1. α,β-Unsaturated N-Acylpyrrole Peptidyl Derivatives: New Proteasome Inhibitors
- Author
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Mauro Marastoni, Federica Destro, Anna Baldisserotto, Roberto Tomatis, Valeria Ferretti, Riccardo Gavioli, and Christian Franceschini
- Subjects
Models, Molecular ,Proteasome Endopeptidase Complex ,Cell Membrane Permeability ,Vinyl Compounds ,Cell Survival ,Stereochemistry ,Antineoplastic Agents ,Apoptosis ,Peptide ,Catalysis ,Structure-Activity Relationship ,Drug Stability ,Catalytic Domain ,Cell Line, Tumor ,Drug Discovery ,Humans ,Moiety ,Pyrroles ,Threonine ,Cell Proliferation ,chemistry.chemical_classification ,Substrate (chemistry) ,Protein Subunits ,chemistry ,Proteasome ,Michael reaction ,Molecular Medicine ,Drug Screening Assays, Antitumor ,Pharmacophore ,Oligopeptides ,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.
- Published
- 2010
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