title: Fluorobenzoyl dipeptidyl derivatives as inhibitors of the Fasciola hepatica cysteine protease cathepsin L1.
abstract: Cathepsins are known to have many important physiological roles and provide a viable target for inhibition. Fluorobenzoyl dipeptide derivatives were synthesized and tested for biological activity in an effort to find an efficient inhibitor of the cysteine protease cathepsin L. Thirty-six novel inhibitors (1-36) were synthesized from protected amino acids via the standard DCC/HOBt coupling protocol, containing a benzyl ester or a nitrile as an electrophilic warhead. The activity of the inhibitors was evaluated against cathepsin L and IC50 values calculated. Modification of both amino acids and terminal groups afforded compounds with single digit micromolar inhibition. Results utilizing the benzoyl-L-leucine-glycine nitrile backbone are comparable to that for the commercially available inhibitor 39.
authors.affiliation: School of Chemical Sciences, National Institute for Cellular Biotechnology, Dublin City University, Dublin, Ireland.
authors.forename: Brian W
authors.initials: BW
authors.lastname: Moran
authors.forename: Frankie P
authors.initials: FP
authors.lastname: Anderson
authors.forename: Deborah M
authors.initials: DM
authors.lastname: Ruth
authors.forename: Ciarán O
authors.initials: CO
authors.lastname: Fágáin
authors.forename: John P
authors.initials: JP
authors.lastname: Dalton
authors.forename: Peter T M
authors.initials: PT
authors.lastname: Kenny
mesh_terms: D000818:Animals; D056668:Cathepsin L / Q000037:antagonists & inhibitors*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D005210:Fasciola hepatica / Q000201:enzymology*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D013055:Spectrophotometry, Infrared
chemical_list: D015853:Cysteine Proteinase Inhibitors; D056668:Cathepsin L