A level – Second generation antimalarial drugs N205 and E209

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N205 and E209 are second generation antimalarial drugs developed by the medicinal chemistry research group at the University of Liverpool and they are potent at killing Plasmodium falciparum (malaria strain) quickly. The molecules were developed as alternatives for the semisynthetic artemisinin derivatives, Artemether and Artesunate, which are used in artemisinin-based combination therapy. Compared to RKA 182 , these drugs contain the adamantane core (orange) for stability and tetraoxane ring, which has proved to be very potent for malaria treatment. The difference between RKA 182, E209 and N205 is the side chain (blue). These compounds are amphiphilic but have poor water solubility, especially in recreated small intestine conditions, therefore there is room for improvement of the drugs in intestinal absorption.

C. M. Woodley, G. L. Nixon, N. Basilico, S. Parapini, W. D. Hong, S. A. Ward, G. A. Biagini, S. C. Leung, D. Taramelli, K. Onuma, T. Hasebe and P. M. O’Neill, ACS Medicinal Chemistry Letters, 2021, 12, 1077-1085.