Inhibition of the glycolytic enzymes in the trypanosome: an approach in the development of new leads in the therapy of parasitic diseases

Pharmacol Ther. 1993 Nov;60(2):347-65. doi: 10.1016/0163-7258(93)90016-7.

Abstract

Glycolysis in the trypanosome represents an important target for the development of new therapeutic agents due to the fact that this metabolism is essential for the parasite, glucose being its sole source of energy. In addition, different features of this metabolism and those associated with glycolytic enzymes offer opportunities for the development of efficient and selective compounds. Examples are given in this work of inhibitors directed to the enzymes aldolase and glyceraldehyde-phosphate-dehydrogenase and also of molecules acting specifically on the clusters of basic amino-acids present at the surfaces of the glycolytic enzymes in the parasite.

Publication types

  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / pharmacology*
  • Enzyme Inhibitors / therapeutic use
  • Fructose-Bisphosphate Aldolase / antagonists & inhibitors*
  • Fructose-Bisphosphate Aldolase / chemistry
  • Fructose-Bisphosphate Aldolase / metabolism
  • Glyceraldehyde-3-Phosphate Dehydrogenases / antagonists & inhibitors*
  • Glyceraldehyde-3-Phosphate Dehydrogenases / chemistry
  • Glyceraldehyde-3-Phosphate Dehydrogenases / metabolism
  • Glycolysis / drug effects
  • Humans
  • Molecular Sequence Data
  • Structure-Activity Relationship
  • Trypanocidal Agents / chemical synthesis
  • Trypanocidal Agents / pharmacology*
  • Trypanocidal Agents / therapeutic use
  • Trypanosoma brucei brucei / drug effects
  • Trypanosoma brucei brucei / enzymology*
  • Trypanosomiasis / drug therapy
  • Trypanosomiasis / enzymology

Substances

  • Enzyme Inhibitors
  • Trypanocidal Agents
  • Glyceraldehyde-3-Phosphate Dehydrogenases
  • Fructose-Bisphosphate Aldolase