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
  • 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.
Products