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ID: ALA1157197

Journal: Bioorg Med Chem

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

Authors: Nowicki MW, Tulloch LB, Worralll L, McNae IW, Hannaert V, Michels PA, Fothergill-Gilmore LA, Walkinshaw MD, Turner NJ.

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 IC(50) values of 23microM and 26microM 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.

CiteXplore: 18387804

DOI: 10.1016/j.bmc.2008.03.045