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.
Minhajul Arfeen  1 ,  Shweta Bhagat  1 ,  Rahul Patel  1 ,  Shivcharan Prasad  2 ,  Ipsita Roy  2 ,  Asit K Chakraborti  1 ,  Prasad V Bharatam  3
Affiliations
  • 1. Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Sector 67, S.A.S. Nagar, 160062, Punjab, India.
  • 2. Department of Biotechnology, National Institute of Pharmaceutical Education and Research, Sector 67, S.A.S. Nagar, 160062, Punjab, India.
  • 3. Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Sector 67, S.A.S. Nagar, 160062, Punjab, India. Electronic address: [email protected].
PMID: 27423119 DOI: 10.1016/j.ejmech.2016.04.075
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.
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