Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 61, Issue 20, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202201668
Keywords
Hydrogen Persulfide Prodrug; Hydrogen Sulfide Prodrug; Sulfur Chemistry; Sulfur Species
Categories
Funding
- 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University [ZYYC21002, ZYJC1803]
- Science and Technology Project of Tibet Autonomous Region [XZ201901-GB-08]
- Chengdu Science and Technology Program [2018-CY02-00042-GX]
- Shanghai Pharmaceuticals Holding Co.,Ltd.
- Clinical Research Innovation Project, West China Hospital [2019HXCX06]
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Persulfide prodrugs, such as hydrogen persulfide (H2S2), show increased pharmacological activities and reduced toxicity compared to hydrogen sulfide (H2S), indicating their potential as better therapeutic options.
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 (H2S), hydrogen persulfide (H2S2), 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 H2S prodrug. In particular, the H2S2 prodrug offers much-elevated analgesic effects compared to the H2S prodrug in vivo. Persulfide prodrugs also possess a reduced level of toxicity compared to the H2S prodrug in vivo, indicating persulfide might represent a better therapeutic paradigm than H2S.
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