Skip to main content
PMC home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1997 Nov;41(11):2533–2539. doi: 10.1128/aac.41.11.2533

Naphthylisoquinoline alkaloids against malaria: evaluation of the curative potentials of dioncophylline C and dioncopeltine A against Plasmodium berghei in vivo.

G François 1, G Timperman 1, W Eling 1, L A Assi 1, J Holenz 1, G Bringmann 1
PMCID: PMC164157  PMID: 9371362

Abstract

Naphthylisoquinoline alkaloid-containing extracts from species of the families Dioncophyllaceae and Ancistrocladaceae and purified alkaloids derived therefrom were shown to exhibit antiparasitic activity in Plasmodium berghei-infected mice. Several extracts and alkaloids, especially dioncophylline C and dioncopeltine A, isolated from Triphyophyllum peltatum (Dioncophyllaceae), displayed high levels of activity. Dioncopeltine A was able to suppress parasitemia almost totally, while dioncophylline C cured infected mice completely after oral treatment with 50 mg kg of body weight(-1) day(-1) for 4 days without noticeable toxic effects. Analysis of the dose-response relationship of dioncophylline C revealed a 50% effective dosage (ED50) of 10.71 mg kg(-1) day(-1) under these conditions. Although four daily treatments with 50 mg kg(-1) day(-1) are needed to achieve radical cure, one oral dose is sufficient to kill 99.6% of the parasites. Intravenous application of dioncophylline C is even more effective, with an ED50 of 1.90 mg kg(-1) day(-1) and no noticeable toxic effects. The compound also suppressed more established P. berghei infections when orally applied at day 3 after infection. Both dioncopeltine A and dioncophylline C are active against the chloroquine-resistant P. berghei Anka CRS parasites. Sustained release of these compounds at 20 mg kg(-1) day(-1) by implanted miniosmotic pumps exhibited curative effects. The naphthylisoquinoline alkaloids are therefore promising new antimalarial agents.

Full Text

The Full Text of this article is available as a PDF (207.8 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Basco L. K., Ringwald P., Simon F., Doury J. C., Le Bras J. Evolution of chloroquine resistance in central and west Africa. Trop Med Parasitol. 1993 Jun;44(2):111–112. [PubMed] [Google Scholar]
  2. Bunnag D., Karbwang J., Thanavibul A., Chittamas S., Ratanapongse Y., Chalermrut K., Bangchang K. N., Harinasuta T. High dose of primaquine in primaquine resistant vivax malaria. Trans R Soc Trop Med Hyg. 1994 Mar-Apr;88(2):218–219. doi: 10.1016/0035-9203(94)90305-0. [DOI] [PubMed] [Google Scholar]
  3. François G., Bringmann G., Dochez C., Schneider C., Timperman G., Aké Assi L. Activities of extracts and naphthylisoquinoline alkaloids from Triphyophyllum peltatum, Ancistrocladus abbreviatus and Ancistrocladus barteri against Plasmodium berghei (Anka strain) in vitro. J Ethnopharmacol. 1995 May;46(2):115–120. doi: 10.1016/0378-8741(95)01240-e. [DOI] [PubMed] [Google Scholar]
  4. François G., Timperman G., Holenz J., Aké Assi L., Geuder T., Maes L., Dubois J., Hanocq M., Bringmann G. Naphthylisoquinoline alkaloids exhibit strong growth-inhibiting activities against Plasmodium falciparum and P. berghei in vitro--structure-activity relationships of dioncophylline C. Ann Trop Med Parasitol. 1996 Apr;90(2):115–123. doi: 10.1080/00034983.1996.11813035. [DOI] [PubMed] [Google Scholar]
  5. François G., Timperman G., Steenackers T., Assi L. A., Holenz J., Bringmann G. In vitro inhibition of liver forms of the rodent malaria parasite Plasmodium berghei by naphthylisoquinoline alkaloids--structure-activity relationships of dioncophyllines A and C and ancistrocladine. Parasitol Res. 1997;83(7):673–679. doi: 10.1007/s004360050318. [DOI] [PubMed] [Google Scholar]
  6. Karbwang J., Na-Bangchang K., Thanavibul A., Ditta-in M., Harinasuta T. A comparative clinical trial of two different regimens of artemether plus mefloquine in multidrug resistant falciparum malaria. Trans R Soc Trop Med Hyg. 1995 May-Jun;89(3):296–298. doi: 10.1016/0035-9203(95)90549-9. [DOI] [PubMed] [Google Scholar]
  7. Mishra S. K., Asthana O. P., Mohanty S., Patnaik J. K., Das B. S., Srivastava J. S., Satpathy S. K., Dash S., Rath P. K., Varghese K. Effectiveness of alpha,beta-arteether in acute falciparum malaria. Trans R Soc Trop Med Hyg. 1995 May-Jun;89(3):299–301. doi: 10.1016/0035-9203(95)90550-2. [DOI] [PubMed] [Google Scholar]
  8. Mons B., Sinden R. E. Laboratory models for research in vivo and in vitro on malaria parasites of mammals: Current status. Parasitol Today. 1990 Jan;6(1):3–7. doi: 10.1016/0169-4758(90)90377-g. [DOI] [PubMed] [Google Scholar]
  9. Murphy G. S., Basri H., Purnomo, Andersen E. M., Bangs M. J., Mount D. L., Gorden J., Lal A. A., Purwokusumo A. R., Harjosuwarno S. Vivax malaria resistant to treatment and prophylaxis with chloroquine. Lancet. 1993 Jan 9;341(8837):96–100. doi: 10.1016/0140-6736(93)92568-e. [DOI] [PubMed] [Google Scholar]
  10. Myat-Phone-Kyaw, Myint-Oo, Myint-Lwin, Thaw-Zin, Kyin-Hla-Aye, Nwe-Nwe-Yin Emergence of chloroquine-resistant Plasmodium vivax in Myanmar (Burma). Trans R Soc Trop Med Hyg. 1993 Nov-Dec;87(6):687–687. doi: 10.1016/0035-9203(93)90294-z. [DOI] [PubMed] [Google Scholar]
  11. Olliaro P. L., Trigg P. I. Status of antimalarial drugs under development. Bull World Health Organ. 1995;73(5):565–571. [PMC free article] [PubMed] [Google Scholar]
  12. Onori E. The problem of Plasmodium falciparum drug resistance in Africa south of the Sahara. Bull World Health Organ. 1984;62 (Suppl):55–62. [PMC free article] [PubMed] [Google Scholar]
  13. Peters W., Porter M. The chemotherapy of rodent malaria, XXVI. The potential value of WR 122,455 (a 9-phenanthrenemethanol) against drug-resistant malaria parasites. Ann Trop Med Parasitol. 1976 Sep;70(3):271–281. doi: 10.1080/00034983.1976.11687123. [DOI] [PubMed] [Google Scholar]
  14. Petralanda I. Quality of antimalarial drugs and resistance to Plasmodium vivax in Amazonian region. Lancet. 1995 Jun 3;345(8962):1433–1433. doi: 10.1016/s0140-6736(95)92620-8. [DOI] [PubMed] [Google Scholar]
  15. Porter M., Peters W. The chemotherapy of rodent malaria, XXV. Antimalarial activity of WR 122,455 (a 9-phenanthrenemethanol) in vivo and in vitro. Ann Trop Med Parasitol. 1976 Sep;70(3):259–270. doi: 10.1080/00034983.1976.11687122. [DOI] [PubMed] [Google Scholar]
  16. Singh B., Agrawal P. K., Thakur R. S. Isolation of trans-Phytol from Phyllanthus niruri1. Planta Med. 1991 Feb;57(1):98–98. doi: 10.1055/s-2006-960039. [DOI] [PubMed] [Google Scholar]
  17. Warrell D. A. Pathophysiology of severe falciparum malaria in man. Parasitology. 1987;94 (Suppl):S53–S76. doi: 10.1017/s0031182000085826. [DOI] [PubMed] [Google Scholar]
  18. White N. J. Antimalarial drug resistance: the pace quickens. J Antimicrob Chemother. 1992 Nov;30(5):571–585. doi: 10.1093/jac/30.5.571. [DOI] [PubMed] [Google Scholar]
  19. White N. J. The treatment of malaria. N Engl J Med. 1996 Sep 12;335(11):800–806. doi: 10.1056/NEJM199609123351107. [DOI] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES