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Malaria is an infectious disease caused by protozoan parasites belonging to the genus Plasmodium.The latest statistics show that each year greater than 250 million clinical cases of malaria are reported,with over 1 million of these cases resulting in death.Approximately 3.2 billion people "mostly in the poorest countries" are at risk from malaria.Historically,natural products have played a major role in the treatment of this infectious disease.For centuries the indigenous people from South America have used the bark from the "fever tree" Cinchona succiruba for the treatment of malaria.The Chinese medicinal plant,Artemisia annua,has likewise been used as an antimalarial herbal remedy for hundreds of years.Chemical investigations of Cinchona succiruba and Artemisia annua identified the major active metabolites to be quinine and artemisinin,respectively.This research has subsequently lead to the development of numerous antimalarial drugs based on these two important plant natural products.Unfortunately,resistance of the malaria parasite to current small molecule therapies and subsequent lack of efficacy has highlighted the need for the discovery and development of new antimalarials.During high-throughput screening of our prefractionated natural product library (>200,000 fractions) we discovered that 145 fractions derived from a variety of plant and marine sources showed activity in a malaria assay.Subsequent mass-directed or bioassay-guided fractionation of the crude biota extracts yielded 65 pure natural products.When tested against two different strains of the parasite Plasmodium falciparum (3D7 and Dd2),8 of these compounds were shown to display IC50 values <97 nM.This presentation will give a brief overview of the malaria drug discovery program at Eskitis,highlighting some of the natural product chemistry and potent antimalarial activity that has been identified.