前药
硝基还原酶
连接器
化学
紫杉醇
硝基咪唑
配体(生物化学)
提拉帕扎明
药理学
组合化学
药品
细胞毒性
选择性
体外
立体化学
生物化学
受体
有机化学
化疗
生物
催化作用
操作系统
遗传学
计算机科学
作者
Qiumeng Zhang,Chen Jin,Jiahui Yu,Wei Lü
出处
期刊:ACS omega
[American Chemical Society]
日期:2018-08-08
卷期号:3 (8): 8813-8818
被引量:8
标识
DOI:10.1021/acsomega.8b01208
摘要
Because of the low selectivity and efficiency of normal antitumor agents, the strategy of ligand-targeted drugs was put forward. In this paper, we designed and synthesized a new bioreductive linker based on 2-nitroimidazole, which was used in three paclitaxel (PTX) prodrugs. The drug release mechanism via six-membered ring was demonstrated by chemical reduction and nitroreductase assay. Glucose and acetazolamide, which have been reported widely as ligands, were attached to compound 7 to afford Glu-PTX and AZO-PTX. The prodrugs were considerably stable in phosphate-buffered saline (pH 7.4) and plasma. What is more, PTX releasing could be triggered by nitroreductase rapidly. In in vitro cytotoxicity assay, the prodrugs exhibited moderate selectivity toward hypoxic tumor cells. We considered that the 2-nitroimidazole linker could accelerate the release of prodrugs under hypoxic condition. It was promising in the development of ligand-targeted drugs.
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