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Quaternary ammonium compounds efficiently inhibit Plasmodium falciparum growth in vitro by impairment of choline transport.

By M L Ancelin and H J Vial


Hemicholinium 3, decamethonium, and decyltrimethylammonium previously have been demonstrated to be efficient inhibitors, with 50% inhibitory concentrations of 4 X 10(-6), 10(-6), and 7 X 10(-7) M, respectively. We show that lengthening of the alkyl chain of decyltrimethylammonium by successive additions of two carbon atoms up to hexadecyltrimethylammonium results in a very low 50% inhibitory concentration of 5 X 10(-7) M for dodecyltrimethylammonium. Furthermore, hemicholinium 3 and decamethonium exerted their antiplasmodial activity, regardless of the developmental stage of the parasite, whereas decyltrimethylammonium was particularly lethal for the mature forms. After infected erythrocytes with radioactive choline were supplied, the determination of the water-soluble choline-containing compounds, as well as the assay of choline kinase activity, showed that the specific inhibition of phosphatidylcholine biosynthesis is related to the impairment of choline entry into erythrocytes. Thus, the impairment of the transport of choline, a natural polar head group of phospholipids, appears to be lethal for Plasmodium falciparum in vitro and could be a reasonable approach for a new malaria chemotherapy

Topics: Research Article
Year: 1986
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Provided by: PubMed Central
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