Synthesis and identification of new 4-arylidene curcumin analogues as potential anticancer agents targeting nuclear factor-κB signaling pathway.

Abstract

A series of curcumin analogues including new 4-arylidene curcumin analogues (4-arylidene-1,7-bisarylhepta-1,6-diene-3,5-diones) were synthesized. Cell growth inhibition assays revealed that most 4-arylidene curcumin analogues can effectively decrease the growth of a panel of lung cancer cells at submicromolar and low micromolar concentrations. High content analysis technology coupled with biochemical studies showed that this new class of 4-arylidene curcumin analogues exhibits significantly improved NF-κB inhibition activity over the parent compound curcumin, at least in part by inhibiting IκB phosphorylation and degradation via IKK blockage; selected 4-arylidene curcumin analogues also reduced the tumorigenic potential of cancer cells in a clonogenic assay.

• Authors: Xu Qiu, Yuhong Du, Bin Lou, Yinglin Zuo, Weiyan Shao, Yingpeng Huo, Jianing Huang, Yanjun Yu, Binhua Zhou, Jun Du, Haian Fu, Xianzhang Bu
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 53 Issue 23 Pg. 8260-73 (Dec 09 2010) ISSN: 1520-4804 [Electronic] United States
• PMID: 21070043 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• NF-kappa B
• Tumor Necrosis Factor-alpha
• Curcumin

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Cell Line, Tumor
• Cell Nucleus (metabolism)
• Curcumin (analogs & derivatives, chemical synthesis, pharmacology)
• Humans
• Inhibitory Concentration 50
• Lung Neoplasms (pathology)
• Magnetic Resonance Spectroscopy
• NF-kappa B (metabolism)
• Signal Transduction (drug effects)
• Tumor Necrosis Factor-alpha (antagonists & inhibitors)