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

作　　者：Shou-mao Shen Dan-dan Yu Lin-mao Ke Li-gong Yao Ming-Zhi Su Yue-wei Guo 

机构地区：[1]Shandong Laboratory of Yantai Drug Discovery,Bohai Rim Advanced Research Institute for Drug Discovery,Yantai 264117,China [2]School of Pharmaceutical Sciences,Guizhou University,Guiyang 550025,China [3]School of Pharmacy,Yancheng Teachers University,Yancheng 224002,China [4]School of Medicine,Shanghai University,Shanghai 200444,China

出　　处：《Acta Pharmacologica Sinica》2025年第1期196-207,共12页中国药理学报(英文版)

基　　金：This research was financially supported by the National Natural Science Foundation of China(Nos.22167010 and 81991521);the National Key Research and Development Program of China(No.2022YFC2804100);the Natural Science Foundation of the Higher Education Institutions of Jiangsu Province(No.23KJB350011);the Shandong Laboratory Program(SYS202205);the Basic Research Project of Guizhou University(No.2023-51).

摘　　要：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 twentyfive 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 ICso values of 1.92-8.82μM,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.

关 键 词：Lobophytum crassum macrocyclic diterpenes cembranoids anticancer agent ROR1 ERBB3 

分 类 号：O62[理学—有机化学]