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?
Angew Chem Int Ed Engl
; 61(20): e202201668, 2022 05 09.
Article
en En
| MEDLINE
| ID: mdl-35218121
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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Profármacos
/
Sulfuro de Hidrógeno
Idioma:
En
Revista:
Angew Chem Int Ed Engl
Año:
2022
Tipo del documento:
Article
País de afiliación:
Estados Unidos