- New C,O-Glycosylflavones from the Genus Silene
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Chromatographic separation of extracts from the aerial parts of three Silene species (Caryophyllaceae) isolated 26 flavonoids including the four new C,O-glycosylflavones acacetin-6-C-(2″-O-β-D-glucopyranosyl)-β-D-glucopyranoside-7-O-β-D-glucopyranoside (s
- Olennikov,Kashchenko
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- Synthesis of cinnamic acids catalyzed by expansive graphite under ultrasound
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Knoevenagel condensation of malonic acid with aromatic aldehydes catalysed by expansive graphite results cinnamic acids in 65-98% yields under ultrasound irradiation.
- Li,Zang,Feng,Li,Li
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- Purification and characterization of a novel aminoacylase from Streptomyces mobaraensis
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A novel aminoacylase was purified to homogeneity from culture broth of Streptomyces mobaraensis, as evidenced by SDS-polyacrylamide gel electrophoresis (PAGE). The enzyme was a monomer with an approximate molecular mass of 100 kDa. The purified enzyme was inhibited by the presence of 1,10-phenanthroline and activated by the addition of Co2+. It was stable at temperatures of up to 60°C for 1 h at pH 7.2. It showed broad substrate specificity to N-acetylated L-amino acids. It catalyzed the hydrolysis of the amide bonds of various N-acetylated L-amino acids, except for Nε-acetyl-L-lysine and N-acetyl-L-proline. Hydrolysis of N-acetyl-L-methionine and N-acetyl-L-histidine followed Michaelis-Menten kinetics with Km values of 1.3 ± 0.1 mM and 2.7 ± 0.1 mM respectively. The enzyme also catalyzed the deacetylation of 7-aminocephalosporanic acid (7-ACA) and cephalosporin C. Moreover, feruloyl-amino acids and L-lysine derivatives of ferulic acid derivatives were synthesized in an aqueous buffer using the enzyme.
- Koreishi, Mayuko,Asayama, Fumiaki,Imanaka, Hiroyuki,Imamura, Koreyoshi,Kadota, Megumi,Tsuno, Takuo,Nakanishi, Kazuhiro
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- New 3-O-acyl betulinic acids from Strychnos vanprukii Craib
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Three new betulinic acid derivatives, 3β-O-trans-feruloylbetulinic acid (1), 3β-O-cis-feruloylbetulinic acid (2), and 3β-O-cis- coumaroylbetulinic acid (4), along with two known triterpenes, 3β-O-trans-coumaroylbetulinic acid (3) and ursolic acid (6) were isolated from the leaves and twigs of Strychnos vanprukii Craib. All isolates showed moderate anti-HIV activity with IC50 values ranging from 3 to 7 μg/mL (5 to 15 μM) in an indicator cell line for HIV infectivity. The structures of the new isolates were elucidated by spectroscopic techniques including 1D and 2D NMR spectroscopy. In addition, the structure of 1 was confirmed by X-ray crystallography.
- Chien, Nguyen Quyet,Van Hung, Nguyen,Santarsiero, Bernard D.,Mesecar, Andrew D.,Cuong, Nguyen Manh,Soejarto, D. Doel,Pezzuto, John M.,Fong, Harry H. S.,Tan, Ghee T.
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- Biotransformation of eugenol to vanillin by a novel strain Bacillus safensis SMS1003
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Due to the extensive applications of vanillin as flavored compound and increasing consumers concern for its natural and environment friendly mode of production, present work was focused on the selection of bacterial isolate capable of producing vanillin using eugenol biotransformation. Bacterial strain SMS1003 is evidenced as the potential strain for vanillin production and identified as Bacillus safensis (GeneBank accession no. MG561863) using biochemical tests and molecular phylogenic analysis of its 16S rDNA gene sequence. Molar yield of vanillin reached up to 10.7% (0.055 g/L) at 96 h of biotransformation using growing culture of B. safensis SMS1003 in following culture conditions: eugenol concentration 500 mg/L; temperature 37 °C; initial pH 7.0; inoculum volume 4%; volume of culture media 10%; and shaking speed 180 rpm. Vanillin was detected as the single metabolite with a molar yield of 26% (0.12 g/L) at 96 h using resting cells of B. safensis SMS1003. Product confirmation was based on spectral scan using photodiode array detector, Fourier-transform infrared spectroscopy, high-performance liquid chromatography, and mass spectroscopy.
- Singh, Archana,Mukhopadhyay, Kunal,Ghosh Sachan, Shashwati
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- Identification and quantification of phenolic compounds from the forage legume sainfoin (Onobrychis viciifolia)
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Phenolic compounds of sainfoin (Onobrychis viciifolia) variety Cotswold Common are assumed to contribute to its nutritive value and bioactive properties. A purified acetone/water extract was separated by Sephadex LH-20 gel chromatography. Sixty-three phen
- Regos, Ionela,Urbanella, Andrea,Treutter, Dieter
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- Novel flavonol glycosides from the aerial parts of lentil (Lens culinaris)
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While the phytochemical composition of lentil (Lens culinaris) seeds is well described in scientific literature, there is very little available data about secondary metabolites from lentil leaves and stems. Our research reveals that the aerial parts of lentil are a rich source of flavonoids. Six kaempferol and twelve quercetin glycosides were isolated, their structures were elucidated using NMR spectroscopy and chemical methods. This group includes 16 compounds which have not been previously described in the scientific literature: quercetin 3-O-P-D-glucopyranosyl(1→2)-β-D-galactopyranoside-7-O-β-D-glucuropyranoside (1), kaempferol 3-O-β-D-glucopyranosyl(1→2)-β-D-galactopyranoside-7-O-β-D-glucuropyranoside (3), their derivatives 4-10,12-15,17,18 acylated with caffeic, p-coumaric, ferulic, or 3,4,5-trihydroxycinnamic acid and kaempferol 3-O-{[(6-O-E - p-coumaroyl)-β-D-glucopyranosyl(1→2)]-α-L-rhamnopyranosyl(1-6)}-β-D-galactopyranoside-7-O-α-L-rhamnopyranoside (11). Their DPPH scavenging activity was also evaluated. This is probably the first detailed description of flavonoids from the aerial parts of lentil.
- Zuchowski, Jerzy,Pecio, Lukasz,Stochmal, Anna
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- Chemical studies on antioxidant mechanism of curcuminoid: Analysis of radical reaction products from curcumin
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In the course of studies on the antioxidant mechanism of curcumin, its radical reaction was investigated. Curcumin was reacted with radical species, which were generated from the pyrolysis of 2,2'-azobis(isobutyronitrile) under an oxygen atmosphere, and the reaction products from curcumin were followed by HPLC. The reaction at 70 °C gave several products, three of which were structurally identified to be vanillin, ferulic acid, and a dimer of curcumin after their isolation. The dimer was a newly identified compound bearing a dihydrofuran moiety, and its chemical structure was elucidated using spectroscopic analyses, especially 2D NMR techniques. A mechanism for the dimer production is proposed and its relation to curcumin's antioxidant activity discussed. The time course and gel permeation chromatography studies of the reaction were also investigated, and the results indicate that the dimer is a radical-terminated product in the initial stage.
- Masuda, Toshiya,Hidaka, Kayo,Shinohara, Ayumi,Maekawa, Tomomi,Takeda, Yoshio,Yamaguchi, Hidemasa
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- New flavonol glycosides from Cardamine komarovii
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Seven new kaempferol glycosides (1-7), together with three known kaempferol glycosides (8-10), were isolated from a MeOH extract of Cardamine komarovii Nakai (Cruciferae). The chemical structures of the new compounds (1-7) were determined on the basis of their MS, 1H-NMR, 13C-NMR, COSY, HMBC, NOESY and TOCSY data, and results of hydrolysis.
- Lee, Il Kyun,Jeong, Eun-Kyung,Choi, Sang Un,Hong, Jongki,Lee, Kang Ro
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- Lavandoside from Lavandula spica flowers
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The new natural compound lavandoside with the structure ferulic acid 4-O-β-D-glucopyranoside was isolated by column chromatography over silica gel and polyamide from the extract of Lavandula spica flowers. The chemical structure of lavandoside was establi
- Kurkin,Lamrini,Klochkov
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- PURIFICATION AND PROPERTIES OF CAFFEIC ACID O-METHYLTRANSFERASE FROM ALFALFA ROOT NODULES
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An O-methyltransferase which catalyses the methylation of caffeic acid to ferulic acid using S-adenosyl-L-methionine as methyl donor has been isolated and purified ca. 70-fold from root nodules of alfalfa.The enzyme also catalysed the methylation of 5-fydroxyferulic acid.Chromatography on 1,6-diaminohexane agarose (AH-Sepharose4B) linked with S-adenosyl-L-homocysteine (SAH) gave 35 percent recovery of enzyme activity.The Km values for caffeic acid ans S-adenosyl-L-methionine were 58 and 4.1 μM, respectively.S-Adenosyl-L-homocysteins was a potent competitive inhibitor of S-adenosyl-L-methionine with a Ki of 0.44 μM.The MW of the enzyme was ca. 103 000 determined by gel filtration chromatography.
- Vance, Carroll P.,Bryan, Jeffrey W.
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- Loganin, Loganic Acid and Periclymenoside, a New Biosidic Ester Iridoid Glucoside from Lonicera periclymenum L. (Caprifoliaceae)
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Loganin (1), loganic acid (2), and periclymenoside (3) have been isolated from Lonicera periclymenum L.The structure of the new compound 3 and the identity of the others have been determined by chemical transformations and interpretation of the spectral data.
- Calis, Ihsan,Lahloub, Mohamed F.,Sticher, Otto
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- Acylated flavonol glycosides from Sedum aizoon
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A new acylated flavonol glycoside (1) and a known compound (2) have been isolated from the whole plant of Sedum aizoon L. Their structures have been established as quercetin 3-O-[β-D-(2?-O-(E)-feruloyl)-xylopyranosyl] -(1→6)-β-D-glucopyranoside (1) and rutin (2) by means of spectroscopic analysis and chemical methods.
- Luo, Qiu-Yan,Li, Wei-Lin,Wu, Li-Qiang
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- HYDROXYCINNAMIC ACID SPERMIDINE AMIDES FROM POLLEN OF CORYLUS AVELLANA L.
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Key Word Index-Corylus avellana; Betulaceae; hazelnut; pollen; hydroxycinnamic acid; polyamine; spermidine; amide.Two hydroxycinnamic acid amides from the pollen of Corylus avellane L. have been identified as (E)-caffeoyl-(E)-feruloylspermidine and di-(E)-feruloylspermidine on the basis of 1H NMR, 13C NMR and mass spectral data.
- Meurer, Barbara,Wray, Victor,Grotjahn, Lutz,Wiermann, Rolf,Strack, Dieter
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- Phenolics from Hypericum geminiflorum
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Five new constituents were isolated from the heartwood and roots of Hypericum geminiflorum. The structures were characterized as (2R,3R)- 3,5,7,2',5'-pentahydroxyflavan, 3,5-dimethoxy-4-hydroxy-1-O-β-D-glucoside, 3'-[γ-hydroxymethyl-(Z)-γ-methylally]-2',4',4-trihydroxychalcone 11'-O- ferulate, named gemichalcone A, 3'-[γ-hydroxymethyl-(Z)-γ-methylallyl]- 2',4',4-trihydroxychalcone 11'-O-coumarate, named gemichalcone B, and 3'- [γ-hydroxymethyl-(E)-γ-methylallyl]-2',4',4-trihydroxychalcone 11'-O- coumarate, named isogemichalcone B.
- Chung, Mei-Ing,Lai, Mei-Hsun,Yen, Ming-Hong,Wu, Ru-Rong,Lin, Chun-Nan
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- Bioactive phenolic constituents from the seeds of Pharbitis nil
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Two new lignans, termed pharsyringaresinol (1) and pharbilignoside (2), a new phenylethanoid glycoside, termed pharbiniloside (3), and 22 known compounds, were isolated from the ethanol extract of the seeds of Pharbitis nil. The structures of the new compounds (1-3) were determined on the basis of spectroscopic analyses, including 2D-NMR and circular dichroism (CD) spectroscopy studies. Among the isolates, compounds 2, 11, 12, and 24 exhibited significant cytotoxicity against human tumor cell lines (A549, SK-OV-3, SK-MEL-2, and HCT-15) with IC50 values ranging from 8.07 to 28.30 μM. In addition, compounds 11, 12 and 24 potently inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-activated BV-2 cells, a microglia cells with IC50 values ranging from 14.7 to 19.9 μM.
- Kim, Ki Hyun,Ha, Sang Keun,Choi, Sang Un,Kim, Sun Yeou,Lee, Kang Ro
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- Two new flavonoid glycosides from Semen Ziziphi Spinosae
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Two novel flavonoid glycosides, 6-dihydrophaseoylspinosin (1) and 6,6-diferuloylspinosin (2), were isolated from the MeOH extract of Semen Ziziphi Spinosae, together with six known flavonoids, isovitexin-2-O-β-(6-O-E- feruloyl)glucopyranoside (3), spinosin (4), isospinosin (5), 6-feruloylspinosin (6), swertisin (7), and isovitexin-2-O-β-d-glucopyranoside (8). The structures of 1 and 2 were elucidated by spectroscopic methods including UV, IR, ESI-TOF-MS, 1D NMR, and 2D NMR experiments.
- Zhang, Lin,Xu, Zhi-Lin,Wu, Chun-Fu,Yang, Jing-Yu,Kano, Yoshihiro,Yuan, Dan
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- Synthesis and antioxidant activity of hydroxycinnamic acid xylan esters
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Naturally occurring hydroxycinnamic acids, such as ferulic and sinapic acids, are known to possess antioxidant activity. In this study, ferulic acid and sinapic acid were covalently attached to oat spelt arabinoxylan and birch wood glucuronoxylan by esterification in a two-step feasible synthesis to generate modified xylans with various degrees of substitution. The obtained derivatives were fully analyzed by FT-IR, NMR, and HPSEC experiments to confirm the esterification of xylans and the degree of substitution. The antioxidative potential of the conjugates was evaluated using the emulsion lipid oxidation test. The results demonstrate that the derivatized xylans inhibited lipid oxidation notably better than the native oat spelt and birch wood xylans. It was found that ferulic acid esters of glucuronoxylan were more efficient antioxidants than those of arabinoxylan and that sinapic acid xylan esters were more efficient than their ferulic acid counterparts.
- Wrigstedt, Pauli,Kylli, Petri,Pitkaenen, Leena,Nousiainen, Paula,Tenkanen, Maija,Sipilae, Jussi
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- Synthesis and biological evaluation of hydroxycinnamic acid hydrazide derivatives as inducer of caspase-3
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In order to generate compounds with superior antitumor activity and reduced toxicity, twelve new hydroxycinnamic acid hydrazide derivatives were synthesized and evaluated for their antiproliferative activities against two cancer cell lines (H1299 lung carcinoma cells and MCF-7 breast cancer cells), and compared to two normal counterparts (NL-20 lung epithelial cells and H184B5F5/M10 breast cells) by MTT method. The results demonstrated that some of these compounds possessed good antiproliferative activity against the two cancer cell lines. Among them, compound 2c was active against the growth of H1299 lung carcinoma cells with IC50 values of 1.50 μM, which was more active than the positive topotecan (IC50 = 4.18 μM). Simultaneously, it showed lower cytotoxic effects on normal NL-20 lung epithelial cells (IC50 > 10 μM). Mechanism studies indicated that it induced cell cycle arrest at G2/M phase followed by activation of caspase-3, and consequently caused the cell death. Further studies on the structure optimization are ongoing.
- Wu, Zheng-Rong,Liu, Jian,Li, Jian-Ying,Zheng, Li-Fang,Li, Yang,Wang, Xing,Xie, Qing-Jian,Wang, Ai-Xia,Li, Ying-Hui,Liu, Rong-Hui,Li, Hong-Yu
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- Functionalized ionic liquid-catalyzed 1-feruloyl-sn-glycerol synthesis
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Feruloyl Glycerol (FG) is a potential antioxidant and UV absorbing ingredient in food and cosmetic industries. Transesterifications of ethyl ferulate (EF) with glycerol to synthesize FG were performed using different functionalized ionic liquids (1-butylsulfonic-3-methylimidazolium tosylate, [BSO3HMIM]TS; 1-propylsulfonic-3-methylimidazolium tosylate, [PSO3HMIM]TS; 1-butylsulfonic-3-methylimidazolium trifluoromethanesulfonate, [BSO3HMIM]OTF; 1-butylsulfonic-3- methylimidazolium hydrogen sulfate, [BSO3HMIM]HSO4; N-methylimidazolium hydrogen sulfate, [HMIM]HSO4; 1-butyl-3-methylimidazolium hydroxide, [BMIM]OH; 1-butyl-3-methylimidazo tetrachloride molysite, [BMIM]FeCl4; and 1-hexyl-3-methylimidazo tetrachloride molysite, [BMIM]FeCl4) as catalysts, respectively. High EF conversion (98.0 ± 1.5 %), 1-FG (1-feruloyl-sn-glycerol) yield (88.7 ± 1.1 %) and reaction selectivity for 1-FG (90.5 ± 2.1 %) were obtained using [BSO3HMIM]TS as catalyst. The activation energy (E a), the Michaelis-Menten kinetic constant (K m), and the maximum initial reaction rate (v max) of the transesterification are 65.9 ± 3.3 kJ/mol, 1.8 ± 0.1 mol/L, and (1.6 ± 0.4) × 10-2 mol/(L min), respectively. Effects of catalyst loading, reaction temperature, and the molar ratio of EF to glycerol on EF conversion and reaction selectivity for 1-FG (1-FG yield/EF conversion) were also investigated.
- Sun, Shangde,Chen, Xiaowei,Bi, Yanlan,Chen, Jingnan,Yang, Guolong,Liu, Wei
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- β-fluoro-coniferyl alcohol does not inhibit lignin biosynthesis in suspension cultures of Picea abies (L.) Karst.
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A fluorinated analogue of coniferyl alcohol has been reported to be a specific inhibitor of oxidases involved in the biosynthesis of lignin. The Z isomer of β-fluoro-coniferyl alcohol was synthesized and used for the preparation of dehydrogenation polymers (DHPs) and was also tested on lignin producing suspension cultures of spruce (Picea abies (L.) Karst.). The growth of the cells or the production of lignin by the suspension cultures was not significantly affected by the addition of fluoroconiferyl alcohol. This analogue did not form polymers quite as easily as did coniferyl alcohol in oxidation with hydrogen peroxide and horseradish peroxidase. In both cases the β-fluoroconiferyl alcohol became incorporated in the polymeric product. We were unable to detect any specific inhibition of peroxidase activity, which is at variance with earlier reports of pronounced inhibition of lignin biosynthesis in poplar plantlets by fluoroconiferin, a potential inhibitor of oxidases involved in lignin biosynthesis.
- Gustafsson, Mikaela,Kaerkoenen, Anna,Simola, Liisa K,Teeri, Teemu H,Sipilae, Jussi,Kilpelaeinen, Ilkka,Brunow, Goesta
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- Two new flavonol glycosides from Sedum Aizoon L.
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Two new flavonol glycosides, Sedacins C (1) and D (2), and two known compounds (3-4), have been isolated from the whole plant of Sedum aizoon L. Their structures have been established as 6′-O-(E)-feruloylquercetin (1) and 6′-O-(E)-feruloylisorhamnetin (2) by means of spectroscopic analysis and chemical methods. The Japan Institute of Heterocyclic Chemistry.
- Li, Wei Lin,Luo, Qiu Yan,Wu, Li Qiang,Xiao, Lei
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- The degradation of coniferyl alcohol and the complementary production of chlorogenic acids in the growth culture of Streptomyces albogriseolus KF977548 isolated from decaying wood residues
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Coniferyl alcohol is one of the major precursors of lignin; the most abundant aromatic compound and a natural resource currently receiving attention because of the value-added metabolites resulting from its degradation. Growth study of Streptomyces albogriseolus KF977548 (strain AOB) isolated from decaying wood residues in a tropical estuarine ecosystem was carried out using coniferyl alcohol as a sole carbon source. Cell growth and metabolite production were monitored at 24?h interval by dry weight measurements and HPLC, LC–MS-DAD analyses. Biochemical and PCR assays were carried out to detect the major catabolic enzymes of interest. Strain AOB utilized coniferyl alcohol completely within 72?h (μ?=?0.204?h?1,?Td?=?3.4?h). Laccase and peroxidase were released into the growth medium up to 0.099 and 98?μmol/mL respectively. Protocatechuate 3, 4-dioxygenase and demethylase were detected in the genome whilst ortho-adipate pathway was clearly indicated. Growth on coniferyl alcohol or caffeic acid as mono substrates resulted in the production of secondary metabolites identified by HPLC–MS as 1-caffeoylquinic and 3,4,5-tricaffeoylquinic acids, known as chlorogenic acids, in the culture medium. The microbial production of chlorogenic acids from a lignin-related substrate base by strain AOB could arouse a plausible biotechnological process.
- Buraimoh, Olanike M.,Ilori, Matthew O.,Amund, Olukayode O.,Isanbor, Chukwuemeka,Michel, Frederick C.
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- A novel feruloyl esterase from a soil metagenomic library with tannase activity
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A gene (tan410) encoding a feruloyl esterase was isolated by screening a cotton soil metagenomic library. Sequence analysis revealed that tan410 encodes a protein of 520 amino acids with a predicted molecular weight of 55 kDa. The gene was further expressed in Escherichia coli BL21 (DE3) using a pET expression system. The recombinant enzyme was purified and characterized. Its optimum temperature and pH were 35 °C and 7.0, respectively. Tan410 activity was enhanced by the addition of Mn2+, Mg2+, NH 4+ and Ni2+. Besides ethyl ferulate, methyl caffeate, and methyl p-coumarate, Tan410 can also hydrolyze methyl gallate, tannic acid, epicatechin gallate, and epigallocatechin gallate which makes Tan410 an interesting enzyme for biotechnological applications.
- Yao, Jian,Chen, Qing Long,Shen, Ai Xi,Cao, Wen,Liu, Yu Huan
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- Easy Access to Quinolin-2(1 H)-ones via a One-Pot Tandem Oxa-Michael-Aldol Sequence
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An efficient strategy for the synthesis of a variety of quinolin-2(1 H)-one derivatives has been developed. The reaction proceeded from cinnamide derivatives via a tandem reaction in the presence of NaOH to afford the corresponding 2- quinolin-2(1 H)-one derivatives in good to excellent yields.
- Jarrige, Lucie,Merad, Jeremy,Zaied, Siwar,Blanchard, Florent,Masson, Géraldine
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- New acylated oligosaccharides from Pistacia integerrima
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Integrisides A (1) and B (2), new acylated oligosaccharides, have been isolated from the n-butanol-soluble sub-fraction of the methanolic extract collected from the aerial parts of Pistacia integerrima. Their structures were elucidated by spectroscopic techniques and hydrolysis.
- Ullah, Zia,Mehmood, Rashad,Imran, Muhammad,Malik, Abdul,Afzal, Rehana A.
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- Repenins A-D, four new antioxidative coumarinolignoids from Duranta repens Linn.
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Phytochemical investigations on the CHCl3-soluble fraction of the whole plant of Duranta repens Linn. led to the isolation of four new coumarinolignoids, Repenins A-D (1-4), along with the known coumarinolignoids, cleomiscosin A (5) and duranti
- Ahmad, Nisar,Zeb, Fozia,Ahmad, Ijaz,Wang, Fanghai
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- Jasmonate-induced changes in flavonoid metabolism in barley (Hordeum vulgare) leaves
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The effects of jasmonic acid (JA) on secondary metabolism in barley (Hordeum vulgare L.) were investigated. A reversed-phase HPLC analysis revealed that the amount of a particular compound increased in excised barley leaf segments that had been treated with JA. This compound was purified and identified as 6?-feruloylsaponarin (1) by spectroscopic analyses and alkaline hydrolysis. A related compound, 6?-sinapoylsaponarin (2), was also found to accumulate in excised leaves independently of the JA treatment. The accumulation of these compounds was accompanied by a decrease in the saponarin (3) content. [8,9-13C]p-Coumaric acid and [2,3,4,5,6- 2H]L-phenylalanine were effectively incorporated into the hydroxycinnamoyl moieties in 1 and 2, while the degree of incorporation of the labeled precursors into the saponarin part was small. These findings indicate that the hydroxycinnamoyl moieties of 1 and 2 are synthesized de novo from phenylalanine via the phenylpropanoid pathway, and that the saponarin part is mainly provided by the constitutive pool of 3.
- Ishihara, Atsushi,Ogura, Yuki,Tebayashi, Shin-Ichi,Iwamura, Hajime
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- Bismuth(III) chloride-mediated, efficient, solvent-free, mwi-enhanced doebner condensation for the synthesis of (E)-cinnamic acids
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A bismuth(III) chloride-mediated green process for the production of (E)-cinnamic acid derivatives using microwave irradiation under solvent-free conditions is described. The (E)-cinnamic acids are obtained in excellent yields. This protocol is green because it employs an established environmentally benign procedure, microwave irradiation. Solvent vapor pollution is not there because it is solvent free, and bismuth(III) chloride is an established nontoxic catalyst. Copyright
- Suresh,Kumar, Dhruva,Sandhu, Jagir S.
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- TOVAROL AND OTHER GERMACRANE DERIVATIVES FROM THAPSIA VILLOSA
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Four tovarol, two epoxytovarol ( = shiromodiol) and one diepoxytovarol esters were the new germacrane esters isolated from the roots of Thapsia villosa var. minor.The structures of these substances were assigned on the basis of spectral data and chemical correlations with shiromodiol.The acid catalysed rearrangement of tavarol yielded 1(10),4-bulgaradiene-8-ol. Key Word Index - Thapsia villosa; Thapsia villosa var. minor; Umbelliferae; germacrane derivatives; tovarol, shiromodiol and epoxytovarol esters; 1(10),4-bulgaradiene-8-ol.
- Teresa, Joaquin de Pascual,Moran, Joaquin R.,Hernandez, Jose M.,Grande, Manuel
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- Acylated iridoid glycosides with hyaluronidase inhibitory activity from the rhizomes of Picrorhiza kurroa Royle ex Benth
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Seven new acylated iridoid glycosides, picrorhizaosides A–G (1–7), were isolated from the methanol extract of the rhizomes of Picrorhiza kurroa Royle ex Benth. (Plantaginaceae), in addition to six known iridoid glycosides (8–13). The structures of these new iridoids, including their stereochemistry, were determined based on chemical and physicochemical evidence derived from NMR and MS analysis. Of the isolates, picrorhizaosides D (4, IC50 = 43.4 μM) and E (5, 35.8 μM); picrosides I (8, 60.7 μM), II (9, 22.3 μM), and IV (11, 59.2 μM); and minecoside (13, 57.2 μM), exhibited a similar or stronger hyaluronidase inhibitory activity than those of the antiallergic medicines disodium cromoglycate (64.8 μM), ketotifen fumarate (76.5 μM), and tranilast (227 μM).
- Morikawa, Toshio,Nakanishi, Yusuke,Inoue, Naoki,Manse, Yoshiaki,Matsuura, Hideyuki,Hamasaki, Shinya,Yoshikawa, Masayuki,Muraoka, Osamu,Ninomiya, Kiyofumi
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- The efficient and selective catalytic oxidation of para-substituted cinnamic acid derivatives by the cytochrome P450 monooxygenase, CYP199A4
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The cytochrome P450 enzyme, CYP199A4, demethylated 4-methoxybenzoic acid, but not 4-methoxyphenylacetic acid, with high product formation activity. The oxidative demethylation of 3-(4-methoxyphenyl)propionic acid was 8-fold more active than 4-methoxyphenylacetic acid and 4-methoxycinnamic acid was efficiently oxidised at a product formation rate of 180 nmol nmol-P450-1 min-1. Accordingly the oxidation of cinnamic acid derivatives was investigated in order to determine the potential of CYP199A4 to act as a biocatalyst for this important class of biological molecules. 4-Methoxy- and 4-methyl-cinnamic acids bound tightly to CYP199A4 and were better substrates for CYP199A4 than cinnamic acid itself. The oxidations of both 4-methoxy- and 4-methyl-cinnamic acids was 100% selective for attack at the para substituent. Certain dimethoxy substituted cinnamic acids were demethylated more efficiently than 4-methoxycinnamic acid and retained the selectivity for the para-methoxy substituent. Only very low product turnover was observed with 3,5-dimethoxycinnamic acid. 4-Isopropylcinnamic acid was hydroxylated and desaturated by CYP199A4 at the isopropyl group. Cinnamic acids with a para-substituted alkyl- and alkyloxy-cinnamic acid framework were a good fit for the active site of the CYP199A4 enzyme and as a consequence were efficiently and selectively oxidised. Whole-cell oxidations resulted in high yields of product and CYP199A4 could be developed for applications in the biocatalytic oxidation of cinnamic acid derivatives and related phenylpropanoids.
- Chao, Rebecca R.,De Voss, James J.,Bell, Stephen G.
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- Triethylamine: A potential N-base surrogate for pyridine in Knoevenagel condensation of aromatic aldehydes and malonic acid
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Cinnamic acids are intermediates with significant potential for synthesis of several industrially important chemicals. Classically, cinnamic acids are produced through Knoevenagel condensation of aromatic aldehydes and malonic acid in the presence of an organocatalyst and large amounts of carcinogenic pyridine. An alternative pyridine free reaction scheme for Knoevenagel condensation of malonic acid and aromatic aldehydes was investigated by replacing pyridine with an aliphatic tertiary amine surrogate in toluene as the reaction medium. Of the three aliphatic tertiary amines used, namely, triethyl amine (TEA), trioctyl amine (TOA) and tributyl amine (TBA), only TEA afforded cinnamic acids in comparable yields to those obtained with pyridine. Validation through a computational analysis is attempted to provide an explanation for the observed role of TEA as an aliphatic N-base instead of TBA and TOA. The use of TEA as a mild base in place of pyridine can be seen as playing the dual role of a base catalyst as well as a phase transfer agent evidenced by the in-process ATR-FITR spectroscopy. Use of the TEA-toluene system in place of pyridine can be seen as resulting in a process that affords ease of handling, separation and recycling of the solvent and the catalyst.
- Pawar, Hitesh S.,Wagh, Adhirath S.,Lali, Arvind M.
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- Biochemical characteristics and gene cloning of a novel thermostable feruloyl esterase from Chaetomium sp.
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A feruloyl esterase from Chaetomium sp. CQ31 was purified and biochemically characterized. The purified feruloyl esterase had a specific activity of 38.6 U/mg. The molecular mass of the enzyme was estimated to be 30.2 kDa by SDS-PAGE, and 29.6 kDa by gel filtration, indicating that the enzyme was a monomer. The optimum pH and temperature of the enzyme were pH 7.5 and 60 C, respectively. It was stable over a broad pH range of 4.0-10.0, and also exhibited good thermostability. The enzyme displayed strict substrate specificity. The K m and Vmax values for methyl ferulate were 0.98 μmol/min/mg and 42.6 U/mg, respectively. Furthermore, the feruloyl esterase gene was cloned and sequenced. Open reading frame (ORF) of the feruloyl esterase gene (879-bp) encodes 274 amino acids. The deduced amino acid sequence of the feruloyl esterase gene exhibited the highest identity (79%) with that of type B feruloyl esterase from Magnaporthe oryzae.
- Yang, Shao-Qing,Tang, Luo,Yan, Qiao-Juan,Zhou, Peng,Xu, Hai-Bo,Jiang, Zheng-Qiang,Zhang, Pan
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- Structural and Conformational Caharacterization of a Stable Anthocyanin from Tradescantia pallida
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Anthocyanins found in some plants of the Commelinaceae family have shown to be very stable compared to other commercially available natural pigments.One source of these stable anthocyanins is found in the plant Tradescantia pallida.Through the use of chemical hydrolysis, mass spectrometry, and 1H NMR, the major anthocyanin from T. pallida was characterized to be 3-O--β-D-glucopyranosyl>-7,3'-di-O-cyanidin.Keywords: Anthocyanins; tradescantia; Commelinaceae; stability pigments; structure characterization.
- Baublis, Alan J.,Berber-Jimenez, M. Dolores
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- A new phenylpropane glycoside from the rhizome of sparganium stoloniferum
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The purification of the MeOH extract from the rhizome of Sparganium stoloniferum Buch.-Hamil. (Sparganiaceae) using column chromatography furnished one new phenylpropanoid glycoside (7) and known phenolic compounds (1-6, and 8-13). The structural elucidation of 7 was based on 1D- and 2D-NMR spectroscopic data analysis to be β-D-(6-O-trans-feruloyl) fructofuranosyl-a-D-O- glucopyranoside. Compounds 1-6, and 8-13 were elucidated by spectroscopy and confirmed by comparison with reported data; 24-methylenecycloartanol (1), phydroxybenzaldehyde (2), ferulic acid (3), p-coumaric acid (4), vanillic acid (5), β-D-(1-O-acetyl- 3-O-trans-feruloyl)fructofuranosy-a-D-2',4',6'.-O- triacetyglucopyranoisde (6), β-D-(1-O-acetyl- 3,6-O-trans-diferuloyl) fructofuranosyl-a-D-2',4',6'.-O-triacetylglucopyranoisde (8), hydroxytyrosol acetate (9), hydroxytyrosol (10), isorhamnetin-3-O-rutinoside (11), n-butyl-a-D-fructofuranoside (12), and n-butyl-β-D-fructopyranoside (13). Compounds 3 and 9-13 were isolated for the first time from this plant. The isolated compounds were tested for cytotoxicity against four human tumor cell lines in vitro using a Sulforhodamin B bioassay.
- Lee, Seung Young,Choi, Sang Un,Lee, Jei Hyun,Lee, Dong Ung,Lee, Kang Ro
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- Isolation and characterization of a novel tannase from a metagenomic library
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A novel gene (designated as tan410) encoding tannase was isolated from a cotton field metagenomic library by functional screening. Sequence analysis revealed that tan410 encoded a protein of 521 amino acids. SDS-PAGE and gel filtration chromatography analysis of purified tannase suggested that Tan410 was a monomeric enzyme with a molecular mass of 55 kDa. The optimum temperature and pH of Tan410 were 30 °C and 6.4. The activity was enhanced by addition of Ca2+, Mg2+ and Cd2+. In addition, Tan410 was stable in the presence of 4 M NaCl. Chlorogenic acid, rosmarinic acid, ethyl ferulate, tannic acid, epicatechin gallate and epigallocathchin gallate were efficiently hydrolyzed by recombinant tannase. All of these excellent properties make Tan410 an interesting enzyme for biotechnological application.
- Yao, Jian,Fan, Xin Jiong,Lu, Yi,Liu, Yu Huan
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- A continuous, quantitative fluorescent assay for plant caffeic acid o-methyltransferases
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Plant caffeic acid O-methyltransferases (COMTs) use S-adenosylmethionine (ado-met), as a methyl donor to transmethylate their preferred (phenolic) substrates in vivo, and will generally utilize a range of phenolic compounds in vitro. Collazo et al. (Anal. Biochem. 2005, 342, 86-92) have published a discrete, end-point fluorescence assay to detect histone methyltransferases using S-adenosyl homocysteine hydrolase and adeonsine deaminase as coupling enzymes and a thiol-specific fluorophore, Thioglo1, as the detecting reagent. Using this previous assay as a guide, we have developed and validated a facile, sensitive and real-time fluorescence assay for characterizing plant COMTs and in the process simplified the original assay as well by obviating the need for adenosine deaminase in the assay, and simultaneously converting an end-point assay into a continuous one. Our assay has been used to kinetically characterize recombinant sorghum COMT (Bmr-12) a key enzyme involved in cell wall lignification, and analyze COMT activity in maturing tillers from switchgrass plants. Data indicated that the calculated Km and Vmax values for the recombinant sorghum COMT using different substrates in the fluorescent assay were similar to published values for COMT enzymes from other plant species. Native COMT activity was greatest in internodes at the top of a tiller and declined in the more basal internodes. This new assay should have broad applicability for characterizing COMTs and potentially other plant methlytransferases that utilize ado-met as a methyl donor. This article not subject to U.S. Copyright. Published 2010 by the American Chemical Society.
- Palmer, Nathan A.,Sattler, Scott E.,Saathoff, Aaron J.,Sarath, Gautam
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- Biomimetic oxidation of curcumin with hydrogen peroxide catalyzed by 5,10,15,20-tetraarylporphyrinatoiron(III) chlorides in dichloromethane.
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The biomimetic oxidation of curcumin, a main turmeric pigment with hydrogen peroxide catalyzed by different 5,10,15,20-tetraarylporphyrinatoiron(III) chlorides [TAPFe(III)Cl] in dichloromethane has been studied to give a C-C coupled curcumin dimer in 40-70% yield. The structure of the dimer has been elucidated by (1)H-, (13)C-NMR, IR and FAB-Mass spectroscopic data.
- Chauhan, Shive Murat Singh,Kandadai, Appan Srinivas,Jain, Nidhi,Kumar, Anil
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- Four New Flavonoids Isolated from the Aerial Parts of Cadaba rotundifolia Forssk. (Qadab)
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Cadaba rotundifolia (Forssk.) (family: Capparaceae; common name: Qadab) is one of four species that grow in the Red Sea costal region in the Kingdom of Saudi Arabia. The roots and leaves of C. rotundifolia is traditionally used to treat tumors and abscesses in Sudan. A previous phytochemical study of the roots yielded a quaternary alkaloid, but no report on chemical constituents of the aerial parts of the C. rotundifolia growing in Saudi Arabia has been issued so far. Oxidative stress and advanced glycation end products (AGEs) are thought as causal factors in many degenerative diseases, such as Alzheimer's disease, diabetes, atherosclerosis and aging. In this study, a total of twenty compounds, including four previously undescribed acylated kaempferol glucosides, were isolated from the aerial parts of C. rotundifolia collected in Saudi Arabia. These new compounds were identified as kaempferol 3-O-[2-O-(trans-feruloyl)-3-O-β-d-glucopyranosyl]-β-d-glucopyranoside (1), kaempferol 3-O-β-neohesperidoside-7-O-[2-O-(cis-p-coumaroyl)-3-O-β-d-glucopyranosyl]-β-d-glucopyranoside (2), kaempferol 3-O-[2,6-di-O-α-l-rhamnopyranosyl]-β-d-glucopyranoside-7-O-[6-O-(trans-feruloyl)]-β-d-glucopyranoside (3) and kaempferol 3-O-[2,6-di-O-α-l-rhamnopyranosyl]-β-d-glucopyranoside-7-O-[6-O-(trans-p-coumaroyl)]-β-d-glucopyranoside (4). Their structures were established based on UV-visible, 1D, 2D NMR, and HR-ESI-MS analyses. Of the assayed compounds, 17 and 18 showed potent radical scavenging activity with IC50 values of 14.5 and 11.7 μM, respectively, and inhibitory activity toward AGEs together with compound 7 with IC50 values 96.5, 34.9 and 85.5 μM, respectively.
- Al-Hamoud, Gadah Abdulaziz,Orfali, Raha Saud,Sugimoto, Sachiko,Yamano, Yoshi,Alothyqi, Nafee,Alzahrani, Ali Mohammed,Matsunami, Katsuyoshi
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- Novel morpholine containing cinnamoyl amides as potent tyrosinase inhibitors
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Tyrosinase enzyme plays a crucial role in melanin biosynthesis and enzymatic browning process of vegetables and fruits. Hence, tyrosinase inhibitors are important in the fields of medicine, cosmetics and agriculture. In this study, novel N-(2-morpholinoethyl)cinnamamide derivatives bearing different substituents on phenyl ring were designed, synthesized and evaluated for their tyrosinase diphenolase inhibitory activity. The compounds were found to be better tyrosinase inhibitors (IC50s were in micro molar range) than cinnamic acid. (E)-3-(3-chlorophenyl)-N-(2-morpholinoethyl)acrylamide (B6) exhibited the highest inhibition with IC50 value of 15.2 ± 0.6 μM which was comparable to that of kojic acid. The inhibition kinetic analysis of B6 indicated that the compound was a mixed-type tyrosinase inhibitor. In silico ADME prediction indicated that B6 might show more skin penetration than kojic acid. Molecular docking analysis confirmed that the active inhibitors well accommodated in the mushroom tyrosinase active site and it was also revealed that B6 formed the most stable drug-receptor complex with the target protein. Therefore, cinnamamide B6 could be introduced as a potent tyrosinase inhibitor that might be a promising lead in cosmetics, medicine and food industry.
- Ghafari, Shahrzad,Ranjbar, Sara,Larijani, Bagher,Amini, Mohsen,Biglar, Mahmood,Mahdavi, Mohammad,Bakhshaei, Maryam,Khoshneviszadeh, Mahsima,Sakhteman, Amirhossein,Khoshneviszadeh, Mehdi
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- Acylated cyanidin glycosides from the pale-violet flowers of Ionopsidium acaule (Desf.) Rchb. (Brassicaceae)
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Three new acylated cyanidin 3-sambubioside-5-glucosides (1-3) and one new acylated cyanidin 3-(3X-glucosylsambubioside)-5-glucoside (4) were isolated from the pale-violet flowers of Ionopsidium acaule (Desf.) Rchb., together with one known anth
- Tatsuzawa, Fumi,Takahashi, Narumi,Kato, Kazuhisa,Shinoda, Koichi,Saito, Norio,Honda, Toshio
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- Photoinduced Regioselective Olefination of Arenes at Proximal and Distal Sites
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The Fujiwara-Moritani reaction has had a profound contribution in the emergence of contemporary C-H activation protocols. Despite the applicability of the traditional approach in different fields, the associated reactivity and regioselectivity issues had
- Ali, Wajid,Anjana, S. S.,Bhattacharya, Trisha,Chandrashekar, Hediyala B.,Goswami, Nupur,Guin, Srimanta,Maiti, Debabrata,Panda, Sanjib,Prakash, Gaurav,Saha, Argha,Sasmal, Sheuli,Sinha, Soumya Kumar
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p. 1929 - 1940
(2022/02/01)
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- Synthesis, spectrophotometric, spectroscopic, microbial studies and analytical applications of Cu(II) and Zn(II) complexes of chalcone ligand
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The ligation behavior of the chalcone ligand namely (E)-3-(4-hydroxy-3-methoxyphenyl) acrylic acid (ferulic acid) (FA) toward the Cu(II) and Zn(II) ions was determined. The structure of the isolated solid complexes was elucidated by elemental analyses, spectral techniques (IR, UV–Vis, 13C– and 1H-NMR spectra) as well as the conductance measurements and thermal analyses. UV–Vis spectra and magnetic moments had suggested square planar and tetrahedral stereochemistry for Cu(II) and Zn(II) complexes, respectively. The kinetic and thermodynamic parameters for some selected decomposition steps have been calculated. Two precise and sensitive spectrophotometric methods were utilized to determine Zn(II) and Cu(II) complexes with ferulic acid using a micellar media of cetylpyridinium bromide (CPB) and sodium lauryl sulfate (SLS) with an absorption maxima of 430 and 465?nm for Zn(II) and Cu(II), respectively. Various analytical conditions, for example, the concentration of the reagent, temperature, the sequence and timing of addition were also looked into. Under optimum conditions, the complexes exhibited good linearity in concentration range of 2.0–70.0 and 4.0–140.0?μg?mL?1; molar absorptivities 1.3161 × 104 and 8.826 × 103 L mol?1?cm?1; and Sandell’s sensitivity 0.00496 and 0.00719?μg?cm?2 for the proposed methods of Zn(II) and Cu(II), respectively. The complexes ratio was found to be 1:2 [Zn(II):FA or Cu(II):FA] and the stability constants were 2.771 × 105 and 2.826 × 105, respectively. Finally, the newly synthesized complexes were shown potent antimicrobial activity.
- Abd El-wahaab, Badr,El-Shwiniy, Walaa H.,Shehab, Wesam S.
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- First total syntheses of four natural bioactive glucosides
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The efficient total syntheses of four biologically interesting natural glucosides Ethylconiferin, Butylconiferin, 2’-Butoxyethylconiferin and Balajaponin B, have been achieved for the first time starting from commercially available Vanilline via concise reaction sequence of 8–10 steps with the overall yield of 26–41%. This work definitely laid the foundation for the further pharmacological study of this kind of natural compounds. Meanwhile, currently developed approach could be used as a general synthetic strategy for the syntheses of other monolignol glucosides and their derivatives, and provides an opportunity for further study of the structure-activity relationship of this kind of glucosides.
- Xu, Guangya,Wu, Min,Yao, Zhongquan,Lou, Hongbin,Du, Weihong,Song, Mingwei,He, Yujiao,Dong, Hongbo
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supporting information
p. 1266 - 1271
(2021/02/06)
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- Discovery of 3-cinnamamido-n-substituted benzamides as potential antimalarial agents
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Background: Malaria is one of the most devastating parasitic diseases, yet the discovery of antimalarial agents remains profoundly challenging. Very few new antimalarials have been developed in the past 50 years, while the emergence of drug-resistance continues to appear. Objective: This study focuses on the discovery, design, synthesis, and antimalarial evaluation of 3- cinnamamido-N-substituted benzamides. Methods: In this study, a screening of our compound library was carried out against the multidrugsensitive Plasmodium falciparum 3D7 strain. Derivatives of the hit were designed, synthesized and tested against P. falciparum 3D7 and the in vivo antimalarial activity of the most active compounds was evaluated using the method of Peters’ 4-day suppressive test. Results: The retrieved hit compound 1 containing a 3-cinnamamido-N-substituted benzamide skeleton showed moderate antimalarial activity (IC50 = 1.20 μM) for the first time. A series of derivatives were then synthesized through a simple four-step workflow, and half of them exhibited slightly better antimalarial effect than the precursor 1 during the subsequent in vitro assays. Additionally, compounds 11, 23, 30 and 31 displayed potent activity with IC50 values of approximately 0.1 μM, and weak cytotoxicity against mammalian cells. However, in vivo antimalarial activity is not effective, which might be ascribed to the poor solubility of these compounds. Conclusion: In this study, the phenotypic screen of our compound library resulted in the first report of a 3-cinnamamide framework with antimalarial activity and 40 derivatives were then designed and synthesized. Subsequent structure-activity studies showed that compounds 11, 23, 30 and 31 exhibited the most potent and selective activity against the P. falciparum 3D7 strain with IC50 values around 0.1 μM. Our work herein sets another example of phenotypic screen-based drug discovery, leading to potentially promising candidates of novel antimalarial agents once given further optimization.
- Futamura, Yushi,Ishiyama, Aki,Iwatsuki, Masato,Liu, Haicheng,Osada, Hiroyuki,Shi, Tao,Wu, Honghai,Zhang, Taotao,Zheng, Qunxiong,Zou, Hongbin,ōmura, Satoshi
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p. 1207 - 1218
(2022/01/06)
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- A Series of Ferulic Acid Amides Reveals Unexpected Peroxiredoxin 1 Inhibitory Activity with in vivo Antidiabetic and Hypolipidemic Effects
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Insulin resistance is a major pathophysiological feature in the development of type 2 diabetes (T2DM). Ferulic acid is known for attenuating the insulin resistance and reducing the blood glucose in T2DM rats. In this work, we designed and synthesized a library of new ferulic acid amides (FAA), which could be considered as ring opening derivatives of the antidiabetic PPARγ agonists Thiazolidinediones (TZDs). However, since these compounds displayed weak PPAR transactivation capacity, we employed a proteomics approach to unravel their molecular target(s) and identified the peroxiredoxin 1 (PRDX1) as a direct binding target of FAAs. Interestingly, PRDX1, a protein with antioxidant and chaperone activity, has been implied in the development of T2DM by inducing hepatic insulin resistance. SPR, mass spectrometry-based studies, docking experiments and in vitro inhibition assay confirmed that compounds VIe and VIf bound PRDX1 and induced a dose-dependent inhibition. Furthermore, VIe and VIf significantly improved hyperglycemia and hyperlipidemia in streptozotocin-nicotinamide (STZ-NA)-induced diabetic rats as confirmed by histopathological examinations. These results provide guidance for developing the current FAAs as new potential antidiabetic agents.
- Yasmin, Sabina,Cerchia, Carmen,Badavath, Vishnu Nayak,Laghezza, Antonio,Dal Piaz, Fabrizio,Mondal, Susanta K.,Atl?, ?zlem,Baysal, Merve,Vadivelan, Sankaran,Shankar,Siddique, Mohd Usman Mohd,Pattnaik, Ashok Kumar,Singh, Ravi Pratap,Loiodice, Fulvio,Jayaprakash, Venkatesan,Lavecchia, Antonio
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p. 484 - 498
(2020/11/02)
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- Kinetics-Driven Drug Design Strategy for Next-Generation Acetylcholinesterase Inhibitors to Clinical Candidate
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The acetylcholinesterase (AChE) inhibitors remain key therapeutic drugs for the treatment of Alzheimer's disease (AD). However, the low-safety window limits their maximum therapeutic benefits. Here, a novel kinetics-driven drug design strategy was employed to discover new-generation AChE inhibitors that possess a longer drug-target residence time and exhibit a larger safety window. After detailed investigations, compound 12 was identified as a highly potent, highly selective, orally bioavailable, and brain preferentially distributed AChE inhibitor. Moreover, it significantly ameliorated cognitive impairments in different mouse models with a lower effective dose than donepezil. The X-ray structure of the cocrystal complex provided a precise binding mode between 12 and AChE. Besides, the data from the phase I trials demonstrated that 12 had good safety, tolerance, and pharmacokinetic profiles at all preset doses in healthy volunteers, providing a solid basis for its further investigation in phase II trials for the treatment of AD.
- Zhou, Yu,Fu, Yan,Yin, Wanchao,Li, Jian,Wang, Wei,Bai, Fang,Xu, Shengtao,Gong, Qi,Peng, Tao,Hong, Yu,Zhang, Dong,Zhang, Dan,Liu, Qiufeng,Xu, Yechun,Xu, H. Eric,Zhang, Haiyan,Jiang, Hualiang,Liu, Hong
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p. 1844 - 1855
(2021/03/01)
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- S-Adenosylhomocysteine Analogue of a Fairy Chemical, Imidazole-4-carboxamide, as its Metabolite in Rice and Yeast and Synthetic Investigations of Related Compounds
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During the course of our investigations of fairy chemicals (FCs), we found S-ICAr-H (8a), as a metabolite of imidazole-4-carboxamide (ICA) in rice and yeast (Saccharomyces cerevisiae). In order to determine its absolute configuration, an efficient synthetic method of 8a was developed. This synthetic strategy was applicable to the preparation of analogues of 8a that might be biologically very important, such as S-ICAr-M (9), S-AICAr-H (10), and S-AICAr-M (11).
- Ouchi, Hitoshi,Namiki, Takuya,Iwamoto, Kenji,Matsuzaki, Nobuo,Inai, Makoto,Kotajima, Mihaya,Wu, Jing,Choi, Jae-Hoon,Kimura, Yoko,Hirai, Hirofumi,Xie, Xiaonan,Kawagishi, Hirokazu,Kan, Toshiyuki
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p. 453 - 458
(2021/02/05)
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- Novel method for preparing ferulic acid
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The invention provides a novel method for preparing ferulic acid, and belongs to the field of medicine synthesis. According to the method, vanillin and Meldrum's acid are taken as initial raw materials, organic acid is taken as a catalyst, and ferulic acid is obtained through reaction. According to the preparation process, cheap and easily available starting raw materials are adopted, the synthesis process is green and environment-friendly, and waste liquid and organic solvents generated in a reaction system and post-treatment are less; the operation process is simple and convenient, the feeding procedure is simple, special equipment does not need to be added, all steps are conventional steps; the control of related parameters can also be in a certain range, and the final yield and purity of the product cannot be influenced by small parameter changes; and the process is stable and suitable for industrial production.
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Paragraph 0018; 0041-0056
(2021/07/09)
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- A chlorogenic acid esterase from a metagenomic library with unique substrate specificity and its application in caffeic and ferulic acid production from agricultural byproducts
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Soil microbes are an abundant source of enzymes with unique properties that may be useful for industrial applications. As most wild-type strains show low chlorogenic acid esterase expression and activity, and most microbes cannot be cultured in the laboratory, a metagenomic approach provides methods of identifying new enzymes. In this study, a gene encoding a chlorogenic acid esterase, named Tan410, was isolated from a soil metagenomic library and overexpressed in Escherichia coli BL21 (DE3). The recombinant enzyme, with a predicted molecular weight of 54.88 kDa, was purified to homogeneity. The K m and V max values for Tan410 were 1.26 mM and 0.33 mM min–1, respectively, with chlorogenic acid as the substrate. Its optimum temperature and pH for reaction were 30 °C and 7.5, respectively. The enzyme exhibited moderate thermostability and broad pH stability (3.0–10.0). Tan410 was also able to hydrolyse ethyl ferulate, methyl caffeate, propyl gallate, ethyl gallate, methyl vanillate, methyl benzoate, ethyl benzoate, methyl 2,5-dihydroxybenzoate, and methyl 3,5-dihydroxybenzoate, and it released caffeic and ferulic acids from agricultural byproducts (destarched wheat bran and coffee pulp). Tan140 has potential for industrial application in biomass valorization.
- Gui, Lun,Long, Qizhang,Yao, Jian
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- Synthesis, characterization, and antioxidant activity of some 2-methoxyphenols derivatives
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Oxidative stress is a causative factor in the pathophysiology of numerous diseases, such as diabetes, atherosclerosis, cancer, and neurodegenerative and cardiovascular diseases. Therapeutic antioxidants are promising candidates for preventing and treating conditions in which oxidative stress is a contributing factor. In this study, we report the design, synthesis and antioxidant activity of six compounds containing the 2-methoxyphenol moiety core structure. The synthesized derivatives were characterized using 1H NMR, 13C NMR, Fourier-transform infrared (FT-IR), and elemental analysis spectroscopy. The antioxidant properties of the compounds were evaluated using the 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS), and oxygen radical absorbance capacity (ORAC) assay. New phenolic acid-derived compounds with antioxidant activity were identified.
- Al Ajeil, Ruba,AlNeyadi, Shaikha S.,Amer, Naheed,Breitener, Priya,Munawar, N.,Thomas, Tony G.
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p. 112 - 122
(2020/10/23)
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- Bioassay of ferulic acid derivatives as influenza neuraminidase inhibitors
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Four series of ferulic acid derivatives were designed, synthesized, and evaluated for their neuraminidase (NA) inhibitory activities against influenza virus H1N1 in vitro. The pharmacological results showed that the majority of the target compounds exhibited moderate influenza NA inhibitory activity, which was also better than that of ferulic acid. The two most potent compounds were 1m and 4a with IC50 values of 12.77 ± 0.47 and 12.96 ± 1.34 μg/ml, respectively. On the basis of the biological results, a preliminary structure–activity relationship (SAR) was derived and discussed. Besides, molecular docking was performed to study the possible interactions of compounds 1p, 2d, 3b, and 4a with the active site of NA. It was found that the 4-OH-3-OMe group and the amide group (CON) of ferulic acid amide derivatives were two key pharmacophores for NA inhibitory activity. It is meaningful to further modify the natural product ferulic acid to improve its influenza NA inhibitory activity.
- Cui, Man-Ying,Xiao, Meng-Wu,Xu, Lv-Jie,Chen, Yun,Liu, Ai-Lin,Ye, Jiao,Hu, Ai-Xi
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- Design, synthesis, and evaluation of novel cinnamic acid-tryptamine hybrid for inhibition of acetylcholinesterase and butyrylcholinesterase
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Background: Acetylcholine deficiencies in hippocampus and cortex, aggregation of β-amyloid, and β-secretase over activity have been introduced as main reasons in pathogenesis of Alzheimer’s disease. Methods: Colorimetric Ellman’s method was used for determination of IC50 value in AChE and BChE inhibitory activity. The kinetic studies, neuroprotective and β-secretase inhibitory activities, evaluation of inhibitory potency on β-amyloid (Aβ) aggregations induced by AChE, and docking study were performed for prediction of the mechanism of action. Result and discussion: A new series of cinnamic acids-tryptamine hybrid was designed, synthesized, and evaluated as dual cholinesterase inhibitors. These compounds demonstrated in-vitro inhibitory activities against acetyl cholinesterase (AChE) and butyryl cholinesterase (BChE). Among of these synthesized compounds, (E)-N-(2-(1H-indol-3-yl)ethyl)-3-(3,4-dimethoxyphenyl)acrylamide (5q) demonstrated the most potent AChE inhibitory activity (IC50 = 11.51?μM) and (E)-N-(2-(1H-indol-3-yl)ethyl)-3-(2-chlorophenyl)acrylamide (5b) were the best anti-BChE (IC50 = 1.95?μM) compounds. In addition, the molecular modeling and kinetic studies depicted 5q and 5b were mixed type inhibitor and bound with both the peripheral anionic site (PAS) and catalytic sites (CAS) of AChE and BChE. Moreover, compound 5q showed mild neuroprotective in PC12 cell line and weak β-secretase inhibitory activities. This compound also inhibited aggregation of β-amyloid (Aβ) in self-induced peptide aggregation test at concentration of 10?μM. Conclusion: It is worth noting that both the kinetic study and the molecular modeling of 5q and 5b depicted that these compounds simultaneously interacted with both the catalytic active site and the peripheral anionic site of AChE and BChE. These findings match with those resulted data from the enzyme inhibition assay. [Figure not available: see fulltext.]
- Ghafary, Shahrzad,Ghobadian, Roshanak,Mahdavi, Mohammad,Nadri, Hamid,Moradi, Alireza,Akbarzadeh, Tahmineh,Najafi, Zahra,Sharifzadeh, Mohammad,Edraki, Najmeh,Moghadam, Farshad Homayouni,Amini, Mohsen
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p. 463 - 477
(2020/05/25)
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- NOVEL SMALL MOLECULES THAT BIND AND/OR MODULATE DIFFERENTFORMS OF TAU OLIGOMERS
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The present invention relates to novel small molecules of Formulas I, II, III, Ilia, Illb, and IV and pharmaceutically acceptable salts thereof, as well as the preparation and the use thereof.
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Page/Page column 34; 35
(2020/11/03)
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- Characterization of a Flavonoid 3’/5’/7-O-Methyltransferase from Citrus reticulata and Evaluation of the in Vitro Cytotoxicity of Its Methylated Products
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O-methylation of flavonoids is an important modification reaction that occurs in plants. O-methylation contributes to the structural diversity of flavonoids, which have several biological and pharmacological functions. In this study, an O-methyltransferase gene (CrOMT2) was isolated from the fruit peel of Citrus reticulata, which encoding a multifunctional O-methyltransferase and could effectively catalyze the methylation of 3’-, 5’-, and 7-OH of flavonoids with vicinal hydroxyl substitutions. Substrate preference assays indicated that this recombinant enzyme favored polymethoxylated flavones (PMF)-type substrates in vitro, thereby providing biochemical evidence for the potential role of the enzyme in plants. Additionally, the cytotoxicity of the methylated products from the enzymatic catalytic reaction was evaluated in vitro using human gastric cell lines SGC-7901 and BGC-823. The results showed that the in vitro cytotoxicity of the flavonoids with the unsaturated C2-C3 bond was increased after being methylated at position 3’. These combined results provide biochemical insight regarding CrOMT2 in vitro and indicate the in vitro cytotoxicity of the products methylated by its catalytic reaction.
- Liu, Xiaojuan,Wang, Yue,Chen, Yezhi,Xu, Shuting,Gong, Qin,Zhao, Chenning,Cao, Jinping,Sun, Chongde
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- Copper and L-(?)-quebrachitol catalyzed hydroxylation and amination of aryl halides under air
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L-(?)-Quebrachitol, a natural product obtained from waste water of the rubber industry, was utilized as an efficient ligand for the copper-catalyzed hydroxylation and amination of aryl halides to selectively give phenols and aryl amines in water or 95percent ethanol. In addition, the hydroxylation of 2-chloro-4-hydroxybenzoic acid was validated on a 100-g scale under air.
- Bao, Xuefei,Chen, Guoliang,Dong, Jinhua,Du, Fangyu,Li, Hui,Liang, Xinjie,Wu, Ying,Zhang, Yongsheng
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supporting information
(2020/08/03)
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- Expeditious and sustainable two-step synthesis of sinapoyl-l-malate and analogues: Towards non-endocrine disruptive bio-based and water-soluble bioactive compounds
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Faced with the increasing demand from both the cosmetic industries and consumers for bio-based, safe and natural skin products, sinapoyl-l-malate, widely described for its UV protection in plants, appears to be an excellent alternative to substitute chemical filters in sunscreens. Unfortunately, the only synthetic routes described in the literature were not only tedious but also exhibit a strong negative environmental impact, thus seriously limiting the industrialization and commercialization of sinapoyl-l-malate. Herein, a shorter and greener synthetic pathway involving Meldrum's acid opening with unprotected naturally occurring hydroxy acids and its subsequent Knoevenagel-Doebner condensation with biomass-derived p-hydroxybenzaldehydes was designed and developed. This two-step procedure, whom sustainability has been assessed using green metrics (atom economy (AE), process atom economy (PAE), E-factor and LCA), is a great alternative to the already reported procedures and allows the access to sinapoyl-l-malate and several analogs in average to good yield. The study of the anti-UV properties, stability against UV radiation, radical scavenging and antimicrobial activities of the targets revealed attractive properties as photostable UV filters, antioxidants and preservatives. Moreover, the water solubility brought by the free carboxylic acids facilitates the incorporation of these molecules in cosmetic formulations. Finally, their innocuousness toward endocrine disruption was demonstrated.
- Peyrot, Cédric,Mention, Matthieu M.,Fournier, Robin,Brunissen, Fanny,Couvreur, Julien,Balaguer, Patrick,Allais, Florent
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supporting information
p. 6510 - 6518
(2020/11/09)
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- Regioselectivity of Cobalamin-Dependent Methyltransferase Can Be Tuned by Reaction Conditions and Substrate
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Regioselective reactions represent a significant challenge for organic chemistry. Here the regioselective methylation of a single hydroxy group of 4-substituted catechols was investigated employing the cobalamin-dependent methyltransferase from Desulfitobacterium hafniense. Catechols substituted in position four were methylated either in meta- or para-position to the substituent depending whether the substituent was polar or apolar. While the biocatalytic cobalamin dependent methylation was meta-selective with 4-substituted catechols bearing hydrophilic groups, it was para-selective for hydrophobic substituents. Furthermore, the presence of water miscible co-solvents had a clear improving influence, whereby THF turned out to enable the formation of a single regioisomer in selected cases. Finally, it was found that also the pH led to an enhancement of regioselectivity for the cases investigated.
- Pompei, Simona,Grimm, Christopher,Farnberger, Judith E.,Schober, Lukas,Kroutil, Wolfgang
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p. 5977 - 5983
(2020/10/06)
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- Substituted cinnamic anhydrides act as selective inhibitors of acetylcholinesterase
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Cinnamic anhydrides have been shown to be more than reactive reagents, but they also act as inhibitors of the enzyme acetylcholinesterease (AChE). Thus, out of a set of 33 synthesised derivatives, several of them were mixed type inhibitors for AChE (from electric eel). Thus, (E)-3-(2,4-dimethoxyphenyl)acrylic anhydride (2c) showed Ki = 8.30 ± 0.94 μM and Ki′ = 9.54 ± 0.38 μM, and for (E)-3-(3-chlorophenyl)acrylic anhydride (2u) Ki = 8.23 ± 0.93 μM and Ki′ = 13.07 ± 0.46 μM were measured. While being not cytotoxic to many human cell lines, these compounds showed an unprecedented and noteworthy inhibitory effect for AChE but not for butyrylcholinesterase (BChE).
- Gie?el, Josephine M.,Serbian, Immo,Loesche, Anne,Csuk, René
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- Synthesis and biological evaluation of 2,2-dimethylbenzopyran derivatives as potent neuroprotection agents
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The development of novel neuroprotection agents is of great significance for the treatment of ischemic stroke. In this study, a series of compounds comprising 2,2-dimethylbenzopyran groups and cinnamic acid groups have been synthesized. Preferential combination principles and bioisostere that improved the neuroprotective effect of the compounds were identified for this series via biological activity assay in vitro. Meanwhile, a functional reversal group of the acrylamide amide resulted in the most active compounds. Among them, BN-07 significantly improved the morphology of neurons and obviously increased cell survival rate of primary neurons induced by oxygen glucose deprivation (OGD), superior to clinically used anti-ischemic stroke drug edaravone (Eda). Overall, our findings may provide an alternative strategy for the design of novel anti-ischemic stroke agents with more potency than Eda.
- Du, Fangyu,Zhou, Qifan,Fu, Xiaoxiao,Shi, Yajie,Chen, Yuanguang,Fang, Wuhong,Yang, Jingyu,Chen, Guoliang
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p. 2498 - 2508
(2019/02/01)
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- CHEMICAL COMPOSITIONS FOR COMBATING HONEY BEE PESTS AND PATHOGENS
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Compositions and methods that reduce Varroa mite populations within a honey bee colony are disclosed. The compositions and methods utilize relatively high concentrations of one or more naturally occurring molecules that are found within honey and/or propolis within a honey bee colony at low concentrations.
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Paragraph 0035
(2019/12/15)
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- Synthesis and biological evaluation of 4-arylcoumarins as potential anti-Alzheimer's disease agents
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Alzheimer's disease (AD) is a progressive neurological degenerative disease that has complex pathogenesis. A variety of studies in humans indicate that several enzymes inhibitors can be useful in the treatment of AD, including acetylcholinesterase (AchE), butyrylcholinesterase (BuChE) and monoamine oxidase (MAO). Various substituted 4-arylcoumarin derivatives were synthesised, and their activity in vitro were investigated, including AChE/BuChE inhibitory activity, MAO inhibitory activity, and antioxidant activity. Most of the compounds were found to exhibit high inhibitory activity, and individual compounds have extremely excellent activities. Therefore 4-arylcoumarins provides an idea for drugs design for the development of therapeutic or preventive agents for AD.
- Miao, Yuhang,Sun, Jie,Wang, Xiaojing,Yang, Jie,Yun, Yinling
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- Specific Residues Expand the Substrate Scope and Enhance the Regioselectivity of a Plant O-Methyltransferase
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An isoeugenol 4-O-methyltransferase (IeOMT), isolated from the plant Clarkia breweri, can be engineered to a caffeic acid 3-O-methyltransferase (CaOMT) by replacing three consecutive residues. Here we further investigated functions of these residues by constructing the triple mutant T133M/A134N/T135Q as well as single mutants of each residue. Phenolics with different chain lengths and different functional groups were investigated. The variant T133M improves the enzymatic activities against all tested substrates by providing beneficial interactions to residues which directly interact with the substrate. Mutant A134N significantly enhanced the regioselectivity. It is meta-selective or even specific against most of the tested substrates but para-specific towards 3,4-dihydroxybenzoic acid. The triple mutant T133M/A134N/T135Q benefits from these two mutations, which not only expand the substrate scope but also enhance the regioselectivity of IeOMT. On the basis of our work, regiospecific methylated phenolics can be produced in high purity by different IeOMT variants.
- Tang, Qingyun,Bornscheuer, Uwe T.,Pavlidis, Ioannis V.
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p. 3227 - 3233
(2019/07/04)
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- New C,O-Glycosylflavones from Melandrium divaricatum
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The aerial part of Melandrium divaricatum Fenzl (Caryophyllaceae) afforded 11 glycosylflavones including two new compounds that were characterized using UV, IR, and NMR spectroscopy and mass spectrometry as apigenin-6-C-(2″ -O-α-L-rhamnopyranosyl)-β-D-glucopyranoside-7-O-(6″″ -O-feruloyl)-β-Dglucopyranoside (divarioside A, 1) and apigenin-6-C-(2″-O-D-glucopyranosyl)- β-D-glucopyranoside-7-O-(6″″-O-feruloyl)- β-D-glucopyranoside (divarioside B, 2).
- Olennikov,Chirikova
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p. 1032 - 1038
(2019/11/26)
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- Application of quebrachitol in hydrolysis reaction of copper-catalyzed aryl halide
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The invention belongs to the technical field of drug synthesis, and provides application of quebrachitol in a hydrolysis reaction of a copper-catalyzed aryl halide. According to the hydrolysis reaction, copper serves as a catalyst, quebrachitol serves as a ligand, and the hydrolysis reaction is carried out on the aryl halide. The invention further provides a catalytic system of the hydrolysis reaction of the aryl halide. The reaction system comprises the copper catalyst, the quebrachitol, alkali and water, and the system is environmentally friendly and is suitable for industrial application.
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Paragraph 0066-0068
(2019/07/16)
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- Comprehensive kinetic and substrate specificity analysis of an arylsulfatase from Helix pomatia using mass spectrometry
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Sulfatases hydrolyze sulfated metabolites to their corresponding alcohols and are present in all domains of life. These enzymes have found major application in metabolic investigation of drugs, doping control analysis and recently in metabolomics. Interest in sulfatases has increased due to a link between metabolic processes involving sulfated metabolites and pathophysiological conditions in humans. Herein, we present the first comprehensive substrate specificity and kinetic analysis of the most commonly used arylsulfatase extracted from the snail Helix pomatia. In the past, this enzyme has been used in the form of a crude mixture of enzymes, however, recently we have purified this sulfatase for a new application in metabolomics-driven discovery of sulfated metabolites. To evaluate the substrate specificity of this promiscuous sulfatase, we have synthesized a series of new sulfated metabolites of diverse structure and employed a mass spectrometric assay for kinetic substrate hydrolysis evaluation. Our analysis of the purified enzyme revealed that the sulfatase has a strong preference for metabolites with a bi- or tricyclic aromatic scaffold and to a lesser extent for monocyclic aromatic phenols. This metabolite library and mass spectrometric method can be applied for the characterization of other sulfatases from humans and gut microbiota to investigate their involvement in disease development.
- Correia, Mário S.P.,Ballet, Caroline,Meistermann, Hannes,Conway, Louis P.,Globisch, Daniel
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p. 955 - 962
(2019/02/09)
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- Lithium perchlorate catalyzed electrophilic activation: A convenient one-pot synthesis of trans-cinnamic acids
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Background: Currently perchlorate catalysts gain much attention in organic synthesis due to ease of operation, wide applicability, high yield, and economy. This is evident through increasing number of citation related to their application in industry as well as other allied fields. The aim of this paper is to describe a methodology using lithium perchlorate to catalyze the Knoevenagel condensation reaction for the synthesis of biologically active trans-cinnamic acid in good to excellent yield. Methods: We discuss herein an economic, user-friendly one-pot synthesis of trans-cinnamic acids by refluxing a mixture of a malonic acid with aryl aldehyde in pyridine. The product was easily isolated via filtration and thereafter washed and characterized by spectroscopic methods. Results: This method is robust, stereoselective and high yielding. It can be utilized to synthesize a wide array of trans-cinnamic acids in good to excellent yield using 20% of lithium perchlorate catalyst. It is also useful in the synthesis of aliphatic α,β-unsaturated carboxylic acid. Conclusion: The role of lithium perchlorate as a mild catalyst in the synthesis of trans-cinnamic acid was explored. The reactions afforded a good yield of various products with simpler isolation.
- Kaur, Paranjeet,Khatik, Gopal L.
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p. 688 - 692
(2018/07/13)
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- Novel piperazine amides of cinnamic acid derivatives as tyrosinase inhibitors
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Background: A series of novel cinnamic acid piperazine amide derivatives has been designed and synthesized, and their biological activities were also evaluated as potential tyrosinase inhibitors. Methods: Compounds 9, 11 and 17 showed the most potent biological activity (IC50 = 66.5, 61.1 and 66 μM, respectively). In silico docking simulation was performed to position compound 11 into the Agaricus bisporus mushroom tyrosinase’s active site to determine the putative binding interactions. Results and Conclusion: The results indicated that compound 11 could serve as a promising lead compound for further development of potent tyrosinase inhibitors.
- Gür, Zehra Tu??e,?enol, Fatma Sezer,Shekfeh, Suhaib,Orhan, ?lkay Erdo?an,Bano?lu, Erden,?ali?kan, Burcu
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- Discovery of caffeic acid phenethyl ester derivatives as novel myeloid differentiation protein 2 inhibitors for treatment of acute lung injury
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Myeloid differentiation protein 2 (MD2) is an essential molecule which recognizes lipopolysaccharide (LPS), leading to initiation of inflammation through the activation of Toll-like receptor 4 (TLR4) signaling. Caffeic acid phenethyl ester (CAPE) from propolis of honeybee hives could interfere interactions between LPS and the TLR4/MD2 complex, and thereby has promising anti-inflammatory properties. In this study, we designed and synthesized 48 CAPE derivatives and evaluated their anti-inflammatory activities in mouse primary peritoneal macrophages (MPMs) activated by LPS. The most active compound, 10s, was found to bind with MD2 with high affinity, which prevented formation of the LPS/MD2/TLR4 complex. The binding mode of 10s revealed that the major interactions with MD2 were established via two key hydrogen bonds and hydrophobic interactions. Furthermore, 10s showed remarkable protective effects against LPS-caused ALI (acute lung injury) in vivo. Taken together, this work provides new lead structures and candidates as MD2 inhibitors for the development of anti-inflammatory drugs.
- Chen, Lingfeng,Jin, Yiyi,Chen, Hongjin,Sun, Chuchu,Fu, Weitao,Zheng, Lulu,Lu, Min,Chen, Pengqin,Chen, Gaozhi,Zhang, Yali,Liu, Zhiguo,Wang, Yi,Song, Zengqiang,Liang, Guang
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p. 361 - 375
(2017/12/07)
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- Synthesis, Crystallization Studies, and in vitro Characterization of Cinnamic Acid Derivatives as SmHDAC8 Inhibitors for the Treatment of Schistosomiasis
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Schistosomiasis is a neglected parasitic disease that affects more than 265 million people worldwide and for which the control strategy relies on mass treatment with only one drug: praziquantel. Based on the 3-chlorobenzothiophene-2-hydroxamic acid J1075, a series of hydroxamic acids with different scaffolds were prepared as potential inhibitors of Schistosoma mansoni histone deacetylase 8 (SmHDAC8). The crystal structures of SmHDAC8 with four inhibitors provided insight into the binding mode and orientation of molecules in the binding pocket as well as the orientation of its flexible amino acid residues. The compounds were evaluated in screens for inhibitory activity against schistosome and human HDACs. The most promising compounds were further investigated for their activity toward the major human HDAC isotypes. The most potent inhibitors were additionally screened for lethality against the schistosome larval stage using a fluorescence-based assay. Two of the compounds showed significant, dose-dependent killing of the schistosome larvae and markedly impaired egg laying of adult worm pairs maintained in culture.
- Bayer, Theresa,Chakrabarti, Alokta,Lancelot, Julien,Shaik, Tajith B.,Hausmann, Kristin,Melesina, Jelena,Schmidtkunz, Karin,Marek, Martin,Erdmann, Frank,Schmidt, Matthias,Robaa, Dina,Romier, Christophe,Pierce, Raymond J.,Jung, Manfred,Sippl, Wolfgang
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p. 1517 - 1529
(2018/08/01)
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- Design, synthesis of N-phenethyl cinnamide derivatives and their biological activities for the treatment of Alzheimer's disease: Antioxidant, beta-amyloid disaggregating and rescue effects on memory loss
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Gx-50 is a bioactive compound for the treatment of Alzheimer's disease (AD) found in Sichuan pepper (Zanthoxylum bungeanum). In order to find a stronger anti-AD lead compound, 20 gx-50 (1-20) analogs have been designed and synthesized, and their molecular structures were determined based on nuclear magnetic resonance (NMR) and mass spectrometry (MS) analysis, as well as comparison with literature data. Compounds 1-20 were evaluated for their anti-AD potential by using DPPH radical scavenging assay for considering their anti-oxidant activity, thioflavin T (ThT) fluorescence assay for considering the inhibitory or disaggregate potency of Ab, and transgenic Drosophila model assay for evaluating their rescue effect on memory loss. Finally, compound 13 was determined as a promising anti-AD candidate.
- Chai, Tian,Zhao, Xiao-Bo,Wang, Wei-Feng,Qiang, Yin,Zhang, Xiao-Yun,Yang, Jun-Li
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- METHOD FOR THE SYNTHESIS AND PRODUCTION OF ALKENYL COMPOUND
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PROBLEM TO BE SOLVED: To provide a method for producing an efficient alkenyl compound conveniently and inexpensively. SOLUTION: A first compound represented by formula (1) reacts with a second compound represented by formula (3), in the presence of amino acid, in solvent containing amine, in a range of 50-200°C, to produce an alkenyl compound represented by formula (A) [where R1 is hydrogen or an optionally substituted C1-C30 alkyl group, R2 is a carboxyl group or the like, R3 and R4 are hydrogen, an optionally substituted C1-C30 alkyl group or the like]. SELECTED DRAWING: None COPYRIGHT: (C)2018,JPOandINPIT
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Paragraph 0081; 0082
(2018/09/20)
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- A biocatalytic method for the chemoselective aerobic oxidation of aldehydes to carboxylic acids
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Herein, we present a study on the oxidation of aldehydes to carboxylic acids using three recombinant aldehyde dehydrogenases (ALDHs). The ALDHs were used in purified form with a nicotinamide oxidase (NOx), which recycles the catalytic NAD+ at the expense of dioxygen (air at atmospheric pressure). The reaction was studied also with lyophilised whole cell as well as resting cell biocatalysts for more convenient practical application. The optimised biocatalytic oxidation runs in phosphate buffer at pH 8.5 and at 40 °C. From a set of sixty-one aliphatic, aryl-Aliphatic, benzylic, hetero-Aromatic and bicyclic aldehydes, fifty were converted with elevated yield (up to >99%). The exceptions were a few ortho-substituted benzaldehydes, bicyclic heteroaromatic aldehydes and 2-phenylpropanal. In all cases, the expected carboxylic acid was shown to be the only product (>99% chemoselectivity). Other oxidisable functionalities within the same molecule (e.g. hydroxyl, alkene, and heteroaromatic nitrogen or sulphur atoms) remained untouched. The reaction was scaled for the oxidation of 5-(hydroxymethyl)furfural (2 g), a bio-based starting material, to afford 5-(hydroxymethyl)furoic acid in 61% isolated yield. The new biocatalytic method avoids the use of toxic or unsafe oxidants, strong acids or bases, or undesired solvents. It shows applicability across a wide range of substrates, and retains perfect chemoselectivity. Alternative oxidisable groups were not converted, and other classical side-reactions (e.g. halogenation of unsaturated functionalities, Dakin-Type oxidation) did not occur. In comparison to other established enzymatic methods such as the use of oxidases (where the concomitant oxidation of alcohols and aldehydes is common), ALDHs offer greatly improved selectivity.
- Knaus, Tanja,Tseliou, Vasilis,Humphreys, Luke D.,Scrutton, Nigel S.,Mutti, Francesco G.
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supporting information
p. 3931 - 3943
(2018/09/11)
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- New enzymatic and mass spectrometric methodology for the selective investigation of gut microbiota-derived metabolites
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Gut microbiota significantly impact human physiology through metabolic interaction. Selective investigation of the co-metabolism of bacteria and their human host is a challenging task and methods for their analysis are limited. One class of metabolites associated with this co-metabolism are O-sulfated compounds. Herein, we describe the development of a new enzymatic assay for the selective mass spectrometric investigation of this phase II modification class. Analysis of human urine and fecal samples resulted in the detection of 206 sulfated metabolites, which is three times more than reported in the Human Metabolome Database. We confirmed the chemical structure of 36 sulfated metabolites including unknown and commonly reported microbiota-derived sulfated metabolites using synthesized internal standards and mass spectrometric fragmentation experiments. Our findings demonstrate that enzymatic sample pre-treatment combined with state-of-the-art metabolomics analysis represents a new and efficient strategy for the discovery of unknown microbiota-derived metabolites in human samples. Our described approach can be adapted for the targeted investigation of other metabolite classes as well as the discovery of biomarkers for diseases affected by microbiota.
- Ballet, Caroline,Correia, Mário S. P.,Conway, Louis P.,Locher, Theresa L.,Lehmann, Laura C.,Garg, Neeraj,Vujasinovic, Miroslav,Deindl, Sebastian,L?hr, J.-Matthias,Globisch, Daniel
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p. 6233 - 6239
(2018/08/07)
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- Transition Metal Free C-N Bond Forming Dearomatizations and Aryl C-H Aminations by in Situ Release of a Hydroxylamine-Based Aminating Agent
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We outline a simple protocol that accesses directly unprotected secondary amines by intramolecular C-N bond forming dearomatization or aryl C-H amination. The method is dependent on the generation of a potent electrophilic aminating agent released by in situ deprotection of O-Ts activated N-Boc hydroxylamines.
- Farndon, Joshua J.,Ma, Xiaofeng,Bower, John F.
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supporting information
p. 14005 - 14008
(2017/10/17)
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- Synthesis and biological evaluation of novel neoflavonoid derivatives as potential antidiabetic agents
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Various substituted neoflavonoid derivatives were synthesized using sulfated montmorillonite K-10 as a catalyst. This method is environmental friendly, sustainable and economical, convenient in isolation and purification processes, with little byproducts, using earth-abundant catalysts and has relatively high yield. Those neoflavonoid derivatives were screened for antioxidant, a-glucosidase inhibitory, aldose reductase 2 (ALR2) inhibitory and advanced glycation end-product formation inhibitory effects. Most compounds exhibited significant antioxidant and advanced glycation end-product (AGE) formation inhibitory activities. It was interesting to note that out of thirty compounds, 8k and 8l were found to have greater ALR2 inhibitory activity than the standard drug quercetin. The pharmacological studies suggested neoflavonoid with adjacent 7,8-dihydroxy groups were more effective in inhibiting ALR2. Antidiabetic activity studies had shown that compounds 8l and 8m were equipotent to the standard drug glibenclamide in vivo. In summary, the target compound 8l provided a potential drug design concept for the development of therapeutic or prophylactic agents of diabetes and diabetes complications.
- Wang, Bing,Li, Na,Liu, Teng,Sun, Jie,Wang, Xiaojing
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p. 34448 - 34460
(2017/07/22)
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- Enantioselective Organocatalytic Intramolecular Aza-Diels–Alder Reaction
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A highly efficient catalytic enantioselective intramolecular Povarov reaction was developed with primary anilines as 2-azadiene precursors. A wide variety of angularly fused azacycles were obtained without column chromatography in high to excellent yields and with excellent diastereo- and enantioselectivity (d.r.>99:1 and up to e.r. 99:1). Furthermore, the catalyst loading could be lowered to 1 mol %, and the obtained azacycles could be used as key intermediates for further transformations to generate additional molecular diversity.
- Jarrige, Lucie,Blanchard, Florent,Masson, Géraldine
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supporting information
p. 10573 - 10576
(2017/08/22)
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- Palladium nanoparticles immobilized on amphiphilic and hyperbranched polymer-functionalized magnetic nanoparticles: An efficient semi-heterogeneous catalyst for Heck reaction
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To address the obstacles facing the use of palladium-based homogeneous and heterogeneous catalysts in C─C cross-coupling reactions, a novel semi-heterogeneous support was developed based on hyperbranched poly(ethylene glycol)-block-poly(citric acid)-functionalized Fe3O4 magnetic nanoparticles (Fe3O4@PCA-b-PEG). Because of the surface modification of the Fe3O4 nanoparticles with amphiphilic and hyperbranched polymers (PCA-b-PEG), these hybrid materials are not only soluble in a wide range of solvents (e.g. water, ethanol and dimethylformamide) but also are able to trap Pd2+ ions via complex formation of free carboxyl groups of the PCA dendrimer with metal ions. The reduction of trapped palladium ions in the dendritic shell of Fe3O4@PCA-b-PEG leads to immobilized palladium nanoparticles. The morphology and structural features of the catalyst were characterized using various microscopic and spectroscopic techniques. The catalyst was effectively used in the palladium-catalysed Mizoroki–Heck coupling reaction in water as a green solvent. In addition, the catalyst can be easily recovered from the reaction mixture by applying an external magnetic field and reused for more than ten consecutive cycles without much loss in activity, exhibiting an example of a sustainable and green methodology.
- Tabatabaei Rezaei, Seyed Jamal,Shamseddin, Azin,Ramazani, Ali,Mashhadi Malekzadeh, Asemeh,Azimzadeh Asiabi, Pegah
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- Optimized synthesis of novel prenyl ferulate performed by feruloyl esterases from Myceliophthora thermophila in microemulsions
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Five feruloyl esterases (FAEs; EC 3.1.1.73), FaeA1, FaeA2, FaeB1, and FaeB2 from Myceliophthora thermophila C1 and MtFae1a from M. thermophila ATCC 42464, were tested for their ability to catalyze the transesterification of vinyl ferulate (VFA) with prenol in detergentless microemulsions. Reaction conditions were optimized investigating parameters such as the medium composition, the substrate concentration, the enzyme load, the pH, the temperature, and agitation. FaeB2 offered the highest transesterification yield (71.5?±?0.2%) after 24?h of incubation at 30?°C using 60?mM VFA, 1?M prenol, and 0.02?mg FAE/mL in a mixture comprising of 53.4:43.4:3.2?v/v/v n-hexane:t-butanol:100?mM MOPS-NaOH, pH 6.0. At these conditions, the competitive side hydrolysis of VFA was 4.7-fold minimized. The ability of prenyl ferulate (PFA) and its corresponding ferulic acid (FA) to scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals was significant and similar (IC50 423.39?μM for PFA, 329.9?μM for FA). PFA was not cytotoxic at 0.8–100?μM (IC50 220.23?μM) and reduced intracellular reactive oxygen species (ROS) in human skin fibroblasts at concentrations ranging between 4 and 20?μM as determined with the dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay.
- Antonopoulou, Io,Leonov, Laura,Jütten, Peter,Cerullo, Gabriella,Faraco, Vincenza,Papadopoulou, Adamantia,Kletsas, Dimitris,Ralli, Marianna,Rova, Ulrika,Christakopoulos, Paul
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p. 3213 - 3226
(2017/04/10)
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- Ruticarpsides A–C, three new ester glycosides from the fruits of Tetradium ruticarpum
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In the course of our ongoing phytochemical investigation on the n-butanol extract of the fruits of Tetradium ruticarpum (Rutaceae), three new compounds, ruticarpsides A–C (1–3), were obtained and their structures were elucidated by a comprehensive analysis of NMR and MS data. Compound 3 showed a weak inhibition effect on nitric oxide production in BV-2 microglial cells stimulated with lipopolysaccharide.
- He, Wei,Jiang, Yong,Zhao, Ming-Bo,Zeng, Ke-Wu,Tu, Peng-Fei
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p. 659 - 665
(2017/05/26)
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- Feruloylated Products from Coconut Oil and Shea Butter
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The synthesis of feruloylated coconut oil and feruloylated shea butter were demonstrated in 0.5-L scale, shaken, batch reactions. Ethyl ferulate and the vegetable oil/fat were combined in a 1.0:1.3?mol ratio in the presence of Candida antartica lipase B immobilized on an acrylic resin (Novozym 435) at 60?°C. The transesterification of ethyl ferulate with coconut oil and shea butter reached equilibrium conversions, after 22?days, of 63 and 70%, respectively, with the shea butter transesterifications producing a white precipitate not observed in the coconut oil transesterifications. The faster transesterification rates, equilibrium conversions and white precipitate were shown to result from di- and monoacylglycerols (DAG and MAG) present in the shea butter. The transesterification of ethyl ferulate and coconut oil was also tested in a continuous, enzymatic, packed-bed bioreactor using Novozym 435 at 60?°C to produce feruloylated coconut oil at rates of 0.5–0.9?kg/day over 4.5?months. The feruloylated coconut oil acylglycerol species were identified by LC–MS analysis of transesterification reactions of ethyl ferulate with medium chain triacylglycerol (TAG) standards, C8–C14. The feruloylated vegetable oils possessed an ultra violet (UV) absorbing λmax 328?nm, making them good UVAII absorbers, as defined by the U.S. Food and Drug Administration. The feruloylated coconut oil possessed a 17.5% higher absorption capacity than feruloylated shea butter on a per weight basis. All the feruloylated vegetable oils possessed rapid antioxidant capacity (50% reduction of initial radical concentration 5?min) at the concentrations tested, 0.5–2.5?mM. Feruloylated coconut oil possessed chemical and physical characteristics that suggested it would be fungible for feruloylated soybean oil in current retail formulations.
- Compton, David L.,Goodell, John R.,Berhow, Mark A.,Kenar, James A.,Cermak, Steven C.,Evans, Kervin O.
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p. 397 - 411
(2017/03/08)
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- Discovery of a New Inhibitor of Myeloid Differentiation 2 from Cinnamamide Derivatives with Anti-Inflammatory Activity in Sepsis and Acute Lung Injury
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Acute inflammatory diseases, including acute lung injury and sepsis, remain the most common life-threatening illness in intensive care units worldwide. Cinnamamide has been incorporated in several synthetic compounds with therapeutic potentials including anti-inflammatory properties. However, the possible mechanism and direct molecular target of cinnamamides for their anti-inflammatory effects were rarely investigated. In this study, we synthesized a series of cinnamamides and evaluated their anti-inflammatory activities. The most active compound, 2i, was found to block LPS-induced MD2/TLR4 pro-inflammatory signaling activation in vitro and to attenuate LPS-caused sepsis and acute lung injury in vivo. Mechanistically, we demonstrated that 2i exerts its anti-inflammatory effects by directly targeting and binding MD2 in Arg90 and Tyr102 residues and inhibiting MD2/TLR4 complex formation. Taken together, this work presents a novel MD2 inhibitor, 2i, which has the potential to be developed as a candidate for the treatment of sepsis, and provides a new lead structure for the development of anti-inflammatory agents targeting MD2.
- Chen, Gaozhi,Zhang, Yali,Liu, Xing,Fang, Qilu,Wang, Zhe,Fu, Lili,Liu, Zhiguo,Wang, Yi,Zhao, Yunjie,Li, Xiaokun,Liang, Guang
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p. 2436 - 2451
(2016/04/10)
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- Synthesis and biological evaluation of N-cinnamoyl and mandelate metformin analogues
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A series of N,N-dimethyl-N1-[3-(substituted phenyl)-1-oxo-2-propenyl]biguanides were synthesized by coupling a solution of metformin in pyridine with different cinnamoyl chloride derivatives in ether for 3 h in addition to synthesis of some five molecules of metformin-mandelates. All the synthesized cinnamoyl metformins and a few metformin-mandelates were characterized by IR, NMR and Mass spectroscopic techniques. All the synthesized compounds were also evaluated for their antioxidant activity by DPPH scavenging method and nitric oxide scavenging method. All the compounds exhibited good antioxidant activity.
- Anitha Kumari,Bharathi,Prabhu,Ponnudurai
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p. 1895 - 1898
(2016/07/06)
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