Studies On The Chemical Constituents And Bioactivities Of Three Coral-associated Marine Organisms

In order to search for natural products with unique structural features and pronounced biological activities from marine organisms, a marine sponge Aaptos suberitoides and two corals Subergorgia ornate and Rumphella aggregate were collected from South China Sea. An extensive chromatographic examination was resulted in the isolation of63compounds from the selected marine sponge and corals, and55compounds’ structures were determined on the basis of MS, NMR, IR, UV, CD method and by comparison with the reported data in literature, including19new ones, as well as36known ones which were discovered from the selected marine sponge and corals for the first time.Eighteen compounds were isolated from the marine sponge Aaptos suberitoides. These compounds were structurally elucidated as fifteen aaptamine alkloids, namely,8,9,9-trimethoxy-9H-benzo[de][1,6]naphthyridine (AS-1), demethyl(oxy)aaptamine (AS-2), Suberitine A (*AS-3), Suberitine B (*AS-4), Suberitine C (*AS-5), Suberitine D (*AS-6), Suberitine E (*AS-7), Suberitine F (*AS-8), Suberitine G (*AS-9), Suberitine H (*AS-10), Suberitine I (*AS-11), Suberitine J (*AS-12), Suberitine K (*AS-13), Suberitine L (*AS-14), Suberitine M (*AS-15); the chiral compounds Suberitine E (*AS-7), Suberitine F (*AS-8), Suberitine H (*AS-10), Suberitine J (*AS-12), Suberitine K (*AS-13), Suberitine L (*AS-14), Suberitine M (*AS-15) were further purified throuth chiral resolution by HPLC to (*AS-7a) and (*AS-7b),(*AS-8a) and (*AS-8b),(*AS-10a) and (*AS-10b),(*AS-14a) and (*AS-14b),(*AS-15a) and (*AS-15b); and one imidazole, namely,8a-methoxy-imidazo[1,5]-alpyridine-1,3-dione)(*AS-16); and one polyketide, namely, methyl-3,6-epoxy-4,6,8-triethyl-2,4,9-dodecatrienoate (AS-17); and one nucleosides, namely,2’-deoxythymidine (AS-18). Among them, there are fourteen new natural products (AS-3-AS-16), and compounds AS-3-AS-15are novel aaptamine alkaloids with two aaptamine skeleton units,8,9,9-trimethoxy-9H-benzo[de][1,6]naphthyridine and demethyl(oxy)aaptamine, linked through a rare C-3-C-3’, C-3-C-6’or C-3-C-9’sigma bond between the [1,6]-naphthyridine rings. Moreover, a possible biosynthetic pathways of aaptamine alkloids AS-1-AS-15were postulated according to their structures and literatures, and some chemical synthesis of compounds AS-3-AS-15was also performed in the paper.From the gorgonian coral Subergorgia ornate, nine compounds were isolated and characterized. The structure types included two miazines, namely, uracil (SO-1), thymine (SO-2); and seven nucleosides, namely, uridine (SO-3),2’-deoxyuridine (SO-4), thymidine (SO-5),2’-deoxythymidine (SO-6), cytidine (SO-7), inosine (SO-8), guanosine (SO-9).From the gorgonian coral Rumphella aggregata, twenty-three compounds were isolated and characterized. The structure types included fifteen sterols, namely, cholesterol (RA-1),(22E)-cholest-5,22-dien-3β-ol (RA-2),(22E)-ergosta-5,22-dien-3β-ol (RA-3), ergosta-5,24(28)-dien-3β-ol (RA-4), stigmaster-5,24(28)-dien-3β?-ol (RA-5), gorgosterol (RA-6),3β-hydroxycholesta-5-en-7-one (RA-7),3β-hydroxyergosta-5-en-7-one(RA-8),(22E)-3β-hydroxyergosta-5,22-dien-7-one (RA-9), cholest-7-ene-3β,5a,6β-triol (RA-10), cholesta-7,22-dien-3β,5a,6β-triol (RA-11), ergosta-7-ene-3β,5a,6β-triol (RA-12),(22E)-ergosta-7,22-dien-3β,5a,6β-triol (RA-13), stigmaster-7-ene-3β,5a,6βtriol (RA-14),(22E)-stigmaster-7,22-dien-3β,5a,6β-triol (RA-15); and one miazines, namely, uracil (RA-16); and one caffeine (RA-17); and one carotenoid, namely, hydratoperidinin (RA-18); and five lipids, namely,5Z,8Z,11Z,14Z-tetraene-methyloctadecanoate (RA-19),5Z,8Z-diene-methyl heptadecanoate (RA-20),5Z,8Z,11Z,14Z,17Z-pentaene-methyleicosanoate (RA-21),5Z,8Z-diene-methyleicosanoate (RA-22),5Z,8Z,11Z-triene-methylheptadeca noate (RA-23).Three tumor cell lines P388(murine leukemia cell), HeLa (human cervical carcinoma cells) and K562(chronic myelogenous leukemia cell lines of the original) were selected for in vitro antitumor activity screening with MTT method, and enzyme-linked immunosorbent assay (ELISA) method was used for most single compounds in the vitro antitumor activity of a preliminary evaluation. The results showed that the aaptamine alkloids, compounds AS-4, AS-6and AS-8showed potent cytotoxicity against P388cell lines, with IC50values of1.8μM,3.5μM and1.6μM, respectively. Compound AS-8also had moderate cytotoxicities against K562cell line with IC50values of9.3μM. Furthermore, Compound AS-8was a potent Receptor tyrosine kinase inhibitor, with IC50values of5.4μM, respectively.