一类多取代吲哚化合物的合成及抗肿瘤活性  

Synthesis and Antitumor Activity of A Series of Polysubstituted Indoles

作　　者：徐琳琳 屈鹏飞 杨向东 焦阳 XU Linlin;QU Pengfei;YANG Xiangdong;JIAO Yang(Key Lab of Human Genetics and Environmental Medicine,School of Public Health,Xuzhou Medical University,Xuzhou 221004,China;General Hospital of Xuzhou Mining Group,Xuzhou 221006,China)

机构地区：[1]徐州医科大学公共卫生学院人类遗传和环境医学重点实验室,江苏徐州221004 [2]徐州医科大学第二附属医院,江苏徐州221006

出　　处：《广州化学》2023年第5期48-50,55,I0003,共5页Guangzhou Chemistry

基　　金：江苏省高等学校大学生创新创业训练计划项目(201910313060Y);徐州市科技发展计划项目(KC19042)。

摘　　要：利用多组分反应方法,以取代氢化吲哚、苯肼、丁炔二酸二酯为原料,合成了10个多取代吲哚衍生物4-取代-(4,5,6,7-四氢-6,6-二甲基-4-氧-1-对苯甲基-1H-吲哚-7-基)-5-羟基-1-苯基-1H-吡唑-3-羧酸酯4a~4j,收率为77%~83%。其结构均通过红外、核磁和质谱等方法加以表征。采用SRB法对目标化合物进行体外抗肿瘤活性的测试,结果表明:目标化合物4对胃癌细胞系SGC7901在浓度为2.5、10、40μg/mL时发挥较强的抑制作用,抑制率从2.29%到77.33%,且化合物的细胞毒性呈浓度依赖性;其中,4g、4h抑制能力最强;进一步检测目标化合物4对肺癌细胞系A549的生长抑制能力,结果显示多数化合物均呈现较强的抑制作用;其中,4a和4e发挥更强的抑制能力。A series of polysubstituted indoles named 4-substituted-(4,5,6,7-tetrahydro-6,6-dimethyl-4-oxo-1-p-tolyl-1H-indol-7-yl)-5-hydroxy-1-phenyl-1H-pyrazole-3-carboxylate 4a~4j were synthesized from substituted hydro-indoles,phenylhydrazine and acetylenedicarboxylate.The target compounds 4 were obtained with 77%~83%yield.The structures of all compounds were characterized by IR,1H NMR and HRMS(ESI).In order to survey the possible bioactivity of these compounds,polysubstituted indole derivatives 4 were subject to the test of in vitro cytotoxicity to malignant stomach cancer cell line SGC7901 and lung cancer cell line A549 by using sulforhodamine B(SRB)protein assay.The results demonstrated that the tested compounds in the three concentrations(2.5,10,40μg/mL)showed moderate or strong cytotoxicity toward SGC7901 with inhibition rate(IR)from 2.29%to 77.33%.As we have seen,the tested compounds could suppress SGC7901 cell growth in a concentration-dependent manner.Among all the compounds,4g and 4h showed the highest inhibitory activity.It was further tested that IC50 values of compounds 4 to lung cancer cell line A549 to evaluate their cytotoxicity.In general,most of the tested compounds displayed moderate to strong cytotoxicity.Among them,4a and 4e played a stronger inhibitory ability.

关 键 词：多取代吲哚化合物 优势骨架构建 抗肿瘤活性 抑制 

分 类 号：O626.1[理学—有机化学]