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Malaria

With over half of the world’s population at risk of malaria every year, it remains one of the most important parasitic diseases and the leading cause of morbidity and mortality in the world. The disease is considered endemic in 104 countries with Africa accounting for over 90% of deaths every year. Children and pregnant women are the most affected especially in low and middle-income countries. 

Over the past years, the emergence of resistance to effective antimalarial drugs, toxicity and high cost has created a high demand for the discovery of new antimalarial drugs with novel chemotypes, molecular targets and pan-activity in line with the new target product profiles (TPP) for malaria. 

Our research on malaria is involves a hit-to-lead multi-directional approach in developing hits arising from both target-based and phenotypic screening. Different approaches are employed in the design leading up to the synthesis of both organic and organometallic target compounds. Some approaches include hybridization, repositioning and the utilization of privileged molecular scaffolds. Our workflow also involves the interrogation of putative targets for phenotypic projects, these include targets involved in hemoglobin degradation pathway of P. falciparum, enzymology, chemoproteomics and live-cell microscopy among others. Our CADD platforms allows for rational design and synthesis of compounds targeting a diverse class of novel malaria targets. Details of our malaria research can be found in our publications [http://www.kellychibaleresearch.uct.ac.za/2020-0]