title: Inhibitors of human histone deacetylase: synthesis and enzyme and cellular activity of straight chain hydroxamates.
abstract: Inhibitors of histone deacetylase (HDAC) have been shown to induce terminal differentiation of human tumor cell lines and to have antitumor effects in vivo. We have prepared analogues of suberoylanilide hydroxamic acid (SAHA) and trichostatin A and have evaluated them in a human HDAC enzyme inhibition assay, a p21(waf1) (p21) promoter assay, and in monolayer growth inhibition assays. One compound, 4-(dimethylamino)-N-[7-(hydroxyamino)-7-oxoheptyl]-benzamide, was found to affect the growth of a panel of eight human tumor cell lines differentially.
authors.forename: Stacy W
authors.initials: SW
authors.lastname: Remiszewski
authors.forename: Lidia C
authors.initials: LC
authors.lastname: Sambucetti
authors.forename: Peter
authors.initials: P
authors.lastname: Atadja
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Bair
authors.forename: Wendy D
authors.initials: WD
authors.lastname: Cornell
authors.forename: Michael A
authors.initials: MA
authors.lastname: Green
authors.forename: Kobporn Lulu
authors.initials: KL
authors.lastname: Howell
authors.forename: Manfred
authors.initials: M
authors.lastname: Jung
authors.forename: Paul
authors.initials: P
authors.lastname: Kwon
authors.forename: Nancy
authors.initials: N
authors.lastname: Trogani
authors.forename: Heather
authors.initials: H
authors.lastname: Walker
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001549:Benzamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; 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; D006898:Hydroxylamines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D011401:Promoter Regions, Genetic; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: C448624:4-(dimethylamino)-N-(7-(hydroxyamino)-7-oxoheptyl)benzamide; D000970:Antineoplastic Agents; D001549:Benzamides; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D006898:Hydroxylamines