In vivo antimalarial activity of the beta-carboline alkaloid manzamine A.
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.
Ang
K K
KK
Department of Biological Sciences, National University of Singapore, Singapore 119260, Singapore.
Holmes
M J
MJ
Higa
T
T
Hamann
M T
MT
Kara
U A
UA
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use; D002227:Carbazoles; D007211:Indoles / Q000494:pharmacology* / Q000627:therapeutic use; D008288:Malaria / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008854:Microscopy, Electron; D010962:Plasmodium berghei / Q000187:drug effects* / Q000254:growth & development / Q000648:ultrastructure; D011758:Pyrroles / Q000494:pharmacology* / Q000627:therapeutic use
D000962:Antimalarials; D002227:Carbazoles; D007211:Indoles; D011758:Pyrroles; C078290:manzamine A