【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BocNHNH2、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α-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。更多还原

【Abstract】 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 H1 NMR 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.更多还原