- Dietary phenolic acids and derivatives. Evaluation of the antioxidant activity of sinapic acid and its alkyl esters
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The action of sinapic acid and its alkyl esters as potential antioxidants has been investigated. For this purpose, a series of sinapic acid ester derivatives was synthesized and their antioxidant activities were evaluated using distinctive analytical meth
- Gaspar, Alexandra,Martins, Marta,Silva, Paulo,Garrido, E. Manuela,Garrido, Jorge,Firuzi, Omidreza,Miri, Ramin,Saso, Luciano,Borges, Fernanda
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- Structure–Activity Relationship Studies of New Sinapic Acid Phenethyl Ester Analogues Targeting the Biosynthesis of 5-Lipoxygenase Products: The Role of Phenolic Moiety, Ester Function, and Bioisosterism
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Sinapic acid is found in many edible plants and fruits, such as rapeseed, where it is the predominant phenolic compound. New sinapic acid phenethyl ester (SAPE) analogues were synthesized and screened as inhibitors of the biosynthesis of 5-lipoxygenase (5-LO) in stimulated HEK293 cells and polymorphonuclear leukocytes (PMNL). Inhibition of leukotriene biosynthesis catalyzed by 5-LO is a validated therapeutic strategy against certain inflammatory diseases and allergies. Unfortunately, the only inhibitor approved to date has limited clinical use because of its poor pharmacokinetic profile and liver toxicity. With the new analogues synthesized in this study, the role of the phenolic moiety, ester function, and bioisosterism was investigated. Several of the 34 compounds inhibited the biosynthesis of 5-LO products, and 20 compounds were 2–11 times more potent than zileuton in PMNL, which are important producers of 5-LO products. Compounds 5i (IC50: 0.20 μM), 5l (IC50: 0.20 μM), and 5o (IC50: 0.21 μM) bearing 4-trifluoromethyl, methyl, or methoxy substituent at meta-position of the phenethyl moiety were 1.5 and 11.5 times more potent than SAPE (IC50: 0.30 μM) and zileuton (IC50: 2.31 μM), respectively. Additionally, compound 9 (IC50: 0.27 μM), which was obtained after acetylation of the 4-hydroxyl of SAPE, was equivalent to SAPE and 8 times more active than zileuton. Furthermore, compound 20b (IC50: 0.27 μM) obtained after the bioisosteric replacement of the ester function of SAPE by the 1,2,4-oxadiazole heterocycle was equivalent to SAPE and 8 times more active than zileuton. Thus, this study provides a basis for the rational design of new molecules that could be developed further as anti 5-LO therapeutics.
- Blanchard, Sébastien,Chiasson, Audrey Isabel,Doiron, Jérémie A.,Faye, Diene Codou,Roy, Pierre-Philippe,Surette, Marc E.,Touaibia, Mohamed
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supporting information
p. 225 - 236
(2022/01/27)
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- Total Syntheses and Anti-inflammatory Activities of Syringin and Its Natural Analogues
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Syringin (1), a natural bioactive glucoside isolated from the root of Acanthopanax senticosus (Rupr. Maxim.) Harms, possesses significant anti-inflammatory activity. In this study, we have accomplished the total syntheses of syringin (1), along with its natural analogues 2-12, from a common starting material, syringaldehyde (13), in 4-8 steps with an overall yields of 11.8-61.3%. The anti-inflammatory activities of these compounds were determined against NO production in the LPS-stimulated RAW264.7 cells. Among them, compounds 1-5, 7, and 9 exhibited different levels of anti-inflammatory activity.
- Dong, Hongbo,Du, Weihong,He, Yujiao,Shi, Zheng,Wang, Yingying,Wu, Min
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supporting information
p. 2866 - 2874
(2021/11/12)
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- Profiling of the formation of lignin-derived monomers and dimers from: Eucalyptus alkali lignin
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Lignin is a renewable and the most abundant aromatic source that can be used for extensive chemicals and materials. Although approximately 50 million tons of lignin are produced annually as a by-product of the pulp and paper industry, it is currently underutilized. It is important to know the structural features of technical lignin when considering its application. In this work, we have demonstrated the formation of low-molecular-weight constituents from hardwood (Eucalyptus) lignin, which produces much more low-molecular-weight constituents than softwood (spruce) lignin, after a chemical pulping process, and analyzed the micromolecular compositions in the alkali lignin after fractionation by dichloromethane (DCM) extraction. By applying analytical methods (gel-permeation chromatography, 2D NMR and GC-MS) with the aid of evidence from authenticated compounds, a great treasure trove of lignin-derived phenolic compounds from Eucalyptus alkali lignin were disclosed. Except for some common monomeric products, as many as 15 new lignin-derived monomers and dimers including syringaglycerol, diarylmethane, 1,2-diarylethanes, 1,2-diarylethenes, (arylvinyl ether)-linked arylglycerol dimers and isomeric syringaresinols were identified in the DCM-soluble fraction. Regarding the formation and evolution of the Cα-condensed β-aryl ether structure, a novel route that is potentially responsible for the high content of β-1 diarylethenes and diarylethanes in the lignin low-molecular-weight fraction, in addition to the β-1 (spirodienone) pathway, was proposed. This work not only provides novel insights into the chemical transformation of S-G lignin during the alkali pulping process, but also discovered lignin-derived phenolic monomers and dimers that can potentially be used as raw materials in the chemical or pharmaceutical industries. This journal is
- Hu, Zhenhua,Li, Suxiang,Lu, Fachuang,Shi, Lanlan,Wang, Chen,Yue, Fengxia,Zhang, Han,Zhao, Chengke
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supporting information
p. 7366 - 7375
(2020/11/18)
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- Investigating isomer specific photoprotection in a model plant sunscreen
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Sinapate esters are used throughout the plant kingdom, for example in photoprotection from ultraviolet radiation. Sinapate esters are naturally produced in their E-isomeric form; however, upon exposure to ultraviolet radiation, photoisomerization drives Z-isomer formation. To elucidate the photoprotection capacity of E vs. Z forms of sinapate esters, we explore the photochemistry of the model system, Z-ethyl sinapate. Following a novel Z-ethyl sinapate synthesis, we demonstrate that photoprotection is isomer independent. This suggests that, regarding photoprotection, there were no evolutionary pressures for biosynthesis of either isomer.
- Horbury,Flourat,Greenough,Allais,Stavros
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supporting information
p. 936 - 939
(2018/02/07)
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- First total synthesis of a new phenylpropanoid glycoside: natural cytotoxic compound from Cirsium japonicum
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Phenylpropanoid glycoside compound 1, the natural anti-tumor compound isolated from the erial parts of Cirsium japonicum, was first totally synthesized using easily available materials in short, convenient route with overall yield of 13.9%.
- Dong, Hong-Bo,Hou, Ming,Ma, Wen-Bo,Zhang, Jing-Xia,Li, Zhe-Yu,Luo, Hong-Bing,Tang, Ke-Hui,Cao, Sheng-Hua
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- Anti selective glycolate aldol reactions of (: S)-4-isopropyl-1-[(R)-1-phenylethyl]imidazolidin-2-one: application towards the asymmetric synthesis of 8-4′-oxyneolignans
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The anti selective glycolate aldol reactions of (S)-4-isopropyl-1-[(R)-1-phenylethyl]imidazolidin-2-one auxiliary have been standardized with high yields and excellent diastereoselectivities on various substituted aryl, allyl and alkyl aldehydes. The optimized reaction conditions were employed for the stereoselective synthesis of oxyneolignans.
- Gangar, Mukesh,Ittuveetil, Avinash,Goyal, Sandeep,Pal, Anang,Harikrishnan,Nair, Vipin A.
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p. 102116 - 102126
(2016/11/09)
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- Discovery of neurotrophic agents based on hydroxycinnamic acid scaffold
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The number of people affected by neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease is rapidly increasing owing to the global increase in life expectancy. Small molecules with neurotrophic effects have great potential for management of these neurological disorders. In this study, different (C1–C12) alkyl ester derivatives of hydroxycinnamic acids (HCAs) were synthesized (a total of 30 compounds). The neurotrophic capacity of the test compounds was examined by measuring promotion of survival in serum-deprived conditions and enhancement of nerve growth factor (NGF)-induced neurite outgrowth in PC12 neuronal cells. p-Coumaric, ferulic, and sinapic acids and their esters did not alter cell survival, while caffeic acid and all its alkyl esters, especially decyl and dodecyl caffeate, significantly promoted neuronal survival at 25?μm. Methyl, ethyl, propyl, and butyl caffeate esters also significantly enhanced NGF-induced neurite outgrowth, among which the most effective ones were propyl and butyl esters, which at 5?μm led to 25- and 22-fold increases in the number of neurites, respectively. The findings of the docking study suggested phosphatidylinositol 3-kinase (PI3K) as the potential molecular target. In conclusion, our findings demonstrate that alkyl esters of caffeic acid can be useful as scaffolds for the discovery of therapeutic agents for neurodegenerative diseases.
- Hosseini, Razieh,Moosavi, Fatemeh,Rajaian, Hamid,Silva, Tiago,Magalh?es e Silva, Diogo,Soares, Pedro,Saso, Luciano,Edraki, Najmeh,Miri, Ramin,Borges, Fernanda,Firuzi, Omidreza
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p. 926 - 937
(2016/11/11)
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- Ligustrazine derivatives. Part 5: Design, synthesis and biological evaluation of novel ligustrazinyloxy-cinnamic acid derivatives as potent cardiovascular agents
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A series of novel ligustrazinyloxy-cinnamic acid derivatives were designed, synthesized and evaluated for their inhibitory effect on adenosine diphosphate (ADP)-induced platelet aggregation in vitro, and also assayed for their protective effect against hydrogen peroxide (H2O2)-induced oxidative damage on ECV-304 cells. Some compounds exhibited high activity in one or both of the assays, of which, compound 2e displayed the highest protective effect on the proliferation of the damaged ECV-304 cells (EC 50 = 0.020 mM), and compound 2f was the most active anti-platelet aggregation agent (EC50 = 0.054 mM). Structure-activity relationships were briefly discussed.
- Chen, Hongfei,Li, Guoning,Zhan, Peng,Liu, Xinyong
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experimental part
p. 5609 - 5615
(2012/01/03)
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- PHENYLALKANOIC ACID AND PHENYLOXYALKANOIC ACID DERIVATIVES AS HPPAR ACTIVATORS
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The present invention provides a compound of formula (I):wherein:R1 and R2 are independently H or C1-3 alkyl;X represents a O or (CH2)n where n is 0, 1 or 2;R3and R4 independently represent H, C1-3 alkyl, -OCH3, -CF3, allyl, or halogen;X1 represents O, S, SO2, SO, or CH2;R5 and R6 independently represent hydrogen, C1-6 alkyl (including branched alkyl and optionally substituted by one or more halogens or C1-6alkoxy), or together with the carbon atom to which they are bonded form a 3-6 membered cycloalkyl ring;R7 represents a phenyl or a 6 membered heteroaryl group containing 1, 2 or 3 nitrogen atoms wherein the phenyl or heteroaryl group is substituted by 1, 2 or 3 moieties selected from the group consisting of halogen, C1-6 alkoxy, C1-6 alkyl, CF3, hydroxy, or phenyl (which may be optionally substituted by one or more C1-3 alkyl, -OC1-3 alkyl, CN, acetyl, hydroxy, halogen or CF3).
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- Sinapate dehydrodimers and sinapate-ferulate heterodimers in cereal dietary fiber
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Two 8-8-coupled sinapic acid dehydrodimers and at least three sinapate-ferulate heterodimers have been identified as saponification products from different insoluble and soluble cereal grain dietary fibers. The two 8-8-disinapates were authenticated by comparison of their GC retention times and mass spectra with authentic dehydrodimers synthesized from methyl or ethyl sinapate using two different single-electron metal oxidant systems. The highest amounts (481 μg/g) were found in wild rice insoluble dietary fiber. Model reactions showed that it is unlikely that the dehydrodisinapates detected are artifacts formed from free sinapic acid during the saponification procedure. The dehydrodisinapates presumably derive from radical coupling of sinapate-polymer esters in the cell wall; the radical coupling origin is further confirmed by finding 8-8 and 8-5 (and possibly 8-0-4) sinapate-ferulate cross-products. Sinapates therefore appear to have an analogous role to ferulates in cross-linking polysaccharides in cereal grains and presumably grass cell walls in general.
- Bunzel, Mirko,Ralph, John,Kim, Hoon,Lu, Fachuang,Ralph, Sally A.,Marita, Jane M.,Hatfield, Ronald D.,Steinhart, Hans
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p. 1427 - 1434
(2007/10/03)
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- Induction of apoptosis in cancer cells
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The present invention provides compounds that are inducers or inhibitors of apoptosis or apoptosis preceded by cell-cycle arrest. In addition, the present invention provides pharmaceutical compositions and methods for treating mammals with leukemia or other forms of cancer or for treating disease conditions caused by apoptosis of cells.
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- First enantioselective synthesis of daphneticin and its regioisomer
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An enantioselective total synthesis of chiral daphneticin and its regioisomer is reported for the first time.
- Ren, Xinfeng,Chen, Xiaochuan,Peng, Kun,Xie, Xingang,Xia, Yamu,Pan, Xinfu
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p. 1799 - 1804
(2007/10/03)
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- Structure-activity relationships of n-(3,5-dimethoxy-4-n-octyloxycinnamoyl)-N′-(3,4-dimethylphenyl) piperazine and analogues as inhibitors of acyl-CoA: Cholesterol O- acyltransferase
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A novel series of acyl-CoA: cholesterol O-acyltransferase (ACAT) inhibitors were synthesized from a lead compound, 1-(4-hydroxy-3-methoxyphenyl)-7-phenylhept-1-en-3-one (1, Yakuchinone B) through a modification of three regions (A, B, C) in the molecule. In this study, the compounds prepared were tested for in vitro inhibitory activity on microsomal ACAT from the liver of rats and for in vivo hypocholesterolemic activity in rats given a high cholesterol diet. N-(3,5-Dimethoxy-4- n-octyloxycinnamoyl)-N′-(3,4-dimethylphenyl)piperazine (45), which belongs to the amide compounds, has finally been discovered. Compound 45 inhibited rat hepatic ACAT in a more striking manner than CI-976, an amide compound ACAT inhibitor, and it exhibited a high level of hypocholesterolemic activity in vivo. Since 45 strongly inhibited both microsomal ACAT prepared from HepG2 (a cell line derived from human hepatocarcinoma) and Caco2 (a cell line derived from human colon adenocarcinoma), there is speculation that 45 might have the ability to inhibit ACAT in both the human intestine and liver independent of the difference in the distribution of ACAT isozymes. On the other hand, 45 did not induce adrenotoxicity in subacute toxicity studies in rats. These results suggest that it has promise for development as a new therapeutic agent for hypercholesterolemia and atherosclerosis.
- Ohishi,Aiyama,Hatano,Yoshida,Wada,Yokoi,Sawada,Watanabe,Yokokura
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p. 830 - 839
(2007/10/03)
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- Amide derivatives and 5-lipoxygenase inhibitors containing the same as an active ingredient
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According to the invention, there are provided novel amide derivatives and 5-lipoxygenase inhibitors containing the same as an effective ingredient. The above-mentioned compounds of the invention have been demonstrated to posses 5-lipoxygenase-inhibiting activities. These compounds can inhibit the production of leucotrienes such as LTC4 and LTD4 which are allergy-inducing factors by inhibiting the activity of 5-lipoxygenase. Accordingly, the amide derivatives can be used as 5-lipoxygenase inhibitors effective for allergic asthma, allergic rhinitis and the like.
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