harman and tetrahydroharmane

The chemical composition of total alkaloids from leaves and roots of Guiera senegalensis was investigated. Three beta-carboline alkaloids were purified: in addition to harman and tetrahydroharman, known in roots and leaves, harmalan (dihydroharman) was isolated for the first time from roots of Guiera senegalensis. Guieranone A, a naphthyl butenone, was also purified from leaves and roots. The in vitro antiplasmodial activity and the cytotoxicity of extracts and pure compounds were evaluated. Each total alkaloid extract and beta-carboline alkaloids presented an interesting antiplasmodial activity associated with a low cytotoxicity. Harmalan was less active than harman and tetrahydroharman. Guieranone A showed a strong antiplasmodial activity associated with a high cytotoxicity toward human monocytes. Its cytotoxicity was performed against two cancer cell lines and normal skin fibroblasts in order to study its anticancer potential: guieranone A presented a strong cytotoxicity against each cell strains. Finally, we evaluated the potent synergistic antimalarial interaction between Guiera senegalensis and two plants commonly associated in traditional remedies: Mitragyna inermis and Pavetta crassipes. Three associations evaluated were additive. A synergistic effect was shown between total alkaloids extracted from leaves of Guiera senegalensis and those of Mitragyna inermis. This result justified the traditional use of the plants in combination to treat malaria.

Topics: Alkaloids; Animals; Antimalarials; Butanones; Carbolines; Cell Survival; Combretaceae; Drug Synergism; Harmaline; Harmine; HeLa Cells; Humans; Inhibitory Concentration 50; Monocytes; Naphthalenes; Oxindoles; Parasitic Sensitivity Tests; Plant Extracts; Plant Leaves; Plant Roots; Plasmodium falciparum; Rubiaceae

1-Methyl-1,2,3,4-tetrahydro-beta-carboline-1-carboxylic acid (1-carboxytetrahydroharman, 1-CTHH) has been detected in the brain of rats following intracerebroventricular injection of tryptamine and pyruvic acid. We now report the metabolism of this compound. Following intraperitoneal injection of 1-CTHH into rats, harmalan was found to be the major metabolite besides tetrahydroharman (THH) and harman. A high concentration of THH was measured in the lung while most of harman was found in the urine. Harmalan and THH could be detected in the brain in low concentrations. The products were separated following extraction from tissues by high-performance liquid chromatography (HPLC) on a reversed phase C18-DB column. The identity of the metabolites was confirmed by mass spectrometry (MS) analysis. The results demonstrate the role of 1-CTHH as a precursor of the biologically active compounds harmalan, THH and harman.

Topics: Animals; Brain; Carbolines; Chromatography, High Pressure Liquid; Female; Harmaline; Harmine; Injections, Intraperitoneal; Rats; Rats, Inbred Strains; Viscera

Acetylcholinesterase (acetylcholine acetylhydrolase, EC 3.1.1.7) activity and muscarinic receptor binding of homogenates from several brain structures were inhibited by beta-carbolines. The inhibition was of the noncompetitive type in the case of the enzyme and of the mixed type in the case of the receptor binding. This effect was most strongly manifested by pyridoindoles(harmane, norharmane), i.e., carbolines containing an aromatic C ring than by the corresponding piperidoindoles (tetrahydroharmane, tetrahydronorharmane), i.e., those with a reduced C ring. The activity of choline acetyltransferase (acetyl-CoA:choline O-acetyltransferase, EC 2.3.1.6) was not altered. These data are further evidence of the interactions between indoleamine derivatives and the cholinergic system. The results are discussed in terms of their possible biological significance.

Topics: Acetylcholinesterase; Alkaloids; Animals; Brain; Carbolines; Cattle; Choline O-Acetyltransferase; Erythrocytes; Harmaline; Harmine; Indoles; Kinetics; Male; Rats; Rats, Inbred Strains; Receptors, Cholinergic; Receptors, Muscarinic; Structure-Activity Relationship