新型L-酪氨酸二肽衍生物的合成及其抗肿瘤活性  

Synthesis and Antitumor Activities of Novel L-tyrosine Dipeptide Derivatives

作　　者：曹盼 曾晓萍[2,3] 梁光义[2,3] 徐必学[2,3] CAO Pan;ZENG Xiao-ping;LIANG Guang-yi;XU Bi-xue(Guizhou University of Traditional Chinese Medicine,Guiyang 550002,China;State Key Laboratory of Functions and Applications of Medicinal Plants,Guizhou Medical University,Guiyang 550014,China;The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences/Guizhou Provincial Engineering Research Center for Natural Drugs,Guiyang 550002,China)

机构地区：[1]贵州中医药大学,贵州贵阳550025 [2]贵州医科大学省部共建药用植物功效与利用国家重点实验室,贵州贵阳550014 [3]贵州省中国科学院天然产物化学重点实验室/贵州省天然药物工程研究中心,贵州贵阳550014

出　　处：《合成化学》2020年第3期167-173,共7页Chinese Journal of Synthetic Chemistry

基　　金：国家自然科学基金资助项目(81760623);贵州省科技厅项目(黔科合平台人才【2016】5678,黔科合平台人才【2017】5737);贵阳中医学院研究生工作站创新项目(GNYL[2017]008号-7-Y)。

摘　　要：以L-酪氨酸甲酯盐酸盐和对羟基苯甲酸(PHBA)为原料,经缩合、水解和亲核取代反应,设计并合成了9个新型的L-酪氨酸二肽衍生物(3b和4a^4h),其结构经1 H NMR、13 C NMR和MS(ESI)表征。采用MTT法评价了化合物对白血病细胞(K562)、人肺癌细胞(A549)和人肝癌细胞(HepG2)的体外抑制活性。结果表明:N-[N-(4-苄氧基-苯甲酰基)-O-二甲氨基丙基-L-酪氨酰基]-L-苯丙氨醇(4e)对HepG2和K542细胞的抑制活性均高于阳性对照药阿霉素,IC 50分别为0.41和11.77μmol·L^-1。Nine novel L-tyrosine dipeptide derivatives(3b,4a^4h)were obtained by condensation reaction,hydrolysis and nucleophilic substitution reactions,using L-tyrosine methyl ester hydrochloride and 4-hydroxy-benzoicacid(PHBA)as starting material.The structures were characterized by 1 H NMR,13 C NMR and MS(ESI).In vitro anticancer activities against three human cancer cell lines(K562,A549 and HepG2)were demonstrated by MTT assays.The results showed that the inhibitory activity of compound 4e on HepG2 and K542 cells were better than the positive control drug doxorubicin,which IC 50 was 0.41 and 11.77μmol·L^-1,respectively.

关 键 词：L-酪氨酸二肽 对羟基苯甲酸 缩合反应 合成 MTT法 抗肿瘤活性 

分 类 号：O626[理学—有机化学]