Abstract
Histone deacetylase (HDAC) inhibition is a recent, clinically validated therapeutic strategy for cancer treatment. Small molecule HDAC inhibitors identified so far fall in to three distinct structural motifs: the zinc-binding group (ZBG), a hydrophobic linker, and a recognition cap group. Here we report the suitability of a 1,2,3-triazole ring as a surface recognition cap group-linking moiety in suberoylanilide hydroxamic acid-like (SAHA-like) HDAC inhibitors. Using "click" chemistry (Huisgen cycloaddition reaction), several triazole-linked SAHA-like hydroxamates were synthesized. Structure-activity relationship revealed that the position of the triazole moiety as well as the identity of the cap group markedly affected the in vitro HDAC inhibition and cell growth inhibitory activities of this class of compounds.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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 Proliferation / drug effects
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Cell Survival / drug effects
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Crystallography, X-Ray
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Dose-Response Relationship, Drug
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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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Enzyme Inhibitors / pharmacology*
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Histone Deacetylase Inhibitors*
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Humans
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Hydroxamic Acids / chemistry
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Models, Molecular
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Molecular Structure
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Molecular Weight
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Stereoisomerism
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Structure-Activity Relationship
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Triazoles / chemical synthesis*
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Triazoles / chemistry
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Triazoles / pharmacology*
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Tumor Cells, Cultured
Substances
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Antineoplastic Agents
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Enzyme Inhibitors
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Histone Deacetylase Inhibitors
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Hydroxamic Acids
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Triazoles