Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1362993 | Bioorganic & Medicinal Chemistry Letters | 2010 | 4 Pages |
The structure–activity relationship of the boronic acid derivatives of tyropeptin, a proteasome inhibitor, was studied. Based on the structure of a previously reported boronate analog of tyropeptin (2), 41 derivatives, which have varying substructure at the N-terminal acyl moiety and P2 position, were synthesized. Among them, 3-phenoxyphenylacetamide 6 and 3-fluoro picolinamide 22 displayed the most potent inhibitory activity toward chymotryptic activity of proteasome and cytotoxicity, respectively. The replacement of the isopropyl group in the P2 side chain to H or Me had negligible effects on the biological activities examined in this study.
Graphical abstractThe structure–activity relationship of the boronic acid derivatives of tyropeptin, a proteasome inhibitor, was studied. Among 41 derivatives, 3-phenoxyphenylacetamide 6 and 3-fluoro picolinamide 22 displayed the most potent inhibitory activity toward chymotryptic activity of proteasome and cytotoxicity, respectively.Figure optionsDownload full-size imageDownload as PowerPoint slide