A Persulfide Donor Responsive to Reactive Oxygen Species: Insights into Reactivity and Therapeutic Potential.

Autor: Powell CR; Department of Chemistry, Virginia Tech Center for Drug Discovery, Macromolecules Innovation Institute, Virginia Tech, Blacksburg, VA, 24061, USA., Dillon KM; Department of Chemistry, Virginia Tech Center for Drug Discovery, Macromolecules Innovation Institute, Virginia Tech, Blacksburg, VA, 24061, USA., Wang Y; Department of Chemistry, Virginia Tech Center for Drug Discovery, Macromolecules Innovation Institute, Virginia Tech, Blacksburg, VA, 24061, USA., Carrazzone RJ; Department of Chemistry, Virginia Tech Center for Drug Discovery, Macromolecules Innovation Institute, Virginia Tech, Blacksburg, VA, 24061, USA., Matson JB; Department of Chemistry, Virginia Tech Center for Drug Discovery, Macromolecules Innovation Institute, Virginia Tech, Blacksburg, VA, 24061, USA.
Jazyk: angličtina
Zdroj: Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2018 May 22; Vol. 57 (21), pp. 6324-6328. Date of Electronic Publication: 2018 Apr 26.
DOI: 10.1002/anie.201803087
Abstrakt: Persulfides (RSSH) have been hypothesized as critical components in sulfur-mediated redox cycles and as potential signaling compounds, similar to hydrogen sulfide (H 2 S). Hindering the study of persulfides is a lack of persulfide-donor compounds with selective triggers that release discrete persulfide species. Reported here is the synthesis and characterization of a ROS-responsive (ROS=reactive oxygen species), self-immolative persulfide donor. The donor, termed BDP-NAC, showed selectivity towards H 2 O 2 over other potential oxidative or nucleophilic triggers, resulting in the sustained release of the persulfide of N-acetyl cysteine (NAC) over the course of 2 h, as measured by LCMS. Exposure of H9C2 cardiomyocytes to H 2 O 2 revealed that BDP-NAC mitigated the effects of a highly oxidative environment in a dose-dependent manner over relevant controls and to a greater degree than common H 2 S donors sodium sulfide (Na 2 S) and GYY4137. BDP-NAC also rescued cells more effectively than a non-persulfide-releasing control compound in concert with common H 2 S donors and thiols.
(© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)
Databáze: MEDLINE
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