七叶内酯衍生物的合成及其生物活性  

Synthesis and Biological Activities of Esculetin Derivatives

作　　者：叶蓁 罗琴 李善斌 覃江克[3] 周先丽[2] 梁成钦[1] Ye Zhen;Luo Qin;Li Shanbin;Qin Jiangke;Zhou Xianli;Liang Chengqin(College of Pharmacy,Guilin Medical University,Guilin 541199;College of Biotechnology,Guilin Medical University,Guangxi Guilin 541199;Science Experiment Center,Guilin Medical University,Guilin 541199 China;State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources,School of Chemistry and Pharmaceutical Sciences of Guangxi Normal University,Guilin 541004,China)

机构地区：[1]桂林医学院药学院,广西桂林541199 [2]桂林医学院生物技术学院,广西桂林541199 [3]广西师范大学药物资源化学与分子工程国家重点实验室,广西桂林541004

出　　处：《广东化工》2020年第24期13-15,共3页Guangdong Chemical Industry

基　　金：广西自然科学基金资助项目:2018GXNSFBA281079;国家自然科学基金地资助项目:82060787和31560100。

摘　　要：目的:设计合成一系列七叶内酯衍生物,并对其抗肿瘤活性,抗HBV活性进行筛选。方法:通过亲核取代反应合成6,7位羟基取代的衍生物,通过NMR,MS对目标化合物结构进行表征。以MTT法检测化合物对五种肿瘤细胞的抑制作用;以Elisa试剂盒检测化合物对HepG2.2.15细胞分泌HbsAg和HbeAg的抑制作用。结果:合成了10个七叶内酯衍生物,其中7个化合物未见文献报道。化合物a7对五种肿瘤细胞均有着明显的抑制作用,IC50分别为23.41(Lovo),16.26(HepG2),28.02(Hela),38.24(NCI-H460)和39.26(T47D)μmol/L。同时,化合物a1, a2对HBV有着良好的抑制作用,其培养第九天对Hbs Ag和HbeAg抑制作用的IC50分别为52.36,43.62 mg/L和45.32,62.51mg/L。结论:七叶内酯的部分衍生物具有明显的抗肿瘤和抗HBV的活性,该结果为进一步研究开发七叶内酯的药用价值提供了基础。Objective: A series of esculetin derivatives were designed and synthesized, and their anti-tumor and anti-HBV activities were tested. Methods: The 6 and 7 hydroxyl modified derivatives were synthesized by nucleophilic substitution reaction, and the structures were characterized by NMR and MS. MTT assay was used to detect the inhibitory effects of the derivatives on five tumor cells. And their inhibitions of HbsAg and HbeAg secretion by HepG2.2.15 cells were detected by Elisa. Results: Ten esculetin derivatives were synthesized, and seven of them have not been reported in the literatures. Compound a7 showed significant inhibitory effects on five tumor cells with IC50 of a7 was 23.41(Lovo), 16.26(HepG2), 28.02(Hela), 38.24(NCI-H460) and 39.26(T47 D) μmol/L, respectively. At the same time, compounds a1 and a2 had a good inhibitory effects on HBV. On the 9 th day of culture, HbsAg and HbeAg were significantly inhibited and their IC50 values were 52.36, 43.62 mg/L and 45.32, 62.51 mg/L, respectively. Conclusion: Some derivatives of esculetin have obvious anti-tumor and anti-HBV activities. These results provide a basis for further research and development of the medicinal value of esculetin.

关 键 词：七叶内酯 催化剂 产率 抗肿瘤活性 抗HBV活性 

分 类 号：TQ[化学工程]