Soft Coral Sarcophyton Ehrenbergi Research Articles

Antimicrobial activities of metabolites isolated from endophytic Aspergillusflavus of Sarcophytonehrenbergi supported by in-silico study and NMR spectroscopy

BackgroundEndophytic Aspergillus species produce countless valuable bioactive secondary metabolites. In the current study, Aspergillus flavus an endophyte from the soft coral Sarcophyton ehrenbergi was chemically explored and the extracted phytoconstituents were subsequently evaluated for antimicrobial activity. This is accomplished by employing nuclear magnetic resonance (NMR) spectroscopy and computational techniques. Additionally, An in vitro anticancer analysis of A. flavus total extract against breast cancer cells (MCF-7) was investigated.ResultSix compounds were separated from the crude alcohol extract of the endophytic Aspergillus flavus out of which anhydro-mevalonolactone was reported for the first time. The anti-fungal and anti-Helicobacter pylori properties of two distinct compounds (Scopularides A and B) were assessed. Additionally, computational research was done to identify the binding mechanisms for all compounds. Both the compounds were found to be active against H. pylori with minimum inhibitory concentration (MIC) values ranging from 7.81 to 15.63 µg/ mL as compared with clarithromycin 1.95 µg/ mL. Scopularides A was potent against both Candida albicans and Aspergillus niger with MIC values ranging from 3.9 to 31.25 µg/ mL, while scopularides B only inhibits Candida albicans with MIC value of 15.63 µg/ mL and weak inhibitory activity against A. niger (MIC = 125 µg/ mL). Furthermore, cytotoxic activity showed a significant effect (IC50: 30.46 mg/mL) against MCF-7 cells.ConclusionOur findings report that cytotoxic activity and molecular docking support the antimicrobial activity of Aspergillus flavus, which could be a promising alternative source as a potential antimicrobial agent.

Further undescribed cembranoids from South China Sea soft coral Sarcophyton ehrenbergi: Structural elucidation and biological evaluation

A detailed chemical investigation of the South China Sea soft coral Sarcophyton ehrenbergi has yield seven undescribed cembranoids, namely isoehrenbergol D and sarcoehrenolides F–K embodying a rare α,β-unsaturated-lactone moiety at C-6 to C-19, along with two known related compounds, ehrenbergol D and sarcoehrenolide A. Their structures and absolute configurations were unambiguously established in the light of extensive spectroscopic data analysis, modified Mosher's method, X-ray diffraction analysis, and quantum chemical computation method. In a bioassay for α-glucosidase inhibition, ehrenbergol D was evaluated as α-glucosidase inhibitor with an IC50 value of 13.57 μM.

Cyclodepsipeptides: Isolation from Endophytic Fungi of Sarcophyton ehrenbergi and Verification of Their Larvicidal Activity via In-Vitro and In-Silico Studies.

Culex pipiens mosquitoes are vectors to many viruses and can transmit diseases such as filariasis and avian malaria. The present study evaluated the larvicidal activity of marine-derived endophytic fungi Aspergillus nomius and Aspergillus flavus from the soft coral Sarcophyton ehrenbergi along with two known cyclodepsipeptide compounds, scopularide A (1) and B (2), isolated from A. flavus extract, against third-instar larvae of C. pipiens, using distilled water as a negative control and toosenedanin as a positive control. The structures of the isolated compounds were confirmed by various spectroscopic analyses. The lethal concentrations (LC50 and LC90) were calculated by probit analysis. Scopularide A was the most potent after 96 h treatment, with LC50 and LC90 values of 58.96 and 994.31 ppm, respectively, and with 82.66% mortality at a concentration of 300 ppm. To unravel the biochemical mechanism of the tested extracts and compounds, their effects against protease, chitinase, phenoloxidases and lipase enzymes from the whole-body tissue of C. pipiens were evaluated after 72 h treatment at LC50 dose. Superior activity was observed for A. flavus extract against all tested enzymes. A molecular docking study was conducted for scopularide A and B on the four tested enzymes, to further verify the observed activity. Results revealed good binding affinities for both compounds as compared to the docked ligands, mainly via a number of hydrogen bonds. This was the first study to report the isolation of endophytic fungi A. flavus and A. nomius from the marine soft coral S. ehrenbergi. The endophytic fungal extract of A. flavus was found to be a promising source for a natural larvicidal agent against C. pipiens populations.

Cembranoids from the Vietnamese soft coral Sarcophyton ehrenbergi

Using various chromatographic separations, two new cembranoids, ehrenbergols F and G (1 and 2), along with three known analogs ehrenbergol D (3), (+)-isosarcophine (4) and sinulariol Z2 (5) were isolated from the soft coral Sarcophyton ehrenbergi. The structural elucidation was done by extensive analysis of the 1 D and 2 D NMR, HR-ESI-QTOF-MS as well as CD experiments. In addition, compounds 1 (IC50 of 38.38 ± 2.89 µM), 3 (IC50 of 37.14 ± 3.22 µM) and 4 (IC50 of 45.01 ± 2.49 µM) revealed moderate inhibitory activity on LPS-induced NO production in RAW264.7 cells, whereas 2 (IC50 of 73.32 ± 1.95 µM) and 5 (IC50 of 64.48 ± 4.93 µM) exhibited weak effect.

Polyhydroxylated steroids from the Vietnamese soft coral Sarcophyton ehrenbergi

Fourteen polyhydroxylated steroids including six new compounds, ehrensteroids A − F (1–6), were isolated from the Vietnamese soft coral Sarcophyton ehrenbergi after applying various chromatographic separations. The structure elucidation was done by detailed analysis of 1D, 2D NMR and HR QTOF mass spectra. In addition, significant cytotoxicity (IC50 values ranging from 8.45 ± 0.56 to 38.27 ± 2.39 μM) against all five tested cancer cell lines as LU-1 (lung cancer), HepG2 (hepatoma cancer), MCF-7 (breast cancer), HL-60 (acute leukemia), and SW480 (colon adenocarcinoma) was observed for compounds 1, 2, 6–10, and 12–14, whereas this activity on LU-1 (IC50 = 21.91 ± 2.72 μM) and HepG2 (IC50 = 20.32 ± 0.03 μM) cell lines was also observed for 4.

Further polyoxygenated cembranoids from South China Sea soft coral Sarcophyton ehrenbergi

Eleven new cembrane diterpenes, namely, sarcoehrenins A–J (1–9, 11) and (2S,11S,12S)-isosarcophytoxide (10), along with six known compounds, gibberosene B (12), (13S)-cembra-1,3,7,11-tetraen-13-ol (13), (+)-sarcophtol (14), cembrene-C (15), (1R,4R,2E,7E,11E)-cembra-2,7,11-trien-4-ol (16) and (1S,4R,2E,7E,11E)-cembratrien-4-ol (17) were isolated from the soft coral Sarcophyton ehrenbergi collected from Weizhou Island, Beibu Gulf, South China Sea. The structures of these compounds were elucidated by a combination of detailed spectroscopic analyses, chemical methods, and comparison with reported data. The absolute configuration of compound 2 was established by the modified Mosher's method in association with TDDFT ECD calculation, while the absolute configuration of compound 3 was assigned by TDDFT ECD approach. In in vitro bioassays, compounds 13 and 17 showed potent TNF-α inhibitory activities being similar to that of positive control dexamethasone. A preliminary structural-activity relationship was also described.

Sarcoehrenbergilides D-F: cytotoxic cembrene diterpenoids from the soft coral Sarcophyton ehrenbergi.

A solvent extract of the soft coral Sarcophyton ehrenbergi afforded cembrene diterpenoids, sarcoehrenbergilid D–F (1–3). Chemical structures were established by modern spectroscopic techniques with absolute stereochemistries determined by circular dichroism (CD) and time-dependent density functional theory electronic CD calculations (TDDFT-ECD). Cytotoxicity activities for 1–3 were evaluated against three human cancer cell lines: lung (A549), colon (Caco-2) and liver (HepG2).

Salicylic acid and its derivatives elicit the production of diterpenes and sterols in corals and their algal symbionts: a metabolomics approach to elicitor SAR

The production of marine drugs in its normal habitats is often low and depends greatly on ecological conditions. Chemical synthesis of marine drugs is not economically feasible owing to their complex structures. Biotechnology application via elicitation represents a promising tool to enhance metabolites yield that has yet to be explored in soft corals. Study the elicitation impact of salicylic acid (SA) and six analogues in addition to a systemic acquired resistance inducer on secondary metabolites accumulation in the soft coral Sarcophyton ehrenbergi along with the symbiont zooxanthellae and if SA elicitation effect is extended to other coral species S. glaucum and Lobophyton pauciliforum. Post elicitation in the three corals and zooxanthella, metabolites were extracted and analyzed via UHPLC-MS coupled with chemometric tools. Multivariate data analysis of the UHPLC-MS data set revealed clear segregation of SA, amino-SA, and acetyl-SA elicited samples. An increased level ca. 6- and 8-fold of the diterpenes viz., sarcophytonolide I, sarcophine and a C28-sterol, was observed in SA and amino-SA groups, respectively. Post elicitation, the level of diepoxy-cembratriene increased 1.5-fold and 2.4-fold in 1mM SA, and acetyl-SA (aspirin) treatment groups, respectively. S. glaucum and Lobophyton pauciliforum showed a 2-fold increase of diepoxy-cembratriene levels. These results suggest that SA could function as a general and somewhat selective diterpene inducing signaling molecule in soft corals. Structural consideration reveals initial structure-activity relationship (SAR) in SA derivatives that seem important for efficient diterpene and sterol elicitation.

Comparative Metabolomics Approach Detects Stress-Specific Responses during Coral Bleaching in Soft Corals.

Chronic exposure to ocean acidification and elevated sea-surface temperatures pose significant stress to marine ecosystems. This in turn necessitates costly acclimation responses in corals in both the symbiont and host, with a reorganization of cell metabolism and structure. A large-scale untargeted metabolomics approach comprising gas chromatography mass spectrometry (GC-MS) and ultraperformance liquid chromatography coupled to high resolution mass spectrometry (UPLC-MS) was applied to profile the metabolite composition of the soft coral Sarcophyton ehrenbergi and its dinoflagellate symbiont. Metabolite profiling compared ambient conditions with response to simulated climate change stressors and with the sister species, S. glaucum. Among ∼300 monitored metabolites, 13 metabolites were modulated. Incubation experiments providing four selected upregulated metabolites (alanine, GABA, nicotinic acid, and proline) in the culturing water failed to subside the bleaching response at temperature-induced stress, despite their known ability to mitigate heat stress in plants or animals. Thus, the results hint to metabolite accumulation (marker) during heat stress. This study provides the first detailed map of metabolic pathways transition in corals in response to different environmental stresses, accounting for the superior thermal tolerance of S. ehrenbergi versus S. glaucum, which can ultimately help maintain a viable symbiosis and mitigate against coral bleaching.

Cembrene Diterpenoids with Ether Linkages from Sarcophyton ehrenbergi: An Anti-Proliferation and Molecular-Docking Assessment.

Three new cembrene diterpenoids, sarcoehrenbergilid A–C (1–3), along with four known diterpenoids, sarcophine (4), (+)-7α,8β-dihydroxydeepoxysarcophine (5), sinulolide A (6), and sinulolide B (7), and one steroid, sardisterol (8), were isolated and characterized from a solvent extract of the Red Sea soft coral Sarcophyton ehrenbergi. Chemical structures were elucidated by NMR and MS analyses with absolute stereochemistry determined by X-ray analysis. Since these isolated cembrene diterpenes contained 10 or more carbons in a large flexible ring, conformer stabilities were examined based on density functional theory calculations. Anti-proliferative activities for 1–8 were evaluated against three human tumor cell lines of different origins including the: lung (A549), colon (Caco-2), and liver (HepG2). Sardisterol (8) was the most potent of the metabolites isolated with an IC50 of 27.3 µM against the A549 cell line. Since an elevated human-cancer occurrence is associated with an aberrant receptor function for the epidermal growth factor receptor (EGFR), molecular docking studies were used to examine preferential metabolite interactions/binding and probe the mode-of-action for metabolite-anti tumor activity.

Metabolomics reveals biotic and abiotic elicitor effects on the soft coral Sarcophyton ehrenbergi terpenoid content

The effects of six biotic and abiotic elicitors, i.e. MeJA (methyl jasmonate), SA (salicylic acid), ZnCl2, glutathione and β-glucan BG (fungal elicitor), and wounding, on the secondary metabolite accumulation in the soft coral Sarcophyton ehrenbergi were assessed. Upon elicitation, metabolites were extracted and analysed by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Except for MeJA, no differences in photosynthetic efficiency were observed after treatments, suggesting the absence of a remarkable stress on primary production. Chemometric analyses of UPLC-MS data showed clear segregation of SA and ZnCl2 elicited samples at 24 and 48 h post elicitation. Levels of acetylated diterpene and sterol viz., sarcophytonolide I and cholesteryl acetate, was increased in ZnCl2 and SA groups, respectively, suggesting an activation of specific acetyl transferases. Post elicitation, sarcophytonolide I level increased 132 and 17-folds at 48 h in 0.1 mM SA and 1 mM ZnCl2 groups, respectively. Interestingly, decrease in sarcophine, a major diterpene was observed only in response to ZnCl2, whereas no change was observed in sesquiterpene content following treatments. To the best of our knowledge, this study provides the first documentation for elicitation effects on a soft corals secondary metabolome and suggests that SA could be applied to increase diterpenoid levels in corals.

New Cembrane-Type Diterpenoids from the South China Sea Soft Coral Sarcophyton ehrenbergi

Chemical investigation on the soft coral Sarcophyton ehrenbergi collected from the Xisha Islands of the South China Sea have led to the isolation of eight cembranoids including five new ones, sarcophytonoxides A–E (1–5). The structures of new cembranoids (1–5) were determined by spectroscopic analysis and comparison of the NMR data with those of related analogues. The cytotoxicities of compounds 1–8 against human ovarian cancer cell line A2780 were also evaluated.

Polyoxygenated cembrane diterpenoids from the soft coral Sarcophyton ehrenbergi.

Five new polyoxygenated cembranoids, named (+)-1,15-epoxy-2-methoxy-12-methoxycarbonyl-11E-sarcophytoxide (1), (+)-2-epi-12-methoxycarbonyl-11E-sarcophine (2), 3,4-epoxyehrenberoxide A (3), ehrenbergol D (4) and ehrenbergol E (5), were obtained from the soft coral Sarcophyton ehrenbergi. The structures of 1–5 were established on the basis of comprehensive NMR and HR-ESI-MS analyses and by comparison with reported data in the literature. Compounds 4 and 5 showed moderate cytotoxicity against P-388 (mouse lymphocytic leukemia) cancer cell line with EC50 values of 2.0 and 3.0 μM, respectively. Compound 2 exhibited slight antiviral activity against HCMV (human cytomegalovirus) with IC50 values of 25.0 μg/mL.

Isolation, structural assignment and synthesis of (SE)-2-methyloctyl 3-(4-methoxyphenyl) propenoate from the marine soft coral Sarcophyton ehrenbergi

A new metabolite 1 has been isolated from the marine soft coral Sarcophyton ehrenbergi along with two known diterpenoids 2 and 3 and cholesterol 4. The structure of 1 was determined by means of detailed spectroscopic analysis and unambiguously confirmed to have the S configuration by the synthesis of both enantiomers using 4-benzyl-2-oxazolidinone auxiliaries. (S)- and (R)-1, 3 and some of the synthetic intermediates were evaluated for cytotoxic activity against human lung cancer (A549), prostate cancer (DU145), cervical cancer (HeLa) and breast cancer (MCF-7) cell lines in an in vitro bioassay.

Prostaglandin Derivatives: Nonaromatic Phosphodiesterase-4 Inhibitors from the Soft Coral Sarcophyton ehrenbergi.

Ten new prostaglandin derivatives (PGs), sarcoehrendins A-J (1-10), together with five known analogues (11-15) were isolated from the soft coral Sarcophyton ehrenbergi. Compounds 4-8 represented the first examples of PGs featuring an 18-ketone group. The structures including the absolute configurations were elucidated on the basis of spectroscopic analysis and chemical evidence. All of the isolates and six synthetic analogues (3a, 3b, 4a, and 11a-11c) were screened for inhibitory activity against phosphodiesterase-4 (PDE4), which is a drug target for the treatment of asthma and chronic obstructive pulmonary disease. Compounds 2, 10, 11a, 11b, and 13-15 exhibited inhibition with IC50 values less than 10 μM, and compound 15 (IC50 = 1.4 μM) showed comparable activity to the positive control rolipram (IC50 = 0.60 μM). The active natural PGs (2, 10, and 13-15) represent the first examples of PDE4 inhibitors without an aromatic moiety, and a preliminary structure-activity relationship is also proposed.

New Terpenes from the Egyptian Soft Coral Sarcophyton ehrenbergi

Chemical investigations of the Egyptian soft coral Sarcophyton ehrenbergi have led to the isolation of compounds 1–3 as well as the previously reported marine cembranoid diterpene sarcophine (4). Structures were elucidated by comprehensive NMR and HRMS experimentation. Isolated compounds were in vitro assayed for cytotoxic activity against human hepatocarcinoma (HepG2) and breast adenocarcinoma (MCF-7) cell lines.

New Diterpenoids from Soft Coral Sarcophyton ehrenbergi

Continuing chemical investigation on the acetone extracts of the soft coral Sarcophyton ehrenbergi collected off the coast of San-hsian-tai, Taitong County, Taiwan led to the isolation of two new diterpenoids, ehrenbergol C and acetyl ehrenberoxide B (1 and 2). The structures of these isolated metabolites were elucidated through extensive spectroscopic analyses. Moreover, in vitro tests show that compounds 1 and 2 displayed antiviral activity towards human cytomegalovirus, with EC50 of 20 and 8.0 µg/mL, respectively.

Ulcerated yellow spot syndrome: implications of aquaculture-related pathogens associated with soft coral Sarcophyton ehrenbergi tissue lesions

We introduce a new marine syndrome called ulcerated yellow spot, affecting the soft coral Sarcophyton ehrenbergi. To identify bacteria associated with tissue lesions, tissue and mucus samples were taken during a 2009 Indo-Pacific research expedition near the Wakatobi Island chain, Indonesia. Polymerase chain reaction targeting the 16S rDNA gene indicated associations with the known fish-disease-causing bacterium Photobacterium damselae, as well as multiple Vibrio species. Results indicate a shift toward decreasing diversity of bacteria in lesioned samples. Photobacterium damselae ssp. piscicida, formerly known as Pasteurella piscicida, is known as the causative agent of fish pasteurellosis and in this study, was isolated solely in lesioned tissues. Globally, fish pasteurellosis is one of the most damaging fish diseases in marine aquaculture. Vibrio alginolyticus, a putative pathogen associated with yellow band disease in scleractinian coral, was also isolated from lesioned tissues. Lesions appear to be inflicting damage on symbiotic zooxanthellae (Symbiodinium sp.), measurable by decreases in mitotic index, cell density and photosynthetic efficiency. Mitotic index of zooxanthellae within infected tissue samples was decreased by ~80%, while zooxanthellae densities were decreased by ~40% in lesioned tissue samples compared with healthy coral. These results provide evidence for the presence of known aquaculture pathogens in lesioned soft coral and may be a concern with respect to cross-species epizootics in the tropics.

Three New Cembranoids from the Taiwanese Soft Coral Sarcophyton ehrenbergi

In order to search for new bioactive substances from marine organisms, we have investigated the acetone extracts of the soft coral Sarcophyton ehrenbergi collected at San-Hsian-Tai, Taitong County, Taiwan. Chromatographic fractionation of the extracts of the octocoral S. ehrenbergi led to the isolation of three new cembranoids, (+)-12-ethoxycarbonyl-11Z-sarcophine (1), ehrenbergol A and B (2 and 3). The structures of these isolated metabolites were elucidated through extensive spectroscopic analyses. Moreover, metabolites 1–3 were evaluated in vitro for their cytotoxicity towards selected cancer cell lines and antiviral activity against human cytomegalovirus (HCMV).

Terpenes from the Soft Corals Litophyton arboreum and Sarcophyton ehrenbergi

The new cembrane diterpene (3E,11E)-cembra-3,8(19),11,15-tetraene-7alpha-ol (1), nephthenol (2), and all-trans-peridinin (3) have been isolated from the soft coral Litophyton arboreum. The tetraterpene 3, (+)-7,8-epoxy-7,8-dihydrocembrene C (4), emblide (5), sarcophytoxide (6), sarcoglaucol-16-one (7), guajacophine (8), and 1,4-peroxymuurol-5-ene (9) have been obtained from the soft coral Sarcophyton ehrenbergi. The compounds were characterized primarily by NMR spectroscopy. Some of the terpenes were tested for their antiproliferative activity against the cell lines HUVEC and K-562 and for cytotoxicity against the cell line HeLa, and they showed moderate activities.