Bicyclic cyclohexenones as inhibitors of NF-κB signaling

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

doi:10.1021/ml300034a

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 journal › Article › peer-review

49 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 language	English (US)
Pages (from-to)	459-464
Number of pages	6
Journal	ACS Medicinal Chemistry Letters
Volume	3
Issue number	6
DOIs	https://doi.org/10.1021/ml300034a
State	Published - May 14 2012

Keywords

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

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1021/ml300034a

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AU - Tello-Aburto, Rodolfo

AU - Struntz, Nicholas B.

AU - Harned, Andrew M.

AU - Harki, Daniel A.

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AB - 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.

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Bicyclic cyclohexenones as inhibitors of NF-κB signaling

Abstract

Keywords

UN SDGs

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