title: Poststatin, a new inhibitor of prolyl endopeptidase. VIII. Endopeptidase inhibitory activity of non-peptidyl poststatin analogues.
abstract: Non-peptidyl postatin analogues, (S)-N-substituted-2-[2-(1-acylpyrrolidinyl)]-2-oxoacetamides were synthesized and examined for their inhibitory activity against prolyl endopeptidase and cathepsin B in vitro. Many compounds showed stronger activity than natural poststatin, a pentapeptide. Among them, (S)-N-cyclohexyl-2-oxo-2-[2-(1-(3-phenoxybenzoyl)pyrrolidinyl)]ace tamide (22) and (S)-N-cyclohexyl-2-[2-(1-(2-naphthoyl)pyrrolidinyl)]-2-oxoacetamide++ + (19) indicated IC50 value of 5.8 and 8.2 ng/ml for prolyl endopeptidase inhibition respectively. None of these compounds possess significant inhibitory activities against cathepsin B, a cysteine protease. These results indicate that these compounds are more selective inhibitors against prolyl endopeptidase than is natural poststatin.
authors.affiliation: Institute of Microbial Chemistry, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Tsuda
authors.forename: Y
authors.initials: Y
authors.lastname: Muraoka
authors.forename: M
authors.initials: M
authors.lastname: Nagai
authors.forename: T
authors.initials: T
authors.lastname: Aoyagi
authors.forename: T
authors.initials: T
authors.lastname: Takeuchi
mesh_terms: D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D010084:Oxidation-Reduction; D000085822:Prolyl Oligopeptidases; D012697:Serine Endopeptidases / Q000187:drug effects*; D015842:Serine Proteinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013329:Structure-Activity Relationship
chemical_list: D009842:Oligopeptides; D015842:Serine Proteinase Inhibitors; C071400:poststatin; D012697:Serine Endopeptidases; D000085822:Prolyl Oligopeptidases