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4'-alkylated analogs of 1-methyl-4-phenylpyridinium ion are potent inhibitors of mitochondrial respiration.

作者信息

Youngster S K, Gluck M R, Heikkila R E, Nicklas W J

机构信息

Department of Neurology, UMDNJ-Robert Wood Johnson Medical School, Piscataway 08854.

出版信息

Biochem Biophys Res Commun. 1990 Jun 15;169(2):758-64. doi: 10.1016/0006-291x(90)90396-5.

DOI:10.1016/0006-291x(90)90396-5
PMID:2357232
Abstract

1-Methyl-4-phenylpyridinium ion, a major brain metabolite of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, is an inhibitor of Complex I of the mitochondrial respiratory chain. We have synthesized several analogs of 1-methyl-4-phenylpyridinium ion containing various alkyl groups in the 4' position of the phenyl ring and have tested them for their abilities to inhibit the oxidation of NADH-linked substrates by intact mouse liver mitochondria. These compounds are considerably more potent inhibitors than MPP+ itself, with potency increasing as the length of the alkyl chain increases. The most potent inhibitor, 1-methyl-4-(4'heptylphenyl)pyridinium ion, was about 200 times as effective as MPP+. These analogs should prove to be useful tools for studying the nature of the process whereby MPP+ and its pyridinium analogs interact with Complex I to inhibit mitochondrial respiration.

摘要

相似文献

1
4'-alkylated analogs of 1-methyl-4-phenylpyridinium ion are potent inhibitors of mitochondrial respiration.
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2
Structural dependence of the inhibition of mitochondrial respiration and of NADH oxidase by 1-methyl-4-phenylpyridinium (MPP+) analogs and their energized accumulation by mitochondria.1-甲基-4-苯基吡啶鎓（MPP+）类似物对线粒体呼吸和NADH氧化酶的抑制作用及其在线粒体中的能量依赖性积累的结构依赖性
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3
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Dopaminergic neurotoxicity of 1-methyl-4-phenylpyridinium analogs in cultured neurons: relationship to the dopamine uptake system and inhibition of mitochondrial respiration.
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Biochem Biophys Res Commun. 1987 Oct 29;148(2):684-93. doi: 10.1016/0006-291x(87)90931-4.

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Evidence that the inhibition sites of the neurotoxic amine 1-methyl-4-phenylpyridinium (MPP+) and of the respiratory chain inhibitor piericidin A are the same.
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