Abstract
A series of bisthiazole-based hydroxamic acids as novel potent HDAC inhibitors was developed during our previous work. In the present work, a new series of highly potent bisthiazole-based compounds were designed and synthesized. Among the prepared compounds, compound H13, which contains an α-(S)-methyl-substituted benzyl group, displays potent inhibitory activity toward human HDACs and several cancer cells lines. Compound H13 has a favorable PK profile and high tissue distribution specificity in the colon, as well as good efficacy in the AOM-DSS mouse model for colitis-associated colonic tumorigenesis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Line, Tumor
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Colitis / complications
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Colonic Neoplasms / etiology
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Colonic Neoplasms / prevention & control
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Drug Design
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Drug Screening Assays, Antitumor
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Histone Deacetylase Inhibitors / chemical synthesis*
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Histone Deacetylase Inhibitors / pharmacokinetics
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Histone Deacetylase Inhibitors / pharmacology*
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Humans
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Mice
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Molecular Docking Simulation
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Structure-Activity Relationship
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Thiazoles / chemical synthesis*
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Thiazoles / pharmacokinetics
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Thiazoles / pharmacology*
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Tissue Distribution
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Xenograft Model Antitumor Assays
Substances
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Histone Deacetylase Inhibitors
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Thiazoles