Isothiouronium modification empowers pyrimidine-substituted curcumin analogs potent cytotoxicity and Golgi localization
Isothiouronium modification empowers pyrimidine-substituted curcumin analogs potent cytotoxicity and Golgi localization
复制标题
异硫脲修饰赋予嘧啶取代的姜黄素类似物强大的细胞毒性和高尔基体定位
DOI：
10.1016/j.ejmech.2016.07.071
复制
发表时间：
2016-11-10
影响因子：
6.7
通讯作者：
Zhang, Lijuan
中科院分区：
文献类型：
--
作者：
Tong, Sheng;Zhang, Meng;Zhang, Lijuan
大多数蛋白质翻译后修饰发生在高尔基体中，许多人类疾病与高尔基体功能异常或高尔基体中蛋白质翻译后修饰不当有关。在这项研究中，我们设计并合成了 4 x 6 系列新型异硫脲修饰的 (E,E)-4,6-双(苯乙烯基)-嘧啶类似物，并发现它们定位于高尔基体，如类似物的内在荧光所显示的那样。异硫脲修饰的类似物在正常细胞（中国仓鼠卵巢或 CHO）和癌细胞中均具有有效的细胞毒性。此外，全甲基化异硫脲修饰类似物显示出癌细胞选择性细胞毒性。使用 7 个 CHO 和 4 个人类癌细胞系研究了异硫脲修饰化合物高尔基体定位的分子机制，结果表明这些化合物在高尔基体中具有结合伴侣。因此，异硫脲修饰的类似物可能是有前途的抗癌剂、新型高尔基体染色试剂以及用于研究正常细胞或癌细胞以及高尔基体相关人类疾病中高尔基体功能的有用研究工具。 (C) 2016 Elsevier Masson SAS。版权所有。
Most of protein post-translational modifications occur in the Golgi and many human diseases are associated with abnormal Golgi function or improper post translational modifications of proteins in the Golgi. In this study, we designed and synthesized 4 x 6 series of novel isothiouronium-modified (E,E)-4,6-bis(styryl)-pyrimidine analogs and found that they localized at the Golgi as visualized by the intrinsic fluorescence of the analogs. The isothiouronium-modified analogs had potent cytotoxicity in both normal (Chinese Hamster Ovary or CHO) and cancer cells. Furthermore, permethylated isothiouronium-modified analogs showed cancer cell-selective cytotoxicity. The molecular mechanisms underlying Golgi localization of isothiouronium-modified compounds were investigated using 7 CHO and 4 human cancer cell lines and the results indicated that the compounds had binding partners in the Golgi. Thus, isothiouronium-modified analogs might be promising anticancer agents, novel Golgi staining reagents, and useful research tools for studying Golgi functions in normal or cancer cells and in Golgi-related human diseases. (C) 2016 Elsevier Masson SAS. All rights reserved.