Iotrochota属海绵及其内生菌中含氮化合物及其抗肿瘤活性研究

Chemical defense built by sponge and associated microorganisms produce a great amount of natural products with new structure and potential chemecology functions. The effect of these functional compounds on human disease need to be investigated deeply. We intent to study the nitrogen compounds of marine sponge Iotrochota and associated microorganisms from south China sea and evaluate their anti-tumor activities base on the former foundation. The characteristic nitrogen compounds should be isolated quickly under the direction of NMR, LC-MS, and other technologies. The anti-tumor activities and mechanism of compounds should be investigated on multiple molecular level model. Relationships between structures and activities together with association of sponge and microorganism would be discussed. This study has the possibility of discovering diverse new compounds, including at least one lead compound for potential drug discovery. The study also provids foundation of investigation on chemecology of sponge and associated microorganisms.

海绵及其内生菌共同建立的化学防御体系提供了大量结构新颖的代谢产物，并具有潜在的化学生态功能，而生态功能成分与抑制人类疾病之间的相关性尚待深入研究。课题在前期活性与色谱/波谱导向基础上，对南海Iotrochota属海绵及其内生菌中含氮化合物进行系统研究并考察其抗肿瘤活性。主要利用NMR、LC-MS/MS等技术手段对特征性含氮化合物快速定位和分离，继而在多种分子模型下探讨其抗肿瘤作用机理。在此基础上分析化合物构效关系以及内生菌和海绵宿主间的结构活性相关性。该研究丰富了海绵及其内生菌的代谢产物多样性，优化获得先导化合物为新药研究提供了模式结构，并为海绵及其内生菌的化学生态学奠定研究基础。

本项目基于海绵独特的化学防御生态功能，以活性含氮化合物为目标，采用NMR、MS等多种光谱学手段为导向，体外抗肿瘤模型筛选进行跟踪，从我国南海海绵Iotrochota purpurea、Stylissa massa和Leucetta chagosensis中分离获得84种天然产物，包括21个新化合物。通过体外细胞水平和激酶水平测试，筛选出6个具有较好抗肿瘤相关活性的化合物，并对部分化合物进行了合成探索和构效关系分析。本研究丰富了海绵代谢产物的多样性，为优化获得抗肿瘤活性先导化合物和新药研究提供了模板，并为海绵的化学生态学研究奠定了基础。