中国南海深远海短足软珊瑚中cladiellin型二萜的化学多样性及靶向EGFR抗肿瘤活性研究

Cladiellin型二萜是短足软珊瑚的特征化合物，具有新颖的结构骨架和丰富的生物学功能，部分化合物呈现显著肿瘤细胞毒活性，值得深入研究。在国家大力开发海洋资源的战略部署及“向海洋要药物”的需求牵引下，在充分文献调研和前期研究基础上，为突破该类化合物的系统性和聚焦性不足以及难以大量获得分子进行深入研究的瓶颈问题，申请人提出本项目申请，在化学成分上聚焦于cladiellin型二萜的结构多样性，在应用目标上聚焦于靶向EGFR的抗肿瘤活性，以深远海为特征的不同采集地等化学生态学因素为导向，以短足软珊瑚为研究对象，充分挖掘其中结构新颖且多样性强的cladiellin型二萜，并以此为模板，结合构效关系分析、靶标虚拟筛选、生物导向合成等关键技术，进行深入结构改造和活性研究，旨在发现具有深入开发价值的靶向抗肿瘤活性的珊瑚来源海洋药物先导化合物，同时为合理开发利用丰富海洋生物资源提供依据。

Cladiellin-type diterpenoids are characteristic metabolites from Cladiella soft corals. They have been reported to comprise novel structural scaffolds and widely biological functions. Some of these compounds were reported to be of remarkable cytotoxicity against various tumor cells, which is worth for further study. In the highly demand of “Search Drugs from the Sea” under the national guidance of the vigorously exploring marine resources, and in order to breakthrough the bottleneck problem of the lack of systematic chemical structural investigation and the lack of a focusing target for the biological activity study, as well as the difficulty of acquiring large quantities of molecules for in-depth medical research, the applicant raised this project. In the chemical study, we will focus on the structural diversity of cladiellin diterpenoids, and in the biological aspect, we will focus on the EGFR-targeted anti-tumor activity. In detail, guided by chemical ecological factors such as different collection seas, taking Cladiella soft corals as the research object, we will first fully excavate the novel and diverse cladiellin diterpenoids, and then use them as the structural templates, by combining with the key technologies such as structure-activity relationship analysis, target virtual screening, molecular docking analysis, and Biology-oriented Synthesis (BIOS), to deeply make the structure modification and biological study, with the aim to find the lead compounds of marine drugs of coral sources with targeted anti-tumor activity, and to provide the guidance for rational exploitation and utilization of abundant marine living resources.