新型青蒿砜-酯类衍生物的合成及其抗癌活性研究
收稿日期: 2014-09-24
修回日期: 2014-10-28
网络出版日期: 2015-01-28
基金资助
国家自然科学基金(Nos.21462032,21062014)和宁夏大学人才引进科研启动基金(No.80020241)资助项目.
Synthesis and Anti-tumor Effect of Artemisone Derivatives
Received date: 2014-09-24
Revised date: 2014-10-28
Online published: 2015-01-28
Supported by
Project supported by the National Natural Science Foundation of China (Nos.21462032, 21062014) and the Research Starting Funds for Imported Talents of Ningxia University (No.80020241).
以双氢青蒿素为起始原料, 经胺化、氧化、烷基化、酯化反应, 快速、高效地合成了一系列青蒿砜系列衍生物, 目标化合物的结构通过IR、1H NMR、13C NMR和HRMS得到了确证; 以四甲基偶氮唑盐比色法(MTT法), 研究了该类化合物对人肝癌细胞株SMMC-7721的抗癌活性. 初步研究结果表明, 该类化合物具有明显地抑制人肝癌细胞增殖、诱导其凋亡的细胞活性, 给药72 h, 半数抑制浓度IC50最优值为0.06 μmol/L. 同时采用Annexin/PI流式细胞分析法检测化合物7b对人肝癌细胞SMMC-7721的凋亡情况, 结果显示实验组与正常对照组相比人肝癌细胞早期凋亡率和总凋亡率均显著增加. 在与青蒿素、双氢青蒿素(DHA)和青蒿砜的对比实验中发现, 该类化合物的抗肿瘤活性明显提高, 表现出了该类化合物在抗癌药物开发方面具有潜在的应用价值.
魏梦雪 , 徐建 , 张和 , 李学强 . 新型青蒿砜-酯类衍生物的合成及其抗癌活性研究[J]. 有机化学, 2015 , 35(5) : 1097 -1103 . DOI: 10.6023/cjoc201409039
The artemisone was rationally designed to be attached with an ester unit, and a series of such artemisone derivatives were practically prepared from dihydroartemisinin. The synthetic route was combined with amination, oxidation, alkylation and esterification. All the new artemisone derivatives were identified by NMR, IR and HRMS technology. The anti-tumor activities of artemisone derivatives against human hepatoma SMMC-7721 cell lines were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric method. It revealed that they could obviously exert their inhibition of proliferation of the liver cancer cells by inducing apoptosis. Compound 7b exhibited the most potent antiproliferative activity with IC50 value of 0.06 μmol/L treatment for 72 h. Compared with artemisinin, dihydroartemisinin and artemisone, the new artemisone derivatives are superior to each of them in antitumor activity. These results are significant to the potential application of artemisone derivatives in the further development of new anticancer drugs.
Key words： artemisinin; artemisone; esters; synthesis; anti-tumor activity
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