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. 2000 Jun;44(6):1645-9.
doi: 10.1128/AAC.44.6.1645-1649.2000.

In vivo antimalarial activity of the beta-carboline alkaloid manzamine A

K K Ang  1 , M J Holmes, T Higa, M T Hamann, U A Kara
Affiliations

In vivo antimalarial activity of the beta-carboline alkaloid manzamine A

K K Ang et al. Antimicrob Agents Chemother. 2000 Jun.

Abstract

Manzamine A, a beta-carboline alkaloid present in several marine sponge species, inhibits the growth of the rodent malaria parasite Plasmodium berghei in vivo. More than 90% of the asexual erythrocytic stages of P. berghei were inhibited after a single intraperitoneal injection of manzamine A into infected mice. A remarkable aspect of manzamine A treatment is its ability to prolong the survival of highly parasitemic mice, with 40% recovery 60 days after a single injection. Oral administration of an oil suspension of manzamine A also produced significant reductions in parasitemia. The plasma manzamine A concentration peaked 4 h after injection and remained high even at 48 h. Morphological changes of P. berghei were observed 1 h after treatment of infected mice. (-)-8-Hydroxymanzamine A also displayed antimalarial activity, whereas manzamine F, a ketone analog of manzamine A, did not. Our results suggest that manzamine A and (-)-8-hydroxymanzamine A are promising new antimalarial agents.

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Figures

FIG. 1
FIG. 1
Structures of manzamines tested for antimalarial activity. The structures of manzamine A (A), (−)-8-hydroxymanzamine A (B), and manzamine F (C) are shown.
FIG. 2
FIG. 2
Transmission electron micrographs of P. berghei treated with manzamine A. (A) Mouse erythrocyte containing untreated P. berghei. Magnification, ×19,000. (B) P. berghei 1 h after administration of manzamine A. Magnification, ×29,000. Electron-dense vesicles are present within the cytoplasm of the parasite (arrows). (C) P. berghei 4 h after manzamine A administration. Magnification, ×29,000. (D) P. berghei 12 h after treatment. Magnification, ×19,000. Increasing numbers of vesicles are present within the parasite.
FIG. 3
FIG. 3
Plasma manzamine A concentration (mean ± standard error) following intraperitoneal administration of 100 μmol/kg into P. berghei-infected mice (n = 5 for each time point).
See this image and copyright information in PMC

References

    1. Ager A L., Jr . Rodent malaria models. In: Peters W, Richards W H G, editors. Antimalarial drugs. I. Biological background, experimental methods and drug resistance. Berlin, Germany: Springer-Verlag; 1984. pp. 225–264.
    1. Cox F E G. Major animal models in malarial research: rodent. In: Wernsdorfer W H, McGregor I, editors. Malaria. Principles and practice of malariology. Edinburgh, Scotland: Churchill Livingstone, Ltd.; 1988. pp. 1503–1543.
    1. Edrada R A, Proksch P, Wray V, Witte L, Muller W E G, Van Soest R W M. Four new bioactive manzamine-type alkaloids from the Philippine marine sponge Xestospongia ashmorica. J Nat Prod. 1996;59:1056–1060. - PubMed
    1. El Sayed K A, Dunbar D C, Goins D K, Cordova C R, Perry T L, Wesson K J, Sanders S C, Janus S A, Hamann M T. The marine environment: a resource for prototype antimalarial agents. J Nat Tox. 1996;5:261–285.
    1. Heiffer M H, Davidson D E, Jr, Korte D W., Jr . Preclinical testing. In: Peters W, Richards W H G, editors. Antimalarial drugs. I. Biological background, experimental methods and drug resistance. Berlin, Germany: Springer-Verlag; 1984. pp. 351–373.

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