Plasmodium falciparum is the leading cause of malaria worldwide with an estimated 250 million cases per year, and 500,000 deaths. While a vaccine for malaria has been developed, the efficacy is considered low/moderate and effective antimalarials for treating the disease are still necessary. Our study looked to see whether targeting the phosphatidylinositol 3-kinase (PI3K) expressed by the parasite would inhibit its growth at pharmacologically relevant concentrations. We investigated 2 drugs that have been shown to target and inhibit the PI3K of mammalian cells, NVP-BEZ235 and PIK-90. Preliminary data demonstrate inhibitory concentrations (IC50) in the nanomolar (nM) to low micromolar (uM) range in a whole cell, erythrocytic stage drug sensitivity assays. Our drug sensitivity assays included a DNA-based assay in a microtiter plate and fluorescent plate reader, coupled with traditional microscopy. We also report on stage-specific effects of the drugs on parasite growth by synchronizing the parasite growth stage in culture and performing ‘wash-out’ experiments of drug exposure to identify at what stage of growth (early trophozoite, trophozoite, or schizont) the compounds are most effective. Our study demonstrates that targeting the PI3-kinase of the P. falciparum parasite is a viable option for future antimalarial development.
