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

A. A. Nagle, S. A. Reddy, H. Bertrand, H. Tajima, T.-M. Dang, S.-C. Wong, J. D. Hayes, G. Wells (Lead / Corresponding author), E.-H. Chew (Lead / Corresponding author)

    Research output: Contribution to journalArticlepeer-review

    10 Citations (Scopus)


    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-?B 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.
    Original languageEnglish
    Pages (from-to)1763-1774
    Number of pages12
    Issue number8
    Publication statusPublished - 2014


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