Neritinaceramides A-E, new ceramides from the marine bryozoan Bugula neritina inhabiting South China Sea and their cytotoxicity

• Published in: Marine drugs 2014-04, Vol.12 (4), p.1987-2003
• Main Authors: Tian, Xiang-Rong, Tang, Hai-Feng, Feng, Jun-Tao, Li, Yu-Shan, Lin, Hou-Wen, Fan, Xiao-Pei, Zhang, Xing
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - chemistry; Antineoplastic Agents - isolation & purification; Antineoplastic Agents - pharmacology; Bryozoa - metabolism; Bugula neritina; Cell Line, Tumor; ceramide; Ceramides - chemistry; Ceramides - isolation & purification; Ceramides - pharmacology; China; cytotoxicity; Hep G2 Cells; Humans; Inhibitory Concentration 50; Marine; marine bryozoan; Neoplasms - drug therapy; Neoplasms - pathology; neritinaceramide; Oceans and Seas
• ISSN: 1660-3397; 1660-3397
• DOI: 10.3390/md12041987

Five new ceramides, neritinaceramides A (1), B (2), C (3), D (4) and E (5), together with six known ceramides (6-11), two known alkyl glycerylethers (12 and 13) and a known nucleoside (14), were isolated from marine bryozoan Bugula neritina, which inhabits the South China Sea. The structures of the new compounds were elucidated as (2S,3R,3'S,4E,8E,10E)-2-(hexadecanoylamino)-4,8,10-octadecatriene-l,3,3'-triol (1), (2S,3R,2'R,4E,8E,10E)-2-(hexadecanoylamino)-4,8,10-octadecatriene-l,3,2'-triol (2), (2S,3R,2'R,4E,8E,10E)-2-(octadecanoylamino)-4,8,10-octadecatriene-l,3,2'-triol (3), (2S,3R,3'S,4E,8E)-2-(hexadecanoylamino)-4,8-octadecadiene-l,3,3'-triol (4) and (2S,3R,3'S,4E)-2-(hexadecanoylamino)-4-octadecene-l,3,3'-triol (5) on the basis of extensive spectral analysis and chemical evidences. The characteristic C-3'S hydroxyl group in the fatty acid moiety in compounds 1, 4 and 5, was a novel structural feature of ceramides. The rare 4E,8E,10E-triene structure in the sphingoid base of compounds 1-3, was found from marine bryozoans for the first time. The new ceramides 1-5 were evaluated for their cytotoxicity against HepG2, NCI-H460 and SGC7901 tumor cell lines, and all of them exhibited selective cytotoxicity against HepG2 and SGC7901 cells with a range of IC50 values from 47.3 μM to 58.1 μM. These chemical and cytotoxic studies on the new neritinaceramides A-E (1-5) added to the chemical diversity of B. neritina and expanded our knowledge of the chemical modifications and biological activity of ceramides.