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

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

作　　者：Shiqi Xu Liyan Zhu Chao Hao Wenqian Liu Chenglong Chen Yongyi Chen Aiqin Liu 许士琪;朱礼岩;郝超;刘文倩;陈成龙;陈泳怡;刘爱芹(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;山东中医药大学药学院,山东济南250355)

机构地区：[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

出　　处：《Journal of Chinese Pharmaceutical Sciences》2021年第9期743-753,共11页中国药学（英文版）

基　　金：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)。

摘　　要：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.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、~(13)C 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：TEGAFUR 5-FLUOROURACIL Amino acid ester Synthesis EVALUATION Antitumor activity 

分 类 号：R916[医药卫生—药学]