Sep 2012 Anti-cancer agents in medicinal chemistry

Design of N-substituted amino caproic hydroxamic acid histone deacetylase inhibitors reveal an essential role for cap atomic composition.

Auteurs

Salmi-Smail C, Restouin A, Prebet T, Vey N, Collette Y

Résumé

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.

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