Combined action of inhibitors of polyamine biosynthetic pathway with a known antimalarial drug chloroquine on Plasmodium falciparum

Abstract

Difluoromethylornithine (α-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 α-DFMO, MDL 27695 and chloroquine was 1.85 mM , 2.0µm and 23 ng ml^-1 respectively. The combined action of MDL 27695 (3µM ) and chloroquine (5 ng ml^-1 on P. falciparum growth showed near additive effect, whereas the combination of α-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 µM and α-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.