Macrocyclic Peptoid-Peptide Hybrids as Inhibitors of Class I Histone Deacetylases

作者：Olsen Christian A; Montero Ana; Leman Luke J; Ghadiri M Reza^*

来源：ACS Medicinal Chemistry Letters, 2012, 3(9): 749-753.

DOI：10.1021/ml300162r

• HDAC inhibitors
• peptides
• peptoids
• macrocycles
• apicidin

We report the design, synthesis, and biological evaluation of the first macrocyclic peptoid-containing histone deacetylase (HDAC) inhibitors. The compounds selectively inhibit human class I HDAC isoforms in vitro, with no inhibition of the tubulin deacetylase activity associated with class IIb HDAC6 in cultured Jurkat cells. Compared to the natural product apicidin (1), one inhibitor (compound 10) showed equivalent potency against K-562 cells, but was more cytoselective across a panel of cancer cell lines.

• 出版日期2012-9