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

Manzamine A, a beta-carboline alkaloid present in several marine sponge spe cies, inhibits the growth of the rodent malaria parasite Plasmodium berghei in vivo. More than 90% of the asexual erythrocytic stages of P. berghei we re inhibited after a single intraperitoneal injection of manzamine A into i nfected mice. A remarkable aspect of manzamine A treatment is its ability t o prolong the survival of highly parasitemic mice, with 40% recovery 60 day s after a single injection. Oral administration of an oil suspension of man zamine A also produced significant reductions in parasitemia, The plasma ma nzamine A concentration peaked 4 h after injection and remained high even a t 48 h, Morphological changes of P, berghei were observed 1 h after treatme nt of infected mice. (-)-8-Hydroxymanzamine A also displayed antimalarial a ctivity, 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.