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

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.

• Authors: K K Ang, M J Holmes, T Higa, M T Hamann, U A Kara
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 44 Issue 6 Pg. 1645-9 (Jun 2000) ISSN: 0066-4804 [Print] United States
• PMID: 10817722 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antimalarials
• Carbazoles
• Indoles
• Pyrroles
• manzamine A

Topics

• Animals
• Antimalarials (pharmacology, therapeutic use)
• Carbazoles
• Indoles (pharmacology, therapeutic use)
• Malaria (drug therapy)
• Male
• Mice
• Microscopy, Electron
• Plasmodium berghei (drug effects, growth & development, ultrastructure)
• Pyrroles (pharmacology, therapeutic use)