| 霍荣迪,赵风菊,刘家越,李学城,孟艳秋.化学通报,2023,86(10):1263-1268,1273. |
| 一种水飞蓟宾恶唑衍生物的合成及体外抗肿瘤活性研究 |
| Synthesis and in vitro antitumor activity of a silybin oxazole derivative |
| 投稿时间：2023-02-13 修订日期：2023-04-10 |
| DOI： |
| 中文关键词: 水飞蓟宾 结构改造 抗肿瘤 HER2 |
| 英文关键词:silybin, structural transformation, Anti-tumor,HER2 |
| 基金项目:国家自然科学基金项目（21372156） |
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| 中文摘要: |
| 水飞蓟宾多作为保肝药使用，近年来因其在抗肿瘤方面显示的良好潜力而备受关注。为提高水飞蓟宾的抗肿瘤活性，以天然产物水飞蓟宾为先导化合物，合成一系列水飞蓟宾衍生物，其化学结构经1H NMR、13C NMR、MS确证。采用MTT法测试目标化合物对人乳腺癌细胞(MCF-7)和人胃癌细胞(SGC-7901)的体外抗肿瘤活性；并运用分子对接的方法分析目标化合物与HER2靶点的作用方式。结果表明，目标化合物对两种癌细胞的抑制率均优于水飞蓟宾，其中衍生物Ⅱ3和Ⅱ9与阳性对照药拉帕替尼和阿法替尼抑制作用相当，衍生物Ⅱ3和Ⅱ9能与HER2靶蛋白周围的氨基酸残基通过氢键紧密结合。本研究可为新型抗肿瘤药物的研发提供参考。 |
| 英文摘要: |
| Silybin is used as a hepatoprotective drug and has attracted much attention in recent years because of its promising antitumor potential. In order to improve the antitumor activity of silybin, a series of silybin derivatives were synthesized with natural silybin as the lead compound, and the structures of these novel compounds were determined by NMR and MS. The antitumor activity of the target compounds against human breast cancer cells (MCF-7) and human gastric cancer cells (SGC-7901) in vitro was tested by MTT assay. And the interaction mode between the target compound with the HER2 target was analyzed by molecular docking method. The results showed that the antitumor activity of the target compounds had better inhibition rate on cancer cells than silybin, and the antitumor activity of compounds II3 and II9 were similar to positive control drugs such as lapatinib and afatinib., and derivatives Ⅱ3 and Ⅱ9 could closely bind with amino acid residues of HER2 target protein. This study can provide a reference for the research of new antitumor drugs. |
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