Fukamiya Narihiko, Lee Kuo-Hsiung, Muhammad Ilias, Murakami Chihiro, Okano Masayohis, Harvey Isabelle, Pelletier Jerry
Faculty of Integrated Arts and Sciences, Hiroshima University, Kagamiyama 1-7-1, Higashi, Hiroshima 739-8521, Japan.
Cancer Lett. 2005 Mar 18;220(1):37-48. doi: 10.1016/j.canlet.2004.04.023.
The effect of 63 quassinoids on eukaryotic protein synthesis has been investigated. Seventeen of the tested compounds showed potent in vitro activity, with IC50s below 2 microM for inhibition in Krebs ascites translation extracts. Sixteen of these quassinoids were also potent inhibitors of in vivo protein synthesis when exposed to Hela cells for 1 h. Our results led to the following structure-activity relationships for quassinoids regarding translation inhibition. Activity is influenced by (i) the nature of the C-15 side chain, (ii) the nature of A ring modifications, (iii) the presence or absence of a sugar moiety, and (iv) the presence of an epoxymethano bridge.
已对63种苦木素类化合物对真核生物蛋白质合成的影响进行了研究。在所测试的化合物中，有17种在体外显示出强效活性，在克雷布斯腹水翻译提取物中抑制作用的IC50低于2 microM。当将这些苦木素类化合物中的16种暴露于Hela细胞1小时时，它们也是体内蛋白质合成的强效抑制剂。我们的研究结果得出了苦木素类化合物在翻译抑制方面的以下构效关系。活性受以下因素影响：（i）C-15侧链的性质，（ii）A环修饰的性质，（iii）糖部分的存在与否，以及（iv）环氧亚甲基桥的存在。
