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  3. Synthesis of novel 4/5-substituted 3-arylidene-2-oxindole derivatives and their biological evaluation as NQO2 ligands and NLRP3 downregulators

Synthesis of novel 4/5-substituted 3-arylidene-2-oxindole derivatives and their biological evaluation as NQO2 ligands and NLRP3 downregulators

  • Bioorg Med Chem Lett. 2025 Dec 15:129:130372. doi: 10.1016/j.bmcl.2025.130372.
Elena N Bezsonova 1,  Meriam Dubar 2,  Daria D Melekhina 2,  Mariia A Salykina 2,  Ivan V Boichenko 2,  Denis A Babkov 3,  Roman D Danilov 3,  Alexander A Spasov 3,  Natalia A Lozinskaya 4
Affiliations

Affiliations

  • 1 Department of Chemistry, Lomonosov Moscow State University, Moscow 119991, Russia. Electronic address: [email protected].
  • 2 Department of Chemistry, Lomonosov Moscow State University, Moscow 119991, Russia.
  • 3 Scientific Center for Innovative Drugs, Volgograd State Medical University, Volgograd 400131, Russia.
  • 4 Department of Chemistry, Lomonosov Moscow State University, Moscow 119991, Russia. Electronic address: [email protected].
PMID: 40818726 DOI: 10.1016/j.bmcl.2025.130372
Abstract

Quinone oxidoreductase II (NQO2) is a flavoprotein implicated in Reactive Oxygen Species production which can be considered a potential target for anti-inflammatory drugs. Previously, we demonstrated that 2-oxindole derivatives are effective inhibitors of NQO2. In this work, novel 4/5-substituted 3-arylidene-2-oxindoles were synthesized and their affinity towards NQO2 was assessed in vitro. The obtained compounds activated NQO2 up to 85 %. Some derived NQO2 activators showed anti-inflammatory activity via NLRP3 inflammasome activation in LPS + ATP-stimulated murine macrophages. The obtained compounds were shown to be non-toxic in LDH-assay.

Keywords

2-oxindole; Anti-inflammatory activity; NLRP3; NQO2.

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