Investigation of Novel Antimalarial Agents and Novel Target Identification Approaches
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Malaria remains a major global health problem causing >600,000 deaths annually . Efforts to control malaria are hampered by parasite drug resistance, insecticide resistance in mosquitoes, and the lack of an effective vaccine. In the last decade only one new chemotype, the spiroindolones, has progressed to clinical trials for malaria treatment [2, 3]. To address this significant problem the identification and development of new antimalarial agents is a priority. Part of this process includes ensuring that sufficient drug leads are available to prime the drug discovery pipeline, particularly those with novel modes of action in order to limit issues of cross-resistance with existing drugs . While high throughput screening campaigns have identified thousands of potential antimalarial compounds from big Pharma libraries [5, 6], antimalarial target information on most compounds are lacking. Screening different libraries and pharmacophores is also recognised as being crucial to ensure chemical diversity . There is also an increasing interest in repurposing existing drugs or drug classes or using them as starting point for discovery of new antimalarial agents. One of the aims of this thesis was to address the need for new antimalarial drug leads by investigating three compound classes with demonstrated clinical efficacy against cancer, HIV and other human diseases in a so called “piggyback” approach.
Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Biomolecular and Physical Sciences
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