合成及鉴定新型 4-芳基丙烯酰基姜黄素类似物作为靶向核因子-κB 信号通路的潜在抗癌剂。
Synthesis and identification of new 4-arylidene curcumin analogues as potential anticancer agents targeting nuclear factor-κB signaling pathway.
机构信息
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510275, China.
出版信息
J Med Chem. 2010 Dec 9;53(23):8260-73. doi: 10.1021/jm1004545. Epub 2010 Nov 11.
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.
摘要
一系列姜黄素类似物，包括新的 4-芳基姜黄素类似物（4-芳基-1,7-双芳基庚-1,6-二烯-3,5-二酮）被合成。细胞生长抑制实验表明，大多数 4-芳基姜黄素类似物能够在亚毫摩尔和低毫摩尔浓度下有效抑制一组肺癌细胞的生长。高内涵分析技术与生化研究相结合表明，与母体化合物姜黄素相比，这一新类 4-芳基姜黄素类似物具有显著提高的 NF-κB 抑制活性，至少部分是通过抑制 IKK 阻断导致 IκB 磷酸化和降解；选定的 4-芳基姜黄素类似物还降低了集落形成实验中癌细胞的致瘤潜力。
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