Abstract
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.
Keywords:
20S Proteasome; naphthoquinone derivatives; pseudodipeptides; synthetic inhibitor.
MeSH terms
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology*
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Dipeptides / chemical synthesis
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Dipeptides / chemistry
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Dipeptides / pharmacology*
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Dose-Response Relationship, Drug
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Drug Screening Assays, Antitumor
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Humans
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Models, Molecular
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Molecular Structure
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Naphthoquinones / chemical synthesis
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Naphthoquinones / chemistry
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Naphthoquinones / pharmacology*
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Proteasome Endopeptidase Complex / metabolism*
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Proteasome Inhibitors / chemical synthesis
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Proteasome Inhibitors / chemistry
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Proteasome Inhibitors / pharmacology*
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Structure-Activity Relationship
Substances
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Antineoplastic Agents
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Dipeptides
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Naphthoquinones
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Proteasome Inhibitors
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Proteasome Endopeptidase Complex