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:Aix-Marseille Universite, Centre de Recherche en Cancerologie de Marseille (CRCM), Laboratory of Integrative Structural & Chemical Biology (iSCB), UMR CNRS 7258, Inserm-U1068, Faculte de Pharmacie, 27 Bd Jean Moulin, 13385 Marseille Cedex 05, France.
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.
