Persulfide Prodrugs

Yu, Bingchen; Yuan, Zhengnan; Wang, Binghe

doi:10.1002/9781119799900.ch12

Cited by 1 publication

(1 citation statement)

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“…To the best of our knowledge, there is a lack of reports on the joint therapeutic potential of H 2 S and glutathione [ 50 ]. We hypothesized that their effects can complement each other, e.g., via the generation of GSSH as a key mediator of H 2 S bioactivities, which reversibly traps and liberates H 2 S, reaching a relatively high concentration in the brain (>100 μM) and the myocardium (ca.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Glutathione Dithiophosphates as Long-Acting H2S Donors

Ishkaeva,

Khaertdinov,

Yakovlev

et al. 2023

IJMS

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Considering the important cytoprotective and signaling roles but relatively narrow therapeutic index of hydrogen sulfide (H2S), advanced H2S donors are required to achieve a therapeutic effect. In this study, we proposed glutathione dithiophosphates as new combination donors of H2S and glutathione. The kinetics of H2S formation in dithiophosphate solutions suggested a continuous H2S release by the donors, which was higher for the dithiophosphate of reduced glutathione than oxidized glutathione. The compounds, unlike NaHS, inhibited the proliferation of C2C12 myoblasts at submillimolar concentrations due to an efficient increase in intracellular H2S. The H2S donors more profoundly affected reactive oxygen species and reduced glutathione levels in C2C12 myocytes, in which these parameters were elevated compared to myoblasts. Oxidized glutathione dithiophosphate as well as control donors exerted antioxidant action toward myocytes, whereas the effect of reduced glutathione dithiophosphate at (sub-)micromolar concentrations was rather modulating. This dithiophosphate showed an enhanced negative inotropic effect mediated by H2S upon contraction of the atrial myocardium, furthermore, its activity was prolonged and reluctant for washing. These findings identify glutathione dithiophosphates as redox-modulating H2S donors with long-acting profile, which are of interest for further pharmacological investigation.

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Section: Discussionmentioning

confidence: 99%