Isolation and characterization of a monoamine oxidase inhibitor from tobacco leaves
Isolation and characterization of a monoamine oxidase inhibitor from tobacco leaves
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DOI：
10.1021/tx990146f
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发表时间：
2000-01-01
影响因子：
4.1
通讯作者：
Castagnoli, N
中科院分区：
文献类型：
--
作者：
Khalil, AA;Steyn, S;Castagnoli, N
最近的正电子发射断层扫描成像研究表明，吸烟者大脑中的单胺氧化酶A和B（MAO-A和MAO-B）活性显著降低，在前吸烟者中观察到正常水平的活性，表明烟草烟雾中存在一种或多种可能抑制这些酶的化合物。在本文中，我们报告的结果，努力确定化合物存在于烤烟烟叶，抑制单胺氧化酶。通过评估烟草叶提取物对肝脏线粒体MAO-B催化的1-甲基-4-（1-甲基吡咯-2-基）-1，2，3，6-四氢吡啶氧化为相应的二氢吡啶代谢物的抑制特性来指导分离过程。从烤烟烟叶提取物的分级分离导致人MAO-A（Ki = 3 μ M）和MAO-B（Ki = 6 μ M）的竞争性抑制剂的分离，其结构可以通过经典的光谱分析来指定，并通过合成来证实。这些信息可能有助于深入了解烟草制品的药理学和毒理学的某些方面。
Recent positron emission tomography imaging studies have demonstrated a significant decrease in both monoamine oxidase A and B (MAO-A and MAO-B) activities in the brains of smokers, Normal levels of activity are observed in former smokers, suggesting the presence of one or more compounds in tobacco smoke that may inhibit these enzymes. In this paper, we report the results of efforts to identify compounds present in flue-cured tobacco leaves that inhibit MAO. The isolation procedure was guided by estimating the inhibitory properties of tobacco leaf extracts on the liver mitochondrial MAO-B-catalyzed oxidation of 1-methyl-4-(1-methylpyrrol-2-yl)-1,2,3,6-tetrahydropyridine to the corresponding dihydropyridinium metabolite. Fractionation of extracts from flue-cured tobacco leaves led to the isolation of a competitive inhibitor of human MAO-A (K-i = 3 mu M) and MAO-B (K-i= 6 mu M), the structure of which could be assigned by classical spectroscopic analysis and confirmed by synthesis. This information may help to provide insights into some aspects of the pharmacology and toxicology of tobacco products.