Studies of C-terminal naphthoquinone dipeptides as 20S proteasome inhibitors.
The ubiquitin proteasome pathway is crucial in regulating many processes in the cell. Modulation of proteasome activities has emerged as a powerful strategy for potential therapies against much important pathologies. In particular, specific inhibitors may represent a useful tool for the treatment of tumors. Here, we report studies of a new series of peptide-based analogues bearing a naphthoquinone pharmacophoric unit at the C-terminal position. Some derivatives showed inhibition in the µM range of the post-acidic-like and chymotrypsin-like active sites of the proteasome.
a Department of Chemical and Pharmaceutical Sciences and.
Alessandra
A
Scotti
a Department of Chemical and Pharmaceutical Sciences and.
Claudio
C
Trapella
a Department of Chemical and Pharmaceutical Sciences and.
Valeria
V
Ferretti
b Department of Life Sciences and Biotechnology , University of Ferrara , Ferrara , Italy.
Eleonora
E
Gallerani
b Department of Life Sciences and Biotechnology , University of Ferrara , Ferrara , Italy.
Riccardo
R
Gavioli
a Department of Chemical and Pharmaceutical Sciences and.
Mauro
M
Marastoni
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004151:Dipeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D009285:Naphthoquinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D061988:Proteasome Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D004151:Dipeptides; D009285:Naphthoquinones; D061988:Proteasome Inhibitors; D046988:Proteasome Endopeptidase Complex
20S Proteasome; naphthoquinone derivatives; pseudodipeptides; synthetic inhibitor