Synthesis and Characterization of New Liver Targeting 5-Fluorouracil-Cholic Acid Conjugates
Synthesis and Characterization of New Liver Targeting 5-Fluorouracil-Cholic Acid Conjugates
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新型肝脏靶向 5-氟尿嘧啶-胆酸缀合物的合成和表征
DOI：
10.1002/ardp.200900075
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发表时间：
2009-09-01
影响因子：
5.1
通讯作者：
Wu, Yong
中科院分区：
文献类型：
--
作者：
Qian, Shan;Wu, Jian-Bo;Wu, Yong
本工作的目的是开发一种肝特异性抗肝癌药物。制备了一系列5-氟尿嘧啶/胆酸偶联物（5-FU-胆酸偶联物），并对其化学特性和生物分布特性进行了测试。体外稳定性试验表明，5-FU-胆酸结合物可以完全水解，加热在70 ℃的酸性溶液中，pH = 1，为5分钟。这些化合物的快速和完全水解可以兼容的快速分离和分析方法，以缩短分析时间。通过测定器官组织中再生5-FU的浓度，评价了5-FU-胆酸结合物在小鼠不同器官中经口给药后若干时间点的分解速度。将结果与口服5-FU的对照组小鼠的结果进行比较。小鼠口服前药后肝组织中5-FU的浓度显著升高，且明显高于单纯口服5-FU。结果表明，以胆酸为载体的肝靶向治疗方法具有提高疗效的可行性。
The objective of this work was to develop a liver-specific antihepato carcinoma agent. A series of 5-fluorouracil / cholic acid conjugates (5-FU-cholic acid conjugates) were prepared and tested for their chemical characteristics and bio-distribution properties. The in-vitro stability trial showed 5-FU-cholic acid conjugates could be completely hydrolyzed by heating at 70 degrees C in an acidic solution, pH = 1, for 5 min. The fast and complete hydrolysis of these compounds could be compatible with a fast separation and analysis method to shorten the analysis time. The decomposition speeds of the 5-FU-cholic acid conjugates in different organs of mice at several time points after oral administration were evaluated by measuring the concentrations of regenerated 5-FU in organ tissue. The results were compared with those of the controls, which was a group of mice orally taking 5-FU. The concentrations of 5-FU in mice liver tissue were remarkably increased after oral administration of the prodrugs, and were much larger than if only orally administered 5-FU. The results suggested the feasibility to improve therapeutic efficiency of liver targeting treatments by using cholic acid as the vector of drugs.