Abstract
The formation of a series of analogs containing a pyridine moiety in place of the natural thiazole heterocycle, based on the potent, naturally occurring HDAC inhibitor Largazole has been accomplished. The synthetic strategy was designed modularly to access multiple inhibitors with different aryl functionalities containing both the natural depsipeptide and peptide isostere variant of the macrocycle. The cytotoxicity and biochemical activity of the library of HDAC inhibitors is described herein.
Keywords:
Class I Histone Deacetylase Inhibitor; Cytotoxic and biochemical assays; Largazole; Pyridine analogs.
Copyright © 2015 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Binding Sites
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Cell Line, Tumor
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Cell Survival / drug effects
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Depsipeptides / chemical synthesis
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Depsipeptides / chemistry*
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Depsipeptides / toxicity
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Drug Design
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Histone Deacetylase Inhibitors / chemical synthesis*
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Histone Deacetylase Inhibitors / chemistry
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Histone Deacetylase Inhibitors / toxicity
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Histone Deacetylases / chemistry*
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Histone Deacetylases / metabolism
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Humans
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Molecular Docking Simulation
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Protein Structure, Tertiary
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Pyridines / chemistry
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Structure-Activity Relationship
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Thiazoles / chemical synthesis
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Thiazoles / chemistry*
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Thiazoles / toxicity
Substances
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Depsipeptides
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Histone Deacetylase Inhibitors
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Pyridines
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Thiazoles
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largazole
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Histone Deacetylases
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pyridine