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

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.

Retarded development of exoerythrocytic stages of the rodent malaria parasite Plasmodium berghei in human hepatoma cells by extracts from Dioncophyllaceae and Ancistrocladaceae species.

Retarded development of exoerythrocytic stages of the rodent malaria parasite Plasmodium berghei in human hepatoma cells by extracts from Dioncophyllaceae and Ancistrocladaceae species. International Journal for Parasitology 27: 29-32. Naphthylisoquinoline alkaloid-containing extracts (10 micrograms ml-1) of species belonging to the Dioncophyllaceae and the Ancistrocladaceae, 2 small tropical plant families, display pronounced in vitro activities against exoerythrocytic stages of Plasmodium berghei (Anka), developing in human hepatoma cells (Hep G2). The highest activities were obtained with CH2Cl2 root and bark extracts, and a CH2Cl2/NH3 leaf extract from Triphyophyllum peltatum, a CH2Cl2/NH3 root extract from Ancistrocladus abbreviatus, and a CH2Cl2 leaf extract from A. tectorius. The degrees of growth inhibition ranged within 27.7-70.0%. The commercially available drug primaquine diphosphate (25 micrograms ml-1) caused a comparable effect (62.1%) in the same test system.

Constituents of Picralima nitida display pronounced inhibitory activities against asexual erythrocytic forms of Plasmodium falciparum in vitro.

The antiplasmodial activities of organic and aqueous extracts from the West African plant Picralima nitida (Apocynaceae) were examined in an in vitro model, against asexual erythrocytic forms of Plasmodium falciparum. Root and leaf extracts of this species had never been examined before. Several extracts displayed considerable inhibitory activities. The highest activities were found in root, stem bark and fruit rind extracts, with IC50 values of 0.188, 0.545 and 1.581 micrograms/ml, respectively. The leaf and seed extracts generally yielded much lower activity or were completely inactive.

Larvicidal activity of the naphthylisoquinoline alkaloid dioncophylline A against the malaria vector Anopheles stephensi.

The larvicidal activity of dionocophylline A, a naphthylisoquinoline alkaloid derived from the tropical vine Triphyophyllum peltatum (Dioncophyllaceae), was investigated against the malaria vector Anopheles stephensi. In direct and indirect inhibition assays it was demonstrated that the younger larval stages were very sensitive towards this natural product, with LC50 values below 1 mg/l. Pronounced effects were observed within 4 h of exposure. Aging larvae, however, were less sensitive, while pupae were totally insensitive to the action of dioncophylline A. The transformations from larvae to pupae and from pupae to adult mosquitoes remained unaffected. Therefore, dioncophylline A can be regarded as a promising specific larvicide.

Naphthylisoquinoline alkaloids exhibit strong growth-inhibiting activities against Plasmodium falciparum and P. berghei in vitro--structure-activity relationships of dioncophylline C.

The growth-inhibiting activities of naturally occurring naphthylisoquinoline alkaloids against asexual blood stages of Plasmodium falciparum (NF 54, clone A1A9) and P. berghei (Anka) were studied in vitro. Three of the alkaloids [7-epi-dioncophylline A (8b), dioncolactone A (4), and 5'-O-demethyl-8-O-methyl-7-epidioncophylline A (11)] displayed good activities against both parasites, with median inhibitory concentrations (IC50) of 1-5 micrograms/ml. Dioncophylline C (2), however, was even better, with IC50 of 0.014 microgram/ml (P. falciparum) and 0.015 microgram/ml (P. berghei) and therefore regarded as a promising lead for studies of structure-activity relationships. The free N- and 8-OH-functions were shown to be prerequisites for the outstanding activity of this molecule against P. falciparum, the presence of at least one free phenolic OH-function appearing to be essential for any activity. Initial experiments with derivatives of ancistrocladine (1) show that, in contrast to 2, N-derivatization of this alkaloid leads to increased activity against P. falciparum.

Activities of extracts and naphthylisoquinoline alkaloids from Triphyophyllum peltatum, Ancistrocladus abbreviatus and Ancistrocladus barteri against Plasmodium berghei (Anka strain) in vitro.

Extracts from three tropical medicinal plant species belonging to the Dioncophyllaceae (Triphyophyllum peltatum) and the Ancistrocladaceae (Ancistrocladus abbreviatus and Ancistrocladus barteri), and pure naphthylisoquinoline alkaloids derived from these species have been examined for the first time for their activity against asexual blood forms of Plasmodium berghei (Anka strain) in vitro. These activities were considerable and comparable with those earlier found against erythrocytic forms of Plasmodium falciparum. The extracts and constituents of species belonging to the Dioncophyllaceae (dioncophylline B, dioncopeltine A and dioncophylline A) appear to be more promising than those from the Ancistrocladaceae.