Abstract
In this work, iminothiazolidin-4-one derivatives were explored as selective GSK-3β inhibitors. Molecular docking analysis was carried to design a series of compounds, which were synthesized using substituted thiourea, 2-bromoacetophenones and benzaldehydes. Out of the twenty five compounds synthesized during this work, the in vitro evaluation against GSK-3 led to the identification of nine compounds with activity in lower nano-molar range (2-85 nM). Further, in vitro evaluation against CDK-2 showed five compounds to be selective towards GSK-3.
Keywords:
CDK-2; GSK-3; Molecular docking; Molecular dynamics; SBDD.
Copyright © 2016 Elsevier Masson SAS. All rights reserved.
MeSH terms
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Adenosine Triphosphate / metabolism
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Binding, Competitive
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Chemistry Techniques, Synthetic
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Drug Design*
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Glycogen Synthase Kinase 3 beta / antagonists & inhibitors*
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Glycogen Synthase Kinase 3 beta / chemistry
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Glycogen Synthase Kinase 3 beta / metabolism
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Humans
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Molecular Docking Simulation
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Molecular Dynamics Simulation
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Protein Conformation
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Protein Kinase Inhibitors / chemical synthesis*
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Protein Kinase Inhibitors / chemistry
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Protein Kinase Inhibitors / metabolism
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Protein Kinase Inhibitors / pharmacology*
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Structure-Activity Relationship
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Thiazolidines / chemical synthesis*
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Thiazolidines / chemistry
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Thiazolidines / metabolism
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Thiazolidines / pharmacology*
Substances
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Protein Kinase Inhibitors
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Thiazolidines
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Adenosine Triphosphate
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Glycogen Synthase Kinase 3 beta