Inhibition of monoamine oxidase A by beta-carboline derivatives
Inhibition of monoamine oxidase A by beta-carboline derivatives
复制标题
DOI：
10.1006/abbi.1996.9771
复制
发表时间：
1997-01-01
影响因子：
3.9
通讯作者：
Ramsay, RR
中科院分区：
文献类型：
--
作者：
Kim, H;Sablin, SO;Ramsay, RR
研究了9种β -卡波林衍生物和4种3,4-二氢化合物与纯化的单胺氧化酶A的相互作用。所有测试的化合物都是选择性MAO A的可逆竞争性抑制剂，与先前的膜制剂研究一致。在更有效的抑制剂存在下，MAO A对kynuramine的氧化在达到稳定状态之前表现出滞后期。结果表明，1-甲基和7-甲氧基取代基对MAO - A的抑制作用明显增强，其中鼠胺、2-甲基鼠胺、2,9-二甲基鼠胺和鼠胺对MAO - A的抑制作用最强，K-i值分别为5、69、15和48 nM。这些抑制剂与共价结合的黄素相互作用，引起明显的光谱变化，其大小与抑制效果相关。更有效的抑制剂可能是MAO A. (C) 1997学术出版社，Inc。
beta-Carbolines are endogenous inhibitors of monoamine oxidase (MAO), The interaction of nine beta-carboline derivatives and four 3,4-dihydro forms with purified MAO A was investigated. All the compounds tested were reversible competitive inhibitors selective for MAO A, in agreement with previous studies on membrane preparations. The oxidation of kynuramine by MAO A in the presence of the more effective inhibitors showed a lag period before reaching the steady state. In general, the 1-methyl and 7-methoxy substituents increased the potency, Harmine, 2-methylharminium, 2,9-dimethylharminium, and harmaline were the most effective inhibitors of the purified MAO A, with low K-i values of 5, 69, 15, and 48 nM, respectively. The inhibitors interacted with the covalently bound flavin to induce distinct spectral changes, the magnitude of which correlated with the efficacy of the inhibition, The more effective inhibitors could be in situ inhibitors of MAO A. (C) 1997 Academic Press, Inc.