胰腺癌是种难以治疗的恶性消化道肿瘤。本项目在极地海洋微生物资源的新颖性和前期发现的分子结构中含“环丙基”的强抗胰腺癌活性二萜分子YA的研究基础上，针对治疗胰腺癌疾病的药物开发需求，建立体外抗胰腺癌活性筛选结合HPLC-DAD-MS/MS等特征谱学联用的技术，对一株极地海洋真菌发酵粗提物中含有“环丙基”特征活性官能团的海松烷二萜分子，进行快速定向深入发掘。一方面，累积足够量的强活性分子YA，实现克级制备，继而从细胞和分子两个层面进行抗胰腺癌作用机制研究；另一方面，继续发掘一批含有“环丙基”官能团的新活性分子，确定其平面和立体结构，评价抗胰腺癌活性，更深层次探讨该类特征分子的构效关系。含“环丙基”海松烷二萜分子的发掘、构效关系及抗胰腺癌作用机制研究，对于发掘抗胰腺癌先导化合物和开发利用极地海洋药用微生物资源具有重要的意义。

Pancreatic cancer is a kind of malignant gastrointestinal cancer and very difficult to treat. Marine microorganisms derived from Polar Regions are the important source of marine drugs. On the base of the previous found molecular YA with “cyclopropyl” group in the structure and potent anti-pancreatic cancer activity, as well as the need for the development of drugs for the treatment of pancreatic cancer, this project focused on the chemical composition of the culture of the selected Polar marine fungus. Pimarane diterpenes with “cyclopropyl” characteristic functional groups was isolated by in vitro anti-pancreatic cancer activity screening method combined with HPLC-DAD-MS/MS chromatography/spectroscopy method. On the one hand, the accumulation of a sufficient amount of molecule YA (grams preparation) was used to research the mechanism of anti-pancreatic cancer from the cells and molecules levels. On the other hand, we continued to find the new microbial active molecules containing “cyclopropyl” functional groups, determined their absolute structure, evaluated their anti-pancreatic cancer activity, and further clarified the structure-activity relationship of these characteristic molecules. The anti-pancreatic cancer biological mechanism of the potent biological metabolites will also be studied. The project intended to discover the new leads with significant potent anti-pancreatic cancer activity, which can provide an important basis for the rational and efficient use of polar marine microorganisms resources.