Ahmed Abdel-Lateff

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.

Modulation of carcinogen metabolizing enzymes by chromanone A; a new chromone derivative from algicolous marine fungus Penicillium sp.

A marine fungal isolate, Penicillium sp. fungus isolated from seaweed, Ulva sp., led to the isolation of a new chromone derivatives, 2-(hydroxymethyl)-8-methoxy-3-methyl-4H-chromen-4-one (chromanone A). The structure was determined by interpretation of their spectroscopic data (1D and 2D NMR, MS, UV and IR). At the nitiation stage of carcinogenesis, carcinogens is activated by cytochrome P-450 1A (CYP1A) and detoxified by glutathione S-transferases (GST), quinine reductase (QR), and epoxide hydrolase (mEH). We tested the modulatory effect of chromanone A on these carcinogen metabolizing enzymes. The results indicated that chromanone A (4μg/ml) is a promising inhibitor of CYP1A activity up to 60% of the stimulated-CYP1A in murine hepatoma cells (Hepa1c1c7), and it significantly induced GST but not total thiols at low concentrations. Chromanone A had no influence on QR activity, while it resulted in a significant dose-dependant enhancement mEH activity in Hepa1c1c7 cells (P<0.05-0.01). Additionally, chromanone A possessed a potent specific radical scavenging activity against hydroxyl radicals more than peroxyl radicals that may be responsible for the inhibitory effect of chromanone A on the induced-DNA damage in cells. In conclusion, this study proved that chromanone A may act as an active tumor anti-initiating via modulation of carcinogen metabolizing enzymes and protection from DNA damage.

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.

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.

Cucurbitacins-type triterpene with potent activity on mouse embryonic fibroblast from Cucumis prophetarum, cucurbitaceae.

Background: Higher plants are considered as a well-known source of the potent anticancer metabolites with diversity of chemical structures. For instance, taxol is an amazing diterpene alkaloid had been lunched since 1990. Objective: To isolate the major compounds from the fruit extract of Cucumis prophetarum, Cucurbitaceae, which are mainly responsible for the bioactivities as anticancer. Materials and Methods: Plant material was shady air dried, extracted with equal volume of chloroform/methanol, and fractionated with different adsorbents. The structures of obtained pure compounds were elucidated with different spectroscopic techniques employing 1D (1H and 13C) and 2D (COSY, HMQC and HMBC) NMR (Nuclear Magnetic Resonance Spectrometry) and ESI-MS (Eelectrospray Ionization Mass Spectrometry) spectroscopy. The pure isolates were tested towards human cancer cell lines, mouse embryonic fibroblast (NIH3T3) and virally transformed form (KA3IT). Results: Two cucurbitacins derivatives, dihydocucurbitacin B (1) and cucurbitacin B (2), had been obtained. Compounds 1 and 2 showed (showed potent inhibitory activities toward NIH3T3 and KA31T with IC50 0.2, 0.15, 2.5 and 2.0 μg/ml, respectively. Conclusion: The naturally cucurbitacin derivatives (dihydocucurbitacin B and cucurbitacin B) showed potent activities towards NIH3T3 and KA31T, could be considered as a lead of discovering a new anticancer natural drug.

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.

Alnuheptanoid A: a new diarylheptanoid derivative from Alnus japonica

Extensive chromatographic investigation of the ethanolic extract of Alnus japonica Steud stem bark led to the isolation of a new diarylheptanoid named alnuheptanoid A [(5S)-7-(3,4-dihydroxyphenyl)-1-(4-hydroxyphenyl)-5-methoxyheptan-3-one] (8), together with seven known diarylheptanoid derivatives: platyphyllenone (5), (5S)-1,7-bis(4-hydroxyphenyl)-5-methoxyheptan-3-one (6), 1-(3,4-dihydroxyphenyl)-7-(4-hydroxyphenyl)-4-hepten-3-one (7), hirsutenone (9), (5R)-O-methylhirsutanonol (10), hirsutanonol (11) and oregonin (13), three triterpenes: α-amyrin (1), betulinaldehyde (3) and betulinic acid (4), and two sterols: β-sitosterol (2) and daucosterol (12). Compound 6 was isolated for the first time from natural source. The structures of the isolated compounds were determined on the basis of spectroscopic measurements (UV, IR, HR-ESI-MS, 1D and 2D NMR).

Ketoisophorone Transformation by Marchantia polymorpha and Nicotiana tabacum Cultured Cells

Stereospecific olefin (C=C) and carbonyl (C=O) reduction of the readily available prochiral compound ketoisophorone (2,2,6-trimethyl-2-cyclohexene-1,4-dione) (1) by Marchantia polymorpha and Nicotiana tabacum cell suspension cultures produce the chiral products (6R)-levodione (2), (4R,5S)-4-hydroxy-3,3,5-trimethylcyclohexanone (3), and (4R,6R)-actinol (4) as well as the minor components (4R)-hydroxyisophorone (5) and (4S)-phorenol (6).