基于特征骨架质谱定位法快速发现海绵中aaptamine生物碱类抗肿瘤先导化合物

项目名称： 基于特征骨架质谱定位法快速发现海绵中aaptamine生物碱类抗肿瘤先导化合物

项目编号： No.21502113

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 环境科学、安全科学

项目作者： 刘磊

作者单位： 上海交通大学

项目金额： 21万元

中文摘要： 海绵中的aaptamine生物碱因其结构新颖、活性显著而备受关注。申请者基于前期获得的30种aaptamine生物碱的结构特征，利用LC-QTRAP-MS/MS的PI扫描结合IDA触发的EPI扫描技术，建立了aaptamine生物碱的质谱快速定位法，从26种西沙海绵中筛选出两种富含aaptamine生物碱海绵：远隔疏海绵和晦海海绵，已分离鉴定18种aaptamine生物碱，包括8个微量新化合物。.本课题拟采用选择性识别aaptamine生物碱特征骨架结构的质谱快速定位法，结合质谱导向的程序性分离方法（开放柱-中压制备-质谱引导自动纯化系统），追踪分离两种海绵中aaptamine生物碱；运用化学和波谱学方法确定其平面及立体结构；评价单体化合物体内外抗肿瘤活性，探讨其构效关系和作用机制。获得1-2种结构特异的aaptamine生物碱类抗肿瘤先导化合物，为新型海洋抗肿瘤药物研究奠定基础。

中文关键词： 海绵；aaptamine；生物碱；抗肿瘤；质谱

英文摘要： The aaptamine derivatives originated from marine sponges have been attracted extensive attention worldwide due to their novel chemical structure, significant bioactivity and potential medicinal value. Based on the successful experience in elucidating the mass fragmentation rule of 30 aaptamine derivatives, a rapid, sensitive and integrated method using LC-QTRAP-MS/MS has been established by the applicant to monitor the aaptamine derivatives in 26 diversified marine sponges. After combination with AutoPurification LC(/MS) and biological activity evaluation, 18 aaptamine derivatives with antitumor activity have been separated and identified preliminarily from two sponge specimens, including Aaptos aaptos and Aaptos suberitoides collected off Xisha islands in our previous study..Therefore, we expected to systematically investigate the chemical diversities and antitumor activities of aaptamine derivatives in the above mentioned two sponge specimens by using LC-QTRAP-MS/MS monitoring and procedural separation guided by AutoPurification LC(/MS). As expected results, more aaptamine derivatives with novel structures and potent antitumor activities will be discovered, the action mechanism and structure-activity relationship of which will be investigated as well. It can not only provide a rapid and orientation tracking method for monitoring trace concentration aaptamine derivatives in complex system, but also have a great significance for the rational exploration of the distant-sea biological resources in the future.

英文关键词： Marine sponge;aaptamine;Alkaloid;Antitumor;Mass spetrometry