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Abstract
Malaria is a devastating parasitic disease that affects more than 200 million people and is a leading cause of mortality in the developing world. Although many potent antimalarial therapies exist, the effectiveness of these compounds has been limited by the emergence of drug resistant Plasmodium parasites, the cost of multi-day treatment, and restrictive mechanisms of action, which often fail to protect against the sexual or liver stage parasites that are responsible for disease transmission. A major priority for antimalarial drug development, and this project, is the identification of multi-stage therapies that are broadly effective as treatments, prophylactics, and transmission blocking agents following a single, oral dose. This project focuses specifically on the cytochrome bc1 complex (cyt bc1) as a target for single-dose, multi-stage therapy. Biologically, cyt bc1 is essential for the regeneration of ubiquinone, which plays an essential role in major metabolic processes for P. falciparum, including heme and pyrimidine biosynthesis.