title: Design of N-substituted amino caproic hydroxamic acid histone deacetylase inhibitors reveal an essential role for cap atomic composition.
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.
authors.affiliation: Aix-Marseille Université, Centre de Recherche en Cancérologie de Marseille-CRCM, Laboratory of Integrative Structural & Chemical Biology-iSCB, UMR CNRS 7258,Inserm-U1068, Faculté de Pharmacie, 27 Bd Jean Moulin, 13385 Marseille Cedex 05, France. bruneljm@yahoo.fr
authors.forename: Jean M
authors.initials: JM
authors.lastname: Brunel
authors.forename: Chanaz
authors.initials: C
authors.lastname: Salmi-Smail
authors.forename: Audrey
authors.initials: A
authors.lastname: Restouin
authors.forename: Thomas
authors.initials: T
authors.lastname: Prebet
authors.forename: Norbert
authors.initials: N
authors.lastname: Vey
authors.forename: Yves
authors.initials: Y
authors.lastname: Collette
mesh_terms: D000614:Aminocaproates / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D006877:Hydroxamic Acids / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000614:Aminocaproates; D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids