Design of N-substituted Amino Caproic Hydroxamic Acid Histone Deacetylase Inhibitors Reveal an Essential Role for Cap Atomic Composition
Jean M. Brunel,
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.
Keywords: N-substituted amino caproic hydroxamic acid, Histone deacetylase inhibitors, Anticancer agents, SAHA derivatives, carcinogenesis, dichloromethane, chromatography, aminohexanoic.
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