dioncophylline-a and Malaria

Topics: Animals; Antimalarials; Humans; Life Cycle Stages; Liver; Malaria; Plasmodium; Structure-Activity Relationship

Naphthylisoquinoline alkaloid-containing extracts from species of the families Dioncophyllaceae and Ancistrocladaceae and purified alkaloids derived therefrom were shown to exhibit antiparasitic activity in Plasmodium berghei-infected mice. Several extracts and alkaloids, especially dioncophylline C and dioncopeltine A, isolated from Triphyophyllum peltatum (Dioncophyllaceae), displayed high levels of activity. Dioncopeltine A was able to suppress parasitemia almost totally, while dioncophylline C cured infected mice completely after oral treatment with 50 mg kg of body weight(-1) day(-1) for 4 days without noticeable toxic effects. Analysis of the dose-response relationship of dioncophylline C revealed a 50% effective dosage (ED50) of 10.71 mg kg(-1) day(-1) under these conditions. Although four daily treatments with 50 mg kg(-1) day(-1) are needed to achieve radical cure, one oral dose is sufficient to kill 99.6% of the parasites. Intravenous application of dioncophylline C is even more effective, with an ED50 of 1.90 mg kg(-1) day(-1) and no noticeable toxic effects. The compound also suppressed more established P. berghei infections when orally applied at day 3 after infection. Both dioncopeltine A and dioncophylline C are active against the chloroquine-resistant P. berghei Anka CRS parasites. Sustained release of these compounds at 20 mg kg(-1) day(-1) by implanted miniosmotic pumps exhibited curative effects. The naphthylisoquinoline alkaloids are therefore promising new antimalarial agents.

Topics: Animals; Antimalarials; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Female; Isoquinolines; Malaria; Mice; Naphthols; Plasmodium berghei

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.

Topics: Alkaloids; Animals; Anopheles; Insect Vectors; Insecticides; Isoquinolines; Larva; Malaria; Plant Extracts; Pupa