Design of N-substituted Amino Caproic Hydroxamic Acid Histone Deacetylase Inhibitors Reveal an Essential Role for Cap Atomic Composition

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.

Cite this article as:

M. Brunel Jean, Salmi-Smail Chanaz, Restouin Audrey, Prebet Thomas, Vey Norbert and Collette Yves, Design of N-substituted Amino Caproic Hydroxamic Acid Histone Deacetylase Inhibitors Reveal an Essential Role for Cap Atomic Composition, Anti-Cancer Agents in Medicinal Chemistry 2012; 12 (7) . https://dx.doi.org/10.2174/187152012802650192