104594-70-9

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antineoplastic, antiinflammatory, immunomodulator, NFkB blocker

Cytotoxic agent against cancer cell lines. Inhibitor of ornithine decarboxylase and protein tyrosine kinase. Found to be a specific inhibitor of the nuclear transcription factor, NF-kB. It has also been shown to significantly suppress the lipoxygenase pathway of arachidonic acid metabolism during inflammation.

Antioxidant, antimitogenic, anticarcinogenic, anti-inflammatory and antiviral. Specifically inhibits NF κ B activation and inhibits the growth of transformed cells. Also suppresses lipid peroxidation and inhibits ornithine decarboxylase, protein tyrosine kinase and lipoxygenase activities.

Phenylethyl caffeate is one of the allergens of propolis (bee glue); also contained in poplar-bud secretions.

ChEBI: Phenethyl caffeate is an alkyl caffeate ester in which 2-phenylethyl is the alkyl component. It has a role as an antineoplastic agent, an anti-inflammatory agent, an immunomodulator, a metabolite, an antioxidant, a neuroprotective agent, an antiviral agent and an antibacterial agent.

CAPE exhibits several properties such as anticarcinogenic, immunomodulatory activities, antioxidant, antiviral, anti-inflammatory, hypoglycaemic effect, cardioprotective and inhibits gastric secretion. It also has an inhibitory effect on fibroblasts growth factor type 2 (FGF-2), a tumor growth factor in breast cancer.

Caffeic acid (3,4-dihydroxycinnamic acid) phenethyl ester (CAPE) is a natural phenolcompound and an active component of propolis from honeybee hives. Torkiet al. (2017)investigated the effect of phosphatidylinositol 3-kinase/AKT/mammaliantarget of rapamycin (PI3K/Akt/mTOR) signaling pathway dual inhibitor, NVP-BEZ235,and CAPE on TNBC cell line (MDA-MB-231), stimulated withtransforming growth factor (TGF)-β1 for 14 days. CAPE in combination with NVP-BEZ235synergistically inhibited cell growth and reduced CXCR4 expression.Also, treatment of MDA-MB-231 cells with CAPE and NVP-BEZ235 time-dependentlyinhibited the expression of p-Forkhead Box O3a (FOXO3a). In a nutshell,these results indicate that tumour metastasis and progression in TNBC cellscan be effectively reduced through the concurrent use of NVP-BEZ235 and CAPE(Torki et al. 2017).

To a solution of (E)-4-(3-oxo-3-phenylethoxyprop-1-enyl)-1,2-phenylene diacetate (474 mg, 1.29 mmol, 1 equiv) in anhydrous THF (15 mL) was added pyrrolidine (catalytic amount). After stirring for 30 min at room temperature, water (10 mL) was added and the reaction mixture was extracted with EtOAc (20 mL). The combined organic layers were washed sequentially with 1N HCl (7 x 20 mL) and brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure to afford phenethyl 3-(3,4-dihydroxyphenyl)acrylate (CAPE 3) as a yellow powder (36.7 mg, 75% yield). The melting point of the product was 125.5 °C. TLC showed Rf = 0.75 (silica gel plate, 40% EtOAc/cyclohexane as unfolding agent).1H NMR (400 MHz, acetone-d6) δ 8.36 (br s, 1H), 8.08 (br s, 1H), 7.60 (d, J = 15.0 Hz, 1H), 7.40 (dd, J = 9.0, 2.0 Hz, 1H), 7.35-7.28 (m, 5H), 7.25 (d, J = 2.0 Hz, 1H), 7.20 (d, J = 9.0 Hz, 1H), 6.30 (d, J = 15.0 Hz, 1H), 4.35 (t, J = 7.0 Hz, 2H), 2.90 (t, J = 7.0 Hz, 2H).13C NMR (101 MHz, acetone-d6) δ 167.4, 148.9, 148.4, 145.9, 139.4, 129.9, 129.4, 127.7, 127.3, 122.6, 116.5, 115.6, 115.3, 65.4, 35.9.

Store at -20° C

1) Sudine et al. (1993) Caffeic acid phenethyl ester as a lipoxygenase inhibitor with antioxidant properties. FEBS Lett. 21 329 2) Natarajan et al. (1996) Caffeic acid phenethyl ester is a potent and specific inhibitor of activation of nuclear transcription factor NF-kappa B. Proc. Natl. Acad. Sci. USA 93 9090 3) Chiao et al. (1995). Apoptosis and altered redox state induced by caffeic acid phenethyl ester (CAPE) in transformed rat fibroblast cells; Cancer Res. 55 3576 4) Orban et.al. (2000), Caffeic acid phenethyl ester induces leukocyte apoptosis, modulates nuclear factor-kappa B and suppresses acute inflammation; Neuroimmunomodulation, 7 99