Plasmodium falciparum: effects of phaeanthine, a naturally-occurring bisbenzylisoquinoline alkaloid, on chloroquine-resistant and -sensitive parasitesin vitro, and its influence on chloroquine activity

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Abstract
Phaeanthine, a bisbenzylisoquinoline alkaloid which occurs naturally in Triclisia species, was extracted from Triclisia patens (Menispermaceae) obtained from Sierra Leone (West Africa). In vitro, phaeanthine was found to be twice as potent against a chloroquine-resistant Plasmodium falciparum strain (K1), as against a chloroquine-sensitive clone (T9–96), with 50% inhibitory concentrations of 365·85 (±11·41) nM and 704·87 (·81·48) nM respectively. At a sub-inhibitory concentration of 80·35 nM, chloroquine resistance was not reversed by phaeanthine. Isobolograms constructed from experiments with chloroquine/phaeanthine combinations showed antagonism in T9-96 and an additive effect in K1. In a 48-hour microtest, phaeanthine at antimalarial concentrations showed no cytotoxicity to mammalian (KB) cells in vitro.

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