Benzo[e]isoindole-1,3-diones as potential inhibitors of glycogen synthase kinase-3 (GSK-3). Synthesis, kinase inhibitory activity, zebrafish phenotype, and modeling of binding mode.

Authors :: Zou H
Zhou L
Li Y
Cui Y
Zhong H
Pan Z
Yang Z
Quan J
Source :: Journal of medicinal chemistry [J Med Chem] 2010 Feb 11; Vol. 53 (3), pp. 994-1003.
Publication Year :: 2010
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.

Subjects :: Animals
Eye Abnormalities embryology
Glycogen Synthase Kinase 3 beta
Models, Molecular
Phenotype
Phthalimides chemistry
Protein Binding
Protein Kinase Inhibitors chemistry
Zebrafish embryology
Embryo, Nonmammalian drug effects
Eye Abnormalities drug therapy
Glycogen Synthase Kinase 3 antagonists & inhibitors
Isoindoles chemistry
Phthalimides chemical synthesis
Phthalimides pharmacology
Protein Kinase Inhibitors chemical synthesis
Protein Kinase Inhibitors pharmacology

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