Abstract
The tetrahydroazepinone pharmacophore is a component of many interesting compounds, including several marine natural products, with anti-cancer properties. The synthesis and biological evaluation of a novel series of pyrroloazepinone and indoloazepinone oximes is reported. These compounds showed promising growth inhibition activity against four human cancer cell lines but did not significantly inhibit the cell cycle regulator cyclin dependent kinase 2. The most active compounds in this series displayed improved anti-proliferative activity over the related synthetic indoloazepine kenpaullone. The structure activity relationships exhibited by the azepinone pharmacophore suggests several novel lead compounds for anti-cancer drug discovery.
Crown Copyright © 2012. Published by Elsevier Masson SAS. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
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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Azepines / chemical synthesis
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Azepines / chemistry*
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Azepines / pharmacology*
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Biological Products / chemical synthesis
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Biological Products / chemistry
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Biological Products / pharmacology*
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Dose-Response Relationship, Drug
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Drug Screening Assays, Antitumor
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Humans
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Indoles / chemical synthesis
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Indoles / chemistry
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Indoles / pharmacology*
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MCF-7 Cells
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Molecular Structure
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Oximes / chemical synthesis
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Oximes / chemistry
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Oximes / pharmacology*
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Pyrroles / chemical synthesis
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Pyrroles / chemistry*
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Pyrroles / pharmacology*
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Structure-Activity Relationship
Substances
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Antineoplastic Agents
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Azepines
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Biological Products
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Indoles
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Oximes
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Pyrroles
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pyrroloazepinone
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hymenialdisine