Plasmodium falciparum is the protozoan parasite that is the causative agent of malaria in humans. The World Health Organization estimates there were 219 million cases of malaria resulting in 435,000 deaths in 2017. Despite recent progress in control and treatment of the disease, malaria remains a major threat due to the emergence of resistance to all known antimalarial drugs. As a result, there is pressing need for the discovery of drugs with novel mechanisms of action to circumvent the current mechanisms of resistance. Protein kinases in Plasmodium serve critical functions in its life cycle and are implicated in multiple stages of cellular progression. These qualities make protein kinases attractive antimalarial drug targets. In addition, a large portion of the Plasmodium kinases have no orthologs in the mammalian kinome, which increases the potential for selective targeting. For these reasons, we hypothesized that targeting the plasmodial kinome may give rise to effective antimalarials. The goal of this study was to identify and characterize plasmodial inhibitors from a kinase-focused library of 2,480 compounds. An initial phenotypic screen was performed at a fixed one micromolar concentration to identify compounds with antiplasmodial activity. From this library, we have identified multiple scaffolds with submicromolar potency and ample selectivity. Further characterization was sought for hits including elucidating the cellular mechanism of action, physiochemical profiling, and structure-activity relationship profiling (SAR). Efforts are currently underway to identify the molecular targets of these compounds. As part of this effort, a probe-based chemoproteomics method was used. This method involved using soluble ATP probes to label kinases in lysates of inhibitor-treated cells. Samples from this experiment are currently undergoing mass spectrometric analysis. These results will help elucidate which kinases are targeted by the compounds of interest. Ultimately, this work will provide a starting point for the development of new therapeutics to treat drug-resistant malaria.

Thesis Completion




Thesis Chair/Advisor

Chakrabarti, Debopam


Bachelor of Science (B.S.)


College of Medicine


Burnett School of Biomedical Sciences



Access Status

Campus Access

Length of Campus-only Access

5 years

Release Date