苯胺基嘧啶/偶氮鎓二醇盐杂合物的设计、合成及其抗非小细胞肺癌活性  

Design,synthesis and anti-NSCLC activity of hybrids of anilinopyrimidines and diazeniumdiolates

作　　者：韩春[1] 吴林韬[1] 胡晓琴[1] 孙龙 黄张建[2,3] 张奕华[2,3] HAN Chun;WU Lintao;HU Xiaoqin;HU Xiaoqin;HUANG Zhangjian;ZHANG Yihua(Department of Chemistry,Changzhi University,Changzhi 046000;Center of Drug Discovery,China Pharmaceutical University,Nanjing 210009;Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases,China Pharmaceutical University,Nanjing 210009,China)

机构地区：[1]长治学院化学系,长治046000 [2]中国药科大学新药研究中心,南京210009 [3]中国药科大学江苏省代谢性疾病药物重点实验室,南京210009

出　　处：《中国药科大学学报》2018年第1期48-55,共8页Journal of China Pharmaceutical University

基　　金：国家自然科学基金资助项目(No.21402012);山西省重点学科建设经费资助项目;长治学院校级科研资助项目(No.GJZXM201604;No.GJZXM201605)~~

摘　　要：为寻找活性强的抗非小细胞肺癌(NSCLC)药物,设计、合成了15个结构新颖的苯胺基嘧啶/偶氮鎓二醇盐杂合物9a^9e、10a^10e、11a^11e,采用MTT法考察其对表皮生长因子受体(EGFR)L858R/T790M突变的人肺腺癌细胞H1975的增殖抑制活性。结果表明,化合物9a^9e显著抑制H1975细胞的增殖,优于对照药吉非替尼(gefitinib)。其中,化合物9b活性最强(IC_(50)=0.65μmol/L)。分子对接提示,化合物9b可能通过氢键和静电作用力等与EGFR T790M活性部分结合,值得进一步研究。To search for potent drugs against non-small-cell lung cancer(NSCLC),a series of hybrids(9a-9e,10a-10e and11a-11e)from anilinopyrimidines and diazeniumdiolates were designed and synthesized.The MTT assay was employed to evaluate their antiproliferative activity against H1975cells harboring epithelial growth factor receptor(EGFR)L858R/T790M mutation.The results showed that compounds9a-9e displayed remarkable inhibitory activity on H1975cells.Among these compounds,the most potent was compound9b(IC50=0.65μmol/L),which was superior to the positive control gefitinib.Additionally,molecular docking study indicated that9b could bind with EGFR T790M by forming hydrogen bond,electrostatic interactions,et al,suggesting that compound9b may be a potential anti-NSCLC agent for further investigation.

关 键 词：苯胺基嘧啶 偶氮鎓二醇盐 表皮生长因子受体 吉非替尼 合成 非小细胞肺癌 抗肿瘤活性 

分 类 号：R914.2[医药卫生—药物化学] R965[医药卫生—药学]