Comparison of the inhibition of human and Trypanosoma cruzi prolyl endopeptidases.
Prolyl endopeptidases (PEPs) have been found in numerous species. Inhibitors of human enzyme could correct cognitive deficits in Alzheimer patients while inhibition of Trypanosoma cruzi PEP could prevent invasion phase in Chagas disease. A structure-activity relationship study carried out in a tetrahydroisoquinoline series allowed to obtain potent competitive inhibitors superior to SUAM-1221. Besides, inhibitors expected to act according to an irreversible mechanism revealed to be superior to JPT-4819, for applications linked to human enzyme inhibition.
Vendeville
Sandrine
S
Institut de Biologie de Lille - Institut Pasteur de Lille, UMR CNRS 8525, Faculté de Pharmacie, Université de Lille II, 1 rue du rofesseur Calmette, BP447, 59021 cedex, Lille, France.
Goossens
Filip
F
Debreu-Fontaine
Marie Ange
MA
Landry
Valérie
V
Davioud-Charvet
Elisabeth
E
Grellier
Philippe
P
Scharpe
Simon
S
Sergheraert
Christian
C
D000818:Animals; D004353:Drug Evaluation, Preclinical; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D000085822:Prolyl Oligopeptidases; D012697:Serine Endopeptidases / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013045:Species Specificity; D013329:Structure-Activity Relationship; D014349:Trypanosoma cruzi / Q000201:enzymology*
D015842:Serine Proteinase Inhibitors; D012697:Serine Endopeptidases; C000705287:PREPL protein, human; D000085822:Prolyl Oligopeptidases