西沙海绵共生微生物中抗肿瘤先导化合物的发现

项目名称： 西沙海绵共生微生物中抗肿瘤先导化合物的发现

项目编号： No.41476121

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 天文学、地球科学

项目作者： 林厚文

作者单位： 上海交通大学

项目金额： 79万元

中文摘要： 海绵是一类最古老复杂的共生体。海绵宿主-微生物通过代谢互作，能使共生双方在营养、能量、化学防御等方面获利，形成各取其利、各避其害的共生互作关系，是海洋药物的宝库。本课题从宿主-微生物互作角度出发，对两种西沙海绵Phakellia fusca和Dysidea avara中可能产生特异次生代谢产物的活性共生菌株进行了优选，拟以活性追踪指导分离筛选，结合HPLC-MS、HPLC-DAD-NMR等色谱/光谱联用技术，重点定向追踪分离共生菌中新型的环肽和萜醌类化合物，运用光谱学技术和化学沟通反应，结合计算化学方法确定活性单体的平面及立体化学结构，从细胞毒、NF-kB抑制和小鼠体内中空纤维三个水平评价单体化合物的抗肿瘤活性，探讨其构效关系，深入研究强活性化合物对NF-kB通路的作用机制，发现活性显著、作用机制明确的新型抗肿瘤先导化合物，为解决海洋药物药源瓶颈问题开辟一条有效途径。

中文关键词： 共生；抗肿瘤；海绵；微生物

英文摘要： Sponge is one of the oldest complex symbiosis. Sponge host-microbe make both symbiotic sides benefit in nutrition, energy, chemical defense and other aspects through metabolic interaction， forming the relationship of obtain their own benefits and avoid harms, respectively. Sponge symbiont is a treasure trove of marine drugs. Based on the host-microbe interactions, the project selected the talent commensal strains from the Paracel Islands marine sponges Dysidea avara and Phakellia fusca which may produce new bioactive secondary metabolites, applied the bio-guided separation combined with HPLC-MS, HPLC-DAD-NMR chromatography/spectroscopy hyphenated techniques to locate the new cyclic peptides and quinone terpenes from the strains. The relative and absolute configurations of the compounds will be determined by spectroscopy technologies, chemical reactions, as well as computational chemistry. The compounds will be texted in the anti-tumor evaluation for three levels: cytotoxicity,NF-kB inhibitory and hollow fiber assays. Their structure-activity relationship will be discussed, their NF-kB pathway inhibitory mechanism will also be studied. The project is plan to discover the new leads with significant potent and mechanism, to seek an effective way to solve the limitation of resource of marine drugs.

英文关键词： symbiosis;antitumor;sponge;microbe