姜黄素类似物2,6-双（亚苄基）-4-苯基环己酮的合成及其细胞毒性特性
Syntheses and cytotoxic properties of the curcumin analogs 2,6-bis(benzylidene)-4-phenylcyclohexanones.
作者信息
Davis Ryan, Das Umashankar, Mackay Hilary, Brown Toni, Mooberry Susan L, Dimmock Jonathan R, Lee Moses, Pati Hari
机构信息
Department of Chemistry, Hope College, Holland, MI 49423, USA.
出版信息
Arch Pharm (Weinheim). 2008 Jul;341(7):440-5. doi: 10.1002/ardp.200800028.
Fifteen curcumin analogs were synthesized and tested for in-vitro cytotoxicity towards B16 and L1210 murine cancer cell lines using an MTT assay. Significant activity was discovered for two analogs: 8 (B16 IC(50) = 1.6 microM; L1210 IC(50) = 0.35 microM) and 9 (B16 IC(50) = 0.51 microM; L1210 IC(50 )= 1.2 microM). Several other analogs exhibited notable cytotoxicity. The data from quantitative structure-activity relationships suggest that large electron-withdrawing substituents placed in the meta-position of the arylidene aryl rings enhance potencies. Compounds 8 and 9 were found using a cell-based assay to have virtually no effects on microtubules at concentrations up to 40 microM. These results suggest that tubulin inhibition is not the principal mechanism by which the curcumin analogs act.
合成了15种姜黄素类似物，并使用MTT法测试了它们对B16和L1210小鼠癌细胞系的体外细胞毒性。发现两种类似物具有显著活性：8（B16细胞半数抑制浓度（IC50）=1.6微摩尔；L1210细胞半数抑制浓度（IC50）=0.35微摩尔）和9（B16细胞半数抑制浓度（IC50）=0.51微摩尔；L1210细胞半数抑制浓度（IC50）=1.2微摩尔）。其他几种类似物也表现出显著的细胞毒性。定量构效关系数据表明，位于亚芳基芳环间位的大吸电子取代基可增强活性。通过基于细胞的试验发现，化合物8和9在浓度高达40微摩尔时对微管几乎没有影响。这些结果表明，微管蛋白抑制不是姜黄素类似物发挥作用的主要机制。
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