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Antimalarial polyamine analogues.

M L Edwards·D M Stemerick·A J Bitonti·J A Dumont·P P McCann·P Bey·A Sjoerdsma
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Abstract

A series of novel tetraamines of the general formula RNH(CH2)xNH(CH2)yNH(CH2)xNHR was synthesized and examined for activity against growth of Plasmodium falciparum in vitro. Within the series, dibenzyl analogues (R = benzyl) were found to be the most effective growth inhibitors, with IC50 values of about 10(-6) M. Further modifications of the tetraamine provided the optimum chain length for antimalarial activity of y = 7, x = 3. Compound 8 (MDL 27,695) with the structure y = 7, x = 3, R = benzyl, in combination with the ornithine decarboxylase inhibitor alpha-(difluoromethyl)ornithine, resulted in radical cures when tested against experimental Plasmodium berghei infections in mice. The structure-activity relationships of the series are discussed.

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AnimalsAntimalarialsChemical PhenomenaChemistryMalariaMicePlasmodium falciparumPolyaminesStructure-Activity RelationshipJournal Article

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M L Edwards, D M Stemerick, A J Bitonti, J A Dumont, P P McCann, P Bey, A Sjoerdsma. 1991. Antimalarial polyamine analogues.. https://doi.org/10.1021/jm00106a015

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