Design, synthesis and trypanocidal activity of lead compounds based on inhibitors of parasite glycolysis

Research output: Contribution to journalArticle

  • External authors:
  • Matthew W. Nowicki
  • Lindsay B. Tulloch
  • Liam Worralll
  • Iain W. McNae
  • Véronique Hannaert
  • Paul A M Michels
  • Linda A. Fothergill-Gilmore
  • Malcolm D. Walkinshaw

Abstract

The glycolytic pathway has been considered a potential drug target against the parasitic protozoan species of Trypanosoma and Leishmania. We report the design and the synthesis of inhibitors targeted against Trypanosoma brucei phosphofructokinase (PFK) and Leishmania mexicana pyruvate kinase (PyK). Stepwise library synthesis and inhibitor design from a rational starting point identified furanose sugar amino amides as a novel class of inhibitors for both enzymes with IC50 values of 23 μM and 26 μM against PFK and PyK, respectively. Trypanocidal activity also showed potency in the low micromolar range and confirms these inhibitors as promising candidates for the development towards the design of anti-trypanosomal drugs. © 2008 Elsevier Ltd. All rights reserved.

Bibliographical metadata

Original languageEnglish
Pages (from-to)5050-5061
Number of pages11
JournalBioorganic and Medicinal Chemistry
Volume16
Issue number9
DOIs
Publication statusPublished - 1 May 2008