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

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.