Combined action of inhibitors of S-adenosylmethionine decarboxylase with an antimalarial drug, chloroquine, on Plasmodium falciparum

Methylglyoxal bis (guanylhydrazone), (MGBG) a potent competitive inhibitor of S-adenosyl-L-methionine decarboxylase activity, Berenil, a trypanocidal agent and chloroquine, the commonly used antimalarial resulted in a dose dependent inhibition of Plasmodium falciparum in vitro. The IC50 values of MGBG, Berenil and chloroquine were 224 mu M, 40 mu M and 42 nM respectively. Parasites treated with different concentrations of MGBG or Berenil were arrested at the trophozoite stage of the erythrocytic cycle. The combined action of chloroquine (10 nM) with either Berenil (0.1 mM) or MGBG (0.1 mM) on P. falciparum growth showed an additive inhibitory effect. The effect of these inhibitors alone and in combination on polyamine biosynthesis is also reported.