Seif-Eldin N. Ayyad

In vitro and in vivo study of cucurbitacins-type triterpene glucoside from Citrullus colocynthis growing in Saudi Arabia against hepatocellular carcinoma

Chromatographic investigation of fruits obtained from Citrullus colocynthis, growing in Saudi Arabia, led to isolation of two compounds; Cucurbitacin E glucoside (Cu E, 1), and Cucurbitacin I glucoside (Cu I, 2). The chemical structures of 1 and 2, were elucidated by spectroscopic analyses include; 1D ((1)H and (13)C) and 2D (COSY, HMQC and HMBC) NMR and ESI-MS spectroscopy. The in vitro cytotoxic activity against hepatoma cell line (HepG2) and mice-bearing tumor of Ehrlichs ascites carcinoma (EAC) of the compounds were estimated. Both compounds had potent inhibitory activity on HepG2 with IC(50) 3.5 and 2.8 nmol/mL, respectively. In addition to these activities, the in vivo study employing EAC, showed the capability of both compounds to prolong the survival time, life span and normalize the biochemical parameters of the infected mice with EAC.

Laurene-type sesquiterpenes from the Red Sea red alga Laurencia obtusa as potential antitumor-antimicrobial agents.

Three new laurene-type sesquiterpenes, 12-hydroxy isolaurene (1), 8,11-dihydro-12-hydroxy isolaurene (2) and isolauraldehyde (3) were isolated from the organic extract of the red alga Laurencia obtusa. The chemical structures of isolates were determined by interpretation of their spectral data 1D and 2D NMR, UV, IR and MS. The newly isolated compounds were tested for their antimicrobial and antitumor activities. Compounds (1-3) exhibited potent activity against the gram-positive Bacillus subtilis and Staphylococcus aureus, where 3 proved to be the most active (MIC 35 and 27 μg/mL, respectively). Moreover, compound 3 exhibited a significant activity against Candida albicans (MIC of 70 μg/mL) and revealed to have very promising activity in an in vitro model of Ehrlich ascites Carcinoma.

Antioxidant, cytotoxic, antitumor, and protective DNA damage metabolites from the red sea brown alga Sargassum sp.

Background: Macroalgae can be viewed as a potential antioxidant and anti-inflammatory sources owing to their capability of producing compounds for its protection from environmental factors such as heat, pollution, stress, oxygen concentration, and UV radiations. Objective: To isolate major compounds which are mainly responsible for the pharmacological activity of brown alga under investigation, Sargassum sp. Materials and Methods: Algal material was air dried, extracted with a mixture of organic solvents, and fractionated with different adsorbents. The structures of obtained pure compounds were elucidated with different spectroscopic techniques, and two pure materials were tested for protection of DNA from damage, antioxidant, antitumor, and cytotoxicity. Results: Four pure compounds were obtained, of which fucosterol (1) and fucoxanthin (4) were tested; it was found that fucoxanthin has strong antioxidant and cytotoxicity against breast cancer (MCF-7) with IC50 = 11.5 μg/ml. Conclusion: The naturally highly conjugated safe compound fucoxanthin could be used as antioxidant and as an antitumor compound.

Cytotoxic and protective DNA damage of three new diterpenoids from the brown alga Dictoyota dichotoma

Three new diterpenes Amijiol acetate (3), dolabellane, Dolabellatrienol (4), and dolastane, Amijiol-7, 10-diacetate (9) were isolated together with the previously described Pachydictyol A (1), Isopachydictyol A (2), 8β-hydroxypachydictyol A (5), Amijiol (6), Isodictyohemiacetal (7) and Dictyol C (8) from the Red Sea brown alga Dictyota dichotoma var. implexa. The structures and relative stereochemistry of the new diterpenoids were proposed on the basis of their spectral data. Compounds 3 and 9 have potent activity against DNA damage, cytotoxicity against WI-38, HepG2, and MCF-7 cell lines, and antioxidant using ABTS and erythrocytes hemolysis.

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.

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.

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 (1H and 13C) 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.

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 (3β,7β,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.

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.

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

Abstract 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 IC50 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 IC50 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 IC50 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.