title: A new series of N5 derivatives of the 1,1,5-trimethyl furo[3,4-c]pyridine-3,4-dione (cerpegin) selectively inhibits the post-acid activity of mammalian 20S proteasomes.
abstract: A large set of N(5)-derivatives of cerpegin (1,1,5-trimethyl furo[3,4-c]pyridine-3,4-dione) was designed and synthesized in high yields by a simple and handy method using various primary amines for a pyridine cycle synthesis. The effects of 29 derivatives on the three types of catalytic sites of purified mammalian 20S proteasomes (CT-L, T-L and PA) were measured. Most of the new compounds specifically inhibited the PA activity, in the micromolar range. Docking experiments support these results. Moreover, neither calpain I nor cathepsin B were inhibited.
authors.affiliation: Enzymologie Moléculaire et Fonctionnelle, UR4-Université de Paris 6, UPMC-Sorbonne Universités, Paris, France. hien_fr@yahoo.fr
authors.forename: The Hien
authors.initials: TH
authors.lastname: Pham
authors.forename: Anna
authors.initials: A
authors.lastname: Hovhannisyan
authors.forename: Dominique
authors.initials: D
authors.lastname: Bouvier
authors.forename: Lei
authors.initials: L
authors.lastname: Tian
authors.forename: Michèle
authors.initials: M
authors.lastname: Reboud-Ravaux
authors.forename: Gagik
authors.initials: G
authors.lastname: Melikyan
authors.forename: Michelle
authors.initials: M
authors.lastname: Bouvier-Durand
mesh_terms: D001665:Binding Sites; D020134:Catalytic Domain; D003198:Computer Simulation; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D011725:Pyridines / Q000737:chemistry*; D011728:Pyridones / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D011480:Protease Inhibitors; D061988:Proteasome Inhibitors; D011725:Pyridines; D011728:Pyridones; C503349:cerpegin; D046988:Proteasome Endopeptidase Complex; C023666:pyridine