title: Alpha,beta-unsaturated N-acylpyrrole peptidyl derivatives: new proteasome inhibitors.
abstract: Because of the encouraging results obtained using vinyl ester derivatives, we synthesized and tested a novel series of peptide-based proteasome inhibitors bearing a new pharmacophore unit at the C-terminal. N-Acylpyrrole moiety is a potential substrate for Michael addition by catalytic threonine. Several analogues have demonstrated a selective inhibition of the multicatalytic complex beta1 subunits, the capacity to permeate cellular membrane, and good pharmacokinetics properties.
authors.affiliation: Department of Pharmaceutical Sciences and Biotechnology Center, University of Ferrara, I-44100 Ferrara, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Baldisserotto
authors.forename: Valeria
authors.initials: V
authors.lastname: Ferretti
authors.forename: Federica
authors.initials: F
authors.lastname: Destro
authors.forename: Christian
authors.initials: C
authors.lastname: Franceschini
authors.forename: Mauro
authors.initials: M
authors.lastname: Marastoni
authors.forename: Riccardo
authors.initials: R
authors.lastname: Gavioli
authors.forename: Roberto
authors.initials: R
authors.lastname: Tomatis
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D020134:Catalytic Domain; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004355:Drug Stability; D006801:Humans; D008958:Models, Molecular; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex / Q000097:blood / Q000737:chemistry; D061988:Proteasome Inhibitors; D021122:Protein Subunits / Q000037:antagonists & inhibitors; D011758:Pyrroles / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014753:Vinyl Compounds / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D009842:Oligopeptides; D061988:Proteasome Inhibitors; D021122:Protein Subunits; D011758:Pyrroles; D014753:Vinyl Compounds; D046988:Proteasome Endopeptidase Complex