4-Methoxycinnamic acid ethyl ester (Ethyl p-methoxycinnamate) is an orally active natural compound found. 4-Methoxycinnamic acid ethyl ester exerts anti-inflammatory effects by inhibiting cyclooxygenase ( COX-1 ( IC50 = 1.12 μM) and COX-2 ( IC50 = 0.83 μM)), NF-κB ( IC50 = 88.7 μM) and cytokine production ( TNF-α ( IC50 = 96.84 μg/mL) and IL-1β ( IC50 = 166.4 μg/mL)). 4-Methoxycinnamic acid ethyl ester inhibits tumor cell proliferation, migration and cancer metabolism and induces apoptosis.4-Methoxycinnamic acid ethyl ester inhibits VEGF expression, thereby inhibiting angiogenesis. 4-Methoxycinnamic acid ethyl ester has a significant inhibitory effect on dengue virus and Mycobacterium tuberculosis. 4-Methoxycinnamic acid ethyl ester has analgesic effects in rats [1] [2] [3] [4] [5] [6] [7].
In Vivo, 4-Methoxycinnamic acid ethyl ester (100-800 mg/kg, i.g., single dose) inhibited paw edema in a dose-dependent manner in rats[4]. 4-Methoxycinnamic acid ethyl ester (200-800 mg/kg, i.g., once daily for 7 days) inhibits the formation of chronic granuloma in a dose-dependent manner in rats[2]. 4-Methoxycinnamic acid ethyl ester (200-800 mg/kg, i.g., single dose) prolongs the tail-flick latency of rats in a dose-dependent manner, showing a significant analgesic effect[2].
In Vitro, 4-Methoxycinnamic acid ethyl ester (25-200 μg/mL, 0-48 h) inhibits the growth of HUVECs with an IC50 of 160 μg/mL and suppresses the migration ability of HUVECs through VEGF[2]. 4-Methoxycinnamic acid ethyl ester (50-200 μg/mL, 6-24 h) dose-dependently impairs the ability of HUVECs to form tube-like structures on Matrigel[2]. 4-Methoxycinnamic acid ethyl ester (50-200 μg/mL, 5 d) significantly inhibits the sprouting and growth of microvessels from rat aortic rings[2]. 4-Methoxycinnamic acid ethyl ester (0.03-0.97 mM, 7 d) inhibits M. tuberculosis H37Ra, H37Rv, drug susceptible and multidrug resistant (MDR) clinical isolates (MIC: 0.242-0.485 mM) and is ineffective against common bacteria such as Mycobacterium smegmatis, Escherichia coli, and Staphylococcus aureus[3]. 4-Methoxycinnamic acid ethyl ester (50 μM, 12 h) significantly reduces the phosphorylation levels of p-p65 (Ser536) and p-Akt (Ser473) in melanoma cells[4]. 4-Methoxycinnamic acid ethyl ester (50 μM, 24 h) significantly inhibits the migration and invasion ability of melanoma cells[4]. 4-Methoxycinnamic acid ethyl ester (1-50 μM, 12-24 h) reverses the resistance of melanoma cells to Paclitaxel [4]. 4-Methoxycinnamic acid ethyl ester (125-500 μM, 24 h) exhibits broad-spectrum antiviral activity against all four dengue serotypes (DENV-1, DENV-2, DENV-3, DENV-4), with EC50 values of 22.58 and 6.17 μM for DENV-2 in HepG2 and A549 cells, respectively[5]. 4-Methoxycinnamic acid ethyl ester (100 μM, 1-24 h) inhibits de novo fatty acid synthesis, rather than glycolysis, to deplete ATP in ehrlich ascites cancer cells (EATCs)[6]. 4-Methoxycinnamic acid ethyl ester (48 h) shows moderate cytotoxicity against MCF-7, HT-29, HCT-116 (IC50 = 42.1 μg/mL), U-937, PC-3 (IC50 = 39 μg/mL), K-562 cells[7]. 4-Methoxycinnamic acid ethyl ester (50-200 μg/mL, 12-48 h) inhibits cell migration and induces apoptosis via the mitochondrial pathway in HCT-116 cells[7]. 4-Methoxycinnamic acid ethyl ester (200 μg/mL, 8 h) significantly activates all tested caspases, including Caspase-9, Caspase-8, and Caspase-3/7 in HCT-116 cells[7].
References:
[1]. Umar MI, et al. Bioactivity-Guided Isolation of Ethyl-p-methoxycinnamate, an Anti-inflammatory Constituent, from Kaempferia galanga L. Extracts. Molecules. 2012 Jul 23;17(7):8720-34.
[2]. Umar MI, et al. Ethyl-p-methoxycinnamate isolated from Kaempferia galanga inhibits inflammation by suppressing interleukin-1, tumor necrosis factor-α, and angiogenesis by blocking endothelial functions. Clinics (Sao Paulo). 2014 Feb;69(2):134-44.
[3]. Lakshmanan D, et al. Ethyl p-methoxycinnamate isolated from a traditional anti-tuberculosis medicinal herb inhibits drug resistant strains of Mycobacterium tuberculosis in vitro. Fitoterapia. 2011 Jun;82(4):757-61.
[4]. Lallo S, et al. Ethyl P-Methoxycinnamate: An Active Anti-Metastasis Agent and Chemosensitizer Targeting NFKB from Kaempferia galanga for Melanoma Cells. Life (Basel). 2022 Mar 24;12(4):337.
[5]. Tarasuk M, et al. Dual action effects of ethyl-p-methoxycinnamate against dengue virus infection and inflammation via NF-kB pathway suppression. Sci Rep. 2024 Apr 23;14(1):9322.
[6]. Sasaki Y, et al. Ethyl p-methoxycinnamate inhibits tumor growth by suppressing fatty acid synthesis and depleting ATP. Sci Rep. 2025 May 2;15(1):15317.
[7]. Umar MI, et al. Cytotoxic and Pro-Apoptotic Properties of Ethyl-p-Methoxycinnamate and Its Hydrophilic Derivative Potassium-p-Methoxycinnamate. Chemistry Africa. 2018 Jul 31;1(1-2):87-95.
In Vivo, 4-Methoxycinnamic acid ethyl ester (100-800 mg/kg, i.g., single dose) inhibited paw edema in a dose-dependent manner in rats[4]. 4-Methoxycinnamic acid ethyl ester (200-800 mg/kg, i.g., once daily for 7 days) inhibits the formation of chronic granuloma in a dose-dependent manner in rats[2]. 4-Methoxycinnamic acid ethyl ester (200-800 mg/kg, i.g., single dose) prolongs the tail-flick latency of rats in a dose-dependent manner, showing a significant analgesic effect[2].
In Vitro, 4-Methoxycinnamic acid ethyl ester (25-200 μg/mL, 0-48 h) inhibits the growth of HUVECs with an IC50 of 160 μg/mL and suppresses the migration ability of HUVECs through VEGF[2]. 4-Methoxycinnamic acid ethyl ester (50-200 μg/mL, 6-24 h) dose-dependently impairs the ability of HUVECs to form tube-like structures on Matrigel[2]. 4-Methoxycinnamic acid ethyl ester (50-200 μg/mL, 5 d) significantly inhibits the sprouting and growth of microvessels from rat aortic rings[2]. 4-Methoxycinnamic acid ethyl ester (0.03-0.97 mM, 7 d) inhibits M. tuberculosis H37Ra, H37Rv, drug susceptible and multidrug resistant (MDR) clinical isolates (MIC: 0.242-0.485 mM) and is ineffective against common bacteria such as Mycobacterium smegmatis, Escherichia coli, and Staphylococcus aureus[3]. 4-Methoxycinnamic acid ethyl ester (50 μM, 12 h) significantly reduces the phosphorylation levels of p-p65 (Ser536) and p-Akt (Ser473) in melanoma cells[4]. 4-Methoxycinnamic acid ethyl ester (50 μM, 24 h) significantly inhibits the migration and invasion ability of melanoma cells[4]. 4-Methoxycinnamic acid ethyl ester (1-50 μM, 12-24 h) reverses the resistance of melanoma cells to Paclitaxel [4]. 4-Methoxycinnamic acid ethyl ester (125-500 μM, 24 h) exhibits broad-spectrum antiviral activity against all four dengue serotypes (DENV-1, DENV-2, DENV-3, DENV-4), with EC50 values of 22.58 and 6.17 μM for DENV-2 in HepG2 and A549 cells, respectively[5]. 4-Methoxycinnamic acid ethyl ester (100 μM, 1-24 h) inhibits de novo fatty acid synthesis, rather than glycolysis, to deplete ATP in ehrlich ascites cancer cells (EATCs)[6]. 4-Methoxycinnamic acid ethyl ester (48 h) shows moderate cytotoxicity against MCF-7, HT-29, HCT-116 (IC50 = 42.1 μg/mL), U-937, PC-3 (IC50 = 39 μg/mL), K-562 cells[7]. 4-Methoxycinnamic acid ethyl ester (50-200 μg/mL, 12-48 h) inhibits cell migration and induces apoptosis via the mitochondrial pathway in HCT-116 cells[7]. 4-Methoxycinnamic acid ethyl ester (200 μg/mL, 8 h) significantly activates all tested caspases, including Caspase-9, Caspase-8, and Caspase-3/7 in HCT-116 cells[7].
References:
[1]. Umar MI, et al. Bioactivity-Guided Isolation of Ethyl-p-methoxycinnamate, an Anti-inflammatory Constituent, from Kaempferia galanga L. Extracts. Molecules. 2012 Jul 23;17(7):8720-34.
[2]. Umar MI, et al. Ethyl-p-methoxycinnamate isolated from Kaempferia galanga inhibits inflammation by suppressing interleukin-1, tumor necrosis factor-α, and angiogenesis by blocking endothelial functions. Clinics (Sao Paulo). 2014 Feb;69(2):134-44.
[3]. Lakshmanan D, et al. Ethyl p-methoxycinnamate isolated from a traditional anti-tuberculosis medicinal herb inhibits drug resistant strains of Mycobacterium tuberculosis in vitro. Fitoterapia. 2011 Jun;82(4):757-61.
[4]. Lallo S, et al. Ethyl P-Methoxycinnamate: An Active Anti-Metastasis Agent and Chemosensitizer Targeting NFKB from Kaempferia galanga for Melanoma Cells. Life (Basel). 2022 Mar 24;12(4):337.
[5]. Tarasuk M, et al. Dual action effects of ethyl-p-methoxycinnamate against dengue virus infection and inflammation via NF-kB pathway suppression. Sci Rep. 2024 Apr 23;14(1):9322.
[6]. Sasaki Y, et al. Ethyl p-methoxycinnamate inhibits tumor growth by suppressing fatty acid synthesis and depleting ATP. Sci Rep. 2025 May 2;15(1):15317.
[7]. Umar MI, et al. Cytotoxic and Pro-Apoptotic Properties of Ethyl-p-Methoxycinnamate and Its Hydrophilic Derivative Potassium-p-Methoxycinnamate. Chemistry Africa. 2018 Jul 31;1(1-2):87-95.