| 魏梦雪,马超,陈凑喜,徐建,张和,李学强.化学通报,2015,78(12):1090-1095. |
| 新型双氢青蒿素哌嗪-芳香酰胺类化合物的合成及其抗肿瘤活性的初步评价 |
| Synthesis and Preliminary Anti-cancer Activities of Novel Dihydroartemisinin-Piperazine Derivatives Containing Amide |
| 投稿时间：2015-04-12 修订日期：2015-04-15 |
| DOI： |
| 中文关键词: 双氢青蒿素 哌嗪衍生物 合成 抗癌活性 |
| 英文关键词:Dihydroartemisinin, Piperazine derivatives, Synthesis, Anti-cancer activities |
| 基金项目:国家自然科学基金项目（21462032，21062014）、宁夏大学人才引进科研启动基金项目（80020241） |
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| 中文摘要: |
| 以双氢青蒿素为起始原料，在草酰氯作用下无需分离，随后在“一锅煮”条件下与哌嗪作用得到胺类化合物，该类化合物与芳香酰氯作用，快速、高效地合成了6种新型芳酰胺类双氢青蒿素哌嗪衍生物。所有化合物通过IR、1H NMR、13C NMR和HR-MS得到结构确认。同时，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的抑制活性。初步研究结果表明，该类化合物具有明显的抑制人肝癌细胞增殖、诱导其凋亡的细胞活性，给药72h，半抑制浓度IC50最优值仅为0.04 μmol/L。在与青蒿素、双氢青蒿素的对比实验中发现，该类化合物的抗癌活性明显提高，表现出该类化合物具有潜在的开发和应用价值。 |
| 英文摘要: |
| Dihydroartemisinin is an important derivative of artemisinin; it and its derivatives have features including better solubility in water, more easily absorbed and have a rapid excretion and metabolism, high efficiency and low toxicity, etc. Some research reported derivatives of dihydroartemisinin containing heterocycle have good anti-malarial, anti-tumor, anti-pregnancy and immunosuppressive effects, their performence has surpassed artemisinin. But the researchonthe synthesis of dihydroartemisinin derivatives containing heterocycle and amide is rare, and structure-activity relationshipstudies on amide drugs is still a most dynamic research area. In order to develop new drug candidates or lead compounds with low toxicity, high activity, good stability and controllable quality, a series of novel piperazine-amide derivatives contained dihydroartemisinin were synthesized commenced with dihydroartemisinin, through esterification, amination, and acylation, and their chemical structures were confirmed by the methods of IR, 1H NMR, 13C NMR and HR-MS. Then their in vitro anti-cancer activities against SMMC-7721were analyzed with MTT method. The preliminary bioassay test showed that compound 3bhas the best inhibition activity against SMMC-7721 with an IC50 of 0.04 μmol/L, providing a new promising lead for further development of new anti-cancer drugs. |
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