中科环渤海（烟台）药物高等研究院郭跃伟等研究人员合作发现发现，海南软珊瑚Lobophytum crassum中的二萜类化合物，可作为具有ErbB3和ROR1抑制潜力的抗癌剂的潜在来源。相关论文于2024年7月29日在线发表在《中国药理学报》杂志上。

对海南软珊瑚Lobophytum crassum的详细化学研究导致了一个大环二萜类化合物（1–28）的发现，包括三种新的柔性西柏烷类，lobophycrasins E–G（2–4），以及二十五种已知的类似物。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、修正的Mosher方法、X射线衍射分析和与文献中报道的数据对比，研究人员阐明了它们的结构。

生物检测结果显示，十六种西柏烷类抑制了H1975、MDA-MB231、A549和H1299细胞的增殖。其中，化合物10、17和20表现出显著的抗增殖活性，IC50值为1.92–8.82 μM，与阳性对照药物多柔比星的活性非常相似。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。该研究可能为发现和利用海洋大环西柏烷类化合物，作为抗癌药物的前导化合物提供了新的见解。

附：英文原文

Title: Polyoxygenated cembrane-type diterpenes from the Hainan soft coral Lobophytum crassum as a promising source of anticancer agents with ErbB3 and ROR1 inhibitory potential

Author: Shen, Shou-mao, Yu, Dan-dan, Ke, Lin-mao, Yao, Li-gong, Su, Ming-zhi, Guo, Yue-wei

Issue&Volume: 2024-07-29

Abstract: 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.

DOI: 10.1038/s41401-024-01347-z

Source: https://www.nature.com/articles/s41401-024-01347-z