西沙群岛海绵中多类型新颖结构次级代谢产物发现及生物活性谱研究

Secondary metabolites from marine sponges play an irreplaceable role in the field of marine natural products and have been attracting a special attention for natural products chemist, because of their unique and challenging chemical structures, high biological activity, and potential available values. However, relative to the offshore sponges, the species distributed in Xisha Islands exhibited more unique geographical features, and up to now, most of which remained an un-studying state. Meanwhile, the poor studies also indicated Xisha sponges featured a remarkable advantage in the discovery of new lead compounds. Therefore, the presented project will systematically study the selected six sponge species from four genera derived of Xisha Islands, for the discovery of new structural secondary metabolites and biological spectrum, on the basis of our previous work on marine natural products, and especially the investigations concerned with the project such as marine sponge resources distribution, literature analysis, as well as preliminary chemical and biological work. As a consequence, it was likely expected that a batch of astonished lead compounds with different structural type and high activity could be found and the potential chemical taxonomic relationships for the different sponge species could be clarified, the ability and levels for identifying the complex natural product structures by mean of multi-techniques could be developed. The project will not only provided some new model molecules for the later in-depth study, but also will disclose the potential exploitation and utilization values for the far-sea resources.

海绵次级代谢产物不仅具有独特和富有挑战的结构类型，更因其高的生物活性和潜在的利用价值一直为天然产物化学家所特别关注，在海洋天然产物研究领域具有不可替代的位置。相对于近海，远海西沙群岛海绵生物多样性具有显著地域特征，丰富的资源有待于系统研究工作的开展。更重要的是，近年来有限的研究显示，西沙海绵在新结构先导化合物发现方面有明显优势。本项目以课题组多年开展海洋天然产物化学研究工作为基础，通过前期充分的资源调查与文献分析，结合初步的化学与生物学预研究，拟以精心选择的西沙群岛未见研究报道的4属6种海绵为对象，聚焦这些海绵中多类型新结构成分的发现和生物活性谱开展研究。通过研究，期待发现若干不同类型的高活性新结构先导化合物，揭示不同种属海绵的化学分类学亲缘关系，发展利用多手段解决复杂结构天然产物的能力与水平，为进一步深入研究提供新的模型分子。项目研究结果对探索我国远海生物资源合理开发利用具有重要价值。

海绵是海洋新颖结构功能分子的优势资源之一.通过本项目的实施,课题组已系统完成四属六种西沙群岛海绵化学成分研究，阐明了六种海绵的化学多样性：Dysidea granulosa（二倍半萜类），Dysidea sp.（混源萜类），Agelas nemoechinata（吡咯生物碱，聚酮类），Agelas sp.（吡咯生物碱），Dactylospongia elegans（混源萜类），以及Stylissa massa（吡咯生物碱）。从六种西沙群岛海绵中共分离纯化鉴定了各类海绵天然产物154个，发现新化合物47个，新骨架化合物8个。针对较复杂结构功能分子的结构鉴定问题，建立和发展了量子化学计算辅助方法，成功解决了部分复杂结构的绝对构型问题。针对已获得的单体化合物，进行了较系统的生物活性筛选和评价，9个化合物显示强的抗肿瘤活性，1个化合物具有显著的促血管生成活性。培养硕士研究生4名，博士研究生2名，发表SCI研究论文10篇，申请国家发明专利2件。