Malaria is a parasitic disease caused by Plasmodium spp. which still ravages many parts of the world, responsible for killing an estimated 781,000 people each year according to the World Health Organisation’s 2010 World Malaria Report. Treatment is frequently associated with the development of resistance and so new drug leads are always needed.
All of the compounds synthesized in this study showed remarkable in vitro activity in the low nanomolar range (0.2–3.7 nM) and several demonstrated promising oral activity in the P. berghei ANKA mouse model of malaria.
A preliminary study suggests that members of this series have improved metabolic stability compared with the parent compound RKA182 and these data coupled with the excellent activity profiles, low ClogP and high aqueous solubilities (e.g. >40mg/ml) make this series an exciting development in the struggle against malaria.
Reproduced by permission from The Royal Society of Chemistry from MedChemComm Blog at http://blogs.rsc.org/md/