Antioxidative properties of harmane and beta-carboline alkaloids.
beta-Carboline alkaloids are derived as a result of condensation between indoleamine (e.g. tryptamine) and short-chain carboxylic acid (e.g. pyruvic acid) or aldehyde (e.g. acetaldehyde), a reaction that occurs readily at room temperature. These compounds have been found endogenously in human and animal tissues and may be formed as a byproduct of secondary metabolism: their endogenous functions however, are not well understood. Indoles and tryptophan derivatives exhibit antioxidative actions by scavenging free radicals and forming resonance stabilized indolyl radicals. Harmane and related compounds exhibited concentration-dependent inhibition of lipid peroxidation (measured as thiobarbiturate reactive products) in a hepatic microsomal preparation incubated with either enzymatic dependent (Fe3+ ADP/NADPH) or non-enzymatic dependent (Fe3+ ADP/dihydroxyfumarate) oxygen radical producing systems. Alkaloids with hydroxyl substitution and a partially desaturated pyridyl ring were found to have the highest antioxidative potencies. Substitution of a hydroxyl group by a methoxyl group at the 6-position resulted in a decrease of greater than 10-fold in the antioxidative activities. Harmane showed high efficacy in an enzymatic system but low efficacy in a non-enzymatic system. The antioxidative effects of harmane in the former system may be attributed to its ability to inhibit oxidative enzymes in the microsomal system. These results suggest that beta-carbolines may also serve as endogenous antioxidants.
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Department of Medicine, George Washington University, Washington, DC 20037.
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D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002243:Carbolines / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005609:Free Radicals; D006246:Harmaline / Q000031:analogs & derivatives / Q000494:pharmacology; D006247:Harmine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism; D008956:Models, Chemical; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D013858:Thiobarbiturates; D014363:Tryptamines / Q000737:chemistry / Q000494:pharmacology*
D000975:Antioxidants; D002243:Carbolines; D005609:Free Radicals; D013858:Thiobarbiturates; D014363:Tryptamines; C007904:harmalol; C030820:tryptamine; C001326:harmol; D006247:Harmine; C005010:harman; D006246:Harmaline; C029684:thiobarbituric acid