Abstract
We designed and synthesized hydroxamic acid derivatives bearing a 4-(3-pyridyl)phenyl group as a cap structure, and found that they exhibit potent histone deacetylase (HDAC) inhibitory activity. A representative compound, 17a, showed more potent growth-inhibitory activity against pancreatic cancer cells and greater upregulation of p21(WAF1/CIP1) expression than the clinically used HDAC inhibitor suberoylanilide hydroxamic acid (Zolinza).
Publication types
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Research Support, Non-U.S. Gov't
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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Cell Line, Tumor
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Cyclin-Dependent Kinase Inhibitor p21 / biosynthesis*
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Dose-Response Relationship, Drug
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Drug Design
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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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Gene Expression Regulation, Neoplastic*
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Histone Deacetylase Inhibitors*
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Humans
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Hydroxamic Acids / chemistry*
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Hydroxamic Acids / pharmacology
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Indoles / chemistry*
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Pancreatic Neoplasms / drug therapy*
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Up-Regulation
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Vorinostat
Substances
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Antineoplastic Agents
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CDKN1A protein, human
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Cyclin-Dependent Kinase Inhibitor p21
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Enzyme Inhibitors
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Histone Deacetylase Inhibitors
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Hydroxamic Acids
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Indoles
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Vorinostat