含1-[4-二-(4-氟苯)甲基]哌嗪官能团的1,4-二取代-1,2,3-三氮唑衍生物的设计合成及抗肿瘤活性研究  

Design,Synthesis and Antitumor Evaluation of Novel 1,4-Disubstituted-1,2,3-triazoles Bearing 1-[4-Bi-(4-fluorophenyl) methyl]-piperazine Group

作　　者：文畅 丁勇[1] 姜芯 吴坤 梁萌 李清寒[1] WEN Chang;DING Yong;JIANG Xin;WU Kun;LIANG Meng;LI Qing-han(College of Chemistry and Environmental Protection Engineering,Southwest Minzu University,Chengdu 610041,China)

机构地区：[1]西南民族大学化学与环境保护工程学院

出　　处：《化学试剂》2019年第12期1327-1333,共7页Chemical Reagents

基　　金：西南民族大学研究生创新基金项目(CX2018SZ-139);四川省科技厅科技支撑计划项目(2015NZ0033)

摘　　要：为寻找活性强、毒性低的新抗肿瘤化合物,以二-(4-氟苯)甲基氯、哌嗪、3-溴丙炔和叠氮化钠为原料合成了12个新的标题化合物,收率为46%~86%。所有化合物的结构均经过质谱、元素分析及氢/碳核磁共振谱确证。在体外对目标化合物进行了抗白血病HL-60及肺癌A-549细胞的活性测试,结果表明,浓度为40μmol/L时,化合物对白血病HL-60细胞的抑制率高达99. 25%,IC50值为3. 17μg/m L。对肺癌A-549细胞的抑制率高达97. 64%,IC50值为12. 95μg/m L。比较化合物的结构和活性,发现吸电子基团更有利于提高化合物的抗癌活性,因此1-取代苄基-4-{1-[4-二-(4-氟苯基)甲基]哌嗪}甲基-1,2,3-三氮唑类衍生物值得进一步深入研究。To look for a new kind of antitumor compounds with high activity and low toxicity,twelve novel title compounds were prepared via three steps starting from bi-(4-fluorophenyl)-methylchloro,piperazine,3-bromoprop-1-yne and sodium azide with good yield(46%~86%).The structures of the new compounds were confirmed by elemental analysis,MS,1HNMR and 13CNMR.The newly compounds exhibited good to excellent inhibitory activity against Leukemia cell HL-60(Inhibition up to 99.25%,IC50 up to 3.17μg/mL)and Lung cancer cell A-549(Inhibition up to 97.64%,IC50 up to 12.95μg/mL)in 40μmol/L.Comparing the structure and activity of compounds,the presence of the electron-withdrawing groups in the molecules is more conducive to improving the anticancer activity of compounds.Therefore,1-substituted benzyl-4-{1-[4-bi-(4-fluorophenyl)methyl]piperazine}methyl-1,2,3-triazole derivatives can be used as lead molecules of anti-cancer drugs for further research.

关 键 词：1-[4-二-(4-氟苯)甲基]哌嗪 3-溴丙炔 1 4-二取代-1 2 3-三氮唑 有机合成 抗肿瘤活性 

分 类 号：O621.3[理学—有机化学]