title: Carbonyl- and sulfur-containing analogs of suberoylanilide hydroxamic acid: Potent inhibition of histone deacetylases.
abstract: Suberoylanilide hydroxamic acid (SAHA), an inhibitor of histone deacetylase, is used in clinical trials for a variety of advanced cancers. Twelve new analogs of SAHA were synthesized and tested as in vitro inhibitors of isolated histone deacetylases (HDACS) and in vivo inhibitors of interferon regulated transcriptional responses (a marker for HDAC activity). The analogs containing an alpha-mercaptoketone or an alpha-thioacetoxyketone were more potent than SAHA in both assays.
authors.affiliation: Department of Chemistry, Northwestern University, Evanston, IL 60208-3113, USA.
authors.forename: Wenxin
authors.initials: W
authors.lastname: Gu
authors.forename: Inna
authors.initials: I
authors.lastname: Nusinzon
authors.forename: Ronald D
authors.initials: RD
authors.lastname: Smith
authors.forename: Curt M
authors.initials: CM
authors.lastname: Horvath
authors.forename: Richard B
authors.initials: RB
authors.lastname: Silverman
mesh_terms: D002478:Cells, Cultured; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D017930:Genes, Reporter; D006367:HeLa Cells; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000187:drug effects; D006801:Humans; D006877:Hydroxamic Acids / Q000737:chemistry* / Q000494:pharmacology*; D007659:Ketones / Q000737:chemistry* / Q000494:pharmacology; D008024:Ligands; D015394:Molecular Structure; D013438:Sulfhydryl Compounds / Q000737:chemistry* / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D000077337:Vorinostat
chemical_list: D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007659:Ketones; D008024:Ligands; D013438:Sulfhydryl Compounds; D000077337:Vorinostat; D006655:Histone Deacetylases