阿魏酸衍生物的合成及其抗肿瘤活性研究  

Study on Synthesis and Antitumor Activity of Ferulic Acid Derivatives

作　　者：黄志勇 黄珍[1] 郭易华 李龙[1] 李荣东[1] HUANG Zhiyong;HUANG Zhen;GUO Yihua;LI Long;LI Rongdong(Hunan University of Chinese Medicine,Changsha 410208,China)

机构地区：[1]湖南中医药大学,长沙410208

出　　处：《中国现代应用药学》2022年第5期589-594,共6页Chinese Journal of Modern Applied Pharmacy

基　　金：中药成药性与制剂制备湖南省重点实验室开放基金资助项目(201702)。

摘　　要：目的设计、合成了一系列含有喹唑啉结构的阿魏酸衍生物,并对其抗肿瘤活性进行研究。方法基于拼接原理,将阿魏酸与喹唑啉进行结合,并对喹唑啉6位进行修饰得到目标化合物,采用CCK-8法测试目标化合物对肺癌细胞A549的抗肿瘤活性,利用分子对接技术对目标化合物与表皮生长因子受体的结合模式进行模拟。结果目标化合物的结构经HRMS(ESI)、^(1)H-NMR进行确证;体外抗肿瘤活性结果表明化合物11d、11f、12d和12g的IC_(50)低于阳性药吉非替尼,11c的IC_(50)值与吉非替尼相当。结论化合物11d(IC_(50)=3.09μmol·L^(-1))对肺癌细胞A549抗肿瘤活性较强,值得深入研究。OBJECTIVE To design and synthesize a series of ferulic acid derivatives containing quinazoline structure,and to study their antitumor activity.METHODS Based on the principle of splicing,ferulic acid was combined with quinazoline,and the 6-position of quinazoline was modified to obtain the target compound.The anti-tumor activity of the target compound against lung cancer cell A549 was tested by CCK-8 method.Molecular docking technology was used to simulate the binding mode of the target compound and epidermal growth factor receptor.RESULTS The structure of the target compound was confirmed by HRMS(ESI)and ^(1)H-NMR.The in vitro antitumor activity results showed that the IC_(50) of compounds 11d,11f,12d and 12g were lower than the positive drug of gefitinib,and the IC_(50) of 11c was comparable to gefitinib.CONCLUSION Compound 11d(IC_(50)=3.09μmol·L^(-1))has strong antitumor activity against lung cancer cell A549,which is worthy of further study.

关 键 词：阿魏酸衍生物 合成 抗肿瘤 表皮生长因子受体 

分 类 号：R914.2[医药卫生—药物化学]