2. Academic Validation
  3. 3-Arylidene-2-oxindoles as GSK3β inhibitors and anti-thrombotic agents

3-Arylidene-2-oxindoles as GSK3β inhibitors and anti-thrombotic agents

  • Bioorg Med Chem Lett. 2023 May 1:87:129283. doi: 10.1016/j.bmcl.2023.129283.
Denis Babkov 1,  Elena Bezsonova 2,  Viktor Sirotenko 3,  Elias Othman 3,  Vladlen Klochkov 3,  Sergey Sosonyuk 2,  Natalia Lozinskaya 2,  Alexander Spasov 4
Affiliations

Affiliations

  • 1 Scientific Center for Innovative Drugs, Volgograd State Medical University, Volgograd 400131, Russian Federation; Department of Pharmacology & Bioinformatics, Volgograd State Medical University, Volgograd 400131, Russian Federation. Electronic address: dababkov@volgmed.ru.
  • 2 Department of Chemistry, Lomonosov Moscow State University, Moscow 119991, Russia.
  • 3 Department of Pharmacology & Bioinformatics, Volgograd State Medical University, Volgograd 400131, Russian Federation.
  • 4 Scientific Center for Innovative Drugs, Volgograd State Medical University, Volgograd 400131, Russian Federation; Department of Pharmacology & Bioinformatics, Volgograd State Medical University, Volgograd 400131, Russian Federation.
PMID: 37054760 DOI: 10.1016/j.bmcl.2023.129283
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.

Keywords

GSK3β; Oxindole; Platelet; Thrombosis.

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