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Updated: Aug 2, 2025

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3-Arylidene-2-oxindoles as GSK3β inhibitors and anti-thrombotic agents
Denis Babkov1, Elena Bezsonova2, Viktor Sirotenko3
1Scientific Center for Innovative Drugs, Volgograd State Medical University, Volgograd 400131, Russian Federation; Department of Pharmacology & Bioinformatics, Volgograd State Medical University, Volgograd 400131, Russian Federation.
Abstract:
Development of novel agents that prevent thrombotic events is an urgent task considering increasing incidence of cardiovascular diseases and coagulopathies that accompany cancer and COVID-19. Enzymatic assay identified novel GSK3β inhibitors in a series of 3-arylidene-2-oxindole derivatives. Considering the putative role of GSK3β in platelet activation, the most active compounds were evaluated for antiplatelet activity and antithrombotic activity. It was found that GSK3β inhibition by 2-oxindoles correlates with inhibition of platelet activation only for compounds 1b and 5a. Albeit, in vitro antiplatelet activity matched well with in vivo anti-thrombosis activity. The most active GSK3β inhibitor 5a exceeds antiplatelet activity of acetylsalicylic acid in vitro by 10.3 times and antithrombotic activity in vivo by 18.7 times (ED50 7.3 mg/kg). These results support the promising role of GSK3β inhibitors for development of novel antithrombotic agents.
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