3‐(2‐Oxoethylidene)indolin‐2‐one Derivatives Activate Nrf2 and Inhibit NF‐κB: Potential Candidates for Chemoprevention. Issue 8 (12th May 2014)

• Record Type: Journal Article
• Authors: Nagle, Amrita A.; Reddy, Shridhivya A.; Bertrand, Helene; Tajima, Hisashi; Dang, Truong‐Minh; Wong, Siew‐Cheng; Hayes, John D.; Wells, Geoffrey; Chew, Eng‐Hui
• Is Part Of: ChemMedChem. Volume 9:Issue 8(2014:Aug.)
• Page Start: 1763
• Page End: 1774
• Publication Date: 2014-05-12
• Subjects: Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.201402038
• Languages: English
• ISSNs: 1860-7179

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>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 (<bold>6</bold>) 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.</p> </abstract>