Isolation and characterization of a monoamine oxidase inhibitor from tobacco leaves.
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 microM) and MAO-B (K(i) = 6 microM), 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.
Khalil
A A
AA
Department of Chemistry, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061-0212, USA.
Steyn
S
S
Castagnoli
N
N
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D002855:Chromatography, Thin Layer; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D005753:Gastric Mucosa / Q000201:enzymology; D006801:Humans; D007413:Intestinal Mucosa / Q000201:enzymology; D007700:Kinetics; D008930:Mitochondria, Liver / Q000201:enzymology; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000737:chemistry* / Q000302:isolation & purification* / Q000494:pharmacology; D010215:Papio; D018515:Plant Leaves / Q000737:chemistry; D010947:Plants, Toxic; D011726:Pyridinium Compounds / Q000378:metabolism; D014026:Nicotiana / Q000737:chemistry*
D008996:Monoamine Oxidase Inhibitors; D011726:Pyridinium Compounds; C044755:1-methyl-4-phenyl-2,3-dihydropyridinium; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D008995:Monoamine Oxidase