- Synthesis, Antibacterial Evaluation, and QSAR of Caffeic Acid Derivatives
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The present study evaluates the antibacterial effects of a set of 16 synthesized caffeic acid ester derivatives against strains of Staphylococcus aureus and Escherichia coli, as well as discusses their structure-activity relationship (SAR). The antibacterial assays were performed using microdilution techniques in 96-well microplates to determine minimal inhibitory concentration (MIC). The results revealed that five of the compounds present strong to optimum antibacterial effect. Of the sixteen ester derivatives evaluated, the products with alkyl side chains, as propyl caffeate (3), butyl caffeate (6), and pentyl caffeate (7), presented the best antibacterial activity with MIC values of around 0.20 μM against Escherichia coli and only butyl caffeate (6) showing the same MIC against Staphylococcus aureus. For products with aryl substituents, the best MIC results against the tested strain of Escherichia coli were 0.23 μM for (di-(4-chlorobenzyl)) caffeate (13) and 0.29 μM for diphenylmethyl caffeate (10) and all were less active against the Staphylococcus aureus strain. Preliminary quantitative structure-activity relationship (QSAR) analyses confirmed that certain structural characteristics, such as a median linear carbon chain and the presence of electron withdrawal substituents at the para position of the aromatic ring, help potentiate antibacterial activity.
- Araújo, Marianna O.,Freire Pessoa, Hilzeth L.,Lira, Andressa B.,Castillo, Yunierkis P.,De Sousa, Dami?o P.
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- New Hydroxycinnamic Acid Esters as Novel 5-Lipoxygenase Inhibitors That Affect Leukotriene Biosynthesis
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Leukotrienes are inflammatory mediators that actively participate in the inflammatory response and host defense against pathogens. However, leukotrienes also participate in chronic inflammatory diseases. 5-lipoxygenase is a key enzyme in the biosynthesis
- Boudreau, Luc H.,Lassalle-Claux, Grégoire,Cormier, Marc,Blanchard, Sébastien,Doucet, Marco S.,Surette, Marc E.,Touaibia, Mohamed
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- Design and synthesis of novel aspirin-caffeic acid ester hybrids for cardioprotection with reduced risk of hemorrhagic stroke
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A series of novel aspirin-caffeic acid ester hybrids for cardioprotection with reduced risk of hemorrhagic stroke were designed and synthesized by coupling aspirin and caffeic acid esters inspired by NCX-4016. The synthesized compounds were evaluated for
- Shi, Zhi-Hao,Li, Nian-Guang,Tang, Yu-Ping,Shi, Qian-Ping,Zhang, Wei,Zhang, Peng-Xuan,Dong, Ze-Xi,Li, Wei,Duan, Jin-Ao
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p. 1342 - 1346
(2016/06/13)
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- A rapid and practical catalytic esterification for the preparation of caffeic acid esters
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A convenient and practical catalytic method for the preparation of caffeic acid esters is reported. This esterification was carried out with high efficiency in the presence of ytterbium triflate in nitromethane without any other auxiliary reagents. The wide scope of application and especially the higher reactivity and more convenient procedure than previous methods make it a valuable application for the synthesis of caffeic acid esters and other cinnamic acid esters.
- Xie, Dongsheng,Yang, Fengzhi,Xie, Jin,Zhang, Man,Liu, Wenlu,Fu, Lei
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p. 695 - 700
(2015/02/05)
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- Antihypertensive effect of caffeic acid and its analogs through dual renin-angiotensin-aldosterone system inhibition
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Hypertension is a crucial risk factor for cardiovascular diseases and contributes to one third of global mortality. In addition to conventional antihypertensive drugs such as captopril, naturally occurring phytochemicals and their analogs are used for red
- Bhullar, Khushwant S.,Lassalle-Claux, Grégoire,Touaibia, Mohamed,Vasantha Rupasinghe
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p. 125 - 132
(2014/04/17)
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- Antiproliferative, antiandrogenic and cytotoxic effects of novel caffeic acid derivatives in LNCaP human androgen-dependent prostate cancer cells
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Caffeic acid and its naturally occurring derivative caffeic acid phenethyl ester (CAPE) have antiproliferative and cytotoxic properties in a variety of cancer cell lines without displaying significant toxicity toward healthy cells, and are considered to be potential anticancer agents. However, little is known about their effects on prostate cancer cells. We synthesized and evaluated the effects of caffeic acid, CAPE (2) and 18 synthetic derivatives on cell viability and androgen-dependent cell proliferation, subcellular localisation and expression of androgen receptor (AR) and secretion of prostate-specific antigen (PSA) in LNCaP human hormone-dependent prostate cancer cells. Several synthetic derivatives of CAPE were strong, concentration-dependent cytotoxic agents in LNCaP cells with IC50 values in the 6.8-26.6 μM range, potencies that were up to five-fold greater than that of CAPE (33.7 ± 4.0 μM). A number of caffeic acid derivatives were inhibitors of androgen-stimulated LNCaP cell proliferation with concomitant inhibition of DHT-stimulated PSA secretion. Compound 24 was the most cytotoxic and antiproliferative caffeic acid derivative (IC50 values of 6.8 ± 0.3 and 2.4 ± 0.8 μM, respectively) inhibiting DHT-stimulated cell proliferation and PSA secretion statistically significantly at concentrations as low as 0.3 μM. Exposure to DHT increased cytoplasmic and nuclear AR levels and co-treatment with increasing concentrations of compound 24 or CAPE (2), notably, further increased these levels. In conclusion, a number of synthetic derivatives of caffeic acid are potent inhibitors of androgen-dependent prostate cancer cell proliferation and viability, acting, at least in part, via an antiandrogenic mechanism that involves increased nuclear accumulation of (presumably inactive) AR.
- Sanderson, J. Thomas,Clabault, Hélène,Patton, Cody,Lassalle-Claux, Grégoire,Jean-Fran?ois, Jacques,Paré, Aurélie F.,Hébert, Martin J.G.,Surette, Marc E.,Touaibia, Mohamed
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p. 7182 - 7193
(2013/11/06)
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- Design, synthesis, and preliminary evaluation of substituted cinnamic acid esters as selective matrix metalloproteinase inhibitors
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Strategy, Management and Health Policy Preclinical Research Substituted cinnamic acid esters with extended P1' groups were synthesized using microwave irradiation and tested for their inhibitory activities on matrix metalloproteinase (MMP)-1, MMP-2, and MMP-9. Preliminary structure-activity relationship analysis and docking studies showed that hydroxyl groups in the benzene ring and the presence of extended spatial structures in the carboxylic acid played key roles in the MMP-2 and MMP-9 inhibitory activity and selectivity over MMP-1.
- Shi, Zhi-Hao,Li, Nian-Guang,Shi, Qian-Ping,Hao-Tang,Tang, Yu-Ping
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p. 317 - 324,8
(2020/07/30)
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- Biological activity evaluation and structure-activity relationships analysis of ferulic acid and caffeic acid derivatives for anticancer
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The anticancer activities of alkyl esters and NO-donors of ferulic acid (FA) and caffeic acid (CA) were assessed by a high-throughout screening (HTS) method, and the structure-activity relationships were described. CA alkyl esters had better anticancer activities than FA alkyl esters with the same alkyl substituent. Mono-nitrates and phenylfuroxan nitrates were more potent than the dual nitrates. Phenylsulfonylfuroxan nitrates of FA, especially compounds 8b-8d, exhibited more potent activities in anticancer.
- Li, Weixia,Li, Nianguang,Tang, Yuping,Li, Baoquan,Liu, Li,Zhang, Xu,Fu, Haian,Duan, Jin-Ao
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p. 6085 - 6088
(2012/10/29)
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- Antinociceptive properties of caffeic acid derivatives in mice
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Ten ester derivatives from caffeic acid were synthesized, and their antinociceptive properties are evaluated in mice. The most active compound, dodecyl ester derivative, exhibited potent and dose-related activity against the writhing test, with a calculated ID50 value of 15.1 (11.9-19.1) μmol/kg and MI of 78.8% being several times more active than reference drugs. It was also effective in other experimental models, such as formalin, capsaicin and glutamate-induced pain tests, but was inactive in the hot-plate test. Although the mechanism of action has still not been elucidated, these results appear to support its therapeutic potential against painful diseases.
- de Campos Buzzi, Fatima,Franzoi, Caroline Liandra,Antonini, Graziele,Fracasso, Mauricio,Filho, Valdir Cechinel,Yunes, Rosendo Augusto,Niero, Rivaldo
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experimental part
p. 4596 - 4602
(2009/12/26)
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- Impact of alkyl esters of caffeic and ferulic acids on tumor cell proliferation, cyclooxygenase enzyme, and lipid peroxidation
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The antioxidant ferulic and caffeic acid phenolics are ubiquitous in plants and abundant in fruits and vegetables. We have synthesized a series of ferulic and caffeic acid esters and tested for tumor cell proliferation, cyclooxygenase enzymes (COX-1 and -2) and lipid peroxidation inhibitory activities in vitro. In the tumor cell proliferation assay, some of these esters showed excellent growth inhibition of colon cancer cells. Among the phenolics esters assayed, compounds 10 (C12-caffeate), 11 (C16-caffeate), 21 (C 8-ferulate), and 23 (C12-ferulate) showed strong growth inhibition with IC50 values of 16.55, 13.46, 18.67, and 7.57 μg/mL in a breast cancer cell line; 9.65, 7.45, 17.05, and 4.35 μg/ mL in a lung cancer cell line; 5.78, 3.5, 4.29, and 2.46 μg/mL in a colon cancer cell line; 12.04, 12.21, 14.63, and 8.09 μg/ mL in a central nervous system cancer cell line; and 8.62, 7.76, 11.0, and 5.37 in a gastric cancer cell line. In COX enzyme inhibitory assays, ferulic and caffeic acid esters significantly inhibited both COX-1 and COX-2 enzymes. Caffeates 5-10 (C4-C 12), inhibited COX-1 enzyme between 50% and 90% and COX-2 enzyme by about 70%, whereas ferulates 15-21 (C3-C8) inhibited COX-1 and COX-2 enzymes by 85-95% 25 μg/mL. Long-chain caffeates 11-14 (C 16-C22) and short-chain ferulates 15-20 (C 3-C5) were the most active in lipid peroxidation inhibition and showed 60-70% activity at 5 μg/mL concentration.
- Jayaprakasam, Bolleddula,Vanisree, Mulabagal,Zhang, Yanjun,Dewitt, David L.,Nair, Muraleedharan G.
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p. 5375 - 5381
(2008/04/03)
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