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

Nowicki, Matthew W.;Tulloch, Lindsay B.;Worralll, Liam;McNae, Iain W.;Turner, Nicholas J.;et.al.
(2008) Bioorganic & Medicinal Chemistry : the tetrahedron journal for research at the interface of chemistry and biology — Vol. 16, n° 9, p. 5050-5061 (2008)

Files

pdfdocument.pdf
  • Restricted Access
  • Adobe PDF
  • 679.25 KB
Request a copy

Details

Authors
  • Nowicki, Matthew W.
    Author
  • Tulloch, Lindsay B.
    Author
  • Worralll, Liam
    Author
  • McNae, Iain W.
    Author
  • Hannaert, VéroniqueUCLouvain
    Author
  • Michels, PaulusUCLouvain
    Author
  • Turner, Nicholas J.
    Author
Show more
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.
Affiliations

Citations

  • APA
  • Chicago
  • FWB

Nowicki, M. W., Tulloch, L. B., Worralll, L., McNae, I. W., Hannaert, V., Michels, P., Fothergill-Gilmore, L. A., Walkinshaw, M. D., & Turner, N. J. (2008). Design, synthesis and trypanocidal activity of lead compounds based on inhibitors of parasite glycolysis. Bioorganic & Medicinal Chemistry : the tetrahedron journal for research at the interface of chemistry and biology, 16(9), 5050-5061. https://doi.org/10.1016/j.bmc.2008.03.045 (Original work published 2008)