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.
MeSH terms
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology
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Benzamides / chemical synthesis*
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Benzamides / chemistry
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Benzamides / pharmacology
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins / metabolism
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Drug Screening Assays, Antitumor
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology
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Histone Deacetylase Inhibitors*
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Humans
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Hydroxamic Acids / chemical synthesis*
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Hydroxamic Acids / chemistry
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Hydroxamic Acids / pharmacology
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Hydroxylamines / chemical synthesis*
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Hydroxylamines / chemistry
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Hydroxylamines / pharmacology
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Models, Molecular
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Promoter Regions, Genetic
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Structure-Activity Relationship
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Tumor Cells, Cultured
Substances
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4-(dimethylamino)-N-(7-(hydroxyamino)-7-oxoheptyl)benzamide
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Antineoplastic Agents
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Benzamides
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CDKN1A protein, human
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins
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Enzyme Inhibitors
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Histone Deacetylase Inhibitors
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Hydroxamic Acids
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Hydroxylamines