3,3'-(取代苯亚甲基)双(吲哚-2-甲酸乙酯)的微波合成及抗肿瘤活性  

Microwave irradiation synthesis and antitumor activity of diethyl 3,3'-(substituted benzylidene)bis(1H-indole-2-carboxylate)

作　　者：李玉龙 蒋龙 孙宏顺 吴明慧 蒋蕻 LI Yu-long;JIANG Long;SUN Hong-shun;WU Ming-hui;JIANG Hong(Targeted MRI Contrast Agents Laboratory of Jiangsu Province,Nanjing Polytechnic Institute,Nanjing 210048,China;College of Chemistry and Molecular Engineering,Nanjing Tech University,Nanjing 211816,China;Jiangsu Sanhua Pharmaceutical Technology CO.Ltd.,Zhenjiang 212000,China)

机构地区：[1]南京科技职业学院,江苏省磁共振靶向显像剂工程实验室,江苏南京210048 [2]江苏三花医药科技有限公司,江苏镇江212000 [3]南京工业大学化学与分子工程学院,江苏南京211816

出　　处：《化学研究与应用》2023年第9期2071-2080,共10页Chemical Research and Application

基　　金：江苏省自然科学基金项目(BK20181486)资助;江苏省高校自然科学基金项目(17KJB320001)资助;南京科技职业学院重点项目(NJPI-2022-02);江苏省青蓝工程项目资助。

摘　　要：以吲哚-2-甲酸乙酯和取代苯甲醛为主要原料,三氟甲基磺酸铋为催化剂,利用微波辐射技术,设计制备了10种新型3,3’-(取代苯亚甲基)双(吲哚-2-甲酸乙酯)衍生物(3a~3j),产物结构经1H-NMR、13C-NMR、ESI-MS和元素分析确证。通过考察微波功率、反应时间、溶剂、催化剂及原料摩尔比等因素,筛选了最佳反应条件。利用溶剂缓慢挥发法,得到了3a、3d、3f、3g和3h五个化合物的单晶。通过细胞毒性试验,筛选出了先导化合物3d,其对A549细胞的IC_(50)值为7.14μmol·L^(-1),优于标准抗癌药物顺铂对A549细胞的IC_(50)值(36μmol·L^(-1)),具有成为叶酸靶向抗肿瘤药物的应用潜力.In this work,ten novel compounds of diethyl 3,3'-(substituted benzylidene)bis(1H-indole-2-carboxylate)derivatives(3a~3j)were designed and synthesized by using bismuth trifluoromethyl sulfonate as catalyst under microwave irradiation.Indole-2-ethyl formate and substituted benzaldehyde were used as main materials.Their structures were confirmed by^(1)H NMR,^(13)C NMR and ESI-MS analysis.The optimized reaction conditions were established by examination of microwave power,reaction time,solvents,catalysts and molar ratio of raw materials.The single crystals of compounds 3a,3d,3f,3g and 3h were obtained by slow solvent evaporation method.The lead compound 3d was screened by cytotoxicity test.Its IC_(50) value against A549 cells was 7.14μmol·L^(-1),which was better than that of the standard anti-cancer drug cisplatin(36μmol·L^(-1)).It showed the potential to be used as folic acid-targeted anti-tumor drug.

关 键 词：双吲哚甲烷 微波合成 晶体结构 抗肿瘤活性 A549细胞 

分 类 号：O626.1[理学—有机化学]