Sensitivity of artemisinin towards different stages of development of the malaria parasite, Plasmodium falciparum.

Artemisinin-based combination therapies (ACTs) serve as a first line of defence against malaria infection. The success of malaria treatment depends closely on the timing of action and the target of this drug. The early inhibitory effect of artemisinin associated with the integrity and pH of the digestive vacuole (DV) of the malaria parasite was investigated. Using the malaria SYBR Green I based-fluorescence assay, artemisinin showed activity against the chloroquine-sensitive strains of 3D7 and D10 higher than that against the chloroquineresistant strain of Dd2. A significant inhibition of parasite growth with marked changes in parasite morphology was seen following treatment with 0.2-60 times the IC value of artemisinin for a period of 4 hours was observed at mid ring, late trophozoite and late schizont stages. The drug had no obvious alterations in the distribution of a pH-sensitive probe, LysoSensor Blue labelling of the DV even at the highest concentration examined. Using a ratiometric pH probe, SNARF-1-dextran, the DV pH of treated trophozoites remained acidic, suggesting the loss of DV pH is probably not the mode of action of artemisinin that causes parasite killing.