title: Bicyclic Cyclohexenones as Inhibitors of NF-κB Signaling.
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 towards 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.
authors.affiliation: Department of Medicinal Chemistry, University of Minnesota, 717 Delaware St SE, Minneapolis, MN, 55414, USA.
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Hexum
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Tello-Aburto
authors.forename: Nicholas B
authors.initials: NB
authors.lastname: Struntz
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Harned
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Harki