新型三甲氧基苯基喹啉衍生物的设计、合成及抗肿瘤活性研究  

Design,Synthesis and Anticancer Activity Studies of Novel Trimethoxyphenyl-quinoline Derivatives

作　　者：吴博文 崔鑫鑫 朱挺 王胜辉 陆超凡 王金杰 党贺祥 张赛扬 丁丽娜[1,3] 金成允 Wu Bowen;Cui Xinxin;Zhu Ting;Wang Shenghui;Lu Chaofan;Wang Jinjie;Dang Hexiang;Zhang Saiyang;Ding Li'na;Jin Chengyun(Collaborative Innovation Center of New Drug Research and Safety Evaluation,Henan Province,Zhengzhou 450001;School of Basic Medical Sciences,Zhengzhou University,Zhengzhou 450001;Key Laboratory of Advanced Drug Preparation Technologies,Ministry of Education,Zhengzhou 450001;Henan Institute of Advanced Technology,Zhengzhou University,Zhengzhou 450001)

机构地区：[1]新药创制与药物安全性评价河南省协同创新中心,郑州450001 [2]郑州大学基础医学院,郑州450001 [3]教育部药物制备关键技术重点实验室,郑州450001 [4]郑州大学河南省先进技术研究院,郑州450001

出　　处：《有机化学》2020年第4期978-987,共10页Chinese Journal of Organic Chemistry

基　　金：国家自然科学基金(Nos.81703541,81673322);中国博士后科学基金(No.2018M632812)资助项目.

摘　　要：为了寻找新型高效抗肿瘤候选药物,设计并合成了一系列新型三甲氧基苯基-喹啉杂合体,并评估了目标化合物对三种不同肿瘤细胞EC-109(人食管癌细胞),PC-3(人前列腺癌细胞)和MGC-803(人胃癌细胞)的抗增殖活性.结果表明N-(3-(氯甲基)苄基)-3,4,5-三甲氧基-N-(喹啉-8-基)苯甲酰胺(12j)对PC-3细胞具有良好的抗增殖活性,IC50值为9.23μmol/L.同时,化合物12j抑制PC-3细胞增殖和克隆形成.进一步机制研究表明,化合物12j可以将PC-3细胞阻滞在G2/M期,并通过激活内源性和外源性凋亡途径诱导细胞凋亡.With the expectation to find out novel and effective anti-tumor agents,a series of novel trimethoxyphenylquinoline hybrids were designed,synthesized and evaluated for antiproliferative activity against three human cancer cell lines(EC-109,human esophageal cancer cells;PC-3,human prostate cancer cells;MGC-803,human gastric cancer cells).N-(3-(Chloromethyl)benzyl)-3,4,5-trimethoxy-N-(quinolin-8-yl)benzamide(12j)showed the most potent antitumor activity against PC-3 cells with IC50 value of 9.23μmol/L.Meanwhile,compound 12j inhibited the cell viability and colony formation of PC-3 cells.Further mechanism studies revealed that compound 12j could arrest PC-3 cells in G2/M phase and induce cell apoptosis via activating intrinsic and extrinsic apoptosis pathway.

关 键 词：喹啉 三甲氧基苯基 抗肿瘤活性 细胞周期阻滞 凋亡 

分 类 号：R914[医药卫生—药物化学] R96[医药卫生—药学] TQ463.5[化学工程—制药化工]