Design, synthesis and biological evaluation of 1,4-benzodiazepine-2,5-dione-based HDAC inhibitors

New histone deacetylase inhibitors have been synthesized and evaluated for their activity against non-small lung cancer cell line H661. These compounds have been designed with diversely substituted 1,4-benzodiazepine-2,5-dione moieties as cyclic peptide mimic cap structures, and a hydroxamate side chain. Biological evaluations demonstrated that benzodiazepine-based HDACi bearing an aromatic substituent at the N1 position exhibited promising antiproliferative and HDAC-inhibitory activities.

Graphical abstractHydroxamic acids containing 1,4-benzodiazepine-2,5-dione cap structures have been synthesized and evaluated for their antiproliferative and HDAC-inhibitory activities against H661 cancer cells.Figure optionsDownload full-size imageDownload as PowerPoint slide