基于LC-MS/MS特征轮廓谱分析方法的姜黄中强抗肿瘤活性微量姜黄素类化合物的快速发现

项目名称： 基于LC-MS/MS特征轮廓谱分析方法的姜黄中强抗肿瘤活性微量姜黄素类化合物的快速发现

项目编号： No.31270392

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 姜宏梁

作者单位： 华中科技大学

项目金额： 75万元

中文摘要： 本课题组前期研究发现姜黄中的新型微量成分具有显著抗肿瘤活性，而且初步LC-MS/MS分析结果表明姜黄中富含该类结构新颖的微量成分。然而，目前还没有能特异、系统地发现和高效分离该类微量成分的报道。本项目拟在前期工作基础上，根据姜黄素类成分的结构特征、质谱裂解规律以及应用QTRAP和LTQ-orbitrap质谱仪的不同功能特点，建立基于LC-MS/MS(MRM)技术的能系统、特异和快速地识别、表征和鉴定该类成分的特征轮廓谱分析方法。进而将该方法应用到整个植化研究过程，以其提供的信息为靶标，指导合理选材、示踪该类成分的分离纯化，提高分离过程的靶标性和有效性，达到高效、系统分离该类微量成分的目的。然后，对所获得的该类成分进行系统的抗肿瘤活性测试、构效关系分析和生物利用度评价。通过以上研究，获得结构新颖的具有较高生物利用度的高效抗肿瘤先导化合物，并为高效发现、分离特定类别的活性成分提供新思路。

中文关键词： 姜黄素；特征轮廓谱；液质联用；抗肿瘤；

英文摘要： In our previous study, novel low abundance curcuminoids in Curcuma longa showed significant antitumor activities. In addition, our preliminary data obtained from LC-MS/MS analysis indicated that Curcuma longa is rich of novel low abundance curcuminoids. However, no reports with regard to effective recognition, discovery, and isolation of thess classes of low abundance curcuminoids are available yet. On top of our previous work, we are planning to establish a LC-MS/MS (MRM) based characteristic metabolite profiling approach according to their chemical structures and the corresponding fragmentation patterns of these compounds in mass spectrometer as well as strategic use of QTRAP and LTQ-orbitrap. This approach can be used to rapidly and specifically recognize, profile, and identify curcuminoids. Furthermore, in order to efficiently and systematically obtain low abundance curcuminoids, this approach will be used to select raw material, monitor and guide the isolation and purification of these classes of compounds. Then, systematic evaluation of their antitumor activity, structure-activity relationships, and bioavailability will be conducted using the individual curcuminoids obtained. Through our study, novel lead compounds with high antitumor activity and acceptable bioavailability will be obtained. In the mean wh

英文关键词： curcuminoids；characteristic metabolic profiling；LC-MS/MS；antitumor activity；