3-(2-oxoethylidene)indolin-2-one derivatives activate Nrf2 and inhibit NF-κB: potential candidates for chemoprevention. - Institut Curie Accéder directement au contenu
Article Dans Une Revue ChemMedChem Année : 2014

3-(2-oxoethylidene)indolin-2-one derivatives activate Nrf2 and inhibit NF-κB: potential candidates for chemoprevention.

Amrita A Nagle
  • Fonction : Auteur
Shridhivya A Reddy
  • Fonction : Auteur
Hisashi Tajima
  • Fonction : Auteur
Truong-Minh Dang
  • Fonction : Auteur
Siew-Cheng Wong
  • Fonction : Auteur
John D Hayes
  • Fonction : Auteur
Geoffrey Wells
  • Fonction : Auteur
Eng-Hui Chew
  • Fonction : Auteur

Résumé

Induction of cytoprotective phase 2 enzymes through inhibition of Keap1, a repressor of transcription factor Nrf2, is a cancer-prevention strategy. Compounds that elicit antiinflammatory and cytoprotective effects are promising candidates for chemoprevention. Novel analogues of 1-methyl-3-(2-oxopropylidene)indolin-2-one ('supercinnamaldehyde'; SCA) were synthesized, and their abilities to induce cytoprotective responses through Nrf2 induction and to suppress inflammatory responses were examined. 1-Methyl-3-(2-oxo-2-phenylethylidene)indolin-2-one (6) was identified as the lead compound. The compounds showed induction of Nrf2-dependent phase 2 enzymes in Keap1+/+ mouse embryonic fibroblasts (MEFs), which was abrogated in Keap1-/- MEFs. The compounds also displayed a suppressive effect on NF-κB signaling that was at least partly responsible for inhibition of lipopolysaccharideinduced inflammatory responses. These SCA analogues exhibited cytoprotective and anti-inflammatory activities and may be developed further as chemopreventive agents.

Domaines

Chimie organique

Dates et versions

hal-01073571 , version 1 (10-10-2014)

Identifiants

Citer

Amrita A Nagle, Shridhivya A Reddy, Helene Bertrand, Hisashi Tajima, Truong-Minh Dang, et al.. 3-(2-oxoethylidene)indolin-2-one derivatives activate Nrf2 and inhibit NF-κB: potential candidates for chemoprevention.. ChemMedChem, 2014, 9 ((8)), pp.1763-74. ⟨10.1002/cmdc.201402038⟩. ⟨hal-01073571⟩
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