Red Sea Soft Coral Sarcophyton Research Articles

LC-HRMS Profiling and Cytotoxic Potential of Actinomycetes Associated with the Red Sea Soft Coral Sarcophyton glaucum: In vitro and In silico Studies.

In the current study, the actinomycetes associated with the red sea-derived soft coral Sarcophyton glaucum were investigated in terms of biological and chemical diversity. Four different media, M1, ISP2, Marine Agar (MA), and Actinomycete isolation agar (AIA) were used for the isolation of three strains of actinomycetes that were identified as Streptomyces sp. UR 25, Micromonospora sp. UR32 and Saccharomonospora sp. UR 19. LC-HRMS analysis was used to investigate the chemical diversity of the isolated actinobacteria. The LC-HRMS data were statistically processed using MetaboAnalyst 5.0 viz to differentiate the extract groups and determine the optimal growth culturing conditions. Multivariate data statistical analysis revealed that the Micromonospora sp. extract cultured on (MA) medium is the most distinctive extract in terms of chemical composition. While, the Streptomyces sp. UR 25 extracts are differ significantly from Micromonospora sp. UR32 and Saccharomonospora sp. UR 19. Biological investigation using in vitro cytotoxic assay for actinobacteria extracts revealed the prominent potentiality of the Streptomyces sp. UR 25 cultured on oligotrophic medium against human hepatoma (HepG2), human breast adenocarcinoma (MCF-7) and human colon adenocarcinoma (CACO2) cell lines (IC50 =3.3, 4.2 and 6.8 μg/mL, respectively). SwissTarget Prediction speculated that among the identified compounds, 16-deethyl, indanomycin (8) could have reasonable affinity on HDM2 active site. In this respect, molecular docking study was performed for compound (8) to reveal a substantial affinity on HDM2 active site. In addition, molecular dynamics simulations were carried out at 200 ns for the most active compound (8) compared to the co-crystallized inhibitor DIZ giving deeper information regarding their thermodynamic and dynamic properties as well.

Unraveling the Red Sea soft coral Sarcophyton convolutum potentials against oxidative and inflammatory stresses in zebrafish

The Red Sea is one of the world's hotspots for biodiversity, and for marine natural products (MNPs) as well. These MNPs attract special interest for their capabilities to combat inflammatory and oxidative stress-related diseases, being some of the most serious health problems worldwide nowadays. The current study aimed to identify the bioactive ingredients of the Red Sea soft coral Sarcophyton convolutum, and to assess its protective potentials against oxidative and inflammatory stresses. Coral extract (CE) was analyzed using GC-MS and HPLC. In a protection trial, adult zebrafish were intraperitoneally injected with two doses of crab extract, i.e. 50 and 500 μg/fish in 1 % DMSO as a vehicle, then challenged with 30 μg L−1 of CuSO4 for 48 h. All groups, but the negative control one, were challenged with 30 μg L−1 of CuSO4. Total antioxidant activity, as well as mRNA levels of proinflammatory markers and antioxidant enzyme genes were measured. The results showed richness of S. convolutum extract with various bioactive ingredients, including phenolic compounds, flavonoids, alkanes, fatty acids, sesquiterpenes, and pheromone-like substances. CuSO4 significantly induced the expected signals of inflammatory and oxidative stress, reducing both the antioxidant activity and increasing proinflammatory marker genes. However, CE, especially the low dose, showed significant capability to reduce proinflammatory markers and elevating the total antioxidant activity. Therefore, we concluded that S. convolutum can be a promising source for future efforts of drug discovery and a wide spectrum of pharmaceutical products.

Investigating the hepatoprotective potentiality of marine-derived steroids as promising inhibitors of liver fibrosis.

It has been reported that organic extracts derived from soft corals belonging to the genus Sarcophyton have exhibited a wide range of therapeutic characteristics. Based on biochemical and histological techniques, we aimed to assess the hepatoprotective role of the organic extract and its principal steroidal contents derived from the Red Sea soft coral Sarcophyton glaucum on acetaminophen-induced liver fibrosis in rats. Serum liver function parameters (ALT, AST, ALP and total bilirubin) were quantified using a spectrophotometer, and both alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) levels were determined by using enzyme-linked immunosorbent assay (ELISA) kits while transformed growth factor beta (TGF-β) and tumor necrosis factor α (TNF-α) in liver tissue homogenate were determined using ELISA, and TGF-β and TNF-α gene expression in liver tissue was determined using real-time PCR following extraction and purification. Histopathological alterations in hepatic tissue were also examined under a microscope. In order to prioritize the isolation and characterization of the most promising marine steroids from the organic extract of the Red Sea soft coral Sarcophyton glaucum as hepatoprotective agents, a computational approach was employed. This approach involved molecular docking (MDock) and analysis of the structure-activity relationship (SAR) against glutathione-S-transferase (GST) and Cu-Zn human superoxide dismutase (Cu-ZnSOD) enzymes. Although the major role in the detoxification of foreign chemicals and toxic metabolites of GST and SOD enzymes is known, there is a lack of knowledge about the mode of action of the hepatoprotective process and those of the targets involved. The present study investigated the multiple interactions of a series of marine steroids with the GST and SOD enzymes, in order to reveal insights into the process of hepatoprotection.

Cembranoids from the Red Sea soft coral Sarcophyton glaucum protect against indomethacin-induced gastric injury.

Soft corals and their secondary metabolites represent an exceptional source of potential drugs. In this regard, Sarcophyton glaucum-derived secondary metabolites were examined for their preventive activities against indomethacin-induced gastric ulcer. Extraction and chromatographic processing of a specimen of S. glaucum collected from the Red Sea waters of Jeddah city resulted in the isolation of eight metabolites including two furanone-based cembranoids (1 and 2), two known pyran-based cembranoids (3 and 4), a known aromadendrene derivative (5), a δ-lactone fatty acid derivative (6), and two known gorgostane-type sterols (7 and 8). Compounds 1 and 6 are new chemical structures, named Δ12(20)-sarcophine and sarcoglaucanoate, respectively. In an initial pilot experiment, compounds 1 and 2 showed significant protective activities against indomethacin-induced peptic ulcer in rats. These datawere evidenced by their ability to ameliorate the elevated ulcer indices and prevent histopathological alterations observed in the untreated animals. Their effects were mediated by enhanced mucin as shown by Alcian blue and periodic acid-Schiff (PAS) staining of stomach sections. Compounds 1 and 2 exerted significant antioxidant properties as they prevent reduced glutathione (GSH) depletion, malondialdehyde (MDA) accumulation, and superoxide dismutase (SOD) exhaustion. Furthermore, immunohistochemical analyses indicated that both compounds inhibited the expression of interleukin-6 (IL-6) and tumor necrosis-α (TNF-α) as compared to indomethacin alone-treated animals. These actions were accompanied by significant enhancement of tumor growth factor-β (TGF-β) expression. In conclusion, two cembranoids exhibited protective activities against indomethacin-induced peptic ulcer. This is, at least partly, mediated by their pro-mucin, antioxidant, anti-inflammatory, and TGF-β stimulating properties.

A new cembranoid from the Red Sea soft coral Sarcophyton acutum

The Red Sea soft coral Sarcophyton acutum ethyl acetate extract has afforded one new cembranoid; sarcacutumolid A (1), along with six known metabolites have been isolated from S. acutum for the first time (2-7). Chemical structures were elucidated by employing several spectroscopic analyses. The cytotoxic potential of the isolated compounds was assessed against four human cancer cell lines; hepatocellular (HepG2), cervical (HeLa), breast (MCF-7) and colorectal cancer (Colo-205). Sarcacutumolid A (1) and gorgosterol (7) inhibited colorectal cancer cell proliferation in a concentration-dependent manner with IC50 values of 35.5 and 44.0 μM, respectively.

Diterpenes and sterols from the Red Sea soft coral Sarcophyton trocheliophorum and their cytotoxicity and anti-leishmanial activities

The ethyl acetate and dichloromethane-soluble fractions, from a soft coral Sarcophyton trocheliophorum total methanolic extract, exhibited significant anti-leishmanial and cytotoxic activities. These active fractions yielded a new cembranoid diterpene (1), two known analogues [sarcotrocheliol (2) and sarcophine (3)], and two sterols [(24S)-24-methylcholesterol (4) and gorgosterol (5)]. The structure of the new diterpene (1) was determined via a detailed analysis of its spectroscopic data. Compounds 3 and 5 demonstrated noticeable cytotoxicity on A549 (IC50 17.4 ± 1.9 µg/ml) and HepG2 (IC50 17.7 ± 1.5 µg/ml) cell lines, respectively. None of the isolates 1‒5 showed detectable anti-leishmanial activity (IC50 >100 µg/ml).

Cytotoxic and Antileishmanial Activities of the Red Sea Soft Coral Sarcophyton glaucum Extract and Some of Its Isolates

Cytotoxic and Antileishmanial Activities of the Red Sea Soft Coral Sarcophyton glaucum Extract and Some of Its Isolates

Sarcoroseolides A-D, four undescribed cembranoids from the Red Sea soft coral Sarcophyton roseum

Four undescribed cembranoids, sarcoroseolides A-D (1-4) along with nine reported related cembranoids (5-13) were isolated from the soft coral Sarcophyton roseum. The chemical structures of sarcoroseolides A-D were elucidated by extensive 1 D and 2 D NMR as well as HR-ESIMS spectroscopic data. Moreover, the geometric and absolute configurations were assigned by the modified Mosher’s method and/or NOESY experiments. The extract and the isolated metabolites were evaluated for their potential anti-inflammatory and cytotoxic activities.

Sarcophine and (7S, 8R)-dihydroxydeepoxysarcophine from the Red Sea soft coral Sarcophyton glaucum as in vitro and in vivo modulators of glycine receptors

The inhibitory glycine receptor (GlyR) is a key mediator of synaptic signalling in spinal cord, brain stem, and higher centres of the central nervous system. We examined the glycinergic activity of sarcophine (SN), a marine terpenoid known for its various biological activities, and its trans-diol derivative (7S, 8R)-dihydroxy-deepoxysarcophine (DSN). SN was isolated from the Red Sea soft coral Sacrophyton glaucum, DSN was semisynthesized by hydrolysis of the epoxide ring. In cytotoxicity tests against HEK293 cells, SN and DSN had LD50 values of 29.3 ± 3.0 mM and 123.5 ± 13.0 mM, respectively. Both compounds were tested against recombinant human α1 glycine receptors in HEK293 cells using whole-cell recording techniques. Both, SN and DSN were shown for the first time to be inhibitors of recombinant glycine receptors, with KIvalues of 2.1 ± 0.3 μM for SN, and 109 ± 9 μM for DSN. Receptor inhibition was also studied in vivo in a mouse model of strychnine toxicity. Surprisingly, in mouse experiments strychnine inhibition was not augmented by either terpenoid. While DSN had no significant effect on strychnine toxicity, SN even delayed strychnine effects. This could be accounted for by assuming that strychnine and sarcophine derivatives compete for the same binding site on the receptor, so the less toxic sarcophine can prevent strychnine from binding. The combination of modulatory activity and low level of toxicity makes sarcophines attractive structures for novel glycinergic drugs.

Diverse bioactive compounds from Sarcophtyton glaucom: structure elucidation and cytotoxic activity studies.

Chemical investigation of the Red Sea soft coral Sarcophyton glaucom collected at the coasts of Hurghada, Egypt, led to the isolation of one new naturally occurring 4-oxo-1,1′-pentanoic acid anhydride (1), along with four diterpenes; sarcophinone (2a), 8-epi-sarcophinone (2b), (+)-7α,8β-dihydroxydeepoxysarcophine (3), sinumaximol G (4), (+)-sarcophine (5), sesquiterpene; prostantherol (6), sterol; 3β,24S-ergost-5-en-ol (7) and hexadecanoic acid. The structures of the obtained compounds were established using diverse spectroscopic techniques including 1D and 2D NMR and HRMS. Biologically, in vitro cytotoxic activities of diterpenes 2–5 and prostantherol (6) were studied against the liver cancer HEPG2 cell line in comparison with the soft coral extract and doxorubicin as reference (IC50: 4.28 μg/mL). Compounds 2–6 exhibited potent–moderate cytotoxicity of IC50 between 9.97 μg/mL [for sinumaximol G (4)] and 17.84 μg/mL [for (+)-7α,8β-dihydroxydeepoxysarcophine (3)], whereas that for soft coral extract was determined at 24.71 μg/mL.

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.

Top ten most accessed AMOR articles in 2015/2016

<p>In 2015/2016, Advances in Modern Oncology Research published a total of 67 articles over eight issues in two separate volumes. These published articles, consisting of editorials, reviews, case reports, and original research, have collectively accumulated 26,320 views as of December 2016. A total of 54 authors and 160 peer-reviewers from across the globe contributed to the journal in its first full year of publication. The journal’s top ten most accessed articles are:</p><p>1. Indoles as anticancer agents (Vol. 1 Issue 1) <br /> <br />2. Pharmacometrics and systems pharmacology of immune checkpoint inhibitor nivolumab in cancer translational medicine (Vol. 2 Issue 1) <br /> <br />3. Hepatocellular carcinoma (HCC); aetiological considerations (Vol. 1 Issue 1) <br /> <br />4. Oligoadenylate synthetase 1 (OAS1) expression in human breast and prostate cancer cases, and its regulation by sex steroid hormones (Vol. 2 Issue 2) <br /> <br />5. Antiproliferative effects of cembranoid derivatives obtained from Red Sea soft coral Sarcophyton glaucum on human colorectal cancer cell lines (Vol. 1 Issue 1) <br /> <br />6. Paraneoplastic pemphigus: A trait d’union between dermatology and oncology (Vol. 1 Issue 2) <br /> <br />7. Cancer cell metastasis; perspectives from the focal adhesion (Vol. 1 Issue 1) <br /> <br />8. Threshold-based parametric analysis of diffusion-weighted magnetic resonance imaging at 3.0 Tesla to identify men with prostate cancer (Vol. 1 Issue 2) <br /> <br />9. Economic burden of patients with inoperable advanced breast cancer receiving early or late capecitabine or trastuzumab as second-line treatment: A population-based study (Vol. 1 Issue 2) <br /> <br />10. Non-coding RNAs: New therapeutic targets and opportunities for hepatocellular carcinoma (Vol. 2 Issue 1)</p>

New antimicrobial biscembrane hydrocarbon and cembranoid diterpenes from the soft coral Sarcophyton trocheliophorum

A new tetracyclic biscembrane hydrocarbon, trocheliane (1), along with two new cembranoid diterpenes, sarcotrocheldiol A (2) and B (3), and the known diterpene cembrene-C (4), were isolated from the Red Sea soft coral Sarcophyton trocheliophorum. The structures and relative stereochemistry of the compounds were elucidated by interpretation of MS, 1 D NMR, and 2 D NMR experiments. The sensitivity of some pathogenic bacteria used as test organisms to the new compounds 1-3 was determined. 1 showed appreciable antimicrobial activity with the diameter of inhibition zones ranging from 11 to 18 mm. 1 was active against the two multidrug resistant bacteria Acinetobacter baumannii and Staphylococcus aureus. Minimal inhibitory concentrations (MICs) of compound 1 were recorded for all the tested bacteria using the fluorescein diacetate method and the recorded MIC values ranged from 4 to 6 $\mu $M.

Mechanism of action of antiepileptic ceramide from Red Sea soft coral Sarcophyton auritum.

Chemical investigation of the Red Sea soft coral Sarcophyton auritum led to the isolation and structure elucidation of a new ceramide N-((2S,3R,4E,6E)-1,3-dihydroxyhenicosa-4,6-dien-2-yl)tridecanamide (1). Structure elucidation was achieved using spectroscopic techniques, including 1D and 2D NMR and HRMS. The anticonvulsant activity of the isolated ceramide was measured in vivo using the pentylenetetrazole (PTZ)-induced seizure model, where it successfully antagonized the lethality of pentylenetetrazole in mice. In addition, the isolated ceramide showed good anxiolytic activity when used in the light–dark transition box and the elevated plus maze compared to diazepam. The molecular modeling studies for the antiepileptic and antianxiety mechanism of the isolated ceramide suggested a CNS depressing activity possibly through GABA and serotonin receptors modulation. The pharmacological activity of the ceramide involved agonistic activity on GABA-A receptors but not 5HT3 receptors.

ChemInform Abstract: Cytotoxic Cembranoids from the Red Sea Soft Coral, Sarcophyton auritum.

Abstract Chemical investigation of the Red Sea soft coral Sarcophyton auritum led to the isolation and structure elucidation of two new diterpene cembranoids; 2- epi -sarcophine ( 2 ) and (1 R ,2 E ,4 S ,6 E ,8 R ,11 R ,12 R )-2,6-cembradiene-4,8,11,12-tetrol ( 4 ), as well as two known diterpene cembranoids, reported for the first time from this species, namely sarcophine ( 1 ) and (+)-7α,8β-dihydroxydeepoxysarcophine ( 3 ). Structure elucidation was achieved using spectroscopic techniques, including 1D and 2D NMR and HRMS. The isolated cembranoids were found to display high cytotoxicity against HepG2 (liver cancer cell line) and MCF-7 (breast cancer cell line).

Evaluation of Anti-melanoma Activities of (1S,2E,4R,6E,8R,11S,12R)-8,12-epoxy-2,6-cembradiene-4,11-diol, (1S,2E,4R,6E,8S,11R,12S)-8,11-epoxy-4,12-epoxy-2,6-cembradiene and (1S,4R,13S)-cembra-2E,7E,11E-trien-4,13-diol from the Red Sea soft coral Sarcophyton glaucum

Three natural cembranoids from the Red Sea soft coral Sarcophyton glaucum namely (1S,2E,4R,6E,8R,11S,12R)-8,12-epoxy-2,6-cembradiene-4,11-diol, (1S,2E,4R,6E,8S,11R,12S)-8,11-epoxy-4,12-epoxy-2,6-cembradiene and (1S,4R,13S)-cembra-2E,7E,11E-trien-4,13-diol were evaluated for their inhibitory effects on mouse melanoma B16F10 cell growth. Results show that all the cembranoids strongly inhibit viability of melanoma cells particularly during 48 -72 hrs treatment and also inhibit de novo DNA synthesis and PARP activity and stimulate fragmentation of DNA. (1S,2E,4R,6E,8R,11S,12R)-8,12-epoxy-2,6-cembradiene-4,11-diol was not cytotoxic to monkey kidney CV-1 cells at the concentration that produces the anti-melanoma effects which indicates that this compound may be a good candidate for further development. (1S,2E,4R,6E,8S,11R,12S)-8,11-epoxy-4,12-epoxy-2,6-cembradiene and (1S,4R,13S)-cembra-2E,7E,11E-trien-4,13-diol were found to be cytotoxic to healthy cells.

Rare pyrane-based cembranoids from the Red Sea soft coral Sarcophyton trocheliophorum as potential antimicrobial–antitumor agents

Two new rare pyrane-based cembranoids, sarcotrocheliol acetate (1) and sarcotrocheliol (2), along with two known cembranoids, cembrene-C (3) and sarcophine (4), and the aromadendrene sesquiterpenoid, palustrol (5), were isolated from the soft coral Sarcophyton trocheliophorum. Chemical structures were determined on the basis of extensive analysis of their spectroscopic data. 1 and 2 displayed significant antibacterial activity, especially against Staphylococcus aureus, Acinetobacter spp., and MRSA with minimal inhibitory concentrations (MICs) ranging from 1.53 to 4.34 µM, while 3 recorded antifungal activity against Aspergillus flavus and Candida albicans with an MIC of 0.68 µM. 4 and 5 showed lower antibacterial and antifungal activities compared to 1, 2, and 3. All the five metabolites displayed no appreciable cytotoxic activity against Artemia salina as test organism, while 4 and 5 recorded antitumor activities against Lymphoma and Erlish cell line with LD50 in the range of 2.5–3.79 µM.

Cytotoxic cembranoids from the Red Sea soft coral, Sarcophyton auritum

Chemical investigation of the Red Sea soft coral Sarcophyton auritum led to the isolation and structure elucidation of two new diterpene cembranoids; 2-epi-sarcophine (2) and (1R,2E,4S,6E,8R,11R,12R)-2,6-cembradiene-4,8,11,12-tetrol (4), as well as two known diterpene cembranoids, reported for the first time from this species, namely sarcophine (1) and (+)-7α,8β-dihydroxydeepoxysarcophine (3). Structure elucidation was achieved using spectroscopic techniques, including 1D and 2D NMR and HRMS. The isolated cembranoids were found to display high cytotoxicity against HepG2 (liver cancer cell line) and MCF-7 (breast cancer cell line).

Three new cembranoid-type diterpenes from Red Sea soft coral Sarcophyton glaucum: Isolation and antiproliferative activity against HepG2 cells

Three new cembranoids: sarcophytolol (1), sarcophytolide B (2), and sarcophytolide C (3), along with three known metabolites: 10(14)aromadendrene (4), deoxosarcophine (5), and sarcophine (6) were obtained from the soft bodied coral Sarcophyton glaucum. The structures were determined based on spectroscopic measurements (NMR, UV, IR and MS). Compounds 1, 3, and 4 had similar significant cytotoxic effects towards HepG2 (Human hepatocellular liver carcinoma; IC50 = 20 μM). 2 and 3 showed activity against MCF-7 (Human breast adenocarcinoma; IC50 25 ± 0.0164 and 29 ± 0.030 μM, respectively). Finally, 4 showed potent activity towards PC-3 (Prostate cancer; IC50 9.3 ± 0.164 μM). The antiproliferative activity of 1, 3 and 4, can be attributed, at least partly, to their ability to induce cellular apoptosis.

Evaluation of the Anti-melanoma Activities of Sarcophine, (+)-7α,8β-Dihydroxydeepoxysarcophine and Sarcophytolide from the Red Sea Soft Coral Sarcophyton glaucum

Three natural cembranoids from the Red Sea soft coral Sarcophyton glaucum namely sarcophine (1), (+)-7alpha,8beta-dihydroxydeepoxysarcophine (2) and sarcophytolide (3) were evaluated for their potential inhibitory effects on growth of mouse melanoma B16F10 cells. Compounds (1) and (2) maximally inhibit viability of melanoma cells during 48 hr and 72 hr treatment at concentrations that show no cytotoxicity on monkey kidney CV-1 cells and also inhibit de novo DNA synthesis and PARP activity. Compound (3) produced cytotoxic effects at the same concentration range it produces its antitumor effects. These data suggest that (1) and (2), but not (3), have potential for further development as antitumor agents against melanoma.