ANTIPROTOZOAL ACTIVITY OF NAPHTHYLISOQUINOLINE ALKALOIDS .9. NAPHTHYLISOQUINOLINE ALKALOIDS AGAINST MALARIA - EVALUATION OF THE CURATIVE POTENTIALS OF DIONCOPHYLLINE-C AND DIONCOPELTINE-A AGAINST PLASMODIUM-BERGHEI IN-VIVO

Naphthylisoquinoline alkaloid-containing extracts from species of the families Dioncophyllaceae and Ancistrocladaceae and purified alkaloids derived therefrom were shown to exhibit antiparasitic activity in Pla smodium berghei-infected mice. Several extracts and alkaloids, especia lly dioncophylline C and dioncopeltine A, isolated from Triphyophyllum peltatum (Dioncophyllaceae), displayed high levels of activity. Dionc opeltine A was able to suppress parasitemia almost totally, while dion cophylline C cured infected mice completely after oral treatment with 50 mg kg of body weight(-1) day(-1) for 4 days without noticeable toxi c effects. Analysis of the dose-response relationship of dioncophyllin e 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 suffic ient to kill 99.6% of the parasites. Intravenous application of dionco phylline 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 agains t the chloroquine-resistant P. berghei Anka CRS parasites. Sustained r elease of these compounds at 20 mg kg(-1) day(-1) by implanted miniosm otic pumps exhibited curative effects. The naphthylisoquinoline alkalo ids are therefore promising new antimalarial agents.