Inhibition of the glycolytic enzymes in the trypanosome: an approach in the development of new leads in the therapy of parasitic diseases.
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.
Perie
J
J
Groupe de Chimie Organique Biologique, URA au CNRS 470, Université Paul Sabatier, Toulouse, France.
Riviere-Alric
I
I
Blonski
C
C
Gefflaut
T
T
Lauth de Viguerie
N
N
Trinquier
M
M
Willson
M
M
Opperdoes
F R
FR
Callens
M
M
D000595:Amino Acid Sequence; D000818:Animals; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D005634:Fructose-Bisphosphate Aldolase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D008969:Molecular Sequence Data; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D014346:Trypanosoma brucei brucei / Q000187:drug effects / Q000201:enzymology*; D014352:Trypanosomiasis / Q000188:drug therapy / Q000201:enzymology
D004791:Enzyme Inhibitors; D014344:Trypanocidal Agents; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D005634:Fructose-Bisphosphate Aldolase