The synthesis and functional evaluation of a mitochondria-targeted hydrogen sulfide donor, (10-oxo-10-(4-(3-thioxo-3H-1,2-dithiol-5-yl)phenoxy)decyl) triphenylphosphonium bromide (AP39)

Sophie Le Trionnaire, Alexis Perry, Bartosz Szczesny, Csaba Szabo, Paul G. Winyard, Jacqueline L. Whatmore, Mark E. Wood, Matthew Whiteman

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Synthesis and bioavailability of the endogenous gasomediator hydrogen sulfide (H2S) is perturbed in many disease states, including those involving mitochondrial dysfunction. There is intense interest in developing pharmacological agents to generate H2S. We have synthesised a novel H2S donor molecule coupled to a mitochondria-targeting moiety (triphenylphosphonium; TPP+) and compared the effectiveness of the compound against a standard non-TPP+ containing H2S donor (GYY4137) in the inhibition of oxidative stress-induced endothelial cell death. Our study suggests mitochondria-targeted H2S donors are useful pharmacological tools to study the mitochondrial physiology of H2S in health and disease.

Original languageEnglish (US)
Pages (from-to)728-736
Number of pages9
JournalMedChemComm
Volume5
Issue number6
DOIs
StatePublished - 2014

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Hydrogen Sulfide
Mitochondria
Bromides
Pharmacology
Oxidative stress
Endothelial cells
Physiology
Cell death
Biological Availability
Oxidative Stress
Cell Death
Endothelial Cells
Health
Molecules
dithiol
decyl bromide
GYY 4137

ASJC Scopus subject areas

  • Biochemistry
  • Pharmaceutical Science

Cite this

The synthesis and functional evaluation of a mitochondria-targeted hydrogen sulfide donor, (10-oxo-10-(4-(3-thioxo-3H-1,2-dithiol-5-yl)phenoxy)decyl) triphenylphosphonium bromide (AP39). / Le Trionnaire, Sophie; Perry, Alexis; Szczesny, Bartosz; Szabo, Csaba; Winyard, Paul G.; Whatmore, Jacqueline L.; Wood, Mark E.; Whiteman, Matthew.

In: MedChemComm, Vol. 5, No. 6, 2014, p. 728-736.

Research output: Contribution to journalArticle

Le Trionnaire, Sophie ; Perry, Alexis ; Szczesny, Bartosz ; Szabo, Csaba ; Winyard, Paul G. ; Whatmore, Jacqueline L. ; Wood, Mark E. ; Whiteman, Matthew. / The synthesis and functional evaluation of a mitochondria-targeted hydrogen sulfide donor, (10-oxo-10-(4-(3-thioxo-3H-1,2-dithiol-5-yl)phenoxy)decyl) triphenylphosphonium bromide (AP39). In: MedChemComm. 2014 ; Vol. 5, No. 6. pp. 728-736.
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