[关键词]
[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1H-NMR、13C-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(IC50)值分别为1.73、3.09 μmol/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。
[Key word]
[Abstract]
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 1H-NMR, 13C-NMR and HRMS. MTT assay showed that some derivatives exhibited good antitumor activities. Among them, compounds 5h showed the most potent antiproliferative activity against MCF-7 and SKOV3 tumor cells with IC50 values of 1.73 μmol/L and 3.09 μmol/L, which was better than that of the positive control drug etoposide. Conclusion Some derivatives show good antitumor activity, and compound 5h was worth further studying.
[中图分类号]
R284.1
[基金项目]
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)