title: Development of potential antitumor agents. Synthesis and biological evaluation of a new set of sulfonamide derivatives as histone deacetylase inhibitors.
abstract: A series of sulfonamide hydroxamic acids and anilides have been synthesized and studied as histone deacetylase (HDAC) inhibitors that can induce hyperacetylation of histones in human cancer cells. The inhibition of HDAC activity represents a novel approach for intervening in cell cycle regulation. The lead candidates were screened in a panel of human tumor and normal cell lines. They selectively inhibit proliferation, cause cell cycle blocks, and induce apoptosis in human cancer cells but not in normal cells. The structure-activity relationships, the antiproliferative activity, and the in vivo efficacy are described.
authors.affiliation: Department of Medicinal Chemistry, MethylGene Inc., 7220 Frederick-Banting, Montréal, Québec H4S 2A1, Canada.
authors.forename: Giliane
authors.initials: G
authors.lastname: Bouchain
authors.forename: Silvana
authors.initials: S
authors.lastname: Leit
authors.forename: Sylvie
authors.initials: S
authors.lastname: Frechette
authors.forename: Elie Abou
authors.initials: EA
authors.lastname: Khalil
authors.forename: Rico
authors.initials: R
authors.lastname: Lavoie
authors.forename: Oscar
authors.initials: O
authors.lastname: Moradei
authors.forename: Soon Hyung
authors.initials: SH
authors.lastname: Woo
authors.forename: Marielle
authors.initials: M
authors.lastname: Fournel
authors.forename: Pu T
authors.initials: PT
authors.lastname: Yan
authors.forename: Ann
authors.initials: A
authors.lastname: Kalita
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Trachy-Bourget
authors.forename: Carole
authors.initials: C
authors.lastname: Beaulieu
authors.forename: Zuomei
authors.initials: Z
authors.lastname: Li
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Robert
authors.forename: A Robert
authors.initials: AR
authors.lastname: MacLeod
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Besterman
authors.forename: Daniel
authors.initials: D
authors.lastname: Delorme
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D006877:Hydroxamic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014183:Transplantation, Heterologous
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D013449:Sulfonamides