Litoamentenes A-K, eleven undescribed cembranoids with cytotoxicity from the South China Sea soft coral Litophyton amentaceum.

Eleven undescribed cembrane-type diterpenoids, named litoamentenes A-K (1-11), were isolated from the soft coral Litophyton amentaceum collected from the South China Sea. Their structures were elucidated by extensive analysis of spectroscopic data, comparison with the literature data, single crystal X-ray diffraction, quantum chemical calculations and TDDFT-ECD calculations. This is the first systematic investigation of L. amentaceum. In particular, compounds 1-3 are cembrane-type norditerpenoids that lack isopropyl side chains. Compound 6 is a cembrane-type norditerpenoid without a methyl group at C-4, the first natural product identified with this carbon skeleton. Compounds 6, 9 and 10 showed modest cytotoxicity against several human cancer cell lines with IC50 values ranging from 3.99 to 14.56 µM.

Marine Prostanoids with Cytotoxic Activity from Octocoral Clavularia spp.

Octocoral of the genus Clavularia is a kind of marine invertebrate possessing abundant cytotoxic secondary metabolites, such as prostanoids and dolabellanes. In our continuous natural product study of C. spp., two previously undescribed prostanoids [clavulone I-15-one (1) and 12-O-deacetylclavulone I (2)] and eleven known analogs (3-13) were identified. The structures of these new compounds were elucidated based on analysis of their 1D and 2D NMR, HRESIMS, and IR data. Additionally, all tested prostanoids (1 and 3-13) showed potent cytotoxic activities against the human oral cancer cell line (Ca9-22). The major compound 3 showed cytotoxic activity against the Ca9-22 cells with the IC50 value of 2.11 ± 0.03 µg/mL, which echoes the cytotoxic effect of the coral extract. In addition, in silico tools were used to predict the possible effects of isolated compounds on human tumor cell lines and nitric oxide production, as well as the pharmacological potentials.

Holistic perilous index-based environmental appraisal of Metal(oid)s in the sole coral-bearing island of northeastern bay of Bengal.

This study aimed to evaluate the concentration, distribution, along with the environmental and human health impact of eight heavy metals-Pb, Cr, Cu, Cd, Zn, Mn, Ni, and As-on St. Martin's Island in the northeastern Bay of Bengal, and in doing so to help implement new legislations to protect the island. Focusing on the island's significance as a tourist destination, with seafood being a prominent dietary component, three sample types (sediment, seawater, and crustaceans) were selected for a comprehensive assessment, considering seasonal variations. Concentration of metals was observed to be lower than the established standards in sediment samples, but in seawater samples, Pb, Cr, Cd and Zn were higher than US-EPA values for natural marine water. The metals displayed a decreasing trend of Zn > Ni > Pb > Cu > Mn > As > Cd > Cr in crustacean samples for both seasons. Crustacean samples displayed higher metal concentrations in winter than in monsoon. Pb exceeded the maximum allowable limit for crustaceans with a concentration of about 3 and 4 mg kg-1 in monsoon and winter respectively; being more than 6-8 times the standard for Bangladesh which is only about 0.5 mg kg-1. Health indices displayed that although adults may suffer less from carcinogenic/non-carcinogenic health effects, the risks are far greater for children. For both age groups, As and Ni displayed possibilities of developing cancer. Principal Component Analysis (PCA)shed light on the sources of metals and showed that most of them were from anthropogenic sources. Overall, this study found that the quality of the environment of the island was better in comparison to previous studies made before the pandemic, and so, if the trend continues, it may lead to a better environment for the organisms around the island and help to keep the negative physiological impacts from the consumption of these organisms to a minimal.

New Diterpenes and Diterpene Glycosides with Antibacterial Activity from Soft Coral Lemnalia bournei.

Five new biflorane-type diterpenoids, biofloranates E-I (1-5), and two new bicyclic diterpene glycosides, lemnaboursides H-I (6-7), along with the known lemnabourside, were isolated from the South China Sea soft coral Lemnalia bournei. Their chemical structures and stereochemistry were determined based on extensive spectroscopic methods, including time-dependent density functional theory (TDDFT) ECD calculations, as well as a comparison of them with the reported values. The antibacterial activities of the isolated compounds were evaluated against five pathogenic bacteria, and all of these diterpenes and diterpene glycosides showed antibacterial activities against Staphylococcus aureus and Bacillus subtilis, with MICs ranging from 4 to 64 µg/mL. In addition, these compounds did not exhibit noticeable cytotoxicities on A549, Hela, and HepG2 cancer cell lines, at 20 µM.

Exploring the chemical diversity of sesquiterpenes from the rarely studied south China sea soft coral Sinularia tumulosa assisted by molecular networking strategy.

Molecular networking strategy-based prioritization of the isolation of the rarely studied soft coral Sinularia tumulosa yielded 14 sesquiterpenes. These isolated constituents consisted of nine different types of carbon frameworks, namely asteriscane, humulane, capillosane, seco-asteriscane, guaiane, dumortane, cadinane, farnesane, and benzofarnesane. Among them, situmulosaols A-C (1, 3 and 4) were previously undescribed ones, whose structures with absolute configurations were established by the combination of extensive spectral data analyses, quantum mechanical-nuclear magnetic resonance and time-dependent density functional theory electronic circular dichroism calculations, the Snatzke's method, and the modified Mosher's method. Notably, situmulosaol C (4) was the second member of capillosane-type sesquiterpenes. The plausible biogenetic relationships of these skeletally different sesquiterpenes were proposed. All sesquiterpenoids were evaluated for their antibacterial, cytotoxic and anti-inflammatory effects. The bioassay results showed compound 14 exhibited significant antibacterial activities against a variety of fish and human pathogenic bacteria with MIC90 values ranging from 3.6 to 33.8 µg/mL. Moreover, moderate cytotoxic effects against HEL cells for components 13 and 14 and moderate inhibitory effect on lipopolysaccharide-induced inflammatory responses in RAW264.7 cells for substance 13 were also observed.

Isolation and Bioactivity Evaluation of Sesquiterpenes from an Alcyonarian of the Genus Lemnalia from the Saudi Arabian Red Sea.

Over the last decades, soft corals have been proven a rich source of biologically active compounds, featuring a wide range of chemical structures. Herein, we investigated the chemistry of an alcyonarian of the genus Lemnalia (Neptheidae), specimens of which were collected from the coral reefs near Al Lith, on the south-west coast of Saudi Arabia. A series of chromatographic separations led to the isolation of 31 sesquiterpenes, featuring mainly the nardosinane and neolemnane carbon skeletons, among which three (13, 14 and 28) are new natural products. The metabolites isolated in sufficient amounts were evaluated in vitro in human tumor and non-cancerous cell lines for a number of biological activities, including their cytotoxic, anti-inflammatory, anti-angiogenic, and neuroprotective activities, as well as for their effect on androgen receptor (AR)-regulated transcription. Among the tested metabolites, compound 12 showed comparable neuroprotective activity to the positive control N-acetylcysteine, albeit at a 10-fold lower concentration.

Proteomic characterization and biological activities of the mucus produced by the zoanthid Palythoa caribaeorum (Duchassaing & Michelotti, 1860).

Mucus, produced by Palythoa caribaeorum has been popularly reported due to healing, anti-inflammatory, and analgesic effects. However, biochemical and pharmacological properties of this mucus remains unexplored. Therefore, the present study aimed to study its proteome profile by 2DE electrophoresis and MALDI-TOF. Furthermore, it was evaluated the cytotoxic, antibacterial, and antioxidant activities of the mucus and from its protein extract (PE). Proteomics study identified14 proteins including proteins involved in the process of tissue regeneration and death of tumor cells. The PE exhibited cell viability below 50% in the MCF-7 and S-180 strains. It showed IC50 of 6.9 µg/mL for the J774 lineage, and also, favored the cellular growth of fibroblasts. Furthermore, PE revealed activity against Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, and Staphylococcus epidermidis (MIC of 250 µg/mL). These findings revealed the mucus produced by Palythoa caribaeorum with biological activities, offering alternative therapies for the treatment of cancer and as a potential antibacterial agent.

Metabolic Profiling, Antiviral Activity and the Microbiome of Some Mauritian Soft Corals.

Soft corals, recognized as sessile marine invertebrates, rely mainly on chemical, rather than physical defense, by secreting intricate secondary metabolites with plausible pharmaceutical implication. Their ecological niche encompasses a diverse community of symbiotic microorganisms which potentially contribute to the biosynthesis of these bioactive metabolites. The emergence of new viruses and heightened viral resistance underscores the urgency to explore novel pharmacological reservoirs. Thus, marine organisms, notably soft corals and their symbionts, have drawn substantial attention. In this study, the chemical composition of four Mauritian soft corals: Sinularia polydactya, Cespitularia simplex, Lobophytum patulum, and Lobophytum crassum was investigated using LC-MS techniques. Concurrently, Illumina 16S metagenomic sequencing was used to identify the associated bacterial communities in the named soft corals. The presence of unique biologically important compounds and vast microbial communities found therein was further followed up to assess their antiviral effects against SARS-CoV-2 and HPV pseudovirus infection. Strikingly, among the studied soft corals, L. patulum displayed an expansive repertoire of unique metabolites alongside a heightened bacterial consort. Moreover, L. patulum extracts exerted some promising antiviral activity against SARS-CoV-2 and HPV pseudovirus infection, and our findings suggest that L. patulum may have the potential to serve as a therapeutic agent in the prevention of infectious diseases, thereby warranting further investigation.

Genus Litophyton: A Hidden Treasure Trove of Structurally Unique and Diversely Bioactive Secondary Metabolites.

Marine soft corals are prolific sources of various natural products that have served as a wealthy reservoir of diverse chemical scaffolds with potential as new drug leads. The genus Litophyton contains almost 100 species but only a small proportion of them has been chemically investigated, which calls for more attentions from global researchers. In the current work, 175 secondary metabolites have been discussed, drawing from published data spanning almost five decades, up to July 2023. The studied species of the genus Litophyton resided in various tropical and temperate regions and encompassed a broad range of biologically active natural products including terpenes, steroids, nitrogen-containing metabolites, lipids, and other metabolites. A wide spectrum of pharmacological effects of these compounds had been evaluated, such as cytotoxic, antiviral, antibacterial, antifungal, anti-malarial, antifeedant, anti-inflammatory, molluscicidal, PTP1B inhibitory, insect growth inhibitory, and neuroprotective activities. This review aims to offer an up-to-date survey of the literature and provide a comprehensive understanding of the chemical structures, taxonomical distributions, and biological activities of the reported metabolites from the title genus whenever available.

Chemical Constituents from Soft Coral Clavularia spp. Demonstrate Antiproliferative Effects on Oral Cancer Cells.

Five new eudensamane-type sesquiterpene lactones, clasamanes A-E (1-5), three new dolabellane-type diterpenes, clabellanes A-C (6-8), and fifteen known compounds (9-23) were isolated from the ethanolic extract of Taiwanese soft coral Clavularia spp. The structures of all undescribed components (1-8) were determined by analysis of IR, mass, NMR, and UV spectroscopic data. The absolute configuration of new compounds was determined by using circular dichroism and DP4+ calculations. The cytotoxic activities of all isolated marine natural products were evaluated. Compound 7 showed a significant cytotoxic effect against oral cancer cell line (Ca9-22) with an IC50 value of 7.26 ± 0.17 µg/mL.

Four New Diterpenoids from the South China Sea Soft Coral Sinularia nanolobata and DFT-Based Structure Elucidation.

Three new cembranoids (1-3) and a new casbanoid (4), along with three known analogues (5-7), have been isolated from the soft coral Sinularia nanolobata collected off Ximao Island. The structures, including the absolute configurations of new compounds, were established using extensive spectroscopic data analysis, time-dependent density functional theory/electronic circular dichroism (TDDFT-ECD) calculations, and the comparison with spectroscopic data of known compounds. In the in vitro bioassay, compounds 1 and 5 exhibited moderate cytotoxic activities against human erythroleukemia (HEL) cell lines, with IC50 values of 37.1 and 42.4 µM, respectively.

New Cytotoxic Monoalkyl Glycerol Ether from the Red Sea Soft Coral Nephthea mollis.

A new monoalkyl glycerol ether, 3-(n-henicosyloxy)propane-1,2-diol (1), was isolated from the CH2 Cl2 /MeOH crude extract of the Red Sea soft coral Nephthea mollis. Additionally, three known related analogs were identified: chimyl alcohol (2), batyl alcohol (3), and 3-(icosyloxy)propane-1,2-diol (4). The chemical structure of 3-(n-henicosyloxy)propane-1,2-diol was determined using advanced spectroscopic analyses, including 1D, 2D Nuclear Magnetic Resonance (NMR), Electron Ionization mass spectra (EI-MS), and High-Resolution Electron Spray Ionization mass spectra (HR-ESI-MS) analyses. Furthermore, the identification of chimyl alcohol, batyl alcohol and 3-(icosyloxy)propane-1,2-diol was achieved by studying their EI mass fragmentation analyses and comparing their mass data with those previously reported in the literature. The cytotoxic activity of the Nephthea mollis crude extract and 3-(n-henicosyloxy)propane-1,2-diol was evaluated against five human cancer cell lines: HepG2 (hepatocellular carcinoma), MCF-7 (breast carcinoma), NCI-1299 (lung carcinoma), HeLa (cervical cancer cell), and HT-29 (colon adenocarcinoma). Moreover, 3-(n-henicosyloxy)propane-1,2-diol revealed moderate cytotoxicity against the HeLa cell lines with an IC50 value of 24.1 µM, while showing inactivity against the remaining cell lines (IC50 >100 µM).

Coral skeletons reveal the impacts of oil pollution on seawater chemistry in the northern South China Sea.

Oil pollution can release trace metals (TMs) with cumulative toxicity into seawater, harming marine ecosystems in the long term. However, the lack of studies has inhibited our understanding of the effects and mechanisms of oil pollution on TMs in seawater. Hence, we investigated the 10-year monthly variation of TMs in Porites coral skeletons from the northern South China Sea (SCS), complemented by spatial distribution of TMs in seawater, sediments and characterization of TMs in fuel oil. The results of principal component-multivariate linear regression showed that the total contribution of oil pollution as a source to TMs in surface seawater was 77.2%, where the residence time of TMs (Ni, V, Cr, Co, Cu, Mn, Fe, and Mo) released from oil spills in surface seawater was approximately 1.4 months. Due to the geochemical nature of the metals, their seasonal variations are controlled by tropical cyclones (Ni, V, Cr, Co, Cu, Mn, Fe, and Mo), winter monsoons (Pb, Cd, Ba, and Zn) and sea surface temperature (Sr). This study shows that coral skeletons can be used as a new tool to study marine oil pollution. This provides valuable reference data for accurately identifying and quantifying the effects of oil pollution on TMs in seawater from a spatial and temporal perspective.

Two New Cembranoids from the Chinese Soft Coral Sarcophyton boettgeri.

Two new cembranoids, namely sarcoboettgerols D and E, together with four known related ones, have been isolated from the soft coral Sarcophyton boettgeri collected from Weizhou Island in the South China Sea. Their structures including absolute configurations were elucidated by extensive spectroscopic analysis, quantum mechanical nuclear magnetic resonance methods, time-dependent density functional theory-electronic circular dichroism calculations, as well as comparison with the reported data in the literature. A plausible biogenetic relationship of four cembranoids was proposed. In bioassays, sarcomililatin B exhibited cytotoxic activity against H1299 cell (IC50 =35.0 µM), whereas sarcomililatin B and sarcomililatin A displayed moderate antibacterial activities (MIC 17.4-34.8 µg/mL).

Matrix-independent boron isotope analysis of silicate and carbonate reference materials by ultraviolet femtosecond laser ablation multi-collector inductively coupled plasma mass spectrometry with application to the cold-water coral Desmophyllum dianthus.

RATIONALE: Boron isotopes are a powerful tool for pH reconstruction in marine carbonates and as a tracer for fluid-mineral interaction in geochemistry. Microanalytical approaches based on laser ablation multi-collector inductively coupled plasma mass spectrometry (LA-MC-ICP-MS) often suffer from effects induced by the sample matrix. In this study, we investigate matrix-independent analyses of B isotopic ratios and apply this technique to cold-water corals. METHODS: We employ a customized 193 nm femtosecond laser ablation system (Solstice, Spectra-Physics) coupled to a MC-ICP-MS system (Nu Plasma II, Nu Instruments) equipped with electron multipliers for in situ measurements of B isotopic ratios (11 B/10 B) at the micrometric scale. We analyzed various reference materials of silicate and carbonate matrices using non-matrix matched calibration without employing any correction. This approach was then applied to investigate defined increments in coral samples from a Chilean fjord. RESULTS: We obtained accurate B isotopic ratios with a reproducibility of ±0.9‰ (2 SD) for various reference materials including silicate glasses (GOR132-G, StHs6/80-G, ATHO-G and NIST SRM 612), clay (IAEA-B-8) and carbonate (JCp-1) using the silicate glass NIST SRM 610 as calibration standard, which shows that neither laser-induced nor ICP-related matrix effects are detectable. The application to cold-water corals (Desmophyllum dianthus) reveals minor intra-skeleton variations in δ11 B with average values between 23.01‰ and 25.86‰. CONCLUSIONS: Our instrumental set-up provides accurate and precise B isotopic ratios independently of the sample matrix at the micrometric scale. This approach opens a wide field of application in geochemistry, including pH reconstruction in biogenic carbonates and deciphering processes related to fluid-mineral interaction.

Seven New Lobane Diterpenoids from the Soft Coral Lobophytum catalai.

Seven new lobane diterpenoids, namely, lobocatalens A-G (1-7), were isolated from the Xisha soft coral Lobophytum catalai. Their structures, including their absolute configurations, were elucidated via spectroscopic analysis, comparison with the literature data, QM-MNR, and TDDFT-ECD calculations. Among them, lobocatalen A (1) is a new lobane diterpenoid with an unusual ether linkage between C-14 and C-18. In addition, compound 7 showed moderate anti-inflammatory activity in the zebrafish models and cytotoxic activity against the K562 human cancer cell line.

Antitumor Cembrane Diterpenoids from the South China Sea Soft Coral Lobophytum sp.

Two new highly functionalized cembrane diterpenoids named ximaolobophytolides A (1) and B (2) as minor components, together with seven related known compounds (3-9), have been isolated and identified from the Ximao soft coral Lobophytum sp. They were characterized by the presence of an α-methylene-γ-lactone moiety. Based on the comprehensive analyses of 1D and 2D NMR spectroscopic data, the absolute configurations of these two new compounds were elucidated by the combination of quantum mechanical (QM)-NMR and time-dependent density functional theory/electronic circular dichroism (TDDFT-ECD) calculation approaches. In the anti-tumor bioassays, compounds 3-9 showed moderate to significant inhibitory effects (IC50 values ranging from 29.66 to 0.39 µM) against the proliferations of five tumor cells HEL, A549, H1975, MDA-MB-231, and H1299. It might be worthy to point out that compounds 4, 7, and 8 exhibited better anti-tumor activities than that of the positive control Doxorubicin.

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.

Extending the Record of Terpenes from Soft Coral Sarcophyton mililatensis.

In the present study, a new polyoxygenated cembranoid named sarcomililatol H (1) as well as six known terpenes 2-7 with different skeletons were isolated from South China Sea soft coral Sarcophyton mililatensis. Based on the comprehensive analyses of 1D and 2D NMR spectroscopic data, the structure of the new compound 1 was established. This new cembranoid was characterized by the presence of the rarely encountered tetrahydropyran ring with the ether linkage across C-2 and C-12. By applying the time-dependent density functional theory electronic circular dichroism (TDDFT ECD) approach, the absolute configuration of sarcomililatol H (1) was determined. All of the isolates were subjected to the anti-inflammatory and anti-tumor bioassays. However, none of them was active in these evaluations. Additionally, the preliminary virtual screening of inhibitory against SARS-CoV-2 by molecular docking showed that diterpene 1 could be regarded as a SARS-CoV-2 main protease (Mpro ) inhibitor (binding energy: -7.63 kcal/mol). The discovery of these terpenes has expanded the chemical diversity and complexity of terpenes from the species S. mililatensis.

Briavioids E-G, Newly Isolated Briarane-Diterpenoids from a Cultured Octocoral Briareum violaceum.

The chemical screening of a cultured soft coral, Briareum violaceum, led to the isolation of eight natural, briarane-related diterpenoids, including three unreported metabolites, briavioids E-G (1-3), and five known briaranes, briacavatolides B (4) and C (5), briaexcavatin L (6), briaexcavatolide U (7) and briarenol K (8). The structures of briaranes 1-8 were established using spectroscopic methods. The absolute configuration of briavioid A (9), obtained in a previous study, was reported for the first time in this study by a single-crystal X-ray diffraction analysis using a copper radiation source. The anti-inflammatory activity of briaranes 1 and 2 and briaranes 4-8 was evaluated by screening their inhibitory ability against the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins in lipopolysaccharide (LPS)-induced RAW 264.7 macrophage cells.