芦荟大黄素-吲哚偶联物的合成及抗肿瘤活性研究  

Synthesis and antitumor evaluation of aloe-emodin-indole hybrids

作　　者：原凤蕉 李晓雪 尚海[2] 李凌宇[2] 宋艳玲 邹忠梅[2,3] YUAN Feng-jiao;LI Xiao-xue;SHANG Hai;LI Ling-yu;SONG Yan-ling;ZOU Zhong-mei(School of Pharmaceutical and Biological Engineering,Shenyang University of Chemical Technology,Shenyang 110142,China;Institute of Medicinal Plant Development,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100193,China;School of Chinese Materia Medica,Shenyang Pharmaceutical University,Shenyang 110016,China)

机构地区：[1]沈阳化工大学制药与生物工程学院,辽宁沈阳110142 [2]中国医学科学院北京协和医学院药用植物研究所,北京100193 [3]沈阳药科大学中药学院,辽宁沈阳110016

出　　处：《中草药》2021年第8期2217-2225,共9页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金资助项目(81502929);中国医学科学院医学与健康科技创新工程经费资助(2016-I2M-3-015);辽宁省教育厅基础科研项目(LJ2020025)。

摘　　要：目的合成芦荟大黄素-吲哚偶联物,并对偶联物进行体外抗肿瘤活性评价。方法以芦荟大黄素为起始原料,通过溴代、叠氮化、click反应等得到目标化合物,采用噻唑蓝(MTT)法考察所合成的目标化合物对人乳腺癌MCF-7细胞、人肝癌HepG2细胞和人胃腺癌AGS细胞等多种肿瘤细胞的体外抗增殖活性。结果合成了17个芦荟大黄素衍生物,其结构经^(1)H-NMR、^(13)C-NMR及HRMS确定。活性测试结果表明,部分衍生物表现出良好的抗肿瘤活性。其中,化合物5h对人乳腺癌MCF-7细胞和人卵巢癌SKOV3细胞2种肿瘤细胞表现出明显的抗增殖活性,半数抑制浓度(IC_(50))值分别为1.73、3.09μmol/L,且活性优于阳性对照药依托泊苷。结论部分芦荟大黄素-吲哚偶联物表现出良好的抗肿瘤活性,化合物5h具有进一步研究价值。Objective To synthesize aloe-emodin-indole hybrids and evaluate the antitumor activities of the derivatives in vitro.Methods Taking aloe-emodin as the starting material,the target compound was obtained by bromination reaction,azide reaction and click reaction.The anti-proliferation activity of the synthesized target compounds on MCF-7,HepG2,AGS and other tumor cells in vitro was investigated by MTT method.Results Seventeen aloe-emodin-indole hybrids were synthesized,and their structures were confirmed by ^(1)H-NMR,^(13)C-NMR and HRMS.MTT assay showed that some derivatives exhibited good antitumor activities.Among them,compounds 5 h showed the most potent antiproliferative activity against MCF-7 and SKOV3 tumor cells with IC_(50) values of 1.73μmol/L and 3.09μmol/L,which was better than that of the positive control drug etoposide.Conclusion Some derivatives show good antitumor activity,and compound 5 h was worth further studying.

关 键 词：芦荟大黄素 吲哚 结构修饰 抗肿瘤活性 构效关系 

分 类 号：R284.1[医药卫生—中药学]