1,3-取代吲哚-2-酮衍生物的合成与肿瘤细胞毒活性研究  

Syntheses and Tumor Cytotoxic Activities of 1,3-Substituted indol-2-one Derivatives

作　　者：田婉蓉 陈瑶 李美美 邓赟[1] Tian Wanrong;Chen Yao;Li Meimei;Deng Yun(State Key Laboratory of Southwestern Chinese Medicine Resources,School of Pharmacy,Chengdu University of Traditional Chinese Medicine,Chengdu,611137)

机构地区：[1]西南特色中药资源国家重点实验室成都中医药大学药学院,成都611137

出　　处：《化学通报》2022年第5期606-612,共7页Chemistry

基　　金：国家自然科学基金项目(U19A2011);中国博士后基金项目(2020M673565XB);成都中医药大学杏林学者人才提升计划项目(BSH2019027);成都中医药大学一流学科建设项目(CZYJC1905)资助。

摘　　要：以苯胺为原料,通过肟化、环合生成二氢吲哚-2,3-二酮,再对其进行N-烷基化、亲核加成和磺酰化反应得到目标化合物5a~5g和7a~7e。通过^(1)H NMR、^(13)C NMR确认其结构。采用噻唑蓝(MTT)法测试了目标化合物对乳腺癌细胞MDA-MB-231、鼠黑色素瘤细胞B16、鼠结肠癌细胞CT26三种肿瘤细胞的体外抑制活性。结果表明,化合物7d、7e具有明显的肿瘤细胞毒活性,其中化合物7d对MDA-MB-231的细胞毒活性比阳性药五氟尿嘧啶更强,IC_(50)为4.63±0.14μmol/L。本文结果可为进一步研究具有肿瘤细胞毒活性的吲哚酮类衍生物提供参考。Indoline-2,3-dione was synthesized via oximation and cyclization reaction using aniline as raw material,and then N-alkylation,nucleophilic addition and sulfonylation reactions were carried out to obtain the target compound 5 a~5 g and 7 a~7 e.Their structures were confirmed by ^(1)H NMR and ^(13)C NMR.In addition,the thiazolyl blue(MTT) method was used to test the in vitro inhibitory activity of the target compounds against breast cancer cells MDA-MB-231,murine melanoma cells B16,and murine colon cancer cells CT26.The results show that the target compounds 7 d and 7 e have obvious tumor cytotoxic activity,and the cytotoxic activity of compound 7 d against breast cancer cell MDA-MB-231 is stronger than the positive drug pentafluorouracil,with an IC_(50) of 4.63±0.14 μmol/L.The results of this article can provide references for further research on indolinone derivatives with tumor cytotoxic activity.

关 键 词：1 3-取代吲哚-2-酮 亲核加成反应 肿瘤细胞毒活性 

分 类 号：O626[理学—有机化学] TQ460.1[理学—化学]