Title:Design of N-substituted Amino Caproic Hydroxamic Acid Histone Deacetylase Inhibitors Reveal an Essential Role for Cap Atomic Composition
Volume: 12
Issue: 7
Author(s): Jean M. Brunel, Chanaz Salmi-Smail, Audrey Restouin, Thomas Prebet, Norbert Vey and Yves Collette
Affiliation:
Keywords:
N-substituted amino caproic hydroxamic acid, Histone deacetylase inhibitors, Anticancer agents, SAHA derivatives, carcinogenesis, dichloromethane, chromatography, aminohexanoic.
Abstract: A series of N-substituted amino caproic hydroxamic acid histone deacetylase inhibitors derivatives was designed in good-toexcellent
yields and evaluated for their antiproliferative activity in a panel of human cancer cell lines, showing half maximum effective
concentration varying from 700 nM to > 100 μM. Interestingly, the replacement of a furyl group by a thienyl one impacted
very significantly the cap role on this antiproliferative activity and on histone acetylation induced by these drugs in cell-based but also in
cell-free enzyme assays, suggesting an important role of the electronic density attached to the oxygen or sulfur atoms.
