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)
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)
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DOI：
10.1039/c3md00323j
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发表时间：
2014-06-01
期刊：
影响因子：
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通讯作者：
Whiteman, Matthew
中科院分区：
文献类型：
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作者：
Le Trionnaire, Sophie;Perry, Alexis;Whiteman, Matthew
内源性气体介质硫化氢（H2S）的合成和生物利用度在许多疾病状态下受到干扰，包括那些涉及线粒体功能障碍的疾病。人们对开发产生H2S的药理学试剂有着浓厚的兴趣。我们合成了一种新的与线粒体靶向片段偶联的H2S供体分子（triphenylphosphonium; TPP+），并将该化合物与标准的不含TPP+的H2S供体（GYY4137）在抑制氧化应激诱导的内皮细胞死亡方面的效果进行了比较。我们的研究表明，线粒体靶向H2S供体是研究H2S在健康和疾病中的线粒体生理学的有用药理学工具。
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.