Synthesis and one-electron reduction characteristics of radiation-activated prodrugs possessing two 5-fluorodeoxyuridine units.
Synthesis and one-electron reduction characteristics of radiation-activated prodrugs possessing two 5-fluorodeoxyuridine units.
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具有两个5-氟脱氧尿苷单元的辐射激活前药的合成和单电子还原特性。
DOI：
10.1016/j.bmc.2012.07.008
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发表时间：
2012
影响因子：
3.5
通讯作者：
S. Nishimoto
中科院分区：
文献类型：
--
作者：
K. Tanabe;M. Sugiura;Takeo Ito;S. Nishimoto
抗肿瘤剂5-氟脱氧尿苷（5-FdUrd）的两个分子在N（3）位通过2-氧代烷基接头（Oxo-linker）连接，以获得辐射活化的前药FdUrd 2A和FdUrd 2B。本研究中的前药通过缺氧X射线照射引发的单电子还原释放5-FdUrd。从FdUrd 2A和FdUrd 2B释放5-FdUrd比先前的前药Oxo-FdUrd（其具有一个5-FdUrd分子）更有效地进行。当FdUrd 2A溶液在给予细胞之前用大剂量X射线照射时，FdUrd 2A显示出对A549细胞的细胞毒性增加。然而，我们观察到，当在FdUrd 2A存在下在缺氧条件下对细胞进行X-照射时，对细胞毒性没有影响，因为细胞中释放的5-FdUrd的量似乎太低而不能诱导细胞毒性活性。
Two molecules of an antitumor agent, 5-fluorodeoxyuridine (5-FdUrd), were connected by a 2-oxoalkyl linker (Oxo-linker) at the N(3) position to obtain radiation-activated prodrugs, FdUrd2A and FdUrd2B. The prodrugs in this study released 5-FdUrd via one-electron reduction initiated by hypoxic X-irradiation. The release of 5-FdUrd from FdUrd2A and FdUrd2B proceeded more efficiently than that of previous prodrug, Oxo-FdUrd, which possessed one molecule of 5-FdUrd. FdUrd2A exhibited increased cytotoxicity against A549 cells when the FdUrd2A solution had been irradiated with a large dose of X-rays before administration to the cells. However, we observed no effect on cytotoxicity when the cells were X-irradiated under hypoxic conditions in the presence of FdUrd2A because the amount of 5-FdUrd released in the cells seemed to be too low to induce cytotoxic activity.
影响因子：
2.7
作者：
Y. Wei;Y. Yan;D. Pei;B. Gong
通讯作者：
Y. Wei;Y. Yan;D. Pei;B. Gong