Identifying New Isatin Derivatives with GSK-3β Inhibition Capacity through Molecular Docking and Bioassays

被引：14

作者：

Britto, Karolinni B. ^{[1
]}

Francisco, Carla S. ^{[2
]}

Ferreira, Debora ^{[3
]}

Borges, Barbara J. P. ^{[1
]}

Conti, Raphael ^{[2
]}

Profeti, Demetrius ^{[4
]}

Rodrigues, Ligia R. ^{[3
]}

Lacerda Jr, Valdemar ^{[2
]}

Morais, Pedro A. B. ^{[4
]}

Borges, Warley S. ^{[1
,2
]}

机构：

[1] Univ Fed Espirito Santo, Programa Posgrad Ciencias Farmaceut, BR-29075910 Vitoria, ES, Brazil

[2] Univ Fed Espirito Santo, Programa Posgrad Quim, BR-29075910 Vitoria, ES, Brazil

[3] Univ Minho, Ctr Biol Engn, Campus Gualtar, P-4710057 Braga, Portugal

[4] Univ Fed Espirito Santo, Ctr Ciencias Exatas Nat & Saude, BR-29500000 Alegre, ES, Brazil

来源：

JOURNAL OF THE BRAZILIAN CHEMICAL SOCIETY | 2020年 / 31卷 / 03期

关键词：

isatin derivatives; GSK-3; beta; molecular docking; GLYCOGEN-SYNTHASE KINASE-3; PROTEIN-KINASE; PHOSPHORYLATION; EXPRESSION; GSK3-BETA; PEPTIDE; DESIGN; ACIDS;

D O I：

10.21577/0103-5053.20190206

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The semi-synthesis of 11 isatin derivatives was achieved through bimolecular nucleophilic substitution and click chemistry. Seven new compounds were obtained. All chemical structures were determined by infrared spectroscopy (IR), nuclear magnetic resonance spectrometry (NMR) and high-resolution mass spectrometry (HRMS) data. These derivatives were evaluated for their anti-GSK-3 beta activity and all isatin derivatives (N-alkyl and 1,2,3-triazolic) exhibited strong inhibitory activity, with 2b and 4h exhibiting remarkable potency. In addition, docking studies were performed with 2b and 2e models to unravel the molecular mechanism underlying the polar interactions on the GSK-3 beta ATP-binding site.

引用

页码：476 / 487

页数：12

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