西沙群岛四种海绵新颖结构抗肿瘤活性成分的发现研究

Marine sponges, with its rich species diversity, novel chemical structures of secondary metabolities and potential medicinal value, represent an irreplaceable role in searching marine drugs. In particular, the sponges from Xisha islands showed vast resources and unique geographical features due to the special habitat, they are thereby known as the ideal investigating objects for marine drugs. However, few of the studies on Xisha sponges were examined so far relative to the offshore ones. Therefore, on the bases of the previously important findings, we expected to systematically investigate the chemical diversities and anti-tumour activities for the four unreported sponge specimens, including Fascaplysinopsis reticulate, Agelas cf. Mauritiana, Cacospongia sp. and Aaptos suberitoides collected off Xisha islands, guided by chemistry and bioactivity. As an expected results, numbers of compounds with novel structures and potent anti-tumour activities will be discovered, which will provide surprising template molecules for further marine drug study, and have a great significance for the rational exploration of the distant-sea biological resources in the future.

海绵以其丰富的物种多样性、次级代谢产物的结构新颖性和潜在的药用价值在海洋药物研究中具有不可替代的地位。我国西沙海绵物种多样性丰富且具有显著的地域特征，是开展海洋药物研究的理想研究对象。相对于近海，远海海洋生物研究报道较少。课题拟在前期对该海域两种海绵Aaptos suberitoides和Plakortis simple初步研究取得重要发现的基础上，对该海域未见研究报道的四种具有显著细胞毒活性的海绵物种Fascaplysinopsis reticulate、Agelas cf. mauritiana、Cacospongia sp.和Aaptos suberitoides，进行系统的化学-生物活性双导向的抗肿瘤活性成分挖掘研究。研究结果将发现一批新颖结构抗肿瘤活性分子，可为进一步的海洋药物研究提供苗头化合物，对探索我国远海生物资源的合理开发利用具有重要意义。

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种西沙群岛海绵化学成分研究，阐明了四种海绵的化学多样性：Aaptos suberitoides（Aaptamin生物碱），Fascaplysinopsis reticulate（吲哚生物碱），Agelas cf. mauritiana（吡咯生物碱），以及Cacospongia sp.（链状二萜和二倍萜衍生物）。从四种西沙群岛海绵中共分离纯化鉴定了各类海绵天然产物106个，发现新化合物47个，新骨架化合物21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，采用MTT和SRB法进行了较系统的抗肿瘤活性筛选和评价。获得9个化合物显示强的抗肿瘤、免疫等活性。培养硕士研究生6名，博士研究生3名，发表SCI研究论文8篇。