Differential sensitivity of erythrocytic stages of the rodent malaria parasite Plasmodium chabaudi chabaudi to dioncophylline B, a highly active naphthylisoquinoline alkaloid

Abstract

Four-week-old OF1 mice, infected with synchronized Plasmodium chabaudi chabaudi blood forms, were intraperitoneally injected with the naphthylisoquinoline alkaloid dioncophylline B (10 mg kg(-1) day(-1)) at three consecutive days. The respective groups were treated when rings, trophozoites, and schizonts were predominant. Microscopical observations of thin blood smears were made every two hours after the start of the experiment. A clear dependency of the effectiveness of dioncophylline B treatments on the timing of drug administration was demonstrated. Based upon the evolution of total parasitaemia and the survival rates, it was concluded that ring stages are insensitive to dioncophylline B, while the drug is highly effective when given at the trophozoite stage and partially effective when given at the schizont stage. Dioncophylline B seems to act by inhibiting the haemozoin degradation, as indicated by pigment clumping, and by impairing the segmentation of schizonts.

Ancistroheynine B and two further 7,3′-coupled naphthylisoquinoline alkaloids from Ancistrocladus heyneanus Wall.

“…Alkaloid 7 exhibited moderate antiplasmodial activities against the K1 strain of Plasmodium falciparum (resistant to chloroquine and pyrimethamine), slightly weaker than the known compounds 3 and 6 (Bringmann et al, 2004). These findings, although not reaching the good results of other naphthylisoquinolines (Bringmann et al, 2003a(Bringmann et al, , 2003bFrançois et al, 1997François et al, , 1999, gave an important contribution to our ongoing QSAR (Quantitative Structure-Activity Relationship) investigations (Bringmann and Rummey, 2003c;Stiefl et al, 2003).…”

A comparison of the stage-specific efficacy of chloroquine, artemether and dioncophylline B against the rodent malaria parasite Plasmodium chabaudi chabaudi in vivo

“…Total and dierential parasitaemias were determined. The developmental stages of P. chabaudi were identi®ed and found conform with previously described de®nitions (Landau 1965;Cambie et al 1991;Chimanuka et al 1997Chimanuka et al , 1999. All surviving mice were kept for several weeks to check for long-term toxic eects.…”

“…The experiments were designed according to previously described procedures (FrancË ois et al 1999), and are summarised here brie¯y. A suspension containing in vitro released merozoites was intravenously (i.v.)…”

“…Indeed, between 17.00 hours and 19.00 hours, the presence of ring forms and few schizonts was more expected (Chimanuka et al 1997(Chimanuka et al , 1999 than the observed abnormally pigmented IRBCs. Also, we noticed that the change in malaria parasite morphology was clear from 17.00 hours, and was completed 2 h later (Fig.…”

“…Dioncophylline B is a naturally occurring naphthylisoquinoline alkaloid with proven in vitro antimalarial activities against Plasmodium falciparum and in vivo against P. chabaudi chabaudi (FrancË ois et al 1994(FrancË ois et al , 1999, but its mode of action still remains to be determined. In this study, we have compared the therapeutic ecacy of artemether, chloroquine and dioncophylline B against ring, trophozoite and schizont forms of P. chabaudi chabaudi.…”