Polyhydroxylated steroids from the soft coral Sinularia dissecta

A repeated silica gel column chromatography followed by HPLC purification on the methanol extract of marine soft coral Sinularia dissecta, resulted in the isolation of fifteen polyhydroxylated steroids (1-15), involving six new C-18 functionalized steroids, 3beta-acetoxy-1alpha,11alpha-dihydroxygorgost-5-en-18-oic acid (1), gorgost-5-en-1alpha,3beta,11alpha,18-tetrol (2), 18-acetoxy-1alpha,3beta,11alpha-trihydroxygorgost-5-ene (3), 24(S)-3beta-acetoxy-1alpha, 11alpha-dihydroxyergost-5-en-18-oic acid (4), 24(S)-ergost-5-en-1alpha,3beta,11alpha,18-tetrol (5), and dissectolide (6). The structures of the new compounds were determined on the basis of extensive spectroscopic data (IR, MS, (1)H and (13)C NMR, HMQC, HMBC, and NOESY) analysis. Compound 6 was found as an unusual sterol bearing a lactone functionality.     

Sterols from a soft coral, Dendronephthya gigantea as farnesoid X-activated receptor antagonists

Three new steroids 3-oxocholest-1,22-dien-12β-ol (1), 3-oxocholest-1,4-dien-20β-ol (2), 3-oxocholest-1,4-dien-12β-ol (3), and three known steroids (20S)-20-Hydroxyergosta-1,4,24(28)-trien-3-one (4) [7a], 5α,8α-Epidioxycholesta-6,22-dien-3β-ol (5) [10] and 5-cholestene-3β,12β-diol (6) [11] were isolated from a soft coral Dendronephthya gigantea. Their chemical structures and relative stereochemistry were elucidated by the analysis of HRMS and 2-D NMR spectroscopic data. The steroids 1 and 2 showed notable inhibitory activity against farnesoid X-activated receptor (FXR) with IC(50)'s 14 and 15μM.     

Three new cytotoxic acylspermidines from the soft coral,Sinularia sp

Three new acylated spermidines and two known related compounds were isolated from the Okinawan soft coral, Sinularia sp. These compounds were N',N",N"-trimethylspermidines that are acylated by a methyl-branched unsaturated fatty acid. These acylspermidines showed potent cytotoxicity against human tumor cell lines at an IC(50) value of 17 ng/ml and the induction of apoptotic phenomena.     

Sinularioside, a triacetylated glycolipid from the Indonesian soft coral Sinularia sp., is an inhibitor of NO release

Chemical analysis of the Indonesian soft coral Sinularia sp. (order Alcyonacea, family Alcyoniidae) afforded a known glucosylcerebroside of the sarcoehrenoside-type and sinularioside (2), a new naturally triacetylated glycolipid containing two α-D-arabinopyranosyl residues and a myristyl alcohol unit. Their complete stereostructures were solved by interpretation of MS and NMR data along with CD analysis of degradation products. Sinularioside proved to moderately inhibit LPS-induced NO release, providing interesting clues into the poorly understood structure-activity relationships for anti-inflammatory glycolipids.     

Bioactive norditerpenoids from the soft coral Sinularia gyrosa

Chemical investigations of the soft coral Sinularia gyrosa resulted in the isolation of six new norcembranolides, gyrosanolides A–F (1–6), a new norcembrane, gyrosanin A (7), and 11 known norditerpenoids 8–18. The structures of the isolated compounds were elucidated through extensive spectroscopic data and by comparison with reported data in the literature. Compounds 1–3, 7–9, 12, and 13 at concentration of 10 μM did not inhibit the COX-2 protein expression, but significantly reduced the levels of the iNOS protein (55.2 ± 14.6%, 18.6 ± 6.7%, 10.6 ± 4.6%, 66.9 ± 5.2%, 10.2 ± 5.1%, 17.4 ± 7.2%, 47.2 ± 11.9%, and 56.3 ± 5.1%, respectively) by LPS stimulation. Compound 8 showed significant antiviral activity against HCMV (human cytomegalovirus) cells with an IC₅₀ of 1.9 μg/mL.     

Anti-inflammatory norditerpenoids from the soft coral Sinularia maxima

Chemical investigation of the soft coral Sinularia maxima resulted in the isolation of seven norditerpenoids, including two new compounds, 12-hydroxy-scabrolide A (2) and 13-epi-scabrolide C (6). The structures of the isolated compounds were elucidated based on extensive spectroscopic evidence including Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) and both one- and two-dimensional nuclear magnetic resonance (1D and 2D NMR, respectively), in comparison with reported data. Compound 6 potently inhibited IL-12 and IL-6 production in LPS-stimulated bone marrow derived dendritic (BMDCs) with IC₅₀ values of 5.30 ± 0.21 and 13.12 ± 0.64 μM, respectively. Compound 1 exhibited moderate inhibitory activity against IL-12 and IL-6 production with IC₅₀ values of 23.52 ± 1.37 and 69.85 ± 4.11 μM, respectively.     

Two polyhydroxylated steroids from the Chinese soft coral Sinularia microclavata.

Two polyhydroxylated steroids have been isolated from the South China Sea soft coral Sinularia microclavata, and their structures were established as 24-methylenecholestane-1 alpha,3 beta,5 alpha,6 beta-tetrol and 1 alpha,3 beta,5 alpha-trihydroxy-24-methylenecholestan-6-one from spectral evidence and from comparison with two reference compounds, numersterol A and 24-methylenecholestane-1 alpha,3 beta,5 alpha,6 beta, 25-pentol, which were isolated from the soft corals, Simularia numerosa and Sarcophyton glaucum, respectively.     

Cell cultures from the symbiotic soft coral Sinularia flexibilis

The symbiotic octocoral Sinularia flexibilis is a producer of potential pharmaceuticals. Sustainable mass production of these corals as a source of such compounds demands innovative approaches, including coral cell culture. We studied various cell dissociation methodologies and the feasibility of cultivation of S. flexibilis cells on different media and cell dissociation methodologies. Mechanical dissociation of coral tissue always yielded the highest number of cells and allowed subsequent cellular growth in all treatments. The best results from chemical dissociation reagents were found with trypsin-ethylene diamine tetraacetic acid. Coral cells obtained from spontaneous dissociation did not grow. Light intensity was found to be important for coral cell culture showing an enduring symbiosis between the cultured cells and their intracellular algae. The Grace's insect medium and Grace's modified insect medium were found to be superior substrates. To confirm the similarity of the cultured cells and those in the coral tissue, a molecular test with Internal Transcribed Spacer primers was performed. Thereby, the presence of similar cells of both the coral cells and zooxanthella in different culture media was confirmed.     

Sinugrandisterols A-D, trihydroxysteroids from the soft coral Sinularia grandilobata

Four new trihydroxysteroids, sinugrandisterols A-D (1-4), have been isolated from the CH₂Cl₂-soluble fraction of the EtOH extract of Sinularia grandilobata. The structures of these metabolites were determined on the basis of spectroscopic (IR, MS, and 1D and 2D NMR) analysis. The cytotoxicity of 1-4 toward a limited panel of cancer cell lines is also reported.     

Bioactive new withanolides from the cultured soft coral Sinularia brassica

Continuing study of the ethyl acetate (EtOAc) extract of the cultured soft coral Sinularia brassica afforded five new withanolides, sinubrasolides H–L (1–5). The structures of the new compounds were elucidated on the basis of spectroscopic analysis. The cytotoxicities of new compounds 1–5 and a known compound sinubrasolide A (6) against the proliferation of a limited panel of cancer cell lines were assayed. The anti-inflammatory activities of compounds 1–6 were evaluated by measuring their ability to suppress N-formyl-methionyl-leucyl-phenyl-alanine/cytochalasin B (fMLP/CB)-induced superoxide anion generation and elastase release in human neutrophils.     

A new 9,11-secosterol from the soft coral Sinularia granosa

Chemical investigations on the EtOAc-soluble fractions from the EtOH extract of Formosa soft coral afforded a new 9,11-secosteroid, 8αH-3β,11-dihydroxy-5α,6α-expoxy-24-methylene-9,11-secocholestan-9-one (1), along with one known steroid 3β,11-dihydroxy-5β,6β-expoxy-24-methylene-9,11-secocholestan-9-one (2) from Sinularia granosa. The structure of the new metabolite was elucidated on the basis of extensive spectroscopic analysis and by comparison of their NMR data with the known compounds, including 2. Both 1 and 2 were shown to significantly inhibit the accumulation of the pro-inflammatory inducible nitric oxide synthase protein, and 1 also was found to effectively reduce the level of cyclooxygenase-2 protein, in lipopolysaccharide-stimulated RAW264.7 macrophage cells at 10 μM. Furthermore, cytotoxic activity of 1 and 2 toward a limited panel of cancer cell lines was also discovered.     

Bioactive polyhydroxylated steroids from the Hainan soft coral Sinularia depressa Tixier-Durivault

Two new steroids, (2β,3β,4α,5α,8β)-4-methylergost-24(28)-ene-2,3,8-triol (1) and (3β,7α)-24-methyl-7-hydroperoxycholest-5,24(28)-diene-3-ol (2), together with 13 known analogues (3–15) were isolated from the soft coral Sinularia depressa Tixier-Durivault. The structures of the new compounds were elucidated by detailed spectroscopic analysis and comparison with reported data. In the bioassay in vitro, compounds 3a, 4, and 14 exhibited potent PTP1B inhibitory activity, being similar as that of positive control oleanolic acid. Compound 14 also displayed a notable neuroprotective activity against both amyloid-β_25–35- and serum deprivation-induced injuries in SH-SY5Y cells while compound 11 showed a considerable antibacterial activity against Staphylococcus aureus. Preliminary structure–activity relationships of these steroids were discussed.     

A new antiangiogenic C24 oxylipin from the soft coral Sinularia numerosa

A new oxylipin, 15-hydroxy-tetracosa-6,9,12,16,18-pentaenoic acid (15-HTPE; 1) was isolated as an inhibitor of tube-formation from the soft coral Sinularia numerosa. Its structure was elucidated by means of spectral analysis and chemical degradation. 15-HTPE inhibited tube formation of EA.hy926 cells at the concentration of 20–40 μM.     

Steroids from the soft coral Dendronephthya sp

Fifteen steroids were isolated from the soft coral Dendronephthya sp., of which five are determined as new compounds, namely (22E)-3-O-beta-formylcholest-5,22-diene (1), (22E)-3-O-beta-formyl-24-methyl-cholest-5,22-diene (2), 2-ethoxycarbonyl-2-beta-hydroxy-A-nor-cholest-5-ene-4-one (3), (22E)-2-ethoxycarbonyl-2-beta-hydroxy-A-nor-cholest-5,22-diene-4-one (4), and (22E)-2-ethoxycarbonyl-2-beta-hydroxy-24-mthyl-A-nor-cholest-5,22-diene-4- one (5). 1 and 2 belonged to 3-O-formylated cholesterol analogues, and 3 to 5 are unique ring A-contracted steroids. Their structures were elucidated by extensive 2D NMR in association with IR, MS analysis.     

Acylspermidine derivatives isolated from a soft coral,Sinularia sp,inhibit plant vacuolar H(+)-pyrophosphatase

H(+)-pyrophosphatase (H(+)-PPase), which pumps H(+) across membranes coupled with PP(i) hydrolysis, is found in most plants, and some parasitic protists, eubacteria and archaebacteria. We assayed a number of extracts derived from 145 marine invertebrates as to their inhibitory effect on plant vacuolar H(+)-PPase. Acylspermidine derivatives [RCONH(CH(2))(3)N(CH(3))(CH(2))(4)N(CH(3))(2)] from a soft coral (Sinularia sp.) inhibited the PPi-hydrolysis activity of purified H(+)-PPase and the PP(i)-dependent H(+) pump activity (half inhibition concentration, 1 micro M) of vacuolar membranes of mung bean. The apparent K(i) was determined to be 0.9 micro M. Acylspermidines did not affect the activity of vacuolar H(+)-ATPase, plasma membrane H(+)-ATPase, mitochondrial ATPase or cytosolic PPase. Acylspermidines inhibited the acidification of vacuoles in protoplasts, as found on monitoring by the acridine orange fluorescent method. These results indicate that acylspermidine derivatives represent new inhibitors of H(+)-PPase with relatively high specificity.     

5,8-Epidioxysterols and related derivatives from a Chinese soft coral Sinularia flexibilis

Chromatographic separation of the methanolic extract of the marine soft coral, Sinularia flexibilis, resulted in the isolation and characterization of four new sterols, 5alpha,8alpha-epidioxygorgosta-6-en-3beta-ol (1), 5alpha,8alpha-epidioxygorgosta-6,9(11)-dien-3beta-ol (2), 22alpha,28-epidioxycholesta-5,23(E)-dien-3beta-ol (3) and its C-22 epimer (4), along with nine known sterols. The structures of the new compounds were determined on the basis of extensive spectroscopic data (IR, MS, 1H and 13C NMR, HMQC, HMBC, and NOESY) analyses.     

Marine sterols X. Minor constituents of the sterols of the soft coral Sarcophyton glaucum

The sterol mixture of the southern Japan soft coral $\text{Sarcophyton glaucum}$ was found to contain a variety of minor components overlooked in a previous study. Five 4α-methylsterols ($\text{1}$ to $\text{5}$) and three 4-demethyl-sterols ($\text{6}$ to $\text{8}$) were isolated and their structures were confirmed.     

Cyclopentenone Derivatives and Polyhydroxylated Steroids from the Soft Coral Sinularia acuta

Four new polyhydroxylated steroids, 1 – 4 , and the racemic form of cyclopentenone 9 , together with four known steroids, 5 – 8 , one known cyclopentenone derivative, 10 , and one known butenolide derivative, 11 , were isolated from the soft coral Sinularia acuta collected from Weizhou Island of Guangxi Province, P. R. China. Their structures were elucidated on the basis of spectroscopic analyses and by comparison of the corresponding data with those previously reported. The cytotoxicities of the isolates 1 – 11 in vitro against the selected tumor cell lines HL‐60, HeLa, and K562 were evaluated. Compounds 2 and 5 showed potent cytotoxicities against HL‐60 cell lines with IC₅₀ values of 7.3 and 9.9 μM , respectively. Compounds 5 and 6 showed moderate activities against K562 cell lines with IC₅₀ values of 10.9 and 11.7 μM , respectively, while compounds 1, 2 , and 6 showed weak activities against HeLa cell lines with respective IC₅₀ values of 44.8, 27.1, and 18.2 μM . This is the first report on chemical and bioactivity research of S. acuta.     

Demographic aspects of the soft coral Sinularia flexibilis leading to local dominance on coral reefs

We evaluated the role that demography may play in the formation of local aggregations of Sinularia flexibilis (Quoy & Gaimard, 1833), a soft coral that commonly dominates inshore coral reefs of the Great Barrier Reef (GBR), Australia. Two populations on inshore reefs of the Palm Islands were censused once a year for 3 years, starting 10 mo after the extensive bleaching mortality in early 1998. Larger colonies became more prevalent over time; mean colony size increasing by 35%, from 276 cm² in 1998 to 373 cm² in 2000. Growth rates were size dependent, with smaller colonies growing proportionally faster than larger colonies. Change in size relative to initial size indicated an expected mean annual growth of 128 cm² for a 50-cm² colony. Zero growth was predicted at 532±21cm², with colonies larger than this likely to undergo fission or shrink. Forty-three percent of colonies were undergoing fission at any time at both localities. Most new colonies were produced by fission (70%, n=285), with the remainder produced by the recruitment of sexually produced larvae (19%) or by colony translocation (11%). The sexual and asexual recruitment rates were 0.24 and 1.0 recruits m- ² year−¹, respectively. Opportunistic recruitment and rapid growth following disturbances are commonly assumed to be the mechanisms leading soft corals to dominate locally. In this study, these mechanisms operated more slowly than expected, with no net change in population size.