Novel cytotoxic nine-membered macrocyclic polysulfur cembranoid lactones from the soft coral Sinularia sp

• Published in: Tetrahedron Vol. 70; no. 38; pp. 6851 - 6858
• Main Authors: Lei, Ling-Fang, Chen, Min-Feng, Wang, Tao, He, Xi-Xin, Liu, Bing-Xin, Deng, Yun, Chen, Xiao-Jie, Li, Yu-Ting, Guan, Shan-Yue, Yao, Jun-Hua, Li, Wei, Ye, Wen-Cai, Zhang, Dong-Mei, Zhang, Cui-Xian
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 23.09.2014; Elsevier
• Subjects: Cembranoids; Chemistry; Chemistry, Organic; Physical Sciences; Science & Technology; Sinularia sp; Soft coral; Trithio-cembranoid lactones; Cembranoids; Soft coral; Trithio-cembranoid lactones; Sinularia sp; CELLS; DITERPENE CYCLASES; SULFUR; 23-HYDROXYBETULINIC ACID; DICTYOPTERIS; IN-VITRO; BRUGUIERA-GYMNORRHIZA; BIOSYNTHESIS; RESISTANCE; DERIVATIVES
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2014.07.042

One novel nine-membered macrocyclic polysulfur cembranoid lactone, sinulariaoid A (1); three new multioxygenated cembranoids, sinulariaoid B (2), sinulariaoid C (3), sinulariaoid D (4); and four known cembranoids, capilloloid (5), dihydrosinularin (6), sinularin (7), and dihydrosinuflexolide (8) were isolated from the soft coral Sinularia sp. collected off of Sanya Bay in the South China Sea. Their stereochemical structures were determined on the basis of extensive spectroscopic methods, including single crystal X-ray diffraction analysis. Sinulariaoid A (1) is the first reported nine-membered macrocyclic polysulfur cembranoid from soft coral. The cytotoxic activities of compounds 1–8 were determined in four human cancer cell lines (HepG2, HepG2/ADM, MCF-7, and MCF-7/ADM). Of these, sinulariaoid A (1) exhibited the most potent anticancer activity in vitro, and its cytotoxicity in HepG2/ADM was more potent than in the other three cell lines. Furthermore, it was found that sinulariaoid A (1) induced apoptosis, and its selective toxicity toward HepG2/ADM cells was not related to P-glycoproteins. [Display omitted] Sinulariaoid A is the only one nine-membered macrocyclic polysulfur cembranoid from the soft coral, and the IC50 was 9.70±1.77 M against HepG2/ADM.