Abstract
HDAC inhibitors show great promise for the treatment of cancer. As part of a broader effort to explore the SAR of HDAC inhibitors, synthesis, biological evaluation, and molecular docking of novel Ugi products containing a zinc-chelating moiety are presented. One compound shows improved inhibitory potencies compared to SAHA, demonstrating that hindered lipophilic residues grafted on the peptide scaffold of the alpha-aminoacylamides can be favorable in the interaction with the enzyme.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Benzamides / chemistry
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Binding Sites
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Carboxylic Acids / chemistry
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Cell Cycle / drug effects
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Cell Line, Tumor
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Chelating Agents / chemistry*
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Drug Design
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / chemistry*
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Enzyme Inhibitors / metabolism
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Enzyme Inhibitors / pharmacology*
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Histone Deacetylase Inhibitors*
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Histone Deacetylases / chemistry
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Histone Deacetylases / metabolism
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Humans
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Models, Molecular*
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Phenylenediamines / chemistry
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Protein Conformation
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Structure-Activity Relationship
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Zinc / chemistry*
Substances
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Benzamides
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Carboxylic Acids
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Chelating Agents
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Enzyme Inhibitors
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Histone Deacetylase Inhibitors
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Phenylenediamines
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1,2-diaminobenzene
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Histone Deacetylases
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Zinc