Studies On The Chemical Constituents And Bioactivities Of The South China Sea Gorgonian Subergorgia Suberosa

The gorgonian Subergorgia suberosa is widely distributed in the Indo-Pacificwaters and has been found to contain structurally diverse secondary metabolitesincluding sesquiterpenes,9,11-secosteroids, pregnane derivatives and alkaloids. Someof these metabolites were reported to exhibit diverse biological activities, e.g.,cytocoxic, antimicrobial or anti-cholinesterase effects.In order to search for biologically active metabolites from marine organisms, amarine gorgonian S. suberosa collected from South China Sea was studied. Ourinvestigation of CHCl-MeOH (1:1, v/v) extract of S. suberosa has now led to theisolation of51compounds whose structures were determined mainly on the basis ofMS, NMR, IR, UV techniques and by comparison with the reported data in literature.Of the51(CBR-1~CBR-51) compounds,16were structurally elucidated as9,11-secosteroids, namely, subergorgol A (CBR-1)， subergorgol B (CBR-2)，subergorgol C (CBR-3)，subergorgol D (CBR-4)， subergorgol E (CBR-5)，subergorgol F (CBR-6)， subergorgol G (CBR-7)， subergorgol H (CBR-8)，subergorgol I (CBR-9)， subergorgol J (CBR-10)， subergorgol K (CBR-11)，9,11-seco-3β,6α,11-trihydroxy-5α-cholest-7-en-9-one (CBR-17),9,11-seco-3β,6α,11-trihydroxy-24-methylene-5α-cholest-7-en-9-one (CBR-18),24-nor-9,11-seco-3β,6α,11-trihydroxy-5α-cholest-7,22(E)-dien-9-one (CBR-19),3β,6α,11-trihydroxy-24-methyl-5α-cholest-9,11-seco-7,22(E)-diene-9-one (CBR-20) and3β,6α,11-trihydroxy-24-methyl-5α-cholest-9,11-seco-7-en-9-one (CBR-21)。All of them shairthe same3β,6α,11-trihydroxy-7-en-9-one-5α-9,11-secosteroid core structure withdiverse side chains and CBR-1~CBR-11are new compounds. In particular,compounds CBR1~5possess side chains hydroxylated at C-20, and compounds CBR6~7feature a unique steroid side chain with20(22) E–double bond and23-methoxyfunctional groups. New compounds subergorgine A-E (CBR-12~CBR-16) are raresesquiterpene-alkaloids with both purine and subergane–type sesquiterpene moieties,and the key differences are among link locations between two moieties. Other compounds are uracil (CBR-22), thymine (CBR-23), uridine (CBR-24), thymidine(CBR-25), inosine (CBR-26), oleic acid (CBR-27), palmitic acid (CBR-28),methyl-3,6-epoxy-4,6,8-triethyl-2,4,9-dodecatrienoate (CBR-29),24β–melthyl-cholest-5,22-dine-3β-ol (CBR-30),24(α)–melthyl-cholest-5,22-dine-3β-ol (CBR-31),cholesterol (CBR-32), ergosta-5,24(28)-diene-3β-ol (CBR-33), cholest-5,22-diene-3β-ol (CBR-34),3β-hydroxy-5α-pregnan-20-one (CBR-35),3β-acetoxy-5α-pregnan-20-one (CBR-36),5α-pregnan-3,20-dione (CBR-37),5α-pregnan-4-ene-3,20-dione (CBR-38),5α-pregnan-1-ene-3,20-dione (CBR-39),5α-pregnan-1,4-diene-3,20-dione (CBR-40),6β-hydroxy-4-ene-pregnen-3,20-dione(CBR-41),pregnan-1,4-diene-3-one-20-carboxylic methyl ether (CBR-42),(3β,5α,6β,22E)-ergosta-7,22-diene-3,5,6-triol (CBR-43), suberosenol A (CBR-44)，suberosanone (CBR-45), subergorgic acid (CBR-46), subergorgic acid methyl ester(CBR-47), subergorgic acid ethyl ester (CBR-48), batyl alcohol (CBR-49),3-(icosyloxy)propane-1,2-diol (CBR-50), and heptadecanol (CBR-51), respectively.Three tumor cell lines of human cervical carcinoma cells (HeLa), human breastcancer cells (MDA-MB-231) and chronic myelogenous leukemia cell lines (K562)were selected for testing antitumor activity in vitro with MTT or SRB method.Compound CBR-9showed significant cytotoxicities toward both K562andMDA-MB-231cell lines with IC50values of5.5and6.2μM, respectively, andcompound CBR-10also showed significant inhibitory activity against K562cell linewith an IC50value of6.5μM.