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

Hydrogen sulfide (H(2)S), a gas transmitter found in eukaryotic organisms, plays an essential role in several physiological processes. H(2)S 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 H(2)S 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). H(2)S donors are compounds that can release H(2)S under certain circumstances. Development of highly targeted H(2)S donors is a key imperative as these can allow for in-depth evaluation of the anti-atherosclerotic effects of exogenous H(2)S. More importantly, identification of an optimal H(2)S donor is critical for the creation of H(2)S anti-atherosclerotic prodrugs. In this review, we discuss a wide range of H(2)S 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 H(2)S donors. This innovative and effective design example sheds new light on the production of highly targeted H(2)S donors.