Abstract
CDC25 phosphatases are considered as attractive targets for anti-cancer therapy. To date, quinone derivatives are among the most potent inhibitors of CDC25 phosphatase activity. We present in this paper the synthesis and the biological evaluation of new quinolinedione and naphthoquinone derivatives, containing carboxylic or malonic acids groups introduced to mimic the role of the phosphate moieties of Cyclin-Dependent Kinase complexes. The most efficient compounds show inhibitory activity against CDC25B with IC(50) values in the 10 microM range, and are cytotoxic against HeLa cells.
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 / pharmacology*
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Carboxylic Acids / chemistry
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Cyclin-Dependent Kinases / chemistry
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Cyclin-Dependent Kinases / metabolism
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / pharmacology*
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HeLa Cells
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Humans
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Inhibitory Concentration 50
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Malonates
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Molecular Mimicry
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Naphthoquinones / chemical synthesis
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Naphthoquinones / pharmacology*
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Phosphates / chemistry
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Quinolones / chemical synthesis
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Quinolones / pharmacology*
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Structure-Activity Relationship
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cdc25 Phosphatases / antagonists & inhibitors*
Substances
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Antineoplastic Agents
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Carboxylic Acids
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Enzyme Inhibitors
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Malonates
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Naphthoquinones
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Phosphates
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Quinolones
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malonic acid
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Cyclin-Dependent Kinases
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cdc25 Phosphatases