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Chapter 7

Drug Discovery for Kinetoplastid Diseases

The past decade has seen a renewed commitment to the discovery of new agents for diseases caused by the kinetoplastid parasites Trypanosoma brucei(human African trypanosomiasis), Leishmania spp. (visceral and cutaneous leishmaniasis) and Trypanosoma cruzi(Chagas disease). The renaissance of research has been driven by the completion of sequencing of the genome of these organisms, the emergence of philanthropic organizations and increased collaboration between academic, industrial and government scientists through public-private partnerships, thus enabling and promoting integrated drug discovery and development programs. This chapter describes a breadth of approaches being taken, which range from discovery of new compound classes such as benzoxaboroles, nitroheterocycles and metal-based antiparasitics from whole-cell screening assays to exploration of drug candidates such as diamidines, protease inhibitors and inhibitors of polyamine metabolism which act on individual biochemical targets essential to parasite survival. Key to many of these efforts, regardless of approach or pathway, has been to find compounds which exhibit selectivity for cidal effects on the parasite(s) relative to the mammalian host. Future development of these new molecules toward clinically useful drug candidates is dependent upon further integration of medicinal chemistry, parasitology, pharmacokinetics and toxicology to meet the stringent regulatory requirements for registration of new treatments of these neglected diseases.

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