滇产三种木兰属植物中抗肿瘤活性倍半萜及其作用机制研究

Malignant tumor is a serious threat to human life and health in worldwide, and the research and development of new antitumor drugs is still a challenging task in the field of medicine. Natural products are important source of antitumor drugs or lead compounds. Magnolia species have important medicinal value and have been used as traditional Chinese medicine (TCM) or folk herbal for the treatment of a variety of ailments. Previous phytochemical investigations on Magnolia plants had resulted in the isolation of a number of diverse sesquiterpenoids with potent antitumor activity, which showed that Magnolia species are one of the important resources for antitumor substances. In our previous study, 33 sesquiterpenoids with different carbon skeleton, including a novel elemane-type sesquiterpenoid with orthoester unit and a trinorgermacrane-type sesquiterpenoid,were isolated from the leaves of M. grandiflora. Some of these compounds exhibited significant antitumor activity. Therefore, the project will take three Magnolia genus plants as research: M. delavayi, M. denudate, M. liliflora. The chemical constituents will be explored by phytochemical methods, and their focused anti-tumor activity, structure-activity relationships and mechanism of action will be conducted by means of chemical and biological methods. The project aims to get antitumor active compounds, and at the same time provide the basis for the rational development and utilization for the Magnolia species and support the further innovation in drug development.

恶性肿瘤是当今世界严重威胁人类生命和健康的重大问题，研发新的抗肿瘤药物依然是医药领域的一项挑战性任务。天然产物是发现抗肿瘤药物或先导化合物的重要源泉。木兰属(Magnolia)植物多作为中药或民间草药使用，具有重要的药用价值，相关研究表明该属植物富含结构多样的倍半萜，抗肿瘤活性显著，是寻找抗癌活性物质的重要资源。项目组前期从荷花玉兰(M. grandiflora)叶中发现33个不同骨架类型的倍半萜，包括一个具有原酸酯官能团的新奇榄香烷倍半萜和一个三降吉玛烷倍半萜，部分化合物具有显著的抗肿瘤活性。基于此，本项目拟对山玉兰、玉兰及紫玉兰三种木兰属植物中倍半萜类成分展开深入的研究，对所分离得到的化合物重点进行抗肿瘤活性评价，以期获得结构新颖的活性成分，并进行初步的构效关系和作用机制研究。该项目的研究为木兰属植物资源的合理开发利用提供依据，并从中寻找抗肿瘤活性成分，为进一步的创新药物研究奠定基础。

木兰科木兰属(Magnolia)植物多作为中药或民间草药使用，具有重要的药用价值，相关研究表明该属植物富含结构多样的倍半萜，抗肿瘤活性显著，是寻找抗癌活性物质的重要资源。本项目系统开展四种木兰属植物荷花玉兰(M. grandiflora)、山玉兰(M. delavayi)、玉兰(M. denudate)、紫玉兰(M. liliflora)的化学成分，从中分离鉴定111个化合物，其中萜类成分70个，包括新结构化合物28个。对部分倍半萜类化合物开展抗肿瘤和抗炎活性评价，发现8个活性显著的抗肿瘤活性化合物和1个活性显著的抗炎活性化合物。对抗肿瘤活性显著化合物开展初步作用机制研究，发现该类化合物作用于NF-κB信号通路。进一步对抗肿瘤活性化合物1β,10α-epoxyparthenolide和micheliolide深入研究，发现这两个化合物作用于p65和 XIAP蛋白。该研究共发表研究论文5篇，包括 SCI论文2篇，中文核心3篇，培养毕业硕士研究生2人，在读硕士生1人。通过本项目的实施进一步丰富了木兰属植物化学成分和活性的多样性，为从该属植物中寻找药物先导化合物和进一步开发利用奠定坚实化学物质基础。