Abstract
Benzo[e]isoindole-1,3-dione derivatives were synthesized, and the effects on GSK-3beta activity and zebrafish embryo growth were evaluated. A series of derivatives show obvious inhibitory activity against GSK-3beta. The most potent inhibitor, 7,8-dimethoxy-5-methylbenzo[e]isoindole-1,3-dione (8a), shows nanomolar IC(50) and obvious phenotype on zebrafish embryo growth associated with the inhibition of GSK-3beta at low micromolar concentration. The interaction mode between 8a and GSK-3beta was characterized by computational modeling.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Embryo, Nonmammalian / drug effects*
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Eye Abnormalities / drug therapy*
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Eye Abnormalities / embryology
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Glycogen Synthase Kinase 3 / antagonists & inhibitors*
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Glycogen Synthase Kinase 3 beta
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Isoindoles / chemistry*
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Models, Molecular
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Phenotype
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Phthalimides / chemical synthesis*
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Phthalimides / chemistry
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Phthalimides / pharmacology*
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Protein Binding
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Protein Kinase Inhibitors / chemical synthesis*
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Protein Kinase Inhibitors / chemistry
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Protein Kinase Inhibitors / pharmacology*
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Zebrafish / embryology
Substances
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7,8-dimethoxy-5-methylbenzo(e)isoindole-1,3-dione
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Isoindoles
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Phthalimides
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Protein Kinase Inhibitors
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Glycogen Synthase Kinase 3 beta
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Glycogen Synthase Kinase 3