A level – History of anti-malarial drugs

Click the structures to view the 3D models

Malaria is a life-threatening disease caused by protozoan parasites that are transmitted to humans via the bites of infected female Anopheles mosquitoes. The main treatment for malaria is artemisinin-based combination therapy (ACTs). However, widespread use of ACTs has led to the emergence of resistance against artemisinin and its derivatives.

Researchers have identified aspartic proteases as a potential drug target because they are essential for the parasite to cause disease. Researchers have studied hydroxyethylamine (HEA) scaffolds as potential antimalarial compounds as their structure is similar to the aspartic protease enzymes. This research has led to the development of ‘clickable’ photoaffinity labelling (PAL) probes based on the HEA scaffold. These probes allow scientists to tag and identify target proteins within living parasites using a chemical reaction called bio-orthogonal ligation. This technique helps researchers better understand how the parasite functions and how new drugs could be designed to combat malaria more effectively.

M. Lisauskaitė, G. L. Nixon, C. M. Woodley, N. G. Berry, A. Coninckx, L. C. Qie, S. C. Leung, D. Taramelli, N. Basilico, S. Parapini, S. A. Ward, O. Vadas, D. Soldati-Favre, W. D. Hong and P. M. O’Neill, RSC Chemical Biology, 2024, 5, 19-29.