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.
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•A few selective GSK-3β Inhibitors were designed and synthesized: 5-benzylidene-2-iminothiazolidin-4-ones.•Structure Based Drug Design techniques were utilized employed to highlight the importance of 2-iminothialidin-4-one ring.•In vitro evaluation of 25 compounds resulted in identification of nine compounds of lower nanomolar range (2.1–84.8 nM).•Six compounds showed selective GSK-3β inhibitory activity against CDK-2 at 2 μM concentration.•MD simulation showed that residues like Lys85, Thr138, and Arg141 play crucial role in selective inhibition.