Bicyclic cyclohexenones as inhibitors of NF-κB signaling

Joseph K. Hexum, Rodolfo Tello-Aburto, Nicholas B. Struntz, Andrew M. Harned, Daniel A. Harki

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

A series of structurally simplified cryptocaryone analogues were synthesized by a facile Pd-catalyzed acetoxylation of alkyne-tethered cyclohexadienones and evaluated as inhibitors of NF-κB signaling. Compounds 10 and 11 were found to possess low micromolar inhibitory properties toward induced NF-κB activity by blocking p50/p65 nuclear protein through a covalent inhibition mechanism. Both compounds were able to inhibit NF-κB-induced IL-8 expression and exhibited antiproliferative activity against two model cancer cell lines. These analogues constitute a promising new scaffold for the development of novel NF-κB inhibitors and anticancer agents.

Original languageEnglish (US)
Pages (from-to)459-464
Number of pages6
JournalACS Medicinal Chemistry Letters
Volume3
Issue number6
DOIs
StatePublished - May 14 2012

Keywords

  • NF-κB inhibitors
  • Natural product analogues
  • Pd-catalyzed acetoxylation
  • anticancer agents

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