新颖结构鸢尾三萜类化合物的发现与抗肿瘤活性研究

项目名称： 新颖结构鸢尾三萜类化合物的发现与抗肿瘤活性研究

项目编号： No.21472245

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 环境科学、安全科学

项目作者： 倪刚

作者单位： 中国医学科学院药物研究所

项目金额： 80万元

中文摘要： 恶性肿瘤严重威胁人类健康与生命。中药射干和鸢尾属药用植物中含有结构新颖的鸢尾型三萜类化合物，药理研究表明它们具有显著的细胞毒活性。然而鸢尾三萜在植物中含量较低导致传统分离方法难以发现和开发。在前期研究中，我们利用现代分离技术建立了该类活性成分的富集方法，并成功从川射干根茎中发现了7个结构新颖的鸢尾三萜类化合物，其中包括一个具有较好细胞毒活性的新骨架化合物。在此基础上本项目将以发现具有抗肿瘤活性的新颖鸢尾三萜为主题，利用已建立的富集方法和快速识别化合物的化学筛选方法(通过HPLC-UV-ESIMS技术实现定向分离)，从中药射干以及鸢尾属药用植物川射干、白花射干、扁竹兰和云南鸢尾中针对性分离微量鸢尾型三萜类化合物，并测定它们的化学结构。对获得的新颖鸢尾三萜进行抗肿瘤活性筛选，选择具有明显抗肿瘤活性的鸢尾三萜为模板进行结构修饰和改造，阐明构效关系，为进一步的新药研究奠定基础。

中文关键词： 射干；鸢尾属；鸢尾三萜；构效关系；抗肿瘤活性

英文摘要： The huamn health and life is seriously threateded by malignant tumor. Novel iridal-type triterpenoids have been isolated from Belamcanda chinensis and medicinal plants of Iris. Pharmacological studies have shown that they have significant cytotoxic activity.However, it is difficult to study the microamount iridal-type triterpenoids with traditional separation strategy. In our recent study, we established the enrichment method of iridal-type triterpenoids by use of modern separate technology, and seven novel triterpenoids were isolated from rhizomes of Iris tectorum including a iridal with new carbon skeleton and significant cytotoxic acitivity. On the basis of the preliminary study, this project will focus on discovery of novel iridals-type triterpenoids with anti-tumor activity by use of established enrichment method of this kind of active ingredients and chemcial screening method (directional separate by HPLC-UV-ESIMS technology) to quickly identify trace iris-type triterpenoids from Belamcanda chinensis and medicinal plants of Iris, Iris tectorum, Iris dichotoma, Iris confusa and Iris forrestii, and the structure of isolated compounds will be determined. The isolated novel iris-type triterpenoids will be screened for anti-tumor activity. The novel iris-type triterpenoids with significant bioactivities will be selected as a template for structural modification and the structure-activity relationships will be summarized to lay the foundation for further drug research.

英文关键词： Belamcanda chinensis;Iris;iridal-type triterpenoids;structure-activity relationships;anti-tumor activity