Naphthylisoquinoline alkaloids against malaria: evaluation of the curative potentials of dioncophylline C and dioncopeltine A against Plasmodium berghei in vivo.

Abstract

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.

• Authors: G François, G Timperman, W Eling, L A Assi, J Holenz, G Bringmann
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 41 Issue 11 Pg. 2533-9 (Nov 1997) ISSN: 0066-4804 [Print] United States
• PMID: 9371362 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antimalarials
• Isoquinolines
• Naphthols
• dioncophylline C
• dioncophylline A

Topics

• Animals
• Antimalarials (therapeutic use)
• Dose-Response Relationship, Drug
• Drug Evaluation, Preclinical
• Female
• Isoquinolines (therapeutic use)
• Malaria (drug therapy)
• Mice
• Naphthols (therapeutic use)
• Plasmodium berghei (drug effects)