- Synthesis and characterization of CAPE derivatives as xanthine oxidase inhibitors with radical scavenging properties
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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.
- Choi, Wonbeen,Villegas, Valente,Istre, Hannah,Heppler, Ben,Gonzalez, Niki,Brusman, Nicole,Snider, Lindsey,Hogle, Emily,Tucker, Janelle,O?ate, Alma,O?ate, Sandra,Ma, Lili,Paula, Stefan
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p. 686 - 695
(2019/03/05)
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- Optimizing the efficiency of antioxidants in emulsions by lipophilization: Tuning interfacial concentrations
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Optimization of the efficiency of antioxidants, AOs, in lipid-based emulsions via chemical modifications of their reactive moieties is not always possible because of the inherent experimental difficulties and because of the regulatory status of AOs. Esterification of hydrophilic AOs may be a practical, convenient, alternative approach. Here we employed a series of caffeic acid derivatives bearing the same reactive moiety but of different hydrophobicity (alkyl chain lengths of 1 to 16 carbon atoms) to investigate the effects of hydrophobicity on the oxidative stability of stripped corn oil-in-water emulsions. AO efficiency was determined by monitoring the production of primary oxidation products (conjugated dienes) with time and a non-linear, parabolic-like, variation of their efficiency with the number of C atoms in their alkyl chain, with a maximum at the C8 derivative, found. To rationalize the results, we also determined the distribution of the AOs between the oil, interfacial and aqueous regions of the same emulsions by employing a recently developed kinetic method that provides the partition constants of the AO between the oil-interfacial, PIO, and water-interfacial, PIW, regions of the intact emulsions. Values of both PIO and PIW range between 180-2000, suggesting that the transfer of the AOs to the interfacial region is spontaneous. The results indicate that the variations of both the percentage of AO in the interfacial region, % AOI, of the emulsions and the AO efficiency with the number of C atoms in the AO alkyl chain parallel each other with a maxima at the C8 derivative. The results illustrate an effective and convenient way to control lipid oxidation by modulation of the hydrophobicity (HLB) of the AOs. An increase in the alkyl chain length of the AOs promote their incorporation into the interfacial region of emulsions but only up to a critical chain length, after which a further increase makes their efficiency decrease as a consequence of the decrease in their % AOI.
- Costa, Marlene,Losada-Barreiro, Sonia,Paiva-Martins, Fátima,Bravo-Díaz, Carlos
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p. 91483 - 91493
(2016/10/09)
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- Synthesis and antitumor activity of feruloyl and caffeoyl derivatives This paper is dedicated to Prof. Wei-xiao Hu for his lifelong commitment to mentoring graduate students
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We developed two efficient protocols for the synthesis of feruloyl and caffeoyl derivatives from commercial vanillin and veratraldehyde. Pharmacological activities were assessed against a panel of human cancer cell lines in vitro. Most synthesized compounds demonstrated attractive cytotoxicity. Several new compounds demonstrated significant antiproliferative and cytotoxic activities against HeLa and Bewo tumor cell lines. In particular, 5-nitro caffeic adamantyl ester showed broad spectrum of tumor inhibition in 10 cell lines, and reduced tumor weight by 36.7% in vivo when administered at a dose of 40 mg kg-1.
- Chen, Hui-Zhen,Chen, You-Bao,Lv, Ya-Ping,Zeng, Fang,Zhang, Juan,Zhou, Yong-Lie,Li, Han-Bing,Chen, Li-Fei,Zhou, Bin-Jie,Gao, Jian-Rong,Xia, Chun-Nian
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supporting information
p. 4367 - 4371
(2015/02/06)
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- Efficient synthesis of dissymmetric malonic acid S, O -esters via monoalcoholysis of symmetric dithiomalonates under neutral conditions
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A novel method for the highly selective synthesis of dissymmetric S,O-malonates starting from symmetric diphenyl dithiomalonates under neutral conditions is described. The key step is the thermal formation of an acylketene, the stability of which would co
- Matsuo, Kazumasa,Shindo, Mitsuru
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supporting information; experimental part
p. 4406 - 4409
(2011/10/08)
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- Synthesis of trans-caffeate analogues and their bioactivities against HIV-1 integrase and cancer cell lines
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Forty caffeate analogues were synthesized via a convenient method starting from vanillin with moderate to good yields. The testing of biological activity of these compounds against HIV-1 integrase indicates that four compounds: bornyl caffeate, bornyl 2-nitrocaffeate, 5-nitrocaffeic acid and 5-nitrocaffeic acid phenethyl ester (5-nitroCAPE) possess a good HIV integrase inhibitory activity, IC50 19.9, 26.8, 25.0 and 13.5 μM, respectively. Twelve caffeate analogues were tested by MTT assay on growth of human hepatocellular carcinoma BEL-7404, human breast MCF-7 adenocarcinoma, human lung A549 adenocarcinoma and human gastric cancer BCG823 cell lines, respectively. And the best result is IC50 5.5 μM for CAPE against BEL-7404.
- Xia, Chun-nian,Li, Hai-bo,liu, Feng,Hu, Wei-xiao
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supporting information; experimental part
p. 6553 - 6557
(2009/09/06)
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- One-pot preparation of caffeic acid esters from 3,4-dihydroxybenzaldehyde
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A convenient one-pot process for preparing various esters of caffeic acid from 3,4-dihydroxybenzaldehyde has been developed. The alcohols or phenols react with Meldrum's acid to form malonic acid mono-esters, which, without separating, immediately react with 3,4-dihydroxybenzaldehyde to afford the desired esters in good yield. The 1H NMR data and X-ray diffraction analyses indicate that these α,β-unsaturated esters are in trans (E) form in accord with natural esters.
- Hu, Wei-Xiao,Xia, Chun-Nian,Wang, Guo-Hong,Zhou, Wei
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p. 586 - 588
(2007/10/03)
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- Synthesis of caffeic acid esters
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A new method for the preparation of caffeic acid esters was investigated. Ten caffeic acid esters were prepared by condensation of protocatechualdehyde with malonic acid mono-esters in moderate yield. Malonic acid mono-esters were prepared from the corresponding malonate di-esters. The conformations of compounds are trans (E) form.
- Xia, Chun-Nian,Hu, Wei-Xiao
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p. 332 - 334
(2007/10/03)
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- SELECTIVE MONOETHERIFICATION AND MONOESTERIFICATION OF DIOLS AND DIACIDS UNDER PHASE-TRANSFER CONDITIONS
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Research on the selectivity of etherification reactions of diols and esterification reactions of diacids by alkyl halides under phase-transfer catalysis has shown that under such conditions, selectivity of monoetherification increases in the order prim sec tert diols, though overall yield of monoether decreases from sec to tert diols.Monoesterification of diacids was accomplished with a high degree of selectivity.Optimal extraction of diols and diacids was found to correspond in general to chain lengths of around 5 carbons.This could mean that the complex formed between the catalyst and the anion to react is stabilized for certain carbon lengths by inner solvation in virtue of its spatial conformation.
- Zerda, Jaime de la,Barak, Gabriela,Sasson, Yoel
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p. 1533 - 1536
(2007/10/02)
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- Process for the preparation of 3,5-dihydrocarbyl-4-hydroxybenzylmalonic acid esters
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Esters of 3,5-dihydrocarbyl-4-hydroxybenzylmalonic acid are prepared by reacting a 2,6-dihydrocarbyl-4-halomethylphenol with an ester of a 1,3-dicarboxylic acid in the presence of an alkali or an alkaline earth metal hydride. The products are useful as antioxidants.
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