Prodrugs of Persulfide and Sulfide: Is There a Pharmacological Difference between the Two in the Context of Rapid Exchanges among Various Sulfur Species In Vivo?. Issue 20 (14th March 2022) - Yu, Bingchen
Abstract: Sulfide and persulfide are chemically different and one might expect persulfide to be more effective in mediating sulfur signaling because persulfide can directly modify protein cysteine residue. However, rapid scrambling, and interconversions occur among sulfur species. Then there is the question of whether the chemical reactivity differences between sulfide and persulfide would translate into pharmacological differences. Utilizing a delivery system to generate pure hydrogen sulfide (H2 S), hydrogen persulfide (H2 S2 ), and N ‐acetyl‐l ‐cysteine persulfide ( N ‐CysSSH), we examined the activities of sulfide and persulfide in vitro and in vivo. Persulfide prodrugs exhibited increased activities compared to the H2 S prodrug. In particular, the H2 S2 prodrug offers much‐elevated analgesic effects compared to the H2 S prodrug in vivo. Persulfide prodrugs also possess a reduced level of toxicity compared to the H2 S prodrug in vivo, indicating persulfide might represent a better therapeutic paradigm than H2 S. Abstract : A delivery system which can release pure H2 S, hydrogen persulfide, and N ‐acetyl‐l ‐cysteine persulfide was used to compare the pharmacological difference of sulfide and persulfide. Persulfide prodrugs exhibited increased activities compared to the H2 S prodrug in vitro and in vivo. Persulfide prodrugs also exhibited reduced toxicity compared to H2 S prodrug in vivo, indicating persulfide might represent a better therapeutic paradigm than H2 S.