| 梁春辉 郭焕利 姚希梅 庞薪莉 周四元.α-亚麻酸- 阿霉素前药的合成以及抗肿瘤活性研究[J].现代生物医学进展英文版,2014,14(27):5242-5246. |
| α-亚麻酸- 阿霉素前药的合成以及抗肿瘤活性研究 |
| The Synthesis of α-Linolenic Acid-Doxorubicin Conjugate and its AntitumorActivity in Vitro |
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| DOI： |
| 中文关键词: α- 亚麻酸 阿霉素 细胞毒性 肿瘤靶向 |
| 英文关键词: α-linolenic acid Doxorubicin Cytotoxicity Tumor targeting |
| 基金项目:陕西省自然科学基金项目（2012KTCL03-18） |
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| 中文摘要: |
| 目的：合成具有酸敏特性的α-亚麻酸-阿霉素前体药物，并观察其抗肿瘤活性以及对肿瘤细胞的靶向性。方法：以Boc-
NHNH2、α- 亚麻酸、阿霉素为主要反应原料，先后合成Boc 保护的α- 亚麻酰肼、α- 亚麻酰肼和α- 亚麻酸- 阿霉素腙键连接物，采用核磁共振、质谱等方法鉴定其结构；采用LC/MS方法研究连接物在不同pH介质中的药物释放行为；采用MTT 法观察连接
物对人肝癌细胞HepG2、乳腺癌细胞MDA-MB-231 和MCF-7 细胞的毒性作用。结果：在1- 乙基-(3- 二甲基氨基丙基)碳酰二亚胺盐酸盐(EDC·HCl)的催化作用下，合成了α-亚麻酸-阿霉素前体药物，波谱分析提示为目标产物。通过在体外酸性条件下水解连接物，我们发现该连接物具有显著的pH值敏感性。同时在体外细胞毒性实验中，我们发现相比于游离阿霉素，该合成连接物α-
亚麻酸- 阿霉素对HepG2、MDA-MB-231 和MCF-7 三种肿瘤细胞具有更强的细胞毒性，而且细胞毒性作用可被外源性α- 亚麻酸抑制。结论：α-亚麻酸- 阿霉素连接物能经α- 亚麻酸受体介导靶向于琢-亚麻酸受体丰富的肿瘤细胞，是一种潜在的新型抗肿
瘤药物。 |
| 英文摘要: |
| Objective:To prepare the pH-sensitive conjugate of α-linolenic acid-doxorubicin and observe its antitumor activity in
vitro.Methods:Boc-LH, LH and L-DOX are synthesized with the catalyst （EDC·HCl）and the main raw materials: BocNHNH2,
α-linolenic acid and doxorubicin, and characterized in terms of H1NMR and MASS. The drugs release characteristic was performed in
different pH media in vitro by the by LC/MS. The cytotoxicity effects of L-DOX on human hepatocellular carcinoma cell HepG2, human
breast cancer cell line MDA-MB-231 and MCF-7 cells was measured by MTT assay.Results:With the help of EDC·HCl, the L-DOX
was synthesized. The cytotoxicity of L-DOX on the three different tumor cells were stronger than doxorubicin at the same concentration,
and could be inhibited by adding the freeα-linolenic acid.Conclusion:L-DOX could be targeted to tumor cells via α-linolenic acid receptor.
It could be a new potential anticancer drug. |
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