新型腙基取代嘧啶衍生物的合成及抗肿瘤活性评价  

Synthesis and Antitumor Activity Evaluation of Novel Hydrazone-Substituted Pyrimidine Derivatives

作　　者：张洋 张路野 刘丽敏 王涛 孟娅琪 栗娜 李二冬 汪正捷 刘秀娟 郑甲信[1,3] 单丽红 刘宏民[1,2,3,4,5] 张秋荣 Zhang Yang;Zhang Luye;Liu Limin;Wang Tao;Meng Yaqi;Li Na;Li Erdong;Wang Zhengjie;Liu Xiujuan;Zheng Jiaxin;Shan Lihong;Liu Hongmin;Zhang Qiurong(School of Pharmaceutical Sciences,Zhengzhou University,Zhengzhou 450001;Collaborative Innovation Center of New Drug Research and Safety Evaluation,Zhengzhou 450001;Key Laboratory of Advanced Drug Preparation Technologies,Ministry of Education,Zhengzhou 450001;Key Laboratory of Henan Province for Drug Quality and Evaluation,Zhengzhou 450001;State Key Laboratory of Esophageal Cancer Prevention&Treatment,Zhengzhou University,Zhengzhou 450052)

机构地区：[1]郑州大学药学院,郑州450001 [2]新药创制与药物安全性评价河南省协同创新中心,郑州450001 [3]教育部药物关键制备技术重点实验室,郑州450001 [4]河南省药品质量与评价重点实验室,郑州450001 [5]省部共建食管癌防治国家重点实验室,郑州450052

出　　处：《有机化学》2020年第6期1731-1736,共6页Chinese Journal of Organic Chemistry

基　　金：国家自然科学基金(No.81773562);国家蛋白质研究项目(No.2018YFE0195100);省部共建食管癌防治国家重点实验室资助的开放基金(No.K2020000X)资助项目.

摘　　要：为了寻找高效的新型抗肿瘤药物,设计并合成了一系列新型腙基取代的2,4,6-取代嘧啶衍生物,并对目标化合物在MCF-7(人乳腺癌细胞), MGC-803(人胃癌细胞系),PC-3(人前列腺癌细胞),Hela(人宫颈癌细胞)和A549(人肺癌细胞)进行抗肿瘤活性评价.结果显示部分化合物对PC-3表现出中度至强效的抗肿瘤活性.其中2-(丙-2-炔-1-基硫基)-4-(2-(吡啶-2-基亚甲基)-肼基)-6-(三氟甲基)嘧啶(12l)对PC-3具有较强的抗增殖活性, IC(50)为1.37μmol·L^-1,抗肿瘤活性明显优于阳性对照药5-氟尿嘧啶,为抗肿瘤药物的研究提供了新的思路.In order to find more effective antitumor drugs,a series of novel hydrazone-substituted pyrimidine derivatives were designed,synthesized and evaluated for their antitumor activity against five different human cancer cell lines including MCF-7(human breast cancer cell),MGC-803(human gastric cancer cell),PC-3(human prostate cancer cell),Hela(human cervical cancer cell)and A549(human lung cancer cell)using methyl thiazolyl tetrazolium(MTT)assay.Most of the target compounds showed moderate to potent antitumor activity against five selected cancer cell lines.Among them,2-(prop-2-yn-1-ylthio)-4-(2-(pyridin-2-ylmethylene)-hydrazinyl)-6-(trifluoromethyl)pyrimidine(12l)displayed the most potent anti-proliferative activity against PC-3 cell line(IC50=1.37µmol•L^-1),which was significantly better than the positive control drug 5-fluorouracil.This work provided clues to discover new antitumor agents.

关 键 词：腙 嘧啶衍生物 合成 抗肿瘤活性 

分 类 号：TQ463[化学工程—制药化工]