Combined action of inhibitors of polyamine biosynthetic pathway with a known antimalarial drug chloroquine on Plasmodium falciparum.
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.
Das
B
B
School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.
Gupta
R
R
Madhubala
R
R
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D015317:Biogenic Polyamines / Q000032:analysis; D002738:Chloroquine / Q000494:pharmacology*; D000518:Eflornithine / Q000494:pharmacology*; D010963:Plasmodium falciparum / Q000737:chemistry / Q000187:drug effects* / Q000254:growth & development; D011073:Polyamines / Q000494:pharmacology*
D000962:Antimalarials; D015317:Biogenic Polyamines; D011073:Polyamines; C058294:MDL 27695; D002738:Chloroquine; D000518:Eflornithine