Design, synthesis and biological evaluation of 5-benzylidene-2-iminothiazolidin-4-ones as selective GSK-3β inhibitors

Eur J Med Chem. 2016 Oct 4:121:727-736. doi: 10.1016/j.ejmech.2016.04.075. Epub 2016 May 7.

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.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Binding, Competitive
  • Chemistry Techniques, Synthetic
  • Drug Design*
  • Glycogen Synthase Kinase 3 beta / antagonists & inhibitors*
  • Glycogen Synthase Kinase 3 beta / chemistry
  • Glycogen Synthase Kinase 3 beta / metabolism
  • Humans
  • Molecular Docking Simulation
  • Molecular Dynamics Simulation
  • Protein Conformation
  • Protein Kinase Inhibitors / chemical synthesis*
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / metabolism
  • Protein Kinase Inhibitors / pharmacology*
  • Structure-Activity Relationship
  • Thiazolidines / chemical synthesis*
  • Thiazolidines / chemistry
  • Thiazolidines / metabolism
  • Thiazolidines / pharmacology*

Substances

  • Protein Kinase Inhibitors
  • Thiazolidines
  • Adenosine Triphosphate
  • Glycogen Synthase Kinase 3 beta