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)

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.