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

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.