title: Design, synthesis, and activity of HDAC inhibitors with a N-formyl hydroxylamine head group.
abstract: Histone deacetylases (HDAC) are promising targets for cancer chemotherapy. HDAC inhibitors are thought to act in part by disrupting normal cell cycle regulation, resulting in apoptosis and/or differentiation of transformed cells. Several HDAC inhibitors, which contain hydrophobic tails and the Zn(2+) chelator hydroxyamic acid as a head group, are potent inhibitors of HDACs both in vitro and in vivo. In this study, a related class of compounds with a N-formyl hydroxylamino head group has been synthesized and their ability to inhibit HDACs have been assayed in biochemical and cellular assays. These compounds were found to have comparable activities to suberoylanilide hydroxyamic acid (SAHA) in HDAC enzymatic assays and histone hyperacetylation cellular assays.
authors.affiliation: Department of Chemistry, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Tom Y H
authors.initials: TY
authors.lastname: Wu
authors.forename: Christian
authors.initials: C
authors.lastname: Hassig
authors.forename: Yiqin
authors.initials: Y
authors.lastname: Wu
authors.forename: Sheng
authors.initials: S
authors.lastname: Ding
authors.forename: Peter G
authors.initials: PG
authors.lastname: Schultz
mesh_terms: D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006367:HeLa Cells; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D019811:Hydroxylamine / Q000138:chemical synthesis* / Q000494:pharmacology; D019169:Jurkat Cells; D020298:U937 Cells
chemical_list: D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D019811:Hydroxylamine; D006655:Histone Deacetylases