| 题名 | 驱虫斑鸠菊化学成分及其生物活性研究 |
| 作者 | 阿不拉江•图拉克 |
| 学位类别 | 博士 |
| 答辩日期 | 2016-06-03 |
| 授予单位 | 中国科学院大学 |
| 授予地点 | 北京 |
| 导师 | 阿吉艾克拜尔·艾萨 |
| 关键词 | 驱虫斑鸠菊 倍半萜二聚体 细胞毒活性 黑素含量 |
| 学位专业 | 有机化学 |
| 中文摘要 | 驱虫斑鸠菊为菊科（Compositae）斑鸠菊属植物驱虫斑鸠菊（Vernonia anthelmintica (L.) Willd.）干燥的种子，主要分布于中国新疆南部、印度、巴基斯坦等地，是历代维吾尔医治疗白癜风的主要药物，目前多种治疗白癜风的制剂以驱虫斑鸠菊种子作为主药。驱虫斑鸠菊始载于《中国植物志》、还被载于《中华人民共和国卫生部药品标准-维吾尔药分册》、《维吾尔药志》、《中华本草-维吾尔分卷》、《新疆植物志》，是一种对白斑病有着神奇疗效的植物。主要功能与主治为清除异常粘液质、驱虫、消肿、散寒止痛。本论文在前期文献调研过程中发现，驱虫斑鸠菊的倍半萜类成分研究较少，并且前期研究也发现了2个罕见的具有较好抗肿瘤活性的榄香内酯类二聚倍半萜化合物。因此本论文以分离倍半萜二聚体和倍半萜类化合物为主要目标对驱虫斑鸠菊种子的石油醚：乙醚：甲醇=1:1:1混合溶剂提取部位进行了分离。采用硅胶柱色谱、ODS柱色谱、Sephadex LH-20、MCI以及全自动纯化系统、半制备液相色谱等多种色谱分离手段分离得51个化合物，其中有20个极性接近的倍半萜二聚体和14个单倍半萜，并运用UV、IR、NMR、HR-ESI-MS以及ECD和计算ECD等方法综合解析鉴定了它们的结构，发现了新化合物27个，其中倍半萜二聚体19个（化合物1 – 19），5个单倍半萜类（化合物20 – 24）、1个贝壳杉烷型二萜（化合物27）、1个黄烷醇苷（化合物25）以及1个其他类型化合物（化合物26）。倍半萜二聚体中，化合物13是由一个榄香内酯类倍半萜和一个愈创木内酯类倍半萜通过Diels-Alder反应生成的产物，化合物15和16是通过酯化反应形成的二聚体。同时分离得到13个其他类型的化合物，分别为8个黄酮类，包括1个双黄酮（化合物38），1个橙酮（化合物39），1个黄烷醇（化合物45）；4个十八碳烯酸类化合物以及1个连二烯类化合物（化合物46）。所有新化合物通过实验测定的ECD图谱和TmoleX软件理论计算的ECD图谱比较，确定了它们的绝对构型。通过分析已分离的化合物的结构和NMR数据，总结了倍半萜及其二聚体的结构特点和NMR特点。对已分离的倍半萜及其二聚体总结了结构间的关联。对驱虫斑鸠菊中分离得到的化合物测定了其对HCT-15 (人结肠癌细胞)、PC-3 (人前列腺癌细胞)、A549 (人肺癌细胞)、T47D (人乳腺癌细胞)和Hela (人宫颈癌细胞)的细胞毒活性。二聚体中，化合物1，2对T47D细胞，化合物5，14对HCT-15细胞具有很强的细胞毒活性，IC50值小于10 μM，尤其是化合物2对T47D细胞的细胞毒活性IC50值小于1 μM。单倍半萜中，化合物23对A549细胞，化合物24对HCT-15、PC-3、A549和Hela细胞，化合物33对HCT-15细胞，化合物36对HCT-15、PC-3细胞有很强的细胞毒活性（IC50<10 μM），尤其是化合物36对HCT-15、PC-3细胞的细胞毒活性IC50值小于1 μM。化合物15对HCT-15、PC-3和A549细胞以及化合物46、47对HCT-15细胞具有无浓度依赖的细胞毒活性。驱虫斑鸠菊中分离得到的黄酮类化合物和部分倍半萜及二聚体测定了其对B16黑色素瘤细胞黑素含量的影响，其中化合物30和37对黑素含量影响非常明显，达到200%以上。 |
| 英文摘要 | Vernonia anthelmintica belonging to the Compositae family, maily distributed in South of Xinjiang, India and Pakistan. The seeds of V. anthelmintica is a famous folk medicine to cure vitiligo in Traditional Uyghur Medicine (TUM). It is the main medicinal materials in most of the preparation for treatment of vitiligo. V. anthelmintica is officially listed in Flora of China; Drug standard of Ministry of Public Health of the People's Republic of China, Uyghur Medicine Medicine part; Chinese Materia Medica, Uyghur Medicine part and Flora of Xinjiang. Ther are very little research about sesquiterpenes of this plant, and previous phytochemical studies yield two novel orthoester elemanolide dimers, with significant cytotoxicity against human cell lines. Therefore, the main purpose of this dissertation is to isolated more dimers with good biological activity from the PE:ether:MeOH=1:1:1 extract part. By using a variety of chromatographic techniques, such as silical gel, ODS, Sephadex LH-20, MCI open column, Autopurification System, and semi-preparative HPLC, after a lengthy and time-consuming separation, 51 compounds were isolated, including 20 dimers and 14 sesquiterpenes. Their structures were elucidated by the extensive analysis of UV, IR, NMR, HR-ESI-MS, ECD and calculated ECD spectrum. Among them, 19 dimers (1 – 19), 5 sesquiterpenes (20 – 24), 1 kaurane diterpene (27), 1 flavanols glycosides (25) are new compounds. 13 is a dimer that formed from an elemanolide and a guaianolide via Diels-Alder reaction, and 15 and 16 are formed by esterification. During the isolation, 13 other compounds are isolated. Absolute configuration of the new compounds are determined by comparison of the experimental ECD and calculated ECD.After analysis of the structures and NMR data of isolated compounds, the characteristic of structures and NMR signals are summarized, and the relations between sesquiterpenes and dimers are also summarized.The compounds isolated from V. anthelmintica were tested their cytotoxicity against HCT-15 (human colon cancer), PC-3 (prostate cancer), A549 (human lung carcinoma), T47D (human breast cancer) and Hela (human cervix cancer) cell lines. Among the dimers, 1 and 2 showed strong cytotoxicity against T47D, 5 and 14 against HCT-15 cell lines with IC50 values less than 10 μM, especially 2 against T47D, IC50 value is less than 1 μM. Among the sesquiterpenes, 23 showed strong cytotoxicity against A549, 24 against HCT-15, PC-3, A549 and Hela cell lines, 33 against HCT-15, 36 against HCT-15, PC-3 cell lines, especially 36 against HCT-15 and PC-3 cell lines, IC50 values are less than 1 μM. 15 against HCT-15、PC-3 and A549 cell lines, and 46, 47 against HCT-15 cell line showed non-concentration dependent cytotoxicity.Flavonoid, some of the sesquiterpenes and dimers are tested their influence of melanin content in B16 melanoma cells, 30 and 37 significantly increased melanin content, more than 200%. |
| 内容类型 | 学位论文 |
| 源URL | [http://ir.xjipc.cas.cn/handle/365002/4597]  |
| 专题 | 新疆理化技术研究所_资源化学研究室 |
| 作者单位 | 中国科学院新疆理化技术研究所 |
| 推荐引用方式 GB/T 7714 | 阿不拉江•图拉克. 驱虫斑鸠菊化学成分及其生物活性研究[D]. 北京. 中国科学院大学. 2016. |
| 个性服务 |
| 查看访问统计 |
| 相关权益政策 |
| 暂无数据 |
| 收藏/分享 |
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。
修改评论