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United States Department of Agriculture

Agricultural Research Service


Location: Natural Products Utilization Research

Title: Cytotoxicity and modulation of cancer-related signaling by (Z)- and (E)- 3,4,3´,5´ tetramethoxystilbene isolated from Eugenia rigida

item Mohamed, Zaki
item Balachandran, Premalatha
item Khan, Shabana
item Wang, Mei
item Mohammed, Rabab
item Hetta, Mona
item Pasco, David
item Muhammad, Ilias

Submitted to: Journal of Natural Products
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/15/2013
Publication Date: 4/2/2013
Citation: Mohamed, Z., Balachandran, P., Khan, S., Wang, M., Mohammed, R., Hetta, M.H., Pasco, D.S., Muhammad, I. 2013. Cytotoxicity and modulation of cancer-related signaling by (Z)- and (E)- 3,4,3´,5´ tetramethoxystilbene isolated from Eugenia rigida. Journal of Natural Products. 76:679–684.

Interpretive Summary: Bioassay- guided fractionation of the leaves of Eugenia rigida yielded three stilbenes, namely Z-3,3´4,5´-tetramethoxystilbene (1), E-3,3´4,5´-tetramethoxystilbene (2) and E-3,4´,5-trimethoxystilbene (3). Their structures were determined using NMR spectroscopy. Compounds 1-3 were tested to assess the activity of many cancer-related signaling pathways. Z-isomer (1), an new compound, was found to be more potent than E- isomer (2) at inhibiting the activation of some enzymes involved in cancer. However, both compounds showed similar inhibition against other enzymes. In addition, 1 demonstrated cytotoxic activity towards human leukemia cells, as well as solid tumor cells of epidermal, breast and cervical carcinomas, and skin melanoma, while 2 was weakly active against leukemia, cervical, and skin melanoma cells. Interestingly, 2 showed antioxidant activity.

Technical Abstract: The leaves of E. rigida DC (Myrtaceae) were collected from Puerto Rico in March, 2006. The sample was identified by Mr. F. Axelrod and a voucher specimen (3008783) was deposited at the Herbarium of Missouri Botanical Garden, St. Louis, MO. Air-dried powdered leaves (107 g) were soaked in n-hexane and sonicated (600 ml x 3 x 2 h each). The combined extract was filtered and dried (2.5 g), and the residue was extracted with CH2Cl2, followed by EtOAc and MeOH, as executed for n-hexane, yielding 3.8, 1.1 and 14.0 g, respectively. The hexane extract fraction demonstrated cytotoxic activity. The hexane extract (2 g) was subjected to centrifugal preparative TLC (CPTLC, Chromatotron®), using a 6 mm custom made reversed phase ChromatorotorTM packed with binder free C18 silica gel. The rotor was mounted on a Chromatotron®, and packed under slow rotation (100 rpm) by applying a slurry of C18 SiO2 (100 g) doped with UV 254 and 365 fluorescent indicators (0.5% each) in H2O-MeOH (1:9; 300 mL). The sample, dissolved in Me2CO, was applied to the rotor under a rotation of 700 rpm, and then the rotor was removed from instrument and left for drying in a desecrator. The dried rotor was mounted on Chromatotron® and eluted with H2O-MeOH (3:7), which afforded fr. 12-21 (174 mg) containing a mixture of compounds 1-3. This fraction was subjected to CPTLC, using a 2 mm silica gel disc, and eluted with 0.5 - 20% Me2CO in n-hexane, which afforded compound 1 (3 mg), followed by 2 (30 mg) and 3 (1 mg), respectively, as monitored and pooled by TLC analyses (silica gel, solvent: toluene: EtOAc 9:1).

Last Modified: 06/22/2017
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