摘要：FAPα激活式多柔比星前药的抗肿瘤效果优于多柔比星药物分子本身，具有低毒性， 高选择性的特点，但其合成方法有很大的改进空间。本文对已知的多柔比星 FAPα酶激活 式前药的合成方法加以改进，在已有合成路线的基础上，针对其反应条件及操作上的缺 点，优化设计了新的合成路线。结果表明：改进的合成路线不仅反应条件温和，即反应 时间缩短，试剂简单易得；操作步骤简化，即不需要麻烦的后处理和严格的 pH 控制；而 且转化率接近 100%，产率达到 90%以上。进一步，通过药理学研究，探索建立了 FAPα酶 激活式前药的生物活性评价体系，为新型化疗药物的 FAPα酶激活式前药研究奠定了基础。76006

毕业论文关键词 多柔比星 FAPα 前药

毕 业 设 计 说 明 书 外 文 摘 要

Title Research on targeting tumor tissue of chemotherapeutic prodrug

Abstract FAPα enzyme-activated doxorubicin prodrug has better antitumor effect than doxorubicin molecule itself, which has characteristics of low toxicity and high selectivity。 However, there is much room for improvement on its synthesis method。 In this paper, the known synthesis method of FAPα enzyme-activated doxorubicin prodrug was improved。 Aiming at the disadvantages on the reaction conditions and operation, the new synthetic route was optimally designed based on the existing route。 The results showed that the improved route not only had the mild reaction conditions, i。e。 the shortened reaction time and the simple and readily available reagents, and had the simplified procedure, i。e。 without a troublesome post-treatment and strict pH control, but also the conversion rate closed to 100% and the yield was more than 90%。 Meanwhile, the biological activity evaluation system of FAPα enzyme-activated prodrug was established by the pharmacology study。 It laid the foundation for research on the novel FAPα enzyme-activated prodrug of chemotherapeutic drug。

Keywords  Doxorubicin    FAPα      Prodrugs

本科毕业设计说明书 第 I 页

目 录

1 引言 1

1。1 多柔比星简介 1

1。1。1 化学性质 1

1。1。2 抗肿瘤机制 2

1。1。3 毒副作用 2

1。1。4 结构修饰 3

1。1。5 前药研究 4

1。2 FAPα简介 5

1。2。1 FAPα结构 5

1。2。2 FAPα活性 5

1。2。3 FAPα与肿瘤细胞关系 6

1。2。4 针对 FAPα的靶向药物治疗 6

1。3 存在问题及本文研究内容 6

2