Progress and perspective on hydrogen sulfide donors and their biomedical applications

Following the discovery of nitric oxide (NO) and carbon monoxide (CO), hydrogen sulfide (H₂S) has been identified as the third gasotransmitter in humans. Increasing evidence have shown that H₂S is of preventive or therapeutic effects on diverse pathological complications. As a consequence, it is of great significance to develop suitable approaches of H₂S-based therapeutics for biomedical applications. H₂S-releasing agents (H₂S donors) play important roles in exploring and understanding the physiological functions of H₂S. More importantly, accumulating studies have validated the theranostic potential of H₂S donors in extensive repertoires of in vitro and in vivo disease models. Thus, it is imperative to summarize and update the literatures in this field. In this review, first, the background of H₂S on its chemical and biological aspects is concisely introduced. Second, the studies regarding the H₂S-releasing compounds are categorized and described, and accordingly, their H₂S-donating mechanisms, biological applications, and therapeutic values are also comprehensively delineated and discussed. Necessary comparisons between related H₂S donors are presented, and the drawbacks of many typical H₂S donors are analyzed and revealed. Finally, several critical challenges encountered in the development of multifunctional H₂S donors are discussed, and the direction of their future development as well as their biomedical applications is proposed. We expect that this review will reach extensive audiences across multiple disciplines and promote the innovation of H₂S biomedicine.