104594-70-9

Basic information

• Product Name: Phenethyl caffeate
• Synonyms: Caffeic Acid 2-Phenylethyl Ester;CAFFEIC ACID PHENETHYLESTER (CAPE);CAPE,PhenethylCaffeate;CAFFEIC ACID PHENETHYL ESTER(CAPE)(P);KAFFEESUREPHENYLETHYLESTER;CAFFEICACIDPHENYLETHERESTER;3-(3,4-Dihydroxyphenyl)-2-propenoic acid 2-phenylethyl ester;Cafestol Acid Phenethyl Ester
• CAS NO: 104594-70-9
• Molecular Formula: C₁₇H₁₆O₄
• Molecular Weight: 284.31
• EINECS: 1592732-453-0
• Product Categories: Miscellaneous Natural Products;Inhibitors;Tyrosine Kinase Inhibitors;Cytokine signaling;HIV/AIDS/Related Products;Apoptosis Inducers
• Mol File: 104594-70-9.mol

Chemical Properties

• Melting Point: 127-129℃
• Boiling Point: 498.6 °C at 760 mmHg
• Flash Point: 185.1 °C
• Appearance: off-white/
• Density: 1.266 g/cm³
• Vapor Pressure: 1.45E-10mmHg at 25°C
• Refractive Index: 1.645
• Storage Temp.: Store at 0°C
• Solubility: Soluble in ethyl acetate at 50mg/ml. Soluble in DMSO and ethanol
• PKA: 8.46±0.20(Predicted)
• Sensitive: Light Sensitive
• Stability: Stable for 2 years from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20° for up to 1 month.
• CAS DataBase Reference: Phenethyl caffeate(CAS DataBase Reference)
• NIST Chemistry Reference: Phenethyl caffeate(104594-70-9)
• EPA Substance Registry System: Phenethyl caffeate(104594-70-9)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38-38-37-36
• Safety Statements: 26-36
• WGK Germany: 3
• RTECS: UD3334375
• Hazardous Substances Data: 104594-70-9(Hazardous Substances Data)

Usage

Uses

Phenethyl caffeate is used as an anti-cancer agent for its cytotoxic effects against cancer cell lines. It inhibits the proliferation of transformed cells and induces apoptosis in transformed fibroblasts, making it a promising candidate for cancer treatment.
Used in Pharmaceutical Industry:
Phenethyl caffeate is used as an anti-inflammatory agent for its ability to significantly suppress the lipoxygenase pathway of arachidonic acid metabolism during inflammation. This property makes it a potential candidate for the development of new anti-inflammatory drugs.
Phenethyl caffeate is used as an immunomodulator for its potential to modulate the immune system, which can be beneficial in the treatment of various immune-related disorders.
Phenethyl caffeate is used as an NF-kB blocker for its ability to specifically inhibit the nuclear transcription factor, NF-kB, which plays a crucial role in various cellular processes, including inflammation and cancer.
Used in Anticancer Applications:
Phenethyl caffeate is employed as an antineoplastic agent, targeting various cancer cell lines and exhibiting cytotoxic effects. It also inhibits ornithine decarboxylase and protein tyrosine kinase, further contributing to its potential as a cancer treatment option.

Biological Activity

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.

Contact allergens

Capee is one of the allergens of propolis (bee glue). It is also contained in poplar bud secretions.

Biochem/physiol Actions

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.

Anticancer Research

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).

References

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

InChI:InChI=1/C17H16O4/c18-15-8-6-14(12-16(15)19)7-9-17(20)21-11-10-13-4-2-1-3-5-13/h1-9,12,18-19H,10-11H2/b9-7+

Upstream product

• 60-12-8 2-phenylethanol 
• 331-39-5 caffeic acid 
• 77201-71-9 (E)-3-(3,4-dihydroxyphenyl)acryloyl chloride 
• 118971-54-3 (E)-4-(3-oxo-3-phenethoxyprop-1-enyl)-1,2-phenylene diacetate 
• 88623-81-8 3,4-diacetoxycinnamic acid 
• 103-82-2 phenylacetic acid 
• 92778-42-2 malonic acid di(2-phenylethyl) ester 
• 139-85-5 3,4-dihydroxybenzaldehyde 
• 848598-50-5 malonic acid monophenethyl ester 
• 103-63-9 1-phenyl-2-bromoethane 
• 538-75-0 dicyclohexyl-carbodiimide 
• 621-59-0 isovanillin 

Related news

Phenethyl caffeate (cas 104594-70-9) benzo[kl]xanthene lignan with DNA interacting properties induces DNA damage and apoptosis in colon cancer cells08/17/2019

AimsPhenethyl caffeate benzoxanthene lignan (PCBL) is a synthetic compound with DNA interacting, antiangiogenic, antiproliferative and tumor cell death inducing abilities. Though PCBL exhibits the qualities of a prospective antitumor agent, the basic mechanism of PCBL induced cell death remains ...detailed

Relevant articles and documents

Development of blood-brain barrier permeable nitrocatechol-based catechol O-methyltransferase inhibitors with reduced potential for hepatotoxicity

Recent efforts have been focused on the development of centrally active COMT inhibitors, which can be valuable assets for neurological disorders such as Parkinson's disease, due to the severe hepatotoxicity risk associated with tolcapone. New nitrocatechol COMT inhibitors based on naturally occurring caffeic acid and caffeic acid phenethyl ester were developed. All nitrocatechol derivatives displayed potent inhibition of peripheral and cerebral COMT within the nanomolar range. Druglike derivatives 13, 15, and 16 were predicted to cross the blood-brain barrier in vitro and were significantly less toxic than tolcapone and entacapone when incubated at 50 μM with rat primary hepatocytes. Moreover, their unique acidity and electrochemical properties decreased the chances of formation of reactive quinone-imines and, as such, the potential for hepatotoxicity. The binding mode of 16 confirmed that the major interactions with COMT were established via the nitrocatechol ring, allowing derivatization of the side chain for future lead optimization efforts.

Synthesis and characterization of CAPE derivatives as xanthine oxidase inhibitors with radical scavenging properties

Inhibitors of the enzyme xanthine oxidase (XO) with radical scavenging properties hold promise as novel agents against reperfusion injuries after ischemic events. By suppressing the formation of damaging reactive oxygen species (ROS) by XO or scavenging ROS from other sources, these compounds may prevent a buildup of ROS in the aftermath of a heart attack or stroke. To combine these two properties in a single molecule, we synthesized and characterized the non-purine XO inhibitor caffeic acid phenethylester (CAPE) and 19 derivatives using a convenient microwave-assisted Knoevenagel condensation protocol. Varying systematically the number and positions of the hydroxyl groups at the two phenyl rings, we derived structure-activity relationships based on experimentally determined XO inhibition data. Molecular docking suggested that critical enzyme/inhibitor interactions involved π-π interactions between the phenolic inhibitor ring and Tyr914, hydrogen bonds between inhibitor hydroxyl groups and Glu802, and hydrophobic interactions between the CAPE phenyl ring and non-polar residues located at the entrance of the binding site. To effectively scavenge the stable radical DPPH, two hydroxyl groups in 1,2- or 1,4-position at the phenyl ring were required. Among all compounds tested, E-phenyl 3-(3,4-dihydroxyphenyl)acrylate, a CAPE analog without the ethyl tether, showed the most promising properties.

Caffeic acid phenethyl ester (CAPE): Synthesis and X-ray crystallographic analysis

The structure of caffeic acid phenethyl ester [2-propenoic acid, 3-(3,4-dihydroxyphenyl)-, 2-phenethyl ester] (1), C17H16O4·1/2C6H 6, synthesized by base-catalyzed alkylation of caffeic acid salt with

Caffeic acid phenethyl ester (CAPE)-derivatives act as selective inhibitors of acetylcholinesterase

Unexpected inhibitory effects against eeAChE could be found for a newly synthesized class of caffeic acid phenethyl ester (CAPE)derivatives. Thus, phenethyl-(E)-3-(3,5-dimethoxy-4-phenethoxyphenyl)-acrylate (Ki = 1.97 ± 0.38 μM, Ki′ = 2.44 ± 0.07 μM)and 4-(2-(((E)-3-(3,4-bis(benzyloxy)phenyl)acryloyl)oxy)ethyl)-1,2-phenylene (2E,2′E)-bis(3-(3,4-bis(benzyloxy)phenyl)acrylate)(Ki = 0.72 ± 0.31 μM, Ki′ = 1.80 ± 0.21 μM)showed very good inhibition of eeAChE, while being non cytotoxic for malignant human cancer cells and non-malignant mouse fibroblasts. Also, they are weak inhibitors for BChE (from equine serum).

Synthesis of Diverse Hydroxycinnamoyl Phenylethanoid Esters Using Escherichia coli

Caffeic acid phenethyl ester (CAPE) is an ester of a hydroxycinnamic acid (phenylpropanoid) and a phenylethanoid (2-phenylethanol; 2-PE), which has long been used in traditional medicine. Here, we synthesized 54 hydroxycinnamic acid-phenylethanoid esters by feeding 64 combinations of hydroxycinnamic acids and phenylethanols to Escherichia coli harboring the rice genes OsPMT and Os4CL. The same approach was applied for ester synthesis with caffeic acid and eight different phenyl alcohols. Two hydroxycinnamoyl phenethyl esters, p-coumaroyl tyrosol and CAPE, were also synthesized from glucose using engineered E. coli by introducing genes for the synthesis of substrates. Consequently, we synthesized approximately 393.4 mg/L p-coumaroyl tyrosol and 23.8 mg/L CAPE with this approach. Overall, these findings demonstrate that the rice PMT and 4CL proteins can be used for the synthesis of diverse hydroxycinnamoyl phenylethanoid esters owing to their promiscuity and that further exploration of the biological activities of these compounds is warranted.

Catechol-based inhibitors of bacterial urease

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Antiproliferative activity and SARs of caffeic acid esters with mono-substituted phenylethanols moiety

A series of CAPE derivatives with mono-substituted phenylethanols moiety were synthesized and evaluated by MTT assay on growth of 4 human cancer cell lines (Hela, DU-145, MCF-7 and ECA-109). The substituent effects on the antiproliferative activity were systematically investigated for the first time. It was found that electron-donating and hydrophobic substituents at 2′-position of phenylethanol moiety could significantly enhance CAPE's antiproliferative activity. 2′-Propoxyl derivative, as a novel caffeic acid ester, exhibited exquisite potency (IC50?=?0.4?±?0.02 & 0.6?±?0.03?μM against Hela and DU-145 respectively).

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A series of cinnamic acid derivatives, amides (1–12) and esters (13–22), were synthesized, and structure–activity relationships for antioxidant activity, and monoamine oxidases (MAO) A and B, acetylcholinesterase, and butyrylcholinesterase (BChE) inhibitory activities were analyzed. Among the synthesized compounds, compounds 1–10, 12–18, and rosmarinic acid (23), which contained catechol, o-methoxyphenol or 5-hydroxy-indole moieties, showed potent 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity. Compounds 9–11, 15, 17–22 showed potent and selective MAO-B inhibitory activity. Compound 20 was the most potent inhibitor of MAO-B. Compounds 18 and 21 showed moderate BChE inhibitory activity. In addition, compound 18 showed potent antioxidant activity and MAO-B inhibitory activity. In a comparison of the cinnamic acid amides and esters, the amides exhibited more potent DPPH free radical scavenging activity, while the esters showed stronger inhibitory activities against MAO-B and BChE. These results suggested that cinnamic acid derivatives such as compound 18, p-coumaric acid 3,4-dihydroxyphenethyl ester, and compound 20, p-coumaric acid phenethyl ester, may serve as lead compounds for the development of novel MAO-B inhibitors and candidate lead compounds for the prevention or treatment of Alzheimer’s disease.

Crystal form II of caffeic acid phenethyl ester, and preparation method and use thereof

The invention provides a crystal form II of caffeic acid phenethyl ester, and a preparation method and a use thereof. The caffeic acid phenethyl ester has a structure represented by formula I, and diffraction peaks represented by 2theta diffraction angles of 6.199 DEG, 18.439 DEG, 22.560 DEG, 26.481 DEG and 30.721 DEG exist in an X-ray powder diffraction map of the crystal form II radiated with CuKalpha. The novel crystal form has a better stability than other forms. The preparation method of the novel crystal form has the characteristics of simple process, high yield and good stability.

A rapid and practical catalytic esterification for the preparation of caffeic acid esters

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