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).

Cytotoxic and anti-bacterial evaluation of two new aromatic A-ring steroids isolated from the Red Sea soft coral Dendronephthya spp.

A successful column chromatography of a CHCl3/MeOH crude extract of Dendronephthya spp. soft coral led to the isolation of two new aromatic A-ring steroids (1-2), together with three known compounds (3-5). Both 1 and 2 are 19-norsteroids. The chemical structures were elucidated based on extensive 1D, 2D NMR, and EIMS analyses. In cytotoxic bioassays, compounds 1-5 were tested against three cancer cell lines: MCF-7, NCI-1299, and HepG2, with IC50 in the ranges of 22.1-85.4, 26.9-88.7, and 25.9-93.7 µM, respectively. Compounds 1, 2, and 5 showed moderate degrees of inhibition against Escherichia coli and Pseudomonas sp. at 100 and 150 µg/mL, while exhibiting weak inhibition against Bacillus cereus and Staphylococcus aureus at 150 µg/mL.

Polymorphisms of interleukin 4 and interleukin 4 receptor genes and bronchial asthma risk among Egyptian children.

BACKGROUND: Interleukin 4 (IL4) is a key cytokine that regulates the inflammatory cascade in bronchial asthma. We investigated the association between the IL4 and IL4R polymorphisms and the susceptibility for bronchial asthma among Egyptian children. METHODS: IL4 VNTR and IL4R c.1902 A>G p.(Q576R) polymorphisms were investigated among 100 children with bronchial asthma and 100 healthy controls using PCR method. Serum levels of IL4 and immunoglobulin E (IgE) were assessed by ELISA. RESULTS: The frequencies of (A1A2 + A2A2) genotypes and A2-allele of the IL4 VNTR variant were significantly higher among asthmatic patients than controls (p = 0.01, OR = 2.34, 95% CI = 1.24-4.44; p = 0.01, OR = 2.27, 95% CI = 1.29-3.99, respectively). The frequencies of (AG + GG) genotypes and G-allele of the IL4R (A1902G) variant were significantly higher among asthmatic patients than controls (p = 0.003, OR = 2.52, 95% CI = 1.39-4.58; p = 0.002, OR = 2.25, 95% CI = 1.35-3.76, respectively). There was a significant association between (A1A2 + A2A2) genotypes of the IL4 VNTR variant and high serum IL4 level among asthmatic patients (p < 0.001). The (AG + GG) genotypes of the IL4R (A1902G) variant were significantly associated with exposure to triggers, atopic dermatitis and higher serum IgE level in asthmatic patients (p = 0.02, 0.04 and 0.01, respectively). CONCLUSION: IL4 VNTR and IL4R (A1902G) polymorphisms could be associated with higher risks of bronchial asthma among Egyptian children.

Gene Expression Profiling to Delineate the Anticancer Potential of a New Alkaloid Isopicrinine From Rhazya stricta.

Background:Rhazya stricta has been used as a folkloric medicinal herb for treating various diseases such as diabetes, inflammatory disorders, and sore throat. Several studies have revealed the potential of this plant as an important source of phytochemicals with anticancer properties. Objective: The present study was designed to isolate a novel anticancer compound from Rhazya stricta and elucidate its mechanism of action using genomics approach. Methods:Rhazya stricta leaves extract was prepared, and several alkaloids were purified and characterized. These alkaloids were screened for their anticancer potential. One of the alkaloids, termed as isopicrinine, showed efficient cytotoxicity against MCF7 breast cancer cell line and was selected for further analysis. RNA-Seq transcription profiling was conducted to identify the affected genes and cellular pathways in MCF7 cells after treatment with isopicrinine alkaloid. Results: In vitro studies revealed that newly identified isopicrinine alkaloid possess efficient anticancer activity. Exposure of MCF7 cells with isopicrinine affected the expression of various genes involved in p53 signaling pathway. One of the crucial proapoptotic genes, significantly upregulated in MCF7 after exposure to alkaloid, was PUMA (p53 upregulated modulator of apoptosis), which is involved in p53-dependent and -independent apoptosis. Moreover, exposure of sublethal dose of isopicrinine alkaloid in breast cancer cell line led to the downregulation of survivin, which is involved in negative regulation of apoptosis. Besides, several genes involved in mitosis and cell proliferation were significantly downregulated. Conclusion: In this article, we report the determination of a new alkaloid isopicrinine from the aerial parts of Rhazya stricta with anticancer property. This compound has the potential to be developed as a drug for curing cancer.

Cytotoxic Metabolites from Callyspongia siphonella Display Antiproliferative Activity by Inducing Apoptosis in HCT-116 Cells.

OBJECTIVES: To evaluate the antiproliferative effect of the isolated metabolites from Callyspongia siphonella. METHODS: Different chromatographic methods have been done on the organic extract of the marine sponge aiming at isolating the bioactive metabolites. The cytotoxicity of the isolated compounds has been evaluated against the human colorectal cancer cell line; HCT-116, employing SRB assay. The flow cytometry assay was applied to measure the cell cycle analysis. RESULTS: Six metabolites (1-6) were obtained. The compounds 4-6 exhibited IC50 values (µM ± SD) of 95.80± 1.34, 14.8 ± 2.33, and 19.8 ± 3.78, respectively. Cell cycle distribution analysis revealed that sipholenol A (5) and sipholenol L (6) induced G2/M and S phase arrest with concomitant increase in the pre-G cell population. Furthermore, 5 and 6 increased the nuclear expression of the pro-apoptotic protein-cleaved caspase-3 that effectively drives cellular apoptosis via caspase-3-dependent pathway. CONCLUSIONS: The antiproliferative activity of 5 and 6 can be recognized, at least partly, due to their ability to induce cellular apoptosis. SUMMARY: Several metabolites were isolated from the marine sponge Callyspongia siphonella. Sipholenol A and sipholenol L exhibited effective cytotoxicity against HCT-116 cells. The observed cytotoxicity involves induction of cellular apoptosis. Abbreviation used: A549 (human lung carcinoma), Caco-2 (Human ColonCarcinoma), CHCl3 (Chloroform), HCT 116 (Human Colon Carcinoma), HepG2 (Liver Hepatocellular Carcinoma), HT-29 (Human Colorectal Adenocarcinoma), MCF-7 (Michigan Cancer Foundation-7; Human Breast Adenocarcinoma), MeOH (Methanol), NMR Nuclear Magnetic Resonance), PBS (Phosphate Buffered Saline), PC-3 (Human Prostate Cancer), PTLC (Preparative Thin Layer Chromatography), RPMI-1640 (Roswell Park Memorial Institute medium), TLC (ThinLayer Chromatography).

Isolation, antimicrobial and antitumor activities of a new polyhydroxysteroid and a new diterpenoid from the soft coral Xenia umbellata.

A new C-30 steroid, 3ß-,5α-,6ß-,11α-,20ß-pentahydroxygorgosterol (1), and a new diterpenoid, xeniumbellal (2), along with three known aromadendrane-type sesquiterpenes, aromadendrene (3), palustrol (4) and viridiflorol (5), were isolated from the soft coral Xenia umbellata. Chemical structures were determined by analyzing their NMR and MS data. The antimicrobial and antitumor activities of the isolated compounds were examined. Both 1 and 2 showed moderate antibacterial activities, especially against the multidrug-resistant Acinetobacter baumannii (MIC 0.22 and 0.28 mM, respectively); while 2 showed antitumor activity against a lymphoma cell line with LD50 0.57 mM and was nontoxic to Artemia salina at all tested concentrations up to about 4 mM.

Antiproliferative effects of triterpenoidal derivatives, obtained from the marine sponge Siphonochalina sp., on human hepatic and colorectal cancer cells.

Three triterpenoidal derivatives [Sipholenol A (1), sipholenol L (2) and sipholenone A (3)] were isolated from the Red Sea sponge Siphonochalina sp. The structures were determined based on spectroscopic measurements (NMR, UV, IR and MS). The isolated compounds were evaluated for their cytotoxic activity against three cancer cell lines; HepG2, Caco-2 and HT-29. Moreover, the effects of these metabolites on cell cycle progression as well as cell cycle regulating proteins were assessed. Compounds 1, 2 and 3 showed moderate activity against HepG2 cells with IC(50) values of 17.18 ± 1.18, 24.01 ± 0.59 and 35.06 ± 1.10 µM, respectively. Compounds 1 and 2 exerted a considerable antiproliferative effect with IC(50) values of 4.80 ± 0.18 and 26.64 ± 0.30 µM, respectively, against Caco-2 cells. Finally, 1 and 2 exhibited antiproliferative activity against colorectal cancer cells (HT-29) with IC(50) values of 24.65 ± 0.80 and 4.48 ± 0.1 µM, respectively. Cell cycle analysis indicated that these compounds induced cell cycle arrest particularly in G0/G1 and S phases. Furthermore, the triterpenoids increased the expression of cyclin-B1, cyclin-D1 and cleaved caspase-3, as determined by immunofluorescence, indicating an important role of apoptosis in cell death induced by these compounds.

Cytotoxic scalarane-type sesterterpenes from the Saudi Red Sea sponge Hyrtios erectus.

The CHCl3/MeOH extract of the marine sponge Hyrtios erectus showed cytotoxicity against three cancer cell lines HepG2, A549, and PC-3 with IC50 0.055, 0.044, and 0.023 µg/ml, respectively. The CH2Cl2 soluble fraction afforded three scalarane sesterterpenes (1-3) along with a cholestane derivative (4) and an indole alkaloid (5). Chemical structures were established by spectroscopic techniques and comparison with data reported in the literature. Scalarinol (1) was found as a new metabolite, while heteronemin (2) and 12-O-deacetyl-19-deoxyscalarin (3) are known compounds. 1-3 exhibited cytotoxic activity against the cancer cell lines with IC50 values ranging from 14 to 230 µM. The molecular affinity to the DNA was employed as marker to examine the proposed mechanism of cytotoxic activities. Compound 2, with IC50 28 µg/ml, displayed the highest affinity to the DNA.

A review of steroids from Sarcophyton species.

This review reports the structural diversity of steroids from Sarcophyton species based on literature from the beginning of marine steroid research until now. There are 65 compounds studied from eight species. Most of them are polyhydroxy-type steroids of C-27-C-31 carbon skeleton. Their biological activities are highly diverse ranging from cytotoxic, antibacterial, antifungal, antiviral, anti-inflammatory, antidiabetic to antiosteoporosis properties.

The role of new eudesmane-type sesquiterpenoid and known eudesmane derivatives from the red alga Laurencia obtusa as potential antifungal-antitumour agents.

A new eudesmane sesquiterpenoid, eudesma-4(15),7-diene-5,11-diol (1) along with the known trinor-sesquiterene, teuhetenone (2), and a seco-eudesmane sesquiterpene, chabrolidione B (3), have been isolated from the Red Sea red alga Laurencia obtusa. The chemical structures were elucidated on the basis of extensive spectroscopic analysis. The antifungal and cytotoxic activities of the isolated metabolites were tested against several fungi, yeast and human mammary carcinoma cell line (MCF-7). Compounds 1 and 3 showed a much better activity [minimum inhibitory concentration (MIC): 2.9 µM] than that of amphotericin B (MIC: 4.6 µM). Interestingly, compound 2, the least active antifungal compound, retained the high anticancer activity against MCF-7 (22 µM) in comparison with cisplatin (59 µM), which was determined by employing lactate dehydrogenase assay. Compounds 1-3 are recorded here for the first time from algal flora. The chemotaxonomic importance of the isolated metabolites was discussed.

Two new polyacetylene derivatives from the Red Sea sponge Xestospongia sp.

Two new polyacetylenes (1 and 2), along with two known C-30 steroids (3 and 4) were identified from the Red Sea sponge, Xestospongia sp. The chemical structures were determined based on extensive spectroscopic measurements 1D (1H, 13C and DEPT) and 2D (COSY, HSQC and HMBC) NMR, UV, IR and MS. The new compounds 1 and 2 were evaluated for their antimicrobial and antitumor activities. 1 and 2 were active against multidrug- resistant bacteria with MICs ranged from 2.2 to 4.5 µM. No toxicity was recorded for the two tested compounds up to 5 µM using Artemia salina as a test organism. Compound 2 showed excellent antifungal activity against some pathogenic fungi such as Aspergillus niger and Candida albicans (MIC 2.2-2.5 µM) and antitumor activity against both Ehrlich ascites carcinoma and lymphocytic leukemia (LD50 5.0 µM).

Differential cytotoxic activity of the petroleum ether extract and its furanosesquiterpenoid constituents from Commiphora molmol resin.

This study revealed a differential cytotoxic activity of the petroleum ether extract (IC50 =5 µg/mL) of the resinous exudates of Commiphora molmol against two mouse cell lines KA31T and NIH3T3 (untransformed and transformed mouse fibroblasts, respectively). Four new compounds (1-4) and five known compounds (5-9) were isolated from the petroleum ether extract. The identity of these new compounds was determined as γ-elemane lactone (1), 5-αH,8-ßH-eudesma-1,3,7(11)-trien-8,12-olide (2), 2-hydroxy-11,12-dihydrofuranodiene (3), and 2-hydroxyfuranodiene (4). 1 and 2 displayed the highest cytotoxic activity against NIH3T3 cells. 7 and 9 exhibited moderate cytotoxic activity against KA31T cells. Compounds 3-6 showed weak cytotoxic activities against both cell lines. These results may explain the high efficacy of the petroleum ether fraction in several myrrh-derived pharmaceutical preparations.

New cytotoxic cyclic peroxide acids from Plakortis sp. marine sponge.

Bioassay-guided fractionation of the extract of Jamaican marine sponge Plakortis sp. followed by preparative TLC and HPLC yielded several known methyl ester cyclic peroxides (1a, 2a, 3a, 4, 5), known plakortides (6,7), known bicyclic lactone (8) and new cyclic peroxide acids (1b, 2b, 3b). The chemical structures were elucidated by extensive interpretation of their spectroscopic data. These natural products showed remarkable in vitro cytotoxicity against several cancer cell lines.

New cytotoxic isoprenoid derivatives from the Red Sea soft coral Sarcophyton glaucum.

Chemical investigation of the soft coral Sarcophyton glaucum collected from the Red Sea led to isolation of 11 isoprenoidal metabolites (1-11). A new sesquiterpenoid, 6-oxo-germacra-4(15),8,11-triene (1), a new natural cembranoid, sarcophinediol, along with two known sesquiterpenoids (2 and 3) and seven known cembranoids (5-11) was obtained. The structures of the compounds were established based on their NMR, MS, IR and UV spectral data. All compounds were evaluated for their cytotoxicity employing three cancer cell lines (HepG2, MCF-7 and HCT116). Compounds 4 and 6 showed significant cytotoxicity towards HepG2 with IC50 values of 18.8 ± 0.07 and 19.9 ± 0.02 µM; respectively. Compounds 5-7 exhibited potent cytotoxicity against MCF-7 cells with IC50 values of 9.9 ± 0.03, 2.4 ± 0.04 and 3.2 ± 0.02 µM, respectively. Compounds 1, 4 and 5 showed significant activities towards HCT116 cells with IC50 values of 29.4 ± 0.03, 19.4 ± 0.02 and 25.8 ± 0.03 µM, respectively.

Cytotoxic neviotane triterpene-type from the red sea sponge Siphonochalina siphonella.

BACKGROUND: Siphonochalina siphonella is a marine sponge collected from saudi Red Sea water and scare study from this region. OBJECTIVE: To isolate the anticancer triterpenes with potent cytotoxicity from marine sponge, Siphonochalina siphonella and state the mode of action in cancer cell lines. MATERIALS AND METHODS: The sponge material was collected, extracted with organic solvent, and fractionated on different adsorbents. The structure of the pure metabolites were elucidated employing different spectroscopic techniques including 1D ((1)H and (13)C) and 2D (COSY, HMQC and HMBC) NMR, and MS spectroscopy. RESULTS: A new Neviotine-C (1) was obtained, along with four known metabolites (2-5). All compounds, except 5, were tested towards MCF-7, PC-3 and A549 and showed effects with IC50 in range 7.9-87 µM, whilst, 3 showed potent anti-proliferative activity against PC-3 and A549 with IC50 = 7.9 ± 0.120 and 8.9 ± 0.010 µM, respectively. CONCLUSION: Compounds (1-4) showed significant cytotoxic activities, while 3 showed potent effect. The antiproliferative of 3 was attributed to significant S-phase cell cycle arrest.

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.

Cytotoxic polyacetylenes from the Red Sea sponge Siphonochalina siphonella.

Two new polyacetylenes, callyspongenol-D (1) and callyspongendiol (2), the known polyacetylene dehydrosiphonochalynol (3), and the known triterpenoid sipholenol-A (4) were isolated from the Red Sea sponge Siphonochalina siphonella. Their chemical structures were elucidated on the basis of spectroscopic analyses. The cytotoxicity of the isolated compounds towards the human mammary carcinoma cell line MCF-7 was determined by the lactate dehydrogenase (LDH) assay, and compounds 4 and 1 were found to be the most toxic of the four, with IC50 values of 8.8 and 11.7 microM, respectively.

Cytotoxic effects of three new metabolites from Red Sea marine sponge, Petrosia sp.

Marine sponges represent an affluent source of biogenetically unprecedented array of biologically active compounds. This study revealed the isolation of ten compounds from marine sponge of Petrosia sp. Their chemical structures were determined by using 1D and 2D NMR, UV, IR and MS measurements. A polyoxygenated steroid (3ß,7ß,9α-trihydroxycholest-5-en (1), a purine-derivative (3,7-dimethyl-2-(methylamino)-3H-purin-6(7H)-one (2) and a sphingolipid (N-((3S,E)-1,3-dihydroxytetracos-4-en-2-yl)stearamide (3) proved to be new compounds. Meanwhile, seven known compounds; (4-10) were also identified. The cytotoxicity of the total extract and the isolated compounds were subjected to cytotoxicity evaluation employing two cancer cell lines; HepG2 and MCF-7. All tested compounds exhibited cytotoxic effect on both cancer cell lines with IC(50) in range of 20-500 µM. The proposed mechanism of cytotoxic activities was examined through its molecular affinity to the DNA. Compound 5 showed the highest affinity to the DNA with IC(50) 30 µg/mL.

Selective cytotoxic effects on human breast carcinoma of new methoxylated flavonoids from Euryops arabicus grown in Saudi Arabia.

The chloroform-methanol extract of Euryops arabicus, collected from Saudi provenance, yielded a new kaurane diterpene (1) and seven methoxylated flavones (2-8), two of which are new (2 and 3). Structures of the compounds were elucidated through interpretation of spectral data of NMR, MS and comparison with literature values. All compounds were evaluated for their anti-tumor activities, employing four different cancer cell lines (WI-38, VERO, HepG2 and MCF-7), ABTS free radical scavenging and immunemodulatory effects. All metabolites had considerable antioxidant and immunestimulatory effects. All compounds showed anticancer activity with IC50 in range 10-125 µM, whilst 2 and 6 showed significant anti-proliferative activity against HepG2 (IC50 = 20 and 15 µM) and MCF-7 (IC50 = 15 and 10 µM), respectively. This effect was attributed to significant S-phase cell cycle arrest.

New diarylheptanoids and a hydroxylated ottelione from Ottelia alismoides.

Ten new diarylheptanoids (2, 3, 4, 5a-d, 6, 7, and 8) have been isolated from an extract of Ottelia alismoides. The structures of these previously unknown metabolites were determined by NMR spectroscopic analysis. A previously unknown, hydroxylated analog of the known otteliones A and B (1a and 1b)--namely, 3a-hydroxyottelione (13)--was also isolated. The 1H NMR analysis of the Mosher esters of alcohols derived from otteliones A and B (S-17/R-17 and S-20/R-20) are also reported.