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.     

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.     

Crassocolides N-P, three cembranoids from the Formosan soft coral Sarcophyton crassocaule

Three new cembranoids crassocolides N-P (1-3), was isolated from the organic extract of a Formosan soft coral Sarcophyton crassocaule. These structures were elucidated on the basis of spectroscopic analyses and by comparison with those previously reported in literature. The cytotoxicity of these compounds toward various cancer cell lines has also been determined.     

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.     

Trochelioid A and B,new cembranoid diterpenes from the Red Sea soft coral Sarcophyton trocheliophorum

Chemical investigations of the soft coral Sarcophyton trocheliophorum, has led to the isolation of six cembranoids, two of which are new, Trochelioid A (1) and B (2), and one, 16-oxosarcophytonin E (3) isolated from nature for the first time. Additionally, two have been isolated from S. trocheliophorum for the first time (4 and 6). Structures were elucidated by employing extensive NMR and HR-FAB-MS experimentation.     

Highly diverse cembranoids from the South China Sea soft coral Sinularia scabra as a new class of potential immunosuppressive agents

The first and in-depth chemical investigation of the South China Sea soft coral Sinularia scabra has resulted to the isolation of a library of diverse cembrane type diterpenoids, including six new compounds, namely xiguscabrates A and B (1 and 2), xiguscabral A (3), xiguscabrols A and B (4 and 5), and 8-epi-xiguscabrol B (6), and twenty-seven known analogs (7–33). Their structures were elucidated by extensive spectroscopic analysis and by the comparison with literature data. In bioassay, several isolates exhibited inhibitory effects on the ConA-induced T lymphocytes and/or LPS-induced B lymphocytes proliferation. Among them, compound 24 showed considerable specific inhibition on B cell proliferation, with IC₅₀ value of 4.4 μM and selectivity index (SI) of 10.9. The structure-activity relationship (SAR) of the tested metabolites was analyzed, and the further mechanism study of the specific B-cell targeted immunosuppressive compound 24 on purified CD19⁺ B cells was also performed to uncover the effects on the function and maturity of B cells, including cytokines production, abnormal activation, antigen presenting capacity and plasma cells formation.     

1alpha,3beta,5beta-trihydroxy-24-methylenecholestan-6-one: a novel steroid from a soft coral Sinularia gibberosa

A novel steroid, 1alpha,3beta,5beta-trihydroxy-24-methylenecholestan-6-one (gibberoketosterol) (1), along with four known steroids, was isolated from the lipophilic extracts of a Taiwanese soft coral Sinularia gibberosa. The structure of the new metabolite was determined on the basis of extensive spectral analyses and chemical reaction. The relative stereochemistry of gibberoketosterol was established by the NOESY experiments and analysis of the pyridine-induced deshielding effect of the axial hydroxy groups. Gibberoketosterol is the first example of 1alpha,3beta,5beta-trihydroxy-6-oxosteroids isolated from natural sources and was found to exhibit a moderate cytotoxicity against the growth of Hepa59T/VGH cancer cells.     

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.     

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.     

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.     

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.     

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.     

Anti-cancer evaluation of carboxamides of furano-sesquiterpene carboxylic acids from the soft coral Sinularia kavarattiensis

The chemical investigation of soft coral Sinularia kavarattiensis is described. It yielded furano-sesquiterpene carboxylic acids 1 and 2 and their methyl esters 3 and 4. Semi-synthesis of furano-sesquiterpene carboxylic acid 1 gave amide derivatives 5–12. Structures of all the compounds were established by IR, NMR and mass spectral analysis. Interestingly all compounds are selectively potent on leukemia cell line. All these compounds were screened for cytotoxic activity against five human cancer cell lines (leukemia, prostate, lung, breast and cervix). Among these compounds 9 and 10 showed promising activity against leukemia and prostate cancer cell lines.     

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.     

Bioactive polyoxygenated cembranoids from a novel Hainan chemotype of the soft coral Sinularia flexibilis

Different chemotypes of Sinularia flexibilis exist in the Hainan island. Thus, a collection of this soft coral from a location different from the one of our previous study afforded three novel cembranoid esters featuring a n-butyl alcohol moiety, a structural element rare in natural products of both terrestrial and marine origin. The structures of the new compounds were elucidated by detailed spectroscopic analysis and by the comparison of their spectroscopic data with those reported in the literature. In addition, the absolute stereochemistry of the previously reported diepoxycembrene (9) was first time determined by the X-ray diffraction analysis. In bioassays, compounds 6–8 exhibited strong anti-inflammatory effect with IC₅₀ values of 2.7, 4.7, and 4.2?μM, respectively, whereas compound 5 displayed cytotoxicity against several cancer cells with IC₅₀ values ranging from 8.9 to 27.4?μM. A preliminary structural-activity relationship (SAR) was also described.     

An unusual spinaceamine-bearing pregnane from a soft coral Scleronephthya sp. inhibits the migration of tumor cells

An unprecedented spinaceamine-bearing pregnane namely scleronine (1) was isolated from a Chinese soft coral Scleronephthya sp. Its structure was determined on the basis of 1D and 2D NMR spectroscopic analyses in association with the HRESIMS data, while the absolute configurations were deduced by the single-crystal X-ray diffraction analysis. In addition, a dehydrogenated analogue (3) was synthesized through six steps with pregna-1,20-dien-3-one (2) as a precursor. The significantly inhibitory effects of 1 and 3 against the migration of tumor cells A549 and B16 accompanying the down-regulation of key genes (TGFβ, TNFα, IL-1β, and IL-6) were observed. These findings suggested that both 1 and 3 are potential for therapeutic usage aiming at cancer metastasis inhibition.     

Anti-Inflammatory Steroids from the South China Sea Soft Coral Lobophytum sarcophytoides

Three new steroids, along with two known related analogs, were isolated from the Xisha Island soft coral Lobophytum sarcophytoides. The structures and absolute configurations of the new compounds were elucidated by extensive spectroscopic data analyses, time dependent density functional theory electronic circular dichroism calculation, and comparison with the spectral data previously reported in the literature. In in vitro bioassay, four compounds showed interesting suppressive effects on lipopolysaccharide (LPS) induced inflammation in BV-2 microglial cells at 10 μM level.     

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.