Inhibitors of Human Histone Deacetylase:  Synthesis and Enzyme and Cellular Activity of Straight Chain Hydroxamates

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 inhibiti...

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Bibliographic Details
Published in:Journal of medicinal chemistry 2002-02, Vol.45 (4), p.753-757
Main Authors: Remiszewski, Stacy W, Sambucetti, Lidia C, Atadja, Peter, Bair, Kenneth W, Cornell, Wendy D, Green, Michael A, Howell, Kobporn Lulu, Jung, Manfred, Kwon, Paul, Trogani, Nancy, Walker, Heather
Format: Article
Language:English
Subjects:
Antineoplastic agents
Antineoplastic Agents - chemical synthesis
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Benzamides - chemical synthesis
Benzamides - chemistry
Benzamides - pharmacology
Biological and medical sciences
Cyclin-Dependent Kinase Inhibitor p21
Cyclins - metabolism
Drug Screening Assays, Antitumor
Enzyme Inhibitors - chemical synthesis
Enzyme Inhibitors - chemistry
Enzyme Inhibitors - pharmacology
General aspects
Histone Deacetylase Inhibitors
Humans
Hydroxamic Acids - chemical synthesis
Hydroxamic Acids - chemistry
Hydroxamic Acids - pharmacology
Hydroxylamines - chemical synthesis
Hydroxylamines - chemistry
Hydroxylamines - pharmacology
Medical sciences
Models, Molecular
Pharmacology. Drug treatments
Promoter Regions, Genetic
Structure-Activity Relationship
Tumor Cells, Cultured
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Summary: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 p21waf1 (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.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm015568c