一种新型含氨基酸基团替加氟前药的合成及其抗肿瘤活性评价

doi:10.5246/jcps.2021.09.062

中国药学(英文版) ›› 2021, Vol. 30 ›› Issue (9): 743-753.DOI: 10.5246/jcps.2021.09.062

一种新型含氨基酸基团替加氟前药的合成及其抗肿瘤活性评价

许士琪¹, 朱礼岩¹, 郝超¹, 刘文倩¹, 陈成龙², 陈泳怡¹, 刘爱芹¹^,^*()

1. 山东省医学科学院药物研究所, 山东第一医科大学, 山东济南 250062
2. 山东中医药大学药学院, 山东济南 250355

收稿日期:2021-04-23 修回日期:2021-07-02 接受日期:2021-08-11 出版日期:2021-09-27 发布日期:2021-09-27
通讯作者: 刘爱芹
作者简介:
+ Tel.: +86-18815314707, E-mail: liuaiqin@sdfmu.edu.cn
基金资助:
Science and Technology Program of Shandong Academy of Medical Sciences (Grant No. 2016-5); National Innovation and Entrepreneurship Training Program for College Students (Grant No. 201810427013).

Synthesis of a novel series of amino acid prodrugs based on tegafur and evaluation of their antitumor activity

Shiqi Xu¹, Liyan Zhu¹, Chao Hao¹, Wenqian Liu¹, Chenglong Chen², Yongyi Chen¹, Aiqin Liu¹^,^*()

1 Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250062, Shandong, China
2 School of Pharmacy, Shandong University?of?Traditional?Chinese?Medicine, Jinan 250355, Shandong, China

Received:2021-04-23 Revised:2021-07-02 Accepted:2021-08-11 Online:2021-09-27 Published:2021-09-27
Contact: Aiqin Liu

摘要/Abstract

摘要：

替加氟是一种转化为5-氟尿嘧啶的口服化疗前药, 主要通过抑制胸苷酸合酶激活并杀死肿瘤细胞。本研究通过取代、水解、缩合合成了20种新的含氨基酸酯基团的替加氟衍生物, 并通过¹H NMR、¹³C NMR和H RMS对其结构进行确证, 并研究了它们对肿瘤细胞生长抑制作用, 结果表明某些化合物有较好的抗肿瘤活性。

关键词: 替加氟, 5-氟尿嘧啶, 氨基酸酯, 合成, 评价, 抗肿瘤活性

Abstract:

As an oral chemotherapy prodrug, tegafur, can be converted to 5-fluorouracil, which is activated to kill tumor cells mainly by the inhibition of thymidylate synthase. In the present study, we synthesized 20 new tegafur derivatives containing amino acid ester groups by substitution, hydrolysis, and condensation. Their structures were confirmed by ¹H NMR, ¹³C NMR, and H RMS, and their inhibitory effects on tumor cell growth were studied. The results showed that some of the compounds had good anti-tumor activity.

Key words: Tegafur, 5-Fluorouracil, Amino acid ester, Synthesis, Evaluation, Antitumor activity

Supporting:

许士琪, 朱礼岩, 郝超, 刘文倩, 陈成龙, 陈泳怡, 刘爱芹. 一种新型含氨基酸基团替加氟前药的合成及其抗肿瘤活性评价[J]. 中国药学(英文版), 2021, 30(9): 743-753.

Shiqi Xu, Liyan Zhu, Chao Hao, Wenqian Liu, Chenglong Chen, Yongyi Chen, Aiqin Liu. Synthesis of a novel series of amino acid prodrugs based on tegafur and evaluation of their antitumor activity[J]. Journal of Chinese Pharmaceutical Sciences, 2021, 30(9): 743-753.

图/表 4

Figure 1. Amino acid (AA) prodrugs in oral drug delivery.

Figure 2. Amino acid structural diversity.

Figure 3. Amino acids structural ester diversity.

Table 1. The in vitro cytotoxic activity of 4a–4t.

参考文献 13

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一种新型含氨基酸基团替加氟前药的合成及其抗肿瘤活性评价

Synthesis of a novel series of amino acid prodrugs based on tegafur and evaluation of their antitumor activity

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