齐墩果酸C-28位四氮唑衍生物的合成及体外抗肿瘤活性  

Synthesis and in vitro Antitumor Activities of Oleanolic Acid C-28 Tetrazole Derivatives

作　　者：孙可微 徐阳荣 宋佳 王洪波[1] 赵风兰[1] 孟庆国[1] SUN Ke-wei;XU Yang-rong;SONG Jia;WANG Hong-bo;ZHAO Feng-lan;MENG Qing-guo(School of Pharmacy,Collaborative Inovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong,Key Laboratory of Molecular Pharmacology and Drug Evaluation(Yantai University),Ministry of Education,Yantai University,Yantai 264005,China;Institute of Pharmacology and Toxicology,Academy of Military Medical Sciences,Academy of Military Sciences,Beijing 100850,China)

机构地区：[1]烟台大学药学院,新型制剂与生物技术药物研究山东省高校协同创新中心、分子药理和药物评价教育部重点实验室(烟台大学),山东烟台264005 [2]军事科学院军事医学研究院,毒物药物研究所,北京100850

出　　处：《烟台大学学报（自然科学与工程版）》2021年第3期282-288,共7页Journal of Yantai University(Natural Science and Engineering Edition)

基　　金：国家自然科学基金资助项目(81473104);烟台市科技创新发展计划项目(2020XDRH105)。

摘　　要：采用亲核取代和Click反应在齐墩果酸的C-28位羧基引入五元氮杂环,合成了15个氮唑骈缀的齐墩果酸新衍生物,结构均经HRMS、1H-NMR和X射线单晶衍射确证,采用MTT法评价了目标物对人胃癌细胞MKN-45、人乳腺癌细胞MCF-7和大鼠胶质瘤C6细胞的体外抗肿瘤活性。结果表明,浓度为10μmol/L时,目标物的体外抗肿瘤活性较齐墩果酸有一定提高。实验结果证实了在齐墩果酸28位羧基缀合各种苄基取代的四唑,有利于提高齐墩果酸的体外抗肿瘤活性,是优化齐墩果酸的一种有效方法。Fifteen new azole-fused derivatives of oleanolic acid are synthesized by using nucleophilic substitution and Click reaction to introduce five-membered N-heterocycle into the C-28 carboxyl group of oleanolic acid,and their structures are confirmed by HRMS,1H-NMR and X-ray single crystal diffraction.Their in vitro anticancer activities towards human gastric cancer cells MKN-45,human breast cancer cells MCF-7 and rat glioma C6 cells are evaluated by MTT method.The results demonstrate that combining various benzyl-substituted tetrazole with C-28 position are beneficial to improve the in vitro anti-tumor activity of oleanolic acid,therefore this is an effective method for optimizing oleanolic acid.

关 键 词：齐墩果酸 衍生物 四氮唑 合成 体外抗肿瘤活性 

分 类 号：R914.5[医药卫生—药物化学]