogen sulfide donors for anti-atherosclerosis therapeutics research: Challenges and future...

Hydrogen sulfide (H₂S), a gas transmitter found in eukaryotic organisms, plays an essential role in several physiological processes. H₂S is one of the three primary biological gas transmission signaling mediators, along with nitric oxide and carbon monoxide. Several animal and in vitro experiments have indicated that H₂S can prevent coronary endothelial mesenchymal transition, reduce the expression of endothelial cell adhesion molecules, and stabilize intravascular plaques, suggesting its potential role in the treatment of atherosclerosis (AS). H₂S donors are compounds that can release H₂S under certain circumstances. Development of highly targeted H₂S donors is a key imperative as these can allow for in-depth evaluation of the anti-atherosclerotic effects of exogenous H₂S. More importantly, identification of an optimal H₂S donor is critical for the creation of H₂S anti-atherosclerotic prodrugs. In this review, we discuss a wide range of H₂S donors with anti-AS potential along with their respective transport pathways and design-related limitations. We also discuss the utilization of nano-synthetic technologies to manufacture H₂S donors. This innovative and effective design example sheds new light on the production of highly targeted H₂S donors.