Inhibition of Plasmodium falciparum phospholipase A2 by chloroquine, quinine, and arteether.

Phospholipase A2 activity was detected in Plasmodium falciparum-infected human erythrocytes but not in uninfected red cells. The activity was similar both for trophozoite- and schizont-infected cells. Enzyme activity was Ca(2+)-independent and had a broad pH optimum, with a maximum at pH 8. No detectable phospholipase A1 activity was found either in infected or uninfected erythrocytes. Phospholipase A2 was inhibited by the anti-malarials chloroquine, quinine, and arteether with concentrations that cause 50% inhibition (IC50) of 1.3, 1.0, and 1.8 mM, respectively. The IC50 value for chloroquine is within the range of concentrations found in the food vacuoles of the malaria parasite. Inhibition of the plasmodial phospholipase A2 may, therefore, be relevant for the therapeutic action of this drug.