Download PDF
Planta Med 2013; 79(05): 334-337
DOI: 10.1055/s-0032-1328283
Biological and Pharmacological Activity
Letters
Georg Thieme Verlag KG Stuttgart · New York

Unusual Amino Acids and Monofluoroacetate from Dichapetalum michelsonii (Umutambasha), a Toxic Plant from Rwanda

Virginie Esters
1   Laboratory of Pharmacognosy, Centre Interfacultaire de Recherche du Médicament (CIRM), Department of Pharmacy, University of Liège, Liège, Belgium
,
Charles Karangwa
2   Laboratory of Pharmacology and Toxicology, Department of Pharmacy, Faculty of Medicine, National University of Rwanda, Butare, Rwanda
,
Monique Tits
1   Laboratory of Pharmacognosy, Centre Interfacultaire de Recherche du Médicament (CIRM), Department of Pharmacy, University of Liège, Liège, Belgium
,
Pierre Francotte
3   Laboratory of Medicinal Chemistry, Centre Interfacultaire de Recherche du Médicament (CIRM), Department of Pharmacy, University of Liège, Liège, Belgium
,
Bernard Pirotte
3   Laboratory of Medicinal Chemistry, Centre Interfacultaire de Recherche du Médicament (CIRM), Department of Pharmacy, University of Liège, Liège, Belgium
,
Anne-Catherine Servais
4   Laboratory of Analytical Pharmaceutical Chemistry, Centre Interfacultaire de Recherche du Médicament (CIRM), Department of Pharmacy, University of Liège, Liège, Belgium
,
Marianne Fillet
4   Laboratory of Analytical Pharmaceutical Chemistry, Centre Interfacultaire de Recherche du Médicament (CIRM), Department of Pharmacy, University of Liège, Liège, Belgium
,
Jacques Crommen
4   Laboratory of Analytical Pharmaceutical Chemistry, Centre Interfacultaire de Recherche du Médicament (CIRM), Department of Pharmacy, University of Liège, Liège, Belgium
,
Elmar Robbrecht
5   Department of Vascular Plants (Spermatophyta-Pteridophyta), National Botanic Garden of Belgium, Meise, Belgium
,
Arlette Minet
6   Center for Cellular and Molecular Neurobiology (CNCM), University of Liège, Liège, Belgium
,
Thierry Grisar
6   Center for Cellular and Molecular Neurobiology (CNCM), University of Liège, Liège, Belgium
,
Luc Angenot
1   Laboratory of Pharmacognosy, Centre Interfacultaire de Recherche du Médicament (CIRM), Department of Pharmacy, University of Liège, Liège, Belgium
,
Michel Frederich
1   Laboratory of Pharmacognosy, Centre Interfacultaire de Recherche du Médicament (CIRM), Department of Pharmacy, University of Liège, Liège, Belgium
› Author Affiliations
Further Information

Publication History

received 19 August 2012
revised 28 January 2013

accepted 30 January 2013

Publication Date:
01 March 2013 (online)

Also available at
    Permissions and Reprints

Abstract

In the course of our investigations on Umutambasha in order to identify its convulsant principles, small quantities of monofluoroacetate were observed in stem bark, leaves, and fruits of this plant newly identified as Dichapetalum michelsonii Hauman. Conclusive evidence for a monofluoroacetate presence came from its isolation from the freeze-dried extract of stem bark. Three free unusual amino acids, named N-methyl-α-alanine, N-methyl-β-alanine, and 2,7-diaminooctan-1,8-dioic acid, described for the first time in a plant, and known trigonelline were also isolated from the stem bark of D. michelsonii. Structure elucidations were mainly achieved by spectroscopic methods (1H-NMR, 2D-NMR, MS) and by comparison with authentic references. These unusual amino acids were detected by a fast, reliable TLC analysis in all our batches of Umutambasha, suggesting that they could be used for identification purposes in case of human or livestock intoxications. Finally, EEG recordings and behavioural observations performed in mice suggested that the convulsive patterns produced by Umutambasha are the consequence of monofluoroacetate presence in D. michelsonii.

Key words

Dichapetalum michelsonii - Dichapetalaceae - Umutambasha - sodium monofluoroacetate - 2,7-diaminooctan-1,8-dioic acid - Magnistipula butayei

Supporting Information

 

  • References

  • 1 Thienpont D, Vandervelden M. Dichapetalum michelsonii Hauman. A new toxic plant for animals of Ruanda-Burundi. Rev Elev Med Vet Pays Trop 1961; 14: 209-211
    PubMedSearch in Google Scholar
  • 2 Desouter S. Umutambasha. In: Desoutier S, editor Pharmacopée humaine et vétérinaire du Rwanda. Tervuren: Musée royal de lʼAfrique Centrale; 1991: 104
    Search in Google Scholar
  • 3 Karangwa C, Esters V, Frederich M, Tits M, Kadima JN, Damas J, Noirfalise A, Angenot L. Chemical and biological investigations of a toxic plant from Central Africa, Magnistipula butayei subsp. montana . J Ethnopharmacol 2006; 103: 433-438
    CrossrefPubMedSearch in Google Scholar
  • 4 Karangwa C, Esters V, Tits M, Minet A, Boland A, Seutin V, Noirfalise A, Angenot L, Grisar T, Foidart A. Characterization of the neurotoxicity induced by the extract of Magnistipula butayei (Chrysobalanaceae) in rat: effects of a new natural convulsive agent. Toxicon 2007; 49: 1109-1119
    CrossrefPubMedSearch in Google Scholar
  • 5 Karangwa C, Esters V, Frédérich M, Tits M, Kadima JN, Damas J, Noirfalise A, Angenot L. Erratum to “Chemical and biological investigations of a toxic plant from Central Africa, Magnistipula butayei subsp. montana” [J Ethnopharmacol 2006; 103: 433–438].. J Ethnopharmacol 2009; 125: 502
    CrossrefPubMedSearch in Google Scholar
  • 6 Karangwa C, Esters V, Tits M, Minet A, Boland A, Seutin V, Noirfalise A, Angenot L, Grisar T, Foidart A. Erratum to «Characterization of the neurotoxicity induced by the extract of Magnistipula butayei (Chrysobalanaceae) in rat: effects of a new natural convulsive agent» published in Toxicon 2007; 49: 1109–1119. Toxicon 2010; 55: 675
    CrossrefPubMedSearch in Google Scholar
  • 7 Hauman L. Deux Dichapetalum nouveaux dʼAfrique Centrale. Bull Jardin Bot de lʼÉtat (Bruxelles) 1958; 28: 73-75
    PubMedSearch in Google Scholar
  • 8 Breteler FJ. The African Dichapetalaceae VIII: a taxonomical revision. Wageningen: Mededelingen Landbouwhogeschool; 1982: 35-39
    Search in Google Scholar
  • 9 Marais JSC. Isolation of the toxic principle “K cymonate” from “Gifblaar” Dichapetalum cymosum. Onderstepoort. J Vet Sci Anim Ind 1943; 18: 203-206
    PubMedSearch in Google Scholar
  • 10 OʼHagan D, Perry R, Lock JM, Meyer M, Dasaradhi L, Hamilton JTG, Harper DB. High levels of monofluoroacetate in Dichapetalum braunii . Phytochemistry 1993; 33: 1043-1045
    CrossrefPubMedSearch in Google Scholar
  • 11 Harper DB, OʼHagan D. The fluorinated natural products. Nat Prod Rep 1994; 11: 123-133
    CrossrefPubMedSearch in Google Scholar
  • 12 Krebs HC, Kemmerling W, Habermehl G. Qualitative and quantitative determination of fluoroacetic acid in Arrabidea bilabiata and Palicourea marcgravii by 19F-NMR spectroscopy. Toxicon 1994; 32: 909-913
    CrossrefPubMedSearch in Google Scholar
  • 13 Baron ML, Bothroyd CM, Rogers GI, Staffa A, Rae ID. Detection and measurement of fluoroacetate in plant extracts by fluorine-19 NMR. Phytochemistry 1987; 26: 2293-2295
    CrossrefPubMedSearch in Google Scholar
  • 14 Vickery B, Vickery ML, Ashu JT. Analysis of plants for fluoroacetic acids. Phytochemistry 1973; 12: 145-147
    CrossrefPubMedSearch in Google Scholar
  • 15 Eloff JN. The occurrence and other aspects of N-methyl alanine (NMA) and N-methyl serine (NMS) in Dichapetalum cymosum (ENGL.) (GIFBLAAR) and other members of the Dichapetalaceae. Trans Royal Soc S Afr 1972; 40: 41-47
    PubMedSearch in Google Scholar
  • 16 Shani J, Goldschmied A, Ahronson Z, Sulman F. Hypoglycaemic effect of Trigonella foenum-graecum and Lupinus termis (Leguminosae) seeds and their major alkaloids in alloxan diabetic and normal rats. Arch Int Pharmacodyn Ther 1974; 210: 27-36
    PubMedSearch in Google Scholar
  • 17 Hossain SJ, Aoshima H, Koda H, Kiso Y. Effects of coffee components on the response of GABAA receptors expressed in Xenopus oocytes . J Agric Food Chem 2003; 51: 7568-7575
    CrossrefPubMedSearch in Google Scholar
  • 18 Temraz TA, Houssen WE, Jaspars M, Woolley DR, Wease KN, Davies SN, Scott RH. A pyridinium derivative from Red Sea soft corals inhibited voltage-activated potassium conductances and increased excitability of rat cultured sensory neurones. BMC Pharmacol 2006; 6: 10
    CrossrefPubMedSearch in Google Scholar
  • 19 Okamoto K, Quastel JH. Effects of N-methylamino acids and convulsants on spontaneous action potentials in guinea-pig cerebellar slices. Br J Pharmacol 1977; 59: 551-560
    CrossrefPubMedSearch in Google Scholar
  • 20 Curtis DR, Phillis JW, Watkins JC. Action of amino-acids on the isolated hemisected spinal cord of the toad. Br J Pharmacol 1961; 16: 262-283
    PubMedSearch in Google Scholar
  • 21 Evans RH, Francis AA, Hunt K, Oakes DJ, Watkins JC. Antagonism of excitatory amino acid-induced responses and of synaptic excitation in the isolated spinal cord of the frog. Br J Pharmacol 1979; 67: 591-603
    CrossrefPubMedSearch in Google Scholar
  • 22 Koerner JF, Cotman CW. Response of Schaffer collateral-CA 1 pyramidal cell synapses of the hippocampus to analogues of acidic amino acids. Brain Res 1982; 251: 105-115
    CrossrefPubMedSearch in Google Scholar
  • 23 Fonnum F, Johnsen A, Hassel B. Use of fluorocitrate and fluoroacetate in the study of brain metabolism. Glia 1997; 21: 106-113
    CrossrefPubMedSearch in Google Scholar
  • 24 Proudfoot AT, Bradberry SM, Vale JA. Sodium fluoroacetate poisoning. Toxicol Rev 2006; 25: 213-219
    CrossrefPubMedSearch in Google Scholar
  • 25 Goncharov NV, Jenkins RO, Radilov AS. Toxicology of fluoroacetate: a review, with possible directions for therapy research. J Appl Toxicol 2006; 26: 148-161
    CrossrefPubMedSearch in Google Scholar
  • 26 Stewart GG, Abbs ET, Roberts DJ. Biochemical effects of fluoroacetate administration in rat brain, heart and blood. Biochem Pharmacol 1970; 19: 1861-1866
    CrossrefPubMedSearch in Google Scholar
  • 27 Defernez M, Gunning YM, Parr AJ, Shepherd LVT, Davies HV, Colquhoun IJ. NMR and HPLC-UV profiling of potatoes with genetic modifications to metabolic pathways. J Agric Food Chem 2004; 52: 6075-6085
    CrossrefPubMedSearch in Google Scholar
  • 28 Troupin G. Flore des plantes ligneuses du Rwanda. Tervuren: Musée Royal de lʼAfrique Centrale; 1982: 747
    Search in Google Scholar