In vitro inhibition of liver forms of the rodent malaria parasite Plasmodium berghei by naphthylisoquinoline alkaloids--structure-activity relationships of dioncophyllines A and C and ancistrocladine

G François, G Timperman, T Steenackers, LA Assi, J Holenz, G Bringmann

    Research output: Contribution to journalA1: Web of Science-article

    Abstract

    Naphthylisoquinoline alkaloids are derived from Dioncophyllaceae and Ancistrocladaceae species and comprise a new class of promising antimalarials with a demonstrated potential against asexual erythrocytic Plasmodium falciparum and P. berghei stages in vitro. We report herein the pronounced activity of pure naphthylisoquinoline alkaloids against exoerythrocytic malaria parasites. P. berghei-infected human hepatoma cells (Hep G2) were incubated with culture medium containing selected alkaloids at 10 micrograms/ml. The most active compounds, showing inhibitory activity of more than 40%, were dioncophylline A (compound 1), dioncophyllacine A (compound 6), and ancistrobarterine A (compound 12). For structure-activity investigations of dioncophyllines A (compound 1) and C (compound 3) and ancistrocladine (compound 7) a selection of their analogs from natural or synthetic sources was examined. Dioncophylline A (compound 16), 5'-O-demethyl-8-O-methyl-7-epi-dioncophylline A (compound 17), N-formyl-8-O-methyl-dioncophylline C (compound 21), and N-formyl-8-O-benzoyldioncophylline C (compound 24) were found to display high levels of activity as well, although the former two compounds caused damage to the host-cell monolayers. As naphthylisoquinoline alkaloids are also highly active against blood forms of Plasmodium spp., they should be regarded as lead compounds for further development as drugs against erythrocytic and exoerythrocytic stages of Plasmodium spp.
    Original languageEnglish
    JournalParasitology Research
    Volume83
    Issue number7
    Pages (from-to)673-679
    ISSN0932-0113
    Publication statusPublished - 1997

    Keywords

    • B780-tropical-medicine
    • Protozoal diseases
    • Malaria
    • Plasmodium berghei
    • Rodents
    • Drug development
    • In vitro
    • Research
    • Inhibition
    • Liver
    • Naphthylisoquinolines
    • Dioncophyllaceae
    • Ancistrocladaceae
    • Laboratory techniques and procedures

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