title: 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.
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.
authors.affiliation: Laboratory of Chemical Genomics, Shenzhen Graduate School, Peking University, Shenzhen, China.
authors.forename: Haixia
authors.initials: H
authors.lastname: Zou
authors.forename: Liyan
authors.initials: L
authors.lastname: Zhou
authors.forename: Yuanzhen
authors.initials: Y
authors.lastname: Li
authors.forename: Yi
authors.initials: Y
authors.lastname: Cui
authors.forename: Hanbing
authors.initials: H
authors.lastname: Zhong
authors.forename: Zhengying
authors.initials: Z
authors.lastname: Pan
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yang
authors.forename: Junmin
authors.initials: J
authors.lastname: Quan
mesh_terms: D000818:Animals; D004625:Embryo, Nonmammalian / Q000187:drug effects*; D005124:Eye Abnormalities / Q000188:drug therapy* / Q000196:embryology; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors*; D000071679:Glycogen Synthase Kinase 3 beta; D054833:Isoindoles / Q000737:chemistry*; D008958:Models, Molecular; D010641:Phenotype; D010797:Phthalimides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015027:Zebrafish / Q000196:embryology
chemical_list: C547670:7,8-dimethoxy-5-methylbenzo(e)isoindole-1,3-dione; D054833:Isoindoles; D010797:Phthalimides; D047428:Protein Kinase Inhibitors; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3