Design, synthesis and preliminary evaluation of a series of histone deacetylase inhibitors carrying a benzodiazepine ring

• A series of hybrids between SAHA or oxamflatin and 5-phenyl-1,4-benzodiazepines has been synthesized.
• The compounds were evaluated in vitro on recombinant hHDAC1 and hHDAC6 and on HeLa nuclear extracts.
• Antiproliferative activity was tested on different cancer cells types.
• Compound (S)-8 displayed interesting activity against hematological and solid malignancies.

A series of new histone deacetylase inhibitors were designed and synthesized based on hybridization between SAHA or oxamflatin and 5-phenyl-1,4-benzodiazepines. The compounds were tested for their enzyme inhibitory activity on HeLa nuclear extracts, and on human recombinant HDAC1 and HDAC6. Antiproliferative activity was tested on different cancer cells types, while proapoptotic activity was primarily tested on NB4 cells. The compounds showed IC50 values similar to those of SAHA. Compound (S)-8 displayed interesting activity against hematological and solid malignancies.

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