紫罗兰酮生物碱异唑衍生物的合成及其抗肿瘤转移活性研究  

Synthesis of isooxazole derivatives of ionone alkaloid and their antitumor metastasis activities

作　　者：贾美琪 刘菁菁 聂江平 段宏泉[1,2] 秦楠[1] JIA Mei-qi;LIU Jing-jing;NIE Jing-ping;DUAN Hong-quan;QIN Nan(School of Pharmacy,Tianjin Medical University,Tianjin 300070,China;Basic Medical Research Center,Tianjin Medical University,Tianjin 300070,China)

机构地区：[1]天津医科大学药学院,天津300070 [2]天津医科大学基础医学研究中心,天津300070

出　　处：《现代药物与临床》2020年第11期2109-2116,共8页Drugs & Clinic

基　　金：国家自然科学基金面上项目(81673310);天津市自然科学基金资助项目(17JCZDJC32900)。

摘　　要：目的设计并合成紫罗兰酮生物碱异唑类衍生物,结合活性筛选,发现具有活性的新型紫罗兰酮生物碱衍生物。方法制备(R)-紫罗兰酮,在此基础上经过11步有机合成反应制备紫罗兰酮生物碱异唑衍生物。目标衍生物经核磁共振波谱和高分辨质谱表征其化学结构。通过乳腺癌细胞趋化迁移实验筛选衍生物的抗肿瘤转移活性。结果共制备8个目标衍生物,经抗肿瘤转移活性筛选发现,化合物12c活性同Ion-31a相当,强于阳性对照化合物PI3K抑制剂LY294002。结论所有目标衍生物均为新化合物,其中苯甲腈取代异唑化合物12c具有显著抗肿瘤转移活性。Objective To design and synthesize the ionone alkaloid isoxazole derivative,and combine with activity screening,to find new bioactive derivatives of ionone alkaloid.Methods(R)-ionone was prepared,and the isooxazole derivative of ionone alkaloid were prepared after 11 steps of organic synthesis.The chemical structure of the target derivatives were characterized by nuclear magnetic resonance spectroscopy and high resolution mass spectrometry.The antitumor metastatic activities of the derivatives were screened by chemotactic migration of breast cancer cells.Results A total of 8 target derivatives were prepared.After screening for anti-tumor metastasis activitys,compound 12c was found had the same activity as Ion-31a,and was stronger than the positive control compound PI3K inhibitor LY294002.Conclusion All the targetderivatives are new compounds,and the benzonitrile substituted isoxazole compound 12c has significant anti-tumor metastasis activity.

关 键 词：手性紫罗兰酮生物碱 异唑 乳腺癌 抗肿瘤转移 

分 类 号：R979.1[医药卫生—药品]