摘要
为了寻找高效低毒的抗肿瘤药物,设计并合成了一系列新型的含N-(3-丙烯酰胺苯基)乙酰胺结构的喹唑啉类衍生物,并采用噻唑蓝(MTT)法测定了目标化合物对H1975(人肺腺癌细胞系),PC-3(人前列腺癌细胞系),MGC-803(人胃癌细胞系)三种肿瘤细胞的抗增殖活性.结果显示大部分化合物具有较好的抗肿瘤活性,其中N-(3-(2-((4-((4-氯苯基)氨基)-7-甲氧基喹唑啉-6-基)氧基)乙酰氨基)苯基)丙烯酰胺(13j)对H1975,MGC-803两种细胞显示出最好的抗增殖活性,IC50值分别为(6.77±0.65)和(4.06±0.34)μmol/L,其活性均优于阳性对照品吉非替尼,为抗肿瘤药物的研究提供了线索.
In order to find efficient and low toxicity anti-tumor drugs,a series of novel quinazoline derivatives containing N-(3-aminophenyl)acrylamide were synthesized and their antiproliferative activities were evaluated against three human cancer cell lines(H1975,PC-3,MGC-803)by using methyl thiazolyl tetrazolium(MTT)assay.The results showed that most compounds exhibited better antiproliferative activities against the four human tumor cell lines.Among them,N-(3-(2-((4-((4-chlorophenyl)amino)-7-methoxy-quinazolin-6-yl)oxy)acetamido)phenyl)acrylamide(13 j)showed the best antiproliferative activity against H1975 and MGC-803 cancer cell lines with IC50 values of(6.77±0.65)and(4.06±0.34)μmol/L,respectively.Its activity was better than the positive control gefitinib.In a nutshell,this work provides clues to discover antitumor agent based on the quinazoline scaffold.
作者
张路野
张洋
汪正捷
王涛
李二冬
刘丽敏
刘秀娟
郑甲信
可钰
单丽红
刘宏民
张秋荣
Zhang Luye;Zhang Yang;Wang Zhengjie;Wang Tao;Li Erdong;Liu Limin;Liu Xiujuan;Zheng Jiaxin;Ke Yu;Shan Lihong;Liu Hongmin;Zhang Qiurong(School of Pharmaceutical Sciences,Zhengzhou University,Zhengzhou 450001;Collaborative Innovation Center of New Drug Research and Safety Evaluation of Henan Province,Zhengzhou 450001;State Key Laboratory of Esophageal Cancer Prevention&Treatment,Zhengzhou 450052;Key Laboratory of Advanced Drug Preparation Technologies,Ministry of Education,Zhengzhou 450001)
出处
《有机化学》
SCIE
CAS
CSCD
北大核心
2020年第9期2804-2810,共7页
Chinese Journal of Organic Chemistry
基金
国家自然科学基金(No.U1904163)
省部共建食管癌防治国家重点实验室开放基金(No.K2020000X)资助项目。
关键词
丙烯酰胺
喹唑啉
合成
抗肿瘤活性
acrylamide
quinazoline
synthesis
antiproliferative activity
