对海南软珊瑚 Lobophytum crassum 的详细化学研究导致鉴定出一类多氧西松烷型大环二萜 (1-28)，包括三种新的柔性西松烷类化合物、叶藻素 E-G (2-4) 和 25 种已知的类似物。通过结合广泛的光谱数据分析、量子力学核磁共振 (QM-NMR) 方法、改进的 Mosher 方法、X 射线衍射分析以及与文献报道的数据比较，阐明了它们的结构。生物测定表明，16 种西松烷内酯可抑制 H1975、MDA-MB231、A549 和 H1299 细胞的增殖。其中，化合物10、17和20表现出显着的抗增殖活性，IC50值为1.92-8.82 μM，与阳性对照阿霉素非常相似。分子机制研究表明，化合物10的抗肿瘤活性与ROR1和ErbB3信号通路的调节密切相关。这项研究可能为海洋大环西松烷类化合物作为抗癌药物先导化合物的发现和利用提供见解。© 2024。作者获得中国科学院上海药物研究所和中国药理学会的独家许可。

A detailed chemical investigation of the Hainan soft coral Lobophytum crassum led to the identification of a class of polyoxygenated cembrane-type macrocyclic diterpenes (1-28), including three new flexible cembranoids, lobophycrasins E-G (2-4), and twenty-five known analogues. Their structures were elucidated by combining extensive spectroscopic data analysis, quantum mechanical-nuclear magnetic resonance (QM-NMR) methods, the modified Mosher's method, X-ray diffraction analysis, and comparison with data reported in the literature. Bioassays revealed that sixteen cembranoids inhibited the proliferation of H1975, MDA-MB231, A549, and H1299 cells. Among them, Compounds 10, 17, and 20 exhibited significant antiproliferative activities with IC50 values of 1.92-8.82 μM, which are very similar to that of the positive control doxorubicin. Molecular mechanistic studies showed that the antitumour activity of Compound 10 was closely related to regulation of the ROR1 and ErbB3 signalling pathways. This study may provide insight into the discovery and utilization of marine macrocyclic cembranoids as lead compounds for anticancer drugs.© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.