title: Comparison of the inhibition of human and Trypanosoma cruzi prolyl endopeptidases.
abstract: 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.
authors.affiliation: 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.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Vendeville
authors.forename: Filip
authors.initials: F
authors.lastname: Goossens
authors.forename: Marie Ange
authors.initials: MA
authors.lastname: Debreu-Fontaine
authors.forename: Valérie
authors.initials: V
authors.lastname: Landry
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Davioud-Charvet
authors.forename: Philippe
authors.initials: P
authors.lastname: Grellier
authors.forename: Simon
authors.initials: S
authors.lastname: Scharpe
authors.forename: Christian
authors.initials: C
authors.lastname: Sergheraert
mesh_terms: 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*
chemical_list: D015842:Serine Proteinase Inhibitors; D012697:Serine Endopeptidases; C000705287:PREPL protein, human; D000085822:Prolyl Oligopeptidases