Combined action of inhibitors of polyamine biosynthetic pathway with a known antimalarial drug chloroquine on plasmodium falciparum
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Difluoromethylornithine (alpha-DFMO), a specific enzyme activated inhibitor of ornithine decarboxylase activity, a bis (benzyl) polyamine analogue (MDL 27695) and chloroquine resulted in a dose-dependent inhibition of the parasite. The IC50 value of alpha-DFMO, MDL 27695 and chloroquine was 1.85 mM, 2.0 microM and 23 ng ml-1 respectively. The combined action of MDL 27695 (3 microM) and chloroquine (5 ng ml-1) on P. falciparum growth showed near additive effect, whereas the combination of alpha-DFMO (1.0 mM) and chloroquine (5 ng ml-1) was more than the effect of each drug individually but not additive. Similarly the combined effect of MDL 27695 (3 microM) and alpha-DFMO (1.0 mM) on P. falciparum growth was not additive. The effect of these inhibitors alone and in combination on polyamine biosynthesis is also reported.
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