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含三氟甲基的2,4-取代嘧啶衍生物,并对目标化合物在EC-109(人食管癌细胞),MGC-803(人胃癌细胞),PC-3(人前列腺癌细胞)和HepG-2(人肝癌细胞)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-(((4-((1-甲基-1H-四唑-5-基)硫基)-6-(三氟甲基)嘧啶-2-基)硫基)甲基)苯并[d]噻唑(13w)对PC-3具有较强的抗肿瘤活性,IC50为1.76 μmol·L-1,抗肿瘤活性明显优于阳性对照药5-氟尿嘧啶.
In order to find more effective antitumor drugs, a series of novel 2,4-substituted pyrimidine derivatives containing trifluoromethyl were designed, synthesized, and evaluated for antitumor activity aganist EC-109 (human esophageal cancer cell), MGC-803 (human gastric cancer cell), PC-3 (human prostate cancer cell) and HepG-2 (human liver cancer cell). The results showed that some compounds displayed moderate to potent antitumor activity against PC-3. Among them, 2-(((4-((1-methyl-1H-tetrazol-5-yl)thio)-6-(trifluoromethyl)pyrimidin-2-yl)thio)methyl)benzo[d]thiazole (13w) possesses strong antitu-mor activity against PC-3 with IC50 value of 1.76 μmol·L-1, and the antitumor activity is significantly better than the positive control drug of 5-fluorouracil.
作者
孟娅琪
李二冬
张洋
刘栓
包崇男
杨鹏
张路野
张丹青
王继宽
陈雅欣
栗娜
辛景超
赵培荣
可钰
张秋荣
刘宏民
Meng Yaqi;Li Erdong;Zhang Yang;Liu Shuan;Bao Chongnan;Yang Peng;Zhang Luye;Zhang Danqing;Wang Jikuan;Chen Yaxin;Li Na;Xin Jingchao;Zhao Peirong;Ke Yu;Zhang Qiurong;Liu Hongmin(School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001;Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou 450001)
出处
《有机化学》
SCIE
CAS
CSCD
北大核心
2019年第9期2541-2548,共8页
Chinese Journal of Organic Chemistry
基金
Project supported by the National Natural Science Foundation of China(No.81430085)
the Natural Science Foundation of Henan Province(No.182300410321)~~
关键词
三氟甲基
2
4-取代嘧啶衍生物
抗肿瘤活性
trifluoromethyl
2,4-substituted pyrimidine derivatives
antitumor activity
