49.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
H. X. Zou, L. Y. Zhou, Y. Z. Li, Y. Cui, H. B. Zhong, Z. Y. Pan, Z. Yang and J. M. Quan
Benzo[e]isoindole-1,3-dione derivatives were synthesized, and the effects on GSK-3β activity and zebrafish embryo growth were evaluated. A series of derivatives show obvious inhibitory activity against GSK-3β. The most potent inhibitor, 7,8-dimethoxy-5-methylbenzo[e]isoindole-1,3-dione (8a), shows nanomolar IC50 and obvious phenotype on zebrafish embryo growth associated with the inhibition of GSK-3β at low micromolar concentration. The interaction mode between 8a and GSK-3β was characterized by computational modeling.
