Abstract
We synthesized biarylalanine-containing hydroxamic acids and tested them on immunoprecipitated HDAC1 and HDAC6 and show a subtype selectivity for HDAC6 that was confirmed in cells by Western blot (tubulin vs histones). We obtained an X-ray structure with a HDAC6-selective inhibitor with the bacterial deacetylase HDAH. Docking studies were carried out using HDAC1 and HDAC6 protein models. Antiproliferative activity was shown on cancer cells for selected compounds.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Blotting, Western
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Computer Simulation
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Crystallography, X-Ray
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / pharmacology
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Histone Deacetylase 1
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Histone Deacetylase 6
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Histone Deacetylase Inhibitors*
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Histone Deacetylases
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Histones
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Humans
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Hydroxamic Acids / chemical synthesis
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Hydroxamic Acids / pharmacology*
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Phenylalanine*
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Protein Binding
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Tubulin
Substances
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Enzyme Inhibitors
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Histone Deacetylase Inhibitors
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Histones
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Hydroxamic Acids
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Tubulin
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Phenylalanine
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HDAC1 protein, human
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HDAC6 protein, human
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Histone Deacetylase 1
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Histone Deacetylase 6
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Histone Deacetylases