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Chapter 3

Antimalarial Agents Targeting Nucleotide Synthesis and Electron Transport: Insight from Structural Biology

Malaria remains a significant global health challenge due to wide-spread drug resistance and the lack of a vaccine. Target-based drug discovery provides an opportunity for the development of new chemical entities to combat the disease. Of the existing antimalarials, those with known targets primarily interfere with pyrimidine biosynthesis and significant effort is ongoing to identify new compounds that target this pathway. Structure-based approaches are being utilized for the design of new inhibitors that circumvent resistance to well-established targets in the pathway such as dihydrofolate reducase and the cytochrome bc1 complex and they are being applied to lead optimization programs for new targets in the pathway, particularly dihydroorotate dehydrogenase. In an effort to expand the number of targets that interfere with the synthesis of DNA and RNA precursors, computational transition state approaches have been used to identify potent inhibitors of purine biosynthesis. This chapter will evaluate the feasibility of redesigning new molecules for old targets, and the likelihood that new targets will be identified in these pathways.

Print publication date: 04 Nov 2011
Copyright year: 2012
Print ISBN: 978-1-84973-192-8
PDF eISBN: 978-1-84973-349-6
From the book series:
Drug Discovery