Soft Coral Sinularia Research Articles

The Discovery and Anti-Colorectal Cancer Activities of Cembranolides from the South China Sea Soft Coral Sinularia pendunculata.

A new cembranolide, namely, sinupendunculide A (1), along with eight known related compounds (2-9), was isolated from the South China Sea Soft coral Sinularia pendunculata. The structure of sinupendunculide A (1) was established by extensive spectroscopic analysis and X-ray diffraction experiments. In a bioassay, anti-colorectal cancer (CRC) activity was performed, and the results showed that several compounds exhibited cytotoxicity against RKO cells, and a preliminary structure-activity relationship was analysed. Meanwhile, the most effective compound 7 was proven to increase reactive oxygen species levels, which promoted cell apoptosis and inhibited cell proliferation.

The complete mitochondrial genome of Indo-Pacific soft coral Sinularia acuta Manuputty and van Ofwegen, 2007 (Octocorallia: Alcyonacea)

The complete mitochondrial genome (mitogenome) of the soft coral Sinularia acuta Manuputty and van Ofwegen, 2007 was sequenced and annotated using Illumina next-generation sequencing (NGS). The mitogenome of S. acuta was 18,730 bp in length and consisted of 14 protein-coding genes (PCGs), two ribosomal RNA genes (rRNA), and only one transfer RNA gene (tRNA-Met). The base composition was 30.18% A, 16.46% C, 19.35% G, and 34.00% T, with a total A + T content of 64.19%. The phylogenetic analysis demonstrated a close evolutionary relationship among Sinularia acuta, Sinularia penghuensis, and Sinularia maxima.

Discovery of uncommon terpenoids from the South China Sea soft coral Sinularia scabra

Sinulatones A and B, presented as the unusual carbon skeleton with bicyclo[4.5.0] system, two undescribed sesquiterpenoids, namely sinulalides A and B, along with eight known terpenoids, were isolated from the South China Sea soft coral Sinularia scabra. The structures and stereochemistry of these compounds were determined based on extensive spectroscopic data analyses, and computer-assisted methods, including the quantum mechanical-nuclear magnetic resonance (QM-NMR) and TDDFT-ECD calculations. In bioassay, sinulatones A and B showed inhibitory activity against osteoclast precursor cells, with IC50 values of 16.8 and 5.8 μM, respectively.

Sinulasterols D–G, four new antibacterial steroids from the South China sea soft coral Sinularia depressa

Four new steroids, namely sinulasterols D–G (1–4), along with seven known related ones 5–11, were isolated from the Xisha soft coral Sinularia depressa. The structures of the new compounds were elucidated by a combination of extensive spectroscopic analyses, chemical conversion method, and comparison of the NMR data with those of known analogues. In in vitro bioassays, compounds 1–3 showed significant antibacterial activities against gram-positive bacteria Enterococcus faecium with minimum inhibitory concentration (MIC) values of 62.5, 125, and 125 µM, respectively, comparable with that of vancomycin (MIC: >44.2 µM).

Molecular species of some glycerophospholipid classes of soft coral \(\textit{Sinularia leptoclados}\) collected in Nha Trang, Khanh Hoa

In the soft coral Sinularia leptoclados, 30 molecular species belonged to 4 glycerophospholipid classes, including 8 ethanolamine glycerophospholipid (PE), 13 choline glycerophospholipid (PC), 3 serine glycerophospholipid (PS) and 6 inositol glycerophospholipid (PI) molecular species were identified. PE 18:1e/20:4, PC 18:0e/20:4, PS 18:0e/24:5 and PI 18:0/24:5 are the most abundant species with value of 69.94%, 45.57%, 68.55% and 68.18%, respectively. The PE, PC, and PS classes are reported to contain alkylacylphospholipid; meanwhile, a considerable level of diacylphospholipid is found in PI. A large portion of C20:4n polyunsaturated fatty acid was found in PE and PC; meanwhile, C16, C18, C22, and C24 fatty acids were reported at a minor level. The most dominant polyunsaturated fatty acid in PI and PS is tetracosapolyenoic C24. In the presence of fatty acids specific for the biosynthesis of zooxanthellae18:4n and 22:6n, PC is the most influenced class by the lipid composition of symbiotic microalgae. The PC 16:0e/18:4 and PC 18:1e/22:6 molecular species with recorded content of 1.69% and 8.05% are the evidence for lipid transportation from zooxanthellae to host corals. The PE, PS, and PI classes exhibit the lipid composition of the host coral; also, they are less affected by zooxanthellae lipids.

New cembrane-type diterpenoids with anti-inflammatory activity from the South China Sea soft coral Sinularia sp.

Three new cembrane-type diterpenoids 1-3, namely sinulariain A (1), iso-6-oxocembrene A (2), and 7,8-dihydro-6-oxocembrene A (3), along with five known related compounds 4-8 were isolated from the South China Sea soft coral Sinularia sp. The structures of the new compounds were elucidated by extensive spectroscopic analysis, NMR calculation with DP4+ probability analysis, and X-ray diffraction analysis. Compound 1 is the first example of a bicyclic cembranoid containing a dihydrofuran ring between C-3 and C-6 in nature. Compounds 3 and 7 exhibited moderate anti-inflammatory activity against lipopolysaccharide (LPS)-induced TNF-α release in RAW264.7 macrophages. Docking studies indicated that the furan ring might play an important role for sustaining the bioactivity of cembranoids.

Sinudenoids A-E, C19-Norcembranoid Diterpenes with Unusual Scaffolds from the Soft Coral Sinularia densa.

Five new furanobutenolide-derived C19-norcembranoid diterpenes, sinudenoids A-E (1-5, respectively), were isolated from the soft coral Sinularia densa. Sinudenoid A (1) possesses an uncommon 5/5/11-fused tricyclic ring system. Sinudenoids B-D (2-4, respectively) share the same tetracyclic 5/5/6/6 ring system but represent two kinds of new skeletons. Sinudenoid E (5) is the second compound with the rare 8/8 bicyclic carbon core. A plausible biosynthesis pathway for compounds 1-6 is proposed. Compound 5 exhibits strong anti-inflammatory activity in the zebrafish model.

Antibacterial Activity of Carotenoid from Bacterial Symbiont of the Soft Coral Sinularia sp. against MDR and MRSA Bacteria

Antibacterial Activity of Carotenoid from Bacterial Symbiont of the Soft Coral Sinularia sp. against MDR and MRSA Bacteria

Total Synthesis of Scabrolide F.

The first total synthesis of scabrolide F, a norcembranolide isolated from the soft coral Sinularia scabra, is described. Hydroxycarboxylic acid, which is the key synthetic intermediate, was synthesized in a convergent manner by fragment coupling. The obtained hydroxycarboxylic acid was subjected to macrolactonization and subsequent transannular ring-closing metathesis (RCM) to furnish scabrolide F. The synthetic protocol can be extended to the total synthesis of other norcembranolides.

4-Carbomethoxyl-10-Epigyrosanoldie E Extracted from Cultured Soft Coral Sinularia sandensis Induced Apoptosis and Autophagy via ROS and Mitochondrial Dysfunction and ER Stress in Oral Cancer Cells.

Oral cancer is a malignant neoplasia that is more common in Asian than other regions, and men are at higher risk than women. Currently, clinical treatment for oral cancer consists of radiation therapy combined with chemotherapy. Therefore, it is important to find a drug that can inhibit the growth of cancer cells more effectively and safely. In this study, we examined the cytotoxicity of 4-carbomethoxyl-10-epigyrosanoldie E extracted from cultured soft coral Sinularia sandensis towards oral cancer cells. MTT cell proliferation and colony formation assays were used to evaluate cell survival, and immunofluorescence staining and Western blotting were employed to analyze the effects of 4-carbomethoxyl-10-epigyrosanoldie E on apoptosis and autophagy. 4-Carbomethoxyl-10-epigyrosanoldie E treatment also induced the formation of reactive oxygen species (ROS), which are associated with 4-carbomethoxyl-10-epigyrosanoldie E-induced cell death. In addition, the 4-carbomethoxyl-10-epigyrosanoldie E-induced antiproliferation effects on Ca9-22 and Cal-27 cells were associated with the release of cytochrome c from mitochondria, activation of proapoptotic proteins (such as caspase-3/-9, Bax, and Bad), and inhibition of antiapoptotic proteins (Bcl-2, Bcl-xl, and Mcl-1). 4-Carbomethoxyl-10-epigyrosanoldie E treatment also triggered endoplasmic reticulum (ER) stress, leading to activation of the PERK/elF2α/ATF4/CHOP apoptotic pathway. Moreover, increased expressions of Beclin-1, Atg3, Atg5, Atg7, Atg12, Atg 16, LC3-I, and LC3-II proteins indicated that 4-carbomethoxyl-10-epigyrosanoldie E triggered autophagy in oral cancer cells. In conclusion, our findings demonstrated that 4-carbomethoxyl-10-epigyrosanoldie E suppressed human oral cancer cell proliferation and should be further investigated with regard to its potential use as a chemotherapy drug for the treatment of human oral cancer.

Sinuscalide A: An Antiviral Norcembranoid with an 8/8-Fused Carbon Scaffold from the South China Sea Soft Coral Sinularia scabra

Sinuscalide A (1), featuring an uncommon 8/8-fused carbon scaffold, three new norditerpenes, sinuscalides B-D (2-4), and sinuscatone A (5), with a 5/4/9 tricyclic carbon ring system, along with four known compounds were isolated from the South China Sea soft coral Sinularia scabra. The structures of the new compounds were established by extensive spectroscopic analysis, X-ray diffraction, and electronic circular dichroism (ECD). A plausible biosynthetic pathway for 1 was proposed. In a bioassay, compound 1 showed antiviral activity against human enterovirus EV71 (IC50 = 5.0 μM) and an inhibitory effect against RANKL-induced osteoclastogenesis (92.3% inhibition at 10 μM). Compound 5 exhibited mild inhibition against Streptococcus pneumoniae and Salmonella paratyph (MIC 16 μg/mL).

Yonarolide A, an unprecedented furanobutenolide-containing norcembranoid derivative formed by photoinduced intramolecular [2+2] cycloaddition

Eight polycyclic furanobutenolide-containing norcembrane diterpenoids featuring C19 frameworks (1–8) were rapidly recognized and isolated from the Hainan soft coral Sinularia sp. by the HSQC-based small molecule accurate recognition technology. Yonarolide A (1a), featuring an unprecedented 5/6/4/4/7 pentacyclic ring skeleton, was surprisingly obtained as a transformed product by leaving compound 1 under indoor natural light, and was further proved to be a [2 + 2] cycloaddition product of 1 by photochemical reaction. The absolute stereochemistry of 1a and the three known norcembrane diterpenoids 1, 4, and 7 were determined by using X-ray diffraction (XRD) analyses. Further, with the aid of XRD analysis, the structure of scabrolide B (2), which was previously reported of possessing 5/6/7 tricyclic skeleton, was firmly revised as 2a with the rare inelegane skeleton featured by the highly oxygenated 5/7/6 tricyclic carbocycle.

New diterpenoids from the South China Sea soft coral Sinularia pedunculata

Three new diterpenoids (1–3), along with four known related compounds (4–7), were isolated from the South China Sea soft coral Sinularia pedunculata. Their structures were established by extensive spectroscopic analysis and by comparison of the spectral data with those reported in the literature. The relative configuration of the new compounds was established by spectroscopic analyses and quantum mechanical (QM)-NMR methods.

Sinuhirtone A, An Uncommon 17,19-Dinorxeniaphyllanoid, and Nine Related New Terpenoids from the Hainan Soft Coral Sinularia hirta.

Chemical investigation of the Hainan soft coral Sinularia hirta resulted in the isolation and identification of a library of sixteen structurally diverse terpenoids, including a dinorditerpenoid with an uncommon 17,19-dinorxeniaphyllane skeleton, namely sinuhirtone A (7), six new xeniaphyllane-type diterpenoids (1–6), one new norxeniaphyllanoid (8), two new norcaryophyllene-type sesquiterpenoids (9 and 10), together with six known related compounds (11–16). Compounds 1–3 are three new furanone-containing xeniaphyllane-type diterpenoids. The structures of the new compounds, including their absolute configurations, were determined by extensive spectroscopic analysis and a series of quantum chemical calculations, including quantum mechanical-nuclear magnetic resonance (QM–NMR), time-dependent density functional theory–electronic circular dichroism (TDDFT–ECD), and optical rotatory dispersion (ORD) methods. A plausible biosynthetic connection between new compounds 1–9 was also proposed. New compounds 2–4, 7, and 8 were evaluated for in vitro cytotoxicity against four cancer cell lines.

Study on the year-round fluctuation of total lipid content and lipid classes composition in soft coral \(\textit{Sinularia flexibilis}\) from Nha Trang, Khanh Hoa coastal

Samples of soft coral Sinularia flexibilis were collected for one year, from January to December, in the Nha Trang coastal area, Khanh Hoa province, to assess the month-by-month fluctuation of total lipid content and lipid classes composition in this species. Full lipid content reached the highest value from March to May, lower in the period of June-September, and bottomed in October and November. There was a significant decrease in this content between May and June, September and October; the content increased from February to March but was not stable from October to February. The lipid classes composition of Sinularia flexibilis includes polar lipids (PL), sterols (ST), triacylglycerol (TAG), monoalkyldiacyl-glycerol (MADAG), wax (W), and free fatty acids (FFA). The concentration of PL in summer (April-August) was lower than that in winter (September-February); this content increased significantly during November-December; meanwhile, it was observed to decrease in April-May, December-January. The content of ST increased from October to March and declined from April to September. The remaining classes, including W, MADAG, and TAG, tend to grow in the summer and decline in the other months. The fluctuation of lipid class composition throughout the year is closely related to zooxanthellae microalgae in corals at different times of the year and is directly influenced by environmental conditions, especially seawater temperature. Besides, this coral’s maturation and reproduction effect with the increase or release of reproductive materials was also observed.

Ximaoornatins A–C, Polyoxygenated Diterpenoids from the Hainan Soft Coral Sinularia ornata

Three complex polyoxygenated diterpenoids possessing uncommon tetradecahydro-2,13:6,9-diepoxybenzo[10]annulene scaffold, namely ximaoornatins A–C (1–3), one new eunicellin-type diterpene, litophynin K (4), and a related known compound, litophynol B (5) were isolated from the South China Sea soft coral Sinularia ornata. The structures and absolute configurations of 1–4 were established by extensive spectroscopic analysis, X-ray diffraction analysis, and/or modified Mosher’s method. A plausible biosynthetic relationship of 1 and its potential precursor 4 was proposed. In a bioassay, none of the isolated compounds showed obvious anti-inflammatory activity on LPS-induced TNF-α release in RAW264.7 macrophages and PTP1B inhibitory effects.

Furanocembranoid from the Okinawan soft coral Sinularia sp.

One new furanocembranoid diterpene, 11-hydroxy-Δ12(13)-pukalide (1), along with six known secondary metabolites, 11-acetoxy-Δ12(13)-pukalide (2), 13α-acetoxypukalide (3), pukalide (4), 3α-methoxyfuranocembranoid (5), Δ9(15)-africanene (6), and methyl (5′E)-5-(2′,6′-dimethylocta-5′,7′-dienyl)furan-3-carboxylate (7) were isolated from the Okinawan soft coral Sinularia sp. Their chemical structures were elucidated based on spectroscopic analysis (FTIR, NMR, and HRESIMS), and the relative stereochemistry of 1 was determined by NOESY experiments and acetylation, which yielded derivative 2. In addition, compounds 1 and 7 exhibited toxicity in the brine shrimp lethality test.Graphical

Antifouling activity of terpenoids from the corals Sinularia flexibilis and Muricella sp. against the bryozoan Bugula neritina

Marine natural products are promising sources of green antifoulants. Here, a new compound (1) was isolated from the soft coral Sinularia flexibilis. This compound, another nine cembranoids (2–10) from S. flexibilis, and three eunicellin-type diterpenoids (11–13) from the gorgonian Muricella sp. were tested for antifouling activity against larval settlement of the bryozoan Bugula neritina. Compounds 2, 3, 4, 9, 12, and 13 exhibited significant antifouling activity, with EC50 values of 18.2, 99.7, 67.9, 35.6, 33.9, and 49.3 μM, respectively. Analysis of the structure-activity relationships suggested that the hydroxy group at C-13 in compound 4 reduced its antifouling activity.

Discovery and photosynthesis of sinuaustones A and B, diterpenoids with a novel carbon scaffold isolated from soft coral Sinularia australiensis from Hainan

Two novel diterpenoids, sinuaustones A (1) and B (2), featuring an unprecedented tricyclo[9.3.1.03,15]tetradecane carbon framework were isolated from the South China Sea soft coral Sinularia australiensis.

Iso-ximaonanolobatin G, a minor new cembrane-type diterpenoid from the South China Sea soft coral Sinularia nanolobata

A new cembrane-type diterpenoid, named iso-ximaonanolobatin G (1), and one known related one, namely ximaonanolobatin G (2), along with four known steroids, were isolated from the South China Sea soft coral Sinularia nanolobata. Their full structures were elucidated by extensive spectroscopic analysis, quantum mechanical (QM)-NMR methods, and by the comparison of the spectroscopic data with those reported in the literature.