Science.gov

Sample records for 2-thiophenecarboxylic acid derivatives

  1. Development of potential manufacturing routes for substituted thiophenes--preparation of halogenated 2-thiophenecarboxylic acid derivatives as building blocks for a new family of 2,6-dihaloaryl 1,2,4-triazole insecticides.

    PubMed

    Hull, John W; Romer, Duane R; Podhorez, David E; Ash, Mezzie L; Brady, Christine H

    2007-09-04

    Dow AgroSciences has been investigating a new family of functionalized 2,6-dihaloaryl 1,2,4-triazole insecticides featuring specifically targeted insecticidal activities coupled with low mammalian toxicity. With broad spectrum control of both chewing and sap-feeding pests in mind, this family of compounds has been under investigation for aphid, mite, and whitefly control in food crop protection as well as ornamental applications. Two specific targets for development have been the 2,6-dihalo 1,2,4-triazoles XR-693 and XR-906, which require a supply of the halogenated 2-thiophenecarboxylic acid derivatives 1, 2, and 3 for assembly of the C-ring portion of the triazole products. Potential manufacturing routes to three halogenated 2-thiophenecarboxylic acid derivatives 4-bromo-3-methyl-2-thiophenecarbonyl chloride 1, 3,4,5-trichloro-2-thiophenecarbonyl chloride 2, and 3,4,5-trichloro-2-thiophenecarbonitrile 3 from commercially available thiophene raw materials have been developed and demonstrated on a laboratory scale. A one-pot bromination/debromination procedure developed for 3-methylthiophene gave 2,4-dibromo-3-methylthiophene. Carboxylic acid functionality was then introduced either by a Grignard metallation followed by carbonation with CO2, or by a palladium catalyzed carbonylation procedure under CO pressure. The vapor phase chlorination of 2-thiophenecarbonitrile with chlorine gas at 500 degrees C with an average residence time of 6 seconds gave 3,4,5-trichloro-2-thiophenenitrile 3 in a 69% distilled yield, a process that was carried out on a multi-kilogram scale in the laboratory. Finally, a route for the preparation of 3,4,5-trichloro-2-thiophenecarbonyl chloride 2 was developed from tetrachlorothiophene via either a lithiation reaction with n-butyllithium in MTBE solvent, or by a previously reported Grignard method using 1,2-dibromoethane as activator, followed by carbonation of the anion with CO2 to give the trichloro-2-thiophenecarboxylic acid, which was

  2. Development of potential manufacturing routes for substituted thiophenes – Preparation of halogenated 2-thiophenecarboxylic acid derivatives as building blocks for a new family of 2,6-dihaloaryl 1,2,4-triazole insecticides

    PubMed Central

    Hull, John W; Romer, Duane R; Podhorez, David E; Ash, Mezzie L; Brady, Christine H

    2007-01-01

    Background Dow AgroSciences has been investigating a new family of functionalized 2,6-dihaloaryl 1,2,4-triazole insecticides featuring specifically targeted insecticidal activities coupled with low mammalian toxicity. With broad spectrum control of both chewing and sap-feeding pests in mind, this family of compounds has been under investigation for aphid, mite, and whitefly control in food crop protection as well as ornamental applications. Two specific targets for development have been the 2,6-dihalo 1,2,4-triazoles XR-693 and XR-906, which require a supply of the halogenated 2-thiophenecarboxylic acid derivatives 1, 2, and 3 for assembly of the C-ring portion of the triazole products. Results Potential manufacturing routes to three halogenated 2-thiophenecarboxylic acid derivatives 4-bromo-3-methyl-2-thiophenecarbonyl chloride 1, 3,4,5-trichloro-2-thiophenecarbonyl chloride 2, and 3,4,5-trichloro-2-thiophenecarbonitrile 3 from commercially available thiophene raw materials have been developed and demonstrated on a laboratory scale. A one-pot bromination/debromination procedure developed for 3-methylthiophene gave 2,4-dibromo-3-methylthiophene. Carboxylic acid functionality was then introduced either by a Grignard metallation followed by carbonation with CO2, or by a palladium catalyzed carbonylation procedure under CO pressure. The vapor phase chlorination of 2-thiophenecarbonitrile with chlorine gas at 500°C with an average residence time of 6 seconds gave 3,4,5-trichloro-2-thiophenenitrile 3 in a 69% distilled yield, a process that was carried out on a multi-kilogram scale in the laboratory. Finally, a route for the preparation of 3,4,5-trichloro-2-thiophenecarbonyl chloride 2 was developed from tetrachlorothiophene via either a lithiation reaction with n-butyllithium in MTBE solvent, or by a previously reported Grignard method using 1,2-dibromoethane as activator, followed by carbonation of the anion with CO2 to give the trichloro-2-thiophenecarboxylic acid

  3. Synthesis, crystal structure and biological activity of two Mn complexes with 4-acyl pyrazolone derivatives.

    PubMed

    Li, Yue; Zhao, Jing; He, Chuan-Chuan; Zhang, Li; Sun, Su-Rong; Xu, Guan-Cheng

    2015-09-01

    In order to study the biological activities of transitional metal complexes based on 4-acyl pyrazolone derivatives, two Mn complexes [Mn(HLa)(La)]·(CH3CN)1.5·H2O (1) and [Mn2(Lb)2(μ-EtO)2(EtOH)2] (2) (H2La = N-(1-phenyl-3-methyl-4-benzoyl-5-pyrazolone)-2-thiophenecarboxylic acid hydrazide, H2Lb = N-(1-phenyl-3-methyl-4-propenylidene-5-pyrazolone)-2-thiophenecarboxylic acid hydrazide) have been synthesized and characterized. Single crystal X-ray diffraction analysis indicated that 1 is a mononuclear complex and 2 exhibits a dinuclear centrosymmetric structure. Binding of the complexes with Herring Sperm DNA (HS-DNA) showed that complexes 1 and 2 could intercalate to DNA with quenching constant of 5.3×10(4) M(-1) and 4.9×10(4) M(-1), respectively. The interactions of the complexes with bovine serum albumin (BSA) indicated that complexes 1 and 2 could quench the intrinsic fluorescence of BSA in a static quenching process. Further, the inhibitory effects of the complexes on the cell population growth of the human esophageal cancer Eca-109 cells and the cervical cancer HeLa cells were determined by MTT assay, which indicated that both 1 and 2 significantly inhibited the growth of Eca-109 and HeLa cells, the inhibitory activity of complex 1 is stronger than that of 2. We further observed that complex 1 inhibited the growth of HeLa cells through inducing the apoptosis and arresting cell cycle at S phase. Our results suggested that both complexes 1 and 2 have DNA- and protein-binding capacity and antitumor activity.

  4. Bicyclic glutamic acid derivatives.

    PubMed

    Meyer, Udo; Bisel, Philippe; Weckert, Edgar; Frahm, August Wilhelm

    2006-05-15

    For the second-generation asymmetric synthesis of the trans-tris(homoglutamic) acids via Strecker reaction of chiral ketimines, the cyanide addition as the key stereodifferentiating step produces mixtures of diastereomeric alpha-amino nitrile esters the composition of which is independent of the reaction temperature and the type of the solvent, respectively. The subsequent hydrolysis is exclusively achieved with concentrated H(2)SO(4) yielding diastereomeric mixtures of three secondary alpha-amino alpha-carbamoyl-gamma-esters and two diastereomeric cis-fused angular alpha-carbamoyl gamma-lactams as bicyclic glutamic acid derivatives, gained from in situ stereomer differentiating cyclisation of the secondary cis-alpha-amino alpha-carbamoyl-gamma-esters. Separation was achieved by CC. The pure secondary trans-alpha-amino alpha-carbamoyl-gamma-esters cyclise on heating and treatment with concentrated H(2)SO(4), respectively, to diastereomeric cis-fused angular secondary alpha-amino imides. Their hydrogenolysis led to the enantiomeric cis-fused angular primary alpha-amino imides. The configuration of all compounds was completely established by NMR methods, CD-spectra, and by X-ray analyses of the (alphaR,1R,5R)-1-carbamoyl-2-(1-phenylethyl)-2-azabicyclo[3.3.0]octan-3-one and of the trans-alphaS,1S,2R-2-ethoxycarbonylmethyl-1-(1-phenylethylamino)cyclopentanecarboxamide.

  5. Phosphorus derivatives of salicylic acid

    NASA Astrophysics Data System (ADS)

    Chvertkina, L. V.; Khoklov, P. S.; Mironov, Vladimir F.

    1992-10-01

    The present state of work on the methods of synthesis, chemical properties, and practical applications of phosphorus-containing derivatives of salicylic acid has been reviewed. The characteristics of the chemical transformations of cyclic and acyclic phosphorus derivatives of salicylic acid related to the coordination state of the phosphorus atom have been examined. The bibliography includes 158 references.

  6. Synthesis of 5-alkoxythieno[2,3-e][1,2,4]triazolo[4,3-c]pyrimidine derivatives and evaluation of their anticonvulsant activities.

    PubMed

    Wang, Shi-Ben; Piao, Guang-Chun; Zhang, Hong-Jian; Quan, Zhe-Shan

    2015-04-15

    This work concerns the design and synthesis of novel, substituted 5-alkoxythieno[2,3-e][1,2,4]triazolo[4,3-c]pyrimidine derivatives 5a-p prepared from 3-amino-2-thiophenecarboxylic acid methyl ester. The final compounds were screened for their in vivo anticonvulsant activity using maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) tests. Neurotoxicity (NT) was tested using a rotarod test. The structure-anticonvulsant activity relationship analysis revealed that the most effective structural motif involves a substituted phenol, especially when substituted with a single chlorine, fluorine or trifluoromethyl group (at the meta-position), or two chlorine atoms. These molecules possessed high activity according to the MES and scPTZ models. Quantitative assessment of the compounds after intraperitoneal administration in mice showed that the most active compound was 5-[3-(trifluoromethyl)phenoxy]thieno[2,3-e] [1,2,4]triazolo[4,3-c]pyrimidine (5o) with ED50 values of 11.5 mg/kg (MES) and 58.9 mg/kg (scPTZ). Furthermore, compound 5o was more effective in the MES and scPTZ tests than the well-known anticonvulsant drugs carbamazepine and ethosuximide.

  7. Metabolism of hop-derived bitter acids.

    PubMed

    Cattoor, Ko; Dresel, Michael; De Bock, Lies; Boussery, Koen; Van Bocxlaer, Jan; Remon, Jean-Paul; De Keukeleire, Denis; Deforce, Dieter; Hofmann, Thomas; Heyerick, Arne

    2013-08-21

    In this study, in vitro metabolism of hop-derived bitter acids was investigated. Besides their well-known use as bitter compounds in beer, in several studies, bioactive properties have been related to these types of molecules. However, scientific data on the absorption, distribution, metabolism, and excretion aspects of these compounds are limited. More specific, in this study, α-acids, β-acids, and iso-α-acids were incubated with rabbit microsomes, and fractions were subjected to LC-MS/MS analysis for identification of oxidative biotransformation products. Metabolism of β-acids was mainly characterized by conversion into hulupones and the formation of a series of tricyclic oxygenated products. The most important metabolites of α-acids were identified as humulinones and hulupones. Iso-α-acids were found to be primarly metabolized into cis- and trans-humulinic acids, next to oxidized alloiso-α-acids. Interestingly, the phase I metabolites were highly similar to the oxidative degradation products in beer. These findings show a first insight into the metabolites of hop-derived bitter acids and could have important practical implications in the bioavailability aspects of these compounds, following ingestion of hop-based food products and nutraceuticals.

  8. Antibacterial anthranilic acid derivatives from Geijera parviflora.

    PubMed

    Shou, Qingyao; Banbury, Linda K; Maccarone, Alan T; Renshaw, Dane E; Mon, Htwe; Griesser, Stefani; Griesser, Hans J; Blanksby, Stephen J; Smith, Joshua E; Wohlmuth, Hans

    2014-03-01

    Five anthranilic acid derivatives, a mixture I of three new compounds 11'-hexadecenoylanthranilic acid (1), 9'-hexadecenoylanthranilic acid (2), and 7'-hexadecenoylanthranilic acid (3), as well as a new compound 9,12,15-octadecatrienoylanthranilic acid (4) together with a new natural product, hexadecanoylanthranilic acid (5), were isolated from Geijera parviflora Lindl. (Rutaceae). Their structures were elucidated by extensive spectroscopic measurements, and the positions of the double bonds in compounds 1-3 of the mixture I were determined by tandem mass spectrometry employing ozone-induced dissociation. The mixture I and compound 5 showed good antibacterial activity against several Gram-positive strains. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. The cytotoxic activity of ursolic acid derivatives.

    PubMed

    Ma, Chao-Mei; Cai, Shao-Qing; Cui, Jing-Rong; Wang, Rui-Qing; Tu, Peng-Fei; Hattori, Masao; Daneshtalab, Mohsen

    2005-06-01

    Ursolic acid and 2alpha-hydroxyursolic acid isolated from apple peels were found to show growth inhibitory activity against four tumor cell lines, HL-60, BGC, Bel-7402 and Hela. Structural modifications were performed on the C-3, C-28 and C-11 positions of ursolic acid and the cytotoxicity of the derivatives was evaluated. The SAR revealed that the triterpenes possessing two hydrogen-bond forming groups (an H-donor and a carbonyl group) at positions 3 and 28 exhibit cytotoxic activity. The configuration at C-3 was found to be important for the activity. Introduction of an amino group increased the cytotoxicity greatly. A 3beta-amino derivative was 20 times more potent than the parent ursolic acid. The 28-aminoalkyl dimer compounds showed selective cytotoxicity.

  10. Ionic liquid crystals derived from amino acids.

    PubMed

    Mansueto, Markus; Frey, Wolfgang; Laschat, Sabine

    2013-11-18

    Novel chiral amino acid derived ionic liquid crystals with amine and amide moieties as spacers between the imidazolium head group and the alkyl chain were synthesised. The key step in the synthesis utilised the relatively uncommon SO3 leaving group in a microwave-assisted reaction. The mesomorphic properties of the mesogens were determined by differential scanning calorimetry (DSC), polarising optical microscopy (POM) and X-ray diffraction. All liquid crystalline salts exhibit a smectic A mesophase geometry with strongly interdigitated bilayer structures. An increase of the steric bulk of the stereogenic centre hindered the formation of mesophases. In case of phenylalanine-derived derivatives a mesomorphic behaviour was observed for shorter alkyl chains as compared to other amino acid derivatives indicating an additional stabilising effect by the phenyl moiety.

  11. Biodegradable polymers derived from amino acids.

    PubMed

    Khan, Wahid; Muthupandian, Saravanan; Farah, Shady; Kumar, Neeraj; Domb, Abraham J

    2011-12-08

    In the past three decades, the use of polymeric materials has increased dramatically for biomedical applications. Many α-amino acids derived biodegradable polymers have also been intensely developed with the main goal to obtain bio-mimicking functional biomaterials. Polymers derived from α-amino acids may offer many advantages, as these polymers: (a) can be modified further to introduce new functions such as imaging, molecular targeting and drugs can be conjugated chemically to these polymers, (b) can improve on better biological properties like cell migration, adhesion and biodegradability, (c) can improve on mechanical and thermal properties and (d) their degradation products are expected to be non-toxic and readily metabolized/excreted from the body. This manuscript focuses on biodegradable polymers derived from natural amino acids, their synthesis, biocompatibility and biomedical applications. It is observed that polymers derived from α-amino acids constitute a promising family of biodegradable materials. These provide innovative multifunctional polymers possessing amino acid side groups with biological activity and with innumerous potential applications.

  12. Enzymatic synthesis of cinnamic acid derivatives.

    PubMed

    Lee, Gia-Sheu; Widjaja, Arief; Ju, Yi-Hsu

    2006-04-01

    Using Novozym 435 as catalyst, the syntheses of ethyl ferulate (EF) from ferulic acid (4-hydroxy 3-methoxy cinnamic acid) and ethanol, and octyl methoxycinnamate (OMC) from p-methoxycinnamic acid and 2-ethyl hexanol were successfully carried out in this study. A conversion of 87% was obtained within 2 days at 75 degrees C for the synthesis of EF. For the synthesis of OMC at 80 degrees C, 90% conversion can be obtained within 1 day. The use of solvent and high reaction temperature resulted in better conversion for the synthesis of cinnamic acid derivatives. Some cinnamic acid esters could also be obtained with higher conversion and shorter reaction times in comparison to other methods reported in the literature. The enzyme can be reused several times before significant activity loss was observed.

  13. Caffeic acid derivatives from Bupleurum chinense

    PubMed Central

    Haghi, G.; Hatami, A.; Mehran, M.; Hosseini, H.

    2014-01-01

    In this study, caffeic acid (CA) and its three derivatives including 3-caffeoylquinic acid (3-CQA, neochlorogenic acid), 4-caffeoylquinic acid (4-CQA, cryptochlorogenic acid), and 5-caffeoylquinic acid (5-CQA, chlorogenic acid) were identified in Bupleurum chinense aerial parts using reverse-phase high-performance liquid chromatography (RP-HPLC) with photodiode array (PDA) detector, reference compounds and chemical reactions. Separation was performed on a C18 column using gradient elution with 4% (v/v) aqueous acetic acid and acetonitrile as mobile phase at ambient temperature. In addition, the flavonoid aglycones were characterized and quantified after acid hydrolysis of the plant material. The flavonols profile showed quercetin (0.36 g per 100 g), kaempferol (1.11 g per 100 g) and isorhamnetin (0.16 g per 100 g). Total phenolic and total flavonoid contents ranged from 7.3 to 18.7% and 0.58 to 2.72% in dry plant material, respectively. PMID:25657804

  14. Novel cajaninstilbene acid derivatives as antibacterial agents.

    PubMed

    Geng, Zhi-Zhong; Zhang, Jian-Jun; Lin, Jing; Huang, Mei-Yan; An, Lin-Kun; Zhang, Hong-Bin; Sun, Ping-Hua; Ye, Wen-Cai; Chen, Wei-Min

    2015-07-15

    Discovery of novel antibacterial agents with new structural scaffolds that combat drug-resistant pathogens is an urgent task. Cajaninstilbene acid, which is isolated from pigeonpea leaves, has shown antibacterial activity. In this study, a series of cajaninstilbene acid derivatives were designed and synthesized. The antibacterial activities of these compounds against gram-negative and gram-positive bacteria, as well as nine strains of methicillin-resistant staphylococcus aureus (MRSA) bacteria are evaluated,and the related structure-activity relationships are discussed. Assays suggest that some of the synthetic cajaninstilbene acid derivatives exhibit potent antibacterial activity against gram-positive bacterial strains and MRSA. Among these compounds, 5b, 5c, 5j and 5k show better antibacterial activity than the positive control compounds. The results of MTT assays illustrate the low cytotoxicity of the active compounds.

  15. Antimycobacterial evaluation of pyrazinoic acid reversible derivatives.

    PubMed

    Dolezal, Martin; Kesetovic, Diana; Zitko, Jan

    2011-01-01

    Design, results of in vitro antimycobacterial evaluation, and study of structure-activity relationships of various pyrazinecarboxylic acid reversible derivatives are presented. This review deals with some pyrazinamide analogues/prodrugs derived from Nphenylpyrazine- 2-carboxamides (1), arylaminopyrazine-2,5-dicarbonitriles (2), aryl/alkylsulphanylpyrazines (3,4), and aroylpyrazines (5) effecting >50% inhibition in the primary antimycobacterial screen. The promising pyrazine candidates for further antimycobacterial evaluation were discovered. Results give good view onto structure-activity relationships of these analogues and promise even better activity of new compounds prepared after some structure optimization experiments.

  16. Evaluation of ascorbic acid in protecting labile folic acid derivatives.

    PubMed

    Wilson, S D; Horne, D W

    1983-11-01

    The use of ascorbic acid as a reducing agent to protect labile, reduced derivatives of folic acid has been evaluated by high-performance liquid chromatographic separations and Lactobacillus casei microbiological assay of eluate fractions. Upon heating for 10 min at 100 degrees C, solutions of tetrahydropteroylglutamic acid (H4PteGlu) in 2% sodium ascorbate gave rise to 5,10-methylene-H4PteGlu and 5-methyl-H4PteGlu. H2PteGlu acid gave rise to 5-methyl-H4PteGlu and PteGlu. 10-Formyl-H4PteGlu gave rise to 5-formyl-H4PteGlu and 10-formyl-PteGlu. 5-Formyl-H4-PteGlu gave rise to a small amount of 10-formyl-PteGlu. 5-Methyl-H4PteGlu and PteGlu appeared stable to these conditions. These interconversions were not seen when solutions of these folate derivatives were kept at 0 degrees C in 1% ascorbate. These observations indicate that elevated temperatures are necessary for the interconversions of folates in ascorbate solutions. Assays of ascorbic acid solutions indicated the presence of formaldehyde (approximately equal to 6 mM). This was confirmed by the identification of 3,5-diacetyl-1,4-dihydrolutidine by UV, visible, and fluorescence spectroscopy and by thin-layer chromatography of chloroform extracts of the reaction mixture of ascorbic acid solutions, acetylacetone, and ammonium acetate. These results indicate that solutions of sodium ascorbate used at elevated temperatures are not suitable for extracting tissue for the subsequent assay of the individual folic acid derivatives.

  17. Evaluation of ascorbic acid in protecting labile folic acid derivatives.

    PubMed Central

    Wilson, S D; Horne, D W

    1983-01-01

    The use of ascorbic acid as a reducing agent to protect labile, reduced derivatives of folic acid has been evaluated by high-performance liquid chromatographic separations and Lactobacillus casei microbiological assay of eluate fractions. Upon heating for 10 min at 100 degrees C, solutions of tetrahydropteroylglutamic acid (H4PteGlu) in 2% sodium ascorbate gave rise to 5,10-methylene-H4PteGlu and 5-methyl-H4PteGlu. H2PteGlu acid gave rise to 5-methyl-H4PteGlu and PteGlu. 10-Formyl-H4PteGlu gave rise to 5-formyl-H4PteGlu and 10-formyl-PteGlu. 5-Formyl-H4-PteGlu gave rise to a small amount of 10-formyl-PteGlu. 5-Methyl-H4PteGlu and PteGlu appeared stable to these conditions. These interconversions were not seen when solutions of these folate derivatives were kept at 0 degrees C in 1% ascorbate. These observations indicate that elevated temperatures are necessary for the interconversions of folates in ascorbate solutions. Assays of ascorbic acid solutions indicated the presence of formaldehyde (approximately equal to 6 mM). This was confirmed by the identification of 3,5-diacetyl-1,4-dihydrolutidine by UV, visible, and fluorescence spectroscopy and by thin-layer chromatography of chloroform extracts of the reaction mixture of ascorbic acid solutions, acetylacetone, and ammonium acetate. These results indicate that solutions of sodium ascorbate used at elevated temperatures are not suitable for extracting tissue for the subsequent assay of the individual folic acid derivatives. PMID:6415653

  18. Amino acids derived from Titan tholins

    NASA Technical Reports Server (NTRS)

    Khare, B. N.; Sagan, C.; Ogino, H.; Nagy, B.; Er, C.; Schram, K. H.; Arakawa, E. T.

    1986-01-01

    An organic heteropolymer (Titan tholin) was produced by continuous dc discharge through a 0.9 N2/0.1 CH4 gas mixture at 0.2 mbar pressure, roughly simulating the cloudtop atmosphere of Titan. Treatment of this tholin with 6N HCl yielded 16 amino acids by gas chromatography after derivatization of N-trifluroacetyl isopropyl esters on two different capillary columns. Identifications were confirmed by GC/MS. Glycine, aspartic acid, and alpha- and beta-alanine were produced in greatest abundance; the total yield of amino acids was approximately 10(-2), approximately equal to the yield of urea. The presence of "nonbiological" amino acids, the absence of serine, and the fact that the amino acids are racemic within experimental error together indicate that these molecules are not due to microbial or other contamination, but are derived from the tholin. In addition to the HCN, HC2CN, and (CN)2 found by Voyager, nitriles and aminonitriles should be sought in the Titanian atmosphere and, eventually, amino acids on the surface. These results suggest that episodes of liquid water in the past or future of Titan might lead to major further steps in prebiological organic chemistry on that body.

  19. 21 CFR 172.862 - Oleic acid derived from tall oil fatty acids.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Oleic acid derived from tall oil fatty acids. 172... FOOD FOR HUMAN CONSUMPTION Multipurpose Additives § 172.862 Oleic acid derived from tall oil fatty acids. The food additive oleic acid derived from tall oil fatty acids may be safely used in food and as...

  20. 21 CFR 172.862 - Oleic acid derived from tall oil fatty acids.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Oleic acid derived from tall oil fatty acids. 172... FOOD FOR HUMAN CONSUMPTION Multipurpose Additives § 172.862 Oleic acid derived from tall oil fatty acids. The food additive oleic acid derived from tall oil fatty acids may be safely used in food and as...

  1. 21 CFR 172.862 - Oleic acid derived from tall oil fatty acids.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Oleic acid derived from tall oil fatty acids. 172... FOOD FOR HUMAN CONSUMPTION Multipurpose Additives § 172.862 Oleic acid derived from tall oil fatty acids. The food additive oleic acid derived from tall oil fatty acids may be safely used in food and...

  2. 21 CFR 172.862 - Oleic acid derived from tall oil fatty acids.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Oleic acid derived from tall oil fatty acids. 172... FOOD FOR HUMAN CONSUMPTION Multipurpose Additives § 172.862 Oleic acid derived from tall oil fatty acids. The food additive oleic acid derived from tall oil fatty acids may be safely used in food and...

  3. 21 CFR 172.862 - Oleic acid derived from tall oil fatty acids.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Oleic acid derived from tall oil fatty acids. 172... Multipurpose Additives § 172.862 Oleic acid derived from tall oil fatty acids. The food additive oleic acid derived from tall oil fatty acids may be safely used in food and as a component in the manufacture of...

  4. Towards Tartaric-Acid-Derived Asymmetric Organocatalysts

    PubMed Central

    Gratzer, Katharina; Gururaja, Guddeangadi N; Waser, Mario

    2013-01-01

    Tartaric acid is one of the most prominent naturally occurring chiral compounds. Whereas its application in the production of chiral ligands for metal-catalysed reactions has been exhaustively investigated, its potential to provide new organocatalysts has been less extensively explored. Nevertheless, some impressive results, such as the use of TADDOLs as chiral H-bonding catalysts or of tartrate-derived asymmetric quaternary ammonium salt catalysts, have been reported over the last decade. The goal of this article is to provide a representative overview of the potential and the limitations of tartaric acid or TADDOLs in the creation of new organocatalysts and to highlight some of the most spectacular applications of these catalysts, as well as to summarize case studies in which other classes of chiral backbones were better suited. PMID:24194674

  5. 40 CFR 721.6097 - Phosphoric acid derivative (generic name).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Phosphoric acid derivative (generic... Specific Chemical Substances § 721.6097 Phosphoric acid derivative (generic name). (a) Chemical substance... phosphoric acid derivative (PMN P-95-284) is subject to reporting under this section for the significant new...

  6. 40 CFR 721.6097 - Phosphoric acid derivative (generic name).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Phosphoric acid derivative (generic... Specific Chemical Substances § 721.6097 Phosphoric acid derivative (generic name). (a) Chemical substance... phosphoric acid derivative (PMN P-95-284) is subject to reporting under this section for the significant new...

  7. 40 CFR 721.6097 - Phosphoric acid derivative (generic name).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Phosphoric acid derivative (generic... Specific Chemical Substances § 721.6097 Phosphoric acid derivative (generic name). (a) Chemical substance... phosphoric acid derivative (PMN P-95-284) is subject to reporting under this section for the significant...

  8. 40 CFR 721.6097 - Phosphoric acid derivative (generic name).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Phosphoric acid derivative (generic... Specific Chemical Substances § 721.6097 Phosphoric acid derivative (generic name). (a) Chemical substance... phosphoric acid derivative (PMN P-95-284) is subject to reporting under this section for the significant...

  9. 40 CFR 721.6097 - Phosphoric acid derivative (generic name).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Phosphoric acid derivative (generic... Specific Chemical Substances § 721.6097 Phosphoric acid derivative (generic name). (a) Chemical substance... phosphoric acid derivative (PMN P-95-284) is subject to reporting under this section for the significant...

  10. 40 CFR 721.10039 - Diethoxybenzenamine derivative, diazotized, coupled with aminonaphthalenesulfonic acid derivative...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Diethoxybenzenamine derivative, diazotized, coupled with aminonaphthalenesulfonic acid derivative, ammonium salt (generic). 721.10039 Section... Substances § 721.10039 Diethoxybenzenamine derivative, diazotized, coupled with aminonaphthalenesulfonic...

  11. 40 CFR 721.10039 - Diethoxybenzenamine derivative, diazotized, coupled with aminonaphthalenesulfonic acid derivative...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Diethoxybenzenamine derivative, diazotized, coupled with aminonaphthalenesulfonic acid derivative, ammonium salt (generic). 721.10039 Section... Substances § 721.10039 Diethoxybenzenamine derivative, diazotized, coupled with aminonaphthalenesulfonic...

  12. 40 CFR 721.10039 - Diethoxybenzenamine derivative, diazotized, coupled with aminonaphthalenesulfonic acid derivative...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Diethoxybenzenamine derivative, diazotized, coupled with aminonaphthalenesulfonic acid derivative, ammonium salt (generic). 721.10039 Section... Substances § 721.10039 Diethoxybenzenamine derivative, diazotized, coupled with aminonaphthalenesulfonic...

  13. 40 CFR 721.10039 - Diethoxybenzenamine derivative, diazotized, coupled with aminonaphthalenesulfonic acid derivative...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Diethoxybenzenamine derivative, diazotized, coupled with aminonaphthalenesulfonic acid derivative, ammonium salt (generic). 721.10039 Section... Substances § 721.10039 Diethoxybenzenamine derivative, diazotized, coupled with aminonaphthalenesulfonic...

  14. 40 CFR 721.10039 - Diethoxybenzenamine derivative, diazotized, coupled with aminonaphthalenesulfonic acid derivative...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Diethoxybenzenamine derivative, diazotized, coupled with aminonaphthalenesulfonic acid derivative, ammonium salt (generic). 721.10039 Section... Substances § 721.10039 Diethoxybenzenamine derivative, diazotized, coupled with aminonaphthalenesulfonic...

  15. Clinical pharmacokinetics of fibric acid derivatives (fibrates).

    PubMed

    Miller, D B; Spence, J D

    1998-02-01

    Beginning with the description of clofibrate in 1962, derivatives of fibric acid (fibrates) have been used clinically to treat dyslipidaemias. Subsequently, gemfibrozil, fenofibrate, bezafibrate, ciprofibrate and long-acting forms of gemfibrozil, fenofibrate and bezafibrate have been developed. Clinically, this class of drugs appears to be most useful in lipoprotein disorders characterised by elevations of very low density lipoprotein and plasma triglycerides, which are often accompanied by reductions in high density lipoprotein (HDL) levels. The principal effects are a reduction in triglyceride and increase in HDL levels, with increases in the activity of hepatic lipase and lipoprotein lipase. There is some reduction of low density lipoprotein (LDL), lipoprotein (a), fibrinogen and uric acid. As a class, these drugs are generally well absorbed from the gastrointestinal tract (immediate-acting fenofibrate being the exception) and display a high degree of binding to albumin. Fibrates are metabolised by the hepatic cytochrome P450 (CYP) 3A4. All members of this class are primarily excreted via the kidneys and display some increase in plasma half-life in individuals with severe renal impairment. The long-acting forms of gemfibrozil and bezafibrate have pharmacokinetic properties similar to those of their immediate-acting parent compounds. The long-acting form of fenofibrate, produced by the process of micronisation, has increased oral bioavailability with less variability in absorption compared with the immediate-acting form of fenofibrate. Drug interactions are seen with other drugs that share a high degree of binding to albumin or are metabolised by CYP3A4. Clinically the most important and most commonly reported drug interactions are with HMG-CoA reductase inhibitors (lovastatin, simvastatin, pravastatin and fluvastatin), warfarin, cyclosporin and oral hypoglycaemic agents [including metformin, tolbutamide and glibenclamide (glyburide)]. The main potential for drug

  16. Caffeic acid derivatives in the roots of yacon (Smallanthus sonchifolius).

    PubMed

    Takenaka, Makiko; Yan, Xiaojun; Ono, Hiroshi; Yoshida, Mitsuru; Nagata, Tadahiro; Nakanishi, Tateo

    2003-01-29

    Five caffeic acid derivatives were found in the roots of yacon, Smallanthus sonchifolius (Poepp. and Endl.) H. Robinson, Asteraceae, as the major water-soluble phenolic compounds. The structures of these compounds were determined by analysis of spectroscopic data. Two of these were chlorogenic acid (3-caffeoylquinic acid) and 3,5-dicaffeoylquinic acid, common phenolic compounds in plants of the family Asteraceae. Three were esters of caffeic acid with the hydroxy groups of aldaric acid, derived from hexose. The structure of the aldaric moiety was determined by hydrolysis and comparison of NMR spectra with those of standard aldaric acids. The compounds were novel caffeic acid esters of altraric acid: 2,4- or 3,5-dicaffeoylaltraric acid, 2,5-dicaffeoylaltraric acid, and 2,3,5- or 2,4,5-tricaffeoylaltraric acid.

  17. Antiprotozoal activity of betulinic acid derivatives.

    PubMed

    Domínguez-Carmona, D B; Escalante-Erosa, F; García-Sosa, K; Ruiz-Pinell, G; Gutierrez-Yapu, D; Chan-Bacab, M J; Giménez-Turba, A; Peña-Rodríguez, L M

    2010-04-01

    Betulinic acid (1), isolated from the crude extract of the leaves of Pentalinon andrieuxii (Apocynaceae), together with betulinic acid acetate (2), betulonic acid (3), betulinic acid methyl ester (4), and betulin (5) were evaluated for their antiprotozoal activity. The results showed that modifying the C-3 position increases leishmanicidal activity while modification of the C-3 and C-28 positions decreases trypanocidal activity.

  18. Antioxidant and antimicrobial activities of cinnamic acid derivatives.

    PubMed

    Sova, M

    2012-07-01

    Cinnamic acid is an organic acid occurring naturally in plants that has low toxicity and a broad spectrum of biological activities. In the search for novel pharmacologically active compounds, cinnamic acid derivatives are important and promising compounds with high potential for development into drugs. Many cinnamic acid derivatives, especially those with the phenolic hydroxyl group, are well-known antioxidants and are supposed to have several health benefits due to their strong free radical scavenging properties. It is also well known that cinnamic acid has antimicrobial activity. Cinnamic acid derivatives, both isolated from plant material and synthesized, have been reported to have antibacterial, antiviral and antifungal properties. Acids, esters, amides, hydrazides and related derivatives of cinnamic acid with such activities are here reviewed.

  19. Prenylated benzoic acid derivatives from the stem of Euodia lepta.

    PubMed

    Zhao, Ming-Bo; Zhou, Si-Xiang; Zhang, Qing-Ying; Wei, Wei-Feng; Li, Ming-Hui; Xing, Jian-Yong; Jiang, Yong; Tu, Peng-Fei

    2017-07-01

    Two new prenylated benzoic acid derivatives, leptoic acid A and (+)-S-anodendroic acid (1-2), along with one known compound, 2,2-dimethyl-2H-1-benzopyran-6-carboxylic acid (3) were isolated from the stem of Euodia lepta (spreng.) Merr. Their structures were elucidated on the basis of the chemical and spectroscopic evidence.

  20. Degradation of benzoic acid and its derivatives in subcritical water.

    PubMed

    Lindquist, Edward; Yang, Yu

    2011-04-15

    In this research, the stability of benzoic acid and three of its derivatives (anthranilic acid, salicylic acid, and syringic acid) under subcritical water conditions was investigated. The stability studies were carried out at temperatures ranging from 50 to 350°C with heating times of 10-630 min. The degradation of the benzoic acid derivatives increased with rising temperature and the acids became less stable with longer heating time. The three benzoic acid derivatives showed very mild degradation at 150°C. Severe degradation of benzoic acid derivatives was observed at 200°C while their complete degradation occurred at 250°C. However, benzoic acid remained stable at temperatures up to 300°C. The degradation products of benzoic acid and the three derivatives were identified and quantified by HPLC and confirmed by GC/MS. Anthranilic acid, salicylic acid, syringic acid, and benzoic acid in high-temperature water underwent decarboxylation to form aniline, phenol, syringol, and benzene, respectively. Copyright © 2010 Elsevier B.V. All rights reserved.

  1. Synthesis of new kojic acid based unnatural α-amino acid derivatives.

    PubMed

    Balakrishna, C; Payili, Nagaraju; Yennam, Satyanarayana; Devi, P Uma; Behera, Manoranjan

    2015-11-01

    An efficient method for the preparation of kojic acid based α-amino acid derivatives by alkylation of glycinate schiff base with bromokojic acids have been described. Using this method, mono as well as di alkylated kojic acid-amino acid conjugates have been prepared. This is the first synthesis of C-linked kojic acid-amino acid conjugate where kojic acid is directly linked to amino acid through a C-C bond.

  2. Bioconversion of cinnamic acid derivatives by Schizophyllum commune.

    PubMed

    Nimura, Yoshifumi; Tsujiyama, Sho-ichi; Ueno, Masayoshi

    2010-10-01

    To investigate the production of useful phenols from plant resources, we examined the metabolism of cinnamic acid derivatives by a wood-rotting fungus, Schizophyllum commune. Four cinnamic acid derivatives (cinnamic, p-coumaric, ferulic, and sinapic acids) were tested as substrates. Two main reactions, reduction and cleavage of the side chain, were observed. Reduction of the side chain was confirmed in cinnamic acid and p-coumaric acid metabolism. The side chain cleavage occurred in p-coumaric acid and ferulic acid metabolism but the initial reactions of these acids differed. Sinapic acid was not metabolized by S. commune. p-Hydroxybenzaldehyde accumulation was observed in the culture to which p-coumaric acid was added. This suggests that S. commune is a useful agent for transforming p-coumaric acid into p-hydroxybenzaldehyde.

  3. Acetylcholinesterase inhibitory properties of some benzoic acid derivatives

    NASA Astrophysics Data System (ADS)

    Yildiz, Melike; Kiliç, Deryanur; Ünver, Yaǧmur; Şentürk, Murat; Askin, Hakan; Küfrevioǧlu, Ömer Irfan

    2016-04-01

    Acetylcholinesterase (AChE) hydrolyses the neurotransmitter acetylcholine to acetic acid and choline. AChE inhibitors are used in treatment of several neurodegeneartive disorder and Alzheimer's disease. In the present study, inhibition of AChE with some benzoic acid derivatives were investigated. 3-Chloro-benzoic acid (1), 2-hydroxy-5-sulfobenzoic acid (2), 2-(sulfooxy) benzoic acid (3), 2-hydroxybenzoic acid (4), 2,3-dimethoxybenzoic (5), and 3,4,5-trimethoxybenzoic (6) were calculated IC50 values AChE enzyme. Kinetic investigations showed that similarly to AChE inhibitors. Benzoic acid derivatives (1-6) investigated are encouraging agents which may be used as lead molecules in order to derivative novel AChE inhibitors that might be useful in medical applications.

  4. Natural cinnamic acids, synthetic derivatives and hybrids with antimicrobial activity.

    PubMed

    Guzman, Juan David

    2014-11-25

    Antimicrobial natural preparations involving cinnamon, storax and propolis have been long used topically for treating infections. Cinnamic acids and related molecules are partly responsible for the therapeutic effects observed in these preparations. Most of the cinnamic acids, their esters, amides, aldehydes and alcohols, show significant growth inhibition against one or several bacterial and fungal species. Of particular interest is the potent antitubercular activity observed for some of these cinnamic derivatives, which may be amenable as future drugs for treating tuberculosis. This review intends to summarize the literature data on the antimicrobial activity of the natural cinnamic acids and related derivatives. In addition, selected hybrids between cinnamic acids and biologically active scaffolds with antimicrobial activity were also included. A comprehensive literature search was performed collating the minimum inhibitory concentration (MIC) of each cinnamic acid or derivative against the reported microorganisms. The MIC data allows the relative comparison between series of molecules and the derivation of structure-activity relationships.

  5. Synthesis of 5'-deoxy-5'-nucleosideacetic acid derivatives

    NASA Technical Reports Server (NTRS)

    Harada, Kazuo; Orgel, Leslie E.

    1990-01-01

    Several new 5'-deoxy-5'-nucleosideacetic acid derivatives have been synthesized by the reactions of alkoxycarbonylmethylene triphenylphosphoranes with nucleoside 5'-aldehydes. The oligomerization of adenine derivatives IIa, IIIa, IV, V and guanine derivatives IIc and IIIc in aqueous solution was studied using a water-soluble carbodiimide as a condensing agent. It is found that the saturated acid (IV) tends to cyclize to the lactone, while IIa and unsaturated acids (IIIa and V) oligomerized efficiently, especially in the presence of poly (U) as a template.

  6. Pharmacokinetics of butyric acid derivative with xylitol.

    PubMed

    Desmet, G; Brazier, M; Cerutti, J; Chany, C; Arnould-Guerin, M L

    1991-01-01

    The short chain fatty acids, especially butyric acid salts have interesting biological properties. In some cases, transformed cells can recover a normal phenotype and in animal, butyrate salts increase antitumor resistance. Butyrate may be considered as possibly useful for antitumor therapy. But these products exhibit two essential disadvantages which restrict their clinical use in man: high concentrations required to achieve therapeutic effects and rapid excretion with short half life. In order to optimize the clinical use of butyrate, we studied a n-butyric acid ester obtained with xylitol selected for its physiological and metabolic inertia. Structure determination of tributyryl xylitol was carried out by mass and NMR spectrometry (MW = 344). The low toxicity and the antitumor effects of this ester, especially in association with Corynebacterium parvum and interferon, confirm its therapeutic interest. The slow excretion of this prodrug should make butyrate clinical use easier by preventing extensive systemic metabolism and metabolic side-effects due to cations of butyrate salts.

  7. A new flavellagic acid derivative and phloroglucinol from Rhodomyrtus tomentosa.

    PubMed

    Hiranrat, A; Chitbankluoi, W; Mahabusarakam, W; Limsuwan, S; Voravuthikunchai, S P

    2012-01-01

    A new flavellagic acid derivative, 3,3',4,4'-tetra-O-methylflavellagic acid and six known compounds were isolated from the stems of Rhodomyrtus tomentosa while a new phloroglucinol, named rhodomyrtosone I, and six known compounds were isolated from the fruit. Their structures were elucidated by spectroscopic analyses as well as by comparisons with related compounds.

  8. Caffeic Acid Derivatives in Dried Lamiaceae and Echinacea purpurea Products

    USDA-ARS?s Scientific Manuscript database

    The concentrations of caffeic acid derivatives within Lamiaceae and Echinacea (herb, spice, tea, and dietary supplement forms) readily available in the U.S. marketplace (n=72) were determined. After the first identification of chicoric acid in Ocimum basilicum (basil), the extent to which chicoric a...

  9. Acid-catalyzed rearrangements of flavans to novelbenzofuran derivatives

    Treesearch

    Richard W. Hemingway; Weiling Peng; Anthony H. Conner; Petrus J. Steynberg; Jan P. Steynberg

    1998-01-01

    The objective of this work was to define reactions that occur when proanthocyanidins and their derivatives are reacted in the presence of acid catalysts. Pure compounds (either as the free phenols, the methyl ether, or the methyl ether-acetate derivatives) were isolated by a variety of chromatographic methods. Proof of their structure was based mainly on 2D-NMR, as...

  10. Acyl Meldrum's acid derivatives: application in organic synthesis

    NASA Astrophysics Data System (ADS)

    Janikowska, K.; Rachoń, J.; Makowiec, S.

    2014-07-01

    This review is focused on an important class of Meldrum's acid derivatives commonly known as acyl Meldrum's acids. The preparation methods of these compounds are considered including the recently proposed and rather rarely used ones. The chemical properties of acyl Meldrum's acids are described in detail, including thermal stability and reactions with various nucleophiles. The possible mechanisms of these transformations are analyzed. The bibliography includes 134 references.

  11. Preparation and characterization of amidated derivatives of alginic acid.

    PubMed

    Taubner, Tomáš; Marounek, Milan; Synytsya, Andriy

    2017-10-01

    Alginic acid is a suitable material for modification to prepare new derivatives because of presence of its carboxyl groups. The high content of carboxyl groups over the entire length of its chain renders it an easily modifiable material with a possibility of achieving a high degree of substitution in the prepared derivatives. The salt of alginic acid (sodium alginate) is readily commercially available and is widely used in many branches of chemistry. Alginic acid was thus selected as the substrate for amidation. The amidation used two-steps: methyl esterification followed by amino-de-alkoxylation. The aim of this study was to prepare highly substituted derivatives with different polysaccharide chain characteristics. As such, the alginic acid was modified by the two-step amidation based on the esterification of the alginic acid carboxyl groups by reaction with methanol and further amino-de-alkoxylation (aminolysis) of the obtained methyl ester with amidation reagents (n-alkylamines, hydrazine and hydroxylamine). The purity and substitution degree of the prepared derivatives were monitored by vibration spectroscopic methods (FTIR and FT Raman) and organic elemental analysis. These analytical methods confirmed the preparation of highly or moderately substituted N-alkylamides, hydrazide and hydroxamic acid of alginic acid. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Acyl quinic acid derivatives from the stems of Erycibe obtusifolia.

    PubMed

    Liu, Zhaozhen; Feng, Ziming; Yang, Yanan; Jiang, Jianshuang; Zhang, Peicheng

    2014-12-01

    Eleven new acyl quinic acid derivatives, 4-O-caffeoyl-3-O-syringoylquinic acid methyl ester (1), 4-O-caffeoyl-3-O-vanilloylquinic acid (2), 4-O-caffeoyl-3-O-vanilloylquinic acid methyl ester (3), 5-O-caffeoyl-3-O-vanilloylquinic acid (4), 5-O-caffeoyl-3-O-vanilloylquinic acid methyl ester (5), 5-O-caffeoyl-3-O-sinapoylquinic acid (6), 5-O-caffeoyl-4-O-vanilloylquinic acid (7), 4-O-(7‴S, 8‴R)-glycosmisoyl-5-O-caffeoylquinic acid methyl ester (8), 4-O-(7‴S, 8‴R)-glycosmisoyl-5-O-caffeoylquinic acid (9), 3-O-(7‴S, 8‴R)-glycosmisoyl-4-O-caffeoylquinic acid (10), and 3-O-(7‴S, 8‴R)-glycosmisoyl-4-O-caffeoylquinic acid methyl ester (11), have been isolated from the stems of Erycibe obtusifolia together with eight known compounds (12-19). Their structures were elucidated on the basis of spectroscopic data analysis (UV, IR, HRESIMS, CD, and 1D and 2D NMR) and chemical evidence. In in vitro assay, compounds 7 and 16-18 exhibited significant neuroprotective effects against rotenone induced PC12 cell damage at 10 μM. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Aspartate-Derived Amino Acid Biosynthesis in Arabidopsis thaliana.

    PubMed

    Jander, Georg; Joshi, Vijay

    2009-01-01

    The aspartate-derived amino acid pathway in plants leads to the biosynthesis of lysine, methionine, threonine, and isoleucine. These four amino acids are essential in the diets of humans and other animals, but are present in growth-limiting quantities in some of the world's major food crops. Genetic and biochemical approaches have been used for the functional analysis of almost all Arabidopsis thaliana enzymes involved in aspartate-derived amino acid biosynthesis. The branch-point enzymes aspartate kinase, dihydrodipicolinate synthase, homoserine dehydrogenase, cystathionine gamma synthase, threonine synthase, and threonine deaminase contain well-studied sites for allosteric regulation by pathway products and other plant metabolites. In contrast, relatively little is known about the transcriptional regulation of amino acid biosynthesis and the mechanisms that are used to balance aspartate-derived amino acid biosynthesis with other plant metabolic needs. The aspartate-derived amino acid pathway provides excellent examples of basic research conducted with A. thaliana that has been used to improve the nutritional quality of crop plants, in particular to increase the accumulation of lysine in maize and methionine in potatoes.

  14. Oleic acid-derived oleoylethanolamide: A nutritional science perspective.

    PubMed

    Bowen, Kate J; Kris-Etherton, Penny M; Shearer, Gregory C; West, Sheila G; Reddivari, Lavanya; Jones, Peter J H

    2017-07-01

    The fatty acid ethanolamide oleoylethanolamide (OEA) is an endogenous lipid mediator derived from the monounsaturated fatty acid, oleic acid. OEA is synthesized from membrane glycerophospholipids and is a high-affinity agonist of the nuclear transcription factor peroxisome proliferator-activated receptor α (PPAR-α). Dietary intake of oleic acid elevates circulating levels of OEA in humans by increasing substrate availability for OEA biosynthesis. Numerous clinical studies demonstrate a beneficial relationship between high-oleic acid diets and body composition, with emerging evidence to suggest OEA may mediate this response through modulation of lipid metabolism and energy intake. OEA exposure has been shown to stimulate fatty acid uptake, lipolysis, and β-oxidation, and also promote food intake control. Future research on high-oleic acid diets and body composition is warranted to confirm these outcomes and elucidate the underlying mechanisms by which oleic acid exerts its biological effects. These findings have significant practical implications, as the oleic acid-derived OEA molecule may be a promising therapeutic agent for weight management and obesity treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Poly(α-hydroxy alkanoic acid)s derived from α-amino acids.

    PubMed

    Cohen-Arazi, Naomi; Domb, Abraham J; Katzhendler, Joshua

    2013-12-01

    Biodegradable polyesters derived from hydrophobic amino acids are synthesized by various techniques, resulting in a wide range of molecular weights. The polymers are prepared via a) direct condensation with p-toluenesulfonic acid (PTSA) as catalyst, b) ring-opening polymerization (ROP) of O-carboxyanhydrides, and c) ROP of cyclic dilactones. The polymers obtained by the first method reach a molecular weight ranging from 1000 to 3000 Da, whereas those formed by the second and third method yield extended molecular weights of 15000-30000 Da. The purity of the monomers as well as their steric bulkiness are key factors affecting the polymerizability of cyclic monomers by ROP. Other parameters such as spatial ring alignment and proximity organization may also play a role.

  16. Potent anticonvulsant urea derivatives of constitutional isomers of valproic acid.

    PubMed

    Shimshoni, Jakob Avi; Bialer, Meir; Wlodarczyk, Bogdan; Finnell, Richard H; Yagen, Boris

    2007-12-13

    Valproic acid (VPA) is a major antiepileptic drug (AED); however, its use is limited by two life-threatening side effects: teratogenicity and hepatotoxicity. Several constitutional isomers of VPA and their amide and urea derivatives were synthesized and evaluated in three different anticonvulsant animal models and a mouse model for AED-induced teratogenicity. The urea derivatives of three VPA constitutional isomers propylisopropylacetylurea, diisopropylacetylurea, and 2-ethyl-3-methyl-pentanoylurea displayed a broad spectrum of anticonvulsant activity in rats with a clear superiority over their corresponding amides and acids. Enanatiomers of propylisopropylacetylurea and propylisopropylacetamide revealed enantioselective anticonvulsant activity, whereas only enantiomers of propylisopropylacetylurea displayed enantioselective teratogenicity. These potent urea derivatives caused neural tube defects, but only at doses markedly exceeding their effective dose, whereas VPA showed no separation between its anticonvulsant activity and teratogenicity. The broad spectrum of anticonvulsant activity of the urea derivatives coupled with their wide safety margin make them potential candidates to become new, potent AEDs.

  17. Retention of caffeic acid derivatives in dried Echinacea purpurea.

    PubMed

    Kim, H O; Durance, T D; Scaman, C H; Kitts, D D

    2000-09-01

    Different drying methods were applied to fresh Canadian-grown Echinacea purpurea flowers to determine optimal drying procedures for preserving caffeic acid derivatives. Fresh flowers of E. purpurea were dried by freeze-drying (FD), vacuum microwave drying with full vacuum (VMD), and air-drying (AD) at 25, 40, and 70 degrees C. Using HPLC, chicoric acid and caftaric acid levels were quantitated in dried flowers. These acids were significantly affected by the drying method conditions used. Although significant (p < 0.05) loss of chicoric acid was observed when flowers were stored at high moisture, VMD flowers with a low moisture content retained the highest levels of chicoric acid and caftaric acid similar to FD flowers. Flowers that were AD at 25 degrees C retained about 50%, while those dried by AD at 70 degrees C resulted in the lowest retention of these acids. Although flowers dried by AD at 40 degrees C retained relatively high amounts of chicoric acid and caftaric acid, the time (55 h) required to reach optimal drying was considerably longer than that (47 min) for VMD.

  18. Design, Synthesis, and Antimycobacterial Activity of Novel Theophylline-7-Acetic Acid Derivatives With Amino Acid Moieties.

    PubMed

    Stavrakov, Georgi; Valcheva, Violeta; Voynikov, Yulian; Philipova, Irena; Atanasova, Mariyana; Konstantinov, Spiro; Peikov, Plamen; Doytchinova, Irini

    2016-03-01

    The theophylline-7-acetic acid (7-TAA) scaffold is a promising novel lead compound for antimycobacterial activity. Here, we derive a model for antitubercular activity prediction based on 14 7-TAA derivatives with amino acid moieties and their methyl esters. The model is applied to a combinatorial library, consisting of 40 amino acid and methyl ester derivatives of 7-TAA. The best three predicted compounds are synthesized and tested against Mycobacterium tuberculosis H37Rv. All of them are stable, non-toxic against human cells and show antimycobacterial activity in the nanomolar range being 60 times more active than ethambutol. © 2015 John Wiley & Sons A/S.

  19. Membrane extraction with thermodynamically unstable diphosphonic acid derivatives

    DOEpatents

    Horwitz, E.P.; Gatrone, R.C.; Nash, K.L.

    1997-10-14

    Thermodynamically-unstable complexing agents which are diphosphonic acids and diphosphonic acid derivatives (or sulphur containing analogs), like carboxyhydroxymethanediphosphonic acid and vinylidene-1,1-diphosphonic acid, are capable of complexing with metal ions, and especially metal ions in the II, III, IV, V and VI oxidation states, to form stable, water-soluble metal ion complexes in moderately alkaline to highly-acidic media. However, the complexing agents can be decomposed, under mild conditions, into non-organic compounds which, for many purposes are environmentally-nondamaging compounds thereby degrading the complex and releasing the metal ion for disposal or recovery. Uses for such complexing agents as well as methods for their manufacture are also described. 1 fig.

  20. Extracting metal ions with diphosphonic acid, or derivative thereof

    DOEpatents

    Horwitz, E.P.; Gatrone, R.C.; Nash, K.L.

    1994-07-26

    Thermodynamically-unstable complexing agents which are diphosphonic acids and diphosphonic acid derivatives (or sulfur containing analogs), like carboxyhydroxymethanediphosphonic acid and vinylidene-1,1-diphosphonic acid, are capable of complexing with metal ions, and especially metal ions in the II, III, IV, V and VI oxidation states, to form stable, water-soluble metal ion complexes in moderately alkaline to highly-acidic media. However, the complexing agents can be decomposed, under mild conditions, into non-organic compounds which, for many purposes are environmentally-nondamaging compounds thereby degrading the complex and releasing the metal ion for disposal or recovery. Uses for such complexing agents as well as methods for their manufacture are also described. 1 fig.

  1. Extracting metal ions with diphosphonic acid, or derivative thereof

    DOEpatents

    Horwitz, Earl P.; Gatrone, Ralph C.; Nash, Kenneth L.

    1994-01-01

    Thermodynamically-unstable complexing agents which are diphosphonic acids and diphosphonic acid derivatives (or sulphur containing analogs), like carboxyhydroxymethanediphosphonic acid and vinylidene-1,1-diphosphonic acid, are capable of complexing with metal ions, and especially metal ions in the II, III, IV, V and VI oxidation states, to form stable, water-soluble metal ion complexes in moderately alkaline to highly-acidic media. However, the complexing agents can be decomposed, under mild conditions, into non-organic compounds which, for many purposes are environmentally-nondamaging compounds thereby degrading the complex and releasing the metal ion for disposal or recovery. Uses for such complexing agents as well as methods for their manufacture are also described.

  2. Membrane extraction with thermodynamically unstable diphosphonic acid derivatives

    DOEpatents

    Horwitz, Earl Philip; Gatrone, Ralph Carl; Nash, Kenneth LaVerne

    1997-01-01

    Thermodynamically-unstable complexing agents which are diphosphonic acids and diphosphonic acid derivatives (or sulphur containing analogs), like carboxyhydroxymethanediphosphonic acid and vinylidene-1,1-diphosphonic acid, are capable of complexing with metal ions, and especially metal ions in the II, III, IV, V and VI oxidation states, to form stable, water-soluble metal ion complexes in moderately alkaline to highly-acidic media. However, the complexing agents can be decomposed, under mild conditions, into non-organic compounds which, for many purposes are environmentally-nondamaging compounds thereby degrading the complex and releasing the metal ion for disposal or recovery. Uses for such complexing agents as well as methods for their manufacture are also described.

  3. Aristolic Acid Derivatives from the Bark of Antidesma ghaesembilla.

    PubMed

    Schäfer, Sibylle; Schwaiger, Stefan; Stuppner, Hermann

    2017-08-01

    Antidesma ghaesembilla is an important medicinal and food plant in many Asian countries. Ten substances could be isolated from the dichloromethane and methanol extract: sitostenone (3), daucosterol (4), chavibetol (5), asperphenamate (6), protocatechuic acid (7), vanillic acid-4-O-β-D-glucoside (8), 1-O-β-D-glucopyranosyl-3-O-methyl-phloroglucinol (9), and aristolic acid II-8-O-β-D-glucoside (10), and two new aristolic acid derivatives, 10-amino-5,7-dimethoxy-aristolic acid II (= 6-amino-9,11-dimethoxyphenanthro[3,4-d]-1,3-dioxole-5-carboxylic acid; 1) and 5,7-dimethoxy-aristolochic acid II (= 9,11-dimethoxy-6-nitrophenantro[3,4-d]-1,3-dioxole-5-carboxylic acid; 2). Exposure to humans of some of these compounds is associated with a severe disease today known as aristolochic acid nephropathy. Therefore, the traditional usage of this plant has to be reconsidered carefully. Georg Thieme Verlag KG Stuttgart · New York.

  4. Derivatives of diphosphonic acids: synthesis and biological activity

    NASA Astrophysics Data System (ADS)

    Zolotukhina, M. M.; Krutikov, V. I.; Lavrent'ev, A. N.

    1993-07-01

    The scientific-technical and patent literature on the synthesis of derivatives of diphosphonic acids is surveyed. Various methods of synthesis of diphosphonate, phosphonylphosphinyl, and phosphonophosphate compounds are described. The principal aspects of the use of the above compounds in medicine, biochemistry, and agriculture are examined. The bibliography includes 174 references.

  5. Palladium(III)-Catalyzed Fluorination of Arylboronic Acid Derivatives

    PubMed Central

    Tang, Pingping; Murphy, Jennifer M.; Ritter, Tobias

    2013-01-01

    A practical, palladium-catalyzed synthesis of aryl fluorides from arylboronic acid derivatives is presented. The reaction is operationally simple and amenable to multi-gram-scale synthesis. Evaluation of the reaction mechanism suggests a single-electron-transfer pathway, involving a Pd(III) intermediate that has been isolated and characterized. PMID:24040932

  6. Palladium(III)-catalyzed fluorination of arylboronic acid derivatives.

    PubMed

    Mazzotti, Anthony R; Campbell, Michael G; Tang, Pingping; Murphy, Jennifer M; Ritter, Tobias

    2013-09-25

    A practical, palladium-catalyzed synthesis of aryl fluorides from arylboronic acid derivatives is presented. The reaction is operationally simple and amenable to multigram-scale synthesis. Evaluation of the reaction mechanism suggests a single-electron-transfer pathway, involving a Pd(III) intermediate that has been isolated and characterized.

  7. The Synthesis and Evaluation of Arctigenin Amino Acid Ester Derivatives.

    PubMed

    Cai, En-Bo; Yang, Li-Min; Jia, Cai-Xia; Zhang, Wei-Yuan; Zhao, Yan; Li, Wei; Song, Xing-Zhuo; Zheng, Man-Ling

    2016-10-01

    The use of arctigenin (ARG), a traditional medicine with many pharmacological activities, has been restricted due to its poor solubility in water. Five amino acid derivatives of ARG have been synthesized using glycine, o-alanine, valine, leucine, and isoleucine, which have t-butyloxy carbonyl (BOC) as a protective group. In this study, we examined the effects of removing these protective groups. The results showed that the amino acid derivatives have better solubility and nitrite-clearing ability than ARG. Among the compounds tested, the amino acid derivatives without protective group were the best. Based on these results, ARG and its two amino acid derivatives without protective group (ARG8, ARG10) were selected to evaluate their anti-tumor activity in vivo at a dosage of 40 mg/kg. The results indicated that ARG8 and ARG10 both exhibit more anti-tumor activity than ARG in H22 tumor-bearing mice. The tumor inhibition rates of ARG8 and ARG10 were 69.27 and 43.58%, which was much higher than ARG. Furthermore, the mice treated with these compounds exhibited less damage to the liver, kidney and immune organs compared with the positive group. Furthermore, ARG8 and ARG10 improved the serum cytokine levels significantly compared to ARG. In brief, this study provides a method to improve the water solubility of drugs, and we also provide a reference basis for new drug development.

  8. Antiprotozoal Activity of Triazole Derivatives of Dehydroabietic Acid and Oleanolic Acid.

    PubMed

    Pertino, Mariano Walter; Vega, Celeste; Rolón, Miriam; Coronel, Cathia; Rojas de Arias, Antonieta; Schmeda-Hirschmann, Guillermo

    2017-02-28

    Tropical parasitic diseases such as Chagas disease and leishmaniasis are considered a major public health problem affecting hundreds of millions of people worldwide. As the drugs currently used to treat these diseases have several disadvantages and side effects, there is an urgent need for new drugs with better selectivity and less toxicity. Structural modifications of naturally occurring and synthetic compounds using click chemistry have enabled access to derivatives with promising antiparasitic activity. The antiprotozoal activity of the terpenes dehydroabietic acid, dehydroabietinol, oleanolic acid, and 34 synthetic derivatives were evaluated against epimastigote forms of Trypanosoma cruzi and promastigotes of Leishmaniabraziliensis and Leishmania infantum. The cytotoxicity of the compounds was assessed on NCTC-Clone 929 cells. The activity of the compounds was moderate and the antiparasitic effect was associated with the linker length between the diterpene and the triazole in dehydroabietinol derivatives. For the oleanolic acid derivatives, a free carboxylic acid function led to better antiparasitic activity.

  9. New derivatives of nonactic and homononactic acids from Bacillus pumilus derived from Breynia fruticosa.

    PubMed

    Han, Li; Huo, Peiyuan; Chen, Huahong; Li, Songtao; Jiang, Yi; Li, Liya; Xu, Lihua; Jiang, Chenglin; Huang, Xueshi

    2014-07-01

    Six new nonactic and homononactic acid derivatives, ethyl homononactate (1), ethyl nonactate (2), homononactyl homononactate (6), ethyl homononactyl nonactate (7), ethyl homononactyl homononactate (8), and ethyl nonactyl nonactate (9), as well as four known compounds, homononactic acid (3), nonactic acid (4), homononactyl nonactate (5), and bishomononactic acid (10), were isolated from culture broth of Bacillus pumilus derived from Breynia fruticosa. The structures of new compounds were elucidated by spectroscopic analysis and chemical methods. The optical purities of 1-6 were determined by HPLC/MS after treatment with L-phenylalanine methyl ester. The dimeric compounds 5-9 showed weak cytotoxic activities against five human cancer cell lines (IC50 19-100 μg/ml). Copyright © 2014 Verlag Helvetica Chimica Acta AG, Zürich.

  10. Natural neo acids and neo alkanes: their analogs and derivatives.

    PubMed

    Dembitsky, Valery M

    2006-04-01

    This review presents more than 260 naturally occurring (as well as 47 synthesized) neo fatty (carboxylic) acids, neo alkanes, and their analogs and derivatives, isolated and identified from plants, algae, fungi, marine invertebrates, and microorganisms, that demonstrate different biological activities. These natural metabolites are good prospects for future chemical preparations as antioxidants, and also as anticancer, antimicrobial, and antibacterial agents. Described also are some synthetic bioactive compounds containing a tertiary butyl group(s) that have shown high anticancer, antifungal, and other activities. Applications of some neo fatty (carboxylic) acid derivatives in cosmetic, agronomic, and pharmaceutical industries also are considered. This is the first review to consider naturally occurring neo fatty (carboxylic) acids, neo alkanes, and other metabolites containing a tertiary butyl group(s) [or tert-butyl unit(s)].

  11. Evaluation of benzoic acid derivatives as sirtuin inhibitors.

    PubMed

    Chen, Yi-Pei; Catbagan, Chad C; Bowler, Jeannette T; Gokey, Trevor; Goodwin, Natalie D M; Guliaev, Anton B; Wu, Weiming; Amagata, Taro

    2014-01-01

    Employing a genetically modified yeast strain as a screening tool, 4-dimethylaminobenzoic acid (5) was isolated from the marine sediment-derived Streptomyces sp. CP27-53 as a weak yeast sirtuin (Sir2p) inhibitor. Using this compound as a scaffold, a series of disubstituted benzene derivatives were evaluated to elucidate the structure activity relationships for Sir2p inhibition. The results suggested that 4-alkyl or 4-alkylaminobenzoic acid is the key structure motif for Sir2p inhibitory activity. The most potent Sir2p inhibitor, 4-tert-butylbenzoic acid (20), among the tested compounds in this study turned out to be a weak but selective SIRT1 inhibitor. The calculated binding free energies between the selected compounds and the catalytic domain of SIRT1 were well correlated to their measured SIRT1 inhibitory activities.

  12. Hydrophobicity and retention coefficient of selected bile Acid oxo derivatives.

    PubMed

    Poša, Mihalj; Pilipović, Mladena Ana Lalić; Popović, Jovan

    2010-12-01

    Retention coefficients (k) of cholic acid and its keto derivatives are determined by means of Reversed Phase High Pressure Liquid Chromatography at different temperatures (303K, 309K, and 313K). At each studied temperature, retention factor decreases if the hydroxyl group in the cholic acid molecule replaces oxo group. In addition, the change of retention coefficient in a function of temperature (Δk/ΔT) is dominant for the cholic acid while by increasing the number of oxo groups it decreases. Introduction of an oxo group in a bile acid molecule leads to the lower hydrophobicity of the β side of the steroid nucleus. Because of that, less interaction happens between β side of the steroid nucleus and stationary phase. For dehydrocholic acid (three- oxo derivative), the value for Δk/ΔT shows an exception of this explanation. This suggests that in this molecule the planar polarity is disturbed. Partition coefficient K of nitrazepam (probe molecule) in micelles of bile acid salts at the examined temperatures shows a high linear correlation with retention factors of the selected bile acids. This indicates the importance of hydrophobic interactions in mixed micelles between the examined drug and bile acid salts. Haemolytic potential (erythrocyte haemolysis, log (Lys50)) represents measure of membranotoxicity of bile acids. In addition, it is shown that haemolytic potential correlates highly with the retention coefficient. All experiments that we conducted to obtain the values of K and log (Lys50) as well as their correlations with k, contribute to significance of retention coefficient as a measure of hydrophobicity in biopharmaceutical experiments.

  13. Anti-Trichomonas vaginalis activity of betulinic acid derivatives.

    PubMed

    Hübner, Dariana Pimentel Gomes; de Brum Vieira, Patrícia; Frasson, Amanda Piccoli; Menezes, Camila Braz; Senger, Franciane Rios; Santos da Silva, Gloria Narjara; Baggio Gnoatto, Simone Cristina; Tasca, Tiana

    2016-12-01

    Caused by Trichomonas vaginalis, trichomoniasis is the most common non-viral STD worldwide. Currently, metronidazole and tinidazole are the only drugs approved for treatment of the condition. However, problems such as metronidazole-resistant T. vaginalis isolates and allergic reactions have been reported. Based on data previously published by our group, structural changes in betulinic acid (1) were performed, generating three new compounds that were tested for in vitro anti-T.vaginalis activity in this study. Whereas derivative 2 did not demonstrate anti-T. vaginalis activity, derivatives 3 and 4 reduced trophozoite viability by 100%, with MIC values of 50μM. The structural difference of two compounds was performed only on the C-28 position. Derivative 3 showed low cytotoxicity against Vero cells in 24h; however, derivative 4 was highly cytotoxic, but efficient when associated with metronidazole in the synergism assay. ROS production by neutrophils was reduced, and derivative 3 showed anti-inflammatory effect. Collectively, the results of this study provide in vitro evidence that betulinic acid derivatives 3 and 4 are potential compounds with anti-T. vaginalis activity.

  14. Self-assembly of fatty acids and hydroxyl derivative salts.

    PubMed

    Novales, Bruno; Navailles, Laurence; Axelos, Monique; Nallet, Frédéric; Douliez, Jean-Paul

    2008-01-01

    We report the dispersions of a fatty acid and hydroxyl derivative salts in aqueous solutions that were further used to produce foams and emulsions. The tetrabutyl-ammonium salts of palmitic acid, 12-hydroxy stearic acid, and omega-hydroxy palmitic acid formed isotropic solutions of micelles, whereas the ethanolamine salts of the same acids formed turbid birefringent lamellar solutions. The structure and dimension of those phases were confirmed by small-angle neutron scattering and NMR. Micelles exhibited a surprisingly small radius of about 20 A, even for hydroxyl fatty acids, suggesting the formation of hydrogen bonds between lipids in the core of the micelles. In the case of ethanolamine salts of palmitic and 12-hydroxy stearic acids, the lipids were arranged in bilayers, with a phase transition from gel to fluid upon heating, whereas for omega-hydroxy palmitic acid, monolayers formed in accordance with the bola shape of this lipid. Foams and emulsions produced from ethanolamine salt solutions were more stable than those obtained from tetrabutyl-ammonium salt solutions. We discuss these results in terms of counterion size, lipid molecular shape, and membrane curvature.

  15. Characterization of hydroxycinnamic acid derivatives binding to bovine serum albumin.

    PubMed

    Jin, Xiao-Ling; Wei, Xia; Qi, Feng-Ming; Yu, Sha-Sha; Zhou, Bo; Bai, Shi

    2012-05-07

    Hydroxycinnamic acid derivatives (HCAs) are a group of naturally occurring polyphenolic compounds which possess various pharmacological activities. In this work, the interactions of bovine serum albumin (BSA) with six HCA derivatives, including chlorogenic acid (CHA), caffeic acid (CFA), m-coumaric acid (m-CA), p-coumaric acid (p-CA), ferulic acid (FA) and sinapic acid (SA) have been investigated by NMR spectroscopic techniques in combination with fluorescence and molecular modeling methods. Competitive STD NMR experiments using warfarin sodium and L-tryptophan as site-selective probes indicated that HCAs bind to site I in the subdomain IIA of BSA. From the analysis of the STD NMR-derived binding epitopes and molecular docking models, it was deduced that CHA, CFA, m-CA and p-CA show similar binding modes and orientation, in which the phenyl ring is in close contact with protein surface, whereas carboxyl group points out of the protein. However, FA and SA showed slightly different binding modes, due to the steric hindrance of methoxy-substituents on the phenyl ring. Relaxation experiments provided detailed information about the relationship between the affinity and structure of HCAs. The binding affinity was the strongest for CHA and ranked in the order CHA > CFA > m-CA ≥ p-CA > FA > SA, which agreed well with the results from fluorescence experiments. Based on our experimental results, we also conclude that HCAs bind to BSA mainly by hydrophobic interaction and hydrogen bonding. This study therefore provides valuable information for elucidating the mechanisms of BSA-HCAs interaction.

  16. Synthesis and biological activity of hydroxylated derivatives of linoleic acid and conjugated linoleic acids.

    PubMed

    Li, Zhen; Tran, Van H; Duke, Rujee K; Ng, Michelle C H; Yang, Depo; Duke, Colin C

    2009-03-01

    Allylic hydroxylated derivatives of the C18 unsaturated fatty acids were prepared from linoleic acid (LA) and conjugated linoleic acids (CLAs). The reaction of LA methyl ester with selenium dioxide (SeO(2)) gave mono-hydroxylated derivatives, 13-hydroxy-9Z,11E-octadecadienoic acid, 13-hydroxy-9E,11E-octadecadienoic acid, 9-hydroxy-10E,12Z-octadecadienoic acid and 9-hydroxy-10E,12E-octadecadienoic acid methyl esters. In contrast, the reaction of CLA methyl ester with SeO(2) gave di-hydroxylated derivatives as novel products including, erythro-12,13-dihydroxy-10E-octadecenoic acid, erythro-11,12-dihydroxy-9E-octadecenoic acid, erythro-10,11-dihydroxy-12E-octadecenoic acid and erythro-9,10-dihydroxy-11E-octadecenoic acid methyl esters. These products were purified by normal-phase short column vacuum chromatography followed by high-performance liquid chromatography (HPLC). Their chemical structures were characterized by liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance spectroscopy (NMR). The allylic hydroxylated derivatives of LA and CLA exhibited moderate in vitro cytotoxicity against a panel of human cancer cell lines including chronic myelogenous leukemia K562, myeloma RPMI8226, hepatocellular carcinoma HepG2 and breast adenocarcinoma MCF-7 cells (IC(50) 10-75 microM). The allylic hydroxylated derivatives of LA and CLA also showed toxicity to brine shrimp with LD(50) values in the range of 2.30-13.8 microM. However these compounds showed insignificant toxicity to honeybee at doses up to 100 microg/bee.

  17. Determination of acidity constants of acid-base indicators by second-derivative spectrophotometry

    NASA Astrophysics Data System (ADS)

    Kara, Derya; Alkan, Mahir

    2000-12-01

    A method for calculation of acid-base dissociation constants of monoprotic weak organic acids whose acid and base species have overlapping spectra from absorptiometric and pH measurements is described. It has been shown that the second-derivative spectrophotometry can effectively be used for determining the dissociation constants, when dissociation constants obtained for methyl orange and bromothymol blue were compared with the values given in the literature.

  18. Biological Activities of Oleanolic Acid Derivatives from Calendula officinalis Seeds.

    PubMed

    Zaki, Ahmed; Ashour, Ahmed; Mira, Amira; Kishikawa, Asuka; Nakagawa, Toshinori; Zhu, Qinchang; Shimizu, Kuniyoshi

    2016-05-01

    Phytochemical examination of butanol fraction of Calendula officinalis seeds led to the isolation of two compounds identified as 28-O-β-D-glucopyranosyl-oleanolic acid 3-O-β-D-glucopyranosyl (1→3)-β-D-glucopyranosiduronic acid (CS1) and oleanolic acid 3-O-β-D-glucopyranosyl (1→3)-β-D-glucopyranosiduronic acid (CS2). Biological evaluation was carried out for these two compounds such as melanin biosynthesis inhibitory, hyaluronic acid production activities, anti obesity using lipase inhibition and adipocyte differentiation as well as evaluation of the protective effect against hydrogen peroxide induced neurotoxicity in neuro-2A cells. The results showed that, compound CS2 has a melanin biosynthesis stimulatory activity; however, compound CS1 has a potent stimulatory effect for the production of hyaluronic acid on normal human dermal fibroblast from adult (NHDF-Ad). Both compounds did not show any inhibitory effect on both lipase and adipocyte differentiation. Compound CS2 could protect neuro-2A cells and increased cell viability against H2 O2 . These activities (melanin biosynthesis stimulatory and protective effect against H2 O2 of CS2 and hyaluronic acid productive activities of these triterpene derivatives) have been reported for the first time. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  19. Synthesis and antifungal activity of bile acid-derived oxazoles.

    PubMed

    Fernández, Lucía R; Svetaz, Laura; Butassi, Estefanía; Zacchino, Susana A; Palermo, Jorge A; Sánchez, Marianela

    2016-04-01

    Peracetylated bile acids (1a-g) were used as starting materials for the preparation of fourteen new derivatives bearing an oxazole moiety in their side chain (6a-g, 8a-g). The key step for the synthetic path was a Dakin-West reaction followed by a Robinson-Gabriel cyclodehydration. A simpler model oxazole (12) was also synthesized. The antifungal activity of the new compounds (6a-g) as well as their starting bile acids (1a-g) was tested against Candida albicans. Compounds 6e and 6g showed the highest percentages of inhibition (63.84% and 61.40% at 250 μg/mL respectively). Deacetylation of compounds 6a-g, led to compounds 8a-g which showed lower activities than the acetylated derivatives.

  20. [Cardioprotective properties of new glutamic acid derivative under stress conditions].

    PubMed

    Perfilova, V N; Sadikova, N V; Berestovitskaia, V M; Vasil'eva, O S

    2014-01-01

    The effect of new glutamic acid derivative on the cardiac ino- and chronotropic functions has been studied in experiments on rats exposed to 24-hour immobilization-and-pain stress. It is established that glutamic acid derivative RGPU-238 (glufimet) at a dose of 28.7 mg/kg increases the increment of myocardial contractility and relaxation rates and left ventricular pressure in stress-tested animals by 13 1,1, 72.4, and 118.6%, respectively, as compared to the control group during the test for adrenoreactivity. Compound RGPU-238 increases the increment of the maximum intensity of myocardium functioning by 196.5 % at 30 sec of isometric workload as compared to the control group. The cardioprotective effect of compound RGPU-238 is 1.5 - 2 times higher than that of the reference drug phenibut.

  1. Gastroprotective effect and cytotoxicity of carnosic acid derivatives.

    PubMed

    Theoduloz, Cristina; Pertino, Mariano Walter; Rodríguez, Jaime A; Schmeda-Hirschmann, Guillermo

    2011-06-01

    Carnosic acid (CA) is the main phenolic diterpene of rosemary (Rosmarinus officinalis L., Lamiaceae) and presents gastroprotective effect in vitro and in vivo. To determine structure-activity relationships, seventeen esters and ethers of CA were prepared, comprising aliphatic, aromatic, and heterocyclic compounds. The naturally occurring 12-O-methylcarnosic acid (14) was also included in the study. The compounds were evaluated for their gastroprotective activity in the HCl/EtOH-induced gastric lesions model in mice, and for cytotoxicity in human adenocarcinoma AGS cells, Hep G2 hepatocellular carcinoma cells, and human lung fibroblasts. At 10 mg/kg, some of the CA derivatives (5, 8, 9, 12, 14, and 18) were more effective preventing gastric lesions than the reference compound lansoprazole at the same dose. The dibenzoate 9, diindoleacetate 12, and the derivative 18 showed the best gastroprotective effect combined with the lowest cytotoxicity. © Georg Thieme Verlag KG Stuttgart · New York.

  2. Microbial production of fatty acid-derived fuels and chemicals

    PubMed Central

    Lennen, Rebecca M; Pfleger, Brian F

    2013-01-01

    Fatty acid metabolism is an attractive route to produce liquid transportation fuels and commodity oleochemicals from renewable feedstocks. Recently, genes and enzymes, which comprise metabolic pathways for producing fatty acid-derived compounds (e.g. esters, alkanes, olefins, ketones, alcohols, polyesters) have been elucidated and used in engineered microbial hosts. The resulting strains often generate products at low percentages of maximum theoretical yields, leaving significant room for metabolic engineering. Economically viable processes will require strains to approach theoretical yields, particularly for replacement of petroleum-derived fuels. This review will describe recent progress toward this goal, highlighting the scientific discoveries of each pathway, ongoing biochemical studies to understand each enzyme, and metabolic engineering strategies that are being used to improve strain performance. PMID:23541503

  3. Quantification of acidic compounds in complex biomass-derived streams

    SciTech Connect

    Karp, Eric M.; Nimlos, Claire T.; Deutch, Steve; Salvachúa, Davinia; Cywar, Robin M.; Beckham, Gregg T.

    2016-01-01

    Biomass-derived streams that contain acidic compounds from the degradation of lignin and polysaccharides (e.g. black liquor, pyrolysis oil, pyrolytic lignin, etc.) are chemically complex solutions prone to instability and degradation during analysis, making quantification of compounds within them challenging. Here we present a robust analytical method to quantify acidic compounds in complex biomass-derived mixtures using ion exchange, sample reconstitution in pyridine and derivatization with BSTFA. The procedure is based on an earlier method originally reported for kraft black liquors and, in this work, is applied to identify and quantify a large slate of acidic compounds in corn stover derived alkaline pretreatment liquor (APL) as a function of pretreatment severity. Analysis of the samples is conducted with GCxGC-TOFMS to achieve good resolution of the components within the complex mixture. The results reveal the dominant low molecular weight components and their concentrations as a function of pretreatment severity. Application of this method is also demonstrated in the context of lignin conversion technologies by applying it to track the microbial conversion of an APL substrate. Here too excellent results are achieved, and the appearance and disappearance of compounds is observed in agreement with the known metabolic pathways of two bacteria, indicating the sample integrity was maintained throughout analysis. Finally, it is shown that this method applies more generally to lignin-rich materials by demonstrating its usefulness in analysis of pyrolysis oil and pyrolytic lignin.

  4. Citric-acid-derived photo-cross-linked biodegradable elastomers.

    PubMed

    Gyawali, Dipendra; Tran, Richard T; Guleserian, Kristine J; Tang, Liping; Yang, Jian

    2010-01-01

    Citric-acid-derived thermally cross-linked biodegradable elastomers (CABEs) have recently received significant attention in various biomedical applications, including tissue-engineering orthopedic devices, bioimaging and implant coatings. However, citric-acid-derived photo-cross-linked biodegradable elastomers are rarely reported. Herein, we report a novel photo-cross-linked biodegradable elastomer, referred to as poly(octamethylene maleate citrate) (POMC), which preserves pendant hydroxyl and carboxylic functionalities after cross-linking for the potential conjugation of biologically active molecules. Pre-POMC is a low-molecular-mass pre-polymer with an average molecular mass between 701 and 1291 Da. POMC networks are soft and elastic with an initial modulus of 0.07 to 1.3 MPa and an elongation-at-break between 38 and 382%. FT-IR-ATR results confirmed the successful surface immobilization of type-I collagen onto POMC films, which enhanced in vitro cellular attachment and proliferation. Photo-polymerized POMC films implanted subcutaneously into Sprague-Dawley rats demonstrated minimal in vivo inflammatory responses. The development of POMC enriches the family of citric-acid-derived biodegradable elastomers and expands the available biodegradable polymers for versatile needs in biomedical applications.

  5. Quantification of acidic compounds in complex biomass-derived streams

    SciTech Connect

    Karp, Eric M.; Nimlos, Claire T.; Deutch, Steve; Salvachúa, Davinia; Cywar, Robin M.; Beckham, Gregg T.

    2016-05-10

    Biomass-derived streams that contain acidic compounds from the degradation of lignin and polysaccharides (e.g. black liquor, pyrolysis oil, pyrolytic lignin, etc.) are chemically complex solutions prone to instability and degradation during analysis, making quantification of compounds within them challenging. Here we present a robust analytical method to quantify acidic compounds in complex biomass-derived mixtures using ion exchange, sample reconstitution in pyridine and derivatization with BSTFA. The procedure is based on an earlier method originally reported for kraft black liquors and, in this work, is applied to identify and quantify a large slate of acidic compounds in corn stover derived alkaline pretreatment liquor (APL) as a function of pretreatment severity. Analysis of the samples is conducted with GCxGC-TOFMS to achieve good resolution of the components within the complex mixture. The results reveal the dominant low molecular weight components and their concentrations as a function of pretreatment severity. Application of this method is also demonstrated in the context of lignin conversion technologies by applying it to track the microbial conversion of an APL substrate. Here as well excellent results are achieved, and the appearance and disappearance of compounds is observed in agreement with the known metabolic pathways of two bacteria, indicating the sample integrity was maintained throughout analysis. Finally, it is shown that this method applies more generally to lignin-rich materials by demonstrating its usefulness in analysis of pyrolysis oil and pyrolytic lignin.

  6. 4-Hydroxybenzyl-substituted amino acid derivatives from Gastrodia elata

    PubMed Central

    Guo, Qinglan; Wang, Yanan; Lin, Sheng; Zhu, Chenggen; Chen, Minghua; Jiang, Zhibo; Xu, Chengbo; Zhang, Dan; Wei, Huailing; Shi, Jiangong

    2015-01-01

    Seven new 4-hydroxybenzyl-substituted amino acid derivatives (1−7), together with 11 known compounds, were isolated from an aqueous extract of the rhizomes of Gastrodia elata Blume. Their structures were determined by spectroscopic and chemical methods. Compounds 1−3 are pyroglutamate derivatives containing 4-hydroxybenzyl units at the N atom and 4−7 are the first examples of natural products with the 4-hydroxybenzyl unit linked via a thioether bond to 2-hydroxy-3-mercaptopropanoic acid (4−6) and 2-hydroxy-4-mercaptobutanoic acid (7), which would be biogenetically derived from cysteine and homocysteine, respectively. The structures of 1 and 2 were verified by synthesis, while the absolute configurations of 4, 5 and 7 were assigned using Mosher’s method based on the MPA determination rule of ΔδRS values. The known compound 4-(hydroxymethyl)-5-nitrobenzene-1,2-diol (8) exhibited activity against Fe2+-cysteine induced rat liver microsomal lipid peroxidation with IC50 values of 9.99×10−6 mol/L. PMID:26579466

  7. Quantification of acidic compounds in complex biomass-derived streams

    DOE PAGES

    Karp, Eric M.; Nimlos, Claire T.; Deutch, Steve; ...

    2016-05-10

    Biomass-derived streams that contain acidic compounds from the degradation of lignin and polysaccharides (e.g. black liquor, pyrolysis oil, pyrolytic lignin, etc.) are chemically complex solutions prone to instability and degradation during analysis, making quantification of compounds within them challenging. Here we present a robust analytical method to quantify acidic compounds in complex biomass-derived mixtures using ion exchange, sample reconstitution in pyridine and derivatization with BSTFA. The procedure is based on an earlier method originally reported for kraft black liquors and, in this work, is applied to identify and quantify a large slate of acidic compounds in corn stover derived alkalinemore » pretreatment liquor (APL) as a function of pretreatment severity. Analysis of the samples is conducted with GCxGC-TOFMS to achieve good resolution of the components within the complex mixture. The results reveal the dominant low molecular weight components and their concentrations as a function of pretreatment severity. Application of this method is also demonstrated in the context of lignin conversion technologies by applying it to track the microbial conversion of an APL substrate. Here as well excellent results are achieved, and the appearance and disappearance of compounds is observed in agreement with the known metabolic pathways of two bacteria, indicating the sample integrity was maintained throughout analysis. Finally, it is shown that this method applies more generally to lignin-rich materials by demonstrating its usefulness in analysis of pyrolysis oil and pyrolytic lignin.« less

  8. Urease inhibitory activities of β-boswellic acid derivatives

    PubMed Central

    2013-01-01

    Background and the purpose of the study Boswellia carterii have been used in traditional medicine for many years for management different gastrointestinal disorders. In this study, we wish to report urease inhibitory activity of four isolated compound of boswellic acid derivative. Methods 4 pentacyclic triterpenoid acids were isolated from Boswellia carterii and identified by NMR and Mass spectroscopic analysis (compounds 1, 3-O-acetyl-9,11-dehydro-β-boswellic acid; 2, 3-O-acetyl-11-hydroxy-β-boswellic acid; 3. 3-O- acetyl-11-keto-β-boswellic acid and 4, 11-keto-β-boswellic acid. Their inhibitory activity on Jack bean urease were evaluated. Docking and pharmacophore analysis using AutoDock 4.2 and Ligandscout 3.03 programs were also performed to explain possible mechanism of interaction between isolated compounds and urease enzyme. Results It was found that compound 1 has the strongest inhibitory activity against Jack bean urease (IC50 = 6.27 ± 0.03 μM), compared with thiourea as a standard inhibitor (IC50 = 21.1 ± 0.3 μM). Conclusion The inhibition potency is probably due to the formation of appropriate hydrogen bonds and hydrophobic interactions between the investigated compounds and urease enzyme active site and confirms its traditional usage. PMID:23351363

  9. Interactions of salicylic acid derivatives with calcite crystals.

    PubMed

    Ukrainczyk, Marko; Gredičak, Matija; Jerić, Ivanka; Kralj, Damir

    2012-01-01

    Investigation of basic interactions between the active pharmaceutical compounds and calcium carbonates is of great importance because of the possibility to use the carbonates as a mineral carrier in drug delivery systems. In this study the mode and extent of interactions of salicylic acid and its amino acid derivates, chosen as pharmaceutically relevant model compounds, with calcite crystals are described. Therefore, the crystal growth kinetics of well defined rhombohedral calcite seed crystals in the systems containing salicylic acid (SA), 5-amino salicylic acid (5-ASA), N-salicyloil-l-aspartic acid (N-Sal-Asp) or N-salicyloil-l-glutamic acid (N-Sal-Glu), were investigated. The precipitation systems were of relatively low initial supersaturation and of apparently neutral pH. The data on the crystal growth rate reductions in the presence of the applied salicylate molecules were analyzed by means of Cabrera & Vermileya's, and Kubota & Mullin's models of interactions of the dissolved additives and crystal surfaces. The crystal growth kinetic experiments were additionally supported with the appropriate electrokinetic, spectroscopic and adsorption measurements. The Langmuir adsorption constants were determined and they were found to be in a good correlation with values obtained from crystal growth kinetic analyses. The results indicated that salicylate molecules preferentially adsorb along the steps on the growing calcite surfaces. The values of average spacing between the adjacent salicylate adsorption active sites and the average distance between the neighboring adsorbed salicylate molecules were also estimated.

  10. Synthesis and biological activity of alkynoic acids derivatives against mycobacteria

    PubMed Central

    Vilchèze, Catherine; Leung, Lawrence W.; Bittman, Robert; Jacobs, William R.

    2015-01-01

    2-alkynoic acids have bactericidal activity against Mycobacterium smegmatis but their activity fall sharply as the length of the carbon chain increased. In this study, derivatives of 2- alkynoic acids were synthesized and tested against fast- and slow-growing mycobacteria. Their activity was first evaluated in M. smegmatis against their parental 2-alkynoic acids, as well as isoniazid, a first-line antituberculosis drug. The introduction of additional unsaturation or heteroatoms into the carbon chain enhanced the antimycobacterial activity of longer chain alkynoic acids (more than 19 carbons long). In contrast, although the modification of the carboxylic group did not improve the antimycobacterial activity, it significantly reduced the toxicity of the compounds against eukaryotic cells. Importantly, 4-(alkylthio)but-2-ynoic acids, had better bactericidal activity than the parental 2-alkynoic acids and on a par with isoniazid against the slow-grower Mycobacterium bovis BCG. These compounds had also low toxicity against eukaryotic cells, suggesting that they could be potential therapeutic agents against other types of topical mycobacterial infections causing skin diseases including Mycobacterium abscessus, Mycobacterium ulcerans, and Mycobacterium leprae. Moreover, they provide a possible scaffold for future drug development. PMID:26256431

  11. Starch Modification by Organic Acids and Their Derivatives: A Review.

    PubMed

    Ačkar, Đurđica; Babić, Jurislav; Jozinović, Antun; Miličević, Borislav; Jokić, Stela; Miličević, Radoslav; Rajič, Marija; Šubarić, Drago

    2015-10-27

    Starch has been an inexhaustible subject of research for many decades. It is an inexpensive, readily-available material with extensive application in the food and processing industry. Researchers are continually trying to improve its properties by different modification procedures and expand its application. What is mostly applied in this view are their chemical modifications, among which organic acids have recently drawn the greatest attention, particularly with respect to the application of starch in the food industry. Namely, organic acids naturally occur in many edible plants and many of them are generally recognized as safe (GRAS), which make them ideal modification agents for starch intended for the food industry. The aim of this review is to give a short literature overview of the progress made in the research of starch esterification, etherification, cross-linking, and dual modification with organic acids and their derivatives.

  12. Template directed reactions of 2-aminoadenylic acid derivatives

    NASA Technical Reports Server (NTRS)

    Webb, T. R.; Orgel, L. E.

    1982-01-01

    The template-directed oligomerization of activated derivatives of 2-aminoadenylic acid (paA) on polyuridylic acid (poly(U)) in aqueous buffers was studied. The reaction differs from that of adenylic acid (pA) under identical conditions, in that only di- and tri-nucleotides are observed as substantial products rather than a longer sequence of oligomers. The reaction of paA also differs from that of pA in that it does not require Mg (2+), and is less susceptible to increased temperature. The relevance of these observations to the chemical evolution of polynucleotide replication is discussed. Improved syntheses of paA and its diphosphate are reported.

  13. Template directed reactions of 2-aminoadenylic acid derivatives

    NASA Technical Reports Server (NTRS)

    Webb, T. R.; Orgel, L. E.

    1982-01-01

    The template-directed oligomerization of activated derivatives of 2-aminoadenylic acid (paA) on polyuridylic acid (poly(U)) in aqueous buffers was studied. The reaction differs from that of adenylic acid (pA) under identical conditions, in that only di- and tri-nucleotides are observed as substantial products rather than a longer sequence of oligomers. The reaction of paA also differs from that of pA in that it does not require Mg (2+), and is less susceptible to increased temperature. The relevance of these observations to the chemical evolution of polynucleotide replication is discussed. Improved syntheses of paA and its diphosphate are reported.

  14. Evaluation of antioxidant properties of monoaromatic derivatives of pulvinic acids.

    PubMed

    Habrant, Damien; Poigny, Stéphane; Ségur-Derai, Muriel; Brunel, Yves; Heurtaux, Benoît; Le Gall, Thierry; Strehle, Axelle; Saladin, Régis; Meunier, Stéphane; Mioskowski, Charles; Wagner, Alain

    2009-04-23

    The natural mushroom pigment Norbadione A and three other pulvinic acids were shown by our group to display very efficient antioxidant properties by comparison with a collection of potent molecules including catechols, flavonoids, stilbenes, or coumarins. Despite numerous publications on robust and straightforward synthetic access to pulvinic acids by us and others, no report has been made to unravel the structure-activity relationships that govern the striking antioxidant activity. Herein is presented the synthesis of 18 diverse pulvinic acid derivatives and the study of their radical scavenging capacities by four different assays. The influence of each of the two phenyl rings, of their substituents and of the lateral chain on the antioxidant properties, was explored to reveal a simplified structure of excellent activity. These results, along with the absence of cytotoxicity, make the synthesized compounds interesting to evaluate for several biological activities and especially for anti-inflammatory effects and skin protection against UV induced oxidative stress.

  15. Plant amino acid-derived vitamins: biosynthesis and function.

    PubMed

    Miret, Javier A; Munné-Bosch, Sergi

    2014-04-01

    Vitamins are essential organic compounds for humans, having lost the ability to de novo synthesize them. Hence, they represent dietary requirements, which are covered by plants as the main dietary source of most vitamins (through food or livestock's feed). Most vitamins synthesized by plants present amino acids as precursors (B1, B2, B3, B5, B7, B9 and E) and are therefore linked to plant nitrogen metabolism. Amino acids play different roles in their biosynthesis and metabolism, either incorporated into the backbone of the vitamin or as amino, sulfur or one-carbon group donors. There is a high natural variation in vitamin contents in crops and its exploitation through breeding, metabolic engineering and agronomic practices can enhance their nutritional quality. While the underlying biochemical roles of vitamins as cosubstrates or cofactors are usually common for most eukaryotes, the impact of vitamins B and E in metabolism and physiology can be quite different on plants and animals. Here, we first aim at giving an overview of the biosynthesis of amino acid-derived vitamins in plants, with a particular focus on how this knowledge can be exploited to increase vitamin contents in crops. Second, we will focus on the functions of these vitamins in both plants and animals (and humans in particular), to unravel common and specific roles for vitamins in evolutionary distant organisms, in which these amino acid-derived vitamins play, however, an essential role.

  16. Three amino acid derivatives of valproic acid: design, synthesis, theoretical and experimental evaluation as anticancer agents.

    PubMed

    Luna-Palencia, Gabriela R; Martinez-Ramos, Federico; Vasquez-Moctezuma, Ismael; Fragoso-Vazquez, Manuel Jonathan; Mendieta-Wejebe, Jessica Elena; Padilla-Martínez, Itzia I; Sixto-Lopez, Yudibeth; Mendez-Luna, David; Trujillo-Ferrara, Jose; Meraz-Rios, Marco A; Fonseca-Sabater, Yadira; Correa-Basurto, Jose

    2014-01-01

    Valproic acid (VPA) is extensively used as an anticonvulsive agent and as a treatment for other neurological disorders. It has been shown that VPA exerts an anti-proliferative effect on several types of cancer cells by inhibiting the activity of histone deacetylases (HDACs), which are involved in replication and differentiation processes. However, VPA has some disadvantages, among which are poor water solubility and hepatotoxicity. Therefore, the aim of the present study was to design and synthesize three derivatives of VPA to improve its physicochemical properties and anti-proliferative effects. For this purpose, the amino acids aspartic acid, glutamic acid and proline were added to the molecular structure of VPA. Docking and molecular dynamics simulations were used to determine the mode of recognition of these three derivatives by different conformations of HDAC8. This receptor was used as the specific target because of its high affinity for this type of substrate. The results demonstrate that, compared to VPA, the test compounds bind to different sites on the enzyme and that hydrogen bonds and hydrophobic interactions play key roles in this difference. The IC50 values of the VPA derivatives, experimentally determined using HeLa cells, were in the mM range. This result indicates that the derivatives have greater antiproliferative effects than the parent compound. Hence, these results suggest that these amino acid derivatives may represent a good alternative for anticancer treatment.

  17. Rosmarinic acid and its derivatives: biotechnology and applications.

    PubMed

    Bulgakov, Victor P; Inyushkina, Yuliya V; Fedoreyev, Sergey A

    2012-09-01

    Rosmarinic acid (RA) is one of the first secondary metabolites produced in plant cell cultures in extremely high yields, up to 19% of the cell dry weight. More complex derivatives of RA, such as rabdosiin and lithospermic acid B, later were also obtained in cell cultures at high yields. RA and its derivatives possess promising biological activities, such as improvement of cognitive performance, prevention of the development of Alzheimer's disease, cardioprotective effects, reduction of the severity of kidney diseases and cancer chemoprevention. The TNF-α-induced NF-κB signaling pathway has emerged as a central target for RA. Despite these impressive activities and high yields, the biotechnological production of these metabolites on an industrial scale has not progressed. We summarized data suggesting that external stimuli, the Ca(2+)-dependent NADPH oxidase pathway and processes of protein phosphorylation/dephosphorylation are involved in the regulation of biosynthesis of these substances in cultured plant cells. In spite of growing information about pathways regulating biosynthesis of RA and its derivatives in cultured plant cells, the exact mechanism of regulation remains unknown. We suggest that further progress in the biotechnology of RA and its derivatives can be achieved by using new high-throughput techniques.

  18. Shoot-derived abscisic acid promotes root growth.

    PubMed

    McAdam, Scott A M; Brodribb, Timothy J; Ross, John J

    2016-03-01

    The phytohormone abscisic acid (ABA) plays a major role in regulating root growth. Most work to date has investigated the influence of root-sourced ABA on root growth during water stress. Here, we tested whether foliage-derived ABA could be transported to the roots, and whether this foliage-derived ABA had an influence on root growth under well-watered conditions. Using both application studies of deuterium-labelled ABA and reciprocal grafting between wild-type and ABA-biosynthetic mutant plants, we show that both ABA levels in the roots and root growth in representative angiosperms are controlled by ABA synthesized in the leaves rather than sourced from the roots. Foliage-derived ABA was found to promote root growth relative to shoot growth but to inhibit the development of lateral roots. Increased root auxin (IAA) levels in plants with ABA-deficient scions suggest that foliage-derived ABA inhibits root growth through the root growth-inhibitor IAA. These results highlight the physiological and morphological importance, beyond the control of stomata, of foliage-derived ABA. The use of foliar ABA as a signal for root growth has important implications for regulating root to shoot growth under normal conditions and suggests that leaf rather than root hydration is the main signal for regulating plant responses to moisture.

  19. Gastroprotective and cytotoxic effect of dehydroabietic acid derivatives.

    PubMed

    Sepúlveda, Beatriz; Astudillo, Luis; Rodríguez, Jaime A; Yáñez, Tania; Theoduloz, Cristina; Schmeda-Hirschmann, Guillermo

    2005-11-01

    Dehydroabietic acid derivatives have been reported to display antisecretory and antipepsin effect in animal models. Some 19 dehydroabietic acid diterpenes were prepared and assessed for gastroprotective activity in the HCl/EtOH-induced gastric lesions in mice as well as for cytotoxicity in human lung fibroblasts (MRC-5) and human epithelial gastric (AGS) cells. At a single oral dose of 100 mg kg(-1), highest gastroprotective effect was provided by dehydroabietanol, its corresponding aldehyde, dehydroabietic acid (DHA) and its methyl ester, N-(m-nitrophenyl)-, N-(o-chlorophenyl)- and N-(p-iodophenyl)abieta-8,11,13-trien-18-amide (compounds 12-14), N-2-aminothiazolyl- and N-benzylabieta-8,11,13-trien-18-amide (compounds 18-19) being as active as lansoprazole at 20 mg kg(-1) and reducing the lesion index by at least 75%. In the compound series including the alcohol, ester, aldehyde, acid and methyl ester at C-18 (compounds 1-9), highest activity was related with the presence of an alcohol, aldehyde, acid or methyl ester at C-18, the activity being strongly reduced after esterification. The cytotoxicity of the compounds 1-9 towards AGS cells and fibroblasts was higher than the values for the amides 10-19. In the compounds 10-19, the best gastroprotective effect was observed for the aromatic amides 12-14 (75-85% inhibition of gastric lesions) bearing a nitro or halogen function in the N-benzoyl moiety. Lowest cytotoxicity was found for the amides, with IC(50) values >1000 microM for fibroblasts and from 200 up to >1000 microM for AGS cells, respectively. The N-2-aminothiazolyl- and N-benzylamide derivatives were also very active as gastroprotectors with higher cytotoxicity against AGS cells.

  20. Antimicrobial activity of rhodanine-3-acetic acid derivatives.

    PubMed

    Krátký, Martin; Vinšová, Jarmila; Stolaříková, Jiřina

    2017-03-15

    Twenty-four 2-(4-oxo-2-thioxothiazolidin-3-yl)acetic acid (rhodanine-3-acetic acid)-based amides, esters and 5-arylalkylidene derivatives were synthesized, characterized and evaluated as potential antimicrobial agents against a panel of bacteria, mycobacteria and fungi. All of the derivatives were active against mycobacteria. N-(4-Chlorophenyl)-2-[5-(2-hydroxybenzylidene)-4-oxo-2-thioxothiazolidin-3-yl]acetamide demonstrated the highest activity against Mycobacterium tuberculosis with minimum inhibitory concentrations (MIC) of 8-16μM. Non-tuberculous mycobacteria were the most susceptible to 2-[5-(2-hydroxybenzylidene)-4-oxo-2-thioxothiazolidin-3-yl]acetic acids (MIC values ⩾32μM). The highest antibacterial activity against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus exhibited 4-(trifluoromethyl)phenyl 2-(4-oxo-2-thioxothiazolidin-3-yl)acetate (MIC⩾15.62μM). Several structure-activity relationships were identified. The activity against Gram-negative and fungal pathogens was marginal. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Antiherbivore prenylated benzoic acid derivatives from Piper kelleyi.

    PubMed

    Jeffrey, Christopher S; Leonard, Michael D; Glassmire, Andrea E; Dodson, Craig D; Richards, Lora A; Kato, Massuo J; Dyer, Lee A

    2014-01-24

    The known prenylated benzoic acid derivative 3-geranyl-4-hydroxy-5-(3″,3″-dimethylallyl)benzoic acid (1) and two new chromane natural products were isolated from the methanolic extract of the leaves of Piper kelleyi Tepe (Piperaceae), a midcanopy tropical shrub that grows in lower montane rain forests in Ecuador and Peru. Structure determination using 1D and 2D NMR analysis led to the structure of the chromene 2 and to the reassignment of the structure of cumanensic acid as 4, an isomeric chromene previously isolated from Piper gaudichaudianum. The structure and relative configuration of new chromane 3 was determined using 1D and 2D NMR spectroscopic analysis and was found to be racemic by ECD spectropolarimetry. The biological activity of 1-3 was evaluated against a lab colony of the generalist caterpillar Spodoptera exigua (Noctuidae), and low concentrations of 2 and 3 were found to significantly reduce fitness. Further consideration of the biosynthetic relationship of the three compounds led to the proposal that 1 is converted to 2 via an oxidative process, whereas 3 is produced through hetero-[4+2] dimerization of a quinone methide derived from the chromene 2.

  2. Planar chiral organoborane Lewis acids derived from naphthylferrocene.

    PubMed

    Chen, Jiawei; Venkatasubbaiah, Krishnan; Pakkirisamy, Thilagar; Doshi, Ami; Yusupov, Andrej; Patel, Yesha; Lalancette, Roger A; Jäkle, Frieder

    2010-08-02

    Enantiomerically pure metalated 2-(1-naphthyl)ferrocene (NpFc) derivatives NpFcM (M=SnMe(3), HgCl) were prepared and characterized by multinuclear NMR and UV/Vis spectroscopy, cyclic voltammetry, and elemental analysis. Optical rotation measurements were performed and the absolute configuration of the new planar chiral ferrocene species was confirmed by single-crystal X-ray diffraction analysis. The mercuriated species NpFcHgCl proved suitable as a reagent for the preparation of the chiral organoborane Lewis acid NpFcBCl(2), which can in turn be converted to other ferrocenylboranes by replacement of Cl with nucleophiles. The highly Lewis acidic perfluoroarylborane derivatives NpFcB(C(6)F(5))Cl and NpFcB(C(6)F(5))(2) were successfully prepared by treatment with CuC(6)F(5). The structures were studied by single-crystal X-ray diffraction and variable-temperature (19)F NMR spectroscopy, which suggested that pi stacking of a C(6)F(5) group on boron with the adjacent naphthyl group is energetically favorable. UV/Vis absorption spectroscopy and cyclic voltammetry measurements were performed to examine the electronic properties of these novel redox-active chiral Lewis acids.

  3. Experimental and theoretical study on benzoic acid derivatives

    NASA Astrophysics Data System (ADS)

    Świsłocka, R.; Regulska, E.; Samsonowicz, M.; Lewandowski, W.

    2013-07-01

    Benzoic (BA), p-hydroxybenzoic (HBA), m-methoxybenzoic (MBA), vanillic (VA) and syringic (SGA) acids were studied using both experimental and theoretical tools. The vibrational (FT-IR, FT-Raman) and 1H and 13C NMR spectra of benzoic acid derivatives were recorded. Characteristic shifts and changes in intensities of bands along the studied series were observed. The changes of chemical shifts of protons (1H NMR) and carbons (13C NMR) in the series of studied compounds were observed too. Optimized geometrical structures of studied compounds were obtained by B3LYP method using 6-31++G**, 6-311+G** and 6-311++G** basis sets. Aromaticity indices, atomic charges, dipole moments and energies were calculated. The theoretical chemical shifts in 1H and 13C NMR spectra and theoretical wavenumbers and intensities of IR and Raman spectra were determined. The calculated parameters were compared to experimental characteristic of studied compounds.

  4. Novel sustainable polymers derived from renewable rosin and fatty acids

    NASA Astrophysics Data System (ADS)

    Wilbon, Perry

    In the work of this dissertation, polymers derived from renewable bio-based resources prepared by various polymerization techniques were investigated. The properties of these polymeric materials were characterized and discussed. Rosin was first converted into acrylate or methacrylate monomers for atom transfer radical polymerization (ATRP). Second, rosin was combined with vegetable oil to produce completely renewable novel polyesters by acyclic diene metathesis (ADMET) polymerization. Third, degradable block copolymers were synthesized composed of polycaprolactone and rosin grafted polycaprolactone with the aid of ring-opening polymerization (ROP). Finally, degradable polyesters were produced using vegetable oil derivatives as starting materials. These new rosin and fatty acid based renewable polymer materials will have potential applications as sustainable thermoplastics, thermoplastic elastomers, etc.

  5. Rare biscoumarins and a chlorogenic acid derivative from Erycibe obtusifolia.

    PubMed

    Liu, Jian; Feng, Ziming; Xu, Jianfu; Wang, Yinghong; Zhang, Peicheng

    2007-07-01

    Three coumarins, 7,7'-dihydroxy-6,6'-dimethoxy-3,3'-biscoumarin (1), 7,7'-dihydroxy-6,6'-dimethoxy-8,8'-biscoumarin (2) and 7-O-[4'-O-(3'',4''-dihydroxycinnamyl)-beta-d-glucopyranosyl]-6-methoxycoumarin (3), and a chlorogenic acid derivative, methyl-3-O-(4''-hydroxy-3'',5''-dimethoxybenzoyl)-chlorogenate (4) were isolated from the roots of Erycibe obtusifolia along with four known coumarins, scopoletin (5), scopolin (6), cleomiscosin A (7) and cleomiscosin B (8). Their structures were elucidated by spectroscopic methods. Among them, compounds (1) and (2) are rare carbon-carbon linked symmetrical biscoumarins.

  6. Esterification of fermentation-derived acids via pervaporation

    DOEpatents

    Datta, Rathin; Tsai, Shih-Perng

    1998-01-01

    A low temperature method for esterifying ammonium- and amine-containing salts is provided whereby the salt is reacted with an alcohol in the presence of heat and a catalyst and then subjected to a dehydration and deamination process using pervaporation. The invention also provides for a method for producing esters of fermentation derived, organic acid salt comprising first cleaving the salt into its cationic part and anionic part, mixing the anionic part with an alcohol to create a mixture; heating the mixture in the presence of a catalyst to create an ester; dehydrating the now heated mixture; and separating the ester from the now-dehydrated mixture.

  7. Esterification of fermentation-derived acids via pervaporation

    DOEpatents

    Datta, R.; Tsai, S.P.

    1998-03-03

    A low temperature method for esterifying ammonium- and amine-containing salts is provided whereby the salt is reacted with an alcohol in the presence of heat and a catalyst and then subjected to a dehydration and deamination process using pervaporation. The invention also provides for a method for producing esters of fermentation derived, organic acid salt comprising first cleaving the salt into its cationic part and anionic part, mixing the anionic part with an alcohol to create a mixture; heating the mixture in the presence of a catalyst to create an ester; dehydrating the now heated mixture; and separating the ester from the now-dehydrated mixture. 2 figs.

  8. Synthesis and biological activity of novel deoxycholic acid derivatives.

    PubMed

    Popadyuk, Irina I; Markov, Andrey V; Salomatina, Oksana V; Logashenko, Evgeniya B; Shernyukov, Andrey V; Zenkova, Marina A; Salakhutdinov, Nariman F

    2015-08-01

    We report the synthesis and biological activity of new semi-synthetic derivatives of naturally occurring deoxycholic acid (DCA) bearing 2-cyano-3-oxo-1-ene, 3-oxo-1(2)-ene or 3-oxo-4(5)-ene moieties in ring A and 12-oxo or 12-oxo-9(11)-ene moieties in ring C. Bioassays using murine macrophage-like cells and tumour cells show that the presence of the 9(11)-double bond associated with the increased polarity of ring A or with isoxazole ring joined to ring A, improves the ability of the compounds to inhibit cancer cell growth. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Injectable hydrogels derived from phosphorylated alginic acid calcium complexes.

    PubMed

    Kim, Han-Sem; Song, Minsoo; Lee, Eun-Jung; Shin, Ueon Sang

    2015-06-01

    Phosphorylation of sodium alginate salt (NaAlg) was carried out using H3PO4/P2O5/Et3PO4 followed by acid-base reaction with Ca(OAc)2 to give phosphorylated alginic acid calcium complexes (CaPAlg), as a water dispersible alginic acid derivative. The modified alginate derivatives including phosphorylated alginic acid (PAlg) and CaPAlg were characterized by nuclear magnetic resonance spectroscopy for (1)H, and (31)P nuclei, high resolution inductively coupled plasma optical emission spectroscopy, Fourier transform infrared spectroscopy, and thermogravimetric analysis. CaPAlg hydrogels were prepared simply by mixing CaPAlg solution (2w/v%) with NaAlg solution (2w/v%) in various ratios (2:8, 4:6, 6:4, 8:2) of volume. No additional calcium salts such as CaSO4 or CaCl2 were added externally. The gelation was completed within about 3-40min indicating a high potential of hydrogel delivery by injection in vivo. Their mechanical properties were tested to be ≤6.7kPa for compressive strength at break and about 8.4kPa/mm for elastic modulus. SEM analysis of the CaPAlg hydrogels showed highly porous morphology with interconnected pores of width in the range of 100-800μm. Cell culture results showed that the injectable hydrogels exhibited comparable properties to the pure alginate hydrogel in terms of cytotoxicity and 3D encapsulation of cells for a short time period. The developed injectable hydrogels showed suitable physicochemical and mechanical properties for injection in vivo, and could therefore be beneficial for the field of soft tissue engineering.

  10. Stabilization of caffeic acid derivatives in Echinacea purpurea L. glycerin extract.

    PubMed

    Bergeron, Chantal; Gafner, Stefan; Batcha, Laura L; Angerhofer, Cindy K

    2002-07-03

    Recent work has shown that enzymatic degradation and oxidation of cichoric acid and other caffeic derivatives occurs in Echinacea preparations. However, very little is known as to the means of stabilizing these phytopreparations. To stabilize the glycerin extract of Echinacea purpurea, we have evaluated the effects of 3 natural antioxidants (citric acid, malic acid, and hibiscus extract) on the stability of the major caffeic acid derivatives (caftaric acid, caffeic acid, cichoric acid, and 2-O-feruloyl-tartaric acid). Chlorogenic acid, which normally occurs in an ethanol extract of E. purpurea, was not present in the glycerin extract. The caffeic acid derivatives, with the exception of 2-O-feruloyl-tartaric acid, were subject to degradation in the control sample. 2-O-Feruloyl-tartaric acid was stable during the whole testing period. All antioxidant treatments greatly improved the stability of caffeic acid derivatives. Stability was dependent upon the concentration of antioxidant added.

  11. Discovery and Synthesis of Amino Acids Modified Deoxycholic Acid Derivatives and in Vitro Antiproliferative Evaluation.

    PubMed

    Zhao, Chunhui; Zhao, Peizhe; Feng, Bin; Hou, Xiyan; Zhao, Longxuan

    2017-03-01

    A series of deoxycholic acid (DCA) derivatives bearing amino acid moiety has been synthesized and investigated for their potential antiproliferative activities. DCA derivative compounds were synthesized by a two or three step synthetic approach. Their bioactivities were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method and Western blotting analysis on three tumor cell lines A549 (human lung cancer cell line), MCF-7 (human breast cancer cell line) and HeLa (human cervical carcinoma cell). The novel derivatives DCA3d, DCA5a, DCA5b, DCA5c, and DCA5d were found to be promising antiproliferative agents. Furthermore, DCA5b showed the greatest cytotoxic activity by induction of apoptosis. These compounds show potentiality for further optimization as antitumor drugs.

  12. 40 CFR 721.6110 - Alkyldi(alkyloxyhydroxypropyl) derivative, phosphoric acid esters, potassium salts.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...) derivative, phosphoric acid esters, potassium salts. 721.6110 Section 721.6110 Protection of Environment...) derivative, phosphoric acid esters, potassium salts. (a) Chemical substance and significant new uses subject...) derivative, phosphoric acid esters, potassium salts (PMN P-91-818) is subject to reporting under this section...

  13. 40 CFR 721.6110 - Alkyldi(alkyloxyhydroxypropyl) derivative, phosphoric acid esters, potassium salts.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...) derivative, phosphoric acid esters, potassium salts. 721.6110 Section 721.6110 Protection of Environment...) derivative, phosphoric acid esters, potassium salts. (a) Chemical substance and significant new uses subject...) derivative, phosphoric acid esters, potassium salts (PMN P-91-818) is subject to reporting under this section...

  14. 40 CFR 721.6110 - Alkyldi(alkyloxyhydroxypropyl) derivative, phosphoric acid esters, potassium salts.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...) derivative, phosphoric acid esters, potassium salts. 721.6110 Section 721.6110 Protection of Environment...) derivative, phosphoric acid esters, potassium salts. (a) Chemical substance and significant new uses subject...) derivative, phosphoric acid esters, potassium salts (PMN P-91-818) is subject to reporting under this section...

  15. 40 CFR 721.6110 - Alkyldi(alkyloxyhydroxypropyl) derivative, phosphoric acid esters, potassium salts.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...) derivative, phosphoric acid esters, potassium salts. 721.6110 Section 721.6110 Protection of Environment...) derivative, phosphoric acid esters, potassium salts. (a) Chemical substance and significant new uses subject...) derivative, phosphoric acid esters, potassium salts (PMN P-91-818) is subject to reporting under this section...

  16. 40 CFR 721.6110 - Alkyldi(alkyloxyhydroxypropyl) derivative, phosphoric acid esters, potassium salts.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...) derivative, phosphoric acid esters, potassium salts. 721.6110 Section 721.6110 Protection of Environment...) derivative, phosphoric acid esters, potassium salts. (a) Chemical substance and significant new uses subject...) derivative, phosphoric acid esters, potassium salts (PMN P-91-818) is subject to reporting under this section...

  17. Derivatives of xanthic acid are novel antioxidants: application to synaptosomes.

    PubMed

    Lauderback, Christopher M; Drake, Jennifer; Zhou, Daohong; Hackett, Janna M; Castegna, Alessandra; Kanski, Jaroslaw; Tsoras, Maria; Varadarajan, Sridhar; Butterfield, D Allan

    2003-04-01

    Xanthic acids have long been known to act as reducing agents. Recently, D609, a tricyclodecanol derivative of xanthic acid, has been reported to have anti-apoptotic and anti-inflammatory properties that are attributed to specific inhibition of phosphatidyl choline phospholipase C (PC-PLC). However, because oxidative stress is involved in both of these cellular responses, the possibility that xanthates may act as antioxidants was investigated in the current study. Finding that xanthates efficiently scavenge hydroxyl radicals, the mechanism by which D609 and other xanthate derivatives may protect against oxidative damage was further examined. The xanthates studied, especially D609, mimic glutathione (GSH). Xanthates scavenge hydroxyl radicals and hydrogen peroxide, form disulfide bonds (dixanthogens), and react with electrophilic products of lipid oxidation (acrolein) in a manner similar to GSH. Further, upon disulfide formation, dixanthogens are reduced by glutathione reductase to a redox active xanthate. Supporting its role as an antioxidant, D609 significantly (p < 0.01) reduces free radical-induced changes in synaptosomal lipid peroxidation (TBARs), protein oxidation (protein carbonyls), and protein conformation. Thus, in addition to inhibitory effects on PC-PLC, D609 may prevent cellular apoptotic and inflammatory cascades by acting as antioxidants and novel GSH mimics. These results are discussed with reference to potential therapeutic application of D609 in oxidative stress conditions.

  18. Activity of dehydroabietic acid derivatives against wood contaminant fungi.

    PubMed

    Savluchinske-Feio, Sonia; Nunes, Lina; Pereira, Pablo Tavares; Silva, Ana M; Roseiro, José C; Gigante, Bárbara; Marcelo Curto, Maria João

    2007-09-01

    The antifungal activity of 10 dehydroabietic acid derivatives with different configuration in A and B rings (cis/trans A/B junction) and different substituents and/or functionalities was evaluated in bioassays in vitro and in situ (pine wood blocks). The test compounds dissolved in acetone were assayed at several concentrations w/w (test compound/culture medium) against the fungi. The Relative Inhibition (RI) was determined by measuring the radial growth of colonies of the fungi treated with the test compounds by comparison with those of control cultures; the results are expressed as EC(50). The results of bioassays in vitro have shown that hydroxyl and aldehyde functions are required for antifungal activity in this group of compounds and deisopropylation can increase the activity. Our assay of antifungal activity in situ (in pine wood blocks) provides a means to investigate the preservative activities of these antifungal compounds under actual conditions of use. The dehydroabietic acid derivative cis-deisopropyldehydroabietanol (10) inhibited the growth of several of the fungi tested, in vitro and in situ. The results obtained in situ with the test compound (10) at 6% and 8% were not significantly different from the reference products and a good level of protection of the wood against the organisms tested was achieved. The results in wood bioassays present new possibilities in the search for natural new compounds in the wood protection, as an alternative to conventional fungicides.

  19. Synthesis and anticancer activity of novel fluorinated asiatic acid derivatives.

    PubMed

    Gonçalves, Bruno M F; Salvador, Jorge A R; Marín, Silvia; Cascante, Marta

    2016-05-23

    A series of novel fluorinated Asiatic Acid (AA) derivatives were successfully synthesized, tested for their antiproliferative activity against HeLa and HT-29 cell lines, and their structure activity relationships were evaluated. The great majority of fluorinated derivatives showed stronger antiproliferative activity than AA in a concentration dependent manner. The most active compounds have a pentameric A-ring containing an α,β-unsaturated carbonyl group. The compounds with better cytotoxic activity were then evaluated against MCF-7, Jurkat, PC-3, A375, MIA PaCa-2 and BJ cell lines. Derivative 14 proved to be the most active compound among all tested derivatives and its mechanism of action was further investigated in HeLa cell line. The results showed that compound 14 induced cell cycle arrest in G0/G1 stage as a consequence of up-regulation of p21(cip1/waf1) and p27(kip1) and down-regulation of cyclin D3 and Cyclin E. Furthermore, compound 14 was found to induce caspase driven-apoptosis with activation of caspases-8 and caspase-3 and the cleavage of PARP. The cleavage of Bid into t-Bid, the up-regulation of Bax and the down-regulation of Bcl-2 were also observed after treatment of HeLa cells with compound 14. Taken together, these mechanistic studies revealed the involvement of extrinsic and intrinsic pathways in the apoptotic process induced by compound 14. Importantly, the antiproliferative activity of this compound on the non-tumor BJ human fibroblast cell line is weaker than in the tested cancer cell lines. The enhanced potency (between 45 and 90-fold more active than AA in a panel of cancer cell lines) and selectivity of this new AA derivative warrant further preclinical evaluation.

  20. Synthesis and antimicrobial activities of new higher amino acid Schiff base derivatives of 6-aminopenicillanic acid and 7-aminocephalosporanic acid

    NASA Astrophysics Data System (ADS)

    Özdemir (nee Güngör), Özlem; Gürkan, Perihan; Özçelik, Berrin; Oyardı, Özlem

    2016-02-01

    Novel β-lactam derivatives (1c-3c) (1d-3d) were produced by using 6-aminopenicillanic acid (6-APA), 7-aminocephalosporanic acid (7-ACA) and the higher amino acid Schiff bases. The synthesized compounds were characterized by elemental analysis, IR, 1H/13C NMR and UV-vis spectra. Antibacterial activities of all the higher amino acid Schiff bases (1a-3a) (1b-3b) and β-lactam derivatives were screened against three gram negative bacteria (Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Acinetobacter baumannii RSKK 02026), three gram positive bacteria (Staphylococcus aureus ATCC 25923, Enterococcus faecalis ATCC 07005, Bacillus subtilis ATCC 6633) and their drug-resistant isolates by using broth microdilution method. Two fungi (Candida albicans and Candida krusei) were used for antifungal activity.

  1. Infrared spectra of hydrogen-bonded salicylic acid and its derivatives : Salicylic acid and acetylsalicylic acid

    NASA Astrophysics Data System (ADS)

    Wójcik, Marek J.

    1981-11-01

    Infrared spectra of hydrogen-bonded salicylic acid, O-deutero-salicylic acid and acetylsalicylic acid crystals have been studied experimentally and theoretically. Interpretation of these spectra was based on the Witkowski-Maréchal model. Semi-quantitative agreement between experimental and theoretical spectra can be achieved with the simplest form of this model, with values of interaction parameters transferable for equivalent intermolecular hydrogen bonds.

  2. Synthesis and cholinesterase inhibition of cativic acid derivatives.

    PubMed

    Alza, Natalia P; Richmond, Victoria; Baier, Carlos J; Freire, Eleonora; Baggio, Ricardo; Murray, Ana Paula

    2014-08-01

    Alzheimer's disease (AD) is a neurodegenerative disorder associated with memory impairment and cognitive deficit. Most of the drugs currently available for the treatment of AD are acetylcholinesterase (AChE) inhibitors. In a preliminary study, significant AChE inhibition was observed for the ethanolic extract of Grindelia ventanensis (IC₅₀=0.79 mg/mL). This result prompted us to isolate the active constituent, a normal labdane diterpenoid identified as 17-hydroxycativic acid (1), through a bioassay guided fractionation. Taking into account that 1 showed moderate inhibition of AChE (IC₅₀=21.1 μM), selectivity over butyrylcholinesterase (BChE) (IC₅₀=171.1 μM) and that it was easily obtained from the plant extract in a very good yield (0.15% w/w), we decided to prepare semisynthetic derivatives of this natural diterpenoid through simple structural modifications. A set of twenty new cativic acid derivatives (3-6) was prepared from 1 through transformations on the carboxylic group at C-15, introducing a C2-C6 linker and a tertiary amine group. They were tested for their inhibitory activity against AChE and BChE and some structure-activity relationships were outlined. The most active derivative was compound 3c, with an IC₅₀ value of 3.2 μM for AChE. Enzyme kinetic studies and docking modeling revealed that this inhibitor targeted both the catalytic active site and the peripheral anionic site of this enzyme. Furthermore, 3c showed significant inhibition of AChE activity in SH-SY5Y human neuroblastoma cells, and was non-cytotoxic.

  3. Stereoselective synthesis of uridine-derived nucleosyl amino acids.

    PubMed

    Spork, Anatol P; Wiegmann, Daniel; Granitzka, Markus; Stalke, Dietmar; Ducho, Christian

    2011-12-16

    Novel hybrid structures of 5'-deoxyuridine and glycine were conceived and synthesized. Such nucleosyl amino acids (NAAs) represent simplified analogues of the core structure of muraymycin nucleoside antibiotics, making them useful synthetic building blocks for structure-activity relationship (SAR) studies. The key step of the developed synthetic route was the efficient and highly diastereoselective asymmetric hydrogenation of didehydro amino acid precursors toward protected NAAs. It was anticipated that the synthesis of unprotected muraymycin derivatives via this route would require a suitable intermediate protecting group at the N-3 of the uracil base. After initial attempts using PMB- and BOM-N-3 protection, both of which resulted in problematic deprotection steps, an N-3 protecting group-free route was envisaged. In spite of the pronounced acidity of the uracil-3-NH, this route worked equally efficient and with identical stereoselectivities as the initial strategies involving N-3 protection. The obtained NAA building blocks were employed for the synthesis of truncated 5'-deoxymuraymycin analogues.

  4. Solubility of sparingly soluble drug derivatives of anthranilic acid.

    PubMed

    Domańska, Urszula; Pobudkowska, Aneta; Pelczarska, Aleksandra

    2011-03-24

    This work is a continuation of our systematic study of the solubility of pharmaceuticals (Pharms). All substances here are derivatives of anthranilic acid, and have an anti-inflammatory direction of action (niflumic acid, flufenamic acid, and diclofenac sodium). The basic thermal properties of pure Pharms, i.e., melting and glass-transition temperatures as well as the enthalpy of melting, have been measured with the differential scanning microcalorimetry technique (DSC). Molar volumes have been calculated with the Barton group contribution method. The equilibrium mole fraction solubilities of three pharmaceuticals were measured in a range of temperatures from 285 to 355 K in three important solvents for Pharm investigations: water, ethanol, and 1-octanol using a dynamic method and spectroscopic UV-vis method. The experimental solubility data have been correlated by means of the commonly known G(E) equation: the NRTL, with the assumption that the systems studied here have revealed simple eutectic mixtures. pK(a) precise measurement values have been investigated with the Bates-Schwarzenbach spectrophotometric method.

  5. Brevianamides and Mycophenolic Acid Derivatives from the Deep-Sea-Derived Fungus Penicillium brevicompactum DFFSCS025.

    PubMed

    Xu, Xinya; Zhang, Xiaoyong; Nong, Xuhua; Wang, Jie; Qi, Shuhua

    2017-02-17

    Four new compounds (1-4), including two brevianamides and two mycochromenic acid derivatives along with six known compounds were isolated from the deep-sea-derived fungus Penicillium brevicompactum DFFSCS025. Their structures were elucidated by spectroscopic analysis. Moreover, the absolute configurations of 1 and 2 were determined by quantum chemical calculations of the electronic circular dichroism (ECD) spectra. Compound 9 showed moderate cytotoxicity against human colon cancer HCT116 cell line with IC50 value of 15.6 μM. In addition, 3 and 5 had significant antifouling activity against Bugula neritina larval settlement with EC50 values of 13.7 and 22.6 μM, respectively. The NMR data of 6, 8, and 9 were assigned for the first time.

  6. Brevianamides and Mycophenolic Acid Derivatives from the Deep-Sea-Derived Fungus Penicillium brevicompactum DFFSCS025

    PubMed Central

    Xu, Xinya; Zhang, Xiaoyong; Nong, Xuhua; Wang, Jie; Qi, Shuhua

    2017-01-01

    Four new compounds (1–4), including two brevianamides and two mycochromenic acid derivatives along with six known compounds were isolated from the deep-sea-derived fungus Penicillium brevicompactum DFFSCS025. Their structures were elucidated by spectroscopic analysis. Moreover, the absolute configurations of 1 and 2 were determined by quantum chemical calculations of the electronic circular dichroism (ECD) spectra. Compound 9 showed moderate cytotoxicity against human colon cancer HCT116 cell line with IC50 value of 15.6 μM. In addition, 3 and 5 had significant antifouling activity against Bugula neritina larval settlement with EC50 values of 13.7 and 22.6 μM, respectively. The NMR data of 6, 8, and 9 were assigned for the first time. PMID:28218640

  7. Bioavailability of hop-derived iso-α-acids and reduced derivatives.

    PubMed

    Cattoor, Ko; Remon, Jean-Paul; Boussery, Koen; Van Bocxlaer, Jan; Bracke, Marc; De Keukeleire, Denis; Deforce, Dieter; Heyerick, Arne

    2011-07-01

    Iso-α-acids (IAA) and their reduced derivatives (dihydro-iso-α-acids (DHIAA) and tetrahydro-iso-α-acids (THIAA)) have been administered to Caco-2 cell monolayers (30, 60, and 120 μM) to investigate epithelial transport, in both absorptive and secretive directions. In addition, 25 mg kg(-1) IAA, DHIAA, and THIAA were applied to New Zealand white rabbits (±3-3.5 kg) in a single intravenous and oral dose. The most important pharmacokinetic parameters (C(max), t(max), half life, clearance, and AUC(0-∞)) and the absolute bioavailability were determined for each class of hop acid. The results from the in vitro Caco-2 study of IAA, DHIAA, and THIAA, showed a higher membrane permeability for IAA and THIAA, both in absorptive (P(appAB) range 1.6-5.6 × 10(-6) cm s(-1)) and secretive directions (P(appBA) range 5.7-16.3 × 10(-6) cm s(-1)), when compared to DHIAA. Factors limiting transport of DHIAA could include phase II metabolism. After oral and i.v. dosing to New Zealand white rabbits, the absolute bioavailability for IAA was determined to be 13.0%. The reduced derivatives reached higher bioavailabilities with 28.0% for DHIAA and 23.0% for THIAA. The area under curve AUC(0-∞) upon oral gavage for DHIAA and THIAA was 70.7 ± 48.4 μg h ml(-1) and 57.4 ± 9.0 μg h ml(-1), respectively, while that for IAA was 10.6 ± 5.3 μg h ml(-1). Phase I metabolism was indicated as the main factor limiting the bioavailability of IAA. Bioavailability of DHIAA is mostly influenced by phase-II metabolism as shown by enzymatic hydrolysis of plasma samples upon administration of DHIAA.

  8. meso-Dihydroguaiaretic acid derivatives with antibacterial and antimycobacterial activity.

    PubMed

    Reyes-Melo, Karen; García, Abraham; Romo-Mancillas, Antonio; Garza-González, Elvira; Rivas-Galindo, Verónica M; Miranda, Luis D; Vargas-Villarreal, Javier; Favela-Hernández, Juan Manuel J; Camacho-Corona, María Del Rayo

    2017-10-15

    Thirty-three meso-dihydroguaiaretic acid (meso-DGA) derivatives bearing esters, ethers, and amino-ethers were synthesized. All derivatives were tested against twelve drug-resistant clinical isolates of Gram-positive and Gram-negative bacteria, including sensitive (H37Rv) and multidrug-resistant Mycobacterium tuberculosis strains. Among the tested compounds, four esters (7, 11, 13, and 17), one ether (23), and three amino-ethers (30, 31, and 33) exhibited moderate activity against methicillin-resistant Staphylococcus aureus, whereas 30 and 31 showed better results than levofloxacin against vancomycin-resistant Enterococcus faecium. Additionally, nineteen meso-DGA derivatives displayed moderate to potent activity against M. tuberculosis H37Rv with minimum inhibitory concentration (MIC) values ranging from 3.125 to 50µg/mL. Seven meso-DGA derivatives bearing amino-ethers (26-31 and 33) exhibited the lowest MICs against M. tuberculosis H37Rv and G122 strains, with 31 being as potent as ethambutol (MICs of 3.125 and 6.25µg/mL). The presence of positively charged group precursors possessing steric and hydrophobic features (e.g. N-ethylpiperidine moieties in meso-31) resulted essential to significantly increase the antimycobacterial properties of parent meso-DGA as supported by the R-group pharmacophoric and field-based QSAR analyses. To investigate the safety profile of the antimycobacterial compounds, cytotoxicity on Vero cells was determined. The amino-ether 31 exhibited a selectivity index value of 23, which indicate it was more toxic to M. tuberculosis than to mammalian cells. Therefore, 31 can be considered as a promising antitubercular agent for further studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Anti-Inflammatory Effects of Cajaninstilbene Acid and Its Derivatives.

    PubMed

    Huang, Mei-Yan; Lin, Jing; Lu, Kuo; Xu, Hong-Gui; Geng, Zhi-Zhong; Sun, Ping-Hua; Chen, Wei-Min

    2016-04-13

    Cajaninstilbene acid (CSA) is one of the active components isolated from pigeon pea leaves. In this study, anti-inflammatory effects of CSA and its synthesized derivatives were fully valued with regard to their activities on the production of nitric oxide (NO) and pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in vitro cell model, as well as their impacts on the migration of neutrophils and macrophages in fluorescent protein labeled zebrafish larvae model by live image analysis. Furthermore, the anti-inflammatory mechanism of this type of compounds was clarified by western-blot and reverse transcription-polymerase chain reaction (RT-PCR). The results showed that CSA, as well as its synthesized derivatives 5c, 5e and 5h, exhibited strong inhibition activity on the release of NO and inflammatory factor TNF-α and IL-6 in lipopolysaccharides (LPS)-stimulated murine macrophages. CSA and 5c greatly inhibited the migration of neutrophils and macrophages in injury zebrafish larvae. CSA and 5c treatment greatly inhibited the phosphorylation of proteins involved in nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. Moreover, we found that peroxisome proliferator-activated receptor gamma (PPARγ) inhibitor GW9662 could reverse partly the roles of CSA and 5c, and CSA and 5c treatment greatly resist the decrease of PPARγ mRNA and protein induced by LPS stimulation. Our results identified the promising anti-inflammatory effects of CSA and its derivatives, which may serve as valuable anti-inflammatory lead compound. Additionally, the mechanism studies demonstrated that the anti-inflammatory activity of CSA and its derivative is associated with the inhibition of NF-κB and MAPK pathways, relying partly on resisting the LPS-induced decrease of PPARγ through improving its expression.

  10. Docosahexaenoic Acid-Derived Fatty Acid Esters of Hydroxy Fatty Acids (FAHFAs) With Anti-inflammatory Properties.

    PubMed

    Kuda, Ondrej; Brezinova, Marie; Rombaldova, Martina; Slavikova, Barbora; Posta, Martin; Beier, Petr; Janovska, Petra; Veleba, Jiri; Kopecky, Jan; Kudova, Eva; Pelikanova, Terezie; Kopecky, Jan

    2016-09-01

    White adipose tissue (WAT) is a complex organ with both metabolic and endocrine functions. Dysregulation of all of these functions of WAT, together with low-grade inflammation of the tissue in obese individuals, contributes to the development of insulin resistance and type 2 diabetes. n-3 polyunsaturated fatty acids (PUFAs) of marine origin play an important role in the resolution of inflammation and exert beneficial metabolic effects. Using experiments in mice and overweight/obese patients with type 2 diabetes, we elucidated the structures of novel members of fatty acid esters of hydroxy fatty acids-lipokines derived from docosahexaenoic acid (DHA) and linoleic acid, which were present in serum and WAT after n-3 PUFA supplementation. These compounds contained DHA esterified to 9- and 13-hydroxyoctadecadienoic acid (HLA) or 14-hydroxydocosahexaenoic acid (HDHA), termed 9-DHAHLA, 13-DHAHLA, and 14-DHAHDHA, and were synthesized by adipocytes at concentrations comparable to those of protectins and resolvins derived from DHA in WAT. 13-DHAHLA exerted anti-inflammatory and proresolving properties while reducing macrophage activation by lipopolysaccharides and enhancing the phagocytosis of zymosan particles. Our results document the existence of novel lipid mediators, which are involved in the beneficial anti-inflammatory effects attributed to n-3 PUFAs, in both mice and humans. © 2016 by the American Diabetes Association.

  11. A potential plant-derived antifungal acetylenic acid mediates its activity by interfering with fatty acid homeostasis

    USDA-ARS?s Scientific Manuscript database

    6-Nonadecynoic acid (6-NDA), a plant-derived acetylenic acid, exhibits strong inhibitory activity against the human fungal pathogens Candida albicans, Aspergillus fumigatus, and Trichophyton mentagrophytes. In the present study, transcriptional profiling coupled with mutant and biochemical analyses...

  12. Anti-inflammatory effects of hydroxycinnamic acid derivatives

    SciTech Connect

    Nagasaka, Reiko; Chotimarkorn, Chatchawan; Shafiqul, Islam Md.; Hori, Masatoshi; Ozaki, Hiroshi; Ushio, Hideki . E-mail: hushio@kaiyodai.ac.jp

    2007-06-29

    NF-{kappa}B family of transcription factors are involved in numerous cellular processes, including differentiation, proliferation, and inflammation. It was reported that hydroxycinnamic acid derivatives (HADs) are inhibitors of NF-{kappa}B activation. Rice bran oil contains a lot of phytosteryl ferulates, one of HADs. We have investigated effects of phytosteryl ferulates on NF-{kappa}B activation in macrophage. Cycloartenyl ferulate (CAF), one of phytosteryl ferulates, significantly reduced lipopolysaccharide (LPS)-induced NO production and mRNA expression of inducible NO synthase and cyclooxygenese-2 but upregulated SOD activity. Electrophoresis mobility shift assay revealed that CAF inhibited DNA-binding of NF-{kappa}B. CAF and phytosteryl ferulates probably have potentially anti-inflammatory properties.

  13. [Acute kidney failure during psoriasis therapy with fumaric acid derivatives].

    PubMed

    Dalhoff, K; Faerber, P; Arnholdt, H; Sack, K; Strubelt, O

    1990-06-29

    24 days after starting treatment of psoriasis with fumaric acid derivatives (0.8-1.0 g orally, plus unknown quantities locally) a 21-year-old woman developed acute oliguric renal failure with a rise of serum creatinine levels to 1094 mumol/l (12.4 mg/dl). Deterioration of renal function had been preceded by severe abdominal symptoms with nausea, vomiting and colicky pain. On admission to hospital she was dehydrated with hyponatraemia and hypokalaemia. There was glomerular microhaematuria, increased excretion of renal epithelia, and tubular proteinuria. Renal biopsy demonstrated acute tubular damage with vacuolization of proximal epithelia, dilated tubules and scattered necroses. After intermittent haemodialysis (13 courses over two weeks) renal function gradually recovered, as demonstrated at a follow-up examination four months after discharge.

  14. Frustrated smectic liquid crystalline phases in lactic acid derivatives

    NASA Astrophysics Data System (ADS)

    Glogarová, M.; Novotná, V.

    2016-08-01

    We have prepared and studied a series of compounds with different types of molecular core and lactate unit in the chiral terminal chain. We draw a survey and comparison of their mesomorphic properties with respect to the occurrence of twist grain boundary (TGB) phases. The materials exhibit extremely wide TGBA phase more than 60K broad, unique TGBA-TGBC-SmC*-SmCA* phase sequence and unique re-entrant TGBA phase below the SmA phase. TGB phases have been induced in binary mixtures of molecules with different molecular shape and chirality (chiral lactic acid derivative and non-chiral hockey-stick mesogen). Unique effect is observed for compounds with TGBA phase, where the applied electric field transforms the planar texture into the homeotropic one, homogeneously dark in crossed polarizers. The process is analogy of the Frederiks transition so far known only for nematics. This effect, changing the bright state to the dark one, is promising for applications.

  15. Ethylenation of aldehydes to 3-propanal, propanol and propanoic acid derivatives.

    PubMed

    Payne, Daniel T; Zhao, Yiming; Fossey, John S

    2017-05-11

    Methodology has been developed for the synthesis of 3-propanaldehydes through a five-step process in 11-67% yield from aldehydes. Aldehydes were reacted with Meldrum's acid through a Knoevenagel condensation to give materials that upon reduction with sodium borohydride and subsequent hydrolysis decarboxylation generated the corresponding 3-propanoic acid derivatives. The -propanoic acid derivatives were reduced to give 3-propanol derivatives, which were readily oxidised to target 3-propanal derivatives.

  16. Synthesis and characterization of bis-thiourea having amino acid derivatives

    NASA Astrophysics Data System (ADS)

    Fakhar, Imran; Yamin, Bohari M.; Hasbullah, Siti Aishah

    2016-11-01

    In this article four new symmetric bis-thiourea derivatives having amino acid linkers were reported with good yield. Isophthaloyl dichloride was used as spacer and L-alanine, L-aspartic acid, L-phenylalanine and L-glutamic acid were used as linkers. Bis-thiourea derivatives were prepared from relatively stable isophthaloyl isothiocyanate intermediate. Newly synthesized bis-thiourea derivatives were characterized by FTIR, H-NMR, 13C-NMR and CHNS-O elemental analysis techniques. Characterization data was in good agreement with the expected derivatives, hence confirmed the synthesis of four new derivatives of bis-thiourea having amino acids.

  17. 40 CFR 721.430 - Oxo-substituted amino-al-kanoic acid derivative.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Oxo-substituted amino-al-kanoic acid... Specific Chemical Substances § 721.430 Oxo-substituted amino-al-kanoic acid derivative. (a) Chemical... as oxo-substituted amino al-kan-oic acid derivative (PMN No. P-92-692) is subject to reporting under...

  18. 40 CFR 721.430 - Oxo-substituted amino-al-kanoic acid derivative.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Oxo-substituted amino-al-kanoic acid... Specific Chemical Substances § 721.430 Oxo-substituted amino-al-kanoic acid derivative. (a) Chemical... as oxo-substituted amino al-kan-oic acid derivative (PMN No. P-92-692) is subject to reporting under...

  19. 40 CFR 721.430 - Oxo-substituted amino-al-kanoic acid derivative.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Oxo-substituted amino-al-kanoic acid... Specific Chemical Substances § 721.430 Oxo-substituted amino-al-kanoic acid derivative. (a) Chemical... as oxo-substituted amino al-kan-oic acid derivative (PMN No. P-92-692) is subject to reporting under...

  20. 40 CFR 721.430 - Oxo-substituted amino-al-kanoic acid derivative.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Oxo-substituted amino-al-kanoic acid... Specific Chemical Substances § 721.430 Oxo-substituted amino-al-kanoic acid derivative. (a) Chemical... as oxo-substituted amino al-kan-oic acid derivative (PMN No. P-92-692) is subject to reporting under...

  1. 40 CFR 721.430 - Oxo-substituted amino-al-kanoic acid derivative.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Oxo-substituted amino-al-kanoic acid... Specific Chemical Substances § 721.430 Oxo-substituted amino-al-kanoic acid derivative. (a) Chemical... as oxo-substituted amino al-kan-oic acid derivative (PMN No. P-92-692) is subject to reporting under...

  2. Gallic acid and gallic acid derivatives: effects on drug metabolizing enzymes.

    PubMed

    Ow, Yin-Yin; Stupans, Ieva

    2003-06-01

    Gallic acid and its structurally related compounds are found widely distributed in fruits and plants. Gallic acid, and its catechin derivatives are also present as one of the main phenolic components of both black and green tea. Esters of gallic acid have a diverse range of industrial uses, as antioxidants in food, in cosmetics and in the pharmaceutical industry. In addition, gallic acid is employed as a source material for inks, paints and colour developers. Studies utilising these compounds have found them to possess many potential therapeutic properties including anti-cancer and antimicrobial properties. In this review, studies of the effects of gallic acid, its esters, and gallic acid catechin derivatives on Phase I and Phase II enzymes are examined. Many published reports of the effects of the in vitro effects of gallic acid and its derivatives on drug metabolising enzymes concern effects directly on substrate (generally drug or mutagen) metabolism or indirectly through observed effects in Ames tests. In the case of the Ames test an antimutagenic effect may be observed through inhibition of CYP activation of indirectly acting mutagens and/or by scavenging of metabolically generated mutagenic electrophiles. There has been considerable interest in the in vivo effects of the gallate esters because of their incorporation into foodstuffs as antioxidants and in the catechin gallates with their potential role as chemoprotective agents. Principally an induction of Phase II enzymes has been observed however more recent studies using HepG2 cells and primary cultures of human hepatocytes provide evidence for the overall complexity of actions of individual components versus complex mixtures, such as those in food. Further systematic studies of mechanisms of induction and inhibition of drug metabolising enzymes by this group of compounds are warranted in the light of their distribution and consequent ingestion, current uses and suggested therapeutic potential. However, it

  3. 40 CFR 721.10045 - Diazotized substituted heteromonocycle coupled with naphthalene sulfonic acid derivative, nickel...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... coupled with naphthalene sulfonic acid derivative, nickel complex, alkaline salt (generic). 721.10045... derivative, nickel complex, alkaline salt (generic). (a) Chemical substance and significant new uses subject... heteromonocycle coupled with naphthalene sulfonic acid derivative, nickel complex, alkaline salt (PMN P-02-737)...

  4. 40 CFR 721.10045 - Diazotized substituted heteromonocycle coupled with naphthalene sulfonic acid derivative, nickel...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... coupled with naphthalene sulfonic acid derivative, nickel complex, alkaline salt (generic). 721.10045... derivative, nickel complex, alkaline salt (generic). (a) Chemical substance and significant new uses subject... heteromonocycle coupled with naphthalene sulfonic acid derivative, nickel complex, alkaline salt (PMN P-02-737)...

  5. 40 CFR 721.10045 - Diazotized substituted heteromonocycle coupled with naphthalene sulfonic acid derivative, nickel...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... coupled with naphthalene sulfonic acid derivative, nickel complex, alkaline salt (generic). 721.10045... derivative, nickel complex, alkaline salt (generic). (a) Chemical substance and significant new uses subject... heteromonocycle coupled with naphthalene sulfonic acid derivative, nickel complex, alkaline salt (PMN P-02-737)...

  6. 40 CFR 721.10045 - Diazotized substituted heteromonocycle coupled with naphthalene sulfonic acid derivative, nickel...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... coupled with naphthalene sulfonic acid derivative, nickel complex, alkaline salt (generic). 721.10045... derivative, nickel complex, alkaline salt (generic). (a) Chemical substance and significant new uses subject... heteromonocycle coupled with naphthalene sulfonic acid derivative, nickel complex, alkaline salt (PMN P-02-737)...

  7. 40 CFR 721.10045 - Diazotized substituted heteromonocycle coupled with naphthalene sulfonic acid derivative, nickel...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... coupled with naphthalene sulfonic acid derivative, nickel complex, alkaline salt (generic). 721.10045... derivative, nickel complex, alkaline salt (generic). (a) Chemical substance and significant new uses subject... heteromonocycle coupled with naphthalene sulfonic acid derivative, nickel complex, alkaline salt (PMN P-02-737)...

  8. Ascorbic acid derivatives as a new class of antiproliferative molecules.

    PubMed

    Bordignon, Benoit; Chiron, Julien; Fontés, Michel

    2013-09-28

    Ascorbic acid (AA) has long been described as an antiproliferative agent. However, the molecule has to be used at a very high concentrations, which necessitates i.v. injection, and the tight regulation of in-blood and in-cell AA concentrations making it impossible to hold very high concentrations for any substantial length of time. Here we report evidence that AA derivates are antiproliferative and cytotoxic molecules at an IC50 lower than AA itself. Among these new molecules, we selected K873 that has cytotoxic and antiproliferative effects on different human tumor cells at tenth micromolar concentration. In a further step, we demonstrated that K873 selectively to kills only cancer cells without being toxic for normal non-dividing (or poorly dividing) cells. Finally, we tested the effect of treatment with K873 (5-10 mg/kg/d by i.p. route) on tumor progression in xenografted immunodeficient mice (BALB/c Nude). Our data suggest that K873 administration strongly inhibits tumor progression. In a previous study using microarrays, we demonstrated that AA decreases the expression of two genes families involved in cell cycle progression, i.e. initiation factor of translation and tRNA synthetases. Here we show that K873 treatment also decreases the expression of four of these genes in xenografted tumors, in proportions similar to that previously observed with AA. Taken together, our data suggest that AA and K873 share similar action. Our findings suggest that AA derivatives could be a promising new class of anti-cancer drugs, either alone or in combination with other molecules. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  9. Farnesylthiosalicylic acid sensitizes hepatocarcinoma cells to artemisinin derivatives

    PubMed Central

    Wu, Liping; Pang, Yilin; Qin, Guiqi; Xi, Gaina; Wu, Shengnan; Wang, Xiaoping; Chen, Tongsheng

    2017-01-01

    Dihydroartemisinin (DHA) and artesunate (ARS), two artemisinin derivatives, have efficacious anticancer activities against human hepatocarcinoma (HCC) cells. This study aims to study the anticancer action of the combination treatment of DHA/ARS and farnesylthiosalicylic acid (FTS), a Ras inhibitor, in HCC cells (Huh-7 and HepG2 cell lines). FTS pretreatment significantly enhanced DHA/ARS-induced phosphatidylserine (PS) externalization, Bak/Bax activation, mitochondrial membrane depolarization, cytochrome c release, and caspase-8 and -9 activations, characteristics of the extrinsic and intrinsic apoptosis. Pretreatment with Z-IETD-FMK (caspase-8 inhibitor) potently prevented the cytotoxicity of the combination treatment of DHA/ARS and FTS, and pretreatment with Z-VAD-FMK (pan-caspase inhibitor) significantly inhibited the loss of ΔΨm induced by DHA/ARS treatment or the combination treatment of DHA/ARS and FTS in HCC cells. Furthermore, silencing Bak/Bax modestly but significantly inhibited the cytotoxicity of the combination treatment of DHA/ARS and FTS. Interestingly, pretreatment with an antioxidant N-Acetyle-Cysteine (NAC) significantly prevented the cytotoxicity of the combination treatment of DHA and FTS instead of the combination treatment of ARS and FTS, suggesting that reactive oxygen species (ROS) played a key role in the anticancer action of the combination treatment of DHA and FTS. Similar to FTS, DHA/ARS also significantly prevented Ras activation. Collectively, our data demonstrate that FTS potently sensitizes Huh-7 and HepG2 cells to artemisinin derivatives via accelerating the extrinsic and intrinsic apoptotic pathways. PMID:28182780

  10. Amino acid derivatives of ligustrazine-oleanolic acid as new cytotoxic agents.

    PubMed

    Chu, Fuhao; Xu, Xin; Li, Guoliang; Gu, Shun; Xu, Kuo; Gong, Yan; Xu, Bing; Wang, Mina; Zhang, Huazheng; Zhang, Yuzhong; Wang, Penglong; Lei, Haimin

    2014-11-07

    A series of novel ligustrazine-oleanolic acid (TOA) derivatives were designed, and synthesized by conjugating amino acids to the 3-hydroxy group of TOA by ester bonds. Their cytotoxicity was evaluated on four cancer cell lines (HepG2, HT-29, Hela and BGC-823) by standard MTT assays. The ClogP values were calculated by means of computer simulation, and logP values of both 3β-glycine ester olean-12-en-28-oic acid-3,5,6-trimethylpyrazin-2-methyl ester (6a) and TOA were determined using a shake flask-ultraviolet spectrophotometry method. It was found that 6a and the 3β-L-lysine ester-6g not only displayed good cytotoxicity (IC50<3.5 μM) but also possessed better hydrophilicity than TOA. Moreover, 6a (IC50=4.884 μM) had lower nephrotoxicity than both 6g (IC50=2.310 μM) and cisplatin (CDDP, IC50=3.691 μM) on MDCK cells. Combining Giemsa and DAPI staining, it was further verified that 6a could induce HepG2 apoptosis via nuclei fragmentation and had lower nephrotoxicity. In addition, the structure-activity relationships of these derivatives are briefly discussed.

  11. Glutamic acid and its derivatives: candidates for rational design of anticancer drugs.

    PubMed

    Ali, Imran; Wani, Waseem A; Haque, Ashanul; Saleem, Kishwar

    2013-05-01

    Throughout the history of human civilizations, cancer has been a major health problem. Its treatment has been interesting but challenging to scientists. Glutamic acid and its derivative glutamine are known to play interesting roles in cancer genesis, hence, it was realized that structurally variant glutamic acid derivatives may be designed and developed and, might be having antagonistic effects on cancer. The present article describes the state-of-art of glutamic acid and its derivatives as anticancer agents. Attempts have been made to explore the effectivity of drug-delivery systems based on glutamic acid for the delivery of anticancer drugs. Moreover, efforts have also been made to discuss the mechanism of action of glutamic acid derivatives as anticancer agents, clinical applications of glutamic acid derivatives, as well as recent developments and future perspectives of glutamic acid drug development have also been discussed.

  12. Energy densification of biomass-derived organic acids

    DOEpatents

    Wheeler, M. Clayton; van Walsum, G. Peter; Schwartz, Thomas J.; van Heiningen, Adriaan

    2013-01-29

    A process for upgrading an organic acid includes neutralizing the organic acid to form a salt and thermally decomposing the resulting salt to form an energy densified product. In certain embodiments, the organic acid is levulinic acid. The process may further include upgrading the energy densified product by conversion to alcohol and subsequent dehydration.

  13. Synthesis of amino Derivatives of Dithio Acids as Potential Radiation Protective Agents

    DTIC Science & Technology

    1984-08-01

    ation Management S SI ____ K> AD Synthesis of Amino Derivatives of Dithio Acids as Potential Radiation Protective Agents * 0 Annual Report "TIi: o DTIC...Sftcuntiy Clatuftcatio") Synthesis of Amino Derivatives of Dithio Acids as PotentitI- Radiation Protective Agents 12l PERISONAL. Ak.TI4OR(S) * William...methyl- picoline derivatives was accomplished. Use of N-mthyl-2,6-dimethylpyridine also allowed the synthesis of a bis(dithioacetic acid) function not

  14. Radioimmunoassay of 5-hydroxyindole acetic acid using an iodinated derivative

    SciTech Connect

    Puizillout, J.J.; Delaage, M.A.

    1981-06-01

    A radioimmunoassay for the main catabolite of serotonin, 5-hydroxyindole acetic acid (5-HIAA), was developed by using specific antibodies and iodinated derivative. The synthesis of a /sup 125/I-iodinated analog was performed by coupling 5-HIAA to (125I-)glycyl-tyrosine without any contact between 5-HIAA and iodine or chloramine T. It was purified on a G25 Sephadex column and diluted in citrate buffer up to 2.5 X 10(5) cpm/ml. Antibodies were obtained by coupling 5-HIAA to human serum albumin with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and tested by equilibrium dialysis. After the third immunogen injection, the four rabbits gave antisera capable of binding 50% of iodinated 5-HIIA-glycyl-tyrosine at 1/2000 final dilution. A chemical conversion of the biological samples gives to the antigen molecules a better resemblance to the immunogen, thus conferring a 100-fold gain in specificity and sensitivity. This assay allows 5-HIAA to be determined in small amounts of tissue, blood, cerebrospinal fluid or perfusate without purification with a sensitivity threshold below 0.1 ng. Some applications in cat and rat are presented.

  15. Discotic liquid crystal derived from zinc tetraaminophthalocyanine and perfluorooctanoic acid

    NASA Astrophysics Data System (ADS)

    Meng, Fanbao; Zhou, Naiyu; Diao, Na; Du, Chang

    2013-12-01

    A novel kind of metallo-phthalocyanine derivative, zinc 2,9,16,23-tetraaminophthalocyanine perfluorooctanoate (Zn-APc-pFOA), was synthesized from zinc tetraaminophthalocyanine and perfluorooctanoic acid. The chemical structure, liquid crystalline behavior, and electrorheological properties were characterized by the use of various experimental techniques, methods, and instruments, including FT-IR and UV-vis spectroscopy, 1H-NMR, x-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, polarized optical microscopy, the four-point method, a relative permittivity test instrument, and a rotating viscometer. Zn-APc-pFOA shows a discotic hexagonal columnar mesophase over a wide temperature range. The dielectric constant and conductivity of Zn-APc-pFOA are 11.4 and 6.34 × 10-3 S cm-1, respectively. The 20 V% silicone oil-Zn-APc-pFOA fluid shows an electrorheological (ER) effect. Zn-APc-pFOA is a semiconductor with a high dielectric constant, causing a mismatch of conductivity and dielectric constant between the Zn-APc-pFOA and silicone oil. Furthermore, some synergistic effect could occur between the semiconducting property and the molecular orientation of the discotic liquid crystals in Zn-APc-pFOA suspensions, resulting in a high ER effect.

  16. Immediate hypersensitivity reactions to ibuprofen and other arylpropionic acid derivatives.

    PubMed

    Blanca-López, N; Pérez-Alzate, D; Andreu, I; Doña, I; Agúndez, J A; García-Martín, E; Salas, M; Miranda, M Á; Torres, M J; Cornejo-García, J A; Blanca, M; Canto, G

    2016-07-01

    Although ibuprofen and other arylpropionic acid derivatives (APs) are the most common medicines involved in hypersensitivity drug reactions (HDRs) to NSAIDs, no patient series studies have been performed regarding immediate selective reactions (SRs) to these drugs. To characterize patients with immediate selective HDRs to ibuprofen and other APs through clinical history and challenge. Subjects who developed an HDR to APs less than 1 h after drug intake were included. Tolerance to aspirin was assessed and challenge was performed with ibuprofen in all cases, and additionally with the culprit drug (if different) in those patients that tolerated ibuprofen. Serum tryptase levels and tryptase immunohistochemical staining in skin biopsies were also assessed in some patients with a positive DPT to ibuprofen. From a total of 245 patients with a confirmed history of HDRs to APs, 17% were classified as selective immediate hypersensitivity reactors by both clinical history and challenge. A selective response to naproxen and dexketoprofen with tolerance to ibuprofen was found in 16 of 20 cases. Significant differences in serum tryptase levels were observed between 2 and 24 h in the 11 cases that were studied further. Within the group of patients with HDRs to NSAIDs, APs can induce immediate SRs. Within this group, selective responses to a single drug or responders to several APs may exist, suggesting potential immunological cross-reactivity. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Brønsted acid-catalyzed Nazarov cyclization of pyrrole derivatives accelerated by microwave irradiation.

    PubMed

    Bachu, Prabhakar; Akiyama, Takahiko

    2009-07-15

    The Brønsted acid-catalyzed Nazarov cyclization of pyrrole derivatives was developed. Microwave irradiation accelerated the Nazarov cyclization significantly at 40 degrees C to give cyclopenta[b]pyrrole derivatives in excellent yields with high trans selectivity.

  18. Benzoic acid derivatives from Piper species and their fungitoxic activity against Cladosporium cladosporioides and C. sphaerospermum.

    PubMed

    Lago, João Henrique G; Ramos, Clécio Sousa; Casanova, Diego Campos C; Morandim, Andreia de A; Bergamo, Debora Cristina B; Cavalheiro, Alberto J; Bolzani, Vanderlan da S; Furlan, Maysa; Guimarães, Elsie F; Young, Maria Claudia M; Kato, Massuo J

    2004-11-01

    Piper crassinervium, P. aduncum, P. hostmannianum, and P. gaudichaudianum contain the new benzoic acid derivatives crassinervic acid (1), aduncumene (8), hostmaniane (18), and gaudichaudianic acid (20), respectively, as major secondary metabolites. Additionally, 19 known compounds such as benzoic acids, chromenes, and flavonoids were isolated and identified. The antifungal activity of these compounds was evaluated by bioautographic TLC assay against Cladosporium cladosporioides and C. sphaerospermum.

  19. Human liver apolipoprotein B-100 cDNA: complete nucleic acid and derived amino acid sequence.

    PubMed Central

    Law, S W; Grant, S M; Higuchi, K; Hospattankar, A; Lackner, K; Lee, N; Brewer, H B

    1986-01-01

    Human apolipoprotein B-100 (apoB-100), the ligand on low density lipoproteins that interacts with the low density lipoprotein receptor and initiates receptor-mediated endocytosis and low density lipoprotein catabolism, has been cloned, and the complete nucleic acid and derived amino acid sequences have been determined. ApoB-100 cDNAs were isolated from normal human liver cDNA libraries utilizing immunoscreening as well as filter hybridization with radiolabeled apoB-100 oligodeoxynucleotides. The apoB-100 mRNA is 14.1 kilobases long encoding a mature apoB-100 protein of 4536 amino acids with a calculated amino acid molecular weight of 512,723. ApoB-100 contains 20 potential glycosylation sites, and 12 of a total of 25 cysteine residues are located in the amino-terminal region of the apolipoprotein providing a potential globular structure of the amino terminus of the protein. ApoB-100 contains relatively few regions of amphipathic helices, but compared to other human apolipoproteins it is enriched in beta-structure. The delineation of the entire human apoB-100 sequence will now permit a detailed analysis of the conformation of the protein, the low density lipoprotein receptor binding domain(s), and the structural relationship between apoB-100 and apoB-48 and will provide the basis for the study of genetic defects in apoB-100 in patients with dyslipoproteinemias. PMID:3464946

  20. Obesity is positively associated with arachidonic acid-derived 5- and 11-hydroxyeicosatetraenoic acid (HETE).

    PubMed

    Pickens, Charles Austin; Sordillo, Lorraine M; Zhang, Chen; Fenton, Jenifer I

    2017-05-01

    Oxylipids are oxygenated polyunsaturated fatty acid (PUFA) metabolites that are responsible for the onset and resolution of the inflammatory response. Enzymatic oxygenation through the lipoxygenase (LOX) or cytochrome P450 (CYP) pathways can form oxylipids that have either proinflammatory or proresolving functions depending on the type of PUFA substrate and degree of metabolism. The objective of this study was to determine how PUFA substrates and their corresponding oxylipids are associated with obesity. Plasma non-esterified FA and oxylipids were isolated from 123 Caucasian males using solid phase extraction and quantified using high performance liquid chromatography-tandem mass spectrometry. Statistical analyses included linear regressions and polytomous logistic regressions, and the responses were body mass index (BMI) and waist circumference (WC), and serum leptin, total adiponectin, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and C-peptide. Models were adjusted for age and smoking, and p-values were corrected for false discovery per Benjamini-Hochberg and Bonferroni. We report that BMI, WC, and several serum cytokines were highly associated arachidonic acid (ARA)-derived hydroxyeicosatetraenoic acids (HETEs), and vicinal diols (i.e., alcohols on adjacent carbon atoms) derived from several PUFAs. There was a significant linear relationship between BMI, WC, and serum leptin, and ARA-derived 5-, 11-, and 15-HETE. Specifically, BMI and WC were positively associated with proinflammatory 5- and 11-hydroxyeicosatetraenoic acid (HETE), even after normalization to ARA concentrations and false discovery p-value correction. Individuals with 5-HETE concentrations >5.01nmol/L or 11-HETE concentrations and >0.89nmol/L were over 5 times more likely to be obese compared to those with ≤1.86nmol/L and ≤0.39nmol/L, respectively. Vicinal diols from linoleic, eicosapentaenoic, and docosahexaenoic acid were inversely associated with obesity. Across all statistical

  1. Hydrogen/deuterium exchange of cross-linkable α-amino acid derivatives in deuterated triflic acid.

    PubMed

    Wang, Lei; Murai, Yuta; Yoshida, Takuma; Okamoto, Masashi; Masuda, Katsuyoshi; Sakihama, Yasuko; Hashidoko, Yasuyuki; Hatanaka, Yasumaru; Hashimoto, Makoto

    2014-01-01

    In this paper we report here a hydrogen/deuterium exchange (H/D exchange) of cross-linkable α-amino acid derivatives with deuterated trifluoromethanesulfonic acid (TfOD). H/D exchange with TfOD was easily applied to o-catechol containing phenylalanine (DOPA) within an hour. A partial H/D exchange was observed for trifluoromethyldiazirinyl (TFMD) phenylalanine derivatives. N-Acetyl-protected natural aromatic α-amino acids (Tyr and Trp) were more effective in H/D exchange than unprotected ones. The N-acetylated TFMD phenylalanine derivative afforded slightly higher H/D exchange than unprotected derivatives. An effective post-deuteration method for cross-linkable α-amino acid derivatives will be useful for the analysis of biological functions of bioactive peptides and proteins by mass spectrometry.

  2. Anti-Inflammatory Activity of Tanzawaic Acid Derivatives from a Marine-Derived Fungus Penicillium steckii 108YD142

    PubMed Central

    Shin, Hee Jae; Pil, Gam Bang; Heo, Soo-Jin; Lee, Hyi-Seung; Lee, Jong Seok; Lee, Yeon-Ju; Lee, Jihoon; Won, Ho Shik

    2016-01-01

    Chemical investigation of a marine-derived fungus, Penicillium steckii 108YD142, resulted in the discovery of a new tanzawaic acid derivative, tanzawaic acid Q (1), together with four known analogues, tanzawaic acids A (2), C (3), D (4), and K (5). The structures of tanzawaic acid derivatives 1–5 were determined by the detailed analysis of 1D, 2D NMR and LC-MS data, along with chemical methods and literature data analysis. These compounds significantly inhibited nitric oxide (NO) production and the new tanzawaic acid Q (1) inhibited the lipopolysaccharide (LPS)-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins and mRNA expressions in RAW 264.7 macrophages. Additionally, compound 1 reduced the mRNA levels of inflammatory cytokines. Taken together, the results of this study demonstrated that the new tanzawaic acid derivative inhibits LPS-induced inflammation. This is the first report on the anti-inflammatory activity of tanzawaic acid Q (1). PMID:26761016

  3. Synthesis of new glycyrrhetinic acid derived ring A azepanone, 29-urea and 29-hydroxamic acid derivatives as selective 11β-hydroxysteroid dehydrogenase 2 inhibitors.

    PubMed

    Gaware, Rawindra; Khunt, Rupesh; Czollner, Laszlo; Stanetty, Christian; Da Cunha, Thierry; Kratschmar, Denise V; Odermatt, Alex; Kosma, Paul; Jordis, Ulrich; Classen-Houben, Dirk

    2011-03-15

    Glycyrrhetinic acid, the metabolite of the natural product glycyrrhizin, is a well known nonselective inhibitor of 11β-hydroxysteroid dehydrogenase (11β-HSD) type 1 and type 2. Whereas inhibition of 11β-HSD1 is currently under consideration for treatment of metabolic diseases, such as obesity and diabetes, 11β-HSD2 inhibitors may find therapeutic applications in chronic inflammatory diseases and certain forms of cancer. Recently, we published a series of hydroxamic acid derivatives of glycyrrhetinic acid showing high selectivity for 11β-HSD2. The most potent and selective compound is active against human 11β-HSD2 in the low nanomolar range with a 350-fold selectivity over human 11β-HSD1. Starting from the lead compounds glycyrrhetinic acid and the hydroxamic acid derivatives, novel triterpene type derivatives were synthesized and analyzed for their biological activity against overexpressed human 11β-HSD1 and 11β-HSD2 in cell lysates. Here we describe novel 29-urea- and 29-hydroxamic acid derivatives of glycyrrhetinic acid as well as derivatives with the Beckman rearrangement of the 3-oxime to a seven-membered ring, and the rearrangement of the C-ring from 11-keto-12-ene to 12-keto-9(11)-ene. The combination of modifications on different positions led to compounds comprising further improved selective inhibition of 11β-HSD2 in the lower nanomolar range with up to 3600-fold selectivity.

  4. Pharmaceuticals and Surfactants from Alga-Derived Feedstock: Amidation of Fatty Acids and Their Derivatives with Amino Alcohols.

    PubMed

    Tkacheva, Anastasia; Dosmagambetova, Inkar; Chapellier, Yann; Mäki-Arvela, Päivi; Hachemi, Imane; Savela, Risto; Leino, Reko; Viegas, Carolina; Kumar, Narendra; Eränen, Kari; Hemming, Jarl; Smeds, Annika; Murzin, Dmitry Yu

    2015-08-24

    Amidation of renewable feedstocks, such as fatty acids, esters, and Chlorella alga based biodiesel, was demonstrated with zeolites and mesoporous materials as catalysts and ethanolamine, alaninol, and leucinol. The last two can be derived from amino acids present in alga. The main products were fatty alkanol amides and the corresponding ester amines, as confirmed by NMR and IR spectroscopy. Thermal amidation of technical-grade oleic acid and stearic acid at 180 °C with ethanolamine were non-negligible; both gave 61% conversion. In the amidation of stearic acid with ethanolamine, the conversion over H-Beta-150 was 80% after 3 h, whereas only 63% conversion was achieved for oleic acid; this shows that a microporous catalyst is not suitable for this acid and exhibits a wrinkled conformation. The highest selectivity to stearoyl ethanolamide of 92% was achieved with mildly acidic H-MCM-41 at 70% conversion in 3 h at 180 °C. Highly acidic catalysts favored the formation of the ester amine, whereas the amide was obtained with a catalyst that exhibited an optimum acidity. The conversion levels achieved with different fatty acids in the range C12-C18 were similar; this shows that the fatty acid length does not affect the amidation rate. The amidation of methyl palmitate and biodiesel gave low conversions over an acidic catalyst, which suggested that the reaction mechanism in the amidation of esters was different.

  5. Metabolic engineering of yeast to produce fatty acid-derived biofuels: bottlenecks and solutions

    PubMed Central

    Sheng, Jiayuan; Feng, Xueyang

    2015-01-01

    Fatty acid-derived biofuels can be a better solution than bioethanol to replace petroleum fuel, since they have similar energy content and combustion properties as current transportation fuels. The environmentally friendly microbial fermentation process has been used to synthesize advanced biofuels from renewable feedstock. Due to their robustness as well as the high tolerance to fermentation inhibitors and phage contamination, yeast strains such as Saccharomyces cerevisiae and Yarrowia lipolytica have attracted tremendous attention in recent studies regarding the production of fatty acid-derived biofuels, including fatty acids, fatty acid ethyl esters, fatty alcohols, and fatty alkanes. However, the native yeast strains cannot produce fatty acids and fatty acid-derived biofuels in large quantities. To this end, we have summarized recent publications in this review on metabolic engineering of yeast strains to improve the production of fatty acid-derived biofuels, identified the bottlenecks that limit the productivity of biofuels, and categorized the appropriate approaches to overcome these obstacles. PMID:26106371

  6. Complete amino acid sequence of chicken liver acyl carrier protein derived from the fatty acid synthase.

    PubMed

    Huang, W Y; Stoops, J K; Wakil, S J

    1989-04-01

    The acyl carrier protein domain of the chicken liver fatty acid synthase has been isolated after tryptic treatment of the synthase. The isolated domain functions as an acceptor of acetyl and malonyl moieties in the synthase-catalyzed transfer of these groups from their coenzyme A esters and therefore indicates that the acyl carrier protein domain exists in the complex as a discrete entity. The amino acid sequence of the acyl carrier protein was derived from analyses of peptide fragments produced by cyanogen bromide cleavage and trypsin and Staphylococcus aureus V8 protease digestions of the molecule. The isolated acyl carrier protein domain consists of 89 amino acid residues and has a calculated molecular weight of 10,127. The protein contains the phosphopantetheine group attached to the serine residue at position 38. The isolated acyl carrier protein peptide shows some sequence homology with the acyl carrier protein of Escherichia coli, particularly in the vicinity of the site of phosphopantetheine attachment, and shows extensive sequence homology with the acyl carrier protein from the uropygial gland of goose.

  7. Efficient oxidation of oleanolic acid derivatives using magnesium bis(monoperoxyphthalate) hexahydrate (MMPP): A convenient 2-step procedure towards 12-oxo-28-carboxylic acid derivatives

    PubMed Central

    Moreira, Vânia M; Pinto, Rui M A; Leal, Ana S; Paixão, José A

    2012-01-01

    Summary A new, straightforward and high yielding procedure to convert oleanolic acid derivatives into the corresponding δ-hydroxy-γ-lactones, by using the convenient oxidizing agent magnesium bis(monoperoxyphthalate) hexahydrate (MMPP) in refluxing acetonitrile, is reported. In addition, a two-step procedure for the preparation of oleanolic 12-oxo-28-carboxylic acid derivatives directly from Δ12-oleananes, without the need for an intermediary work-up, and keeping the same reaction solvent in both steps, is described as applied to the synthesis of 3,12-dioxoolean-28-oic acid. PMID:22423283

  8. Utilization of acidic α-amino acids as acyl donors: an effective stereo-controllable synthesis of aryl-keto α-amino acids and their derivatives.

    PubMed

    Wang, Lei; Murai, Yuta; Yoshida, Takuma; Okamoto, Masashi; Tachrim, Zetryana Puteri; Hashidoko, Yasuyuki; Hashimoto, Makoto

    2014-05-16

    Aryl-keto-containing α-amino acids are of great importance in organic chemistry and biochemistry. They are valuable intermediates for the construction of hydroxyl α-amino acids, nonproteinogenic α-amino acids, as well as other biofunctional components. Friedel-Crafts acylation is an effective method to prepare aryl-keto derivatives. In this review, we summarize the preparation of aryl-keto containing α-amino acids by Friedel-Crafts acylation using acidic α-amino acids as acyl-donors and Lewis acids or Brönsted acids as catalysts.

  9. Electrophilic amination of amino acids with N-Boc-oxaziridines: efficient preparation of N-orthogonally diprotected hydrazino acids and piperazic acid derivatives.

    PubMed

    Hannachi, Jean-Christophe; Vidal, Joëlle; Mulatier, Jean-Christophe; Collet, André

    2004-04-02

    A general two-step preparation of enantiopure N(alpha),N(beta)-orthogonally diprotected alpha-hydrazino acids 1 is developed on a multigram scale. The key reaction is the efficient electrophilic amination of N-benzyl amino acids 6 with N-Boc-oxaziridine 7 and accommodates various functional groups encountered in side chains of amino acids. The cyclic 2,3,4,5-tetrahydro-3-pyridazine carboxylic acid (piperazic acid) derivatives 2 and 3 or the cyclic 3,4-dihydro-3-pyrazolecarboxylate 4 are conveniently prepared from glutamic acid or aspartic acid via orthogonally diprotected alpha-hydrazino acids 1m and 1n.

  10. Synthesis and antimicrobial evaluation of amide derivatives of benzodifuran-2-carboxylic acid.

    PubMed

    Soni, Jigar N; Soman, Shubhangi S

    2014-03-21

    We have synthesized various amide derivatives of benzodifuran-2-carboxylic acid from resorcinol. Reaction of 7-hydroxy-4-methylcoumarin with chloroacetone in anhydrous K2CO3 and dry acetone gave ether derivative of 7-hydroxy-4-methylcoumarin 3 which on reaction with N-bromosuccinimide in chloroform gave corresponding 3-bromo derivative 4. Cyclization of bromo derivative in 10% ethanolic KOH gave benzodifuran-2-carboxylic acid 5. This acid was converted into acid chloride using oxalyl chloride and then substituted with different amines in presence of base, triethylamine to give amide derivatives of benzodifuran-2-carboxylic acid 6. All compounds were screened for antimicrobial activity against two Gram positive bacteria Staphylococus aureus and Bacillus subtilis, two Gram negative bacteria E. coli and P. aeruginosa and one fungus Candida albicans.

  11. Synthesis and biological activity of glutamic acid derivatives.

    PubMed

    Receveur, J M; Guiramand, J; Récasens, M; Roumestant, M L; Viallefont, P; Martinez, J

    1998-01-20

    In order to develop new specific glutamate analogues at metabotropic glutamate receptors, Diels-Alder, 1-4 ionic and radical reactions were performed starting from (2S)-4-methyleneglutamic acid. Preliminary pharmacological evaluation by measuring IP accumulation using rat forebrain synaptoneurosomes has shown that (2S)-4-(2-phthalimidoethyl)glutamic acid (3a), (2S)-4-(4-phthalimidobutyl)glutamic acid (3b) and 1-[(S)-2-amino-2-carboxyethyl]-3,4-dimethylcyclohex-3-ene-1-carbox ylic acid (8) presented moderate antagonist activities.

  12. Fatty acid-derived diisocyanate and biobased polyurethane produced from vegetable oil: synthesis, polymerization, and characterization.

    PubMed

    Hojabri, Leila; Kong, Xiaohua; Narine, Suresh S

    2009-04-13

    A new linear saturated terminal diisocyanate was synthesized from oleic acid via Curtius rearrangement, and its chemical structure was identified by FTIR, (1)H and (13)C NMR, and MS. The feasibility of utilizing this new diisocyanate for the production of polyurethanes (PUs) was demonstrated by reacting it with commercial petroleum-derived polyols and canola oil-derived polyols, respectively. The physical properties of the PUs prepared from fatty acid-derived diisocyanate were compared to those prepared from the same polyols with a similar but petroleum-derived commercially available diisocyanate: 1,6-hexamethylene diisocyanate. It was found that the fatty acid-derived diisocyanate was capable of producing PUs with comparable properties within acceptable tolerances. This work is the first that establishes the production of linear saturated terminal diisocyanate derived from fatty acids and corresponding PUs mostly from lipid feedstock.

  13. Salicylic acid and some of its derivatives as antibacterial agents for viscose fabric.

    PubMed

    Kantouch, A; El-Sayed, A Atef; Salama, M; El-Kheir, A Abou; Mowafi, S

    2013-11-01

    Salicylic acid and three of its derivatives were used to provide antibacterial properties to viscose fabrics. The four bactericides used were bonded to the viscose fabrics using epichlorohydrin or polymer binders. Optimization of the salicylic acid and its derivatives as well as the concentration of polymers was reported. The ability of the polymer binders to attract and bind the four bactericides was observed. The overall results show that the antibacterial reactivity of salicylic acid and its derivatives are in the following order 5-bromosalicylic acid>salicylic acid>5-chlorosalicylic acid>4-chlorosalicylic acid. Using epichlorohydrin as a binding agent, unfortunately, inhibits the bactericidal activity of the four bactericides. The FTIR study concludes that the reaction between salicylic acid as well as its derivatives with epichlorohydrin takes place through the phenolic group of the acids. The unexpected deterioration in the bactericidal properties of salicylic acid and its derivatives as a result of the treatment with epichlorohydrin could be due to the nature of interaction between the epichlorohydrin molecule and the acids molecules. PVP and PU show superior ability to sustain the four bactericides used even after 10 washing cycles.

  14. Hydroxyoctadecadienoic acids: Oxidised derivatives of linoleic acid and their role in inflammation associated with metabolic syndrome and cancer.

    PubMed

    Vangaveti, Venkat N; Jansen, Holger; Kennedy, Richard Lee; Malabu, Usman H

    2016-08-15

    Linoleic acid (LA) is a major constituent of low-density lipoproteins. An essential fatty acid, LA is a polyunsaturated fatty acid, which is oxidised by endogenous enzymes and reactive oxygen species in the circulation. Increased levels of low-density lipoproteins coupled with oxidative stress and lack of antioxidants drive the oxidative processes. This results in synthesis of a range of oxidised derivatives, which play a vital role in regulation of inflammatory processes. The derivatives of LA include, hydroxyoctadecadienoic acids, oxo-​octadecadienoic acids, epoxy octadecadecenoic acid and epoxy-keto-octadecenoic acids. In this review, we examine the role of LA derivatives and their actions on regulation of inflammation relevant to metabolic processes associated with atherogenesis and cancer. The processes affected by LA derivatives include, alteration of airway smooth muscles and vascular wall, affecting sensitivity to pain, and regulating endogenous steroid hormones associated with metabolic syndrome. LA derivatives alter cell adhesion molecules, this initial step, is pivotal in regulating inflammatory processes involving transcription factor peroxisome proliferator-activated receptor pathways, thus, leading to alteration of metabolic processes. The derivatives are known to elicit pleiotropic effects that are either beneficial or detrimental in nature hence making it difficult to determine the exact role of these derivatives in the progress of an assumed target disorder. The key may lie in understanding the role of these derivatives at various stages of development of a disorder. Novel pharmacological approaches in altering the synthesis or introduction of synthesised LA derivatives could possibly help drive processes that could regulate inflammation in a beneficial manner. Chemical Compounds: Linoleic acid (PubChem CID: 5280450), 9- hydroxyoctadecadienoic acid (PubChem CID: 5312830), 13- hydroxyoctadecadienoic acid (PubChem CID: 6443013), 9-oxo

  15. Reversible covalent interactions of β-aminoboronic acids with carbohydrate derivatives.

    PubMed

    Garrett, Graham E; Diaz, Diego B; Yudin, Andrei K; Taylor, Mark S

    2017-02-07

    β-Aminoalkylboronic acids are capable of binding to carbohydrate derivatives through reversible covalent interactions. An anthracene-bearing β-aminoboronic acid has been synthesized, enabling determinations of association constants for binding of sugars by fluorescence spectroscopy. The diol-binding properties of β-aminoboronic acids are also useful in catalysis: one such compound displays remarkably high activity for regioselective O-acylation of a pyranoside derivative.

  16. Quantification of amino acids in fermentation media by isocratic HPLC analysis of their α-hydroxy acid derivatives.

    PubMed

    Pleissner, Daniel; Wimmer, Reinhard; Eriksen, Niels T

    2011-01-01

    In this paper we describe a novel method for quantification of amino acids. First, α-hydroxy acid derivatives of amino acids were formed after reaction with dinitrogen trioxide by the van Slyke reaction. Second, the α-hydroxy acid derivatives were separated on an Aminex HPX-87H column (Bio-Rad) eluted isocratically with 5 mM H(2)SO(4) and quantified by refractive index detection. We were able to measure the reaction products of 13 of the 20 classical amino acids: glycine, l-alanine, l-valine, l-leucine, l-isoleucine, l-methionine, l-serine, l-threonine, l-asparagine, l-glutamine, l-aspartic acid, l-glutamic acid, and l-proline. We obtained linear relationships between the product peak areas and initial amino acid concentration, whereby the concentrations of these amino acids could be quantified on the basis of the quantification of their products. The method can be used to analyze amino acids in parallel with other small molecules, such as sugars or short chain fatty acids, and was used for parallel quantification of glycine, l-alanine, or l-glutamic acid, and glucose uptake in cultures of the heterotrophic dinoflagellate Crypthecodinium cohnii . The method can also be used to quantify other amines, as demonstrated by detection of Tris (2-amino-2-(hydroxymethyl)propane-1,3-diol).

  17. Production and applications of carbohydrate-derived sugar acids as generic biobased chemicals.

    PubMed

    Mehtiö, Tuomas; Toivari, Mervi; Wiebe, Marilyn G; Harlin, Ali; Penttilä, Merja; Koivula, Anu

    2016-10-01

    This review considers the chemical and biotechnological synthesis of acids that are obtained by direct oxidation of mono- or oligosaccharide, referred to as sugar acids. It focuses on sugar acids which can be readily derived from plant biomass sources and their current and future applications. The three main classes of sugar acids are aldonic, aldaric and uronic acids. Interest in organic acids derived from sugars has recently increased, as part of the interest to develop biorefineries which produce not only biofuels, but also chemicals to replace those currently derived from petroleum. More than half of the most desirable biologically produced platform chemicals are organic acids. Currently, the only sugar acid with high commercial production is d-gluconic acid. However, other sugar acids such as d-glucaric and meso-galactaric acids are being produced at a lower scale. The sugar acids have application as sequestering agents and binders, corrosion inhibitors, biodegradable chelators for pharmaceuticals and pH regulators. There is also considerable interest in the use of these molecules in the production of synthetic polymers, including polyamides, polyesters and hydrogels. Further development of these sugar acids will lead to higher volume production of the appropriate sugar acids and will help support the next generation of biorefineries.

  18. Distillation of natural fatty acids and their chemical derivatives

    USDA-ARS?s Scientific Manuscript database

    Well over 1,000 different fatty acids are known which are natural components of fats, oils (triacylglycerols), and other related compounds. These fatty acids can have different alkyl chain lengths, 0-6 carbon-carbon double bonds possessing cis- or trans-geometry, and can contain a variety of functio...

  19. Ellagic acid derivatives from Syzygium cumini stem bark: investigation of their antiplasmodial activity.

    PubMed

    Simões-Pires, Claudia A; Vargas, Sandra; Marston, Andrew; Ioset, Jean-Robert; Paulo, Marçal Q; Matheeussen, An; Maes, Louis

    2009-10-01

    Bioguided fractionation of Syzygium cumini (Myrtaceae) bark decoction for antiplasmodial activity was performed, leading to the isolation of three known ellagic acid derivatives (ellagic acid, ellagic acid 4-O-alpha-L-2"-acetylrhamnopyranoside, 3-O-methylellagic acid 3'-O-alpha-L-rhamnopyranoside), as well as the new derivative 3-O-methylellagic acid 3'-O-beta-D-glucopyranoside. Activity investigation was based on the reduction of P. falciparum (PfK1) parasitaemia in vitro and the inhibition of beta-hematin formation, a known mechanism of action of some antimalarial drugs. Among the investigated ellagic acid derivatives, only ellagic acid was able to reduce P. falciparum parasitaemia in vitro and inhibit beta-hematin formation, suggesting that free hydroxyl groups are necessary for activity within this class of compounds.

  20. Sophorolipid-derived unsaturated and epoxy fatty acid estolides as plasticizers for poly(3-hydroxybutyrate)

    USDA-ARS?s Scientific Manuscript database

    Unsaturated and epoxy fatty acid estolides were synthesized from the omega and omega-1 hydroxy fatty acids derived from sophorolipids (SLs) prepared by fermentation from glucose:soybean oil and glucose:oleic acid, respectively. These estolides were utilized as additives in solution-cast poly(3-hydro...

  1. Betulinic acid derived hydroxamates and betulin derived carbamates are interesting scaffolds for the synthesis of novel cytotoxic compounds.

    PubMed

    Wiemann, Jana; Heller, Lucie; Perl, Vincent; Kluge, Ralph; Ströhl, Dieter; Csuk, René

    2015-12-01

    The betulinic acid-derived hydroxamates 5-18, the amides 19-24, and betulin-derived bis-carbamates 25-28 as well as the carbamates 31-40 and 44-48 were prepared and evaluated for their antiproliferative activity in a photometric sulforhodamine B (SRB) assay against several human cancer cell lines and nonmalignant mouse fibroblasts (NIH 3T3). While for 3-O-acetyl hydroxamic acid 5 EC50 values as low as EC50 = 1.3 μM were found, N,O-bis-alkyl substituted hydroxamates showed lowered cytotoxicity (EC50 = 16-20 μM). In general, hydroxamic acid derivatives showed only reduced selectivity for tumor cells, except for allyl substituted compound 13 (EC50 = 5.9 μM for A2780 human ovarian carcinoma cells and EC50 > 30 μM for nonmalignant mouse fibroblasts). The cytotoxicity of betulinic acid derived amides 19-24 and of betulin derived bis-carbamates 25-28 was low, except for N-ethyl substituted 25. Hexyl substituted 39 showed EC50 = 5.6 μM (518A2 cells) while for mouse fibroblasts EC50 > 30 was determined.

  2. Caffeoylglycolic and caffeoylamino acid derivatives, halfmers of L-chicoric acid, as new HIV-1 integrase inhibitors.

    PubMed

    Lee, Seung Uk; Shin, Cha-Gyun; Lee, Chong-Kyo; Lee, Yong Sup

    2007-10-01

    Human immunodeficiency virus (HIV) integrase (IN) catalyzes the integration of HIV DNA copy into the host cell DNA. L-Chicoric acid (1) has been found to be one of the most potent HIV-1 integrase inhibitor. Caffeoylglycolic and caffeoylamino acid derivatives' halfmeric structures of L-chicoric acid 2 were synthesized for the purpose of simplifying the structure of L-chicoric acid. Among synthesized, compounds 2c and 3f showed HIV-1 IN inhibitory activities with IC(50) values of 10.5 and 12.0 microM, respectively, comparable to that of parent compound L-chicoric acid (IC(50)=15.7 microM).

  3. Antiparasitic activity of prenylated benzoic acid derivatives from Piper species.

    PubMed

    Flores, Ninoska; Jiménez, Ignacio A; Giménez, Alberto; Ruiz, Grace; Gutiérrez, David; Bourdy, Genevieve; Bazzocchi, Isabel L

    2009-03-01

    Fractionation of dichloromethane extracts from the leaves of Piper heterophyllum and P. aduncum afforded three prenylated hydroxybenzoic acids, 3-[(2E,6E,10E)-11-carboxy-3,7,15-trimethyl-2,6,10,14-hexadecatetraenyl)-4,5-dihydroxybenzoic acid, 3-[(2E,6E,10E)-11-carboxy-13-hydroxy-3,7,15-trimethyl-2,6,10,14-hexadecatetraenyl]-4,5-dihydroxybenzoic acid and 3-[(2E,6E,10E)-11-carboxy-14-hydroxy-3,7,15-trimethyl-2,6,10,15-hexadecatetraenyl]-4,5-dihydroxybenzoic acid, along with the known compounds, 4,5-dihydroxy-3-(E,E,E-11-formyl-3,7,15-trimethyl-hexadeca-2,6,10,14-tetraenyl)benzoic acid (arieianal), 3,4-dihydroxy-5-(E,E,E-3,7,11,15-tetramethyl-hexadeca-2,6,10,14-tetraenyl)benzoic acid, 4-hydroxy-3-(E,E,E-3,7,11,15-tetramethyl-hexadeca-2,6,10,14-tetraenyl)benzoic acid, 3-(3,7-dimethyl-2,6-octadienyl)-4-methoxy-benzoic acid, 4-hydroxy-3-(3,7-dimethyl-2,6-octadienyl)benzoic acid and 4-hydroxy-3-(3-methyl-1-oxo-2-butenyl)-5-(3-methyl-2-butenyl)benzoic acid. Their structures were elucidated on the basis of spectroscopic data, including homo- and heteronuclear correlation NMR experiments (COSY, HSQC and HMBC) and comparison with data reported in the literature. Riguera ester reactions and optical rotation measurements established the compounds as racemates. The antiparasitic activity of the compounds were tested against three strains of Leishmania spp., Trypanosoma cruzi and Plasmodium falciparum. The results showed that 3-(3,7-dimethyl-2,6-octadienyl)-4-methoxy-benzoic acid exhibited potent and selective activity against L. braziliensis (IC(50) 6.5 microg/ml), higher that pentamidine used as control. Moreover, 3-[(2E,6E,10E)-11-carboxy-3,7,15-trimethyl- 2,6,10,14-hexadecatetraenyl)-4,5-dihydroxybenzoic acid and 4-hydroxy-3-(3-methyl-1-oxo-2-butenyl)-5-(3-methyl-2-butenyl)benzoic acid showed moderate antiplasmodial (IC(50) 3.2 microg/ml) and trypanocidal (16.5 microg/ml) activities, respectively.

  4. Bio-Based Production of Dimethyl Itaconate From Rice Wine Waste-Derived Itaconic Acid.

    PubMed

    Joo, Young-Chul; You, Seung Kyou; Shin, Sang Kyu; Ko, Young Jin; Jung, Ki Ho; Sim, Sang A; Han, Sung Ok

    2017-08-28

    Dimethyl itaconate is an important raw material for copolymerization, but it is not synthesized from itaconic acid by organisms. Moreover, Corynebacterium glutamicum is used as an important industrial host for the production of organic acids, but it does not metabolize itaconic acid. Therefore, the biosynthetic route toward dimethyl itaconate from itaconic acid is highly needed. In this study, a biological procedure for dimethyl itaconate production is developed from rice wine waste-derived itaconic acid using the engineered C. glutamicum strain. The first step is to investigate the effect of the co-overexpression of the codon-optimized cis-aconitic acid decarboxylase (CadA*) and a transcriptional regulator of genes involved in acetic acid metabolism (RamA) on itaconic acid production. The second step is to convert itaconic acid into dimethyl itaconate by lipase-catalyzed esterification. The CadA* and RamA-overexpressing CG4 strain increases the itaconic acid concentration under N-starvation with glucose and acetic acid compared with the concentration produced in the base mCGXII medium with glucose. Furthermore, the rice wine waste-derived itaconic acid is successfully converted into dimethyl itaconate using lipase from Rhizomucor miehei and a methanol substrate. This study is the first trial for bio-based production of dimethyl itaconate from rice wine waste-derived itaconic acid. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Antibacterial activity of triterpene acids and semi-synthetic derivatives against oral pathogens.

    PubMed

    Scalon Cunha, Luis C; Andrade e Silva, Márcio L; Cardoso Furtado, Niege A J; Vinhólis, Adriana H C; Gomes Martins, Carlos H; da Silva Filho, Ademar A; Cunha, Wilson R

    2007-01-01

    Triterpene acids (ursolic, oleanoic, gypsogenic, and sumaresinolic acids) isolated from Miconia species, along with a mixture of ursolic and oleanolic acids and a mixture of maslinic and 2-a-hydroxyursolic acids, as well as ursolic acid derivatives were evaluated against the following microorganisms: Streptococcus mutans, Streptococcus mitis, Streptococcus sanguinis, Streptococcus salivarius, Streptococcus sobrinus, and Enterococcus faecalis, which are potentially responsible for the formation of dental caries in humans. The microdilution method was used for the determination of the minimum inhibitory concentration (MIC) during the evaluation of the antibacterial activity. All the isolated compounds, mixtures, and semi-synthetic derivatives displayed activity against all the tested bacteria, showing that they are promising antiplaque and anticaries agents. Ursolic and oleanolic acids displayed the most intense antibacterial effect, with MIC values ranging from 30 microg/mL to 80 microg/mL. The MIC values of ursolic acid derivatives, as well as those obtained for the mixture of ursolic and oleanolic acids showed that these compounds do not have higher antibacterial activity when compared with the activity observed with either ursolic acid or oleanolic acid alone. With regard to the structure-activity relationship of triterpene acids and derivatives, it is suggested that both hydroxy and carboxy groups present in the triterpenes are important for their antibacterial activity against oral pathogens.

  6. Reaction of acetaldehyde with 5-aminolevulinic acid via dihydropyrazine derivative.

    PubMed

    Suzuki, Toshinori; Yasuhara, Naoki; Ueda, Takashi; Inukai, Michiyo; Mio, Mitsunobu

    2015-01-01

    When a solution of 5-aminolevulinic acid (ALA) was incubated with acetaldehyde at neutral pH, a product was generated. This product was identified as 3-ethylpyrazine-2,5-dipropanoic acid (ETPY). ETPY was stable at neutral pH. It has been reported that ALA dimerizes at neutral pH generating 3,6-dihydropyrazine-2,5-dipropanoic acid (DHPY), and subsequently resulting in pyrazine-2,5-dipropanoic acid (PY) by autoxidation. In the present reaction, DHPY generated from ALA reacted with acetaldehyde, resulting in ETPY. Preadministration of ALA 3 min prior to acetaldehyde injection supressed the toxicity of acetaldehyde in male mice. These results suggest that ALA may be useful as a scavenger for acetaldehyde.

  7. Biotransformation of coal derived humic acids by Basidiomycetes

    NASA Astrophysics Data System (ADS)

    Klein, O. I.; Kulikova, N. A.; Stepanova, E. V.; Koroleva, O. V.

    2009-04-01

    Introduction Low energetic coals and wastes of coal industry are promising sources for biologically active compounds including humic acids (HA). Aside from evident advantages of biocatalytic approaches for coal slime conversion such as environmental safety and cost efficiency they also could be used for the improving of HAs biological activity [1, 2]. The aim of the present study was to provide molecular characterization of the HAs formed during biotransformation of coal slime by Basidiomycetes under different cultivation conditions. Materials and methods Biotransformation of brown coal from Solncevskoe deposit (Sakhalin, Russia) was performed by liquid surface cultivation of pure culture Coriolus hirsutus 075 (Wulf. Ex. Fr.) Quel. with rich (contained glucose as a carbon source) and poor (without readily available carbon source) nutrition medium. After 30 days of cultivation coal HAs were separated by alkaline extraction followed by dialysis desalting and drying at 50C. HAs derived were characterized using size-exclusion chromatography, Fourier transformed infrared (FTIR) and 13C NMR spectroscopy. Results and discussion Molecular weight distribution of HA was not significantly affected by Basidiomycetes under all cultivation conditions studied in comparison to HAs extracted from non-conversed coal. FTIR spectra of HA obtained were typical for HAs. Biotransformation of coal did not result in appearance of new functional groups. The exception was observed under rich media conditions where absorbance at 1700 cm-1 was determined related to carbonyl groups of carboxyl and ketonic fragments. Therefore, the revealed phenomena could be explained with additional formation of the above carbonyl groups in the course of biotransformation process. Quantification of 13C NMR spectra revealed decrease of aromatic structures in HA extracted from coal after biotransformation under poor media conditions. Also a significant increase in carboxylic fragments content was observed. So

  8. Effect of molecular parameters on the binding of phenoxyacetic acid derivatives to albumins.

    PubMed

    Cserháti, T; Forgács, E; Deyl, Z; Miksík, I

    2001-03-25

    The interaction of 12 phenoxyacetic acid derivatives with human and serum albumin as well as with egg albumin was studied by charge-transfer reversed-phase (RP) thin-layer chromatography (TLC) and the relative strength of interaction was calculated. Each phenoxyacetic acid derivative interacted with human and bovine serum albumins whereas no interaction was observed with egg albumin. Stepwise regression analysis proved that the lipophilicity of the derivatives exert a significant impact on their capacity to bind to serum albumins. This result supports the hypothesis that the binding of phenoxyacetic acid derivatives to albumins may involve hydrophobic forces occurring between the corresponding apolar substructures of these derivatives and the amino acid side chains.

  9. Inhibition of free radical-induced erythrocyte hemolysis by 2-O-substituted ascorbic acid derivatives.

    PubMed

    Takebayashi, Jun; Kaji, Hiroaki; Ichiyama, Kenji; Makino, Kazutaka; Gohda, Eiichi; Yamamoto, Itaru; Tai, Akihiro

    2007-10-15

    Inhibitory effects of 2-O-substituted ascorbic acid derivatives, ascorbic acid 2-glucoside (AA-2G), ascorbic acid 2-phosphate (AA-2P), and ascorbic acid 2-sulfate (AA-2S), on 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH)-induced oxidative hemolysis of sheep erythrocytes were studied and were compared with those of ascorbic acid (AA) and other antioxidants. The order of the inhibition efficiency was AA-2S> or =Trolox=uric acid> or =AA-2P> or =AA-2G=AA>glutathione. Although the reactivity of the AA derivatives against AAPH-derived peroxyl radical (ROO(*)) was much lower than that of AA, the derivatives exerted equal or more potent protective effects on AAPH-induced hemolysis and membrane protein oxidation. In addition, the AA derivatives were found to react per se with ROO(*), not via AA as an intermediate. These findings suggest that secondary reactions between the AA derivative radical and ROO(*) play a part in hemolysis inhibition. Delayed addition of the AA derivatives after AAPH-induced oxidation of erythrocytes had already proceeded showed weaker inhibition of hemolysis compared to that of AA. These results suggest that the AA derivatives per se act as biologically effective antioxidants under moderate oxidative stress and that AA-2G and AA-2P may be able to act under severe oxidative stress after enzymatic conversion to AA in vivo.

  10. Acid catalysed degradation of some spiramycin derivatives found in the antibiotic bitespiramycin.

    PubMed

    Shi, Xiangguo; Zhang, Shuqiu; Fawcett, J Paul; Zhong, Dafang

    2004-11-15

    Bitespiramycin is a novel antibiotic containing a number of 4''-acylated spiramycin derivatives (isovalerylspiramycins I-III, butanoylspiramycin III, propanoylspiramycin III and acetylspiramycin III) as major components. These spiramycin derivatives are susceptible to degradation in acid solution. Liquid chromatography-ion trap mass spectrometry (LC/MS(n)) was used to study the degradation of these spiramycin derivatives in simulated gastric fluid at 37 degrees C. All derivatives degraded by first-order reactions for which rate constants (k) and half-lives (t(1/2)) were calculated. Acyl groups at position 3 had less effect on acid-stability of spiramycin derivatives than acyl groups at position 4''. The introduction of 4''-acyl groups enhanced the acid-stability of spiramycin derivatives and altered the degradation pathway in simulated gastric fluid such that loss of forosamine rather than loss of mycarose becomes the major degradation pathway.

  11. Bicyclic alpha,omega-dicarboxylic acid derivatives from a colonial tunicate of the family Polyclinidae.

    PubMed

    Bao, Baoquan; Dang, Hung The; Zhang, Ping; Hong, Jongki; Lee, Chong-O; Cho, Hee Young; Jung, Jee H

    2009-11-01

    In the course of our search for bioactive metabolites from a colonial tunicate of the family Polyclinidae, six new (1-6) cyclic fatty acid derivatives were isolated. Their planar structures were established on the basis of NMR and MS spectroscopic analyses. The relative configuration was determined by NOESY experiment. Compounds 1-6 represent a fused bicyclic skeleton possibly derived from alpha,omega-dicarboxylic acids such as eicosanedioic acid or docosanedioic acid via a Diels-Alder type of cyclization. Compounds 1-4 and 6 showed mild cytotoxicity against a panel of five human solid tumor cell lines.

  12. Actions of derivatives of lysergic acid on the heart of venus mercenaria

    PubMed Central

    Wright, Anne McCoy; Moorhead, Merilyn; Welsh, J. H.

    1962-01-01

    5-Hydroxytryptamine and a number of (+)-lysergic acid derivatives have been tested on the heart of Venus mercenaria. One group of derivatives was found to increase the amplitude and frequency of heart beat in a manner much like 5-hydroxytryptamine. It included the monoethylamide, diethylamide, propanolamide (ergometrine), butanolamide (methylergometrine) and certain peptide derivatives of lysergic acid without substituents in positions 1 or 2. Of these, lysergic acid diethylamide was the most active. Given sufficient time (up to 4 hr), as little as 10 ml. of 10-16 M lysergic acid diethylamide produced a maximum increase in amplitude and frequency in about one-half of the 80 hearts on which it was tested. Its action was very slowly reversed by washing, as was true of all lysergic acid derivatives. A second group of lysergic acid derivatives, substituted in positions 1 or 2, had weak excitor action, if any, and specific 5-hydroxytryptamine blocking action. This group consisted of 1-methyl-, 1-acetyl-, and 2-bromo-lysergic acid diethylamide and 1-methyllysergic acid butanolamide (methysergide). Of these, the last showed least signs of excitor action, usually none up to 10-4 M, and it blocked 5-hydroxytryptamine in a molar ratio of about one to one. PMID:14008412

  13. Technetium radiodiagnostic fatty acids derived from bisamide bisthiol ligands

    DOEpatents

    Jones, Alun G.; Lister-James, John; Davison, Alan

    1988-05-24

    A bisamide-bisthiol ligand containing fatty acid substituted thiol useful for producing Tc-labelled radiodiagnostic imaging agents is described. The ligand forms a complex with the radionuclide .sup.99m Tc suitable for administration as a radiopharmaceutical to obtain images of the heart for diagnosis of myocardial disfunction.

  14. Spectroscopic studies on the interaction of cinnamic acid and its hydroxyl derivatives with human serum albumin

    NASA Astrophysics Data System (ADS)

    Min, Jiang; Meng-Xia, Xie; Dong, Zheng; Yuan, Liu; Xiao-Yu, Li; Xing, Chen

    2004-04-01

    Cinnamic acid and its derivatives possess various biological effects in remedy of many diseases. Interaction of cinnamic acid and its hydroxyl derivatives, p-coumaric acid and caffeic acid, with human serum albumin (HSA), and concomitant changes in its conformation were studied using fluorescence and Fourier transform infrared spectroscopic methods. Fluorescence data revealed the presence of one binding site on HSA for cinnamic acid and its hydroxyl derivatives, and their binding constants ( KA) are caffeic acid> p-coumaric acid> cinnamic acid when Cdrug/ CHSA ranging from 1 to 10. The changes of the secondary structure of HSA after interacting with the three drugs are estimated, respectively by combining the curve-fitting results of amid I and amid III bands. The α-helix structure has a decrease of ≈9, 5 and 3% after HSA interacted with caffeic acid, p-coumaric acid and cinnamic acid, respectively. It was found that the hydroxyls substituted on aromatic ring of the drugs play an important role in the changes of protein's secondary structure. Combining the result of fluorescence quenching and the changes of secondary structure of HSA after interaction with the three drugs, the drug-HSA interaction mode was discussed.

  15. Rhodium-catalyzed asymmetric addition of arylboronic acids to cyclic N-sulfonyl ketimines towards the synthesis of α,α-diaryl-α-amino acid derivatives.

    PubMed

    Takechi, Ryosuke; Nishimura, Takahiro

    2015-05-07

    Rhodium/chiral diene complex-catalyzed asymmetric addition of arylboronic acids to cyclic ketimines having an ester group proceeded to give the corresponding α-amino acid derivatives in high yields with high enantioselectivity. The cyclic amino acid derivative was transformed into a linear α,α-diaryl-substituted α-N-methylamino acid ester.

  16. Platelet-derived Factor Concentrates with Hyaluronic Acid Scaffolds for Treatment of Deep Burn Wounds

    PubMed Central

    Minabe, Toshiharu; Yamakawa, Tomomi; Araki, Jun; Sano, Hitomi; Yoshimura, Kotaro

    2016-01-01

    Summary: A deep burn wound is a critical condition that generally necessitates vascularized tissue coverage. We performed the injection of platelet-derived factor concentrates combined with non–cross-linked hyaluronic acid scaffolds for 2 patients with critical burn wounds with bone and tendon exposure and achieved successful healing. Hyaluronic acid was considered to have served as a controlled-release carrier of platelet-derived factors, being clinically effective for the treatment of deep burn wounds. PMID:27826482

  17. Cyclooxygenase-derived proangiogenic metabolites of epoxyeicosatrienoic acids.

    PubMed

    Rand, Amy A; Barnych, Bogdan; Morisseau, Christophe; Cajka, Tomas; Lee, Kin Sing Stephen; Panigrahy, Dipak; Hammock, Bruce D

    2017-04-25

    Arachidonic acid (ARA) is metabolized by cyclooxygenase (COX) and cytochrome P450 to produce proangiogenic metabolites. Specifically, epoxyeicosatrienoic acids (EETs) produced from the P450 pathway are angiogenic, inducing cancer tumor growth. A previous study showed that inhibiting soluble epoxide hydrolase (sEH) increased EET concentration and mildly promoted tumor growth. However, inhibiting both sEH and COX led to a dramatic decrease in tumor growth, suggesting that the contribution of EETs to angiogenesis and subsequent tumor growth may be attributed to downstream metabolites formed by COX. This study explores the fate of EETs with COX, the angiogenic activity of the primary metabolites formed, and their subsequent hydrolysis by sEH and microsomal EH. Three EET regioisomers were found to be substrates for COX, based on oxygen consumption and product formation. EET substrate preference for both COX-1 and COX-2 were estimated as 8,9-EET > 5,6-EET > 11,12-EET, whereas 14,15-EET was inactive. The structure of two major products formed from 8,9-EET in this COX pathway were confirmed by chemical synthesis: ct-8,9-epoxy-11-hydroxy-eicosatrienoic acid (ct-8,9-E-11-HET) and ct-8,9-epoxy-15-hydroxy-eicosatrienoic acid (ct-8,9-E-15-HET). ct-8,9-E-11-HET and ct-8,9-E-15-HET are further metabolized by sEH, with ct-8,9-E-11-HET being hydrolyzed much more slowly. Using an s.c. Matrigel assay, we showed that ct-8,9-E-11-HET is proangiogenic, whereas ct-8,9-E-15-HET is not active. This study identifies a functional link between EETs and COX and identifies ct-8,9-E-11-HET as an angiogenic lipid, suggesting a physiological role for COX metabolites of EETs.

  18. Mathematical models of antisickling activities of benzoic acid derivatives on red blood cells of sicklers.

    PubMed

    Fasanmade, A A; Olaniyi, A A; Ab-Yisak, W

    1994-12-01

    A classical drug design technique based on the quantitative structure--activity relationship is applied to a series of synthetic benzoic acid derivatives. Some of the active derivatives tested include; p-toluic acid, p-dimethyl-amino benzoic acid, p-fluorobenzoic acid, p-chlorobenzoic acid, m-chlorobenzoic acid, p-bromobenzoic acid, p-nitrobenzoic acid, and p-iodobenzoic acid. The Hansch lipophilicity, pi, and the Hammett electronic parameters; sigma, were found to predict activities of the agents on the reversal of sickle-shaped deoxygenated sickle red blood cell to normal morphology. A series of equations correlating the biological activities with the structure of the tested compounds were analysed using multiple regression techniques. The most applicable of the equations was found to be; Log BR = -A sigma + B pi--C pi 2 + K Interpretation of this equation in terms of the biological action of the drugs on red blood cells was attempted. In designing a potent antisickling agent, the benzoic acid should have strong electron donating group(s) attached to the benzene ring and should be made averagely lipophilic to satisfy the relationship derived in this study.

  19. Critical micellar concentrations of keto derivatives of selected bile acids: thermodynamic functions of micelle formation.

    PubMed

    Posa, Mihalj; Kevresan, Slavko; Mikov, Momir; Cirin-Novta, Vera; Kuhajda, Ksenija

    2008-07-15

    The knowledge of the process of formation of molecular aggregates of bile acids in aqueous media and of the corresponding critical micellar concentrations (CMCs) is of great significance because of the biological importance of these compounds and their pharmacological applications. In view of this, the present study is concerned with the determination of CMCs of cholic and chenodeoxycholic acids and their keto derivatives at different temperatures with the aim to calculate the standard thermodynamic functions of micelle formation. Based on the molecular descriptors for tested compounds and entropy of micelle formation, the method of principal component analysis (PCA) allowed grouping of the behavior of tested molecules at 30, 50 and 70 degrees C. To one group belong cholic acid and its keto derivatives, the other group consisting of chenodeoxycholic and deoxycholic acids and their keto derivatives. For each group, the derived multiple linear regression equations of the entropy dependence on temperature contains different independent variables. A main difference between the two groups of tested bile acids is in the energy of dipole-dipole interaction, which appears to be temperature dependent, and in the case of the latter group comes into play as an independent variable already in the regression equation derived for 30 degrees C. The most remarkable changes of the descriptors with temperature were observed in the group of cholic acid and its derivatives.

  20. Pd(II)-catalysed meta-C-H functionalizations of benzoic acid derivatives.

    PubMed

    Li, Shangda; Cai, Lei; Ji, Huafang; Yang, Long; Li, Gang

    2016-01-27

    Benzoic acids are highly important structural motifs in drug molecules and natural products. Selective C-H bond functionalization of benzoic acids will provide synthetically useful tools for step-economical organic synthesis. Although direct ortho-C-H functionalizations of benzoic acids or their derivatives have been intensely studied, the ability to activate meta-C-H bond of benzoic acids or their derivatives in a general manner via transition-metal catalysis has been largely unsuccessful. Although chelation-assisted meta-C-H functionalization of electron-rich arenes was reported, chelation-assisted meta-C-H activation of electron-poor arenes such as benzoic acid derivatives remains a formidable challenge. Herein, we report a general protocol for meta-C-H olefination of benzoic acid derivatives using a nitrile-based sulfonamide template. A broad range of benzoic acid derivatives are meta-selectively olefinated using molecular oxygen as the terminal oxidant. The meta-C-H acetoxylation, product of which is further transformed at the meta-position, is also reported.

  1. Pd(II)-catalysed meta-C–H functionalizations of benzoic acid derivatives

    PubMed Central

    Li, Shangda; Cai, Lei; Ji, Huafang; Yang, Long; Li, Gang

    2016-01-01

    Benzoic acids are highly important structural motifs in drug molecules and natural products. Selective C–H bond functionalization of benzoic acids will provide synthetically useful tools for step-economical organic synthesis. Although direct ortho-C–H functionalizations of benzoic acids or their derivatives have been intensely studied, the ability to activate meta-C–H bond of benzoic acids or their derivatives in a general manner via transition-metal catalysis has been largely unsuccessful. Although chelation-assisted meta-C–H functionalization of electron-rich arenes was reported, chelation-assisted meta-C–H activation of electron-poor arenes such as benzoic acid derivatives remains a formidable challenge. Herein, we report a general protocol for meta-C–H olefination of benzoic acid derivatives using a nitrile-based sulfonamide template. A broad range of benzoic acid derivatives are meta-selectively olefinated using molecular oxygen as the terminal oxidant. The meta-C–H acetoxylation, product of which is further transformed at the meta-position, is also reported. PMID:26813919

  2. Anti-Clostridium difficile potential of tetramic acid derivatives from Pseudomonas aeruginosa quorum-sensing autoinducers.

    PubMed

    Ueda, Chihiro; Tateda, Kazuhiro; Horikawa, Manabu; Kimura, Soichiro; Ishii, Yoshikazu; Nomura, Kaoru; Yamada, Kanako; Suematsu, Takashi; Inoue, Yasuhisa; Ishiguro, Masaji; Miyairi, Shinichi; Yamaguchi, Keizo

    2010-02-01

    We have examined the potential bactericidal activities of several tetramic acids derived from Pseudomonas autoinducers against Clostridium difficile, a cause of antibiotic-associated pseudomembranous colitis. Clinical isolates of C. difficile (n=4) were incubated in broth with a chemically synthesized Pseudomonas autoinducer and its tetramic acid derivatives. The structure-activity relationship and the mechanisms of action were examined by a time-killing assay and by determination of the morphological/staining characteristics. The use of some tetramic acids derived from N-3-oxododecanoyl L-homoserine lactone resulted in more than 3-log reductions in the viability of C. difficile within 30 min at 30 microM. The outer membrane was suggested to be one of the targets for the bactericidal activity of tetramic acid, because disturbance of the bacterial outer surface was demonstrated by alteration of the Gram-staining characteristic and electron microscopy. The data for the tetramic acid derivatives demonstrate that the keto-enol structure and the length of the acyl side chain of tetramic acid may be essential for the antibacterial activity of this molecule. These results suggest the potential for tetramic acid derivatives to be novel agents with activity against C. difficile.

  3. Monoterpene-based chiral β-amino acid derivatives prepared from natural sources: syntheses and applications.

    PubMed

    Szakonyi, Zsolt; Fülöp, Ferenc

    2011-08-01

    Natural monoterpenes have proved to be good starting materials for the synthesis of β-amino acid derivatives. In the past decade, a number of well-known synthetic procedures have been applied for the preparation of monoterpene-based β-amino acid derivatives, e.g. from β-lactams via the 1,2-dipolar cycloaddition of chlorosulfonyl isocyanate to commercial or readily available monoterpenes [e.g. (+)- and (-)-α- or δ-pinene, (+)-3- and 2-carene, (+)- and (-)-apopinene], the conjugate addition of amides to monoterpene-based α,β-unsaturated esters or the transformations of (-)-cis-pinonoic acid prepared by the oxidative cleavage of (+)- and (-)-verbenone. β-Amino acid derivatives are excellent building blocks for versatile transformations, e.g. multicomponent reactions resulting in β-lactams, syntheses of 1,3-heterocycles and diaminopyrimidine derivatives or the formation of peptides containing an H12 helix. 1,3-Amino alcohol derivatives prepared from β-amino esters have been applied as chiral catalysts in enantioselective transformations. Several of these compounds are of noteworthy pharmacological importance, such as tyrosine kinase Axl inhibitor diaminopyrimidine-coupled β-aminocarboxamides, MDR inhibitor thiourea derivatives of β-amino esters or 2-imino-1,3-oxazines, which exhibit marked growth inhibitory activity on multiple cancer cell lines. The present review summarizes recent developments relating to the syntheses, applications and pharmaceutical importance of monoterpene-based β-amino acids and their derivatives.

  4. Simultaneous determination of acetylsalicylic and salicylic acids by first derivative spectrometry in pharmaceutical preparations

    NASA Astrophysics Data System (ADS)

    Rogić, Dunja

    1993-03-01

    A multicomponent first derivative UV spectrometric procedure for determination of acetylsalicylic acid (aspirin) and salicylic acid in the solution containing 1 % (w/v) of citric acid in some pharmaceutical preparations is presented. The method is based on the use of the first derivative minimum spectrometric measurements at 286 nm for aspirin and at 318 nm for salicylic acid. Four kinds of cmmercial Aspirin tablets were assayed without a long pretreatment of the pharmaceuticals from the tablet additives. Beer's law is obeyed from 13.62-68.1 μg ml -1 of aspirin and from 2.723-13.616 μg ml -1 of salicylic acid. Detection limits at the 0.05 level of significance were calculated to be 1.24 and 0.25 μg ml -1 with relative standard deviations of 1.09 % and 1.2 % of aspirin and salicylic acid, respectively.

  5. Formation of dopamine adducts derived from brain polyunsaturated fatty acids: mechanism for Parkinson disease.

    PubMed

    Liu, Xuebo; Yamada, Naruomi; Maruyama, Wakako; Osawa, Toshihiko

    2008-12-12

    Oxidative stress appears to be directly involved in the pathogenesis of the neurodegeneration of dopaminergic systems in Parkinson disease. In this study, we formed four dopamine modification adducts derived from docosahexaenoic acid (C22:6/omega-3) and arachidonic acid (C18:4/omega-6), which are known as the major polyunsaturated fatty acids in the brain. Upon incubation of dopamine with fatty acid hydroperoxides and an in vivo experiment using rat brain tissue, all four dopamine adducts were detected. Furthermore, hexanoyl dopamine (HED), an arachidonic acid-derived adduct, caused severe cytotoxicity in human dopaminergic neuroblastoma SH-SY5Y cells, whereas the other adducts were only slightly affected. The HED-induced cell death was found to include apoptosis, which also seems to be mediated by reactive oxygen species generation and mitochondrial abnormality. Additionally, the experiments using monoamine transporter inhibitor and mouse embryonic fibroblast NIH-3T3 cells that lack the monoamine transporter indicate that the HED-induced cytotoxicity might specially occur in the neuronal cells. These data suggest that the formation of the docosahexaenoic acid- and arachidonic acid-derived dopamine adducts in vitro and in vivo, and HED, the arachidonic acid-derived dopamine modification adduct, which caused selective cytotoxicity of neuronal cells, may indicate a novel mechanism responsible for the pathogenesis in Parkinson disease.

  6. Mass spectral analysis of C3 and C4 aliphatic amino acid derivatives.

    NASA Technical Reports Server (NTRS)

    Lawless, J. G.; Chadha, M. S.

    1971-01-01

    Diagnostic criteria are obtained for the distinction of alpha, beta, gamma, and N-methyl isomers of the C3 and C4 aliphatic amino acids, using mass spectral analysis of the derivatives of these acids. The use of deuterium labeling has helped in the understanding of certain fragmentation pathways.

  7. Acid-catalyzed Grob fragmentation reactions of acetonides derived from terpenes.

    PubMed

    Barluenga, José; Alvarez-Pérez, Mónica; Wuerth, Kirsten; Rodríguez, Félix; Fañanás, Francisco J

    2003-03-20

    [reaction: see text] Acetonides derived from different terpenes undergo Grob fragmentation by treatment with a catalytic amount of acid, triflic acid, or boron trifluoride, giving aldehydes containing a cyclopropane or cyclobutane ring with good yields and complete diastereoselectivity. The structure and the stereochemistry of the starting acetonide have a crucial influence on the reaction course.

  8. Biodiesel Derived from a Source Enriched in Palmitoleic Acid, Macadamia Nut Oil

    USDA-ARS?s Scientific Manuscript database

    Biodiesel is an alternative diesel fuel commonly produced from commodity vegetable oils such as palm, rapeseeed (canola) and soybean. These oils generally have fatty acid profiles that vary within the range of C16 and C18 fatty acids. Thus, the biodiesel fuels derived from these oils possess the c...

  9. Chiral BINOL-derived phosphoric acids: privileged Brønsted acid organocatalysts for C-C bond formation reactions.

    PubMed

    Zamfir, Alexandru; Schenker, Sebastian; Freund, Matthias; Tsogoeva, Svetlana B

    2010-12-07

    BINOL-derived phosphoric acids have emerged during the last five years as powerful chiral Brønsted acid catalysts in many enantioselective processes. The most successful transformations carried out with chiral BINOL phosphates include C-C bond formation reactions. The recent advances have been reviewed in this article with a focus being placed on hydrocyanations, aldol-type, Mannich, Friedel-Crafts, aza-ene-type, Diels-Alder, as well as cascade and multi-component reactions.

  10. A novel trans-4-hydroxycinnamic acid derivative from Meyer lemon (Citrus meyeri).

    PubMed

    Miyake, Yoshiaki; Ito, Chihiro; Itoigawa, Masataka

    2012-12-15

    Isolation and structural elucidation of a new trans-4-hydroxycinnamic acid derivative from Meyer lemon (Citrus meyeri hort. ex Y. Tanaka) was carried out. The derivative exhibited the antioxidative activity by ORAC (oxygen radical absorbance capacity) assay and was found in the flavedo and alvedo of Meyer lemon peel. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. Diastereodivergent Synthesis of Fluorinated Cyclic β(3)-Amino Acid Derivatives.

    PubMed

    Aparici, Isabel; Guerola, Marta; Dialer, Clemens; Simón-Fuentes, Antonio; Sánchez-Roselló, María; del Pozo, Carlos; Fustero, Santos

    2015-11-06

    The ability of 2-p-tolylbenzyl carbanions to behave as a source of chiral benzylic nucleophiles has been shown in its reaction with fluorinated imines. The process takes place with high levels of stereocontrol, rendering the corresponding amines as single diastereoisomers. Subsequent cross-metathesis followed by intramolecular aza-Michael reaction makes the synthesis of fluorinated homoproline derivatives bearing three stereogenic centers possible. Furthermore, the selectivity of the cyclization process can easily be tuned up in a diastereodivergent manner simply by changing the reaction conditions.

  12. The developmental toxicity of perfluoroalkyl acids and their derivatives.

    PubMed

    Lau, Christopher; Butenhoff, John L; Rogers, John M

    2004-07-15

    Perfluoroalkyl acids such as perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) have applications in numerous industrial and consumer products. Although the toxicology of some of these compounds has been investigated in the past, the widespread prevalence of PFOS and PFOA in humans, as demonstrated in recent bio-monitoring studies, has drawn considerable interest from the public and regulatory agencies as well as renewed efforts to better understand the hazards that may be inherent in these compounds. This review provides a brief overview of the perfluoroalkyl chemicals and a summary of the available information on the developmental toxicity of the eight-carbon compounds, PFOS and PFOA. Although the teratological potentials of some of these chemicals had been studied in the past and the findings were generally unremarkable, results from recent postnatal studies on developmental and reproductive indices have prompted consideration of their relevance to human health risk. Based on current understanding of the developmental effects of PFOS and PFOA in rodents, several avenues of research are suggested that would further support the risk assessment of these perfluorinated organic chemicals.

  13. On the peroxyl scavenging activity of hydroxycinnamic acid derivatives: mechanisms, kinetics, and importance of the acid-base equilibrium.

    PubMed

    León-Carmona, Jorge Rafael; Alvarez-Idaboy, Juan Raúl; Galano, Annia

    2012-09-28

    The peroxyl radical scavenging activity of four hydroxycinnamic acid derivatives (HCAD) has been studied in non-polar and aqueous solutions, using the density functional theory. The studied HCAD are: ferulic acid (4-hydroxy-3-methoxycinnamic acid), p-coumaric acid (trans-4-hydroxycinnamic acid), caffeic acid (3,4-dihydroxycinnamic acid), and dihydrocaffeic acid (3-(3,4-dihydroxyphenyl)-2-propionic acid). It was found that the polarity of the environment plays an important role in the relative efficiency of these compounds as peroxyl scavengers. It was also found that in aqueous solution the pH is a key factor for the overall reactivity of HCAD towards peroxyl radicals, for their relative antioxidant capacity, and for the relative importance of the different mechanisms of reaction. The H transfer from the phenolic OH has been identified as the main mechanism of reaction in non-polar media and in aqueous solution at acid pHs. On the other hand, the single electron transfer mechanism from the phenoxide anion is proposed to be the one contributing the most to the overall peroxyl scavenging activity of HCAD in aqueous solution at physiological pH (7.4). This process is also predicted to be a key factor in the reactivity of these compounds towards a large variety of free radicals.

  14. Synthesis and Bioactivity of (R)-Ricinoleic Acid Derivatives: A Review.

    PubMed

    Pabiś, Sylwia; Kula, Józef

    2016-01-01

    (R)-Ricinoleic acid (RA) [(12R,9Z)-hydroxyoctadecenoic acid], the main compound of castor seed oil, because of its unusual structure readily undergoes multi-directional chemical and biochemical transformations to produce derivatives with the retained carbon skeleton or with its degradation. Many of these are of high biological activity, as documented by an in vitro study, and possess therapeutic potential. This review article provides an overview of the recent developments in the area of synthesis of RA based compounds with anticancer and antimicrobial activities. Moreover, the antiinflammatory and analgesic properties of some ricinoleic acid derivatives are also highlighted.

  15. HYPERSENSITIVITY TO PENICILLENIC ACID DERIVATIVES IN HUMAN BEINGS WITH PENICILLIN ALLERGY

    PubMed Central

    Parker, Charles W.; Shapiro, Jack; Kern, Milton; Eisen, Herman N.

    1962-01-01

    Multifunctional derivatives of penicillenic acid are effective elicitors of wheal-and-erythema skin responses in humans allergic to penicillin. Of the effective derivatives, penicilloyl-polylysines are particularly attractive as skin test reagents because they appear to be incapable of inducing antibody formation. The skin responses are specifically inhibitable in most instances by homologous unifunctional haptens. The penicillenic acid derivatives which appear to be determinants of human allergic reactions to penicillin are: penicilloyl, penicillenate, and groups of the penamaldate-penilloaldehyde type. Of these, the most significant appears to be the penicilloyl-lysyl determinant. PMID:14483916

  16. Synthesis of novel oleanolic acid and ursolic acid in C-28 position derivatives as potential anticancer agents.

    PubMed

    Tian, Tian; Liu, Xinyu; Lee, Eung-Seok; Sun, Jingyang; Feng, Zhonghua; Zhao, Longxuan; Zhao, Chunhui

    2017-04-01

    A series of nitrogen-containing derivatives of oleanolic acid and ursolic acid were prepared by a modification at C-28 position via esterification with 2-hydroxyacetic acid followed by amidation with amines, such as piperazine, N-methylpiperazine, and alkane-1, 2-diamines, alkane-1, 4-diamines, alkane-1, 6-diamines. In vitro antiproliferative activities of the compounds prepared towards MCF-7, Hela and A549 cell lines were evaluated by a MTT method to show that OA-5a, OA-5b, OA-5c and UA-5a showed somewhat improved antiproliferative activities against MCF-7, Hela and A549 cells comparing to that of the positive control, gefitinib.

  17. Decay resistance of wood treated with boric acid and tall oil derivates.

    PubMed

    Temiz, Ali; Alfredsen, Gry; Eikenes, Morten; Terziev, Nasko

    2008-05-01

    In this study, the effect of two boric acid concentrations (1% and 2%) and four derivates of tall oil with varying chemical composition were tested separately and in combination. The tall oil derivates were chosen in a way that they consist of different amounts of free fatty, resin acids and neutral compounds. Decay tests using two brown rot fungi (Postia placenta and Coniophora puteana) were performed on both unleached and leached test samples. Boric acid showed a low weight loss in test samples when exposed to fungal decay before leaching, but no effect after leaching. The tall oil derivates gave better efficacy against decay fungi compared to control, but are not within the range of the efficacy needed for a wood preservative. Double impregnation with boric acid and tall oil derivates gave synergistic effects for several of the double treatments both in unleached and leached samples. In the unleached samples the double treatment gave a better efficacy against decay fungi than tall oil alone. In leached samples a better efficacy against brown rot fungi were achieved than in samples with boron alone and a nearly similar or better efficacy than for tall oil alone. Boric acid at 2% concentration combined with the tall oil derivate consisting of 90% free resin acids (TO-III) showed the best performance against the two decay fungi with a weight loss less than 3% after a modified pure culture test.

  18. Synthesis and preliminary biological evaluations of (+)-isocampholenic acid-derived amides.

    PubMed

    Grošelj, Uroš; Golobič, Amalija; Knez, Damijan; Hrast, Martina; Gobec, Stanislav; Ričko, Sebastijan; Svete, Jurij

    2016-08-01

    The synthesis of two novel (+)-isocampholenic acid-derived amines has been realized starting from commercially available (1S)-(+)-10-camphorsulfonic acid. The novel amines as well as (+)-isocampholenic acid have been used as building blocks in the construction of a library of amides using various aliphatic, aromatic, and amino acid-derived coupling partners using BPC and CDI as activating agents. Amide derivatives have been assayed against several enzymes that hold potential for the development of new drugs to battle bacterial infections and Alzheimer's disease. Compounds 20c and 20e showed promising selective sub-micromolar inhibition of human butyrylcholinesterase [Formula: see text] ([Formula: see text] values [Formula: see text] and [Formula: see text], respectively).

  19. Hydroxycinnamic Acid Derivatives Obtained from a Commercial Crataegus Extract and from Authentic Crataegus spp.

    PubMed

    Kuczkowiak, Ulrich; Petereit, Frank; Nahrstedt, Adolf

    2014-01-01

    Eleven hydroxycinnamic acid derivatives were isolated from a 70% methanolic Crataegus extract (Crataegi folium cum flore) and partly verified and quantified for individual Crataegus species (C. laevigata, C. monogyna, C. nigra, C. pentagyna) by HPLC: 3-O-(E)-p-coumaroylquinic acid (1), 5-O-(E)-p-coumaroyl-quinic acid (2), 4-O-(E)-p-coumaroylquinic acid (3), 3-O-(E)-caffeoylquinic acid (4), 4-O-(E)-caffeoylquinic acid (5), 5-O-(E)-caffeoylquinic acid (6), 3,5-di-O-(E)-caffeoylquinic acid (7), 4,5-di-O-(E)-caffeoylquinic acid (8), (-)-2-O-(E)-caffeoyl-L-threonic acid (9), (-)-4-O-(E)-caffeoyl-L-threonic acid (10), and (-)-4-O-(E)-p-coumaroyl-L-threonic acid (11). Further, (-)-2-O-(E)-caffeoyl-D-malic acid (12) was isolated from C. submollis and also identified for C. pentagyna and C. nigra by co-chromatography. The isolates 10 and 11 were not found in the authentic fresh specimen, indicating that they may be formed during extraction by acyl migration from the 2-O-acylderivatives. Also, 9 and 11 are described here for the first time. All structures were assigned on the basis of their spectroscopic data ((1)H-, (13)C-NMR, MS, optical rotation).

  20. Hydroxycinnamic Acid Derivatives Obtained from a Commercial Crataegus Extract and from Authentic Crataegus spp.§

    PubMed Central

    Kuczkowiak, Ulrich; Petereit, Frank; Nahrstedt, Adolf

    2014-01-01

    Abstract Eleven hydroxycinnamic acid derivatives were isolated from a 70% methanolic Crataegus extract (Crataegi folium cum flore) and partly verified and quantified for individual Crataegus species (C. laevigata, C. monogyna, C. nigra, C. pentagyna) by HPLC: 3-O-(E)-p-coumaroylquinic acid (1), 5-O-(E)-p-coumaroyl-quinic acid (2), 4-O-(E)-p-coumaroylquinic acid (3), 3-O-(E)-caffeoylquinic acid (4), 4-O-(E)-caffeoylquinic acid (5), 5-O-(E)-caffeoylquinic acid (6), 3,5-di-O-(E)-caffeoylquinic acid (7), 4,5-di-O-(E)-caffeoylquinic acid (8), (-)-2-O-(E)-caffeoyl-L-threonic acid (9), (-)-4-O-(E)-caffeoyl-L-threonic acid (10), and (-)-4-O-(E)-p-coumaroyl-L-threonic acid (11). Further, (-)-2-O-(E)-caffeoyl-D-malic acid (12) was isolated from C. submollis and also identified for C. pentagyna and C. nigra by co-chromatography. The isolates 10 and 11 were not found in the authentic fresh specimen, indicating that they may be formed during extraction by acyl migration from the 2-O-acylderivatives. Also, 9 and 11 are described here for the first time. All structures were assigned on the basis of their spectroscopic data (1H-, 13C-NMR, MS, optical rotation). PMID:26171328

  1. Formation of taste-active amino acids, amino acid derivatives and peptides in food fermentations - A review.

    PubMed

    Zhao, Cindy J; Schieber, Andreas; Gänzle, Michael G

    2016-11-01

    Fermented foods are valued for their rich and complex odour and taste. The metabolic activity of food-fermenting microorganisms determines food quality and generates odour and taste compounds. This communication reviews the formation of taste-active amino acids, amino acid derivatives and peptides in food fermentations. Pathways of the generation of taste compounds are presented for soy sauce, cheese, fermented meats, and bread. Proteolysis or autolysis during food fermentations generates taste-active amino acids and peptides; peptides derived from proteolysis particularly impart umami taste (e.g. α-glutamyl peptides) or bitter taste (e.g. hydrophobic peptides containing proline). Taste active peptide derivatives include pyroglutamyl peptides, γ-glutamyl peptides, and succinyl- or lactoyl amino acids. The influence of fermentation microbiota on proteolysis, and peptide hydrolysis, and the metabolism of glutamate and arginine is well understood, however, the understanding of microbial metabolic activities related to the formation of taste-active peptide derivatives is incomplete. Improved knowledge of the interactions between taste-active compounds will enable the development of novel fermentation strategies to develop tastier, less bitter, and low-salt food products, and may provide novel and "clean label" ingredients to improve the taste of other food products. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Tolerance of the nanocellulose-producing bacterium Gluconacetobacter xylinus to lignocellulose-derived acids and aldehydes.

    PubMed

    Zhang, Shuo; Winestrand, Sandra; Chen, Lin; Li, Dengxin; Jönsson, Leif J; Hong, Feng

    2014-10-08

    Lignocellulosic biomass serves as a potential alternative feedstock for production of bacterial nanocellulose (BNC), a high-value-added product of bacteria such as Gluconacetobacter xylinus. The tolerance of G. xylinus to lignocellulose-derived inhibitors (formic acid, acetic acid, levulinic acid, furfural, and 5-hydroxymethylfurfural) was investigated. Whereas 100 mM formic acid completely suppressed the metabolism of G. xylinus, 250 mM of either acetic acid or levulinic acid still allowed glucose metabolism and BNC production to occur. Complete suppression of glucose utilization and BNC production was observed after inclusion of 20 and 30 mM furfural and 5-hydroxymethylfurfural, respectively. The bacterium oxidized furfural and 5-hydroxymethylfurfural to furoic acid and 5-hydroxymethyl-2-furoic acid, respectively. The highest yields observed were 88% for furoic acid/furfural and 76% for 5-hydroxymethyl-2-furoic acid/5-hydroxymethylfurfural. These results are the first demonstration of the capability of G. xylinus to tolerate lignocellulose-derived inhibitors and to convert furan aldehydes.

  3. Identification and quantitation of new glutamic acid derivatives in soy sauce by UPLC/MS/MS.

    PubMed

    Frerot, Eric; Chen, Ting

    2013-10-01

    Glutamic acid is an abundant amino acid that lends a characteristic umami taste to foods. In fermented foods, glutamic acid can be found as a free amino acid formed by proteolysis or as a non-proteolytic derivative formed by microorganisms. The aim of the present study was to identify different structures of glutamic acid derivatives in a typical fermented protein-based food product, soy sauce. An acidic fraction was prepared with anion-exchange solid-phase extraction (SPE) and analyzed by UPLC/MS/MS and UPLC/TOF-MS. α-Glutamyl, γ-glutamyl, and pyroglutamyl dipeptides, as well as lactoyl amino acids, were identified in the acidic fraction of soy sauce. They were chemically synthesized for confirmation of their occurrence and quantified in the selected reaction monitoring (SRM) mode. Pyroglutamyl dipeptides accounted for 770 mg/kg of soy sauce, followed by lactoyl amino acids (135 mg/kg) and γ-glutamyl dipeptides (70 mg/kg). In addition, N-succinoylglutamic acid was identified for the first time in food as a minor compound in soy sauce (5 mg/kg). Copyright © 2013 Verlag Helvetica Chimica Acta AG, Zürich.

  4. A biosynthetic pathway for a prominent class of microbiota-derived bile acids

    PubMed Central

    Devlin, A. Sloan; Fischbach, Michael A.

    2015-01-01

    The gut bile acid pool is millimolar in concentration, varies widely in composition among individuals, and is linked to metabolic disease and cancer. Although these molecules derive almost exclusively from the microbiota, remarkably little is known about which bacterial species and genes are responsible for their biosynthesis. Here, we report a biosynthetic pathway for the second most abundant class in the gut, iso (3β-hydroxy) bile acids, whose levels exceed 300 µM in some humans and are absent in others. We show, for the first time, that iso bile acids are produced by Ruminococcus gnavus, a far more abundant commensal than previously known producers; and that the iso bile acid pathway detoxifies deoxycholic acid, favoring the growth of the keystone genus Bacteroides. By revealing the biosynthetic genes for an abundant class of bile acids, our work sets the stage for predicting and rationally altering the composition of the bile acid pool. PMID:26192599

  5. Microbial production of amino acids and derived chemicals: synthetic biology approaches to strain development.

    PubMed

    Wendisch, Volker F

    2014-12-01

    Amino acids are produced at the multi-million-ton-scale with fermentative production of l-glutamate and l-lysine alone being estimated to amount to more than five million tons in the year 2013. Metabolic engineering constantly improves productivities of amino acid producing strains, mainly Corynebacterium glutamicum and Escherichia coli strains. Classical mutagenesis and screening have been accelerated by combination with intracellular metabolite sensing. Synthetic biology approaches have allowed access to new carbon sources to realize a flexible feedstock concept. Moreover, new pathways for amino acid production as well as fermentative production of non-native compounds derived from amino acids or their metabolic precursors were developed. These include dipeptides, α,ω-diamines, α,ω-diacids, keto acids, acetylated amino acids and ω-amino acids.

  6. New hydroxamic acid derivatives of fluoroquinolones: synthesis and evaluation of antibacterial and anticancer properties.

    PubMed

    Rajulu, Gavara Govinda; Bhojya Naik, Halehatty Seephya; Viswanadhan, Abhilash; Thiruvengadam, Jayaraman; Rajesh, Kondodiyil; Ganesh, Sambasivam; Jagadheshan, Hiriyan; Kesavan, Poonimangadu Koppolu

    2014-01-01

    A series of new hydroxamic acid derivatives (6a-f) at C-3 position of fluoroquinolones were designed and synthesized through multistep synthesis. The design concept involved replacement of the 3-carboxylic acid in fluoquinolones with hydroxamic acid as an acid mimicking group. The synthetic work employed in this work provides a good example for the synthesis of pure hydroxamic acid based fluoroquinolones. The synthesized compounds were characterized by (1)H-NMR, electrospray ionization (ESI)-MS and IR. The new compounds were tested for their in vitro antimicrobial and anti-proliferative activity. Out of the six derivatives, compound 6e exhibited moderate antibacterial activity by inhibiting the growth of Escherichia coli and Klebsiella pneumoniae (MIC: 4.00-8.00 µg/mL). Compounds 6b and 6f displayed good growth inhibition against A549 Lung adenocarcinoma and HCT-116 Colon carcinoma cell lines.

  7. A biosynthetic pathway for a prominent class of microbiota-derived bile acids.

    PubMed

    Devlin, A Sloan; Fischbach, Michael A

    2015-09-01

    The gut bile acid pool is millimolar in concentration, varies widely in composition among individuals and is linked to metabolic disease and cancer. Although these molecules are derived almost exclusively from the microbiota, remarkably little is known about which bacterial species and genes are responsible for their biosynthesis. Here we report a biosynthetic pathway for the second most abundant class in the gut, 3β-hydroxy(iso)-bile acids, whose levels exceed 300 μM in some humans and are absent in others. We show, for the first time, that iso-bile acids are produced by Ruminococcus gnavus, a far more abundant commensal than previously known producers, and that the iso-bile acid pathway detoxifies deoxycholic acid and thus favors the growth of the keystone genus Bacteroides. By revealing the biosynthetic genes for an abundant class of bile acids, our work sets the stage for predicting and rationally altering the composition of the bile acid pool.

  8. Synthesis and cytotoxicity of triterpenoids derived from betulin and betulinic acid via click chemistry.

    PubMed

    Shi, Wei; Tang, Ning; Yan, Wei-Dong

    2015-01-01

    In this study, a series of triazole substituted betulin and betulinic acid derivatives was designed and synthesized via click chemistry at C-30 position. Eighteen target compounds were evaluated in vitro for their antitumor activities against leukemia cell-line HL-60. Seventeen compounds have not reported before. The cytotoxic experiment showed that most of betulinic acid derived triazoles have higher cytotoxic profile than betulinic acid. Among them, compound 30-[4-(4-fluorophenyl)-1H-1,2,3-triazol-1-yl] betulinic acid (7b) showed the best IC50 value (1.3 μM) against leukemia cell-line HL-60 (eight- to ninefold higher potency than betulinic acid).

  9. Discovery of a novel activator of 5-lipoxygenase from an anacardic acid derived compound collection

    PubMed Central

    Wisastra, Rosalina; Kok, Petra A.M; Eleftheriadis, Nikolaos; Baumgartner, Matthew P.; Camacho, Carlos J.; Haisma, Hidde J.; Dekker, Frank J.

    2013-01-01

    Lipoxygenases (LOXs) and cyclooxygenases (COXs) metabolize poly-unsaturated fatty acids into inflammatory signaling molecules. Modulation of the activity of these enzymes may provide new approaches for therapy of inflammatory diseases. In this study, we screened novel anacardic acid derivatives as modulators of human 5-LOX and COX-2 activity. Interestingly, a novel salicylate derivative 23a was identified as a surprisingly potent activator of human 5-LOX. This compound showed both non-competitive activation towards the human 5-LOX activator adenosine triphosphate (ATP) and non-essential mixed type activation against the substrate linoleic acid, while having no effect on the conversion of the substrate arachidonic acid. The kinetic analysis demonstrated a non-essential activation of the linoleic acid conversion with a KA of 8.65 μM, αKA of 0.38 μM and a β value of 1.76. It is also of interest that a comparable derivative 23d showed a mixed type inhibition for linoleic acid conversion. These observations indicate the presence of an allosteric binding site in human 5-LOX distinct from the ATP binding site. The activatory and inhibitory behavior of 23a and 23d on the conversion of linoleic compared to arachidonic acid are rationalized by docking studies, which suggest that the activator 23a stabilizes linoleic acid, whereas the larger inhibitor 23d blocks the enzyme active site. PMID:24231650

  10. Bioconversion of volatile fatty acids derived from waste activated sludge into lipids by Cryptococcus curvatus.

    PubMed

    Liu, Jia; Liu, Jia-Nan; Yuan, Ming; Shen, Zi-Heng; Peng, Kai-Ming; Lu, Li-Jun; Huang, Xiang-Feng

    2016-07-01

    Pure volatile fatty acid (VFA) solution derived from waste activated sludge (WAS) was used to produce microbial lipids as culture medium in this study, which aimed to realize the resource recovery of WAS and provide low-cost feedstock for biodiesel production simultaneously. Cryptococcus curvatus was selected among three oleaginous yeast to produce lipids with VFAs derived from WAS. In batch cultivation, lipid contents increased from 10.2% to 16.8% when carbon to nitrogen ratio increased from about 3.5 to 165 after removal of ammonia nitrogen by struvite precipitation. The lipid content further increased to 39.6% and the biomass increased from 1.56g/L to 4.53g/L after cultivation for five cycles using sequencing batch culture (SBC) strategy. The lipids produced from WAS-derived VFA solution contained nearly 50% of monounsaturated fatty acids, including palmitic acid, heptadecanoic acid, ginkgolic acid, stearic acid, oleic acid, and linoleic acid, which showed the adequacy of biodiesel production. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Astrocyte-derived phosphatidic acid promotes dendritic branching.

    PubMed

    Zhu, Yan-Bing; Gao, Weizhen; Zhang, Yongbo; Jia, Feng; Zhang, Hai-Long; Liu, Ying-Zi; Sun, Xue-Fang; Yin, Yuhua; Yin, Dong-Min

    2016-02-17

    Astrocytes play critical roles in neural circuit formation and function. Recent studies have revealed several secreted and contact-mediated signals from astrocytes which are essential for neurite outgrowth and synapse formation. However, the mechanisms underlying the regulation of dendritic branching by astrocytes remain elusive. Phospholipase D1 (PLD1), which catalyzes the hydrolysis of phosphatidylcholine (PC) to generate phosphatidic acid (PA) and choline, has been implicated in the regulation of neurite outgrowth. Here we showed that knockdown of PLD1 selectively in astrocytes reduced dendritic branching of neurons in neuron-glia mixed culture. Further studies from sandwich-like cocultures and astrocyte conditioned medium suggested that astrocyte PLD1 regulated dendritic branching through secreted signals. We later demonstrated that PA was the key mediator for astrocyte PLD1 to regulate dendritic branching. Moreover, PA itself was sufficient to promote dendritic branching of neurons. Lastly, we showed that PA could activate protein kinase A (PKA) in neurons and promote dendritic branching through PKA signaling. Taken together, our results demonstrate that astrocyte PLD1 and its lipid product PA are essential regulators of dendritic branching in neurons. These results may provide new insight into mechanisms underlying how astrocytes regulate dendrite growth of neurons.

  12. Irbic acid, a dicaffeoylquinic acid derivative from Centella asiatica cell cultures.

    PubMed

    Antognoni, Fabiana; Perellino, Nicoletta Crespi; Crippa, Sergio; Dal Toso, Roberto; Danieli, Bruno; Minghetti, Anacleto; Poli, Ferruccio; Pressi, Giovanna

    2011-10-01

    3,5-O-dicaffeoyl-4-O-malonilquinic acid (1) (irbic acid) has been isolated for the first time from cell cultures of Centella asiatica and till now it has never been reported to be present in the intact plant. Evidence of its structure was obtained by spectroscopic analyses (MS/NMR). Besides 1, cell cultures produce also the known 3,5-O-dicaffeoylquinic acid, chlorogenic acid, and the triferulic acid 2 (4-O-8'/4'-O-8″-didehydrotriferulic acid). Biological activities were evaluated for compound 1, which showed to have a strong radical scavenging capacity, together with a high inhibitory activity on collagenase. This suggests a possible utilization of this substance as a topical agent to reduce the skin ageing process.

  13. Acidity constant determination of novel drug precursor benzothiazolon derivatives including acyl and piperazine moieties

    NASA Astrophysics Data System (ADS)

    Sıdır, İsa; Gülseven Sıdır, Yadigar; Berber, Halil

    2013-07-01

    In this study, protonation and deprotonation behaviors of eight new drug precursor benzothiazolon derivatives in all of acidic and basic scale (super acidic, pH, super basic regions) are analyzed by using UV-visible spectrophotometric technique. Acidity constants (pKa), elucidation of the structure and protonation mechanisms of the studied molecules are obtained. Substituent effect on acidity constant values is discussed. These molecules are protonated from oxygen atom of acetamide group in the keto form. The protonation is found to be considerably contributed by the keto form.

  14. Cinnamic Acid and Its Derivatives: Mechanisms for Prevention and Management of Diabetes and Its Complications

    PubMed Central

    Adisakwattana, Sirichai

    2017-01-01

    With recent insight into the development of dietary supplements and functional foods, search of effective phytochemical compounds and their mechanisms involved in prevention and management of diabetes and its complications are now being assessed. Cinnamic acid and its derivatives occur naturally in high levels of plant-based foods. Among various biological activities, cinnamic acid and its derivatives are associated with a beneficial influence on diabetes and its complications. The aim of the review is to summarize the potential mechanisms of these compounds for prevention and management of diabetes and its complications. Based on several in vitro studies and animal models, cinnamic acid and its derivatives act on different mechanism of actions, including stimulation of insulin secretion, improvement of pancreatic β-cell functionality, inhibition of hepatic gluconeogenesis, enhanced glucose uptake, increased insulin signaling pathway, delay of carbohydrate digestion and glucose absorption, and inhibition of protein glycation and insulin fibrillation. However, due to the limited intestinal absorption being a result of low bioavailability of cinnamic acid and its derivatives, current improvement efforts with entrapping into solid and liquid particles are highlighted. Further human clinical studies are needed to clarify the effects of cinnamic acid and its derivatives in diabetic patients. PMID:28230764

  15. Boronic acid-tethered amphiphilic hyaluronic acid derivative-based nanoassemblies for tumor targeting and penetration.

    PubMed

    Jeong, Jae Young; Hong, Eun-Hye; Lee, Song Yi; Lee, Jae-Young; Song, Jae-Hyoung; Ko, Seung-Hak; Shim, Jae-Seong; Choe, Sunghwa; Kim, Dae-Duk; Ko, Hyun-Jeong; Cho, Hyun-Jong

    2017-02-16

    (3-Aminomethylphenyl)boronic acid (AMPB)-installed hyaluronic acid-ceramide (HACE)-based nanoparticles (NPs), including manassantin B (MB), were fabricated for tumor-targeted delivery. The amine group of AMPB was conjugated to the carboxylic acid group of hyaluronic acid (HA) via amide bond formation, and synthesis was confirmed by spectroscopic methods. HACE-AMPB/MB NPs with a 239-nm mean diameter, narrow size distribution, negative zeta potential, and >90% drug encapsulation efficiency were fabricated. Exposed AMPB in the outer surface of HACE-AMPB NPs (in the aqueous environment) may react with sialic acid of cancer cells. The improved cellular accumulation efficiency, in vitro antitumor efficacy, and tumor penetration efficiency of HACE-AMPB/MB NPs, compared with HACE/MB NPs, in MDA-MB-231 cells (CD44 receptor-positive human breast adenocarcinoma cells) may be based on the CD44 receptor-mediated endocytosis and phenylboronic acid-sialic acid interaction. Enhanced in vivo tumor targetability, infiltration efficiency, and antitumor efficacies of HACE-AMPB NPs, compared with HACE NPs, were observed in a MDA-MB-231 tumor-xenografted mouse model. In addition to passive tumor targeting (based on an enhanced permeability and retention effect) and active tumor targeting (interaction between HA and CD44 receptor), the phenylboronic acid-sialic acid interaction can play important roles in augmented tumor targeting and penetration of HACE-AMPB NPs. STATEMENT OF SIGNIFICANCE: (3-Aminomethylphenyl)boronic acid (AMPB)-tethered hyaluronic acid-ceramide (HACE)-based nanoparticles (NPs), including manassantin B (MB), were fabricated and their tumor targeting and penetration efficiencies were assessed in MDA-MB-231 (CD44 receptor-positive human adenocarcinoma) tumor models. MB, which exhibited antitumor efficacies via the inhibition of angiogenesis and hypoxia inducible factor (HIF)-1, was entrapped in HACE-AMPB NPs in this study. Phenylboronic acid located in the outer surface

  16. Sinapic acid or its derivatives interfere with abscisic acid homeostasis during Arabidopsis thaliana seed germination.

    PubMed

    Bi, Baodi; Tang, Jingliang; Han, Shuang; Guo, Jinggong; Miao, Yuchen

    2017-06-06

    Sinapic acid and its esters have broad functions in different stages of seed germination and plant development and are thought to play a role in protecting against ultraviolet irradiation. To better understand the interactions between sinapic acid esters and seed germination processes in response to various stresses, we analyzed the role of the plant hormone abscisic acid (ABA) in the regulation of sinapic acid esters involved in seed germination and early seedling growth. We found that exogenous sinapic acid promotes seed germination in a dose-dependent manner in Arabidopsis thaliana. High-performance liquid chromatography mass spectrometry analysis showed that exogenous sinapic acid increased the sinapoylcholine content of imbibed seeds. Furthermore, sinapic acid affected ABA catabolism, resulting in reduced ABA levels and increased levels of the ABA-glucose ester. Using mutants deficient in the synthesis of sinapate esters, we showed that the germination of mutant sinapoylglucose accumulator 2 (sng2) and bright trichomes 1 (brt1) seeds was more sensitive to ABA than the wild-type. Moreover, Arabidopsis mutants deficient in either abscisic acid deficient 2 (ABA2) or abscisic acid insensitive 3 (ABI3) displayed increased expression of the sinapoylglucose:choline sinapoyltransferase (SCT) and sinapoylcholine esterase (SCE) genes with sinapic acid treatment. This treatment also affected the accumulation of sinapoylcholine and free choline during seed germination. We demonstrated that sinapoylcholine, which constitutes the major phenolic component in seeds among various minor sinapate esters, affected ABA homeostasis during seed germination and early seedling growth in Arabidopsis. Our findings provide insights into the role of sinapic acid and its esters in regulating ABA-mediated inhibition of Arabidopsis seed germination in response to drought stress.

  17. Haemolytic activity of formyl- and acetyl-derivatives of bile acids and their gramine salts.

    PubMed

    Kozanecka-Okupnik, Weronika; Jasiewicz, Beata; Pospieszny, Tomasz; Matuszak, Monika; Mrówczyńska, Lucyna

    2017-10-01

    Bile acids (lithocholic: LCA, deoxycholic: DCA and cholic: CA) and their formyl- and acetyl-derivatives can be used as starting material in chemical synthesis of compounds with different biological activity strongly depended on their chemical structures. Our previous studies showed that biological activity of bile acids salts with gramine toward human erythrocytes was significantly different from the activity of bile acids alone. Moreover, gramine effectively modified the membrane perturbing activity of other steroids. As a continuation of our work, the haemolytic activity of formyl- and acetyl-substituet bile acids as well as their gramine salts was studied in vitro. The structures of new compounds were confirmed by spectral (NMR, FT-IR) analysis, mass spectrometry (ESI-MS) as well as PM5 semiempirical methods. The results shown that the haemolytic activity of formyl- and acetyl-LCA and DCA was significantly higher in comparison with their native forms at the whole concentration range. At high concentration, formyl derivative of CA was as effective as LCA and DCA derivatives whereas at lower concentration its haemolytic activity was at the level of original acid. The acetyl-CA was not active as membrane perturbing agents. Furthermore, gramine significantly decreased the membrane-perturbing activity of hydrophobic bile acids derivatives. The results obtained with the cellular system are in line with physicochemical calculation. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Biotechnological production of caffeic acid derivatives from cell and organ cultures of Echinacea species.

    PubMed

    Murthy, Hosakatte Niranjana; Kim, Yun-Soo; Park, So-Young; Paek, Kee-Yoeup

    2014-09-01

    Caffeic acid derivatives (CADs) are a group of bioactive compounds which are produced in Echinacea species especially Echinacea purpurea, Echinacea angustifolia, and Echinacea pallida. Echinacea is a popular herbal medicine used in the treatment of common cold and it is also a prominent dietary supplement used throughout the world. Caffeic acid, chlorogenic acid (5-O-caffeoylquinic acid), caftaric acid (2-O-caffeoyltartaric acid), cichoric acid (2, 3-O-dicaffeoyltartaric acid), cynarin, and echinacoside are some of the important CADs which have varied pharmacological activities. The concentrations of these bioactive compounds are species specific and also they vary considerably with the cultivated Echinacea species due to geographical location, stage of development, time of harvest, and growth conditions. Due to these reasons, plant cell and organ cultures have become attractive alternative for the production of biomass and caffeic acid derivatives. Adventitious and hairy roots have been induced in E. pupurea and E. angustifolia, and suspension cultures have been established from flask to bioreactor scale for the production of biomass and CADs. Tremendous progress has been made in this area; various bioprocess methods and strategies have been developed for constant high-quality productivity of biomass and secondary products. This review is aimed to discuss biotechnological methods and approaches employed for the sustainable production of CADs.

  19. Theophylline-7-acetic acid derivatives with amino acids as anti-tuberculosis agents.

    PubMed

    Voynikov, Yulian; Valcheva, Violeta; Momekov, Georgi; Peikov, Plamen; Stavrakov, Georgi

    2014-07-15

    A series of amides were synthesized by condensation of theophylline-7-acetic acid and eight commercially available amino acid methyl ester hydrochlorides. Consecutive hydrolysis of six of the amido-esters resulted in the formation of corresponding amido-acids. The newly synthesized compounds were evaluated for their in vitro activity against Mycobacterium tuberculosis H37Rv. The activity varied depending on the amino acid fragments and in seven cases exerted excellent values with MICs 0.46-0.26 μM. Assessment of the cytotoxicity revealed that the compounds were not cytotoxic against the human embryonal kidney cell line HEK-293T. The theophylline-7-acetamides containing amino acid moieties appear to be promising lead compounds for the development of antimycobacterial agents. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Synthesis of conjugated linoleic acid by the linoleate isomerase complex in food-derived lactobacilli.

    PubMed

    Yang, B; Chen, H; Gu, Z; Tian, F; Ross, R P; Stanton, C; Chen, Y Q; Chen, W; Zhang, H

    2014-08-01

    To assess strains of lactobacilli for their capacity to produce functional fatty acid-conjugated linoleic acid. To assess the linoleate isomerase for CLA production in the most efficient CLA producer. In this study, strains of food-derived lactobacilli were cultured in media with linoleic acid and CLA production was assessed. Most of the selected strains produced CLA at different levels, with Lactobacillus plantarum ZS2058 being the most efficient CLA producer converting over 50% of linoleic acid to c9, t11-CLA and t9, t11-CLA. Some intermediates 10-hydroxy-cis-12-octadecenoic acid, 10-oxo-cis-12-octadecenoic acid and 10-oxo-trans-11-octadecenoic acid were determined via GC-MS. The genes coding the multicomponent linoleate isomerase containing myosin-cross-reactive antigen, short-chain dehydrogenase/oxidoreductase and acetoacetate decarboxylase for CLA production in Lact. plantarum ZS2058 were cloned and expressed in Escherichia coli. With the mixture of recombinant E. coli, c9, t11-CLA and three kinds of intermediates were produced from linoleic acid, which were in line with those in the lactobacilli. The ability for CLA production by lactobacilli exhibited variation. Lactobacillus plantarum and Lact. bulgaricus were the most efficient producers in the selected strains. Lact. plantarum ZS2058 converted linoleic acid to CLAs with 10-hydroxy-cis-12-octadecenoic acid, 10-oxo-cis-12-octadecenoic acid and 10-oxo-trans-11-octadecenoic acid as intermediates. The multiple-step reactions for CLA production catalysed by multicomponent linoleate isomerase in Lact. plantarum ZS2058 were confirmed successfully. Multicomponent linoleate isomerase provides important results for the illustration of the mechanism for CLA production in lactic acid bacteria. Food-derived lactobacilli with CLA production ability offers novel opportunities for functional foods development. © 2014 The Society for Applied Microbiology.

  1. Synthesis of conjugated linoleic acid by the linoleate isomerase complex in food-derived lactobacilli

    PubMed Central

    Yang, B.; Chen, H.; Gu, Z.; Tian, F.; Ross, R. P.; Stanton, C.; Chen, Y. Q.; Chen, W.; Zhang, H.

    2015-01-01

    Aims To assess strains of lactobacilli for their capacity to produce functional fatty acid-conjugated linoleic acid. To assess the linoleate isomerase for CLA production in the most efficient CLA producer. Methods and Results In this study, strains of food-derived lactobacilli were cultured in media with linoleic acid and CLA production was assessed. Most of the selected strains produced CLA at different levels, with Lactobacillus plantarum ZS2058 being the most efficient CLA producer converting over 50% of linoleic acid to c9, t11-CLA and t9, t11-CLA. Some intermediates 10-hydroxy-cis-12-octadecenoic acid, 10-oxo-cis-12-octadecenoic acid and 10-oxo-trans-11-octadecenoic acid were determined via GC-MS. The genes coding the multicomponent linoleate isomerase containing myosin-cross-reactive antigen, short-chain dehydrogenase/oxidoreductase and acetoacetate decarboxylase for CLA production in Lact. plantarum ZS2058 were cloned and expressed in Escherichia coli. With the mixture of recombinant E. coli, c9, t11-CLA and three kinds of intermediates were produced from linoleic acid, which were in line with those in the lactobacilli. Conclusions The ability for CLA production by lactobacilli exhibited variation. Lactobacillus plantarum and Lact. bulgaricus were the most efficient producers in the selected strains. Lact. plantarum ZS2058 converted linoleic acid to CLAs with 10-hydroxy-cis-12-octadecenoic acid, 10-oxo-cis-12-octadecenoic acid and 10-oxo-trans-11-octadecenoic acid as intermediates. The multiple-step reactions for CLA production catalysed by multicomponent linoleate isomerase in Lact. plantarum ZS2058 were confirmed successfully. Significance and Impact of the study Multicomponent linoleate isomerase provides important results for the illustration of the mechanism for CLA production in lactic acid bacteria. Food-derived lactobacilli with CLA production ability offers novel opportunities for functional foods development. PMID:24750362

  2. Synthesis of α-amino acids based on chiral tricycloiminolactone derived from natural (+)-camphor.

    PubMed

    Luo, Yong-Chun; Zhang, Huan-Huan; Wang, Yao; Xu, Peng-Fei

    2010-10-19

    Amino acids are one of the most important classes of the building blocks of life: they are the structural subunits of proteins, peptides, and many secondary metabolites. In addition to the 20 α-amino acids that constitute the backbone of proteins, hundreds of other natural α-amino acids have been discovered either in free form or as components in natural products. The difference between these molecules is the substituents at the chiral carbon situated between the amino and carboxyl moieties; this carbon (and any atom along a chain attached to it) is thus an important synthetic target. Because tailor-made α-amino acids are increasingly popular in biochemistry and organic synthesis, further refinement in synthetic methods to generate both natural (L-configuration) and unnatural (D-configuration) amino acids is a very active area of current research. In this Account, we examine the tricycloiminolactones, which are versatile glycine equivalents derived from natural camphor. We have developed the tricycloiminolactones in our laboratory and used them in the synthesis of several kinds of enantiopure α-amino acids. As nucleophiles, enolated tricycloiminolactones were shown to successfully participate in alkylations, Aldol reactions, Michael additions, and Mannich reactions. These reactions all gave excellent stereoselectivities and high yields. Simple conversion of the products offered α-alkyl-α-amino acids, α,α-dialkyl-α-amino acids, β-hydroxy-α-amino acids, α,γ-diamino acids, and α,β-diamino acids. One particular advantage is that the same electrophile can react with two chiral templates in the same way, thus affording access to both enantiomeric amino acids. In other words, some natural (L-configuration) α-amino acids and their unnatural (D-configuration) counterparts can be prepared very conveniently. The relation between substrate structures and product stereoconformations derived from our investigations serves as a convenient guide in the synthesis of

  3. Induction of hepatocyte growth factor production in human dermal fibroblasts by caffeic acid derivatives.

    PubMed

    Kurisu, Manami; Nakasone, Rie; Miyamae, Yusaku; Matsuura, Daisuke; Kanatani, Hirotoshi; Yano, Shingo; Shigemori, Hideyuki

    2013-01-01

    Hepatocyte growth factor (HGF) has mitogenic, motogenic, and morphogenic activities in epithelial cells. Induction of HGF production may be involved in organ regeneration, wound healing and embryogenesis. In this study, we examined the effects of caffeic acid derivatives including 4,5-di-O-caffeoylquinic acid (1) and acteoside (2) on HGF production in Neonatal Normal Human Dermal Fibroblasts (NHDF). Both 4,5-di-O-caffeoylquinic acid (1) and acteoside (2) significantly induced HGF production dose-dependent manner. To know the important substructure for HGF production activity, we next investigated the effect of the partial structure of these caffeic acid derivatives. From the results, caffeic acid (3) showed strong activity on the promotion of HGF production, while hydroxytyrosol (4) and quinic acid (5) didn't show any activity. Our findings suggest that the caffeoyl moiety of caffeic acid derivatives is essential for accelerated production of HGF. The compound which has the caffeoyl moiety may be useful for the treatment of some intractable organ disease.

  4. Neuraminidase inhibition of Dietary chlorogenic acids and derivatives - potential antivirals from dietary sources.

    PubMed

    Gamaleldin Elsadig Karar, Mohamed; Matei, Marius-Febi; Jaiswal, Rakesh; Illenberger, Susanne; Kuhnert, Nikolai

    2016-04-01

    Plants rich in chlorogenic acids (CGAs), caffeic acids and their derivatives have been found to exert antiviral effects against influenza virus neuroaminidase. In this study several dietary naturally occurring chlorogenic acids, phenolic acids and derivatives were screened for their inhibitory activity against neuroaminidases (NAs) from C. perfringens, H5N1 and recombinant H5N1 (N-His)-Tag using a fluorometric assay. There was no significant difference in inhibition between the different NA enzymes. The enzyme inhibition results indicated that chlorogenic acids and selected derivatives, exhibited high activities against NAs. It seems that the catechol group from caffeic acid was important for the activity. Dietary CGA therefore show promise as potential antiviral agents. However, caffeoyl quinic acids show low bioavailibility and are intensly metabolized by the gut micro flora, only low nM concentrations are observed in plasma and urine, therefore a systemic antiviral effect of these compounds is unlikely. Nevertheless, gut floral metabolites with a catechol moiety or structurally related dietary phenolics with a catechol moiety might serve as interesting compounds for future investigations.

  5. Lanthanum(III) and praseodymium(III) derivatives with dithiocarbamates derived from alpha-amino acids.

    PubMed

    Rai, Anita; Sengupta, Soumitra K; Pandey, Om P

    2006-06-01

    Lanthanum(III) and praseodymium(III) complexes with dithiocarbamates have been synthesized by the reactions of lanthanum(III) and praseodymium(III) chloride with barium dithiocarbamate and complexes of type [LnCl(L)H2O]n have been obtained (where Ln=La(III) or Pr(III); L=barium salt of dithiocarbamate derived from glycine, L-leucine, L-valine, DL-alanine). The complexes have been characterized by elemental analysis, molar conductance, electronic absorption and fluorescence, infrared, far infrared, 1H NMR spectral studies. The presence of coordinated water molecule is inferred from thermogravimetric analysis which indicates the loss of one water molecule at 150-170 degrees C. The oscillator strength, Judd-Ofelt intensity parameter, stimulated emission cross-section, etc. have been obtained for different transitions of Pr3+.

  6. Electrochemical Coupling of Biomass-Derived Acids: New C8 Platforms for Renewable Polymers and Fuels.

    PubMed

    Wu, Linglin; Mascal, Mark; Farmer, Thomas J; Arnaud, Sacha Pérocheau; Wong Chang, Maria-Angelica

    2017-01-10

    Electrolysis of biomass-derived carbonyl compounds is an alternative to condensation chemistry for supplying products with chain length >C6 for biofuels and renewable materials production. Kolbe coupling of biomass-derived levulinic acid is used to obtain 2,7-octanedione, a new platform molecule only two low process-intensity steps removed from raw biomass. Hydrogenation to 2,7-octanediol provides a chiral secondary diol largely unknown to polymer chemistry, whereas intramolecular aldol condensation followed by hydrogenation yields branched cycloalkanes suitable for use as high-octane, cellulosic gasoline. Analogous electrolysis of an itaconic acid-derived methylsuccinic monoester yields a chiral 2,5-dimethyladipic acid diester, another underutilized monomer owing to lack of availability.

  7. An elementary derivation of the hard/soft-acid/base principle.

    PubMed

    Ayers, Paul W

    2005-04-08

    The hard/soft-acid/base (HSAB) principle indicates that hard acids prefer binding to hard bases (often forming bonds with substantial ionic character) while soft acids prefer binding to soft bases (often forming bonds with substantial covalent character). Though the HSAB principle is a foundational concept of the modern theory of acids and bases, the theoretical underpinnings of the HSAB principle remain murky. This paper examines the exchange reaction, wherein two molecules, one the product of reacting a hard acid and a soft base and the other the product of reacting a soft acid with a hard base, exchange substituents to form the preferred hard-hard and soft-soft product. A simple derivation shows that this reaction is exothermic, proving the validity of the HSAB principle. The analysis leads to the simple and conceptually appealing conclusion that the HSAB principle is a driven by simple electron transfer effects.

  8. Weakening of salmonella with selected microbial metabolites of berry-derived phenolic compounds and organic acids.

    PubMed

    Alakomi, Hanna-Leena; Puupponen-Pimiä, Riitta; Aura, Anna-Marja; Helander, Ilkka M; Nohynek, Liisa; Oksman-Caldentey, Kirsi-Marja; Saarela, Maria

    2007-05-16

    Gram-negative bacteria are important food spoilage and pathogenic bacteria. Their unique outer membrane (OM) provides them with a hydrophilic surface structure, which makes them inherently resistant to many antimicrobial agents, thus hindering their control. However, with permeabilizers, compounds that disintegrate and weaken the OM, Gram-negative cells can be sensitized to several external agents. Although antimicrobial activity of plant-derived phenolic compounds has been widely reported, their mechanisms of action have not yet been well demonstrated. The aim of our study was to elucidate the role of selected colonic microbial metabolites of berry-derived phenolic compounds in the weakening of the Gram-negative OM. The effect of the agents on the OM permeability of Salmonella was studied utilizing a fluorescence probe uptake assay, sensitization to hydrophobic antibiotics, and lipopolysaccharide (LPS) release. Our results show that 3,4-dihydroxyphenylacetic acid, 3-hydroxyphenylacetic acid, 3-(3,4-dihydroxyphenyl)propionic acid (3,4-diHPP), 3-(4-hydroxyphenyl)propionic acid, 3-phenylpropionic acid, and 3-(3-hydroxyphenyl)propionic acid efficiently destabilized the OM of Salmonella enterica subsp. enterica serovar Typhimurium and S. enterica subsp. enterica serovar Infantis as indicated by an increase in the uptake of the fluorescent probe 1-N-phenylnaphthylamine (NPN). The OM-destabilizing activity of the compounds was partially abolished by MgCl2 addition, indicating that part of their activity is based on removal of OM-stabilizing divalent cations. Furthermore, 3,4-dihydroxyphenylacetic acid, 3-hydroxyphenylacetic acid, and 3,4-diHPP increased the susceptibility of S. enterica subsp. enterica serovar Typhimurium strains for novobiocin. In addition, organic acids present in berries, such as malic acid, sorbic acid, and benzoic acid, were shown to be efficient permeabilizers of Salmonella as shown by an increase in the NPN uptake assay and by LPS release.

  9. Regioselective Enzymatic β-Carboxylation of para-Hydroxy- styrene Derivatives Catalyzed by Phenolic Acid Decarboxylases

    PubMed Central

    Wuensch, Christiane; Pavkov-Keller, Tea; Steinkellner, Georg; Gross, Johannes; Fuchs, Michael; Hromic, Altijana; Lyskowski, Andrzej; Fauland, Kerstin; Gruber, Karl; Glueck, Silvia M; Faber, Kurt

    2015-01-01

    We report on a ‘green’ method for the utilization of carbon dioxide as C1 unit for the regioselective synthesis of (E)-cinnamic acids via regioselective enzymatic carboxylation of para-hydroxystyrenes. Phenolic acid decarboxylases from bacterial sources catalyzed the β-carboxylation of para-hydroxystyrene derivatives with excellent regio- and (E/Z)-stereoselectivity by exclusively acting at the β-carbon atom of the C=C side chain to furnish the corresponding (E)-cinnamic acid derivatives in up to 40% conversion at the expense of bicarbonate as carbon dioxide source. Studies on the substrate scope of this strategy are presented and a catalytic mechanism is proposed based on molecular modelling studies supported by mutagenesis of amino acid residues in the active site. PMID:26190963

  10. Camphorquinone-10-sulfonic acid and derivatives: convenient reagents for reversible modification of arginine residues

    SciTech Connect

    Pande, C.S.; Pelzig, M.; Glass, J.D.

    1980-02-01

    Camphorquinone-10-sulfonic acid hydrate was prepared by the action of selenous acid on camphor-10-sulfonic acid. Camphorquinone-10-sulfonylnorleucine was prepared either from the sulfonic acid via the sulfonyl chloride or by selenous acid oxidation of camphor-10-sulfonylnorleucine. These reagents are useful for specific, reversible modification of the guanidino groups of arginine residues. Camphorquinonsulfonic acid is a crystalline water-soluble reagent that is especially suitable for use with small arginine-containing molecules, because the sulfonic acid group of the reagent is a convenient handle for analytical and preparative separation of products. Camphorquinonesulfonylnorleucine is more useful for work with large polypeptides and proteins, because hydrolysates of modified proteins may be analyzed for norleucine to determine the extent of arginine modification. The adducts of the camphorquinone derivatives with the guanidino group are stable to 0.5 M hydroxylamine solutions at pH 7, the recommended conditions for cleavage of the corresponding cyclohexanedione adducts. At pH 8-9 the adducts of the camphorquinone derivatives with the guanidino group are cleaved by o-phenylenediamine. The modification and regeneration of arginine, of the dipeptide arginylaspartic acid, of ribonuclease S-peptide, and of soybean trypsin inhibitor are presented as demonstrations of the use of the reagents.The use of camphorquinonesulfonyl chloride to prepare polymers containing arginine-specific ligands is discussed.

  11. Nitrogenous compounds stimulate glucose-derived acid production by oral Streptococcus and Actinomyces.

    PubMed

    Norimatsu, Yuka; Kawashima, Junko; Takano-Yamamoto, Teruko; Takahashi, Nobuhiro

    2015-09-01

    Both Streptococcus and Actinomyces can produce acids from dietary sugars and are frequently found in caries lesions. In the oral cavity, nitrogenous compounds, such as peptides and amino acids, are provided continuously by saliva and crevicular gingival fluid. Given that these bacteria can also utilize nitrogen compounds for their growth, it was hypothesized that nitrogenous compounds may influence their acid production; however, no previous studies have examined this topic. Therefore, the present study aimed to assess the effects of nitrogenous compounds (tryptone and glutamate) on glucose-derived acid production by Streptococcus and Actinomyces. Acid production was evaluated using a pH-stat method under anaerobic conditions, whereas the amounts of metabolic end-products were quantified using high performance liquid chromatography. Tryptone enhanced glucose-derived acid production by up to 2.68-fold, whereas glutamate enhanced Streptococcus species only. However, neither tryptone nor glutamate altered the end-product profiles, indicating that the nitrogenous compounds stimulate the whole metabolic pathways involving in acid production from glucose, but are not actively metabolized, nor do they alter metabolic pathways. These results suggest that nitrogenous compounds in the oral cavity promote acid production by Streptococcus and Actinomyces in vivo.

  12. Membrane-enclosed multienzyme (MEME) synthesis of 2,7-anhydro-sialic acid derivatives.

    PubMed

    Monestier, Marie; Latousakis, Dimitrios; Bell, Andrew; Tribolo, Sandra; Tailford, Louise E; Colquhoun, Ian J; Le Gall, Gwenaelle; Yu, Hai; Chen, Xi; Rejzek, Martin; Dedola, Simone; Field, Robert A; Juge, Nathalie

    2017-08-19

    Naturally occurring 2,7-anhydro-alpha-N-acetylneuraminic acid (2,7-anhydro-Neu5Ac) is a transglycosylation product of bacterial intramolecular trans-sialidases (IT-sialidases). A facile one-pot two-enzyme approach has been established for the synthesis of 2,7-anhydro-sialic acid derivatives including those containing different sialic acid forms such as Neu5Ac and N-glycolylneuraminic acid (Neu5Gc). The approach is based on the use of Ruminoccocus gnavus IT-sialidase for the release of 2,7-anhydro-sialic acid from glycoproteins, and the conversion of free sialic acid by a sialic acid aldolase. This synthetic method, which is based on a membrane-enclosed enzymatic synthesis, can be performed on a preparative scale. Using fetuin as a substrate, high-yield and cost-effective production of 2,7-anhydro-Neu5Ac was obtained to high-purity. This method was also applied to the synthesis of 2,7-anhydro-Neu5Gc. The membrane-enclosed multienzyme (MEME) strategy reported here provides an efficient approach to produce a variety of sialic acid derivatives. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  13. Anticancer mechanisms of action of two small amphipathic β(2,2)-amino acid derivatives derived from antimicrobial peptides.

    PubMed

    Ausbacher, Dominik; Svineng, Gunbjørg; Hansen, Terkel; Strøm, Morten B

    2012-11-01

    We have recently discovered that small antimicrobial β(2,2)-amino acid derivatives (Mw<500) also display activity against cancer cells. To explore their drug potential, we have presently investigated the mechanisms of action of two derivatives BAA-1 (IC(50) 8.1μg/ml) and BAA-2 (IC(50) 3.8μg/ml) on Ramos human Burkitt's lymphoma cells. Studies using annexin-V-FITC/propidium iodide staining and flow cytometry revealed essential mechanistic differences, which was confirmed by screening for active caspases, investigation of mitochondrial membrane potential, and electron microscopy studies. Our results indicated that BAA-1 killed Ramos cells by destabilizing the cell membrane, whereas BAA-2 caused apoptosis by the mitochondrial-mediated pathway. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. Synthesis and transformations of a pyrazole containing alpha, beta-didehydro-alpha-amino acid derivatives.

    PubMed

    Vranicar, L; Pozgan, F; Polanc, S; Kocevar, M

    2003-04-01

    2H-Pyran-2-ones 1 were transformed with various hydrazines into (E)- or (Z)-alpha, beta-didehydro-alpha-amino acid (DDAA) derivatives 4 (and 7) containing a highly substituted pyrazolyl moiety attached at the beta-position. With heterocyclic hydrazines, the products 4 were accompanied also by decarboxylated enamines E-6. In order to separate (E/Z)-mixtures of acids, they were transformed to the corresponding methyl esters 9 and 10 by the application of diazomethane. Catalytic hydrogenation under high pressures with Pd/C as a catalyst resulted in the formation of racemic alanine derivatives 11.

  15. Synthesis, in vitro and in vivo antitumor activity of pyrazole-fused 23-hydroxybetulinic acid derivatives.

    PubMed

    Zhang, Hengyuan; Zhu, Peiqing; Liu, Jie; Lin, Yan; Yao, Hequan; Jiang, Jieyun; Ye, Wencai; Wu, Xiaoming; Xu, Jinyi

    2015-02-01

    A collection of pyrazole-fused 23-hydroxybetulinic acid derivatives were designed, synthesized and evaluated for their antitumor activity. Most of the newly synthesized compounds exhibited significant antiproliferative activity. Especially compound 15e displayed the most potent activity with the IC50 values of 5.58 and 6.13μM against B16 and SF763 cancer cell lines, respectively. Furthermore, the significant in vivo antitumor activity of 15e was validated in H22 liver cancer and B16 melanoma xenograft mouse models. The structure-activity relationships of these 23-hydroxybetulinic acid derivatives were also discussed based on the present investigation.

  16. Nucleosides of 4-methylthio-1,2,3-triazol-5-yl-carboxylic acid derivatives

    SciTech Connect

    Shingarova, I.D.; Yartseva, I.V.; Preobrazhenskaya, M.N.

    1987-08-01

    2-..beta..-D-Ribofuranosyl-4-methylthio-5-methoxycarbonyl-1,2,3-triazole was obtained by fusing 4-methylthio-5-methoxycarbonyl-1,2,3-triazole together with tetraacyl-D-ribofuranose, followed by deacylation, and its amide and hydrazide were prepared. The structures of the new nucleosides were established by converting them into known 2-nucleosides of 1,2,3-triazol-4-yl-carboxylic acid derivatives. By comparing PMR spectra with previously reported PMR spectra for the isomeric 1- and 2-nucleosides of 1,2,3-triazol-4-yl-carboxylic acid derivatives, the synthesized nucleosides could be assigned to 2-substituted triazoles.

  17. Development, characterization and commercial application of palm based dihydroxystearic acid and its derivatives: an overview.

    PubMed

    Koay, Gregory F L; Chuah, Teong-Guan; Zainal-Abidin, Sumaiya; Ahmad, Salmiah; Choong, Thomas S Y

    2011-01-01

    Hydroxyl fatty acids and their derivatives are of high value due to their wide range of industrial application, including cosmetic, food, personal care and pharmaceutical products. Realizing the importance of hydroxyl fatty acids, and yet due to the absence of the conventional starting raw materials, Malaysia has developed 9,10-dihydroxystearic acid (9,10-DHSA) and its derivatives from locally abundant palm based oils. The aim of this article is to provide a general description of the works that have thus far being done on palm based 9,10-DHSA: starting from its conception and production from commercial grade palm based crude oleic acid via epoxidation and hydrolysis, purification through solvent crystallization and characterization through wet and analytical chemistry, moving on to developmental works done on producing its derivatives through blending, esterification, amidation and polymerization, and completing with applications of 9,10-DHSA and its derivatives, e.g. DHSA-stearates and DHSA-estolides, in commercial products such as soaps, deodorant sticks and shampoos. This article incorporates some of the patent filed technological knowhow on 9,10-DHSA and its derivatives, and will also point out some of the shortcomings in previously published documents and provide some recommendations for future research works in mitigating these shortcomings.

  18. Technological and economic potential of poly(lactic acid) and lactic acid derivatives

    SciTech Connect

    Datta, R.; Tsai, S.P.; Bonsignore, P.; Moon, S.H.; Frank, J.R.

    1993-10-01

    Lactic acid has been an intermediate-volume specialty chemical (world production {approximately}40,000 tons/yr) used in a wide range of food processing and industrial applications. lactic acid h,as the potential of becoming a very large volume, commodity-chemical intermediate produced from renewable carbohydrates for use as feedstocks for biodegradable polymers, oxygenated chemicals, plant growth regulators, environmentally friendly ``green`` solvents, and specially chemical intermediates. In the past, efficient and economical technologies for the recovery and purification of lactic acid from crude fermentation broths and the conversion of tactic acid to the chemical or polymer intermediates had been the key technology impediments and main process cost centers. The development and deployment of novel separations technologies, such as electrodialysis (ED) with bipolar membranes, extractive distillations integrated with fermentation, and chemical conversion, can enable low-cost production with continuous processes in large-scale operations. The use of bipolar ED can virtually eliminate the salt or gypsum waste produced in the current lactic acid processes. In this paper, the recent technical advances in tactic and polylactic acid processes are discussed. The economic potential and manufacturing cost estimates of several products and process options are presented. The technical accomplishments at Argonne National Laboratory (ANL) and the future directions of this program at ANL are discussed.

  19. Glycotargeting: the preparation of glyco-amino acids and derivatives from unprotected reducing sugars.

    PubMed

    Monsigny, M; Quétard, C; Bourgerie, S; Delay, D; Pichon, C; Midoux, P; Mayer, R; Roche, A C

    1998-02-01

    Lectins are present on the surface of many cells. Many lectins actively recycle from membrane to endosomes and efficiently take up glycoconjugates in a sugar-dependent manner. On this basis, glycoconjugates, specially those obtained by chemical means, are good candidates as carriers of drugs, oligonucleotides or genes. In this paper, we present a panel of methods suitable to transform unprotected reducing oligosaccharides into glycosynthons designed to be easily linked to therapeutic agents. All the glycosynthons presented here are glycosylamines or derivatives, mainly glyco-amino acids or glycopeptides. Glycosylamines are easy to obtain, but they are very labile in slightly acidic or neutral medium; they must be stabilized, by acylation for instance. The coupling efficiency of a reducing sugar with ammonia as well as an alkylamine or an arylamine is higher at high temperature, however, because of the Amadori rearrangement, special conditions have to be selected to prepare the expected glycosylamine derivative with a high yield. Glycosylamines are easily acylated by N-protected amino acids, or by halogeno acids which can then be transformed into amino acids. Alternatively, unprotected reducing oligosaccharides may very efficiently be transformed into N-glycosyl-amino acids and then protected by N-acylation. With a glutamyl derivative having both the alpha-amino and the gamma-carboxylic groups free, the coupling and the acylation, which is intramolecular, are roughly quantitative. N-oligosaccharyl-amino acid derivatives are interesting glycosynthons, because their sugar moiety bears the specificity towards membrane lectins while the amino acid part has the capacity to easily substitute a therapeutic agent.

  20. Synthesis of unnatural amino acids from serine derivatives by beta-fragmentation of primary alkoxyl radicals.

    PubMed

    Boto, Alicia; Gallardo, Juan A; Hernández, Dacil; Hernández, Rosendo

    2007-09-14

    The fragmentation of primary alkoxyl radicals has been scarcely used in synthesis since other competing processes (such as oxidation or hydrogen abstraction) usually predominate. However, when serine derivatives were used as substrates, the scission took place in excellent yields. Tandem scission-allylation, -alkylation, or -arylation reactions were subsequently developed. This one-pot methodology was applied to the synthesis of unnatural amino acids, which are useful synthetic blocks or amino acid surrogates in peptidomimetics.

  1. Paecilonic acids A and B, bicyclic fatty acids from the jellyfish-derived fungus Paecilomyces variotii J08NF-1.

    PubMed

    Wang, Haibo; Hong, Jongki; Yin, Jun; Liu, Juan; Liu, Yonghong; Choi, Jae Sue; Jung, Jee H

    2016-05-01

    Two new bicyclic fatty acids, paecilonic acids A and B (1 and 2), were isolated from the culture broth of the marine fungus Paecilomyces variotii derived from the jellyfish Nemopilema nomurai. Compounds 1 and 2 share the same molecular formula and possess a 6,8-dioxabicyclo[3.2.1]octane core skeleton. The planar structures of compounds 1 and 2 were established by spectroscopic analysis, which included NMR and ESI-MS/MS. Relative and absolute configurations were determined by analyzing coupling constants, NOESY correlations, and optical rotations. Copyright © 2016. Published by Elsevier Ltd.

  2. Asymmetric Synthesis of Glutamic Acid Derivatives by Silver-Catalyzed Conjugate Addition-Elimination Reactions.

    PubMed

    Yuan, Yang; Yu, Bo; Bai, Xing-Feng; Xu, Zheng; Zheng, Zhan-Jiang; Cui, Yu-Ming; Cao, Jian; Xu, Li-Wen

    2017-09-15

    The enantioselective construction of a family of chiral glycine-derived aldimino esters is described. The asymmetric tandem conjugate addition-elimination procedure is characterized by its exceptional mild reaction conditions and features with an exquisite enantioselectivity profile using commercially available silver/DTBM-SegPhos catalyst, allowing for the facile preparation of a variety of substituted and chiral glutamic acid derivatives (up to 99% ee) bearing Schiff base in a straightforward manner.

  3. A Direct, Biomass-Based Synthesis of Benzoic Acid: Formic Acid-Mediated Deoxygenation of the Glucose-Derived Materials Quinic Acid and Shikimic Acid

    SciTech Connect

    Arceo, Elena; Ellman, Jonathan; Bergman, Robert

    2010-05-03

    An alternative biomass-based route to benzoic acid from the renewable starting materials quinic acid and shikimic acid is described. Benzoic acid is obtained selectively using a highly efficient, one-step formic acid-mediated deoxygenation method.

  4. Syntheses of biodiesel precursors: sulfonic acid catalysts for condensation of biomass-derived platform molecules.

    PubMed

    Balakrishnan, Madhesan; Sacia, Eric R; Bell, Alexis T

    2014-04-01

    Synthesis of transportation fuel from lignocellulosic biomass is an attractive solution to the green alternative-energy problem. The production of biodiesel, in particular, involves the process of upgrading biomass-derived small molecules to diesel precursors containing a specific carbon range (C11 -C23). Herein, a carbon-upgrading process utilizing an acid-catalyzed condensation of furanic platform molecules from biomass is described. Various types of sulfonic acid catalysts have been evaluated for this process, including biphasic and solid supported catalysts. A silica-bound alkyl sulfonic acid catalyst has been developed for promoting carbon-carbon bond formation of biomass-derived carbonyl compounds with 2-methylfuran. This hydrophobic solid acid catalyst exhibits activity and selectivity that are comparable to those of a soluble acid catalyst. The catalyst can be readily recovered and recycled, possesses appreciable hydrolytic stability in the presence of water, and retains its acidity over multiple reaction cycles. Application of this catalyst to biomass-derived platform molecules led to the synthesis of a variety of furanic compounds, which are potential biodiesel precursors.

  5. Ursolic acid derivatives for pharmaceutical use: a patent review (2012-2016).

    PubMed

    Hussain, Hidayat; Green, Ivan R; Ali, Iftikhar; Khan, Ikhlas A; Ali, Zulfiqar; Al-Sadi, Abdullah M; Ahmed, Ishtiaq

    2017-09-01

    Ursolic acid (UA), belongs to a group of pentacyclic triterpenoids and is known to possess some very interesting biological properties. Protocols have been developed in order to synthesize bioactive UA analogs which have resulted in numerous ursolic acid analogs being synthesized during the period 2012-2016. Ursolic acid and its analogues can be employed to treat various cancers, inflammatory diseases, diabetes, Parkinson's disease, Alzheimer's disease, hepatitis B, hepatitis C and AIDS to mention but a few. Areas covered: This review covers patents on therapeutic activities of ursolic acid (UA) and its synthetic derivatives published during the four year period 2012-2016. A discussion about structure-activity relationships (SAR) of these analogs is also included. Expert opinion: Ursolic acid and its synthetic derivatives demonstrated excellent anticancer, antidiabetic, antiarrhythmic, anti-hyperlipidemic, antimicrobial, anti-hypercholesterolemic, and anti-cardiovascular properties. Additionally, various ursolic acid analogues have been synthesized through modification at positions C2-OH, C3-OH and C17-CO2H. It is noteworthy that the C-17 amide and amino analogs of UA possessed better anticancer activity compared to the parent compound (UA). Most importantly, UA has the potential to conjugate with other anticancer drugs or be transformed into its halo derivatives since this will greatly facilitate scientists to get lead compounds in cancer drug discovery.

  6. Diversity in prokaryotic glycosylation: an archaeal-derived N-linked glycan contains legionaminic acid.

    PubMed

    Kandiba, Lina; Aitio, Olli; Helin, Jari; Guan, Ziqiang; Permi, Perttu; Bamford, Dennis H; Eichler, Jerry; Roine, Elina

    2012-05-01

    VP4, the major structural protein of the haloarchaeal pleomorphic virus, HRPV-1, is glycosylated. To define the glycan structure attached to this protein, oligosaccharides released by β-elimination were analysed by mass spectrometry and nuclear magnetic resonance spectroscopy. Such analyses showed that the major VP4-derived glycan is a pentasaccharide comprising glucose, glucuronic acid, mannose, sulphated glucuronic acid and a terminal 5-N-formyl-legionaminic acid residue. This is the first observation of legionaminic acid, a sialic acid-like sugar, in an archaeal-derived glycan structure. The importance of this residue for viral infection was demonstrated upon incubation with N-acetylneuraminic acid, a similar monosaccharide. Such treatment reduced progeny virus production by half 4 h post infection. LC-ESI/MS analysis confirmed the presence of pentasaccharide precursors on two different VP4-derived peptides bearing the N-glycosylation signal, NTT. The same sites modified by the native host, Halorubrum sp. strain PV6, were also recognized by the Haloferax volcanii N-glycosylation apparatus, as determined by LC-ESI/MS of heterologously expressed VP4. Here, however, the N-linked pentasaccharide was the same as shown to decorate the S-layer glycoprotein in this species. Hence, N-glycosylation of the haloarchaeal viral protein, VP4, is host-specific. These results thus present additional examples of archaeal N-glycosylation diversity and show the ability of Archaea to modify heterologously expressed proteins.

  7. Human Neutrophils Convert the Sebum-derived Polyunsaturated Fatty Acid Sebaleic Acid to a Potent Granulocyte Chemoattractant*

    PubMed Central

    Cossette, Chantal; Patel, Pranav; Anumolu, Jaganmohan R.; Sivendran, Sashikala; Lee, Gue Jae; Gravel, Sylvie; Graham, François D.; Lesimple, Alain; Mamer, Orval A.; Rokach, Joshua; Powell, William S.

    2008-01-01

    Sebaleic acid (5,8-octadecadienoic acid) is the major polyunsaturated fatty acid in human sebum and skin surface lipids. The objective of the present study was to investigate the metabolism of this fatty acid by human neutrophils and to determine whether its metabolites are biologically active. Neutrophils converted sebaleic acid to four major products, which were identified by their chromatographic properties, UV absorbance, and mass spectra as 5-hydroxy-(6E,8Z)-octadecadienoic acid (5-HODE), 5-oxo-(6E,8Z)-octadecadienoic acid (5-oxo-ODE), 5S,18-dihydroxy-(6E,8Z)-octadecadienoic acid, and 5-oxo-18-hydroxy-(6E,8Z)-octadecadienoic acid. The identities of these metabolites were confirmed by comparison of their properties with those of authentic chemically synthesized standards. Both neutrophils and human keratinocytes converted 5-HODE to 5-oxo-ODE. This reaction was stimulated in neutrophils by phorbol myristate acetate and in keratinocytes by oxidative stress (t-butyl-hydroperoxide). Both treatments dramatically elevated intracellular levels of NADP+, the cofactor required by 5-hydroxyeicosanoid dehydrogenase. In keratinocytes, this was accompanied by a rapid increase in intracellular GSSG levels, consistent with the involvement of glutathione peroxidase. 5-Oxo-ODE stimulated calcium mobilization in human neutrophils and induced desensitization to 5-oxo-6,8,11,14-eicosatetraenoic acid but not leukotriene B4, indicating that this effect was mediated by the OXE receptor. 5-Oxo-ODE and its 8-trans isomer were equipotent with 5-oxo-6,8,11,14-eicosatetraenoic acid in stimulating actin polymerization and chemotaxis in human neutrophils, whereas 5-HODE, 5-oxo-18-hydroxy-(6E,8Z)-octadecadienoic acid, and 5S,18-dihydroxy-(6E,8Z)-octadecadienoic acid were much less active. We conclude that neutrophil 5-lipoxygenase converts sebaleic acid to 5-HODE, which can be further metabolized to 5-oxo-ODE by 5-hydroxyeicosanoid dehydrogenase in neutrophils and keratinocytes. Because of

  8. Human neutrophils convert the sebum-derived polyunsaturated fatty acid Sebaleic acid to a potent granulocyte chemoattractant.

    PubMed

    Cossette, Chantal; Patel, Pranav; Anumolu, Jaganmohan R; Sivendran, Sashikala; Lee, Gue Jae; Gravel, Sylvie; Graham, François D; Lesimple, Alain; Mamer, Orval A; Rokach, Joshua; Powell, William S

    2008-04-25

    Sebaleic acid (5,8-octadecadienoic acid) is the major polyunsaturated fatty acid in human sebum and skin surface lipids. The objective of the present study was to investigate the metabolism of this fatty acid by human neutrophils and to determine whether its metabolites are biologically active. Neutrophils converted sebaleic acid to four major products, which were identified by their chromatographic properties, UV absorbance, and mass spectra as 5-hydroxy-(6E,8Z)-octadecadienoic acid (5-HODE), 5-oxo-(6E,8Z)-octadecadienoic acid (5-oxo-ODE), 5S,18-dihydroxy-(6E,8Z)-octadecadienoic acid, and 5-oxo-18-hydroxy-(6E,8Z)-octadecadienoic acid. The identities of these metabolites were confirmed by comparison of their properties with those of authentic chemically synthesized standards. Both neutrophils and human keratinocytes converted 5-HODE to 5-oxo-ODE. This reaction was stimulated in neutrophils by phorbol myristate acetate and in keratinocytes by oxidative stress (t-butyl-hydroperoxide). Both treatments dramatically elevated intracellular levels of NADP(+), the cofactor required by 5-hydroxyeicosanoid dehydrogenase. In keratinocytes, this was accompanied by a rapid increase in intracellular GSSG levels, consistent with the involvement of glutathione peroxidase. 5-Oxo-ODE stimulated calcium mobilization in human neutrophils and induced desensitization to 5-oxo-6,8,11,14-eicosatetraenoic acid but not leukotriene B(4), indicating that this effect was mediated by the OXE receptor. 5-Oxo-ODE and its 8-trans isomer were equipotent with 5-oxo-6,8,11,14-eicosatetraenoic acid in stimulating actin polymerization and chemotaxis in human neutrophils, whereas 5-HODE, 5-oxo-18-hydroxy-(6E,8Z)-octadecadienoic acid, and 5S,18-dihydroxy-(6E,8Z)-octadecadienoic acid were much less active. We conclude that neutrophil 5-lipoxygenase converts sebaleic acid to 5-HODE, which can be further metabolized to 5-oxo-ODE by 5-hydroxyeicosanoid dehydrogenase in neutrophils and keratinocytes. Because

  9. Microbiological degradation of bile acids. Nitrogenous hexahydroindane derivatives formed from cholic acid by Streptomyces rubescens.

    PubMed Central

    Hayakawa, S; Hashimoto, S; Onaka, T

    1976-01-01

    The metabolism of cholic acid (I) by Streptomyces rubescens was investigated. This organism effected ring A cleavage, side-chain shortening and amide bond formation and gave the following metabolites: (4R)-4-[4alpha-(2-carboxyethyl)-3aalpha-hexahydro-7abeta-methyl-5-oxoindan-1 beta-yl]valeric acid (IIa) and its mono-amide (valeramide) (IIb); and 2,3,4,6, 6abeta,7,8,9,9aalpha,9bbeta-decahydro-6abeta-methyl-1H-cyclopenta[f]quinoline-3,7-dione(IIIe)and its homologues with the beta-oriented side chains, valeric acid, valeramide, butanone and propionic acid, in the place of the oxo group at C-7, i.e.compounds (IIIa), (IIIb), (IIIc) and (IIId) respectively. All the nitrogenous metabolites were new compounds, and their structures were established by partial synthesis except for the metabolite (IIIc). The mechanism of formation of these metabolites is considered. A degradative pathway of cholic acid (I) into the metabolites is also tentatively proposed. PMID:1016253

  10. Hop (Humulus lupulus)-derived bitter acids as multipotent bioactive compounds.

    PubMed

    Van Cleemput, Marjan; Cattoor, Ko; De Bosscher, Karolien; Haegeman, Guy; De Keukeleire, Denis; Heyerick, Arne

    2009-06-01

    Hop acids, a family of bitter compounds derived from the hop plant (Humulus lupulus), have been reported to exert a wide range of effects, both in vitro and in vivo. They exhibit potential anticancer activity by inhibiting cell proliferation and angiogenesis, by inducing apoptosis, and by increasing the expression of cytochrome P450 detoxification enzymes. Furthermore, hop bitter acids are effective against inflammatory and metabolic disorders, which makes them challenging candidates for the treatment of diabetes mellitus, cardiovascular diseases, and metabolic syndrome. This review summarizes the current knowledge on hop bitter acids, including both phytochemical aspects, as well as the biological and pharmacological properties of these compounds.

  11. Modulation by glycyrrhetinic acid derivatives of TPA-induced mouse ear oedema.

    PubMed Central

    Inoue, H.; Mori, T.; Shibata, S.; Koshihara, Y.

    1989-01-01

    1. The anti-inflammatory effects of glycyrrhetinic acid and its derivatives on TPA (12-O-tetradecanoylphorbol-13-acetate)-induced mouse ear oedema were studied. The mechanisms of TPA-induced ear oedema were first investigated with respect to the chemical mediators. 2. The formation of ear oedema reached a maximum 5 h after TPA application (2 micrograms per ear) and the prostaglandin E2 (PGE2) production of mouse ear increased with the oedema formation. 3. TPA-induced ear oedema was prevented by actinomycin D and cycloheximide (0.1 mg per ear, respectively) when applied during 60 min after TPA treatment. 4. Of glycyrrhetinic acid derivatives examined, dihemiphthalate derivatives (IIe, IIe', IIIa, IIIa', IVa, IVa') most strongly inhibited ear oedema on both topical (ID50, 1.6 mg per ear for IIe, 2.0 mg per ear for IIIa and 1.6 mg per ear for IVa) and oral (ID50, 88 mg kg-1 for IIe', 130 mg kg-1 for IIIa' and 92 mg kg-1 for IVa') administration. 5. Glycyrrhetinic acid (Ia) and its derivatives applied 30 min before TPA treatment were much more effective in inhibiting oedema than when applied 30 min after TPA. A dihemiphthalate of triterpenoid compound IVa completely inhibited oedema, even when applied 3 h before TPA treatment. 6. Glycyrrhetinic acid (Ia) and deoxoglycyrrhetol (IIa), the parent compounds, produced little inhibition by oral administration at less than 200 mg kg-1. 7. These results suggest that the dihemiphthalate derivatives of triterpenes derived from glycyrrhetinic acid by chemical modification are useful for the treatment of skin inflammation by both topical and oral application. PMID:2924072

  12. Synthesis and biological evaluation of pseudolaric acid B derivatives as potential immunosuppressive agents.

    PubMed

    Chen, Shou-Qiang; Wang, Jie; Zhao, Chuan; Sun, Qiang-Wen; Wang, Yi-Teng; Ai, Ting; Li, Tan; Gao, Ying; Wang, Huo; Chen, Hong

    2015-01-01

    Pseudolaric acid B (PB) derivatives with immunosuppressive activity were found by our group. In order to find potential immunosuppressive agents with high efficacy and low toxicity, a series of novel PB derivatives were synthesized and evaluated on their immunosuppressive activities. Most of the synthesized compounds were tested in vitro on murine T and B proliferation. In particular, compound 11 exhibited excellent inhibitory activity toward murine T cells (up to 19-fold enhancement compared to that of mycophenolatemofetil) and little cytotoxicity toward normal murine spleen cells. These experimental data demonstrated that some of these PB derivatives have great potential for future immunosuppressive studies.

  13. Facile synthesis of a fullerene-barbituric acid derivative and supramolecular catalysis of its photoinduced dimerization.

    PubMed

    McClenaghan, Nathan D; Absalon, Christelle; Bassani, Dario M

    2003-10-29

    A straightforward synthesis of a fullerene derivative appended with a barbituric acid molecular recognition motif is described. The presence of two nonself-complementary hydrogen-bonding sites is shown to be conducive to the construction of supramolecular assemblies. In the presence of a melamine derivative possessing complementary hydrogen-bonding sites, enhanced efficiency toward photodimerization of the fullerene moiety is observed. This represents the first example of intermolecular photodimerization of a fullerene derivative in homogeneous solution, made possible by the formation of supramolecular assemblies in which the fullerenes are maintained in close proximity.

  14. Selective growth inhibition of human malignant melanoma cells by syringic acid-derived proteasome inhibitors

    PubMed Central

    2013-01-01

    Background It has been shown that proteasome inhibition leads to growth arrest in the G1 phase of the cell cycle and/or induction of apoptosis. However, it was found that some of these inhibitors do not induce apoptosis in several human normal cell lines. This selective activity makes proteasome inhibition a promising target for new generation of anticancer drugs. Clinical validation of the proteasome, as a therapeutic target in oncology, has been provided by the dipeptide boronic acid derivative; bortezomib. Bortezomib has proven to be effective as a single agent in multiple myeloma and some forms of non-Hodgkin’s lymphoma. Syringic acid (4-hydroxy-3,5-dimethoxybenzoic acid, 1), a known phenolic acid, was isolated from the methanol extract of Tamarix aucheriana and was shown to possess proteasome inhibitory activity. Methods Using Surflex-Dock program interfaced with SYBYL, the docking affinities of syringic acid and its proposed derivatives to 20S proteasome were studied. Several derivatives were virtually proposed, however, five derivatives: benzyl 4-hydroxy-3,5-dimethoxybenzoate (2), benzyl 4-(benzyloxy)-3,5-dimethoxybenzoate (3), 3'-methoxybenzyl 3,5-dimethoxy-4-(3'-methoxybenzyloxy)benzoate (4), 3'-methoxybenzyl 4-hydroxy-3,5-dimethoxybenzoate (5) and 3',5'-dimethoxybenzyl 4-hydroxy-3,5-dimethoxybenzoate (6), were selected based on high docking scores, synthesized, and tested for their anti-mitogenic activity against human colorectal, breast and malignant melanoma cells as well as normal human fibroblast cells. Results Derivatives 2, 5, and 6 showed selective dose-dependent anti-mitogenic effect against human malignant melanoma cell lines HTB66 and HTB68 with minimal cytotoxicity on colorectal and breast cancer cells as well as normal human fibroblast cells. Derivatives 2, 5 and 6 significantly (p ≤ 0.0001) inhibited the various proteasomal chymotrypsin, PGPH, and trypsin like activities. They growth arrested the growth of HTB66 cells at G1 and G2

  15. Versatile phosphoramidation reactions for nucleic acid conjugations with peptides, proteins, chromophores, and biotin derivatives.

    PubMed

    Wang, Tzu-Pin; Chiou, Yi-Jang; Chen, Yi; Wang, Eng-Chi; Hwang, Long-Chih; Chen, Bing-Hung; Chen, Yen-Hsu; Ko, Chun-Han

    2010-09-15

    Chemical conjugations of nucleic acids with macromolecules or small molecules are common approaches to study nucleic acids in chemistry and biology and to exploit nucleic acids for medical applications. The conjugation of nucleic acids such as oligonucleotides with peptides is especially useful to circumvent cell delivery and specificity problems of oligonucleotides as therapeutic agents. However, current approaches are limited and inefficient in their ability to afford peptide-oligonucleotide conjugates (POCs). Here, we report an effective and reproducible approach to prepare POCs and other nucleic acid conjugates based on a newly developed nucleic acid phosphoramidation method. The development of a new nucleic acid phosphoramidation reaction was achieved by our successful synthesis of a novel amine-containing biotin derivative used to systematically optimize the reactions. The improved phosphoramidation reactions dramatically increased yields of nucleic acid-biotin conjugates up to 80% after 3 h reaction. Any nucleic acids with a terminal phosphate group are suitable reactants in phosphoramidation reactions to conjugate with amine-containing molecules such as biotin and fluorescein derivatives, proteins, and, most importantly, peptides to enable the synthesis of POCs for therapeutic applications. Polymerase chain reactions (PCRs) to study incorporation of biotin or fluorescein-tagged DNA primers into the reaction products demonstrated that appropriate controls of nucleic acid phosphoramidation reactions incur minimum adverse effects on inherited base-pairing characteristics of nucleotides in nucleic acids. The phosphoramidation approach preserves the integrity of hybridization specificity in nucleic acids when preparing POCs. By retaining integrity of the nucleic acids, their effectiveness as therapeutic reagents for gene silencing, gene therapy, and RNA interference is ensured. The potential for POC use was demonstrated by two-step phosphoramidation reactions to

  16. Novel Acid Catalysts from Waste-Tire-Derived Carbon: Application in Waste-to-Biofuel Conversion

    DOE PAGES

    Hood, Zachary D.; Adhikari, Shiba P.; Li, Yunchao; ...

    2017-06-21

    Many inexpensive biofuel feedstocks, including those containing free fatty acids (FFAs) in high concentrations, are typically disposed of as waste due to our inability to efficiently convert them into usable biofuels. Here we demonstrate that carbon derived from waste tires could be functionalized with sulfonic acid (-SO3H) to effectively catalyze the esterification of oleic acid or a mixture of fatty acids to usable biofuels. Waste tires were converted to hard carbon, then functionalized with catalytically active -SO3H groups on the surface through an environmentally benign process that involved the sequential treatment with L-cysteine, dithiothreitol, and H2O2. In conclusion, when benchmarkedmore » against the same waste-tire derived carbon material treated with concentrated sulfuric acid at 150 °C, similar catalytic activity was observed. Both catalysts could also effectively convert oleic acid or a mixture of fatty acids and soybean oil to usable biofuels at 65 °C and 1 atm without leaching of the catalytic sites.« less

  17. Copper extraction by fatty hydroxamic acids derivatives synthesized based on palm kernel oil.

    PubMed

    Haron, Jelas; Jahangirian, Hossein; Silong, Sidik; Yusof, Nor Azah; Kassim, Anuar; Moghaddam, Roshanak Rafiee; Peyda, Mazyar; Abdollahi, Yadollah; Amin, Jamileh; Gharayebi, Yadollah

    2012-01-01

    Fatty hydroxamic acids derivatives based on palm kernel oil which are phenyl fatty hydroxamic acids (PFHAs), methyl fatty hydroxamic acids (MFHAs), isopropyl fatty hydroxamic acids (IPFHAs) and benzyl fatty hydroxamic acids (BFHAs) were applied as chelating agent for copper liquid-liquid extraction. The extraction of copper from aqueous solution by MFHAs, PFHAs, BFHAs or IPFHAs were carried out in hexane as an organic phase through the formation of copper methyl fatty hydroxamate (Cu-MFHs), copper phenyl fatty hydroxamate (Cu-PFHs), copper benzyl fatty hydroxamate (Cu-BFHs) and copper isopropyl fatty hydroxamate (Cu-IPFHs). The results showed that the fatty hydroxamic acid derivatives could extract copper at pH 6.2 effectively with high percentage of extraction (the percentages of copper extraction by MFHAs, PFHAs, IPFHs and BFHAs were found to be 99.3, 87.5, 82.3 and 90.2%, respectively). The extracted copper could be quantitatively stripped back into sulphuric acid (3M) aqueous solution. The obtained results showed that the copper recovery percentages from Cu-MFHs, Cu-PFHs, Cu-BFHs and Cu-IPFHs are 99.1, 99.4, 99.6 and 99.9 respectively. The copper extraction was not affected by the presence of a large amount of Mg (II), Ni (II), Al (III), Mn (II) and Co (II) ions in the aqueous solution.

  18. A Surprising Mechanistic “Switch” in Lewis Acid Activation: A Bifunctional, Asymmetric Approach to α-Hydroxy Acid Derivatives

    PubMed Central

    Abraham, Ciby J.; Paull, Daniel H.; Bekele, Tefsit; Scerba, Michael T.; Dudding, Travis; Lectka, Thomas

    2009-01-01

    We report a detailed synthetic and mechanistic study of an unusual bifunctional, sequential hetero-Diels–Alder/ring-opening reaction in which chiral, metal complexed ketene enolates react with o-quinones to afford highly enantioenriched, α-hydroxylated carbonyl derivatives in excellent yield. A number of Lewis acids were screened in tandem with cinchona alkaloid derivatives; surprisingly, trans-(Ph3P)2PdCl2 was found to afford the most dramatic increase in yield and rate of reaction. A series of Lewis acid binding motifs were explored through molecular modeling, as well as IR, UV and NMR spectroscopy. Our observations document a fundamental mechanistic “switch” – namely the formation of a tandem Lewis base/Lewis acid activated metal enolate in preference to a metal-coordinated quinone species (as observed in other reactions of o-quinone derivatives). This new method was applied to the syntheses of several pharmaceutical targets, each of which was obtained in high yield and enantioselectivity. PMID:19053448

  19. Fruit maturity and juice extraction influences ellagic acid derivatives and other antioxidant polyphenolics in muscadine grapes.

    PubMed

    Lee, Joon-Hee; Talcott, Stephen T

    2004-01-28

    Polyphenolic compounds including ellagic acid, ellagic acid derivatives, and anthocyanins were characterized and quantified by novel chromatographic conditions in eight muscadine grape (Vitis rotundifolia) cultivars and evaluated for antioxidant capacity as influenced by two ripening stages and their location within the fruit (skin, pulp, and juice). All polyphenolics generally increased as fruit ripened and the highest concentrations were located in the skins. Free ellagic acid, ellagic acid glycosides, and total ellagic acid ranged from 8 to 162, 7 to 115, and 587 to 1900 mg/kg, respectively, in the skin of ripe grapes. Hot-pressed juices contained considerably lower polyphenolic concentrations than were present in whole grapes. Five anthocyanidins were present in each cultivar in variable concentrations (delphinidin > petunidin > malvidin + peonidin > cyanidin). Antioxidant capacity was appreciably influenced by cultivar, maturity, and location in the fruit with good correlations to soluble phenolics found in both methanolic and ethyl acetate extracts (r = 0.83 and 0.92, respectively).

  20. Steric hindrance of 2,6-disubstituted benzoic acid derivatives on the uptake via monocarboxylic acid transporters from the apical membranes of Caco-2 cells.

    PubMed

    Tsukagoshi, Kensuke; Kimura, Osamu; Endo, Tetsuya

    2014-05-01

    Benzoic acid is a typical substrate for monocarboxylic acid transporters (MCTs), and easily taken up from the apical membranes of Caco-2 cells by MCTs. However, some benzoic acid derivatives were sparingly taken up by Caco-2 cells. To elucidate the mechanism of lower uptake of the derivatives, we investigated the effect of substitution of benzene ring on the uptake by MCTs using Caco-2 cells. Among the benzoic acid derivatives tested, the uptake of 2,6-disubstituted benzoic acids was markedly lower than that of other benzoic acids. Co-incubation of the 2,6-disubstituted derivatives with benzoic acid did not decrease the uptake of benzoic acid, while co-incubation with other derivatives significantly decreased the uptake of benzoic acid. Kinetic analyses elucidated that the uptake of 2,6-dichlorobenzoic acid and 2,3,6-trichlorobenzoic acid did not involve the carrier-mediated process. The 2,6-disubstitution of benzoic acid may prevent the access of carboxylic acid group to MCTs expressed on the apical membranes of Caco-2 cells. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Pyrazinamide and Pyrazinoic Acid Derivatives Directed to Mycobacterial Enzymes Against Tuberculosis.

    PubMed

    Corrêa, Michelle Fidelis; Fernandes, João Paulo-dos Santos

    2016-01-01

    Tuberculosis (TB) is an infectious diseases responsible for thousands of deaths worldwide. Due to the use of antimycobacterial drugs, TB prevalence seemed to be controlled, but with the appearance of resistant tuberculosis cases, the concern about the disease had become significant again, as well as the need for new alternatives to TB treatment. Since pyrazinamide (PZA) is part of the firstline agents in TB treatment, several derivatives of this drug were described, besides pyrazinoic acid (POA) derivatives, the active form of PZA. POA has been used mainly to design prodrugs to be activated by mycobacterial esterases, while PZA derivatives should be activated specifically by the nicotinamidase/ pyrazinamidase (PZAse), or other PZAse-independent pathways. The intention of this paper is to discuss the state of art of PZA and POA derivatives and their activity against Mycobacterium tuberculosis and other mycobacteria, besides the therapeutic potential. Focus was given in prodrugs and derivatives directed to mycobacterial enzymes involved in its activation or mechanism of action.

  2. Precious-Metal-Free Heteroarylation of Azlactones: Direct Synthesis of α-Pyridyl, α-Substituted Amino Acid Derivatives.

    PubMed

    Johnson, Tarn C; Marsden, Stephen P

    2016-10-21

    A one-pot, three-component synthesis of α-pyridyl, α-substituted amino acid derivatives is described. The key transformation is a direct, precious-metal-free heteroarylation of readily available, amino acid derived azlactones with electrophilically activated pyridine N-oxides. The resulting intermediates can be used directly as efficient acylating agents for a range of nucleophiles, leading to the heteroarylated amino acid derivatives in a single vessel.

  3. Hyodeoxycholic acid derivatives as liver X receptor α and G-protein-coupled bile acid receptor agonists

    NASA Astrophysics Data System (ADS)

    de Marino, Simona; Carino, Adriana; Masullo, Dario; Finamore, Claudia; Marchianò, Silvia; Cipriani, Sabrina; di Leva, Francesco Saverio; Catalanotti, Bruno; Novellino, Ettore; Limongelli, Vittorio; Fiorucci, Stefano; Zampella, Angela

    2017-02-01

    Bile acids are extensively investigated for their potential in the treatment of human disorders. The liver X receptors (LXRs), activated by oxysterols and by a secondary bile acid named hyodeoxycholic acid (HDCA), have been found essential in the regulation of lipid homeostasis in mammals. Unfortunately, LXRα activates lipogenic enzymes causing accumulation of lipid in the liver. In addition to LXRs, HDCA has been also shown to function as ligand for GPBAR1, a G protein coupled receptor for secondary bile acids whose activation represents a promising approach to liver steatosis. In the present study, we report a library of HDCA derivatives endowed with modulatory activity on the two receptors. The lead optimization of HDCA moiety was rationally driven by the structural information on the binding site of the two targets and results from pharmacological characterization allowed the identification of hyodeoxycholane derivatives with selective agonistic activity toward LXRα and GPBAR1 and notably to the identification of the first example of potent dual LXRα/GPBAR1 agonists. The new chemical entities might hold utility in the treatment of dyslipidemic disorders.

  4. Monitoring of the fermentation media of citric acid by the trimethylsilyl derivatives of the organic acids formed.

    PubMed

    Ghassempour, Alireza; Nojavan, Saeed; Talebpour, Zahra; Amiri, Ali Asghar; Najafi, Nahid Mashkouri

    2004-10-20

    In this approach, a derivatization method is described for monitoring of organic acids in fermentation media without any separation step. The aqueous phase of fermentation media was evaporated and heated in a silylation reagent to form trimethylsilyl (TMS) derivatives. The silylated compounds are analyzed by 29Si nuclear magnetic resonance (29Si NMR) and gas chromatography-mass spectrometry (GC-MS). 29Si NMR can qualitatively monitor the components produced in the Krebs cycle. Quantification of these compounds is investigated by using selected ion monitoring mode of mass spectrometry. In this mode, mass to charge (m/z) values of their [M - 15]+ ions, which are 465, 275, 247, 221, 335, 251, and 313 of TMS derivatives of citric, alpha-ketoglutaric, succinic, fumaric, l-malic, oxaloacetic, and palmitic (as an internal standard), acids, respectively, are used. The limit of detection and the linear working range for derivatized citric acid were found to be 0.1 mg L(-1) and 10-3 x 10(4) mg L(-1). The relative standard deviation of the method for five replicates was 2.1%. The average recovery efficiency for citric acid added to culture media was approximately 97.2%. Quantitative results of GC-MS are compared with those obtained by an ultraviolet-visible method. Copyright 2004 American Chemical Society

  5. Hyodeoxycholic acid derivatives as liver X receptor α and G-protein-coupled bile acid receptor agonists

    PubMed Central

    De Marino, Simona; Carino, Adriana; Masullo, Dario; Finamore, Claudia; Marchianò, Silvia; Cipriani, Sabrina; Di Leva, Francesco Saverio; Catalanotti, Bruno; Novellino, Ettore; Limongelli, Vittorio; Fiorucci, Stefano; Zampella, Angela

    2017-01-01

    Bile acids are extensively investigated for their potential in the treatment of human disorders. The liver X receptors (LXRs), activated by oxysterols and by a secondary bile acid named hyodeoxycholic acid (HDCA), have been found essential in the regulation of lipid homeostasis in mammals. Unfortunately, LXRα activates lipogenic enzymes causing accumulation of lipid in the liver. In addition to LXRs, HDCA has been also shown to function as ligand for GPBAR1, a G protein coupled receptor for secondary bile acids whose activation represents a promising approach to liver steatosis. In the present study, we report a library of HDCA derivatives endowed with modulatory activity on the two receptors. The lead optimization of HDCA moiety was rationally driven by the structural information on the binding site of the two targets and results from pharmacological characterization allowed the identification of hyodeoxycholane derivatives with selective agonistic activity toward LXRα and GPBAR1 and notably to the identification of the first example of potent dual LXRα/GPBAR1 agonists. The new chemical entities might hold utility in the treatment of dyslipidemic disorders. PMID:28233865

  6. Simultaneous determination of 2-naphthoxyacetic acid and indole-3-acetic acid by first derivation synchronous fluorescence spectroscopy

    NASA Astrophysics Data System (ADS)

    Liu, Xiangxiang; Wan, Yiqun

    2013-07-01

    A simple, rapid, sensitive and selective method for simultaneously determining 2-naphthoxyacetic acid (BNOA) and Indole-3-Acetic Acid (IAA) in mixtures has been developed using derivation synchronous fluorescence spectroscopy based on their synchronous fluorescence. The synchronous fluorescence spectra were obtained with Δλ = 100 nm in a pH 8.5 NaH2PO4-NaOH buffer solution, and the detected wavelengths of quantitative analysis were set at 239 nm for BNOA and 293 nm for IAA respectively. The over lapped fluorescence spectra were well separated by the synchronous derivative method. Under optimized conditions, the limits of detection (LOD) were 0.003 μg/mL for BNOA and 0.012 μg/mL for IAA. This method is simple and expeditious, and it has been successfully applied to the determination of 2-naphthoxyacetic acid and indole-3-acetic acid in fruit juice samples with satisfactory results. The samples were only filtrated through a 0.45 μm membrane filter, which was free from the tedious separation procedures. The obtaining recoveries were in the range of 83.88-87.43% for BNOA and 80.76-86.68% for IAA, and the relative standard deviations were all less than 5.0%. Statistical comparison of the results with high performance liquid chromatography Mass Spectrometry (HPLC-MS) method revealed good agreement and proved that there were no significant difference in the accuracy and precision between these two methods.

  7. Simultaneous determination of 2-naphthoxyacetic acid and indole-3-acetic acid by first derivation synchronous fluorescence spectroscopy.

    PubMed

    Liu, Xiangxiang; Wan, Yiqun

    2013-07-01

    A simple, rapid, sensitive and selective method for simultaneously determining 2-naphthoxyacetic acid (BNOA) and Indole-3-Acetic Acid (IAA) in mixtures has been developed using derivation synchronous fluorescence spectroscopy based on their synchronous fluorescence. The synchronous fluorescence spectra were obtained with Δλ=100 nm in a pH 8.5 NaH2PO4-NaOH buffer solution, and the detected wavelengths of quantitative analysis were set at 239 nm for BNOA and 293 nm for IAA respectively. The over lapped fluorescence spectra were well separated by the synchronous derivative method. Under optimized conditions, the limits of detection (LOD) were 0.003 μg/mL for BNOA and 0.012 μg/mL for IAA. This method is simple and expeditious, and it has been successfully applied to the determination of 2-naphthoxyacetic acid and indole-3-acetic acid in fruit juice samples with satisfactory results. The samples were only filtrated through a 0.45 μm membrane filter, which was free from the tedious separation procedures. The obtaining recoveries were in the range of 83.88-87.43% for BNOA and 80.76-86.68% for IAA, and the relative standard deviations were all less than 5.0%. Statistical comparison of the results with high performance liquid chromatography Mass Spectrometry (HPLC-MS) method revealed good agreement and proved that there were no significant difference in the accuracy and precision between these two methods.

  8. Heterogeneous catalysts for the transformation of fatty acid triglycerides and their derivatives to fuel hydrocarbons

    NASA Astrophysics Data System (ADS)

    Yakovlev, Vadim A.; Khromova, Sofia A.; Bukhtiyarov, Valerii I.

    2011-10-01

    The results of studies devoted to the catalysts for transformation of fatty acid triglycerides and their derivatives to fuel hydrocarbons are presented and described systematically. Various approaches to the use of heterogeneous catalysts for the production of biofuel from these raw materials are considered. The bibliography includes 134 references.

  9. Cyathenosin A, a spiropyranosyl derivative of protocatechuic acid from Cyathea phalerata.

    PubMed

    Pizzolatti, Moacir Geraldo; Brighente, Ines Maria Costa; Bortoluzzi, Adailton João; Schripsema, Jan; Verdi, Luiz Gonzaga

    2007-05-01

    Cyathenosin A, a spiropyranosyl derivative of protocatechuic acid was isolated from the stem pith of Cyathea phalerata Mart. Its structure was determined by MS, 1D and 2D NMR spectroscopic analyses and confirmed by single crystal X-ray analysis. Cyathenosin A is the first example of a naturally occurring compound containing a spirocyclic orthoester pyranosidic structure.

  10. Antioxidant glucosylated caffeoylquinic acid derivatives in the invasive tropical soda apple, Solanum viarum

    USDA-ARS?s Scientific Manuscript database

    The eggplant (Solanum melongena) and other species within the “spiny solanums” (Solanum subgenus Leptostemonum) contain diverse and abundant antioxidant caffeoylquinic acid (CQA) derivatives. The fruit of an aggressive invasive species in the spiny solanums, Solanum viarum, contain numerous CQA deri...

  11. Diet derived phenolic acids regulate osteoblast and adipocyte lineage commitment and differentiation in young mice

    USDA-ARS?s Scientific Manuscript database

    A blueberry (BB) supplemented diet previously has been shown to significantly stimulate bone formation in rapidly growing male and female rodents. Phenolic acids (PAs) are metabolites derived from polyphenols found in fruits and vegetables as a result of the actions of gut bacteria, and they were fo...

  12. Benzyl benzoate glycoside and 3-deoxy-D-manno-2-octulosonic acid derivatives from Solidago decurrens.

    PubMed

    Shiraiwa, Ken; Yuan, Shen; Fujiyama, Ayako; Matsuo, Yosuke; Tanaka, Takashi; Jiang, Zhi-Hong; Kouno, Isao

    2012-01-27

    A new benzyl benzoate glycoside and five new 3-deoxy-D-manno-2-octulosonic acid derivatives were isolated from the entire plant of Solidago decurrens together with three known compounds. Their structures were established by extensive analyses of their 1D and 2D NMR spectra and by comparison with physical data of known compounds.

  13. [The identification of barbituric acid derivatives in the old blood stains on textiles].

    PubMed

    Kirichek, A V; Shabalina, A E; Rassinskaya, L A

    Thus article was designed to report a few cases of the identification of barbituric acid derivatives in the old blood stains on the clothes and other textiles. The data presented give evidence that barbiturates are capable of persisting in dry blood stains during rather a long period. The authors emphasize the necessity of mandatory control investigations to avoid obtaining the false positive results.

  14. An Overview of Stereoselective Synthesis of α-Aminophosphonic Acids and Derivatives

    PubMed Central

    Ordóñez, Mario; Rojas-Cabrera, Haydée; Cativiela, Carlos

    2009-01-01

    An overview of all methodologies published during the last few years focused to the stereoselective (diastereoselective or enantioselective) synthesis of α-aminophosphonic acids and derivatives is reported. The procedures have been classified according a retrosynthetic strategy and taking into account the formation of each one of the bonds connected to the chiral centre. PMID:20871799

  15. Nickel(II) and copper(II) complexes with humic acid anions and their derivatives

    SciTech Connect

    Ryabova, I.N.

    2008-01-15

    Complexation of Ni(II) and Cu(II) in aqueous solutions with anions of humic acids, extracted from naturally oxidized coal, and with their hydroxymethyl derivatives is studied spectrophotometrically and potentiometrically. The complexation stoichiometry and the stability constants of the complexes are determined.

  16. Correlation between chemical structure and rodent repellency of benzoic acid derivatives

    USGS Publications Warehouse

    Fearn, J.E.; DeWitt, J.B.

    1965-01-01

    Sixty-five benzoic acid derivatives were either prepared or obtained from commercial concerns, tested for rat repellency, and their indices of repellency computed. The data from these tests were considered analytically for any correlation between chemical structure and rat repellency. The results suggest a qualitative relationship which is useful in deciding probability of repellency in other compounds.

  17. An NMR study of merocyanine-type dyes derived from barbituric acid.

    PubMed

    Rezende, Marcos Caroli; Flores, Patricio; Guerrero, Juan; Villarroel, Luis

    2004-06-01

    The 13C NMR of two solvatochromic dyes derived from a barbituric acid acceptor and dimethylaminophenyl donor fragments, compound 1 and the related merocyanine 2, were recorded in various solvents. The observed chemical-shift variations were used to interpret their structural differences and solvatochromic behavior in solution.

  18. Mass spectral studies of the carboxylic acid ionophore antibiotic griseochelin and its derivatives.

    PubMed

    Schade, W; Gräfe, U; Schmidt, J

    1988-04-01

    The electron impact (EI) mass spectra (75 eV) of the new carboxylic acid ionophore griseochelin and some of its derivatives are discussed. The mass spectral fragmentation was studied using exact mass measurements and deuterium labelling. Furthermore, the negative ion mass spectra (2-4 eV) of these compounds are compared with their EI mass spectra.

  19. Tracking of Drug Release and Material Fate for Naturally Derived Omega-3 Fatty Acid Biomaterials.

    PubMed

    Faucher, Keith M; Artzi, Natalie; Beck, Moshe; Beckerman, Rita; Moodie, Geoff; Albergo, Theresa; Conroy, Suzanne; Dale, Alicia; Corbeil, Scott; Martakos, Paul; Edelman, Elazer R

    2016-03-01

    In vitro and in vivo studies were conducted on omega-3 fatty acid-derived biomaterials to determine their utility as an implantable material for adhesion prevention following soft tissue hernia repair and as a means to allow for the local delivery of antimicrobial or antibiofilm agents. Naturally derived biomaterials offer several advantages over synthetic materials in the field of medical device development. These advantages include enhanced biocompatibility, elimination of risks posed by the presence of toxic catalysts and chemical crosslinking agents, and derivation from renewable resources. Omega-3 fatty acids are readily available from fish and plant sources and can be used to create implantable biomaterials either as a stand-alone device or as a device coating that can be utilized in local drug delivery applications. In-depth characterization of material erosion degradation over time using non-destructive imaging and chemical characterization techniques provided mechanistic insight into material structure: function relationship. This in turn guided rational tailoring of the material based on varying fatty acid composition to control material residence time and hence drug release. These studies demonstrate the utility of omega-3 fatty acid derived biomaterials as an absorbable material for soft tissue hernia repair and drug delivery applications.

  20. Quality improvement of acidic soils by biochar derived from renewable materials.

    PubMed

    Moon, Deok Hyun; Hwang, Inseong; Chang, Yoon-Young; Koutsospyros, Agamemnon; Cheong, Kyung Hoon; Ji, Won Hyun; Park, Jeong-Hun

    2017-02-01

    Biochar derived from waste plant materials and agricultural residues was used to improve the quality of an acidic soil. The acidic soil was treated for 1 month with both soy bean stover-derived biochar and oak-derived biochar in the range of 1 to 5 wt% for pH improvement and exchangeable cation enhancement. Following 1 month of treatment, the soil pH was monitored and exchangeable cations were measured. Moreover, a maize growth experiment was performed for 14 days with selected treated soil samples to confirm the effectiveness of the treatment. The results showed that the pH of the treated acidic soil increased by more than 2 units, and the exchangeable cation values were greatly enhanced upon treatment with 5 wt% of both biochars, after 1 month of curing. Maize growth was superior in the 3 wt% biochar-treated samples compared to the control sample. The presented results demonstrate the effective use of biochar derived from renewable materials such as waste plant materials and agricultural residues for quality improvement of acidic soils.

  1. Production of Fatty Acid-Derived Valuable Chemicals in Synthetic Microbes

    PubMed Central

    Yu, Ai-Qun; Pratomo Juwono, Nina Kurniasih; Leong, Susanna Su Jan; Chang, Matthew Wook

    2014-01-01

    Fatty acid derivatives, such as hydroxy fatty acids, fatty alcohols, fatty acid methyl/ethyl esters, and fatty alka(e)nes, have a wide range of industrial applications including plastics, lubricants, and fuels. Currently, these chemicals are obtained mainly through chemical synthesis, which is complex and costly, and their availability from natural biological sources is extremely limited. Metabolic engineering of microorganisms has provided a platform for effective production of these valuable biochemicals. Notably, synthetic biology-based metabolic engineering strategies have been extensively applied to refactor microorganisms for improved biochemical production. Here, we reviewed: (i) the current status of metabolic engineering of microbes that produce fatty acid-derived valuable chemicals, and (ii) the recent progress of synthetic biology approaches that assist metabolic engineering, such as mRNA secondary structure engineering, sensor-regulator system, regulatable expression system, ultrasensitive input/output control system, and computer science-based design of complex gene circuits. Furthermore, key challenges and strategies were discussed. Finally, we concluded that synthetic biology provides useful metabolic engineering strategies for economically viable production of fatty acid-derived valuable chemicals in engineered microbes. PMID:25566540

  2. Production of Fatty Acid-derived valuable chemicals in synthetic microbes.

    PubMed

    Yu, Ai-Qun; Pratomo Juwono, Nina Kurniasih; Leong, Susanna Su Jan; Chang, Matthew Wook

    2014-01-01

    Fatty acid derivatives, such as hydroxy fatty acids, fatty alcohols, fatty acid methyl/ethyl esters, and fatty alka(e)nes, have a wide range of industrial applications including plastics, lubricants, and fuels. Currently, these chemicals are obtained mainly through chemical synthesis, which is complex and costly, and their availability from natural biological sources is extremely limited. Metabolic engineering of microorganisms has provided a platform for effective production of these valuable biochemicals. Notably, synthetic biology-based metabolic engineering strategies have been extensively applied to refactor microorganisms for improved biochemical production. Here, we reviewed: (i) the current status of metabolic engineering of microbes that produce fatty acid-derived valuable chemicals, and (ii) the recent progress of synthetic biology approaches that assist metabolic engineering, such as mRNA secondary structure engineering, sensor-regulator system, regulatable expression system, ultrasensitive input/output control system, and computer science-based design of complex gene circuits. Furthermore, key challenges and strategies were discussed. Finally, we concluded that synthetic biology provides useful metabolic engineering strategies for economically viable production of fatty acid-derived valuable chemicals in engineered microbes.

  3. Structure-activity relationships of anthraquinone derivatives derived from bromaminic acid as inhibitors of ectonucleoside triphosphate diphosphohydrolases (E-NTPDases)

    PubMed Central

    Baqi, Younis; Weyler, Stefanie; Iqbal, Jamshed; Zimmermann, Herbert

    2008-01-01

    Reactive blue 2 (RB-2) had been characterized as a relatively potent ectonucleoside triphosphate diphosphohydrolase (E-NTPDase) inhibitor with some selectivity for NTPDase3. In search for the pharmacophore and to analyze structure-activity relationships we synthesized a series of truncated derivatives and analogs of RB-2, including 1-amino-2-sulfo-4-ar(alk)ylaminoanthraquinones, 1-amino-2-methyl-4-arylaminoanthraquinones, 1-amino-4-bromoanthraquinone 2-sulfonic acid esters and sulfonamides, and bis-(1-amino-4-bromoanthraquinone) sulfonamides, and investigated them in preparations of rat NTPDase1, 2, and 3 using a capillary electrophoresis assay. Several 1-amino-2-sulfo-4-ar(alk)ylaminoanthraquinone derivatives inhibited E-NTPDases in a concentration-dependent manner. The 2-sulfonate group was found to be required for inhibitory activity, since 2-methyl-substituted derivatives were inactive. 1-Amino-2-sulfo-4-p-chloroanilinoanthraquinone (18) was identified as a nonselective competitive blocker of NTPDases1, 2, and 3 (Ki 16–18 μM), while 1-amino-2-sulfo-4-(2-naphthylamino)anthraquinone (21) was a potent inhibitor with preference for NTPDase1 (Ki 0.328 μM) and NTPDase3 (Ki 2.22 μM). Its isomer, 1-amino-2-sulfo-4-(1-naphthylamino)anthraquinone (20), was a potent and selective inhibitor of rat NTPDase3 (Ki 1.5 μM). PMID:18528783

  4. A Potent Plant-Derived Antifungal Acetylenic Acid Mediates Its Activity by Interfering with Fatty Acid Homeostasis

    PubMed Central

    Xu, Tao; Tripathi, Siddharth K.; Feng, Qin; Lorenz, Michael C.; Wright, Marsha A.; Jacob, Melissa R.; Mask, Melanie M.; Baerson, Scott R.; Li, Xing-Cong; Clark, Alice M.

    2012-01-01

    6-Nonadecynoic acid (6-NDA), a plant-derived acetylenic acid, exhibits strong inhibitory activity against the human fungal pathogens Candida albicans, Aspergillus fumigatus, and Trichophyton mentagrophytes. In the present study, transcriptional profiling coupled with mutant and biochemical analyses were conducted using the model yeast Saccharomyces cerevisiae to investigate its mechanism of action. 6-NDA elicited a transcriptome response indicative of fatty acid stress, altering the expression of genes that are required for yeast growth in the presence of oleate. Mutants of S. cerevisiae lacking transcription factors that regulate fatty acid β-oxidation showed increased sensitivity to 6-NDA. Fatty acid profile analysis indicated that 6-NDA inhibited the formation of fatty acids longer than 14 carbons in length. In addition, the growth inhibitory effect of 6-NDA was rescued in the presence of exogenously supplied oleate. To investigate the response of a pathogenic fungal species to 6-NDA, transcriptional profiling and biochemical analyses were also conducted in C. albicans. The transcriptional response and fatty acid profile of C. albicans were comparable to those obtained in S. cerevisiae, and the rescue of growth inhibition with exogenous oleate was also observed in C. albicans. In a fluconazole-resistant clinical isolate of C. albicans, a fungicidal effect was produced when fluconazole was combined with 6-NDA. In hyphal growth assays, 6-NDA inhibited the formation of long hyphal filaments in C. albicans. Collectively, our results indicate that the antifungal activity of 6-NDA is mediated by a disruption in fatty acid homeostasis and that 6-NDA has potential utility in the treatment of superficial Candida infections. PMID:22430960

  5. Mono- and disalicylic acid derivatives: PTP1B inhibitors as potential anti-obesity drugs.

    PubMed

    Shrestha, Suja; Bhattarai, Bharat Raj; Lee, Keun-Hyeung; Cho, Hyeongjin

    2007-10-15

    A series of compounds containing one or two salicylic acid moieties were synthesized, and their efficacy to inhibit the phosphohydrolase activity of PTP1B examined. Some of the methylenedisalicylic acid derivatives were potent inhibitors of PTP1B. Of those derivatives, 3c exhibited about a 14-fold selectivity against TC-PTP, and this compound was tested in a mouse model for its efficacy to prevent diet-induced obesity. It effectively suppressed the increases in body weight and adipose mass, without any noticeable toxic effect. The compound also prevented increases in the plasma triglyceride, cholesterol, and nonesterified fatty acid concentrations; thus, expanding its therapeutic potential to other related metabolic diseases, such as hyperlipidemia and hypercholesterolemia.

  6. Complete oxidative conversion of lignocellulose derived non-glucose sugars to sugar acids by Gluconobacter oxydans.

    PubMed

    Yao, Ruimiao; Hou, Weiliang; Bao, Jie

    2017-11-01

    Non-glucose sugars derived from lignocellulose cover approximately 40% of the total carbohydrates of lignocellulose biomass. The conversion of the non-glucose sugars to the target products is an important task of lignocellulose biorefining research. Here we report a fast and complete conversion of the total non-glucose sugars from corn stover into the corresponding sugar acids by whole cell catalysis and aerobic fermentation of Gluconobacter oxydans. The conversions include xylose to xylonate, arabinose to arabonate, mannose to mannonate, and galactose to galactonate, as well as with glucose into gluconate. These cellulosic non-glucose sugar acids showed the excellent cement retard setting property. The mixed cellulosic sugar acids could be used as cement retard additives without separation. The conversion of the non-glucose sugars not only makes full use of lignocellulose derived sugars, but also effectively reduces the wastewater treatment burden by removal of residual sugars. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Glycyrrhizic acid derivatives as influenza A/H1N1 virus inhibitors.

    PubMed

    Baltina, Lidia A; Zarubaev, Vladimir V; Baltina, Lia A; Orshanskaya, Iana A; Fairushina, Alina I; Kiselev, Oleg I; Yunusov, Marat S

    2015-04-15

    This Letter describes the synthesis and antiviral activity study of some glycyrrhizic acid (GL) derivatives against influenza A/H1N1/pdm09 virus in MDCK cells. Conjugation of GL with l-amino acids or their methyl esters, and amino sugar (d-galactose amine) dramatically changed its activity. The most active compounds were GL conjugates with aromatic amino acids methyl esters (phenylalanine and tyrosine) (SI=61 and 38), and S-benzyl-cysteine (SI=71). Thus modification of GL is a perspective route in the search of new antivirals, and some of GL derivatives are potent as anti-influenza A/H1N1 agents. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Reactive Derivatives of Nucleic Acids and Their Components as Affinity Reagents

    NASA Astrophysics Data System (ADS)

    Knorre, Dmitrii G.; Vlasov, Valentin V.

    1985-09-01

    The review is devoted to derivatives of nucleic acids and their components — nucleotides, nucleoside triphosphates, and oligonucleotides carrying reactive groups. Such derivatives are important tools for the investigation of protein-nucleic acid interactions and the functional topography of complex protein and nucleoprotein structures and can give rise to the prospect of being able to influence in a highly selective manner living organisms, including the nucleic acids and the nucleoproteins of the genetic apparatus. The review considers the principal groups of such reagents, the methods of their synthesis, and their properties which determine the possibility of their use for the selective (affinity) modification of biopolymers. The general principles of the construction of affinity reagents and their applications are analysed in relation to nucleotide affinity reagents. The bibliography includes 121 references.

  9. Synthesis, structure and cytotoxic activity of acetylenic derivatives of betulonic and betulinic acids

    NASA Astrophysics Data System (ADS)

    Bębenek, Ewa; Chrobak, Elwira; Wietrzyk, Joanna; Kadela, Monika; Chrobak, Artur; Kusz, Joachim; Książek, Maria; Jastrzębska, Maria; Boryczka, Stanisław

    2016-02-01

    A series of acetylenic derivatives of betulonic and betulinic acids has been synthesized and characterized by 1H and 13C NMR, IR and MS spectroscopy. The structure of propargyl betulonate 4 and propargyl betulinate-DMF solvate 8A was solved by X-ray diffraction. Thermal properties were examined using a DSC technique. The resulting alkynyl derivatives, as well as betulin 1 and betulinic acid 3, were evaluated in vitro for their cytotoxic activity against human T47D breast cancer, CCRF/CEM leukemia, SW707 colorectal, murine P388 leukemia and BALB3T3 normal fibroblasts cell lines. Several of the obtained compounds have a favorable cytotoxic profile than betulin 1. Propargyl betulinate 8 was the most active derivative, being up to 3-fold more potent than betulin 1 against the human leukemia (CCRF/CEM) cell line, with an IC50 value of 3.9 μg/mL.

  10. New neolignan glycoside and an unusual benzoyl malic acid derivative from Maytenus senegalensis leaves.

    PubMed

    Okoye, Festus Basden Chiedu; Agbo, Matthias Onyebuchi; Nworu, Chukwuemeka Sylvester; Nwodo, Ngozi Justina; Esimone, Charles Okechukwu; Osadebe, Patience Ogoamaka; Proksch, Peter

    2015-01-01

    Further investigation of the methanol leaf extract of Maytenus senegalensis led to the isolation of six compounds, including mayselignoside (1) and an unusual benzoyl malic acid derivative, benzoyl R-(+)-malic acid (2). Two known lignan derivatives (+)-lyoniresinol (3) and (-)-isolariciresinol (4), a known neolignan derivative dihydrodehydrodiconiferyl alcohol (5) and the triterpenoid, β-amyrin (6) were also isolated. The structures of these compounds were elucidated by a combination of 1D and 2D NMR and mass spectroscopy. All compounds were tested for cytotoxicity against mouse lymphoma cell line (L5178Y) and for antimicrobial activity against strains of bacteria and fungi. None of the compounds showed promising cytotoxic and/or antimicrobial activities.

  11. Electrochemical Coupling of Biomass‐Derived Acids: New C8 Platforms for Renewable Polymers and Fuels

    PubMed Central

    Wu, Linglin; Farmer, Thomas J.; Arnaud, Sacha Pérocheau; Wong Chang, Maria‐Angelica

    2016-01-01

    Abstract Electrolysis of biomass‐derived carbonyl compounds is an alternative to condensation chemistry for supplying products with chain length >C6 for biofuels and renewable materials production. Kolbe coupling of biomass‐derived levulinic acid is used to obtain 2,7‐octanedione, a new platform molecule only two low process‐intensity steps removed from raw biomass. Hydrogenation to 2,7‐octanediol provides a chiral secondary diol largely unknown to polymer chemistry, whereas intramolecular aldol condensation followed by hydrogenation yields branched cycloalkanes suitable for use as high‐octane, cellulosic gasoline. Analogous electrolysis of an itaconic acid‐derived methylsuccinic monoester yields a chiral 2,5‐dimethyladipic acid diester, another underutilized monomer owing to lack of availability. PMID:27873475

  12. Synthesis, saccharide-binding and anti-cancer cell proliferation properties of arylboronic acid derivatives of indoquinolines.

    PubMed

    Meng, Junxiu; Yu, Shaoqing; Wan, Shengbiao; Ren, Sumei; Jiang, Tao

    2011-11-01

    A facile synthesis of a series of saccharide-binding arylboronic acid derivatives of indoloquinoline was described. The key synthetic steps were polyphosphoric acid-mediated cyclization, chlorinative aromatization, and amidation. Mass spectrometry experiments revealed these synthetic arylboronic acid derivatives of indoquinolines could bind to biologically important carbohydrates (sialic acid, fucose, glucose, and galactose) by forming boronate di-esters in alkaline aqueous solution. Most of the arylboronic acid derivatives of indoquinolines inhibited human breast cancer cell (MDA-231) proliferation at a concentration of 5 μm, whereas the compound 17 exhibited highest percentages (76.74%) of the cancer cell proliferation inhibition.

  13. Enhanced Lignin Monomer Production Caused by Cinnamic Acid and Its Hydroxylated Derivatives Inhibits Soybean Root Growth

    PubMed Central

    Lima, Rogério Barbosa; Salvador, Victor Hugo; dos Santos, Wanderley Dantas; Bubna, Gisele Adriana; Finger-Teixeira, Aline; Soares, Anderson Ricardo; Marchiosi, Rogério; Ferrarese, Maria de Lourdes Lucio; Ferrarese-Filho, Osvaldo

    2013-01-01

    Cinnamic acid and its hydroxylated derivatives (p-coumaric, caffeic, ferulic and sinapic acids) are known allelochemicals that affect the seed germination and root growth of many plant species. Recent studies have indicated that the reduction of root growth by these allelochemicals is associated with premature cell wall lignification. We hypothesized that an influx of these compounds into the phenylpropanoid pathway increases the lignin monomer content and reduces the root growth. To confirm this hypothesis, we evaluated the effects of cinnamic, p-coumaric, caffeic, ferulic and sinapic acids on soybean root growth, lignin and the composition of p-hydroxyphenyl (H), guaiacyl (G) and syringyl (S) monomers. To this end, three-day-old seedlings were cultivated in nutrient solution with or without allelochemical (or selective enzymatic inhibitors of the phenylpropanoid pathway) in a growth chamber for 24 h. In general, the results showed that 1) cinnamic, p-coumaric, caffeic and ferulic acids reduced root growth and increased lignin content; 2) cinnamic and p-coumaric acids increased p-hydroxyphenyl (H) monomer content, whereas p-coumaric, caffeic and ferulic acids increased guaiacyl (G) content, and sinapic acid increased sinapyl (S) content; 3) when applied in conjunction with piperonylic acid (PIP, an inhibitor of the cinnamate 4-hydroxylase, C4H), cinnamic acid reduced H, G and S contents; and 4) when applied in conjunction with 3,4-(methylenedioxy)cinnamic acid (MDCA, an inhibitor of the 4-coumarate:CoA ligase, 4CL), p-coumaric acid reduced H, G and S contents, whereas caffeic, ferulic and sinapic acids reduced G and S contents. These results confirm our hypothesis that exogenously applied allelochemicals are channeled into the phenylpropanoid pathway causing excessive production of lignin and its main monomers. By consequence, an enhanced stiffening of the cell wall restricts soybean root growth. PMID:24312480

  14. Enhanced lignin monomer production caused by cinnamic Acid and its hydroxylated derivatives inhibits soybean root growth.

    PubMed

    Lima, Rogério Barbosa; Salvador, Victor Hugo; dos Santos, Wanderley Dantas; Bubna, Gisele Adriana; Finger-Teixeira, Aline; Soares, Anderson Ricardo; Marchiosi, Rogério; Ferrarese, Maria de Lourdes Lucio; Ferrarese-Filho, Osvaldo

    2013-01-01

    Cinnamic acid and its hydroxylated derivatives (p-coumaric, caffeic, ferulic and sinapic acids) are known allelochemicals that affect the seed germination and root growth of many plant species. Recent studies have indicated that the reduction of root growth by these allelochemicals is associated with premature cell wall lignification. We hypothesized that an influx of these compounds into the phenylpropanoid pathway increases the lignin monomer content and reduces the root growth. To confirm this hypothesis, we evaluated the effects of cinnamic, p-coumaric, caffeic, ferulic and sinapic acids on soybean root growth, lignin and the composition of p-hydroxyphenyl (H), guaiacyl (G) and syringyl (S) monomers. To this end, three-day-old seedlings were cultivated in nutrient solution with or without allelochemical (or selective enzymatic inhibitors of the phenylpropanoid pathway) in a growth chamber for 24 h. In general, the results showed that 1) cinnamic, p-coumaric, caffeic and ferulic acids reduced root growth and increased lignin content; 2) cinnamic and p-coumaric acids increased p-hydroxyphenyl (H) monomer content, whereas p-coumaric, caffeic and ferulic acids increased guaiacyl (G) content, and sinapic acid increased sinapyl (S) content; 3) when applied in conjunction with piperonylic acid (PIP, an inhibitor of the cinnamate 4-hydroxylase, C4H), cinnamic acid reduced H, G and S contents; and 4) when applied in conjunction with 3,4-(methylenedioxy)cinnamic acid (MDCA, an inhibitor of the 4-coumarate:CoA ligase, 4CL), p-coumaric acid reduced H, G and S contents, whereas caffeic, ferulic and sinapic acids reduced G and S contents. These results confirm our hypothesis that exogenously applied allelochemicals are channeled into the phenylpropanoid pathway causing excessive production of lignin and its main monomers. By consequence, an enhanced stiffening of the cell wall restricts soybean root growth.

  15. Potential Biological Applications of Bio-Based Anacardic Acids and Their Derivatives

    PubMed Central

    Hamad, Fatma B.; Mubofu, Egid B.

    2015-01-01

    Cashew nut shells (CNS), which are agro wastes from cashew nut processing factories, have proven to be among the most versatile bio-based renewable materials in the search for functional materials and chemicals from renewable resources. CNS are produced in the cashew nut processing process as waste, but they contain cashew nut shell liquid (CNSL) up to about 30–35 wt. % of the nut shell weight depending on the method of extraction. CNSL is a mixture of anacardic acid, cardanol, cardol, and methyl cardol, and the structures of these phenols offer opportunities for the development of diverse products. For anacardic acid, the combination of phenolic, carboxylic, and a 15-carbon alkyl side chain functional group makes it attractive in biological applications or as a synthon for the synthesis of a multitude of bioactive compounds. Anacardic acid, which is about 65% of a CNSL mixture, can be extracted from the agro waste. This shows that CNS waste can be used to extract useful chemicals and thus provide alternative green sources of chemicals, apart from relying only on the otherwise declining petroleum based sources. This paper reviews the potential of anacardic acids and their semi-synthetic derivatives for antibacterial, antitumor, and antioxidant activities. The review focuses on natural anacardic acids from CNS and other plants and their semi-synthetic derivatives as possible lead compounds in medicine. In addition, the use of anacardic acid as a starting material for the synthesis of various biologically active compounds and complexes is reported. PMID:25894225

  16. Incorporation of salicylic acid derivatives to hydrophilic copolymer systems with biomedical applications.

    PubMed

    Elvira, C; Gallardo, A; Lacroix, N; Schacht, E; San Román, J

    2001-06-01

    Hydrogels based on polymeric derivatives of salicylic acid have been prepared for biomedical applications by free radical copolymerization of 2-hydroxy-4-methacrylamidobenzoic acid, 4HMA, and 2-hydroxy-5-methacrylamidobenzoic acid, 5HMA, with 2- hydroxyethylmethacrylate, HEMA, in a wide range of compositions. The reactivity ratios of 4HMA and 5HMA with HEMA in radical copolymerization processes have been determined from their 1H NMR spectra by applying linearization methods and non-linear least square treatments. Tgs of the corresponding copolymers were analyzed by DSC. The swelling behavior in water of the prepared copolymers was studied in comparison to poly-(HEMA), poly-(4HMA) and poly-(5HMA) hydration degrees, being in all cases superior to 35%. The hydrolytical behavior of the synthesized copolymers was studied at three different pHs (2, 7.4 and 10) determining the release percentage of the salicylic acid derivatives, 4-amino salicylic acid, 4ASA, and 5-amino salicylic acid, 5ASA, analyzed by high performance liquid chromatography (HPLC). The release analysis was followed during 230 days and a pH dependence was observed obtaining the highest release percentages at pH=10, whereas at physiological pH (7.4) the release percentages were in range from 2 to 5% at that time for all copolymer systems. The hydrolytical stability is enough for long-term applications like bone cements, ionomers, etc.

  17. Synthesis of benzamide derivatives of anacardic acid and their cytotoxic activity.

    PubMed

    Chandregowda, Venkateshappa; Kush, Anil; Reddy, Goukanapalli Chandrasekara

    2009-06-01

    Several benzamide derivatives were synthesized from anacardic acid (1a) which was the product of hydrogenation of the naturally occurring anacardic acid mixture (1a-d), a major constituent of cashew nut shell liquid. Anacardic acid (1a) was first alkylated followed by hydrolysis of the ester to obtain synthones namely, 2-ethoxy-6-pentadecylbenzoic acid (5) and 2-isopropoxy-6-pentadecylbenzoic acid (6). These salicylic acid derivatives were then coupled with a variety of anilines to obtain novel benzamide compounds (7-39). Cytotoxic effect of these synthesized compounds was tested on HeLa cell line of wild type with relatively high expression of p300 and on HCT-15, which is p300 negative. Of all the compounds, 2-isopropoxy-6-pentadecyl-N-pyridin-4-ylbenzamide (27), 2-ethoxy-N-(3-nitrophenyl)-6-pentadecylbenzamide (22) and 2-ethoxy-6-pentadecyl-N-pyridin-4-ylbenzamide (10) were found to be more potent with the respective IC(50) values 11.02 microM, 13.55 microM, 15.29 microM on HeLa cell line. Their activities are comparable with garcinol which is a cell permeable histone acetyltransferase (HAT) inhibitor and 10 fold more active than p300 HAT activators so far reported.

  18. Potential biological applications of bio-based anacardic acids and their derivatives.

    PubMed

    Hamad, Fatma B; Mubofu, Egid B

    2015-04-16

    Cashew nut shells (CNS), which are agro wastes from cashew nut processing factories, have proven to be among the most versatile bio-based renewable materials in the search for functional materials and chemicals from renewable resources. CNS are produced in the cashew nut processing process as waste, but they contain cashew nut shell liquid (CNSL) up to about 30-35 wt. % of the nut shell weight depending on the method of extraction. CNSL is a mixture of anacardic acid, cardanol, cardol, and methyl cardol, and the structures of these phenols offer opportunities for the development of diverse products. For anacardic acid, the combination of phenolic, carboxylic, and a 15-carbon alkyl side chain functional group makes it attractive in biological applications or as a synthon for the synthesis of a multitude of bioactive compounds. Anacardic acid, which is about 65% of a CNSL mixture, can be extracted from the agro waste. This shows that CNS waste can be used to extract useful chemicals and thus provide alternative green sources of chemicals, apart from relying only on the otherwise declining petroleum based sources. This paper reviews the potential of anacardic acids and their semi-synthetic derivatives for antibacterial, antitumor, and antioxidant activities. The review focuses on natural anacardic acids from CNS and other plants and their semi-synthetic derivatives as possible lead compounds in medicine. In addition, the use of anacardic acid as a starting material for the synthesis of various biologically active compounds and complexes is reported.

  19. Gastroprotective mechanisms of action of semisynthetic carnosic acid derivatives in human cells.

    PubMed

    Theoduloz, Cristina; Pertino, Mariano Walter; Schmeda-Hirschmann, Guillermo

    2014-01-06

    Carnosic acid (CA) and its semisynthetic derivatives display relevant gastroprotective effects on HCl/ethanol induced gastric lesions in mice. However, little is known on the mechanisms of action of the new compounds. The aim of the present work was to assess the gastroprotective action mechanisms of CA and its derivatives using human cell culture models. A human gastric adenocarcinoma cell line (AGS) and lung fibroblasts (MRC-5) were used to reveal the possible mechanisms involved. The ability of the compounds to protect cells against sodium taurocholate (NaT)-induced damage, and to increase the cellular reduced glutathione (GSH) and prostaglandin E2 (PGE2) content was determined using AGS cells. Stimulation of cell proliferation was studied employing MRC-5 fibroblasts. Carnosic acid and its derivatives 10-18 raised GSH levels in AGS cells. While CA did not increase the PGE2 content in AGS cells, all derivatives significantly stimulated PGE2 synthesis, the best effect being found for the 12-O-indolebutyrylmethylcarnosate 13. A significant increase in MRC-5 fibroblast proliferation was observed for the derivatives 7 and 16-18. The antioxidant effect of the compounds was assessed by the inhibition of lipid peroxidation in human erythrocyte membranes, scavenging of superoxide anion and DPPH discoloration assay. The new CA derivatives showed gastroprotective effects by different mechanisms, including protection against cell damage induced by NaT, increase in GSH content, stimulation of PGE2 synthesis and cell proliferation.

  20. Detection and quantification of protein adduction by electrophilic fatty acids: mitochondrial generation of fatty acid nitroalkene derivatives.

    PubMed

    Schopfer, F J; Batthyany, C; Baker, P R S; Bonacci, G; Cole, M P; Rudolph, V; Groeger, A L; Rudolph, T K; Nadtochiy, S; Brookes, P S; Freeman, B A

    2009-05-01

    Nitroalkene fatty acid derivatives manifest a strong electrophilic nature, are clinically detectable, and induce multiple transcriptionally regulated anti-inflammatory responses. At present, the characterization and quantification of endogenous electrophilic lipids are compromised by their Michael addition with protein and small-molecule nucleophilic targets. Herein, we report a trans-nitroalkylation reaction of nitro-fatty acids with beta-mercaptoethanol (BME) and apply this reaction to the unbiased identification and quantification of reaction with nucleophilic targets. Trans-nitroalkylation yields are maximal at pH 7 to 8 and occur with physiological concentrations of target nucleophiles. This reaction is also amenable to sensitive mass spectrometry-based quantification of electrophilic fatty acid-protein adducts upon electrophoretic resolution of proteins. In-gel trans-nitroalkylation reactions also permit the identification of protein targets without the bias and lack of sensitivity of current proteomic approaches. Using this approach, it was observed that fatty acid nitroalkenes are rapidly metabolized in vivo by a nitroalkene reductase activity and mitochondrial beta-oxidation, yielding a variety of electrophilic and nonelectrophilic products that could be structurally characterized upon BME-based trans-nitroalkylation reaction. This strategy was applied to the detection and quantification of fatty acid nitration in mitochondria in response to oxidative inflammatory conditions induced by myocardial ischemia-reoxygenation.

  1. Absorption of dimethoxycinnamic acid derivatives in vitro and pharmacokinetic profile in human plasma following coffee consumption.

    PubMed

    Farrell, Tracy L; Gomez-Juaristi, Miren; Poquet, Laure; Redeuil, Karine; Nagy, Kornél; Renouf, Mathieu; Williamson, Gary

    2012-09-01

    This study reports the 24 h human plasma pharmacokinetics of 3,4-dimethoxycinnamic acid (dimethoxycinnamic acid) after consumption of coffee, and the membrane transport characteristics of certain dimethoxycinnamic acid derivatives, as present in coffee. Eight healthy human volunteers consumed a low-polyphenol diet for 24 h before drinking 400 mL of commercially available coffee. Plasma samples were collected over 24 h and analyzed by HPLC-MS(2) . Investigation of the mechanism of absorption and metabolism was performed using an intestinal Caco-2 cell model. For the first time, we show that dimethoxycinnamic acid appears in plasma as the free aglycone. The time to reach the C(max) value of approximately 0.5 μM was rapid, T(max) = 30 min, and showed an additional peak at 2-4 h for several subjects. In contrast, smaller amounts of dimethoxy-dihydrocinnamic acid (C(max) ∼ 0.1 μM) peaked between 8 and 12 h after coffee intake. In the cell model, dimethoxycinnamic acid was preferentially transported in the free form by passive diffusion, and a small amount of dimethoxycinnamoylquinic acid hydrolysis was observed. These findings show that dimethoxycinnamic acid, previously identified in plasma after coffee consumption, was rapidly absorbed in the free form most likely by passive diffusion in the upper gastrointestinal tract. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Liquid chromatographic enantiomer separation of 1-naphthylamides of chiral acids using several amylose- and cellulose-derived chiral stationary phases.

    PubMed

    Islam, Md F; Adhikari, Suraj; Paik, Man-Jeong; Lee, Wonjae

    2017-03-01

    The liquid chromatographic enantiomer separation of various chiral acids as 1-naphthylamides was performed using several chiral stationary phases (CSPs). The CSPs used in this study were six covalently bonded and four coated type CSPs derived from amylose and cellulose derivatives as chiral selectors. The degree of enantioseparation is affected by the structure of chiral acids and the CSPs used, which have different chiral selectors and types of immobilization. For the enantiomer resolution of chiral acids as 1-naphthylamide derivatives, the performance of the coated type Lux Cellulose-1 was superior to those of the other CSPs, except for 2-aryloxypropionic acid derivatives. Owing to the strong ultraviolet absorbance of the 1-naphthyl group, the convenient analytical method developed and validated in this study could be expected to be very useful for the enantiomer separation of various chiral acids as 1-naphthylamide derivatives using polysaccharide-derived CSPs.

  3. Scaleable production and separation of fermentation-derived acetic acid. Final CRADA report.

    SciTech Connect

    Snyder, S. W.; Energy Systems

    2010-02-08

    Half of U.S. acetic acid production is used in manufacturing vinyl acetate monomer (VAM) and is economical only in very large production plants. Nearly 80% of the VAM is produced by methanol carbonylation, which requires high temperatures and exotic construction materials and is energy intensive. Fermentation-derived acetic acid production allows for small-scale production at low temperatures, significantly reducing the energy requirement of the process. The goal of the project is to develop a scaleable production and separation process for fermentation-derived acetic acid. Synthesis gas (syngas) will be fermented to acetic acid, and the fermentation broth will be continuously neutralized with ammonia. The acetic acid product will be recovered from the ammonium acid broth using vapor-based membrane separation technology. The process is summarized in Figure 1. The two technical challenges to success are selecting and developing (1) microbial strains that efficiently ferment syngas to acetic acid in high salt environments and (2) membranes that efficiently separate ammonia from the acetic acid/water mixture and are stable at high enough temperature to facilitate high thermal cracking of the ammonium acetate salt. Fermentation - Microbial strains were procured from a variety of public culture collections (Table 1). Strains were incubated and grown in the presence of the ammonium acetate product and the fastest growing cultures were selected and incubated at higher product concentrations. An example of the performance of a selected culture is shown in Figure 2. Separations - Several membranes were considered. Testing was performed on a new product line produced by Sulzer Chemtech (Germany). These are tubular ceramic membranes with weak acid functionality (see Figure 3). The following results were observed: (1) The membranes were relatively fragile in a laboratory setting; (2) Thermally stable {at} 130 C in hot organic acids; (3) Acetic acid rejection > 99%; and (4

  4. Radical-derived oxidation products of 5-aminosalicylic acid and N-acetyl-5-aminosalicylic acid.

    PubMed

    Fischer, C; Klotz, U

    1994-11-04

    5-Aminosalicylic acid is an agent effective in the treatment of chronic inflammatory bowel diseases. Its ability to scavenge radicals is considered to be a major factor responsible for its therapeutic efficacy. In this study oxidation products of aminosalicylates with hydroxyl radicals were produced. The compounds that could be discovered by gas chromatographic-mass spectrometric analysis originate from a 1,4-benzoquinone monoimine intermediate which subsequently undergoes multiple reactions such as hydrolysis, reductive 1,4-Michael addition, reoxidation and decarboxylation. Some of these products could represent metabolites formed under in vivo conditions and thus provide a tool for screening biological material from subjects under different clinical conditions.

  5. The influence of the crystal structure on aggregation-induced luminescence of derivatives of aminobenzoic acid

    NASA Astrophysics Data System (ADS)

    Nosova, D. A.; Zarochentseva, E. P.; Vysotskaya, S. O.; Klemesheva, N. A.; Korotkov, V. I.

    2014-12-01

    The luminescence of three derivatives of 2-(phenylamino)-benzoic acid (N-phenylanthranilic, mefenamic, and niflumic acids) in benzene solution, in the polycrystalline state, and in the hexamethylbenzene matrix is studied. In the crystalline state, these compounds exhibit intense aggregation-induced luminescence. An increase in luminescence is also observed in the impurity crystal. The hexamethylbenzene crystal lattice restricts the mobility of molecules, thus ensuring the rigidity of the molecular structure of acids, which decreases the efficiency of nonradiative electron energy degradation. The main reason for the increase in the luminescence intensity in the case of fixation in a crystalline matrix is the formation of intramolecular hydrogen bonds and dimers of acid molecules.

  6. EIMS Fragmentation Pathways and MRM Quantification of 7α/β-Hydroxy-Dehydroabietic Acid TMS Derivatives.

    PubMed

    Rontani, Jean-François; Aubert, Claude; Belt, Simon T

    2015-09-01

    EI mass fragmentation pathways of TMS derivatives οf 7α/β-hydroxy-dehydroabietic acids resulting from NaBH(4)-reduction of oxidation products of dehydroabietic acid (a component of conifers) were investigated and deduced by a combination of (1) low energy CID-GC-MS/MS, (2) deuterium labeling, (3) different derivatization methods, and (4) GC-QTOF accurate mass measurements. Having identified the main fragmentation pathways, the TMS-derivatized 7α/β-hydroxy-dehydroabietic acids could be quantified in multiple reaction monitoring (MRM) mode in sea ice and sediment samples collected from the Arctic. These newly characterized transformation products of dehydroabietic acid constitute potential tracers of biotic and abiotic degradation of terrestrial higher plants in the environment.

  7. Synthesis and characteristics of (Hydrogenated) ferulic acid derivatives as potential antiviral agents with insecticidal activity

    PubMed Central

    2013-01-01

    Background Plant viruses cause many serious plant diseases and are currently suppressed with the simultaneous use of virucides and insecticides. The use of such materials, however, increases the amounts of pollutants in the environment. To reduce environmental contaminants, virucides with insecticidal activity is an attractive option. Results A series of substituted ferulic acid amide derivatives 7 and the corresponding hydrogenated ferulic acid amide derivatives 13 were synthesized and evaluated for their antiviral and insecticidal activities. The majority of the synthesized compounds exhibited good levels of antiviral activity against the tobacco mosaic virus (TMW), with compounds 7a, 7b and 7d in particular providing higher levels of protective and curative activities against TMV at 500 μg/mL than the control compound ribavirin. Furthermore, these compounds displayed good insecticidal activities against insects with piercing-sucking mouthparts, which can spread plant viruses between and within crops. Conclusions Two series of ferulic acid derivatives have been synthesized efficiently. The bioassay showed title compounds not only inhibit the plant viral infection, but also prevented the spread of plant virus by insect vectors. These findings therefore demonstrate that the ferulic acid amides represent a new template for future antiviral studies. PMID:23409923

  8. Photoaffinity labeling of a bacterial sialidase with an aryl azide derivative of sialic acid

    SciTech Connect

    van der Horst, G.T.; Mancini, G.M.; Brossmer, R.; Rose, U.; Verheijen, F.W. )

    1990-07-05

    A photoreactive radioiodinatable derivative of 2-deoxy-2,3-didehydro-5-N-acetylneuraminic acid (NeuAc2en), 5-N-acetyl-9-(4-azidosalicoylamido)-2-deoxy-2,3-didehydroneuram inic acid (ASA-NeuAc2-en) has been synthesized and used to label the active site of Clostridium perfringens sialidase. Like NeuAc2en, its aryl azide derivative is a strong competitive inhibitor of sialidase (Ki approximately 15 microM). The absorbance spectrum of ASA-NeuAc2en shows a characteristic aryl azide peak, which disappears upon photolysis with UV light. When its radioiodinated counterpart 5-N-acetyl-9-(4-iodoazidosalicoylamido)-2-deoxy-2,3-didehydrone uraminic acid (({sup 125}I)IASA-NeuAc2en) was photolyzed in the presence of C. perfringens sialidase a 72-kDa protein was labeled. Labeling occurred specifically in the active site since it was inhibited in the presence of NeuAc2en. Chemical cleavage of the photoaffinity-labeled 72-kDa protein demonstrates that specifically labeled peptides involved in the formation of the active site can easily be determined. ASA-NeuAc2en is a valuable new tool for the identification and structural/functional analysis of sialidases and other proteins, recognizing this sialic acid derivative.

  9. An Overview of Structurally Modified Glycyrrhetinic Acid Derivatives as Antitumor Agents.

    PubMed

    Xu, Bing; Wu, Gao-Rong; Zhang, Xin-Yu; Yan, Meng-Meng; Zhao, Rui; Xue, Nan-Nan; Fang, Kang; Wang, Hui; Chen, Meng; Guo, Wen-Bo; Wang, Peng-Long; Lei, Hai-Min

    2017-06-02

    Glycyrrhetinic Acid (GA), a triterpenoid aglycone component of the natural product glycyrrhizinic acid, was found to possess remarkable anti-proliferative and apoptosis-inducing activity in various cancer cell lines. Though GA was not as active as other triterpenes, such as betulinic acid and oleanolic acid, it could trigger apoptosis in tumor cells and it can be obtained easily and cheaply, which has stimulated scientific interest in using GA as a scaffold to synthesize new antitumor agents. The structural modifications of GA reported in recent decades can be divided into four groups, which include structural modifications on ring-A, ring-C, ring-E and multiple ring modifications. The lack of a comprehensive and recent review on this topic prompted us to gather more new information. This overview is dedicated to summarizing and updating the structural modification of GA to improve its antitumor activity published between 2005 and 2016. We reviewed a total of 210 GA derivatives that we encountered and compiled the most active GA derivatives along with their activity profile in different series. Furthermore, the structure activity relationships of these derivatives are briefly discussed. The included information is expected to be of benefit to further studies of structural modifications of GA to enhance its antitumor activity.

  10. Antiparasitic evaluation of betulinic acid derivatives reveals effective and selective anti-Trypanosoma cruzi inhibitors.

    PubMed

    Meira, Cássio Santana; Barbosa-Filho, José Maria; Lanfredi-Rangel, Adriana; Guimarães, Elisalva Teixeira; Moreira, Diogo Rodrigo Magalhães; Soares, Milena Botelho Pereira

    2016-07-01

    Betulinic acid is a pentacyclic triterpenoid with several biological properties already described, including antiparasitic activity. Here, the anti-Trypanosoma cruzi activity of betulinic acid and its semi-synthetic amide derivatives (BA1-BA8) was investigated. The anti-Trypanosoma cruzi activity and selectivity were enhanced in semi-synthetic derivatives, specially on derivatives BA5, BA6 and BA8. To understand the mechanism of action underlying betulinic acid anti-T. cruzi activity, we investigated ultrastructural changes by electron microscopy. Ultrastructural studies showed that trypomastigotes incubated with BA5 had membrane blebling, flagella retraction, atypical cytoplasmic vacuoles and Golgi cisternae dilatation. Flow cytometry analysis showed that parasite death is mainly caused by necrosis. Treatment with derivatives BA5, BA6 or BA8 reduced the invasion process, as well as intracellular parasite development in host cells, with a potency and selectivity similar to that observed in benznidazole-treated cells. More importantly, the combination of BA5 and benznidazole revealed synergistic effects on trypomastigote and amastigote forms of T. cruzi. In conclusion, we demonstrated that BA5 compound is an effective and selective anti-T. cruzi agent. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Carboxylic Acid Fullerene (C60) Derivatives Attenuated Neuroinflammatory Responses by Modulating Mitochondrial Dynamics

    NASA Astrophysics Data System (ADS)

    Ye, Shefang; Zhou, Tong; Cheng, Keman; Chen, Mingliang; Wang, Yange; Jiang, Yuanqin; Yang, Peiyan

    2015-05-01

    Fullerene (C60) derivatives, a unique class of compounds with potent antioxidant properties, have been reported to exert a wide variety of biological activities including neuroprotective properties. Mitochondrial dynamics are an important constituent of cellular quality control and function, and an imbalance of the dynamics eventually leads to mitochondria disruption and cell dysfunctions. This study aimed to assess the effects of carboxylic acid C60 derivatives (C60-COOH) on mitochondrial dynamics and elucidate its associated mechanisms in lipopolysaccharide (LPS)-stimulated BV-2 microglial cell model. Using a cell-based functional screening system labeled with DsRed2-mito in BV-2 cells, we showed that LPS stimulation led to excessive mitochondrial fission, increased mitochondrial localization of dynamin-related protein 1 (Drp1), both of which were markedly suppressed by C60-COOH pretreatment. LPS-induced mitochondria reactive oxygen species (ROS) generation and collapse of mitochondrial membrane potential (Δ Ψm) were also significantly inhibited by C60-COOH. Moreover, we also found that C60-COOH pretreatment resulted in the attenuation of LPS-mediated activation of nuclear factor (NF)-κB and mitogen-activated protein kinase (MAPK) signaling, as well as the production of pro-inflammatory mediators. Taken together, these findings demonstrated that carboxylic acid C60 derivatives may exert neuroprotective effects through regulating mitochondrial dynamics and functions in microglial cells, thus providing novel insights into the mechanisms of the neuroprotective properties of carboxylic acid C60 derivatives.

  12. Bile acid-derived mono- and diketals--synthesis, structural characterization and self-assembling properties.

    PubMed

    Ikonen, Satu; Nonappa; Valkonen, Arto; Juvonen, Raija; Salo, Hannu; Kolehmainen, Erkki

    2010-06-21

    Three oxo-derivatives of bile acid methyl esters have been used as starting compounds in the preparation of novel bile acid monoketals with 1,2-benzenediol (catechol) and 2,3-naphthalenediol, as well as mono- and diketals with pentaerythritol. Monoketals of pentaerythritol showed a tendency to form thermoreversible gels in many aromatic solvents and the methyl lithocholate derivative proved to be a supergelator able to form a gel with t-butylbenzene at a concentration as low as 0.5% w/v. Whereas the naphthalenediol ketals formed film-type materials in the studied solvents, the catechol ketals underwent rapid crystallization into X-ray quality single crystals. Single crystal X-ray structures of the catechol ketals have been determined. The monoketal obtained from methyl-3,7,12-trioxo-5beta-cholan-24-oate (dehydrocholate) revealed to have an unusual packing pattern in its solid state compared to other bile acid derivatives reported in the literature. The synthesis of diketals from pentaerythritol furnished a mixture of two diastereomers which, in the case of the methyl lithocholate derivative, have been separated and the X-ray crystal structure of one isomer resolved.

  13. Anticancer activity of small amphipathic β²,²-amino acid derivatives.

    PubMed

    Hansen, Terkel; Ausbacher, Dominik; Zachariassen, Zack G; Anderssen, Trude; Havelkova, Martina; Strøm, Morten B

    2012-12-01

    We report the anticancer activity from screening of a series of synthetic β(2,2)-amino acid derivatives that were prepared to confirm the pharmacophore model of short cationic antimicrobial peptides with high anti-Staphylococcal activity. The most potent derivatives against human Burkitt's lymphoma (Ramos) cells displayed IC(50) values below 8 μM, and low toxicity against human red blood cells (EC(50) > 200 μM). A more than 5-fold preference for Ramos cancer cells compared to human lung fibroblasts (MRC-5 cells) was also obtained for the most promising β(2,2)-amino acid derivative 3-amino-N-(2-aminoethyl)-2,2-bis(naphthalen-2-ylmethyl)propanamide (5c). Screening of 5c at the National Cancer Institute (NCI, USA) confirmed its anticancer potency and revealed a very broad range of anticancer activity with IC(50) values of 0.32-3.89 μM against 59 different cancer cell lines. Highest potency was obtained against the colon cancer cell lines, a non-small cell lung cancer, a melanoma, and three leukemia cell lines included in the NCI screening panel. The reported β(2,2)-amino acid derivatives constitute a promising new class of anticancer agents based on their high anticancer potency, ease of synthesis, mode-of-action, and optimized pharmacokinetic properties compared to much larger antimicrobial peptides. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  14. Dienophile-Modified Mannosamine Derivatives for Metabolic Labeling of Sialic Acids: A Comparative Study.

    PubMed

    Dold, Jeremias E G A; Pfotzer, Jessica; Späte, Anne-Katrin; Wittmann, Valentin

    2017-03-20

    Sialic acids play an important role in numerous cell adhesion processes and sialylation levels are known to be altered under certain pathogenic conditions such as cancer. Metabolic glycoengineering with mannosamine derivatives is a convenient way to introduce non-natural chemical reporter groups into sialylated glycoconjugates offering the opportunity to label sialic acids using bioorthogonal ligation chemistry. The labeling intensity not only depends on the rate of the ligation reaction but also on the extent to which the natural sialic acids are replaced by the modified ones, i.e. the incorporation efficiency. Here we present a comparative study of eight mannosamine derivatives featuring terminal alkenes as chemical reporter groups that can be labeled by an inverse-electron-demand Diels-Alder (DAinv) reaction. The derivatives differ in chain length as well as the type of linkage (comprising carbamates, amides, and a urea) that connects the terminal alkene to the sugar. As a general trend, increasing chain lengths result in higher DAinv reactivity and at the same time reduced incorporation efficiency. Carbamates are better accepted than amides with the same chain length; nevertheless do the latter result in more intense cell-surface staining visible in life-cell fluorescence microscopy. Finally, a urea derivative was shown to be accepted.

  15. The influence of humic acids derived from earthworm-processed organic wastes on plant growth.

    PubMed

    Atiyeh, R M; Lee, S; Edwards, C A; Arancon, N Q; Metzger, J D

    2002-08-01

    Some effects of humic acids, formed during the breakdown of organic wastes by earthworms (vermicomposting), on plant growth were evaluated. In the first experiment, humic acids were extracted from pig manure vermicompost using the classic alkali/acid fractionation procedure and mixed with a soilless container medium (Metro-Mix 360), to provide a range of 0, 50, 100, 150, 200, 250, 500, 1,000, 2,000, and 4,000 mg of humate per kg of dry weight of container medium, and tomato seedlings were grown in the mixtures. In the second experiment, humates extracted from pig manure and food wastes vermicomposts were mixed with vermiculite to provide a range of 0, 50, 125, 250, 500, 1,000, and 4,000 mg of humate per kg of dry weight of the container medium, and cucumber seedlings were grown in the mixtures. Both tomato and cucumber seedlings were watered daily with a solution containing all nutrients required to ensure that any differences in growth responses were not nutrient-mediated. The incorporation of both types of vermicompost-derived humic acids, into either type of soilless plant growth media, increased the growth of tomato and cucumber plants significantly, in terms of plant heights, leaf areas, shoot and root dry weights. Plant growth increased with increasing concentrations of humic acids incorporated into the medium up to a certain proportion, but this differed according to the plant species, the source of the vermicompost, and the nature of the container medium. Plant growth tended to be increased by treatments of the plants with 50-500 mg/kg humic acids, but often decreased significantly when the concentrations of humic acids derived in the container medium exceeded 500-1,000 mg/kg. These growth responses were most probably due to hormone-like activity of humic acids from the vermicomposts or could have been due to plant growth hormones adsorbed onto the humates.

  16. Composition, assimilation and degradation of Phaeocystis globosa-derived fatty acids in the North Sea

    NASA Astrophysics Data System (ADS)

    Hamm, Christian E.; Rousseau, Veronique

    2003-12-01

    The fate of a Phaeocystis globosa bloom in the southern North Sea off Belgium, the Netherlands and Germany in May 1995 was investigated during a cruise with RV 'Belgica'. We used fatty acids as biomarkers to follow the fate of Phaeocystis-derived biomass of a Phaeocystis-dominated spring bloom. The bloom, in which up to >99% of the biomass was contributed by Phaeocystis, showed a fatty acid composition with a characteristically high abundance of polyunsaturated C 18-fatty acids, which increased in concentration with number of double bonds up to 18:5 (n-3), and high concentrations of 20:5 (n-3) and 22:6 (n-3). In contrast to most previous studies, fatty acid analysis of the mesozooplankton community (mainly calanoid copepods) and meroplankton ( Carcinus maenas megalope) indicated that P. globosa was a major component (ca. 70% and 50%, respectively) in the diet of these organisms. Massive accumulations of amorphous grey aggregates, in which Phaeocystis colonies were major components, were dominated by saturated fatty acids and contained only few of the polyunsaturated C 18-fatty acids. A hydrophobic surface slick that covered the water surface during the bloom showed very similar patterns. Foam patches contained few Phaeocystis-typical fatty acids, but increased amounts of diatom-typical compounds such as 16:1 (n-7) and 20:5 (n-3), and 38% fatty alcohols, indicating that wax esters dominated the lipid fraction in the foam with ca. 76% (w/w). The fatty acid compositions of surface sediment showed that no sedimentation of fresh Phaeocystis occurred during the study. The results indicate that Phaeocystis-derived organic matter degraded while floating or in suspension, and had not reached the sediment in substantial amounts.

  17. Deriving environmental quality standards for perfluorooctanoic acid (PFOA) and related short chain perfluorinated alkyl acids.

    PubMed

    Valsecchi, Sara; Conti, Daniela; Crebelli, Riccardo; Polesello, Stefano; Rusconi, Marianna; Mazzoni, Michela; Preziosi, Elisabetta; Carere, Mario; Lucentini, Luca; Ferretti, Emanuele; Balzamo, Stefania; Simeone, Maria Gabriella; Aste, Fiorella

    2017-02-05

    The evidence that in Northern Italy significant sources of perfluoroalkylacids (PFAA) are present induced the Italian government to establish a Working Group on Environmental Quality Standard (EQS) for PFAA in order to include some of them in the list of national specific pollutants for surface water monitoring according to the Water Framework Directive (2000/60/EC). The list of substances included perfluorooctanoate (PFOA) and related short chain PFAA such as perfluorobutanoate (PFBA), perfluoropentanoate (PFPeA), perfluorohexanoate (PFHxA) and perfluorobutanesulfonate (PFBS), which is a substitute of perfluorooctanesulfonate. For each of them a dossier collects available data on regulation, physico-chemical properties, emission and sources, occurrence, acute and chronic toxicity on aquatic species and mammals, including humans. Quality standards (QS) were derived for the different protection objectives (pelagic and benthic communities, predators by secondary poisoning, human health via consumption of fishery products and water) according to the European guideline. The lowest QS is finally chosen as the relevant EQS. For PFOA a QS for biota was derived for protection from secondary poisoning and the corresponding QS for water was back-calculated, obtaining a freshwater EQS of 0.1μgL(-1). For PFBA, PFPeA, PFHxA and PFBS threshold limits proposed for drinking waters were adopted as EQS. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Efficient synthesis of 1-azadienes derived from alpha-aminoesters. Regioselective preparation of alpha-dehydroamino acids, vinylglycines, and alpha-amino acids.

    PubMed

    Palacios, Francisco; Vicario, Javier; Aparicio, Domitila

    2006-09-29

    An efficient synthesis of 1-azadienes derived from alpha-aminoesters is achieved through an aza-Wittig reaction of phosphazenes with beta,gamma-unsaturated alpha-ketoesters. Regioselective 1,2-reduction of these functionalized 1-azadienes affords vinylglycine derivatives, while conjugative 1,4-reduction gives alpha-dehydroamino acid compounds. Reduction of both the carbon-carbon and the imine-carbon-nitrogen double bonds leads to the formation of alpha-amino acid derivatives.

  19. Mononuclear phagocyte accumulates a stearic acid derivative during differentiation into macrophages. Effects of stearic acid on macrophage differentiation and Mycobacterium tuberculosis control.

    PubMed

    Mosquera-Restrepo, Sergio Fabián; Caro, Ana Cecilia; Peláez-Jaramillo, Carlos Alberto; Rojas, Mauricio

    2016-05-01

    The fatty acid composition of monocytes changes substantially during differentiation into macrophages, increasing the proportion of saturated fatty acids. These changes prompted us to investigate whether fatty acid accumulation in the extracellular milieu could affect the differentiation of bystander mononuclear phagocytes. An esterified fatty acid derivative, stearate, was the only fatty acid that significantly increased in macrophage supernatants, and there were higher levels when cells differentiated in the presence of Mycobacterium tuberculosis H37Rv or purified protein derivative (PPD). Exogenous stearic acid enhanced the expression of HLA-DR and CD64; there was also accumulation of IL-12, TNF-α, IL-6, MIP-1 α and β and a reduction in MCP-1 and the bacterial load. These results suggested that during differentiation, a derivative of stearic acid, which promotes the process as well as the effector mechanisms of phagocytes against the mycobacterium, accumulates in the cell supernatants.

  20. Cobalt(II)-catalyzed 1,4-addition of organoboronic acids to activated alkenes: an application to highly cis-stereoselective synthesis of aminoindane carboxylic acid derivatives.

    PubMed

    Chen, Min-Hsien; Mannathan, Subramaniyan; Lin, Pao-Shun; Cheng, Chien-Hong

    2012-11-19

    It all adds up: The 1,4-addition of organoboronic acids to activated alkenes catalyzed by [Co(dppe)Cl(2)] is described. A [3+2]-annulation reaction of ortho-iminoarylboronic acids with acrylates to give various aminoindane carboxylic acid derivatives with cis-stereoselectivity is also demonstrated (see scheme; dppe = 1,2-bis(diphenylphosphino)ethane).

  1. 15-Oxoeicosatetraenoic acid is a 15-hydroxyprostaglandin dehydrogenase-derived electrophilic mediator of inflammatory signaling pathways.

    PubMed

    Snyder, Nathaniel W; Golin-Bisello, Franca; Gao, Yang; Blair, Ian A; Freeman, Bruce A; Wendell, Stacy Gelhaus

    2015-06-05

    Bioactive lipids govern cellular homeostasis and pathogenic inflammatory processes. Current dogma holds that bioactive lipids, such as prostaglandins and lipoxins, are inactivated by 15-hydroxyprostaglandin dehydrogenase (15PGDH). In contrast, the present results reveal that catabolic "inactivation" of hydroxylated polyunsaturated fatty acids (PUFAs) yields electrophilic α,β-unsaturated ketone derivatives. These endogenously produced species are chemically reactive signaling mediators that induce tissue protective events. Electrophilic fatty acids diversify the proteome through post-translational alkylation of nucleophilic cysteines in key transcriptional regulatory proteins and enzymes that govern cellular metabolic and inflammatory homeostasis. 15PGDH regulates these processes as it is responsible for the formation of numerous electrophilic fatty acids including the arachidonic acid metabolite, 15-oxoeicosatetraenoic acid (15-oxoETE). Herein, the role of 15-oxoETE in regulating signaling responses is reported. In cell cultures, 15-oxoETE activates Nrf2-regulated antioxidant responses (AR) and inhibits NF-κB-mediated pro-inflammatory responses via IKKβ inhibition. Inhibition of glutathione S-transferases using ethacrynic acid incrementally increased the signaling capacity of 15-oxoETE by decreasing 15-oxoETE-GSH adduct formation. This work demonstrates that 15PGDH plays a role in the regulation of cell and tissue homeostasis via the production of electrophilic fatty acid signaling mediators.

  2. Oxidation of cyclohexanediol derivatives with 12-tungstophosphoric acid-hydrogen peroxide system.

    PubMed

    Fujitani, Kango; Mizutani, Toshihiro; Oida, Tatsuo; Kawase, Tokuzo

    2009-01-01

    Oxidation of cyclohexanediol derivatives with 12-tungstophospholic acid-hydrogen peroxide system was investigated focusing on a reaction mechanism in the preparation of dicarboxylic acids from olefin because oxidative cleavage of vicinal diols would be a rate-determining step in oxidative cleavage of carbon-carbon double bonds. trans-1,2-Cyclohexanediol (DHC) was converted to adipic acid almost quantatively, while 1-hydroxy-2-methoxycyclohexane (HMC) gave a mixture of adipic acid, glutaric acid and monomethyl adipate. In the case of 1,4-cyclohexanediol, 4-hydroxy-cyclohexanone and many hyperoxidated products were obtained. Based on results for HMC, it is concluded that following route would be also reasonable in oxidative cleavage of vicinal diol with 12-tungstophospholic acid-hydrogen peroxide system: (1) first oxidation of vicinal diol to alpha-hydroxyketone, (2) nucleophilic attack of hydrogen peroxide attacks to carbonyl carbon, (3) Baiyer-Villiger rearrangement of dihydroxy-hydroperoxide to a cyclic ester, (4) hydrolysis and final oxidation to dicarboxylic acid.

  3. Comparison of inhibition effects of some benzoic acid derivatives on sheep heart carbonic anhydrase

    NASA Astrophysics Data System (ADS)

    Kiliç, Deryanur; Yildiz, Melike; Şentürk, Murat; Erdoǧan, Orhan; Küfrevioǧlu, Ömer Irfan

    2016-04-01

    Carbonic anhydrase (CA) is a family of metalloenzymes that requires Zn as a cofactor and catalyze the quick conversion of CO2 to HCO3- and H+. Inhibitors of the carbonic anhydrases (CAs) have medical usage of significant diseases such as glaucoma, epilepsy, gastroduodenal ulcers, acid-base disequilibria and neurological disorders. In the present study, inhibition of CA with some benzoic derivatives (1-6) were investigated. Sheep heart CA (shCA) enzyme was isolated by means of designed affinity chromatography gel (cellulose-benzyl-sulfanylamide) 42.45-fold in a yield of 44 % with 564.65 EU/mg. Purified shCA enzyme was used in vitro studies. In the studies, IC50 values were calculated for 3-aminobenzoic acid (1), 4-aminobenzoic acid (2), 2-hydroxybenzoic acid (3), 2-benzoylbenzoic acid (4), 2,3-dimethoxybenzoic acid (5), and 3,4,5-trimethoxybenzoic acid (6), showing the inhibition effects on the purified enzyme. Such molecules can be used as pioneer for discovery of novel effective CA inhibitors for medicinal chemistry applications.

  4. Highly efficient production of D-lactic acid from chicory-derived inulin by Lactobacillus bulgaricus.

    PubMed

    Xu, Qianqian; Zang, Ying; Zhou, Jie; Liu, Peng; Li, Xin; Yong, Qiang; Ouyang, Jia

    2016-11-01

    Inulin is a readily available feedstock for cost-effective production of biochemicals. To date, several studies have explored the production of bioethanol, high-fructose syrup and fructooligosaccharide, but there are no studies regarding the production of D-lactic acid using inulin as a carbon source. In the present study, chicory-derived inulin was used for D-lactic acid biosynthesis by Lactobacillus bulgaricus CGMCC 1.6970. Compared with separate hydrolysis and fermentation processes, simultaneous saccharification and fermentation (SSF) has demonstrated the best performance of D-lactic acid production. Because it prevents fructose inhibition and promotes the complete hydrolysis of inulin, the highest D-lactic acid concentration (123.6 ± 0.9 g/L) with a yield of 97.9 % was obtained from 120 g/L inulin by SSF. Moreover, SSF by L. bulgaricus CGMCC 1.6970 offered another distinct advantage with respect to the higher optical purity of D-lactic acid (>99.9 %) and reduced number of residual sugars. The excellent performance of D-lactic acid production from inulin by SSF represents a high-yield method for D-lactic acid production from non-food grains.

  5. Cytochrome P450-generated metabolites derived from ω-3 fatty acids attenuate neovascularization

    PubMed Central

    Yanai, Ryoji; Mulki, Lama; Hasegawa, Eiichi; Takeuchi, Kimio; Sweigard, Harry; Suzuki, Jun; Gaissert, Philipp; Vavvas, Demetrios G.; Sonoda, Koh-Hei; Rothe, Michael; Schunck, Wolf-Hagen; Miller, Joan W.; Connor, Kip M.

    2014-01-01

    Ocular neovascularization, including age-related macular degeneration (AMD), is a primary cause of blindness in individuals of industrialized countries. With a projected increase in the prevalence of these blinding neovascular diseases, there is an urgent need for new pharmacological interventions for their treatment or prevention. Increasing evidence has implicated eicosanoid-like metabolites of long-chain polyunsaturated fatty acids (LCPUFAs) in the regulation of neovascular disease. In particular, metabolites generated by the cytochrome P450 (CYP)–epoxygenase pathway have been shown to be potent modulators of angiogenesis, making this pathway a reasonable previously unidentified target for intervention in neovascular ocular disease. Here we show that dietary supplementation with ω-3 LCPUFAs promotes regression of choroidal neovessels in a well-characterized mouse model of neovascular AMD. Leukocyte recruitment and adhesion molecule expression in choroidal neovascular lesions were down-regulated in mice fed ω-3 LCPUFAs. The serum of these mice showed increased levels of anti-inflammatory eicosanoids derived from eicosapentaenoic acid and docosahexaenoic acid. 17,18-epoxyeicosatetraenoic acid and 19,20-epoxydocosapentaenoic acid, the major CYP-generated metabolites of these primary ω-3 LCPUFAs, were identified as key lipid mediators of disease resolution. We conclude that CYP-derived bioactive lipid metabolites from ω-3 LCPUFAs are potent inhibitors of intraocular neovascular disease and show promising therapeutic potential for resolution of neovascular AMD. PMID:24979774

  6. D-Lactic acid biosynthesis from biomass-derived sugars via Lactobacillus delbrueckii fermentation.

    PubMed

    Zhang, Yixing; Vadlani, Praveen V

    2013-12-01

    Poly-lactic acid (PLA) derived from renewable resources is considered to be a good substitute for petroleum-based plastics. The number of poly L-lactic acid applications is increased by the introduction of a stereocomplex PLA, which consists of both poly-L and D-lactic acid and has a higher melting temperature. To date, several studies have explored the production of L-lactic acid, but information on biosynthesis of D-lactic acid is limited. Pulp and corn stover are abundant, renewable lignocellulosic materials that can be hydrolyzed to sugars and used in biosynthesis of D-lactic acid. In our study, saccharification of pulp and corn stover was done by cellulase CTec2 and sugars generated from hydrolysis were converted to D-lactic acid by a homofermentative strain, L. delbrueckii, through a sequential hydrolysis and fermentation process (SHF) and a simultaneous saccharification and fermentation process (SSF). 36.3 g L(-1) of D-lactic acid with 99.8 % optical purity was obtained in the batch fermentation of pulp and attained highest yield and productivity of 0.83 g g(-1) and 1.01 g L(-1) h(-1), respectively. Luedeking-Piret model described the mixed growth-associated production of D-lactic acid with a maximum specific growth rate 0.2 h(-1) and product formation rate 0.026 h(-1), obtained for this strain. The efficient synthesis of D-lactic acid having high optical purity and melting point will lead to unique stereocomplex PLA with innovative applications in polymer industry.

  7. Simultaneous Derivative Spectrophotometric Analysis of Doxylamine Succinate, Pyridoxine Hydrochloride and Folic Acid in Combined Dosage Forms

    PubMed Central

    Pathak, A.; Rajput, S. J.

    2008-01-01

    Two UV spectrophotometric methods have been developed, based on first derivative spectrophotometry for simultaneous estimation of doxylamine succinate, pyridoxine hydrochloride, and folic acid in tablet formulations. In method I, the concentrations of these drugs were determined by using linear regression equation. Method II is also based on first derivative spectrophotometry however simultaneous equations (Vierdot's method) were derived on derivative spectra. The first derivative amplitudes at 270.0, 332.8 and 309.2 nm were utilized for simultaneous estimation of these drugs respectively by both methods. In both the methods, linearity was obtained in the concentration range 2.5-50 μg/ml, 1-40 μg/ml and 1-30 μg/ml for doxylamine succinate, pyridoxine hydrochloride, and folic acid respectively. The developed methods show best results in terms of linearity, accuracy, precision, LOD, LOQ and ruggedness for standard laboratory mixtures of pure drugs and marketed formulations. The common excipients and additives did not interfere in their determinations. PMID:20046784

  8. Simultaneous derivative spectrophotometric analysis of doxylamine succinate, pyridoxine hydrochloride and folic Acid in combined dosage forms.

    PubMed

    Pathak, A; Rajput, S J

    2008-01-01

    Two UV spectrophotometric methods have been developed, based on first derivative spectrophotometry for simultaneous estimation of doxylamine succinate, pyridoxine hydrochloride, and folic acid in tablet formulations. In method I, the concentrations of these drugs were determined by using linear regression equation. Method II is also based on first derivative spectrophotometry however simultaneous equations (Vierdot's method) were derived on derivative spectra. The first derivative amplitudes at 270.0, 332.8 and 309.2 nm were utilized for simultaneous estimation of these drugs respectively by both methods. In both the methods, linearity was obtained in the concentration range 2.5-50 mug/ml, 1-40 mug/ml and 1-30 mug/ml for doxylamine succinate, pyridoxine hydrochloride, and folic acid respectively. The developed methods show best results in terms of linearity, accuracy, precision, LOD, LOQ and ruggedness for standard laboratory mixtures of pure drugs and marketed formulations. The common excipients and additives did not interfere in their determinations.

  9. Acid Dissociation Constants of Melamine Derivatives from Density Functional Theory Calculations

    NASA Astrophysics Data System (ADS)

    Jang, Yun Hee; Hwang, Sungu; Chang, Seo Bong; Ku, Jamin; Chung, Doo Soo

    2009-10-01

    Melamine and its hydrolysis products (ammeline, ammelide, and cyanuric acid) recently attracted great attention as major food contaminants. Developing analytical tools to quantify them requires exact knowledge of their acid dissociation constants (pKa values). Herein, we calculated the pKa values of these melamine derivatives in water, using a density functional theory quantum mechanical method [B3LYP/6-311++G(d,p)] in combination with the Poisson-Boltzmann continuum solvation model. The excellent agreement of the calculated values with the experimental ones shows that our method can be used to predict such properties of other food contaminants.

  10. Derivatives of pyrazinecarboxylic acid: 1H, 13C and 15N NMR spectroscopic investigations.

    PubMed

    Holzer, Wolfgang; Eller, Gernot A; Datterl, Barbara; Habicht, Daniela

    2009-07-01

    NMR spectroscopic studies are undertaken with derivatives of 2-pyrazinecarboxylic acid. Complete and unambiguous assignment of chemical shifts ((1)H, (13)C, (15)N) and coupling constants ((1)H,(1)H; (13)C,(1)H; (15)N,(1)H) is achieved by combined application of various 1D and 2D NMR spectroscopic techniques. Unequivocal mapping of (13)C,(1)H spin coupling constants is accomplished by 2D (delta,J) long-range INEPT spectra with selective excitation. Phenomena such as the tautomerism of 3-hydroxy-2-pyrazinecarboxylic acid are discussed.

  11. Bioinspired bioadhesive polymers: dopa-modified poly(acrylic acid) derivatives.

    PubMed

    Laulicht, Bryan; Mancini, Alexis; Geman, Nathanael; Cho, Daniel; Estrellas, Kenneth; Furtado, Stacia; Hopson, Russell; Tripathi, Anubhav; Mathiowitz, Edith

    2012-11-01

    The one-step synthesis and characterization of novel bioinspired bioadhesive polymers that contain Dopa, implicated in the extremely adhesive byssal fibers of certain gastropods, is reported. The novel polymers consist of combinations of either of two polyanhydride backbones and one of three amino acids, phenylalanine, tyrosine, or Dopa, grafted as side chains. Dopa-grafted hydrophobic backbone polymers exhibit as much as 2.5 × the fracture strength and 2.8 × the tensile work of bioadhesion of a commercially available poly(acrylic acid) derivative as tested on live, excised, rat intestinal tissue. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Photochromism and holographic recording in polymer film containing chiral azo molecules derived from amino acid

    NASA Astrophysics Data System (ADS)

    Zhang, Yanjie; Lu, Zifeng; Deng, Xuefeng; Liu, Yichun; Tan, Changhui; Zhao, Yingying; Kong, Xianggui

    2003-05-01

    A kind of chiral azo molecule derived from amino acid, N-[4-(4-octyloxyphenylazo)benzoyl]- L-glutamic acid (C 8-Azo- L-Glu), was synthesized and the photochromism, photoinduced birefringence, and holographic recording in C 8-Azo- L-Glu doped poly(methyl methacrylate) (PMMA) films were studied. C 8-Azo- L-Glu underwent a reversible trans-cis-trans isomerization in the polymer matrix. The photoinduced birefringence was investigated at various intensities of Ar laser (488 nm) beam. A reversible hologram was recorded in this media and the dependence of the first order diffraction efficiency on the recording beam intensities was also presented.

  13. Synthesis of Functionalized Dialkyl Ketones From Carboxylic Acid Derivatives and Alkyl Halides

    PubMed Central

    Wotal, Alexander C.; Weix, Daniel J.

    2012-01-01

    Unsymmetrical dialkyl ketones can be directly prepared by the nickel-catalyzed reductive coupling of carboxylic acid chlorides or (2-pyridyl)thioesters with alkyl iodides or benzylic chlorides. A wide variety of functional groups are tolerated by this process, including common nitrogen protecting groups and C-B bonds. Even hindered ketones flanked by tertiary and secondary centers can be formed. The mechanism is proposed to involve the reaction of a (L)Ni(alkyl)2 intermediate with the carboxylic acid derivative. PMID:22360350

  14. Synthesis and biological evaluation of new heteroaryl carboxylic acid derivatives as anti-inflammatory-analgesic agents.

    PubMed

    Abouzid, Khaled Abouzid Mohamed; Khalil, Nadia Abdalla; Ahmed, Eman Mohamed; Zaitone, Sawsan Abo-Bakr

    2013-01-01

    A series of nicotinic acid derivatives structurally related to niflumic acid and certain pyridazine-containing compounds have been synthesized and characterized by analytical and spectral data. All compounds were screened for their potential analgesic and anti-inflammatory activities. The compounds which displayed analgesic and anti-inflammatory activities were tested for ulcerogenicity and screened for in vivo inhibition of certain inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and cyclooxygenase-2 (COX-2). Compounds 1c, 2a, 2b, and 5a have shown potent analgesic and anti-inflammatory activities.

  15. New ethacrynic acid derivatives as potent cytoskeletal modulators in trabecular meshwork cells.

    PubMed

    Shimazaki, Atsushi; Suhara, Hiroshi; Ichikawa, Masaki; Matsugi, Takeshi; Konomi, Koji; Takagi, Yasutaka; Hara, Hideaki; Rao, Ponugoti Vasantha; Epstein, David Lee

    2004-06-01

    A series of ethacrynic acid (ECA) derivatives were synthesized and examined for ocular hypotensive activity. Efficacy was evaluated in a cell-shape assay, using human trabecular meshwork cells, and cytotoxicity in a (3-(4,5-dimethylthiazole-2-yl)-5-(3-carboxymethoxy phenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay, using cultured bovine trabecular meshwork cells. Many of the derivatives demonstrated efficacy equal to or greater than that of ECA. SA9000 was selected as the most promising candidate for a novel ocular hypotensive drug with few side effects.

  16. Stability of vitamin C derivatives in topical formulations containing lipoic acid, vitamins A and E.

    PubMed

    Segall, A I; Moyano, M A

    2008-12-01

    The stability of ascorbyl palmitate, sodium ascorbyl phosphate and magnesium ascorbyl phosphate in topical formulations was investigated by direct reverse phase high performance liquid chromatography after sample dilution with a suitable buffer - organic solvent mixture. Ascorbyl palmitate, sodium ascorbyl phosphate and magnesium ascorbyl phosphate are derivatives of ascorbic acid which differ in hydrolipophilic properties. They are widely used in cosmetic and pharmaceutical preparations. According to the results, ascorbyl esters showed significant differences: sodium ascorbyl phosphate and magnesium ascorbyl phosphate are more stable derivatives of vitamin C than ascorbyl palmitate and may be easily used in cosmetic products.

  17. Separation of D-lysergic acid diethylamide derivatives using micellar electrokinetic capillary chromatography.

    PubMed

    Djordjevic, M N; Fitzpatrick, F; Houdiere, F

    2000-03-01

    By adjusting column temperature and applied electric field, a fast separation in micellar electrokinetic capillary chromatography was developed for the separation of D-lysergic acid diethylamide derivatives. A baseline separation of nine derivatives was accomplished with a run time of less than 12 min by utilizing elevated column temperature (60 degrees C) and an applied electric field of 387 V/cm. The number of plates generated per unit time for the separations completed at elevated temperatures was significantly higher when compared to separations at the same applied electric field but at lower temperatures (20 degrees C).

  18. A benzoic acid derivative and flavokawains from Piper species as schistosomiasis vector controls.

    PubMed

    Rapado, Ludmila N; Freitas, Giovana C; Polpo, Adriano; Rojas-Cardozo, Maritza; Rincón, Javier V; Scotti, Marcus T; Kato, Massuo J; Nakano, Eliana; Yamaguchi, Lydia F

    2014-04-23

    The search of alternative compounds to control tropical diseases such as schistosomiasis has pointed to secondary metabolites derived from natural sources. Piper species are candidates in strategies to control the transmission of schistosomiasis due to their production of molluscicidal compounds. A new benzoic acid derivative and three flavokawains from Piper diospyrifolium, P. cumanense and P. gaudichaudianum displayed significant activities against Biomphalaria glabrata snails. Additionally, "in silico" studies were performed using docking assays and Molecular Interaction Fields to evaluate the physical-chemical differences among the compounds in order to characterize the observed activities of the test compounds against Biomphalaria glabrata snails.

  19. Untargeted metabolomics analysis reveals dynamic changes in azelaic acid- and salicylic acid derivatives in LPS-treated Nicotiana tabacum cells.

    PubMed

    Mhlongo, M I; Tugizimana, F; Piater, L A; Steenkamp, P A; Madala, N E; Dubery, I A

    2017-01-22

    To counteract biotic stress factors, plants employ multilayered defense mechanisms responsive to pathogen-derived elicitor molecules, and regulated by different phytohormones and signaling molecules. Here, lipopolysaccharide (LPS), a microbe-associated molecular pattern (MAMP) molecule, was used to induce defense responses in Nicotiana tabacum cell suspensions. Intracellular metabolites were extracted with methanol and analyzed using a liquid chromatography-mass spectrometry (UHPLC-qTOF-MS/MS) platform. The generated data were processed and examined with multivariate and univariate statistical tools. The results show time-dependent dynamic changes and accumulation of glycosylated signaling molecules, specifically those of azelaic acid, salicylic acid and methyl-salicylate as contributors to the altered metabolomic state in LPS-treated cells. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Structural and spectroscopic investigation on a new potentially bioactive di-hydrazone containing thiophene heterocyclic rings

    NASA Astrophysics Data System (ADS)

    Nogueira, Vanessa de S.; Ramalho Freitas, Maria Clara; Cruz, Wellington S.; Ribeiro, Tatiana S.; Resende, Jackson A. L. C.; Rey, Nicolás A.

    2016-02-01

    Hydrazones and several substituted hydrazones are associated with a broad spectrum of biological activities, as well as compounds containing the thiophene ring. In this context, a novel di-hydrazone derived from 2-thiophenecarboxylic acid hydrazide was synthesized and completely characterized by elemental analysis, XRD, FT-IR, Raman and UV-Vis spectroscopies, thermogravimetry, 1H NMR, 1H-1H COSY and 1H-1H ROESY. A preliminary in silico pharmacological evaluation was also performed in order to assess the performance of the new compound regarding some molecular properties relevant for a drug's pharmacokinetics in the human body.

  1. Biosynthesis, biological effects, and receptors of hydroxyeicosatetraenoic acids (HETEs) and oxoeicosatetraenoic acids (oxo-ETEs) derived from arachidonic acid.

    PubMed

    Powell, William S; Rokach, Joshua

    2015-04-01

    Arachidonic acid can be oxygenated by a variety of different enzymes, including lipoxygenases, cyclooxygenases, and cytochrome P450s, and can be converted to a complex mixture of oxygenated products as a result of lipid peroxidation. The initial products in these reactions are hydroperoxyeicosatetraenoic acids (HpETEs) and hydroxyeicosatetraenoic acids (HETEs). Oxoeicosatetraenoic acids (oxo-ETEs) can be formed by the actions of various dehydrogenases on HETEs or by dehydration of HpETEs. Although a large number of different HETEs and oxo-ETEs have been identified, this review will focus principally on 5-oxo-ETE, 5S-HETE, 12S-HETE, and 15S-HETE. Other related arachidonic acid metabolites will also be discussed in less detail. 5-Oxo-ETE is synthesized by oxidation of the 5-lipoxygenase product 5S-HETE by the selective enzyme, 5-hydroxyeicosanoid dehydrogenase. It actions are mediated by the selective OXE receptor, which is highly expressed on eosinophils, suggesting that it may be important in eosinophilic diseases such as asthma. 5-Oxo-ETE also appears to stimulate tumor cell proliferation and may also be involved in cancer. Highly selective and potent OXE receptor antagonists have recently become available and could help to clarify its pathophysiological role. The 12-lipoxygenase product 12S-HETE acts by the GPR31 receptor and promotes tumor cell proliferation and metastasis and could therefore be a promising target in cancer therapy. It may also be involved as a proinflammatory mediator in diabetes. In contrast, 15S-HETE may have a protective effect in cancer. In addition to GPCRs, higher concentration of HETEs and oxo-ETEs can activate peroxisome proliferator-activated receptors (PPARs) and could potentially regulate a variety of processes by this mechanism. This article is part of a Special Issue entitled "Oxygenated metabolism of PUFA: analysis and biological relevance".

  2. Structure-dependent effects of pyridine derivatives on mechanisms of intestinal fatty acid uptake: regulation of nicotinic acid receptor and fatty acid transporter expression.

    PubMed

    Riedel, Annett; Lang, Roman; Rohm, Barbara; Rubach, Malte; Hofmann, Thomas; Somoza, Veronika

    2014-07-01

    Pyridines are widely distributed in foods. Nicotinic acid (NA), a carboxylated pyridine derivative, inhibits lipolysis in adipocytes by activation of the orphan NA receptor (HM74A) and is applied to treat hyperlipidemia. However, knowledge on the impact of pyridine derivatives on intestinal lipid metabolism is scarce. This study was performed to identify the structural determinants of pyridines for their effects on fatty acid uptake in enterocyte-like Caco-2 cells and to elucidate the mechanisms of action. The impact of 17 pyridine derivatives on fatty acid uptake was tested. Multiple regression analysis revealed the presence of a methyl group to be the structural determinant at 0.1 mM, whereas at 1 mM, the presence of a carboxylic group and the N-methylation presented further structural characteristics to affect the fatty acid uptake. NA, showing a stimulating effect on FA uptake, and N-methyl-4-phenylpyridinium (MPP), inhibiting FA uptake, were selected for mechanistic studies. Gene expression of the fatty acid transporters CD36, FATP2 and FATP4, and the lipid metabolism regulating transcription factors peroxisome proliferator-activated receptor (PPAR) α and PPARγ was up-regulated upon NA treatment. Caco-2 cells were demonstrated to express the low-affinity NA receptor HM74 of which the gene expression was up-regulated upon NA treatment. We hypothesize that the NA-induced fatty acid uptake might result from NA receptor activation and related intracellular signaling cascades. In contrast, MPP increased transepithelial electrical resistance. We therefore conclude that NA and MPP, both sharing the pyridine motif core, exhibit their contrary effects on intestinal FA uptake by activation of different mechanisms. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Humic acid batteries derived from vermicomposts at different C/N ratios

    NASA Astrophysics Data System (ADS)

    Shamsuddin, R. M.; Borhan, A.; Lim, W. K.

    2017-06-01

    Humic acid is a known fertilizer derived from decomposed organic matters. Organic wastes are normally landfilled for disposal which had contributed negatively to the environment. From waste-to-wealth perspective, such wastes are potential precursors for compost fertilizers. When worms are added into a composting process, the process is termed as vermicomposting. In this work, humic acid from vermicompost derived from campus green wastes was developed into a battery. This adds value proposition to compost instead of being traditionally used solely as soil improver. This research work aimed to study the correlation between electrical potential generated by humic acid at different Carbon to Nitrogen (C/N) ratios of vermicompost at 20, 25, 30 and 35. The temperature and pH profiles of composting revealed that the compost was ready after 55 days. The humic acid was extracted from compost via alkaline extraction followed by precipitation in a strong acid. The extracted humic acid together with other additives were packed into a compartment and termed as vermibattery. Another set of battery running only on the additives was also prepared as a control. The net voltage produced by a single vermibattery cell with Zn and PbO electrodes was in the range of 0.31 to 0.44 V with compost at C/N ratio of 30 gave the highest voltage. The battery can be connected in series to increase the voltage generation. Quality assessment on the compost revealed that the final carbon content is between 16 to 23 wt%, nitrogen content of 0.4 to 0.5 wt%, humic acid yield of 0.7 to 1.5 wt% and final compost mass reduction of 10 to 35 wt%. Composting campus green wastes carries multi-fold benefits of reducing labour requirement, generating fertilizer for campus greenery and green battery construction.

  4. Quinic acid derivatives from Pimpinella brachycarpa exert anti-neuroinflammatory activity in lipopolysaccharide-induced microglia.

    PubMed

    Lee, Seung Young; Moon, Eunjung; Kim, Sun Yeou; Lee, Kang Ro

    2013-04-01

    Five new quinic acid derivatives (1-5), together with 10 known quinic acid derivatives (6-15), were isolated from the MeOH extract of Pimpinella brachycarpa (Umbelliferae). Their structures were established on the basis of spectroscopic analyses including extensive 2D NMR studies (COSY, HMQC and HMBC). Isolated compounds 1-15 were evaluated for their inhibitory activities on nitric oxide (NO) production in an activated murine microglial cell line. Compounds 2, 3, 8 and 11 significantly inhibited NO production without high cell toxicity in lipopolysaccharide (LPS)-activated BV-2 cells, a microglia cell line (IC50=4.66, 12.52, 9.04 and 12.11 μM, respectively). Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Synthesis, characterisation and antioxidant features of procyanidin B4 and malvidin-3-glucoside stearic acid derivatives.

    PubMed

    Cruz, Luis; Fernandes, Virgínia C; Araújo, Paula; Mateus, Nuno; de Freitas, Victor

    2015-05-01

    The acylation of procyanidin B4 with a saturated fatty acid chloride containing 18 carbon atoms was studied in order to obtain procyanidin B4 3-O-di-stearic acid conjugate. This compound was structurally characterised by mass spectrometry and 1D and 2D NMR techniques. Derivatization of malvidin-3-glucoside using stearoyl chloride in acetonitrile was also performed yielding mono-, di- and tri-stearic ester derivatives. The novel derivatives obtained revealed significant antioxidant activity, although lower than the respective precursors. However, the chemical modification of anthocyanins and procyanidins (water soluble pigments) to more lipophilic compounds has the advantage of increased bioavailability in biological matrices, and to potentiate their application in food matrices and cosmetic products. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Stereoselective Synthesis of α-Amino-C-phosphinic Acids and Derivatives.

    PubMed

    Viveros-Ceballos, José Luis; Ordóñez, Mario; Sayago, Francisco J; Cativiela, Carlos

    2016-08-29

    α-Amino-C-phosphinic acids and derivatives are an important group of compounds of synthetic and medicinal interest and particular attention has been dedicated to their stereoselective synthesis in recent years. Among these, phosphinic pseudopeptides have acquired pharmacological importance in influencing physiologic and pathologic processes, primarily acting as inhibitors for proteolytic enzymes where molecular stereochemistry has proven to be critical. This review summarizes the latest developments in the asymmetric synthesis of acyclic and phosphacyclic α-amino-C-phosphinic acids and derivatives, following in the first case an order according to the strategy used, whereas for cyclic compounds the nitrogen embedding in the heterocyclic core is considered. In addition selected examples of pharmacological implications of title compounds are also disclosed.

  7. Transition-Metal-Free ipso-Functionalization of Arylboronic Acids and Derivatives.

    PubMed

    Zhu, Chen; Falck, John R

    2014-08-11

    Arylboronic acids and their derivatives have been widely exploited as important synthetic precursors in organic synthesis, materials science, and pharmaceutical development. In addition to numerous applications in transition-metal-mediated cross-coupling reactions, transition-metal-free transformations involving arylboronic acids and derivatives have recently received a surge of attention for converting the C-B bond to C-C, C-N, C-O, and many other C-X bonds. Consequently, a wide range of useful compounds, e.g., phenols, anilines, nitroarenes, and haloarenes, have been readily synthesized. Amongst these efforts, many versatile reagents have been developed and a lot of practical approaches demonstrated. The research in this promising field is summarized in the current review and organized on the basis of the type of bonds being formed.

  8. Synthesis and pro-apoptotic activity of novel glycyrrhetinic acid derivatives.

    PubMed

    Logashenko, Evgeniya B; Salomatina, Oksana V; Markov, A V; Korchagina, Dina V; Salakhutdinov, Nariman F; Tolstikov, Genrikh A; Vlassov, Valentin V; Zenkova, Marina A

    2011-03-21

    Triterpenoids are used for medicinal purposes in many countries. Some, such as oleanolic and glycyrrhetinic acids, are known to be anti-inflammatory and anticarcinogenic. However, the biological activities of these naturally occurring molecules against their particular targets are weak, so the synthesis of new synthetic analogues with enhanced potency is needed. By combining modifications to both the A and C rings of 18βH-glycyrrhetinic acid, the novel synthetic derivative methyl 2-cyano-3,12-dioxo-18βH-olean-9(11),1(2)-dien-30-oate was obtained. This derivative displays high antiproliferative activity in cancer cells, including a cell line with a multidrug-resistance phenotype. It causes cell death by inducing the intrinsic caspase-dependent apoptotic pathway. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Synthesis and Pro-Apoptotic Activity of Novel Glycyrrhetinic Acid Derivatives

    PubMed Central

    Logashenko, Evgeniya B; Salomatina, Oksana V; Markov, A V; Korchagina, Dina V; Salakhutdinov, Nariman F; Tolstikov, Genrikh A; Vlassov, Valentin V; Zenkova, Marina A

    2011-01-01

    Triterpenoids are used for medicinal purposes in many countries. Some, such as oleanolic and glycyrrhetinic acids, are known to be anti-inflammatory and anticarcinogenic. However, the biological activities of these naturally occurring molecules against their particular targets are weak, so the synthesis of new synthetic analogues with enhanced potency is needed. By combining modifications to both the A and C rings of 18βH-glycyrrhetinic acid, the novel synthetic derivative methyl 2-cyano-3,12-dioxo-18βH-olean-9(11),1(2)-dien-30-oate was obtained. This derivative displays high antiproliferative activity in cancer cells, including a cell line with a multidrug-resistance phenotype. It causes cell death by inducing the intrinsic caspase-dependent apoptotic pathway. PMID:21328513

  10. Supramolecular chiral host-guest nanoarchitecture induced by the selective assembly of barbituric acid derivative enantiomers

    NASA Astrophysics Data System (ADS)

    Sun, Xiaonan; Silly, Fabien; Maurel, Francois; Dong, Changzhi

    2016-10-01

    Barbituric acid derivatives are prochiral molecules, i.e. they are chiral upon adsorption on surfaces. Scanning tunneling microscopy reveals that barbituric acid derivatives self-assemble into a chiral guest-host supramolecular architecture at the solid-liquid interface on graphite. The host nanoarchitecture has a sophisticated wavy shape pattern and paired guest molecules are nested insides the cavities of the host structure. Each unit cell of the host structure is composed of both enantiomers with a ratio of 1:1. Furthermore, the wavy patterns of the nanoarchitecture are formed from alternative appearance of left- and right-handed chiral building blocks, which makes the network heterochiral. The functional guest-host nanoarchitecture is the result of two-dimensional chiral amplification from single enantiomers to organizational heterochiral supramolecular self-assembly.

  11. Syntheses and Cellular Investigations of 173-, 152- and 131-Amino Acid Derivatives of Chlorin e61

    PubMed Central

    Waruna Jinadasa, R. G.; Hu, Xiaoke; Vicente, M. Graça H.; Smith, Kevin M.

    2011-01-01

    A series of amino acid conjugates of chlorin e6, containing lysine or aspartic acid residues in positions 173, 152 or 131 of the macrocycle were synthesized and investigated as photosensitizers for photodynamic therapy of tumors. All three regioisomers were synthesized in good yields and in 5 steps or less from pheophytin a (1). In vitro investigations using human carcinoma HEp2 cells show that the 152-lysyl regioisomers accumulate the most within cells, and the most phototoxic are the 131 regioisomers. The main determinant of biological efficacy appears to be the conjugation site, probably because of molecular conformation. Molecular modeling investigations reveal that the 173-substituted chlorin e6 conjugates are L-shaped, the 152 and 131 regioisomers assume extended conformations, and the 131 derivatives are nearly linear. It is hypothesized that the 131-aspartylchlorin e6 conjugate may be a more efficient photosensitizer for PDT than the commercial currently used 152 derivative. PMID:21936519

  12. Establishment of adventitious root cultures of Echinacea purpurea for the production of caffeic acid derivatives.

    PubMed

    Paek, Kee-Yoeup; Murthy, Hosakatte Niranjana; Hahn, Eun-Joo

    2009-01-01

    Echinacace purpurea (purple cone flower) is an important medicinal plant, and widely used for phytochemical purposes. The roots are traditionally used in herbal medicines and dietary supplements as an immunostimulant in treating inflammatory and viral diseases. Extensive research work has been carried out on both the induction of adventitious roots from E. purpurea as well as established small-scale (shake flask) to large-scale (bioreactor) cultures for the production of adventitious root biomass and caffeic acid derivatives. This chapter describes the methodologies of induction of adventitious roots from explants of E. purpurea, propagation of adventitious roots in suspension cultures, estimation of total phenolics, flavonoids, and antioxidant activities. The detailed methodology for high-performance liquid chromatographic analysis of caffeic acid derivatives present in the adventitious roots is also discussed.

  13. Transition-Metal-Free ipso-Functionalization of Arylboronic Acids and Derivatives

    PubMed Central

    Zhu, Chen; Falck, John R.

    2014-01-01

    Arylboronic acids and their derivatives have been widely exploited as important synthetic precursors in organic synthesis, materials science, and pharmaceutical development. In addition to numerous applications in transition-metal-mediated cross-coupling reactions, transition-metal-free transformations involving arylboronic acids and derivatives have recently received a surge of attention for converting the C-B bond to C-C, C-N, C-O, and many other C-X bonds. Consequently, a wide range of useful compounds, e.g., phenols, anilines, nitroarenes, and haloarenes, have been readily synthesized. Amongst these efforts, many versatile reagents have been developed and a lot of practical approaches demonstrated. The research in this promising field is summarized in the current review and organized on the basis of the type of bonds being formed. PMID:25414624

  14. Synthesis and antitumour activity of arctigenin amino acid ester derivatives against H22 hepatocellular carcinoma.

    PubMed

    Cai, Enbo; Guo, Shijie; Yang, Limin; Han, Mei; Xia, Jing; Zhao, Yan; Gao, Xiaorui; Wang, Yu

    2017-04-18

    Arctigenin (ARG) is famous in its abundant pharmacological activity. However, many researches in it entered the bottleneck period because of its poor water solubility. The derivatives of ARG have been synthesised with five amino acids which have t-Butyloxy carbonyl (BOC) as a protective group. We examined the effects of removing BOC. The results showed that the amino acid derivatives without protective group have better water solubility and nitrite-clearing ability than ARG. Based on these results, ARG6' and ARG9' were selected at a dosage of 40 mg/kg to evaluate their antitumour activity. The percentage inhibition rate of ARG6' and ARG9' were 55.87 and 51.40, respectively, which was twice as much as ARG. Furthermore, they could increase liver and kidney indexes and produce less damage in these organs. In brief, this study provides a basis for new drug development.

  15. The synthesis of ethacrynic acid thiazole derivatives as glutathione S-transferase pi inhibitors.

    PubMed

    Li, Ting; Liu, Guyue; Li, Hongcai; Yang, Xinmei; Jing, Yongkui; Zhao, Guisen

    2012-04-01

    Glutathione S-transferase pi (GSTpi) is a phase II enzyme which protects cells from death and detoxifies chemotherapeutic agents in cancer cells. Ethacrynic acid (EA) is a weak GSTpi inhibitor. Structure modifications were done to improve the ability of EA to inhibit GSTpi activity. Eighteen EA thiazole derivatives were designed and synthesized. Compounds 9a, 9b and 9c with a replacement of carboxyl group of EA by a heterocyclic thiazole exhibited improvement over EA to inhibit GSTpi activity.

  16. Synthesis of sulfonic acid derivatives by oxidative deprotection of thiols using tert-butyl hypochlorite.

    PubMed

    Joyard, Yoann; Papamicaël, Cyril; Bohn, Pierre; Bischoff, Laurent

    2013-05-03

    Starting from alkyl halides or Michael acceptors, thioacetates were prepared in situ and further treated with t-BuOCl, affording the corresponding sulfonyl chlorides which were trapped with nucleophiles such as water, alcohol, or amines. The three steps can be achieved in a one-pot procedure. Oxidative deprotection also proved to be efficient with S-trityl and S-tert-butyl groups, making it a convenient route toward cysteic acid derivatives.

  17. Catalytic enantioselective Michael additions to unsaturated ester derivatives using chiral copper(II) Lewis acid complexes.

    PubMed

    Evans, D A; Willis, M C; Johnston, J N

    1999-09-23

    [formula: see text] Chiral Cu(II) bisoxazoline (box) Lewis acids have been developed as catalysts of the Michael addition of enolsilanes to unsaturated ester derivatives. While enantioselection is stereoregular, the sense of diastereoselection is directly related to thioester enolsilane geometry: (E) enolsilanes give anti adducts and (Z) enolsilanes afford syn adducts. The size of the enolsilane alkylthio substituent directly impacts the magnitude of diastereoselection.

  18. Heterogeneous and homogeneous catalysis for the hydrogenation of carboxylic acid derivatives: history, advances and future directions.

    PubMed

    Pritchard, James; Filonenko, Georgy A; van Putten, Robbert; Hensen, Emiel J M; Pidko, Evgeny A

    2015-06-07

    The catalytic reduction of carboxylic acid derivatives has witnessed a rapid development in recent years. These reactions, involving molecular hydrogen as the reducing agent, can be promoted by heterogeneous and homogeneous catalysts. The milestone achievements and recent results by both approaches are discussed in this Review. In particular, we focus on the mechanistic aspects of the catalytic hydrogenation and highlight the bifunctional nature of the mechanism that is preferred for supported metal catalysts as well as homogeneous transition metal complexes.

  19. New glutaramic acid derivatives with potent competitive and specific cholecystokinin-antagonistic activity.

    PubMed

    Makovec, F; Chistè, R; Bani, M; Pacini, M A; Setnikar, I; Rovati, L A

    1985-01-01

    New glutaramic acid derivatives were evaluated for anti-cholecystokinin (CCK) activity in vitro on guinea pig gallbladder. The compounds are competitive and specific CCK-antagonists, causing a parallel right shift of the cumulative dose-response curve of the agonist. The affinity for the binding site of the CCK-receptor for some of these compounds was hundreds of times higher than that of pro-glumide, the model compound.

  20. Anti-MRSA cephems. Part 3: additional C-7 acid derivatives.

    PubMed

    Springer, Dane M; Luh, Bing Yu; Goodrich, Jason T; Bronson, Joanne J

    2003-01-17

    Twenty-seven novel cephalosporin derivatives with activity against methicillin-resistant Staphylococcus aureus (MRSA) are described. The compounds contain novel acid moieties at C-7 that were synthesized using nucleophilic aromatic substitution reactions and Stille couplings. The most interesting compound (6) displayed an MIC(90) against MRSA of 3.7 microg/mL, and an average PD(50) of 3.9 mg/kg.

  1. First intermolecular cyclopropanation of Fischer dialkylaminocarbene complexes. Synthesis of 1-aminocyclopropanecarboxylic acid derivatives.

    PubMed

    Barluenga, José; Aznar, Fernando; Gutiérrez, Ignacio; García-Granda, Santiago; Llorca-Baragaño, M Amparo

    2002-11-28

    [reaction: see text] The first cyclopropanation reaction of olefins with Fischer dialkylaminocarbene complexes is presented. The reaction yields 1-aminocyclopropanecarboxylic acid derivatives in a single step, usually with high diastereoselectivity. An approach to the asymmetric version of this reaction is also presented. The synthetic utility of the procedure is exemplified by the synthesis of both cycles of metanoproline in a single step. In addition, the synthesis of the first Fischer carbene containing a halocarbonyl group is reported.

  2. [Amino acid and peptide derivatives of the tylosin family of macrolide antibiotics modified at the aldehyde group].

    PubMed

    Sumbatian, N V; Kuznetsova, I V; Karpenko, V V; Fedorova, N V; Chertkov, V A; Korshunova, G A; Bogdanov, A A

    2010-01-01

    Fourteen new functionally active amino acid and peptide derivatives of the antibiotics tylosin, desmycosin, and 5-O-mycaminosyltylonolide were synthesized in order to study the interaction of the growing polypeptide chain with the ribosomal tunnel. The conjugation of various amino acids and peptides with a macrolide aldehyde group was carried out by two methods: direct reductive amination with the isolation of the intermediate Schiff bases or through binding via oxime using the preliminarily obtained derivatives of 2-aminooxyacetic acid.

  3. Multiwavelength spectrophotometric determination of acid dissociation constants: Part II. First derivative vs. target factor analysis.

    PubMed

    Tam, K Y; Takács-Novák, K

    1999-03-01

    Acid dissociation constants (pKa values) denote the extent of ionization of drug molecules at different pH values, which is important in understanding their penetration through biological membranes and their interaction with the receptors. However, many drug molecules are sparingly soluble in water or contain ionization centres with overlapping pKa values, making precise pKa determination difficult using conventional spectrophotometric titration. In this work, we investigate a multiwavelength spectrophotometric titration (WApH) method for the determination of pKa values. Spectral changes which arise during pH-metric titrations of substances with concentration of about 10(-5) M were captured by means of an optical system developed in this study. All experiments were carried out in 0.15 M KCI solution at 25 +/- 0.5 degrees C. Mathematical treatments based on the first derivative spectrophotometry procedure and the target factor analysis method were applied to calculate the pKa values from the multiwavelength absorption titration data. pKa values were determined by the WApH technique for six ionizable substances, namely, benzoic acid, phenol, phthalic acid, nicotinic acid, p-aminosalicylic acid and phenolphthalein. The pKa values measured using the WApH technique are in excellent agreement with those measured pH-metrically. We have demonstrated that the first derivative spectrophometry procedure provides a relatively simple way to visualize the pKa values which are consistent with those determined using the target factor analysis method. However, for ionization systems with insufficient spectral data obtained around the sought pKa values or with closely overlapping pKa values, the target factor analysis method outperforms the first derivative procedure in terms of obtaining the results. Using the target factor analysis method, it has been shown that the two-step ionization of phenolphthalein involves a colorless anion intermediate and a red colored di-anion.

  4. A modulatory effect of novel kojic acid derivatives on cancer cell proliferation and macrophage activation.

    PubMed

    Yoo, Dae Sung; Lee, Jaehwi; Choi, Sun Shim; Rho, Ho Sik; Cho, Dong Ha; Shin, Won Cheol; Cho, Jae Youl

    2010-04-01

    We examined whether several newly synthesized derivatives of kojic acid, a compound with known antiinflammatory, anti-proliferative, and anti-oxidative properties, were able to modulate glioma cell proliferation and Toll-like receptor (TLR) 4-mediated functional activation of macrophage-managed tumor microenvironments. Anti-cancer effects on C6 glioma and SYF cells were examined by cell proliferation assays, DNA laddering assays, nuclear staining experiments, and Western blot analysis. The anti-inflammatory activities of the derivatives were assessed by measuring the production of nitric oxide (NO) and cytokine expression in macrophages (RAW264.7 cells) stimulated with the TLR 4 ligand lipopolysacchride (LPS). Among the various derivatives tested, RHS-0110 exhibited the strongest inhibitory activity on the proliferation of C6 glioma cells, with an IC50 value of 4.7 microM. However, the inhibitory effect of this compound was abrogated with respect to the proliferation of SYF cells, a cell line lacking Src, Yes, and Fyn kinases, similar to effects observed with the Src kinase inhibitor PP2. In agreement with these findings, RHS-0110 decreased the expression of Src but not the activation of Yes and Fyn. Based on DNA laddering tests and nucleus staining experiments, the anti-proliferative effects of RHS-0110 appeared to be due to a necrotic pathway. Kojic acid derivatives also suppressed LPS-induced NO production and interleukin (IL)-6 expression in RAW264.7 cells under lowered or non-cytotoxic concentrations of compounds. Because of their anti-proliferative and anti-TLR4-mediated microenvironmental formation features, our results suggest that kojic acid derivatives, including RHS-0110, may be useful as novel anti-cancer drugs.

  5. Investigations on the immunosuppressive activity of derivatives of mycophenolic acid in immature dendritic cells.

    PubMed

    Iwaszkiewicz-Grzes, Dorota; Cholewinski, Grzegorz; Kot-Wasik, Agata; Trzonkowski, Piotr; Dzierzbicka, Krystyna

    2017-03-01

    The main activity of mycophenolic acid 1 (MPA) and its analogs is the inhibition of proliferation of T cells. Here, we hypothesized that MPA and its conjugates inhibits also the activity of antigen-presenting cells (APC) including dendritic cells (DCs). We tested the effect of novel amino acid derivatives of MPA and conjugates of MPA with acridines/acridones on DCs by flow cytometry, ELISA and MLR assay. Both acridines/acridone derivatives could inhibit the maturation of DC, as shown by the decreased expression of B7 family receptors. It was confirmed in the mixed leucocyte reaction (MLR), in which T cells challenged with DCs pretreated with the analogs showed decreased proliferation and reduced cytokine secretion. The most interesting activity in this series of studies, that is, the suppression of CD86 receptor expression, decreased cytokine production and suppressed mixed leucocyte reaction, exhibited (mycophenoyl-N-3-propyl)-9-acridone-4-carboxamide ester 5a and (mycophenoyl-N-5-pentyl)-9-acridone-4-carboxamide ester 5b. These compounds reduced also the secretion of IL-2 and IL-15. In addition, they increased secretion of suppressive IL-10. Equally promising results were obtained for the N-mycophenoyl-D-glutamic acid 4b, which previously gave the highest value of selectivity. Acridone derivatives of MPA are therefore good immunosuppressive drug candidates for further testing.

  6. Combined anticalcification treatment of bovine pericardium with decellularization and hyaluronic acid derivative.

    PubMed

    Zhu, Deyi; Jin, Liqiang; Wang, Xuemei; Xu, Li; Liu, Tianqi

    2014-01-01

    The objective of this work was to evaluate the effect of decellularization and hyaluronic acid derivative on the improvement of anticalcification of glutaraldehyde fixed bovine pericardium (GFBP) using a rat subcutaneous implantation model A cell extraction process was employed to remove the cells and cellular components from bovine pericardium (BP), leaving a framework of largely insoluble collagen. Then acellular BP was cross-linked by glutaraldehyde solution and treated with hyaluronic acid derivative (HA-ADH) which was obtained by coupling adipic dihydrazide (ADH) on-COOH of hyaluronic acid (HA). The results of in vivo calcification tests showed that the calcium content was decreased dramatically by decellularization alone (from 28.07 ± 18.87 to 2.44 ± 0.55 μg Ca/mg dry tissue after 8 weeks' implantation), and even less concentration was shown by the combination of HA derivative treatment and decellularization (GFaBP-HA group) (0.25 ± 0.08 μg Ca/mg dry tissue after 8 weeks' implantation). In addition, GFaBP-HA group not only presented a lower degree of calcification, but also showed lower ratios of Ca/P molar, which corresponded to amorphous calcium phosphates. The obtained results indicated that GFaBP-HA was a potential candidate for the manufacture of anticalcification bioprostheses.

  7. Fluorescence studies on binding of pyrene and its derivatives to humic acid.

    PubMed

    Nakashima, K; Maki, M; Ishikawa, F; Yoshikawa, T; Gong, Y-K; Miyajima, T

    2007-07-01

    Binding of pyrene (PyH) and its derivatives to humic acid (HA) has been studied by fluorescence spectroscopy. The nature of the interaction between HA and pyrene derivatives are extensively investigated by employing three derivatives ranging from anionic to cationic compounds: 1-pyrenebutylic acid (PyA), 1-pyrenemethanol (PyM), and 1-pyrenebutyltrimethylammonium bromide (PyB). Binding constants between HA and PyX (X=H, A, M, B) are obtained by steady-state fluorescence quenching techniques, and it is found that PyB has a markedly large binding constant among the pyrene family. This is attributed to a strong electrostatic interaction between cationic PyB and anionic HA. The result suggests that an electrostatic interaction plays a dominant role in binding of pyrenes to humic acid. The importance of electrostatic interaction was also confirmed by a salt effect on the binding constant. Influence of collisional quenching on the binding constant, which causes overestimation of the binding constant, was examined by time-resolved fluorescence spectroscopy as well as temperature effect in steady-state fluorescence measurements. It is elucidated that collisional quenching does not much bring overestimation into the binding constants.

  8. The investigation of thermosensitive properties of phosphazene derivatives bearing amino acid ester groups

    NASA Astrophysics Data System (ADS)

    Uslu, Aylin; Mutlu Balcı, Ceylan; Yuksel, Fatma; Özcan, Elif; Dural, Sevilay; Beşli, Serap

    2017-05-01

    In this study, a series of phosphazene derivatives having amino acid esters were synthesized from the reactions of amino acid esters with cyclophosphazenes. Hexachlorocyclotriphosphazene, (N3P3Cl6) and octachlorocyclotetraphosphazene (N4P4Cl8) have been reacted with carboxylic amino acid esters; glycine ethyl ester hydrochloride, glycine methyl ester hydrochloride, β-alanine ethyl ester hydrochloride, β-alanine methyl ester hydrochloride and methyl 6-aminohexanoate hydrochloride to obtain cyclophosphazene compounds containing amino acid esters as side groups. All obtained compounds (1-9) were characterized using spectroscopic methods and elemental analysis. The molecular structures of compounds 2, 5 and 6 were also characterized by X-ray crystallographic studies. Hydrolytic degradations of compounds (1-9) were observed by 31P NMR spectroscopy under acidic condition (pH = 1-3) and at body temperature (35-38 °C). Concentration-dependent lower critical solution temperatures (LCST) of compounds were examined to determine their thermosensitive behaviors in aqueous solution. It is found that all compounds degraded to harmless products such as amino acid, phosphates, ammonium salts. LCSTs of compounds 1, 2 and 6 were found to be around body temperature that is important for biomedical applications.

  9. Metabolic engineering of Saccharomyces cerevisiae for production of fatty acid-derived biofuels and chemicals.

    PubMed

    Runguphan, Weerawat; Keasling, Jay D

    2014-01-01

    As the serious effects of global climate change become apparent and access to fossil fuels becomes more limited, metabolic engineers and synthetic biologists are looking towards greener sources for transportation fuels. In recent years, microbial production of high-energy fuels by economically efficient bioprocesses has emerged as an attractive alternative to the traditional production of transportation fuels. Here, we engineered the budding yeast Saccharomyces cerevisiae to produce fatty acid-derived biofuels and chemicals from simple sugars. Specifically, we overexpressed all three fatty acid biosynthesis genes, namely acetyl-CoA carboxylase (ACC1), fatty acid synthase 1 (FAS1) and fatty acid synthase 2 (FAS2), in S. cerevisiae. When coupled to triacylglycerol (TAG) production, the engineered strain accumulated lipid to more than 17% of its dry cell weight, a four-fold improvement over the control strain. Understanding that TAG cannot be used directly as fuels, we also engineered S. cerevisiae to produce drop-in fuels and chemicals. Altering the terminal "converting enzyme" in the engineered strain led to the production of free fatty acids at a titer of approximately 400 mg/L, fatty alcohols at approximately 100mg/L and fatty acid ethyl esters (biodiesel) at approximately 5 mg/L directly from simple sugars. We envision that our approach will provide a scalable, controllable and economic route to this important class of chemicals. Copyright © 2013 International Metabolic Engineering Society. All rights reserved.

  10. Nucleation modeling of the Antarctic stratospheric CN layer and derivation of sulfuric acid profiles

    NASA Astrophysics Data System (ADS)

    Münch, Steffen; Curtius, Joachim

    2017-06-01

    Recent analysis of long-term balloon-borne measurements of Antarctic stratospheric condensation nuclei (CN) between July and October showed the formation of a volatile CN layer at 21-27 km altitude in a background of existing particles. We use the nucleation model SAWNUC to simulate these CN in subsiding air parcels and study their nucleation and coagulation characteristics. Our simulations confirm recent analysis that the development of the CN layer can be explained with neutral sulfuric acid-water nucleation and we show that outside the CN layer the measured CN concentrations are well reproduced just considering coagulation and the subsidence of the air parcels. While ion-induced nucleation is expected as the dominating formation process at higher temperatures, it does not play a significant role during the CN layer formation as the charged clusters recombine too fast. Further, we derive sulfuric acid concentrations for the CN layer formation. Our concentrations are about 1 order of magnitude higher than previously presented concentrations as our simulations consider that nucleated clusters have to grow to CN size and can coagulate with preexisting particles. Finally, we calculate threshold sulfuric acid profiles that show which concentration of sulfuric acid is necessary for nucleation and growth to observable size. These threshold profiles should represent upper limits of the actual sulfuric acid outside the CN layer. According to our profiles, sulfuric acid concentrations seem to be below midlatitude average during Antarctic winter but above midlatitude average for the CN layer formation.

  11. Chemoselective amide formation using O-(4-nitrophenyl)hydroxylamines and pyruvic acid derivatives.

    PubMed

    Kumar, Sonali; Sharma, Rashi; Garcia, Megan; Kamel, Joseph; McCarthy, Caroline; Muth, Aaron; Phanstiel, Otto

    2012-12-07

    A series of O-(4-nitrophenyl)hydroxylamines were synthesized from their respective oximes using a pulsed addition of excess NaBH(3)CN at pH 3 in 65-75% yield. Steric hindrance near the oxime functional group played a key role in both the ease by which the oxime could be reduced and the subsequent reactivity of the respective hydroxylamine. Reaction of the respective hydroxylamines with pyruvic acid derivatives generated the desired amides in good yields. A comparison of phenethylamine systems bearing different leaving groups revealed significant differences in the rates of these systems and suggested that the leaving group ability of the N-OR substituent plays an important role in determining their reactivity with pyruvic acid. Competition experiments (in 68% DMSO/phosphate buffered saline) using 1 equiv of N-phenethyl-O-(4-nitrophenyl)hydroxylamine and 2 equiv of pyruvic acid in the presence of other nucleophiles such as glycine, cysteine, phenol, hexanoic acid, and lysine demonstrated that significant chemoselectivity is present in this reaction. The results suggest that this chemoselective reaction can occur in the presence of excess α-amino acids, phenols, acids, thiols, and amines.

  12. Synthesis and biological activity of thiazolyl-acetic acid derivatives as possible antimicrobial agents.

    PubMed

    Shirai, Akihiro; Fumoto, Yasuko; Shouno, Tomoaki; Maseda, Hideaki; Omasa, Takeshi

    2013-01-01

    5a-h, a series of (5-substituted-2-methyl-1,3-thiazole-4-yl) acetic acids as heterocyclic acetic acid derivatives, was designed and synthesized from ethyl acetoacetate. The synthesized compounds were screened for their antimicrobial activities against bacterial and fungal strains, and their characteristics were investigated by assays under various temperature and pH conditions. Cytotoxicity was evaluated with the use of sheep erythrocytes and human neonate dermal fibroblasts. Similarly, agents such as lauric acid 6 and parabens 7a-b, which are used as preservative agents for commercial cosmetics and detergents, were assayed for comparison. Although the structure of 5a is simple, comprising a thiazole attached with an octyl group and acetic acid moiety, the compound showed stronger and broader antibacterial and antifungal activities among the 5 series against the tested microbes other than gram-negative bacteria. Interestingly, 5a overcame the weak antifungal activity of parabens 7a-b. Also, the cytotoxicity of 5a was less than that of parabens 7a-b, especially to human dermal fibroblasts. These results suggest that thiazolyl-acetic acid 5a is a potentially effective biocide, and that it could be used as a preservative agent in commercially sold cosmetics and detergents, facilitated by the hydrophilic and charge properties of its carboxylic acid moiety.

  13. Plasmodium falciparum-Derived Uric Acid Precipitates Induce Maturation of Dendritic Cells

    PubMed Central

    van de Hoef, Diana L.; Coppens, Isabelle; Holowka, Thomas; Ben Mamoun, Choukri; Branch, OraLee; Rodriguez, Ana

    2013-01-01

    Malaria is characterized by cyclical fevers and high levels of inflammation, and while an early inflammatory response contributes to parasite clearance, excessive and persistent inflammation can lead to severe forms of the disease. Here, we show that Plasmodium falciparum-infected erythrocytes contain uric acid precipitates in the cytoplasm of the parasitophorous vacuole, which are released when erythrocytes rupture. Uric acid precipitates are highly inflammatory molecules that are considered a danger signal for innate immunity and are the causative agent in gout. We determined that P. falciparum-derived uric acid precipitates induce maturation of human dendritic cells, increasing the expression of cell surface co-stimulatory molecules such as CD80 and CD86, while decreasing human leukocyte antigen-DR expression. In accordance with this, uric acid accounts for a significant proportion of the total stimulatory activity induced by parasite-infected erythrocytes. Moreover, the identification of uric acid precipitates in P. falciparum- and P. vivax-infected erythrocytes obtained directly from malaria patients underscores the in vivo and clinical relevance of our findings. Altogether, our data implicate uric acid precipitates as a potentially important contributor to the innate immune response to Plasmodium infection and may provide a novel target for adjunct therapies. PMID:23405174

  14. Recent developments in altering the fatty acid composition of ruminant-derived foods.

    PubMed

    Shingfield, K J; Bonnet, M; Scollan, N D

    2013-03-01

    There is increasing evidence to indicate that nutrition is an important factor involved in the onset and development of several chronic human diseases including cancer, cardiovascular disease (CVD), type II diabetes and obesity. Clinical studies implicate excessive consumption of medium-chain saturated fatty acids (SFA) and trans-fatty acids (TFA) as risk factors for CVD, and in the aetiology of other chronic conditions. Ruminant-derived foods are significant sources of medium-chain SFA and TFA in the human diet, but also provide high-quality protein, essential micronutrients and several bioactive lipids. Altering the fatty acid composition of ruminant-derived foods offers the opportunity to align the consumption of fatty acids in human populations with public health policies without the need for substantial changes in eating habits. Replacing conserved forages with fresh grass or dietary plant oil and oilseed supplements can be used to lower medium-chain and total SFA content and increase cis-9 18:1, total conjugated linoleic acid (CLA), n-3 and n-6 polyunsaturated fatty acids (PUFA) to a variable extent in ruminant milk. However, inclusion of fish oil or marine algae in the ruminant diet results in marginal enrichment of 20- or 22-carbon PUFA in milk. Studies in growing ruminants have confirmed that the same nutritional strategies improve the balance of n-6/n-3 PUFA, and increase CLA and long-chain n-3 PUFA in ruminant meat, but the potential to lower medium-chain and total SFA is limited. Attempts to alter meat and milk fatty acid composition through changes in the diet fed to ruminants are often accompanied by several-fold increases in TFA concentrations. In extreme cases, the distribution of trans 18:1 and 18:2 isomers in ruminant foods may resemble that of partially hydrogenated plant oils. Changes in milk fat or muscle lipid composition in response to diet are now known to be accompanied by tissue-specific alterations in the expression of one or more

  15. [Anxiolytic and antidepressant effects of 3-oxypiridine and succinic acid derivatives in alloxan diabetes].

    PubMed

    Volchegorskii, L A; Miroshnichenko, I Yu; Rassokhina, L M; Faizullin, R M; Pryakhina, K E; Kalugina, A V

    2015-03-01

    The effects of 3-oxypyridine and succinic acid derivatives (emoxipine, reamberin and mexidol) on affective disorders in rats with alloxan diabetes were studied. The efficiency of emoxipine, reamberin and mexidol was compared to alpha-lipoic acid, which is considered a "golden standard" in treatment of diabetic neuropathies. Emoxipine, reamberin and mexidol after seven administrations in single doses, that are equivalent to therapeutic range in humans, corrected the anxiety-depressive disorders in rats with alloxan diabetes. Unlike reamberin and alpha-lipoic acid, emoxipine and mexidol corrected the affective status concurrently with the decrease in hyperglycemia. At the same time, emoxipine outperformed mexidol in tranquilizing action (in maximal doses) but yielded mexidol in the antidepressant effect (in minimal doses).

  16. Antioxidative properties of hydroxycinnamic acid derivatives and a phenylpropanoid glycoside. A pulse radiolysis study

    NASA Astrophysics Data System (ADS)

    Lin, Weizhen; Navaratnam, Suppiah; Yao, Side; Lin, Nianyun

    1998-10-01

    Spectral and redox properties of the phenoxyl radicals from hydroxycinnamic acid derivatives and one selected component of phenylpropanoid glycosides, verbascoside, were studied using pulse radiolysis techniques. On the basis of the pH dependence of phenoxyl radical absorptions, the p Ka values for deprotonation of sinapic acid radical and ferulic acid radical are 4.9 and 5.2. The rate constants of one electron oxidation of those antioxidants by azide radical and bromide radical ion were determined at pH 7. The redox potentials of those antioxidants were determined as 0.59-0.71 V vs NHE at pH 7 with reference standard 4-methoxyphenol and resorcinol.

  17. Quantitative structure-activity relationships of antimicrobial fatty acids and derivatives against Staphylococcus aureus *

    PubMed Central

    Zhang, Hui; Zhang, Lu; Peng, Li-juan; Dong, Xiao-wu; Wu, Di; Wu, Vivian Chi-Hua; Feng, Feng-qin

    2012-01-01

    Fatty acids and derivatives (FADs) are resources for natural antimicrobials. In order to screen for additional potent antimicrobial agents, the antimicrobial activities of FADs against Staphylococcus aureus were examined using a microplate assay. Monoglycerides of fatty acids were the most potent class of fatty acids, among which monotridecanoin possessed the most potent antimicrobial activity. The conventional quantitative structure-activity relationship (QSAR) and comparative molecular field analysis (CoMFA) were performed to establish two statistically reliable models (conventional QSAR: R 2=0.942, Q 2 LOO=0.910; CoMFA: R 2=0.979, Q 2=0.588, respectively). Improved forecasting can be achieved by the combination of these two models that provide a good insight into the structure-activity relationships of the FADs and that may be useful to design new FADs as antimicrobial agents. PMID:22302421

  18. Safety assessment of animal- and plant-derived amino acids as used in cosmetics.

    PubMed

    Burnett, Christina; Heldreth, Bart; Bergfeld, Wilma F; Belsito, Donald V; Hill, Ronald A; Klaassen, Curtis D; Liebler, Daniel C; Marks, James G; Shank, Ronald C; Slaga, Thomas J; Snyder, Paul W; Andersen, F Alan

    2014-01-01

    The Cosmetic Ingredient Review Expert Panel (Panel) reviewed the safety of animal- and plant-derived amino acid mixtures, which function as skin and hair conditioning agents. The safety of α-amino acids as direct food additives has been well established, based on extensive research through acute and chronic dietary exposures and the Panel previously has reviewed the safety of individual α-amino acids in cosmetics. The Panel focused its review on dermal irritation and sensitization data relevant to the use of these ingredients in topical cosmetics. The Panel concluded that these 21 ingredients are safe in the present practices of use and concentration as used in cosmetics. © The Author(s) 2014.

  19. Effect of pH on fecal recovery of energy derived from volatile fatty acids.

    PubMed

    Kien, C L; Liechty, E A

    1987-01-01

    We assessed the effect of pH on volatilization of short-chain fatty acids during lyophilization. Acetic, propionic, valeric, and butyric acids were added to a fecal homogenate in amounts sufficient to raise the energy density by 18-27%. Fecal homogenate samples were either acidified (pH 2.8-3.2), alkalinized (pH 7.9-8.7), or left unchanged (4.0-4.8) prior to lyophilization and subsequent bomb calorimetry. Alkalinizing the fecal samples prevented the 20% loss of energy derived from each of these volatile fatty acids observed in samples either acidified or without pH adjustment. These data suggest that in energy balance studies involving subjects with active colonic fermentation, fecal samples should be alkalinized prior to lyophilization and bomb calorimetry.

  20. Fatty Acid-Derived Biofuels and Chemicals Production in Saccharomyces cerevisiae.

    PubMed

    Zhou, Yongjin J; Buijs, Nicolaas A; Siewers, Verena; Nielsen, Jens

    2014-01-01

    Volatile energy costs and environmental concerns have spurred interest in the development of alternative, renewable, sustainable, and cost-effective energy resources. Environment-friendly processes involving microbes can be used to synthesize advanced biofuels. These fuels have the potential to replace fossil fuels in supporting high-power demanding machinery such as aircrafts and trucks. From an engineering perspective, the pathway for fatty acid biosynthesis is an attractive route for the production of advanced fuels such as fatty acid ethyl esters, fatty alcohols, and alkanes. The robustness and excellent accessibility to molecular genetics make the yeast Saccharomyces cerevisiae a suitable host for the purpose of bio-manufacturing. Recent advances in metabolic engineering, as well as systems and synthetic biology, have now provided the opportunity to engineer yeast metabolism for the production of fatty acid-derived fuels and chemicals.

  1. A 3D-QSAR Study on Betulinic Acid Derivatives as Anti-Tumor Agents and the Synthesis of Novel Derivatives for Modeling Validation.

    PubMed

    Ding, Weimin; Zhang, Sheng; Zhu, Meixuan; Wang, Shaoming; Xu, Tao; Qu, Haijing; Yu, Tao; Yan, Xiufeng; Wang, Yang

    2017-01-01

    Betulinic acid is a lupane-type triterpene firstly extracted from the bark of white birch. It has displayed anti-inflammatory, antioxidant, anti-HIV and selective cytotoxicity. To understand the structure- anti-tumor activity relationship of betulinic acid and betulin derivatives and to synthesize novel anti-tumor derivatives of betulinic acid and betulin. The 3D-QSAR methods including CoMFA and CoMSIA methods were performed to study the structureanti- tumor activity relationship of betulinic acid (BA) and betulin (BE) derivatives. According to the models, near the C-3 site, non-bulky, negatively charged electron-donating, hydrophobic, non-hydrogen-bond-donating and hydrogen-bond-accepting groups are favored to the activity. Around the C-28 site, the bulky, positively charged electron-withdrawing and hydrophobic groups are favored, whereas hydrophilic groups may be introduced at the terminal of the side chain. Based on the models, BA and BE were esterified with substituted amino acid derivatives achieving novel derivatives for the modeling validation. The experimental results verified the modeling rules, and showed when different rules may apply to the new structures, the steric effects might be more important. The synthesized derivatives were showed promising cytotoxicity against tested cancer cell lines. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  2. Optical and thermal properties of azo derivatives of salicylic acid thin films.

    PubMed

    Ghoneim, M M; El-Ghamaz, N A; El-Sonbati, A Z; Diab, M A; El-Bindary, A A; Serag, L S

    2015-02-25

    N-acryloyl-4-aminosalicylic acid (4-AMSA), monomer (HL) and 5-(4'-alkyl phenylazo)-N-acryloyl-4-aminosalicylic acid (HLn) are synthesized and characterized with various physico-chemical techniques. Thin films of 5-(4'-alkyl phenylazo)-N-acryloyl-4-aminosalicylic acid (HLn) are prepared by spin coating technique. The X-ray diffraction (XRD) patterns of 4-aminosalicylic acid (4-ASA) and its derivatives are investigated in powder and thin film forms. Thermal properties of the compounds are investigated by thermogravemetric analysis (TGA). The optical energy gap and the type of optical transition are investigated in the wavelength range (200-2500 nm) for 4-ASA, HL and HLn. The values of fundamental energy gap (Eg) are in the range 3.60-3.69 eV for all compounds and the type of optical transition is found to be indirect allowed. The onset energy gap Eg(∗) appeared only for azodye compounds is found to be in the range 0.95-1.55 eV depending on the substituent function groups. The refractive index, n, shows a normal dispersion in the wavelength range 650-2500 nm, while shows anomalous dispersion in the wavelength rang 200-650 nm. The dispersion parameters ε∞, εL, Ed, Eo and N/m(∗) are calculated. The photoluminescence phenomena (PL) appear for thin films of 4-ASA and its derivatives show three main emission transitions.

  3. Optical and thermal properties of azo derivatives of salicylic acid thin films

    NASA Astrophysics Data System (ADS)

    Ghoneim, M. M.; El-Ghamaz, N. A.; El-Sonbati, A. Z.; Diab, M. A.; El-Bindary, A. A.; Serag, L. S.

    2015-02-01

    N-acryloyl-4-aminosalicylic acid (4-AMSA), monomer (HL) and 5-(4‧-alkyl phenylazo)-N-acryloyl-4-aminosalicylic acid (HLn) are synthesized and characterized with various physico-chemical techniques. Thin films of 5-(4‧-alkyl phenylazo)-N-acryloyl-4-aminosalicylic acid (HLn) are prepared by spin coating technique. The X-ray diffraction (XRD) patterns of 4-aminosalicylic acid (4-ASA) and its derivatives are investigated in powder and thin film forms. Thermal properties of the compounds are investigated by thermogravemetric analysis (TGA). The optical energy gap and the type of optical transition are investigated in the wavelength range (200-2500 nm) for 4-ASA, HL and HLn. The values of fundamental energy gap (Eg) are in the range 3.60-3.69 eV for all compounds and the type of optical transition is found to be indirect allowed. The onset energy gap Eg∗ appeared only for azodye compounds is found to be in the range 0.95-1.55 eV depending on the substituent function groups. The refractive index, n, shows a normal dispersion in the wavelength range 650-2500 nm, while shows anomalous dispersion in the wavelength rang 200-650 nm. The dispersion parameters ε∞, εL, Ed, Eo and N /m∗ are calculated. The photoluminescence phenomena (PL) appear for thin films of 4-ASA and its derivatives show three main emission transitions.

  4. Poly(L-aspartic acid) derivative soluble in a volatile organic solvent for biomedical application.

    PubMed

    Oh, Nam Muk; Oh, Kyung Taek; Youn, Yu Seok; Lee, Eun Seong

    2012-09-01

    In order to develop a novel functional poly(L-amino acid) that can dissolve in volatile organic solvents, we prepared poly[L-aspartic acid-g-(3-diethylaminopropyl)]-b-poly(ethylene glycol) [poly(L-Asp-g-DEAP)-b-PEG] via the conjugation of 3-diethylaminopropyl (DEAP) to carboxylate groups of poly(L-Asp) (M(n) 4 K)-b-PEG (M(n) 2 K). This poly(L-aspartic acid) derivative evidenced a relatively high solubility in volatile organic solvents such as dichloromethane, chloroform, and acetone. We fabricated a model nanostructure (i.e., polymeric micelle) using poly(L-Asp-g-DEAP)-b-PEG by the film rehydration method, which involves the simple removal of the volatile organic solvent (dichloromethane) used to dissolve polymer, reducing concerns about organic solvents remaining in a nano-sized particle. Interestingly, this micelle showed the pH-stimulated release of encapsulated model drug [i.e., doxorubicin (DOX)] due to the protonation of DEAP according to the pH of the solution. We expect that this poly(L-aspartic acid) derivative promises to provide pharmaceutical potential for constituting a new stimuli-sensitive drug carrier for various drug molecules.

  5. Hydroxycinnamic Acids and Their Derivatives: Cosmeceutical Significance, Challenges and Future Perspectives, a Review.

    PubMed

    Taofiq, Oludemi; González-Paramás, Ana M; Barreiro, Maria Filomena; Ferreira, Isabel C F R

    2017-02-13

    Bioactive compounds from natural sources, due to their widely-recognized benefits, have been exploited as cosmeceutical ingredients. Among them, phenolic acids emerge with a very interesting potential. In this context, this review analyzes hydroxycinnamic acids and their derivatives as multifunctional ingredients for topical application, as well as the limitations associated with their use in cosmetic formulations. Hydroxycinnamic acids and their derivatives display antioxidant, anti-collagenase, anti-inflammatory, antimicrobial and anti-tyrosinase activities, as well as ultraviolet (UV) protective effects, suggesting that they can be exploited as anti-aging and anti-inflammatory agents, preservatives and hyperpigmentation-correcting ingredients. Due to their poor stability, easy degradation and oxidation, microencapsulation techniques have been employed for topical application, preventing them from degradation and enabling a sustained release. Based on the above findings, hydroxycinnamic acids present high cosmetic potential, but studies addressing the validation of their benefits in cosmetic formulations are still scarce. Furthermore, studies dealing with skin permeation are scarcely available and need to be conducted in order to predict the topical bioavailability of these compounds after application.

  6. Crystal structures of complexes of vitamin D receptor ligand-binding domain with lithocholic acid derivatives

    PubMed Central

    Masuno, Hiroyuki; Ikura, Teikichi; Morizono, Daisuke; Orita, Isamu; Yamada, Sachiko; Shimizu, Masato; Ito, Nobutoshi

    2013-01-01

    The secondary bile acid lithocholic acid (LCA) and its derivatives act as selective modulators of the vitamin D receptor (VDR), although their structures fundamentally differ from that of the natural hormone 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3)]. Here, we have determined the crystal structures of the ligand-binding domain of rat VDR (VDR-LBD) in ternary complexes with a synthetic partial peptide of the coactivator MED1 (mediator of RNA polymerase II transcription subunit 1) and four ligands, LCA, 3-keto LCA, LCA acetate, and LCA propionate, with the goal of elucidating their agonistic mechanism. LCA and its derivatives bind to the same ligand-binding pocket (LBP) of VDR-LBD that 1,25(OH)2D3 binds to, but in the opposite orientation; their A-ring is positioned at the top of the LBP, whereas their acyclic tail is located at the bottom of the LBP. However, most of the hydrophobic and hydrophilic interactions observed in the complex with 1,25(OH)2D3 are reproduced in the complexes with LCA and its derivatives. Additional interactions between VDR-LBD and the C-3 substituents of the A-ring are also observed in the complexes with LCA and its derivatives. These may result in the observed difference in the potency among the LCA-type ligands. PMID:23723390

  7. Synthesis and biological evaluation of quinic acid derivatives as anti-inflammatory agents.

    PubMed

    Zeng, Kui; Thompson, Karin Emmons; Yates, Charles R; Miller, Duane D

    2009-09-15

    Quinic acid (QA) esters found in hot water extracts of Uncaria tomentosa (a.k.a. cat's claw) exert anti-inflammatory activity through mechanisms involving inhibition of the pro-inflammatory transcription factor nuclear factor kappa B (NF-kappaB). Herein, we describe the synthesis and biological testing of novel QA derivatives. Inhibition of NF-kappaB was assessed using A549 (Type II alveolar epithelial-like) cells that stably express a secreted alkaline phosphatase (SEAP) reporter driven by an NF-kappaB response element. A549-NF-kappaB cells were stimulated with TNF-alpha (10 ng/mL) in the presence or absence of QA derivative for 18 hours followed by measurement of SEAP activity. Amide substitution at the carboxylic acid position yielded potent inhibitors of NF-kappaB. A variety of modifications to the amide substitution were tolerated with the N-propyl amide derivative being the most potent. Further examination of the SAR demonstrated that acetylation of the hydroxyl groups reduced NF-kappaB inhibitory activity. QA amide derivatives lacked anti-oxidant activity and were found to be neither anti-proliferative nor cytotoxic at concentrations up to 100 microM. In conclusion, we have discovered a novel series of non-toxic QA amides that potently inhibit NF-kappaB, despite their lack of anti-oxidant activity. Mechanistic studies and pre-clinical efficacy studies in various inflammatory animal models are on-going.

  8. Characterization of pH-fractionated humic acids derived from Chinese weathered coal.

    PubMed

    Zhang, Shuiqin; Yuan, Liang; Li, Wei; Lin, Zhian; Li, Yanting; Hu, Shuwen; Zhao, Bingqiang

    2017-01-01

    To reduce the compositional and structural heterogeneity of humic acids (HAs) and achieve better use of HA resources, in this study, we report a new sequential dissolution method for HAs derived from Chinese weathered coal. This method was used to separate HAs into seven fractions by adjusting the pH (3-10) of the extraction solution. The results showed that the HA fractions derived from Chinese weathered coal were concentrated up to 90.31% in the lower pH solutions (3-7). The compositional and structural characteristics of the HA fractions were determined by elemental analysis; ultraviolet-visible (UV-Vis), Fourier transform infrared (FTIR), and solid-state (13)C-nuclear magnetic resonance (NMR) spectroscopies; and other techniques. The results showed significant differences among the HA fractions. The concentrations of the total acidic groups and the carboxyl groups decreased with the increasing pH of the extraction solution. However, the HA fractions derived from extraction solutions with pH 3-4 had relatively lower aromaticity but a higher protonated carbon content. The HA fractions derived from extraction solutions with pH 6-7 had the highest aromaticity and the greatest abundance of COO/N-C=O. This study demonstrated that adjusting the pH of the extraction solution is one way to fractionate HAs from Chinese weathered coal and to obtain HA fractions with compositions and structures that could serve as useful material for study and utilization.

  9. Synthesis and hypoglycemic activity of S-acyl derivatives of 3-mercaptopicolinic acid.

    PubMed

    Blank, B; DiTullio, N W; Deviney, L; Roberts, J T; Saunders, H L

    1977-04-01

    A series of S-alkanoyl and benzoyl derivatives of 3-mercaptopicolinic acid (3-MPA) was prepared and studied for hypoglycemic activity. Three alkanoyl derivatives (propionyl, pivaloyl, and 1-adamantanecarbonyl, 19-21) were prepared with increasing bulk around the thio ester bond. The benzoyl derivatives contained aromatic substituents chosen from a sigma-pi cluster chart so that the esters prepared had a wide range of electronic and solubility properties. In general, compounds with substituents which increased lipid solubility [p-chlorobenzoyl (4), p-trifluoromethylbenzoyl (6), and pivaloyl (20)] had the greatest potency at a dose of 300 mg/kg. Hydrolysis rates, measured at pH 6 and 8, indicated that in vivo breakdown to 3-MPA probably did not account for the observed hypoglycemic activity of the esters. 4, 6, and 20 were less potent than 3-MPA in comparative dose range studies.

  10. [Synthesis and characterization of some new rutin and 7-aminocephalosporanic acid derivatives].

    PubMed

    Lupaşcu, D; Tuchiluş, Cristina; Sutu, Maria; Neagu, Alexandra; Profire, Lenuţa

    2011-01-01

    Many studies show that flavonoids have a numerous biological properties, antimicrobial effects included. It is also known that rutin is able to increase the antibacterial activity of other compounds. Starting from these facts, we synthesised some water soluble rutin derivatives treating rutin with 1, 3-dichloro-2-propanol, 1-bromo-3-chloro-propane, 2-dibromethane, and dibrommethane, and than with 7-amino-cephalosporanic acid. The antimicrobial activity of the new compounds was determined by disc diffusion method. Molecular formula, weight, yield, melting points and solubility of the new derivatives have been determined. Elemental analysis and spectral analysis (UV and IR) confirmed the structure of new compounds. CONCLUSIONS. These derivatives are water-soluble and have a good antimicrobial activity, both on Gram-positive and Gram-negative bacteria, comparable with that of tetracycline.

  11. Synthesis, evaluation and molecular docking studies of amino acid derived N-glycoconjugates as antibacterial agents.

    PubMed

    Baig, Noorullah; Singh, Rajnish Prakash; Chander, Subhash; Jha, Prabhat Nath; Murugesan, Sankaranarayanan; Sah, Ajay K

    2015-12-01

    Six amino acid derived N-glycoconjugates of d-glucose were synthesized, characterized and tested for antibacterial activity against G(+)ve (Bacillus cereus) as well as G(-)ve (Escherichia coli and Klebsiella pneumoniae) bacterial strains. All the tested compounds exhibited moderate to good antibacterial activity against these bacterial strains. The results were compared with the antibacterial activity of standard drug Chloramphenicol, where results of A5 (Tryptophan derived glycoconjugates) against E. coli and A4 (Isoleucine derived glycoconjugates) against K. pneumoniae bacterial strains are comparable with the standard drug molecule. In silico docking studies were also performed in order to understand the mode of action and binding interactions of these molecules. The docking studies revealed that, occupation of compound A5 at the ATP binding site of subunit GyrB (DNA gyrase, PDB ID: 3TTZ) via hydrophobic and hydrogen bonding interactions may be the reason for its significant in vitro antibacterial activity.

  12. Structure-activity relationship studies of microbiologically active thiosemicarbazides derived from hydroxybenzoic acid hydrazides.

    PubMed

    Plech, Tomasz; Paneth, Agata; Kaproń, Barbara; Kosikowska, Urszula; Malm, Anna; Strzelczyk, Aleksandra; Stączek, Paweł

    2015-03-01

    Forty-five derivatives of thiosemicarbazide were synthesized, and their antibacterial activity against Gram-positive and Gram-negative bacteria was evaluated. Some of the described compounds exhibited interesting activity against reference strains of Gram-positive bacteria, whereas only two derivatives had the ability to inhibit the growth of Gram-negative species (Escherichia coli ATCC 25922, Klebsiella pneumoniae ATCC 13883, Proteus mirabilis ATCC 12453). The most potent antimicrobial activity was observed in the cases of salicylic acid hydrazide derivatives. The differences in activity inspired us to conduct conformational analysis using molecular mechanics level. The obtained results suggest that the molecule geometry, especially at the N4-terminus of thiosemicarbazide skeleton, determines the antibacterial activity. Unfortunately, in opposition to what we expected, only one of the tested compounds inhibited the activity of the topoIV enzyme, and none of them was active against DNA gyrase. © 2014 John Wiley & Sons A/S.

  13. Quantitative structure activity relationships of some pyridine derivatives as corrosion inhibitors of steel in acidic medium.

    PubMed

    El Ashry, El Sayed H; El Nemr, Ahmed; Ragab, Safaa

    2012-03-01

    Quantum chemical calculations using the density functional theory (B3LYP/6-31G DFT) and semi-empirical AM1 methods were performed on ten pyridine derivatives used as corrosion inhibitors for mild steel in acidic medium to determine the relationship between molecular structure and their inhibition efficiencies. Quantum chemical parameters such as total negative charge (TNC) on the molecule, energy of highest occupied molecular orbital (E (HOMO)), energy of lowest unoccupied molecular orbital (E (LUMO)) and dipole moment (μ) as well as linear solvation energy terms, molecular volume (Vi) and dipolar-polarization (π) were correlated to corrosion inhibition efficiency of ten pyridine derivatives. A possible correlation between corrosion inhibition efficiencies and structural properties was searched to reduce the number of compounds to be selected for testing from a library of compounds. It was found that theoretical data support the experimental results. The results were used to predict the corrosion inhibition of 24 related pyridine derivatives.

  14. Protective effect of bile acid derivatives in phalloidin-induced rat liver toxicity

    SciTech Connect

    Herraez, Elisa; Macias, Rocio I.R.; Vazquez-Tato, Jose; Hierro, Carlos; Monte, Maria J.; Marin, Jose J.G.

    2009-08-15

    Phalloidin causes severe liver damage characterized by marked cholestasis, which is due in part to irreversible polymerization of actin filaments. Liver uptake of this toxin through the transporter OATP1B1 is inhibited by the bile acid derivative BALU-1, which does not inhibit the sodium-dependent bile acid transporter NTCP. The aim of the present study was to investigate whether BALU-1 prevents liver uptake of phalloidin without impairing endogenous bile acid handling and hence may have protective effects against the hepatotoxicity induced by this toxin. In anaesthetized rats, i.v. administration of BALU-1 increased bile flow more than taurocholic acid (TCA). Phalloidin administration decreased basal (- 60%) and TCA-stimulated bile flow (- 55%) without impairing bile acid output. Phalloidin-induced cholestasis was accompanied by liver necrosis, nephrotoxicity and haematuria. In BALU-1-treated animals, phalloidin-induced cholestasis was partially prevented. Moreover haematuria was not observed, which was consistent with histological evidences of BALU-1-prevented injury of liver and kidney tissue. HPLC-MS/MS analysis revealed that BALU-1 was secreted in bile mainly in non-conjugated form, although a small proportion (< 5%) of tauro-BALU-1 was detected. BALU-1 did not inhibit the biliary secretion of endogenous bile acids. When highly choleretic bile acids, - ursodeoxycholic (UDCA) and dehydrocholic acid (DHCA) - were administered, they were found less efficient than BALU-1 in preventing phalloidin-induced cholestasis. Biliary phalloidin elimination was low but it was increased by BALU-1 > TCA > DHCA > UDCA. In conclusion, BALU-1 is able to protect against phalloidin-induced hepatotoxicity, probably due to an inhibition of the liver uptake and an enhanced biliary secretion of this toxin.

  15. Analysis of naphthenic acid mixtures as pentafluorobenzyl derivatives by gas chromatography-electron impact mass spectrometry.

    PubMed

    Gutierrez-Villagomez, Juan Manuel; Vázquez-Martínez, Juan; Ramírez-Chávez, Enrique; Molina-Torres, Jorge; Trudeau, Vance L

    2017-01-01

    In this study, we report for the first time the efficiency of pentafluorobenzyl bromide (PFBBr) for naphthenic acid (NA) mixtures derivatization, and the comparison in the optimal conditions to the most common NAs derivatization reagents, BF3/MeOH and N-(t-butyldimethylsilyl)-N-methyltrifluoroacetamide (MTBSTFA). Naphthenic acids are carboxylic acid mixtures of petrochemical origin. These compounds are important for the oil industry because of their corrosive properties, which can damage oil distillation infrastructure. Moreover, NAs are commercially used in a wide range of products such as paint and ink driers, wood and fabric preservatives, fuel additives, emulsifiers, and surfactants. Naphthenic acids have also been found in sediments after major oils spills in the United States and South Korea. Furthermore, the toxicity of the oil sands process-affected water (OSPW), product of the oil sands extraction activities in Canada's oil sands, has largely been attributed to NAs. One of the main challenges for the chromatographic analysis of these mixtures is the resolution of the components. The derivatization optimization was achieved using surface response analysis with molar ratio and time as factors for derivatization signal yield. After gas chromatography-electron impact mass spectrometry (GC/EIMS) analysis of a mixture of NA standards, it was found that the signal produced by PFB-derivatives was 2.3 and 1.4 times higher than the signal produced by methylated and MTBS-derivatives, respectively. The pentafluorobenzyl derivatives have a characteristic fragment ion at 181m/z that is diagnostic for the differentiation of carboxylic and non-carboxylic acid components within mixtures. In the analysis of a Sigma and a Merichem derivatized oil extract NA mixtures, it was found that some peaks lack the characteristic fragment ion; therefore they are not carboxylic acids. Open column chromatography was used to obtain a hexane and a methanol fraction of the Sigma and

  16. Correlating enzymatic browning inhibition and antioxidant ability of Maillard reaction products derived from different amino acids.

    PubMed

    Xu, Haining; Zhang, Xiaoming; Karangwa, Eric; Xia, Shuqin

    2017-09-01

    Up to now, only limited research on enzymatic browning inhibition capacity (BIC) of Maillard reaction products (MRPs) has been reported and there are still no overall and systematic researches on MRPs derived from different amino acids. In the present study, BIC and antioxidant capacity, including 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity and Fe(2+) reducing power activity, of the MRPs derived from 12 different amino acids and three reducing sugars were investigated. The MRPs of cysteine (Cys), cystine, arginine (Arg) and histidine (His) showed higher BIC compared to other amino acids. Lysine (Lys)-MRPs showed the highest absorbance value at 420 nm (A420 ) but very limited BIC, whereas Cys-MRPs, showed the highest BIC and the lowest A420 . The A420 can roughly reflect the trend of BIC of MRPs from different amino acids, except Cys and Lys. MRPs from tyrosine (Tyr) showed the most potent antioxidant capacity but very limited BIC, whereas Cys-MRPs showed both higher antioxidant capacity and BIC compared to other amino acids. Partial least squares regression analysis showed positive and significant correlation between BIC and Fe(2+) reducing power of MRPs from 12 amino acids with glucose or fructose, except Lys, Cys and Tyr. The suitable pH for generating efficient browning inhibition compounds varies depending on different amino acids: acidic pH was favorable for Cys, whereas neutral and alkaline pH were suitable for His and Arg, respectively. Increasing both heating temperature and time over a certain range could improve the BIC of MRPs of Cys, His and Arg, whereas any further increase deteriorates their browning inhibition efficiencies. The types of amino acid, initial pH, temperature and time of the Maillard reaction were found to greatly influence the BIC and antioxidant capacity of the resulting MRPs. There is no clear relationship between BIC and the antioxidant capacity of MRPs when reactant type and processing parameters of the Maillard

  17. Metal cation dependence of interactions with amino acids: bond dissociation energies of Rb(+) and Cs(+) to the acidic amino acids and their amide derivatives.

    PubMed

    Armentrout, P B; Yang, Bo; Rodgers, M T

    2014-04-24

    Metal cation-amino acid interactions are key components controlling the secondary structure and biological function of proteins, enzymes, and macromolecular complexes comprising these species. Determination of pairwise interactions of alkali metal cations with amino acids provides a thermodynamic vocabulary that begins to quantify these fundamental processes. In the present work, we expand a systematic study of such interactions by examining rubidium and cesium cations binding with the acidic amino acids (AA), aspartic acid (Asp) and glutamic acid (Glu), and their amide derivatives, asparagine (Asn) and glutamine (Gln). These eight complexes are formed using electrospray ionization and their bond dissociation energies (BDEs) are determined experimentally using threshold collision-induced dissociation with xenon in a guided ion beam tandem mass spectrometer. Analyses of the energy-dependent cross sections include consideration of unimolecular decay rates, internal energy of the reactant ions, and multiple ion-neutral collisions. Quantum chemical calculations are conducted at the B3LYP, MP2(full), and M06 levels of theory using def2-TZVPPD basis sets, with results showing reasonable agreement with experiment. At 0 and 298 K, most levels of theory predict that the ground-state conformers for M(+)(Asp) and M(+)(Asn) involve tridentate binding of the metal cation to the backbone carbonyl, amino, and side-chain carbonyl groups, although tridentate binding to the carboxylic acid group and side-chain carbonyl is competitive for M(+)(Asn). For the two longer side-chain amino acids, Glu and Gln, multiple structures are competitive. A comparison of these results to those for the smaller alkali cations, Na(+) and K(+), provides insight into the trends in binding energies associated with the molecular polarizability and dipole moment of the side chain. For all four metal cations, the BDEs are inversely correlated with the size of the metal cation and follow the order Asp < Glu

  18. Use of humic acids derived from peat and lignite as phenanthrene sorbents

    NASA Astrophysics Data System (ADS)

    Sofikitis, Elias; Giannouli, Andriana; Kalaitzidis, Stavros; Christanis, Kimon; Karapanagioti, Hrissi K.; Papanicolaou, Cassiani

    2015-04-01

    A broad range of materials is being applied for environmental remediation of water, among them sorbents such as humic acids. Being natural substances, the extraction and purification of humic acids might be cheaper than the production of synthetic sorbents. Having higher absorbing capacity than most of the sorbents used to date, humic acids have a competitive advantage against commonly used sorbents such as active charcoals and biochar. Humic acids are "complex colloidal super-mixtures" that are characterized by their functional groups. Therefore, composition and molecular formula can vary depending on the properties of the parent material. The aim of this project was (a) to study the sorption capacity of humic acids derived from peat and lignite samples picked up from deposits spread throughout Greece and (b) to compare the results with these of the parent materials. This comparison provides an insight to which matrix samples are suitable for further chemical treatment for the isolation of humic acids to be used as sorbents. The selected model pollutant was phenanthrene, which is a PAH that consists of three fused benzene rings. Humic acids were extracted according to the methodology proposed by the IHSS, slightly modified, in order to fit better to the properties of organic sediments. Sorption experiments were conducted by mixing 0.004 g of the sorbent (peat or lignite or humic acid) with aqueous solutions of phenanthrene at different concentrations of 30, 50, 100, 300, and 500 μg/L. The results show that phenanthrene sorption is higher for the humic acid than for the original lignite and peat samples. The original samples display higher sorption at the lower phenanthere solutions (30 μg/L; Kd ranges from 15,000 to 47,000 L/kg) than at the higher one (500 μg/L; Kd ranges from 4,100 to 13,000 L/Kg) suggesting non-linear sorption. The humic acids display mainly linear isotherms with Kd ranges from 6,600 to 120,000 L/kg. Concerning the suitability of the studied

  19. [Antihypoxic effect of 3-hydroxypyridine and succinic acid derivatives and their nootropic action in alloxan diabetes].

    PubMed

    Volchegorskiĭ, I A; Rassokhina, L M; Miroshnichenko, I Iu

    2011-01-01

    Relationship between the antihypoxic effect of 3-hydroxypyridine and succinic acid derivatives (emoxipine, reamberin and mexidol) and their effect on conditional learning, glycemia, and lipidemia was studied in rats with alloxan-induced diabetes. In parallel, the analogous relationship was investigated for alpha-lipoic acid that is regarded as a "gold standard" in treatment of diabetic neuropathy. It was established that single administration of emoxipine and mexidol in mice in doses equivalent to therapeutic-range doses in humans produces antihypoxic effect manifested by increased resistance to acute hypoxic hypoxia in test animals. Alpha-lipoic acid is inferior to emoxipin and mexidol in the degree of antihypoxic action. Reamberin does not exhibit this effect. The introduction of emoxipin, reamberin, mexidol, and alpha-lipoic acid in rats with alloxan diabetes during 7 or 14 days in doses equivalent to therapeutic-range doses in humans corrects conditional learning disorders in direct relationship with the antihypoxic activity of these drugs. The development of the nootropic effect of emoxipin, mexidol, and alpha-lipoic acid is related to a decrease in hyperglycemia and hyperlipidemia in rats with alloxan diabetes. The nootropic action of reamberin is accompanied by a transient hypoglycemizing effect and aggravation of dyslipidemic disorders. The antihypoxic activity of investigated drugs determines the direction and expression of their lipidemic effect, but is not correlated with the hypoglycemizing action these drugs on test animals with alloxan diabetes.

  20. Natural derivatives of diphenolic acid as substitutes for bisphenol-A

    NASA Astrophysics Data System (ADS)

    Ertl, Johanna; Cerri, Elisa; Rizzuto, Matteo; Caretti, Daniele

    2014-05-01

    Diphenolic acid had been originally used in the first epoxy resins and was later on forgotten as it was substituted by the cheaper bisphenol A. But in the recent years major health concerns have been raised as bisphenol A has a pseudo-hormonal effect on the body, playing the role of estrogen it can cause a severe impact on the organism, especially in males. Moreover it is produced from acetone and phenol, both from fossil, and thus limited resources. On the contrary, diphenolic acid is synthesized from levulinic acid and phenol. Levulinic acid being directly produced by hydrolysis of biomass. By substituting the fossil phenol with natural phenols from lignin or plant extraction we are able to synthesize a fully renewable substitute for bisphenol A. The reactions to yield an epoxy resin have been examined and the reactivity with epichlorohydrin is satisfying. Moreover, some of the derivatives of diphenolic acid have interesting curing properties and preliminary results show excellent properties of the cured resin, including thermal stability and pencil hardness.

  1. Chirality of meteoritic free and IOM-derived monocarboxylic acids and implications for prebiotic organic synthesis

    NASA Astrophysics Data System (ADS)

    Aponte, José C.; Tarozo, Rafael; Alexandre, Marcelo R.; Alexander, Conel M. O.'D.; Charnley, Steven B.; Hallmann, Christian; Summons, Roger E.; Huang, Yongsong

    2014-04-01

    The origin of homochirality and its role in the development of life on Earth are among the most intriguing questions in science. It has been suggested that carbonaceous chondrites seeded primitive Earth with the initial organic compounds necessary for the origin of life. One of the strongest pieces of evidence supporting this theory is that certain amino acids in carbonaceous chondrites display a significant L-enantiomeric excess (ee), similar to those use by terrestrial life. Analyses of ee in meteoritic molecules other than amino acids would shed more light on the origins of homochirality. In this study we investigated the stereochemistry of two groups of compounds: (1) free monocarboxylic acids (MCAs) from CM2 meteorites LON 94101 and Murchison; and (2) the aliphatic side chains present in the insoluble organic matter (IOM) and extracted in the form of monocarboxylic acids (MCAs) from EET 87770 (CR2) and Orgueil (CI1). Contrary to the well-known ee observed for amino acids in meteorites, we found that meteoritic branched free and IOM-derived MCAs with 5-8 carbon atoms are essentially racemic. The racemic nature of these compounds is used to discuss the possible influence of ultraviolet circularly polarized light (UVCPL) and aqueous alterations on the parent body on chirality observed in in carbonaceous chondrites.

  2. Production of chlorogenic acid and its derivatives in hairy root cultures of Stevia rebaudiana.

    PubMed

    Fu, Xiao; Yin, Zhong-Ping; Chen, Ji-Guang; Shangguan, Xin-Chen; Wang, Xiaoqiang; Zhang, Qing-Feng; Peng, Da-Yong

    2015-01-14

    Chlorogenic acid and its derivatives (CADs) are valuable bioactive plant secondary metabolites with many health benefits. In the present study, Stevia rebaudiana hairy root cultures were established, and the culture conditions for the production of CADs were optimized. The hairy roots were induced by coculture of S. rebaudiana leaves and Agrobacterium rhizogenes (C58C1) after infection, which were further verified by PCR detection of rolB and rolC genes. HPLC-MS and HPLC analysis showed that chlorogenic acid (3-caffeoylquinic acid, 3-CQA), 3,5-dicaffeoylquinic acid (3,5-CQA), and 4,5-dicaffeoylquinic acid (4,5-CQA) were the major CADs in the hairy roots. Eight single roots with rapid growth rate were selected. Among them, T3 had the highest yield of CADs. B5 medium supplemented with 40 g/L sucrose was more suitable for the production of CADs than others. Under optimal culture conditions, the total content of these three compounds reached 105.58 mg/g and total yield was 234.40 mg/100 mL.

  3. Thioesterases for ethylmalonyl-CoA pathway derived dicarboxylic acid production in Methylobacterium extorquens AM1.

    PubMed

    Sonntag, Frank; Buchhaupt, Markus; Schrader, Jens

    2014-05-01

    The ethylmalonyl-coenzyme A pathway (EMCP) is a recently discovered pathway present in diverse α-proteobacteria such as the well studied methylotroph Methylobacterium extorquens AM1. Its glyoxylate regeneration function is obligatory during growth on C1 carbon sources like methanol. The EMCP contains special CoA esters, of which dicarboxylic acid derivatives are of high interest as building blocks for chemical industry. The possible production of dicarboxylic acids out of the alternative, non-food competing C-source methanol could lead to sustainable and economic processes. In this work we present a testing of functional thioesterases being active towards the EMCP CoA esters including in vitro enzymatic assays and in vivo acid production. Five thioesterases including TesB from Escherichia coli and M. extorquens, YciA from E. coli, Bch from Bacillus subtilis and Acot4 from Mus musculus showed activity towards EMCP CoA esters in vitro at which YciA was most active. Expressing yciA in M. extorquens AM1 led to release of 70 mg/l mesaconic and 60 mg/l methylsuccinic acid into culture supernatant during exponential growth phase. Our data demonstrates the biotechnological applicability of the thioesterase YciA and the possibility of EMCP dicarboxylic acid production from methanol using M. extorquens AM1.

  4. A novel acidic pH fluorescent probe based on a benzothiazole derivative.

    PubMed

    Ma, Qiujuan; Li, Xian; Feng, Suxiang; Liang, Beibei; Zhou, Tiqiang; Xu, Min; Ma, Zhuoyi

    2017-04-15

    A novel acidic pH fluorescent probe 1 based on a benzothiazole derivative has been designed, synthesized and developed. The linear response range covers the acidic pH range from 3.44 to 6.46, which is valuable for pH researches in acidic environment. The evaluated pKa value of the probe 1 is 4.23. The fluorescence enhancement of the studied probe 1 with an increase in hydrogen ions concentration is based on the hindering of enhanced photo-induced electron transfer (PET) process. Moreover, the pH sensor possesses a highly selective response to H(+) in the presence of metal ions, anions and other bioactive small molecules which would be interfere with its fluorescent pH response. Furthermore, the probe 1 responds to acidic pH with short response time that was less than 1min. The probe 1 has been successfully applied to confocal fluorescence imaging in live HeLa cells and can selectively stain lysosomes. All of such good properties prove it can be used to monitoring pH fluctuations in acidic environment with high sensitivity, pH dependence and short response time.

  5. Novel phage display-derived mycolic acid-specific antibodies with potential for tuberculosis diagnosis.

    PubMed

    Chan, Conrad E; Zhao, Bryan Z; Cazenave-Gassiot, Amaury; Pang, Shyue-Wei; Bendt, Anne K; Wenk, Markus R; MacAry, Paul A; Hanson, Brendon J

    2013-10-01

    Tuberculosis is a major cause of mortality and morbidity due to infectious disease. However, current clinical diagnostic methodologies such as PCR, sputum culture, or smear microscopy are not ideal. Antibody-based assays are a suitable alternative but require specific antibodies against a suitable biomarker. Mycolic acid, which has been found in patient sputum samples and comprises a large portion of the mycobacterial cell wall, is an ideal target. However, generating anti-lipid antibodies using traditional hybridoma methodologies is challenging and has limited the exploitation of this lipid as a diagnostic marker. We describe here the isolation and characterization of four anti-mycolic acid antibodies from a nonimmune antibody phage display library that can detect mycolic acids down to a limit of 4.5ng. All antibodies were specific for the methoxy subclass of mycolic acid with weak binding for α mycolic acid and did not show any binding to closely related lipids or other Mycobacterium tuberculosis (Mtb) derived lipids. We also determined the clinical utility of these antibodies based on their limit of detection for mycobacteria colony forming units (CFU). In combination with an optimized alkaline hydrolysis method for rapid lipid extraction, these antibodies can detect 10(5) CFU of Mycobacterium bovis BCG, a close relative of Mtb and therefore represent a novel approach for the development of diagnostic assays for lipid biomarkers.

  6. A novel acidic pH fluorescent probe based on a benzothiazole derivative

    NASA Astrophysics Data System (ADS)

    Ma, Qiujuan; Li, Xian; Feng, Suxiang; Liang, Beibei; Zhou, Tiqiang; Xu, Min; Ma, Zhuoyi

    2017-04-01

    A novel acidic pH fluorescent probe 1 based on a benzothiazole derivative has been designed, synthesized and developed. The linear response range covers the acidic pH range from 3.44 to 6.46, which is valuable for pH researches in acidic environment. The evaluated pKa value of the probe 1 is 4.23. The fluorescence enhancement of the studied probe 1 with an increase in hydrogen ions concentration is based on the hindering of enhanced photo-induced electron transfer (PET) process. Moreover, the pH sensor possesses a highly selective response to H+ in the presence of metal ions, anions and other bioactive small molecules which would be interfere with its fluorescent pH response. Furthermore, the probe 1 responds to acidic pH with short response time that was less than 1 min. The probe 1 has been successfully applied to confocal fluorescence imaging in live HeLa cells and can selectively stain lysosomes. All of such good properties prove it can be used to monitoring pH fluctuations in acidic environment with high sensitivity, pH dependence and short response time.

  7. Comparative inhibitory effects of niflumic acid and novel synthetic derivatives on the rat isolated stomach fundus.

    PubMed

    Criddle, David N; Meireles, AnaVanescaP; Macêdo, Liana B; Leal-Cardoso, José H; Scarparo, Henrique C; Jaffar, Mohammed

    2002-02-01

    Novel derivatives of 2-[3-(trifluoromethyl)-analino]nicotinic acid (niflumic acid) were synthesized. The compounds were compared for their inhibitory effects on 5-hydroxytryptamine (5-HT)- and KCI-induced contraction of the rat fundus. The aim was to assess structure-activity relationships regarding the selectivity and potency of these compounds. Niflumic acid (1-100 microM) concentration-dependently inhibited 5-HT-induced tonic contractions with an IC50 value (concentration reducing the control contractile response by 50%, calculated from semi-log graphs) of 0.24 x 10(4) M (n = 9). In contrast, it was significantly less potent at inhibiting KCl-induced responses (IC50 = 1.49 x 10(4) M, n = 9). The methyl ester (NFAme) and amido (NFAm) analogues showed no selectivity between 5-HT- and KCl-induced contractions with IC50 values of 1.64 x 10(-4) M (n = 8) and 1.87 x 10(-4) M (n = 9) for 5-HT responses, and 2.61 x 10(-4) M (n = 8) and 2.55 x 10(-4) M (n = 7) for KCl-induced responses, respectively. Our results suggest that alteration of the carboxylic acid moiety of niflumic acid reduces the selectivity and potency of its inhibitory action on 5-HT-induced contractile responses of the rat fundus, possibly via a reduced interaction with calcium-activated chloride channels.

  8. A pseudaminic acid or a legionaminic acid derivative transferase is strain-specifically implicated in the general protein O-glycosylation system of the periodontal pathogen Tannerella forsythia.

    PubMed

    Tomek, Markus B; Janesch, Bettina; Maresch, Daniel; Windwarder, Markus; Altmann, Friedrich; Messner, Paul; Schäffer, Christina

    2017-03-16

    The occurrence of nonulosonic acids in bacteria is wide-spread and linked to pathogenicity. However, the knowledge of cognate nonulosonic acid transferases is scarce. In the periodontopathogen Tannerella forsythia, several proposed virulence factors carry strain-specifically either a pseudaminic or a legionaminic acid derivative as terminal sugar on an otherwise structurally identical, protein-bound oligosaccharide. This study aims to shed light on the transfer of either nonulosonic acid derivative on a proximal N-acetylmannosaminuronic acid residue within the O-glycan structure, exemplified with the bacterium's abundant S-layer glycoproteins. Bioinformatic analyses provided the candidate genes Tanf_01245 (strain ATCC 43037) and TFUB4_00887 (strain UB4), encoding a putative pseudaminic and a legionaminic acid derivative transferase, respectively. These transferases have identical C-termini and contain motifs typical of glycosyltransferases (DXD) and bacterial sialyltransferases (D/E-D/E-G and HP). They share homology to type B glycosyltransferases and TagB, an enzyme catalyzing glycerol transfer to an N-acetylmannosamine residue in teichoic acid biosynthesis. Analysis of a cellular pool of nucleotide-activated sugars confirmed the presence of the CMP-activated nonulosonic acid derivatives, which are most likely serving as substrates for the corresponding transferase. Single gene knock-out mutants targeted at either transferase were analyzed for S-layer O-glycan composition by ESI-MS, confirming the loss of the nonulosonic acid derivative. Cross-complementation of the mutants with the nonnative nonulosonic acid transferase was not successful indicating high stringency of the enzymes. This study identified plausible candidates for a pseudaminic and a legionaminic acid derivative transferase; these may serve as valuable tools for engineering of novel sialoglycoconjugates.

  9. Endogenous Generation and Signaling Actions of Omega-3 Fatty Acid Electrophilic Derivatives

    PubMed Central

    Cipollina, Chiara

    2015-01-01

    Dietary omega-3 polyunsaturated fatty acids (PUFAs) are beneficial for a number of conditions ranging from cardiovascular disease to chronic airways disorders, neurodegeneration, and cancer. Growing evidence has shown that bioactive oxygenated derivatives are responsible for transducing these salutary effects. Electrophilic oxo-derivatives of omega-3 PUFAs represent a class of oxidized derivatives that can be generated via enzymatic and nonenzymatic pathways. Inflammation and oxidative stress favor the formation of these signaling species to promote the resolution of inflammation within a fine autoregulatory loop. Endogenous generation of electrophilic oxo-derivatives of omega-3 PUFAs has been observed in in vitro and ex vivo human models and dietary supplementation of omega-3 PUFAs has been reported to increase their formation. Due to the presence of an α,β-unsaturated ketone moiety, these compounds covalently and reversibly react with nucleophilic residues on target proteins triggering the activation of cytoprotective pathways, including the Nrf2 antioxidant response, the heat shock response, and the peroxisome proliferator activated receptor γ (PPARγ) and suppressing the NF-κB proinflammatory pathway. The endogenous nature of electrophilic oxo-derivatives of omega-3 PUFAs combined with their ability to simultaneously activate multiple cytoprotective pathways has made these compounds attractive for the development of new therapies for the treatment of chronic disorders and acute events characterized by inflammation and oxidative stress. PMID:26339618

  10. Rheological characterization of hyaluronic acid derivatives as injectable materials toward nucleus pulposus regeneration.

    PubMed

    Gloria, Antonio; Borzacchiello, Assunta; Causa, Filippo; Ambrosio, Luigi

    2012-02-01

    Nucleus pulposus (NP) is the soft center of the intervertebral disc (IVD), able to resist compressive loads, while the annulus fibrosus withstands tension and gives mechanical strength. NP function may be altered as consequence of several pathologies or injury and when a damaged IVD does not properly play its role. In the past years, a great effort has been devoted to the design of injectable systems as NP substitutes. The different synthetic- and natural hydrogel-based materials proposed, present many drawbacks and, in particular, they do not seem to mimic the required behavior. In the search for natural-based systems a dodecylamide of hyaluronic acid (HA), HYADD3®, has been proved as bioactive and suitable vehicle to carry cells for NP tissue engineering, while a crosslinked HA ester, HYAFF120® showed interesting results if used as injectable acellular material. Even though these derivatives showed appropriate biological behavior up to now, data on mechanical behavior of these derivatives are still missing. In this frame, the aim of this study was to provide a rheological characterization of these HA derivatives to asses their biomechanical compatibility with the NP tissue. To this, the rheological properties of these derivatives were studied through dynamic shear tests before and after injection through needles used in the current surgical procedure. Both HA derivatives showed a 'gel-like' rheological behavior similar to the native NP tissue and this behavior was not altered by injection. © The Author(s), 2010.

  11. Compost-derived humic acids as regulators for reductive degradation of nitrobenzene.

    PubMed

    Yuan, Ying; Xi, Beidou; He, Xiaosong; Tan, Wenbing; Gao, Rutai; Zhang, Hui; Yang, Chao; Zhao, Xinyu; Huang, Caihong; Li, Dan

    2017-10-05

    Nitrobenzene (NB) is a major class of contaminants in soil and groundwater. The current methods involved in the reductive degradation of NB suffer either cost-ineffective or slow conversion rate. Here, we investigated the mechanisms regarding compost-derived humic acids (HAs) as cost-effective regulators to enhance the reduction of NB to aniline (AN). Our results show that the compost-derived HAs, which have been reduced by a Pd-H2 catalytic system, were able to reduce NB to AN, and their redox properties were the main factors governing the reduction of NB to AN. The decreasing reduction of NB was mainly caused by the decreasing phenol content of compost-derived HAs during composting. In addition, the results reveal that the increase in the generation content of AN was mainly attributed to the increase in the quinones, aromaticity and humic-like components of compost-derived HAs. The findings demonstrate that the HAs derived from compost are effective regulators to enhance the reduction of NB to AN, and that they exert a bright application prospect for the remediation of the NB-contaminated soil. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Membrane protein complexes catalyze both 4- and 3-hydroxylation of cinnamic acid derivatives in monolignol biosynthesis

    PubMed Central

    Chen, Hsi-Chuan; Li, Quanzi; Shuford, Christopher M.; Liu, Jie; Muddiman, David C.; Sederoff, Ronald R.; Chiang, Vincent L.

    2011-01-01

    The hydroxylation of 4- and 3-ring carbons of cinnamic acid derivatives during monolignol biosynthesis are key steps that determine the structure and properties of lignin. Individual enzymes have been thought to catalyze these reactions. In stem differentiating xylem (SDX) of Populus trichocarpa, two cinnamic acid 4-hydroxylases (PtrC4H1 and PtrC4H2) and a p-coumaroyl ester 3-hydroxylase (PtrC3H3) are the enzymes involved in these reactions. Here we present evidence that these hydroxylases interact, forming heterodimeric (PtrC4H1/C4H2, PtrC4H1/C3H3, and PtrC4H2/C3H3) and heterotrimeric (PtrC4H1/C4H2/C3H3) membrane protein complexes. Enzyme kinetics using yeast recombinant proteins demonstrated that the enzymatic efficiency (Vmax/km) for any of the complexes is 70–6,500 times greater than that of the individual proteins. The highest increase in efficiency was found for the PtrC4H1/C4H2/C3H3-mediated p-coumaroyl ester 3-hydroxylation. Affinity purification-quantitative mass spectrometry, bimolecular fluorescence complementation, chemical cross-linking, and reciprocal coimmunoprecipitation provide further evidence for these multiprotein complexes. The activities of the recombinant and SDX plant proteins demonstrate two protein-complex–mediated 3-hydroxylation paths in monolignol biosynthesis in P. trichocarpa SDX; one converts p-coumaric acid to caffeic acid and the other converts p-coumaroyl shikimic acid to caffeoyl shikimic acid. Cinnamic acid 4-hydroxylation is also mediated by the same protein complexes. These results provide direct evidence for functional involvement of membrane protein complexes in monolignol biosynthesis. PMID:22160716

  13. Multi-Component synthesis and computational studies of three novel thio-barbituric acid carbohydrate derivatives

    NASA Astrophysics Data System (ADS)

    Gupta, Stuti; Khare, Naveen K.

    2017-01-01

    The thio-barbituric acid is convenient starting compound for the preparation of fused heterocycles and its 5-substituted derivatives which are pharmacologically one of the most important classes of compounds. The fused compounds of thio-barbituric acid, 4-(1R,2S,3S,4S)-1,2,3,4,5-tetrahydroxy pentyl-10-phenyl-1,3,6,8,9,10 hexahydro-2,7-dithiooxopyrido [2,3-d; 6,5'] dipyrimidine-4,5 diones (1), 4-(1S,2S,3S,4S)-1,2,3,4,5-tetrahydroxy pentyl-10-phenyl-1,3,6,8,9,10 hexahydro-2,7-dithiooxopyrido [2,3-d; 6,5'] dipyrimidine-4,5 diones (2), 3-(1R,2S,3S)-1,2,3,4-tetrahydroxy butyl-10-phenyl-1,3,6,8,9,10 hexahydro-2,7-dithiooxopyrido [2,3-d; 6,5'] dipyrimidine-4,5 diones (3) have been synthesized in single step by the condensation of thio-barbituric acid with sugars (L-rhamnose, L-fucose and L-arabinose) & aniline using para-toluene sulfonic acid (p-TSA) as an effective acid catalyst under refluxing conditions. The molecular structure and detailed spectroscopic analysis of all three novel synthesized thiones derivatives have been performed using experimental techniques like 1H, 13C NMR, 2D (COSY, HSQC, DEPT-135 and DEPT-90) as well as theoretical calculations by density functional theory (DFT) using B3LYP and 6-311G + (d, p) basis set. The strength and nature of weak intramolecular interactions have been studied by atom in molecule (AIM) approach. Global reactivity descriptors have been computed to predict reactivity and reactive sites in the molecule.

  14. Generation and Dietary Modulation of Anti-Inflammatory Electrophilic Omega-3 Fatty Acid Derivatives

    PubMed Central

    Cipollina, Chiara; Salvatore, Sonia R.; Muldoon, Matthew F.; Freeman, Bruce A.; Schopfer, Francisco J.

    2014-01-01

    Dietary ω-3 polyunsaturated fatty acids (PUFAs) decrease cardiovascular risk via suppression of inflammation. The generation of electrophilic α,β-unsaturated ketone derivatives of the ω-3 PUFAs docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA) in activated human macrophages is catalyzed by cyclooxygenase-2 (Cox-2). These derivatives are potent pleiotropic anti-inflammatory signaling mediators that act via mechanisms including the activation of Nrf2-dependent phase 2 gene expression and suppression of pro-inflammatory NF-κB-driven gene expression. Herein, the endogenous generation of ω-3 PUFAs electrophilic ketone derivatives and their hydroxy precursors was evaluated in human neutrophils. In addition, their dietary modulation was assessed through a randomized clinical trial. Methods Endogenous generation of electrophilic omega-3 PUFAs and their hydroxy precursors was evaluated by mass spectrometry in neutrophils isolated from healthy subjects, both at baseline and upon stimulation with calcium ionophore. For the clinical trial, participants were healthy adults 30–55 years of age with a reported EPA+DHA consumption of ≤300 mg/day randomly assigned to parallel groups receiving daily oil capsule supplements for a period of 4 months containing either 1.4 g of EPA+DHA (active condition, n = 24) or identical appearing soybean oil (control condition, n = 21). Participants and laboratory technicians remained blinded to treatment assignments. Results 5-lypoxygenase-dependent endogenous generation of 7-oxo-DHA, 7-oxo-DPA and 5-oxo-EPA and their hydroxy precursors is reported in human neutrophils stimulated with calcium ionophore and phorbol 12-myristate 13-acetate (PMA). Dietary EPA+DHA supplementation significantly increased the formation of 7-oxo-DHA and 5-oxo-EPA, with no significant modulation of arachidonic acid (AA) metabolite levels. Conclusions The endogenous detection of these electrophilic ω-3 fatty acid ketone derivatives supports the

  15. Generation and dietary modulation of anti-inflammatory electrophilic omega-3 fatty acid derivatives.

    PubMed

    Cipollina, Chiara; Salvatore, Sonia R; Muldoon, Matthew F; Freeman, Bruce A; Schopfer, Francisco J

    2014-01-01

    Dietary ω-3 polyunsaturated fatty acids (PUFAs) decrease cardiovascular risk via suppression of inflammation. The generation of electrophilic α,β-unsaturated ketone derivatives of the ω-3 PUFAs docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA) in activated human macrophages is catalyzed by cyclooxygenase-2 (Cox-2). These derivatives are potent pleiotropic anti-inflammatory signaling mediators that act via mechanisms including the activation of Nrf2-dependent phase 2 gene expression and suppression of pro-inflammatory NF-κB-driven gene expression. Herein, the endogenous generation of ω-3 PUFAs electrophilic ketone derivatives and their hydroxy precursors was evaluated in human neutrophils. In addition, their dietary modulation was assessed through a randomized clinical trial. Endogenous generation of electrophilic omega-3 PUFAs and their hydroxy precursors was evaluated by mass spectrometry in neutrophils isolated from healthy subjects, both at baseline and upon stimulation with calcium ionophore. For the clinical trial, participants were healthy adults 30-55 years of age with a reported EPA+DHA consumption of ≤300 mg/day randomly assigned to parallel groups receiving daily oil capsule supplements for a period of 4 months containing either 1.4 g of EPA+DHA (active condition, n = 24) or identical appearing soybean oil (control condition, n = 21). Participants and laboratory technicians remained blinded to treatment assignments. 5-lypoxygenase-dependent endogenous generation of 7-oxo-DHA, 7-oxo-DPA and 5-oxo-EPA and their hydroxy precursors is reported in human neutrophils stimulated with calcium ionophore and phorbol 12-myristate 13-acetate (PMA). Dietary EPA+DHA supplementation significantly increased the formation of 7-oxo-DHA and 5-oxo-EPA, with no significant modulation of arachidonic acid (AA) metabolite levels. The endogenous detection of these electrophilic ω-3 fatty acid ketone derivatives supports the precept that the benefit of

  16. Regioselective Copper-Catalyzed Amination of Chlorobenzoic Acids: Synthesis and Solid-State Structures of N-Aryl Anthranilic Acid Derivatives

    PubMed Central

    Mei, Xuefeng; August, Adam T.; Wolf, Christian

    2008-01-01

    A chemo- and regioselective copper-catalyzed cross-coupling reaction for effective amination of 2-chlorobenzoic acids with aniline derivatives has been developed. The method eliminates the need for acid protection and produces a wide range of N-aryl anthranilic acid derivatives in up to 99%. The amination was found to proceed with both electron-rich and electron-deficient aryl chlorides and anilines and also utilizes sterically hindered anilines such as 2,6-dimethylaniline and 2-tert-butylaniline. The conformational isomerism of appropriately substituted N-aryl anthranilic acids has been investigated in the solid state. Crystallographic analysis of seven anthranilic acid derivatives showed formation of two distinct supramolecular architectures exhibiting trans-anti- and unprecedented trans-syn-dimeric structures. PMID:16388629

  17. Amino acid composition, including key derivatives of eccrine sweat: potential biomarkers of certain atopic skin conditions.

    PubMed

    Mark, Harker; Harding, Clive R

    2013-04-01

    The free amino acid (AA) composition of eccrine sweat is different from other biological fluids, for reasons which are not properly understood. We undertook the detailed analysis of the AA composition of freshly isolated pure human eccrine sweat, including some of the key derivatives of AA metabolism, to better understand the key biological mechanisms governing its composition. Eccrine sweat was collected from the axillae of 12 healthy subjects immediately upon formation. Free AA analysis was performed using an automatic AA analyser after ninhydrin derivatization. Pyrrolidine-5-carboxylic acid (PCA) and urocanic acid (UCA) levels were determined using GC/MS. The free AA composition of sweat was dominated by the presence of serine accounting for just over one-fifth of the total free AA composition. Glycine was the next most abundant followed by PCA, alanine, citrulline and threonine, respectively. The data obtained indicate that the AA content of sweat bears a remarkable similarity to the AA composition of the epidermal protein profilaggrin. This protein is the key source of free AAs and their derivatives that form a major part of the natural moisturizing factor (NMF) within the stratum corneum (SC) and plays a major role in maintaining the barrier integrity of human skin. As perturbations in the production of NMF can lead to abnormal barrier function and can arise as a consequence of filaggrin genotype, we propose the quantification of AAs in sweat may serve as a non-invasive diagnostic biomarker for certain atopic skin conditions, that is, atopic dermatitis (AD).

  18. Precision synthesis of bio-based acrylic thermoplastic elastomer by RAFT polymerization of itaconic acid derivatives.

    PubMed

    Satoh, Kotaro; Lee, Dong-Hyung; Nagai, Kanji; Kamigaito, Masami

    2014-01-01

    Bio-based polymer materials from renewable resources have recently become a growing research focus. Herein, a novel thermoplastic elastomer is developed via controlled/living radical polymerization of plant-derived itaconic acid derivatives, which are some of the most abundant renewable acrylic monomers obtained via the fermentation of starch. The reversible addition-fragmentation chain-transfer (RAFT) polymerizations of itaconic acid imides, such as N-phenylitaconimide and N-(p-tolyl)itaconimide, and itaconic acid esters, such as di-n-butyl itaconate and bis(2-ethylhexyl) itaconate, are examined using a series of RAFT agents to afford well-defined polymers. The number-average molecular weights of these polymers increase with the monomer conversion while retaining relatively narrow molecular weight distributions. Based on the successful controlled/living polymerization, sequential block copolymerization is subsequently investigated using mono- and di-functional RAFT agents to produce block copolymers with soft poly(itaconate) and hard poly(itaconimide) segments. The properties of the obtained triblock copolymer are evaluated as bio-based acrylic thermoplastic elastomers. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Anti-HIV activities of natural antioxidant caffeic acid derivatives: toward an antiviral supplementation diet.

    PubMed

    Bailly, Fabrice; Cotelle, Philippe

    2005-01-01

    Since 1996, highly active antiretroviral therapy (HAART) was designed to rapidly control HIV replication. It has had a significant impact on patient health and progression of AIDS in developed countries, but its success has not been complete. HAART strategy still suffers from issues of patient compliance, cost, deleterious side effects and emerging drug resistance. Therefore, expansion of novel anti-HIV drugs and targets will be critical in the coming years. In this context, discovering anti-HIV agents from natural sources and particularly from plants, may highlight the principle of a nutritional antioxidant antiretroviral diet. In this paper, we review the putative anti-HIV activity of simple caffeic acid derivatives, together with their antioxidant properties. Toxicity, metabolism and bioavailability, when known, will also be detailed. Well-known caffeic acid derivatives, such as chicoric, rosmarinic and lithospermic acids, may be designed as future leads multi-target anti-HIV compounds and the plants and vegetables containing them as potent nutritional therapeutic supplementation source. They are not expected to replace the actual antiretroviral therapy, but more likely, to complete and perhaps lighten it by adapted diet.

  20. A Dicarboxylic Fatty Acid Derivative of Paclitaxel for Albumin Assisted Drug Delivery

    PubMed Central

    Hackett, Michael J.; Joolakanti, Shyamsunder; Hartranft, Megan E.; Guley, Patrick C.; Cho, Moo J.

    2013-01-01

    Paclitaxel is a potent chemotherapy for many cancers but it suffers from very poor solubility. Consequently the TAXOL formulation uses copious amounts of the surfactant Cremophor EL to solubilize the drug for injection resulting in severe hypersensitivity and neutropenia. In contrast to Cremophor EL, presented is a way to solubilize paclitaxel (PTX) by conjugation of a dicarboxylic fatty acid for specific binding to the ubiquitous protein, serum albumin. The conjugation chemistry was simplified to a single step using the activated anhydride form of 3-pentadecylglutaric (PDG) acid which is reactive to a variety of nucleophiles. The PDG derivative is less cytotoxic than the parent compound and was found to slowly hydrolyze to PTX (~5% over 72 h) in serum, tumor cytosol, and tumor tissue homogenate. When injected intravenously to tumor bearing mice, [3H]-PTX in the TAXOL formulation was cleared rapidly with a half-life of 7 hours. In the case of the PDG derivative of PTX, the drug is quickly distributed and approximately 20% of the injected dose remained in the vasculature experiencing a 23-h half-life. These improvements from modifying PTX with the PDG fatty acid present the opportunity for PDG to become a generic modification for the improvement of many therapeutics. PMID:22674061

  1. Production of fatty acid-derived oleochemicals and biofuels by synthetic yeast cell factories

    PubMed Central

    Zhou, Yongjin J.; Buijs, Nicolaas A.; Zhu, Zhiwei; Qin, Jiufu; Siewers, Verena; Nielsen, Jens

    2016-01-01

    Sustainable production of oleochemicals requires establishment of cell factory platform strains. The yeast Saccharomyces cerevisiae is an attractive cell factory as new strains can be rapidly implemented into existing infrastructures such as bioethanol production plants. Here we show high-level production of free fatty acids (FFAs) in a yeast cell factory, and the production of alkanes and fatty alcohols from its descendants. The engineered strain produces up to 10.4 g l−1 of FFAs, which is the highest reported titre to date. Furthermore, through screening of specific pathway enzymes, endogenous alcohol dehydrogenases and aldehyde reductases, we reconstruct efficient pathways for conversion of fatty acids to alkanes (0.8 mg l−1) and fatty alcohols (1.5 g l−1), to our knowledge the highest titres reported in S. cerevisiae. This should facilitate the construction of yeast cell factories for production of fatty acids derived products and even aldehyde-derived chemicals of high value. PMID:27222209

  2. Hydrolysis of tannic acid catalyzed by immobilized-stabilized derivatives of Tannase from Lactobacillus plantarum.

    PubMed

    Curiel, Jose Antonio; Betancor, Lorena; de las Rivas, Blanca; Muñoz, Rosario; Guisan, Jose M; Fernández-Lorente, Gloria

    2010-05-26

    A recombinant tannase from Lactobacillus plantarum , overexpressed in Escherichia coli , was purified in a single step by metal chelate affinity chromatography on poorly activated nickel supports. It was possible to obtain 0.9 g of a pure enzyme by using only 20 mL of chromatographic support. The pure enzyme was immobilized and stabilized by multipoint covalent immobilization on highly activated glyoxyl agarose. Derivatives obtained by multipoint and multisubunit immobilization were 500- and 1000-fold more stable than both the soluble enzyme and the one-point-immobilized enzyme in experiments of thermal and cosolvent inactivation, respectively. In addition, up to 70 mg of pure enzyme was immobilized on 1 g of wet support. The hydrolysis of tannic acid was optimized by using the new immobilized tannase derivative. The optimal reaction conditions were 30% diglyme at pH 5.0 and 4 degrees C. Under these conditions, it was possible to obtain 47.5 mM gallic acid from 5 mM tannic acid as substrate. The product was pure as proved by HPLC. On the other hand, the immobilized biocatalyst preserved >95% of its initial activity after 1 month of incubation under the optimal reaction conditions.

  3. Regulation of aspartate-derived amino-acid metabolism in Zygosaccharomyces rouxii compared to Saccharomyces cerevisiae.

    PubMed

    van der Sluis C; Smit; Hartmans; ter Schure EG; Tramper; Wijffels

    2000-07-01

    To elucidate the growth inhibitory effect of threonine, the regulation of the aspartate-derived amino-acid metabolism in Zygosaccharomyces rouxii, an important yeast for the flavor development in soy sauce, was investigated. It was shown that threonine inhibited the growth of Z. rouxii by blocking the methionine synthesis. It seemed that threonine blocked this synthesis by inhibiting the conversion of aspartate. In addition, it was shown that the growth of Z. rouxii, unlike that of Saccharomyces cerevisiae, was not inhibited by the herbicide sulfometuron methyl (SMM). From enzyme assays, it was concluded that the acetohydroxy acid synthase in Z. rouxii, unlike that in S. cerevisiae, was not sensitive to SMM. Furthermore, the enzyme assays demonstrated that the activity of threonine deaminase in Z. rouxii, like in S. cerevisiae, was strongly inhibited by isoleucine and stimulated by valine. From this work, it is clear that the aspartate-derived amino-acid metabolism in Z. rouxii only partly resembles that in S. cerevisiae.

  4. Relative and absolute reliability of measures of linoleic acid-derived oxylipins in human plasma.

    PubMed

    Gouveia-Figueira, Sandra; Bosson, Jenny A; Unosson, Jon; Behndig, Annelie F; Nording, Malin L; Fowler, Christopher J

    2015-09-01

    Modern analytical techniques allow for the measurement of oxylipins derived from linoleic acid in biological samples. Most validatory work has concerned extraction techniques, repeated analysis of aliquots from the same biological sample, and the influence of external factors such as diet and heparin treatment upon their levels, whereas less is known about the relative and absolute reliability of measurements undertaken on different days. A cohort of nineteen healthy males were used, where samples were taken at the same time of day on two occasions, at least 7 days apart. Relative reliability was assessed using Lin's concordance correlation coefficients (CCC) and intraclass correlation coefficients (ICC). Absolute reliability was assessed by Bland-Altman analyses. Nine linoleic acid oxylipins were investigated. ICC and CCC values ranged from acceptable (0.56 [13-HODE]) to poor (near zero [9(10)- and 12(13)-EpOME]). Bland-Altman limits of agreement were in general quite wide, ranging from ±0.5 (12,13-DiHOME) to ±2 (9(10)-EpOME; log10 scale). It is concluded that relative reliability of linoleic acid-derived oxylipins varies between lipids with compounds such as the HODEs showing better relative reliability than compounds such as the EpOMEs. These differences should be kept in mind when designing and interpreting experiments correlating plasma levels of these lipids with factors such as age, body mass index, rating scales etc.

  5. The effects of a vegetable-derived probiotic lactic acid bacterium on the immune response.

    PubMed

    Chon, Heeson; Choi, Byungryul

    2010-04-01

    The objective of this study was to investigate the probiotic properties of the fermented vegetable derived lactic acid bacterium, L. plantarum. L. plantarum 10hk2 showed antibacterial activity against pathogenic bacteria and immunomodulating effects on murine macrophage cell lines. RAW 264.7 cells stimulated with viable cells of this probiotic strain increased the amounts of pro-inflammatory mediators such as IL-1beta, IL-6 and TNF-alpha, as well as the anti-inflammatory mediator, IL-10. ICR mice fed with viable cells of L. plantarum 10hk2 had reduced numbers of enteric Salmonella and Shigella species in comparison to controls from 2 weeks after supplementation, and this effect was observed for up to 4 weeks. The findings of this study suggest that this specific lactic acid bacterial strain, which is derived from vegetable fermentation, holds great promise for use in probiotics and as a food additive since it can reduce the number of some pathogenic bacteria through production of lactic acids.

  6. Chemical and immunochemical identification of propanoyllysine derived from oxidized n-3 polyunsaturated fatty acid.

    PubMed

    Hisaka, Shinsuke; Kato, Yoji; Kitamoto, Noritoshi; Yoshida, Akihiro; Kubushiro, Yoshiko; Naito, Michitaka; Osawa, Toshihiko

    2009-06-01

    It is known that n-3 polyunsaturated fatty acids (PUFAs), such as docosahexaenoic acid and eicosapentaenoic acid, are rapidly oxidized in vitro. Nvarepsilon-(propanoyl)lysine (propionyllysine, or PRL) is formed from the reaction of the oxidized products of n-3 PUFAs and lysine. To evaluate the oxidized n-3 PUFA-derived protein modifications in vivo, we have developed detection methods using a novel monoclonal antibody against PRL as well as liquid chromatography-mass spectrometry (LC/MS/MS). The antibody obtained specifically recognized PRL. A strong positive staining in atherosclerotic lesions of hypercholesterolemic rabbits was observed. We have also simultaneously identified and quantified both urinary PRL and urinary Nvarepsilon-(hexanoyl)lysine, using LC/MS/MS using isotope dilution methods. The level of urinary PRL (21.6+/-10.6 micromol/mol of creatinine) significantly correlated with the other oxidative stress markers, 8-oxo-deoxyguanosine, dityrosine, and isoprostanes. The increase in the excretion of amide adducts into the urine of diabetic patients was also confirmed compared to healthy subjects. These results suggest that PRL may be good marker for n-3 PUFA-derived oxidative stress in vivo.

  7. Gastroprotective activity of oleanolic acid derivatives on experimentally induced gastric lesions in rats and mice.

    PubMed

    Astudillo, Luis; Rodriguez, Jaime A; Schmeda-Hirschmann, Guillermo

    2002-04-01

    The gastroprotective effect of the triterpene oleanolic acid (OA) was assessed on gastric ulceration in rats. The effect of a single oral dose of OA was evaluated at 50, 100 and 200 mg kg(-1) in the following models: pylorus ligature (Shay), and aspirin- and ethanol-induced gastric ulcers. A single oral administration of OA at doses of 50, 100 and 200 mg kg-' inhibited the appearance of gastric lesions induced by ethanol, aspirin and pylorus ligature. In the pylorus ligature and aspirin models, the effect of OA at the selected concentrations was comparable with that of ranitidine at 50 mg kg(-1). In the ethanol-induced gastric lesion model, OA showed a dose-dependent activity, and at 100 and 200 mg kg(-1) was as active as omeprazole at 20 mg kg(-1). The effect of OA, its acetylated and methoxylated derivatives, oleanonic acid and its methyl ester were assessed on HCI/ethanol-induced ulcers in mice at 200 mg kg(-1). OA and its methoxylated (OAM) and acetylated (OAAM, OAA) derivatives proved to be active in this animal model. The semisynthetic derivatives OAM and OAAM had the greatest gastroprotective activity, but their effect was not significantly greater than OA. In an acute toxicity test on mice, intraperitoneal administration of OA showed no toxicity at doses up to 600 mg kg(-1).

  8. Valorizing dairy waste: thermophilic biosynthesis of a novel ascorbic acid derivative.

    PubMed

    Yang, Jingwen; Perez, Bianca; Anankanbil, Sampson; Li, Jingbo; Zhou, Ye; Gao, Renjun; Guo, Zheng

    2017-09-26

    L-ascorbic acid (L-AA) is an essential nutrient that is extremely instable and cannot be synthesized by the human body. Therefore, attempts have been done to develop biological active L-AA derivatives with improved stability. This work presents a facile, scalable and efficient enzymatic transgalactosylation of lactose to L-AA using β-glucosidase (TN0602) from Thermotoga naphthophila RKU-10. β-Glucosidase TN0602 displayshigh transgalactosylation activity at pH 5.0, 75°C and L-AA/lactose ratio 2/1, to form a novel L-AA derivative (2-O-β-D-Galactopyranosyl L-Ascorbic Acid, L-AA-Gal) with a maximal productivity of 138.88mmol L-1 in 12h, which is higher than most reports of enzymatic synthesis of L-AA-α-glucoside. Synthetic L-AA-Gal retains most of L-AA antioxidant capability and presents dramatically higher stability than L-AA in oxidative environment (Cu2+). In conclusion, this work report a new way to valorize dairy waste lactose into a novel molecule L-AA-Gal, which could be a promising L-AA derivative to be used in a wide range of applications.

  9. Synthesis and iron(III) binding properties of 3-hydroxypyrid-4-ones derived from kojic acid.

    PubMed

    Molenda, J J; Basinger, M A; Hanusa, T P; Jones, M M

    1994-08-01

    In an attempt to reduce the toxicity of the 3-hydroxypyrid-4-ones, the more hydrophilic derivatives of kojic acid were explored and compared to the standard, 1,2-dimethyl-3-hydroxypyrid-4-one, L1. The synthesis and iron(III) binding properties of these chelators are described. Neither these compounds nor the clinically effective 1,2-dimethyl-3-hydroxypyrid-4 one is able to completely remove all of the iron(III) from the Fe(III)EDTA complex in sodium acetate buffered solutions, when the 3-hydroxypyrid-4-one: Fe(III) ratio is 6:1. The ability of these compounds to enhance the urinary excretion of iron in rats indicates that the behavior of the 3-hydroxypyrid-4-ones derived from kojic acid is comparable to the analogous derivatives of maltol and ethyl maltol. The structure of the iron(III) complex of 3-hydroxy-6-hydroxymethyl-1-methylpyrid-4-one was determined by x-ray diffraction and found to be similar to the previously reported structure of the iron(III) complex of L1.

  10. The effect of trinitrobenzene sulfonic acid on gut-derived smooth muscle cell arachidonic acid metabolism: role of endogenous prostanoids.

    PubMed

    Longo, W E; Smith, G S; Deshpande, Y; Reickenberg, C; Kaminski, D L

    1997-01-01

    The contribution of smooth muscle cells as a potential source of eicosanoid production during inflammatory states remains to be elucidated. We investigated the effect of trinitrobenzene sulfonic acid (TNB), a known pro-inflammatory agent, on jejunal smooth muscle cell eicosanoid production. Human gut-derived smooth muscle cells (HISM) were incubated with TNB for 1 hour. Additionally, some cells were preincubated with either dimethylthiourea, or indomethacin for 1 hour before exposure to identical concentrations of TNB. Incubation with TNB led to significant increases in PGE(2) and 6-keto PGF-1(alpha) release, but not leukotriene B(4) release; responses which were both inhibited by dimethylthiourea and indomethacin treatment. Our results suggest that gutderived smooth muscle cells may represent an important source of proinflammatory prostanoids but not leukotrienes during inflammatory states of the intestine. The inhibition of prostanoid activity by thiourea may be mediated by suppression of cyclooxygenase activity in this cell line.

  11. Stereoselectivity of formation of monoterpene - Amino acids hybrid molecules in the reaction of monoterpene nitroso chlorides with α-amino acid derivatives.

    PubMed

    Marenin, K S; Gatilov, Yu V; Agafontsev, A M; Tkachev, A V

    2017-01-01

    Reaction of nitrosochlorides of natural monoterpene hydrocarbons (+)-3-carene and (-)-α-pinene with L-amino acids and their methyl esters results in stereoselective formation of terpene-amino acids hybrids, which belong to the series of α-substituted amino oximes. The reaction with an excess of racemic DL-amino acids and their derivatives induces partial resolution of the amino acid components and formation of the diastereomeric mixtures of the terpene-amino acids hybrids, with diastereomeric excess varying from 0 to 100%. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Antileishmanial activity of semisynthetic lupane triterpenoids betulin and betulinic acid derivatives: synergistic effects with miltefosine.

    PubMed

    Sousa, Maria C; Varandas, Raquel; Santos, Rita C; Santos-Rosa, Manuel; Alves, Vera; Salvador, Jorge A R

    2014-01-01

    Leishmaniasis is a neglected tropical disease (NTDs), endemic in 88 countries, affecting more than 12 million people. The treatment consists in pentavalent antimony compounds, amphotericin B, pentamidine and miltefosine, among others. However, these current drugs are limited due to their toxicity, development of biological resistance, length of treatment and high cost. Thus, it is important to continue the search for new effective and less toxic treatments. The anti-Leishmania activity of sixteen semisynthetic lupane triterpenoids derivatives of betulin (BT01 to BT09) and betulinic acid (AB10 to AB16) were evaluated. Drug interactions between the active compounds and one current antileishmanial drug, miltefosine, were assessed using the fixed ratio isobologram method. In addition, effects on the cell cycle, apoptosis/necrosis events, morphology and DNA integrity were studied. The derivatives BT06 (3β-Hydroxy-(20R)-lupan-29-oxo-28-yl-1H-imidazole-1-carboxylate) and AB13 (28-(1H-imidazole-1-yl)-3,28-dioxo-lup-1,20(29)-dien-2-yl-1H-imidazole-1-carboxylate) were found to be the most active, with IC50 values of 50.8 µM and 25.8 µM, respectively. Interactions between these two compounds and miltefosine were classified as synergistic, with the most effective association being between AB13 and miltefosine, where decreases of IC50 values to 6 µM were observed, similar to the miltefosine activity alone. AB13 induced significant morphological changes, while both derivatives produced anti-proliferative activity through cell cycle arrest at the G0/G1 phase. Neither of these derivatives induced significant apoptosis/necrosis, as indicated by phosphatidylserine externalization and DNA fragmentation assays. In addition, neither of the derivatives induced death in macrophage cell lines. Thus, they do not present any potential risk of toxicity for the host cells. This study has identified the betulin derivative BT06 and the betulinic acid derivative AB13 as promising molecules

  13. Effects of amino acid derivatives on physical, mental, and physiological activities.

    PubMed

    Luckose, Feby; Pandey, Mohan Chandra; Radhakrishna, Kolpe

    2015-01-01

    Nutritional ergogenic aids have been in use for a long time to enhance exercise and sports performance. Dietary components that exhibit ergogenic activity are numerous and their consumption is common and popular among athletes. They often come under scrutiny by legal authorities for their claimed benefits and safety concerns. Amino acid derivatives are propagated as being effective aids to enhance physical and mental performance in many ways, even though studies have pointed out that individuals who are deficient are more likely to benefit from dietary supplementation of amino acid derivatives than normal humans. In this review, some of the most common and widely used amino acids derivatives in sports and athletics namely creatine, tyrosine, carnitine, HMB, and taurine have been discussed for their effects on exercise performance, mental activity as well as body strength and composition. Creatine, carnitine, HMB, and taurine are reported to delay the onset of fatigue, improve exercise performance, and body strength. HMB helps in increasing fat-free mass and reduce exercise induced muscle injury. Taurine has been found to reduce oxidative stress during exercise and also act as an antihypertensive agent. Although, studies have not been able to find any favorable effect of tyrosine administration on exercise performance, it has been proved to be very effective in fighting stress, improving mood and cognitive performance particularly in sleep-deprived subjects. While available data from published studies and findings are equivocal about the efficacy of creatine, tyrosine, and HMB, more comprehensive researches on carnitine and taurine are necessary to provide evidence for the theoretical basis of their ergogenic role in nutritional modification and supplementation.

  14. Arginine derivatives of dicarboxylic acids from the parotid gland secretions of common toad Bufo bufo-New agonists of ionotropic γ-aminobutyric acid receptors.

    PubMed

    Lebedev, D S; Ivanov, I A; Kryukova, E V; Starkov, V G; Tsetlin, V I; Utkin, Yu N

    2017-05-01

    Compounds activating γ-aminobutyric acid type A receptor were isolated from the toad Bufo bufo venom as a result of chromatographic separation. Analysis of the structure of these compounds by mass spectrometry and nuclear magnetic resonance showed that they are arginine derivatives of dicarboxylic acids and represent suberylarginine, pimeloylarginine, and adipoylarginine.

  15. Comparison of Aromatic Dithiophoshinic and Phosphinic Acid Derivatives for Minor Actinide Extraction

    SciTech Connect

    John R. Klaehn; Dean R. Peterman; Mason K. Harrup; Richard D. Tillotson; Mitchell R. Greenhalgh; Thomas A. Luther; Jack D. Law; Lee M. Daniels

    2008-03-01

    A new extractant for the separation of actinide(III) and lanthanide(III), bis(otrifluoromethylphenyl) phosphinic acid (O-PA) was synthesized. The synthetic route employed mirrors one that was employed to produce the sulfur containing analog bis(otrifluoromethylphenyl) dithiophosphinic acid (S-PA). Multinuclear NMR spectroscopy was used for elementary characterization of the new O-PA derivative. This new O-PA extractant was used to perform Am(III)/Eu(III) separations and the results were directly compared to those obtained in identical separation experiments using S-PA, an extractant that is known to exhibit separation factors of ~100,000 at low pH. The separations data are presented and discussed in terms comparing the nature of the oxygen atom as a donor to that of the sulfur atom in extractants that are otherwise identical.

  16. Comparison of Dithiophosphinic and Phosphinic Acid Derivatives for Minor Actinide Extraction

    SciTech Connect

    Mason K Harrup; Dean R. Peterman; Thomas A. Luther; Mitchell R. Greenhalgh; John R. Klaehn

    2008-03-01

    A new extractant for the separation of actinide(III) and lanthanide(III), bis(otrifluoromethylphenyl) phosphinic acid (O-PA) was synthesized. The synthetic route employed mirrors one that was employed to produce the sulfur containing analog bis(otrifluoromethylphenyl) dithiophosphinic acid (S-PA). Multinuclear NMR spectroscopy was used for elementary characterization of the new O-PA derivative. This new O-PA extractant was used to perform Am(III)/Eu(III) separations and the results were directly compared to those obtained in identical separation experiments using S-PA, an extractant that is known to exhibit separation factors of ~100,000 at low pH. The separations data are presented and discussed in terms comparing the nature of the oxygen atom as a donor to that of the sulfur atom in extractants that are otherwise identical.

  17. Molecular interaction of acetylcholinesterase with carnosic acid derivatives: a neuroinformatics study.

    PubMed

    Merad, M; Soufi, W; Ghalem, S; Boukli, F; Baig, M H; Ahmad, K; Kamal, Mohammad A

    2014-04-01

    Alzheimer's disease is a progressive degenerative disease of the brain marked by gradual and irreversible declines in cognitive functions. Acetylcholinesterase (AChE) plays a biological role in the termination of nerve impulse transmissions at cholinergic synapses by rapid hydrolysis of its substrate, "acetylcholine". The deficit level of acetylcholine leads to deprived nerve impulse transmission. Thus the cholinesterase inhibitors would reverse the deficit in acetylcholine level and consequently may reverse the memory impairments, which is characteristic of the Alzheimer's disease. The molecular interactions between AChE and Carnosic acid, a well known antioxidant substance found in the leaves of the rosemary plant has always been an area of interest. Here in this study we have performed in silico approach to identify carnosic acid derivatives having the potential of being a possible drug candidate against AChE. The best candidates were selected on the basis of the results of different scoring functions.

  18. A-ring modified betulinic acid derivatives as potent cancer preventive agents.

    PubMed

    Hung, Hsin-Yi; Nakagawa-Goto, Kyoko; Tokuda, Harukuni; Iida, Akira; Suzuki, Nobutaka; Bori, Ibrahim D; Qian, Keduo; Lee, Kuo-Hsiung

    2014-02-01

    Ten new 3,4-seco betulinic acid (BA) derivatives were designed and synthesized. Among them, compounds 7-15 exhibited enhanced chemopreventive ability in an in vitro short-term 12-O-tetradecanoylphorbol-13-acetate (TPA) induced Epstein-Barr virus early antigen (EBV-EA) activation assay in Raji cells. Specifically, analogs with a free C-28 carboxylic acid, including 7, 8, 11, and 13, inhibited EBV-EA activation significantly. The most potent compound 8 displayed 100% inhibition at 1×10(3) mol ratio/TPA and 73.4%, 35.9%, and 8.4% inhibition at 5×10(2), 1×10(2), and 1×10 mol ratio/TPA, respectively, comparable with curcumin at high concentration and better than curcumin at low concentration. The potent chemopreventive activity of novel seco A-ring BAs (8 and 11) was further confirmed in an in vivo mouse skin carcinogenesis assay.

  19. Four new amide derivatives of pyridinecarboxylic acids. Synthesis, structure and spectroscopic characterization

    NASA Astrophysics Data System (ADS)

    Kwiatek, Dorota; Kubicki, Maciej; Barczyński, Piotr; Lis, Stefan; Hnatejko, Zbigniew

    2017-10-01

    This study treats about four new pyridine amide derivatives obtained by a simple and inexpensive method of synthesis which consisted in amide coupling of pyridine-2-carboxylic acid and pyridine-4-carboxylic acid chlorides and aromatic amines: methyl 2-amino-3-methylbenzoate (Ea), methyl 3-amino-2-methylbenzoate (Eb), methyl 3-amino-4-methylbenzoate (Ec). All products of synthesis: L1, L2, L3, L4 were analyzed in detail by FT-IR, 1H, 13C, COSY 2D, HSQC, HMBC NMR spectroscopy, elemental, TGA and X-ray analysis. The excitation and emission spectra for obtained amides were also registered. An exact examination of results confirmed receiving four amide compounds with higher potential ability to metal ion coordination than the substrates alone.

  20. Synthesis of Novel N9-Substituted Purine Derivatives from Polymer Supported α-Amino Acids.

    PubMed

    Vanda, David; Jorda, Radek; Lemrová, Barbora; Volná, Tereza; Kryštof, Vladimír; McMaster, Claire; Soural, Miroslav

    2015-07-13

    Solid-phase synthesis of purine derivatives bearing an α-amino acid motif in position 9 is described herein. Polymer supported amines were acylated with various Fmoc-α-amino acids and, after cleavage of the protecting group, arylation with 4,6-dichloro-5-nitropyrimidine or 2,4-dichloro-5-nitropyrimidine was performed. The second chlorine atom was replaced with various amines. Subsequent reduction of the nitro group, followed by reaction with aldehydes, afforded the purine scaffold. After cleavage from the polymer support, the target compounds were obtained in very good crude purity, good overall yields, and excellent enantiomeric purity. The anticancer activity of prepared compounds was tested in vitro against human cancer cell lines MCF7 and K562, and they were found to have mild, but clear dose-dependent effects.

  1. Design and synthesis of N-benzoyl amino acid derivatives as DNA methylation inhibitors.

    PubMed

    Garella, Davide; Atlante, Sandra; Borretto, Emily; Cocco, Mattia; Giorgis, Marta; Costale, Annalisa; Stevanato, Livio; Miglio, Gianluca; Cencioni, Chiara; Fernández-de Gortari, Eli; Medina-Franco, José L; Spallotta, Francesco; Gaetano, Carlo; Bertinaria, Massimo

    2016-11-01

    The inhibition of human DNA Methyl Transferases (DNMT) is a novel promising approach to address the epigenetic dysregulation of gene expression in different diseases. Inspired by the validated virtual screening hit NSC137546, a series of N-benzoyl amino acid analogues was synthesized and obtained compounds were assessed for their ability to inhibit DNMT-dependent DNA methylation in vitro. The biological screening allowed the definition of a set of preliminary structure-activity relationships and the identification of compounds promising for further development. Among the synthesized compounds, L-glutamic acid derivatives 22, 23, and 24 showed the highest ability to prevent DNA methylation in a total cell lysate. Compound 22 inhibited DNMT1 and DNMT3A activity in a concentration-dependent manner in the micromolar range. In addition, compound 22 proved to be stable in human serum and it was thus selected as a starting point for further biological studies. © 2016 John Wiley & Sons A/S.

  2. Endiandric Acid Derivatives and Other Constituents of Plants from the Genera Beilschmiedia and Endiandra (Lauraceae)

    PubMed Central

    Ndjakou Lenta, Bruno; Chouna, Jean Rodolphe; Nkeng-Efouet, Pepin Alango; Sewald, Norbert

    2015-01-01

    Plants of the Lauraceae family are widely used in traditional medicine and are sources of various classes of secondary metabolites. Two genera of this family, Beilschmiedia and Endiandra, have been the subject of numerous investigations over the past decades because of their application in traditional medicine. They are the only source of bioactive endiandric acid derivatives. Noteworthy is that their biosynthesis contains two consecutive non-enzymatic electrocyclic reactions. Several interesting biological activities for this specific class of secondary metabolites and other constituents of the two genera have been reported, including antimicrobial, enzymes inhibitory and cytotoxic properties. This review compiles information on the structures of the compounds described between January 1960 and March 2015, their biological activities and information on endiandric acid biosynthesis, with 104 references being cited. PMID:26117852

  3. Endiandric Acid Derivatives and Other Constituents of Plants from the Genera Beilschmiedia and Endiandra (Lauraceae).

    PubMed

    Lenta, Bruno Ndjakou; Chouna, Jean Rodolphe; Nkeng-Efouet, Pepin Alango; Sewald, Norbert

    2015-01-01

    Plants of the Lauraceae family are widely used in traditional medicine and are sources of various classes of secondary metabolites. Two genera of this family, Beilschmiedia and Endiandra, have been the subject of numerous investigations over the past decades because of their application in traditional medicine. They are the only source of bioactive endiandric acid derivatives. Noteworthy is that their biosynthesis contains two consecutive non-enzymatic electrocyclic reactions. Several interesting biological activities for this specific class of secondary metabolites and other constituents of the two genera have been reported, including antimicrobial, enzymes inhibitory and cytotoxic properties. This review compiles information on the structures of the compounds described between January 1960 and March 2015, their biological activities and information on endiandric acid biosynthesis, with 104 references being cited.

  4. Amino-modified tetraphenylethene derivatives as nucleic acid stain: relationship between the structure and sensitivity.

    PubMed

    Xu, Li; Zhu, Zece; Wei, Danqing; Zhou, Xiang; Qin, Jingui; Yang, Chuluo

    2014-10-22

    A series of new amino-functionalized tetraphenylethene (TPE) derivatives were designed and synthesized to study the effect of molecular structures on the detection of nucleic acid. Contrastive studies revealed that the number of binding groups, the length of hydrophobic linking arm and the configuration of TPE molecule all play important roles on the sensitivity of the probes in nucleic acid detection. Z-TPE3 with two binding amino groups, long linking arms, and cis configuration was found to be the most sensitive dye in both solution and gel matrix. Z-TPE3 is able to stain dsDNA with the lowest amount of 1 ng and exclusively stain 40 ng of short oligonucleotide with only 10 nt. This work is of important significance for the further design of TPE probes as biosensors with higher sensitivity.

  5. Preparation and application of abietic acid-derived optically active helical polymers and their chiral hydrogels.

    PubMed

    Yao, Fei; Zhang, Dongyue; Zhang, Chaohong; Yang, Wantai; Deng, Jianping

    2013-02-01

    A novel chiral monomer N-propargyl abietamide, M1, was synthesized from abietic acid and catalytically polymerized with (nbd)Rh+B-(C6H5)4 (nbd=norbornadiene), providing polymer [poly(1)] with a molecular weight of 13,000-36,000 at a yield of 59-84%. Poly(1) did not form stable helices in tetrahydrofuran at room temperature whereas copolymerization of M1 and the achiral N-propargylamide monomer, M2, led to the formation of helical optically active copolymers as indicated by circular dichroism studies, UV-vis spectroscopy, and specific optical rotation measurements. Hydrogels were prepared based on an optically active helical copolymer, poly(M1(0.32)-co-M2(0.68)) that exhibited enantioselective recognition toward l-alanine. The novel chiral polymers derived from abietic acid are expected to find applications in such areas as chiral recognition, chiral resolution, and chiral catalysis.

  6. N-( p-Ethynylbenzoyl) derivatives of amino acid and dipeptide methyl esters - Synthesis and structural study

    NASA Astrophysics Data System (ADS)

    Eißmann, Frank; Weber, Edwin

    2011-11-01

    A series of N-( p-ethynylbenzoyl) derivatives ( 1-4) of the amino acids glycine and L-alanine as well as the dipeptides glycylglycine and L-alanylglycine has been synthesized via a two-step reaction sequence including the reaction of an appropriate N-( p-bromobenzoyl) precursor with trimethylsilylacetylene followed by deprotection of the trimethylsilyl protecting group, respectively. X-ray crystal structures of the amino acid and dipeptide methyl esters 1-4 are reported. The amide and peptide bonds within each molecular structure are planar and adopt the trans-configuration. The packing structures are governed by N sbnd H⋯O interactions leading to the formation of characteristic strand motifs. Further stabilization results from weaker C sbnd H⋯O and C sbnd H⋯π contacts.

  7. Solvatochromic behavior of the electronic absorption spectra of gallic acid and some of its azo derivatives

    NASA Astrophysics Data System (ADS)

    Masoud, Mamdouh S.; Hagagg, Sawsan S.; Ali, Alaa E.; Nasr, Nessma M.

    The electronic absorption spectra of gallic acid and its azo derivatives have been studied in various solvents of different polarities. Multiple regression techniques were applied to calculate the regression and correlation coefficients based on an equation that relates the wavenumbers of the absorption band maxima (υmax-) to the solvent parameters; refractive index (n), dielectric constant (D), empirical Kamlet-Taft solvent parameters, π*(dipolarity/polarizability), α (solvent hydrogen-bond donor acidity) and β (solvent hydrogen-bond acceptor basicity). The fitting coefficient obtained from this analysis allows estimating the contribution of each type of interactions relative to total spectral shifts in solution. The dependence of υmax- on the solvent parameters indicates that the obtained bands are affected by specific and non-specific solute-solvent interactions.

  8. Evolution in medicinal chemistry of ursolic acid derivatives as anticancer agents.

    PubMed

    Chen, Haijun; Gao, Yu; Wang, Ailan; Zhou, Xiaobin; Zheng, Yunquan; Zhou, Jia

    2015-03-06

    Currently, there is a renewed interest in common dietaries and plant-based traditional medicines for the prevention and treatment of cancer. In the search for potential anticancer agents from natural sources, ursolic acid (UA), a pentacyclic triterpenoid widely found in various medicinal herbs and fruits, exhibits powerful biological effects including its attractive anticancer activity against various types of cancer cells. However, the limited solubility, rapid metabolism and poor bioavailability of UA restricted its further clinical applications. In the past decade, with substantial progress toward the development of new chemical entities for the treatment of cancer, numerous UA derivatives have been designed and prepared to overcome its disadvantages. Despite extensive effort, discovery of effective UA derivatives has so far met with only limited success. This review summarizes the current status of the structural diversity and evolution in medicinal chemistry of UA analogues and provides a detailed discussion of future direction for further research in the chemical modifications of UA.

  9. Evolution in Medicinal Chemistry of Ursolic Acid Derivatives as Anticancer Agents

    PubMed Central

    Chen, Haijun; Gao, Yu; Wang, Ailan; Zhou, Xiaobin; Zheng, Yunquan; Zhou, Jia

    2015-01-01

    Currently, there is a renewed interest in common dietaries and plant-based traditional medicines for the prevention and treatment of cancer. In the search for potential anticancer agents from natural sources, ursolic acid (UA), a pentacyclic triterpenoid widely found in various medicinal herbs and fruits, exhibits powerful biological effects including its attractive anticancer activity against various types of cancer cells. However, the limited solubility, rapid metabolism and poor bioavailability of UA restricted its further clinical applications. In the past decade, with substantial progress toward the development of new chemical entities for the treatment of cancer, numerous UA derivatives have been designed and prepared to overcome its disadvantages. Despite extensive effort, discovery of effective UA derivatives has so far met with only limited success. This review summarizes the current status of the structural diversity and evolution in medicinal chemistry of UA analogues and provides a detailed discussion of future direction for further research in the chemical modifications of UA. PMID:25617694

  10. Arachidonic Acid Derivatives and Their Role in Peripheral Nerve Degeneration and Regeneration

    PubMed Central

    Camara-Lemarroy, Carlos Rodrigo; Gonzalez-Moreno, Emmanuel Irineo; Guzman-de la Garza, Francisco Javier; Fernandez-Garza, Nancy Esthela

    2012-01-01

    After peripheral nerve injury, a process of axonal degradation, debris clearance, and subsequent regeneration is initiated by complex local signaling, called Wallerian degeneration (WD). This process is in part mediated by neuroglia as well as infiltrating inflammatory cells and regulated by inflammatory mediators such as cytokines, chemokines, and the activation of transcription factors also related to the inflammatory response. Part of this neuroimmune signaling is mediated by the innate immune system, including arachidonic acid (AA) derivatives such as prostaglandins and leukotrienes. The enzymes responsible for their production, cyclooxygenases and lipooxygenases, also participate in nerve degeneration and regeneration. The interactions between signals for nerve regeneration and neuroinflammation go all the way down to the molecular level. In this paper, we discuss the role that AA derivatives might play during WD and nerve regeneration, and the therapeutic possibilities that arise. PMID:22997489

  11. Metformin inhibits Branched Chain Amino Acid (BCAA) derived ketoacidosis and promotes metabolic homeostasis in MSUD

    PubMed Central

    S. Sonnet, Davis; N. O’Leary, Monique; A. Gutierrez, Mark; M. Nguyen, Steven; Mateen, Samiha; Hsu, Yuehmei; P. Mitchell, Kylie; J. Lopez, Antonio; Vockley, Jerry; K. Kennedy, Brian; Ramanathan, Arvind

    2016-01-01

    Maple Syrup Urine Disease (MSUD) is an inherited disorder caused by the dysfunction in the branched chain keto-acid dehydrogenase (BCKDH) enzyme. This leads to buildup of branched-chain keto-acids (BCKA) and branched-chain amino acids (BCAA) in body fluids (e.g. keto-isocaproic acid from the BCAA leucine), leading to numerous clinical features including a less understood skeletal muscle dysfunction in patients. KIC is an inhibitor of mitochondrial function at disease relevant concentrations. A murine model of intermediate MSUD (iMSUD) shows significant skeletal muscle dysfunction as by judged decreased muscle fiber diameter. MSUD is an orphan disease with a need for novel drug interventions. Here using a 96-well plate (liquid chromatography- mass spectrometry (LC-MS) based drug-screening platform we show that Metformin, a widely used anti-diabetic drug, reduces levels of KIC in patient-derived fibroblasts by 20–50%. This Metformin-mediated effect was conserved in vivo; Metformin-treatment significantly reduced levels of KIC in the muscle (by 69%) and serum (by 56%) isolated from iMSUD mice, and restored levels of mitochondrial metabolites (e.g. AMP and other TCA). The drug also decreased the expression of mitochondrial branched chain amino transferase (BCAT) which produces KIC in skeletal muscle. This suggests that Metformin can restore skeletal muscle homeostasis in MSUD by decreasing mitochondrial KIC production. PMID:27373929

  12. Green Synthesis and Urease Inhibitory Activity of Spiro-Pyrimidinethiones/Spiro-Pyrimidinones-Barbituric Acid Derivatives

    PubMed Central

    Mohammadi Ziarani, Ghodsi; Asadi, Shima; Faramarzi, Sakineh; Amanlou, Massoud

    2015-01-01

    Sulfonic acid functionalized SBA-15 (SBA-Pr-SO3H) with pore size 6 nm as an efficient heterogeneous nanoporous solid acid catalyst exhibited good catalytic activity in the Biginelli-like reaction in the synthesis of spiroheterobicyclic rings with good yield and good recyclability. Spiro-pyrimidinethiones/spiro-pyrimidinones-barbituric acid derivatives were synthesized in a simple and efficient method using the one-pot three-component reaction of a cyclic 1,3- dicarbonyl compounds (barbituric acid), an aromatic aldehyde and urea or thiourea in the presence of nanoporous silica SBA-Pr-SO3H under solvent free conditions. Urease inhibitory activity of spiro compounds were tested against Jack bean urease using Berthelot alkaline phenol–hypochlorite method. Five of 13 compounds were inhibitor and two of them were enzyme activators. Analysis of the docking results showed that, in most of the spiro molecules, one of the carbonyl groups is coordinated with both nickel atoms, while the other one is involved in the formation of hydrogen bonds with important active-site residues. The effect of inserting two methyl groups on N atoms of barbiturate ring, S substituted, ortho, meta and para substituted compounds were investigated too. PMID:26664377

  13. Metformin inhibits Branched Chain Amino Acid (BCAA) derived ketoacidosis and promotes metabolic homeostasis in MSUD.

    PubMed

    S Sonnet, Davis; N O'Leary, Monique; A Gutierrez, Mark; M Nguyen, Steven; Mateen, Samiha; Hsu, Yuehmei; P Mitchell, Kylie; J Lopez, Antonio; Vockley, Jerry; K Kennedy, Brian; Ramanathan, Arvind

    2016-07-04

    Maple Syrup Urine Disease (MSUD) is an inherited disorder caused by the dysfunction in the branched chain keto-acid dehydrogenase (BCKDH) enzyme. This leads to buildup of branched-chain keto-acids (BCKA) and branched-chain amino acids (BCAA) in body fluids (e.g. keto-isocaproic acid from the BCAA leucine), leading to numerous clinical features including a less understood skeletal muscle dysfunction in patients. KIC is an inhibitor of mitochondrial function at disease relevant concentrations. A murine model of intermediate MSUD (iMSUD) shows significant skeletal muscle dysfunction as by judged decreased muscle fiber diameter. MSUD is an orphan disease with a need for novel drug interventions. Here using a 96-well plate (liquid chromatography- mass spectrometry (LC-MS) based drug-screening platform we show that Metformin, a widely used anti-diabetic drug, reduces levels of KIC in patient-derived fibroblasts by 20-50%. This Metformin-mediated effect was conserved in vivo; Metformin-treatment significantly reduced levels of KIC in the muscle (by 69%) and serum (by 56%) isolated from iMSUD mice, and restored levels of mitochondrial metabolites (e.g. AMP and other TCA). The drug also decreased the expression of mitochondrial branched chain amino transferase (BCAT) which produces KIC in skeletal muscle. This suggests that Metformin can restore skeletal muscle homeostasis in MSUD by decreasing mitochondrial KIC production.

  14. Modification of nucleic acids by azobenzene derivatives and their applications in biotechnology and nanotechnology.

    PubMed

    Li, Jing; Wang, Xingyu; Liang, Xingguo

    2014-12-01

    Azobenzene has been widely used as a photoregulator due to its reversible photoisomerization, large structural change between E and Z isomers, high photoisomerization yield, and high chemical stability. On the other hand, some azobenzene derivatives can be used as universal quenchers for many fluorophores. Nucleic acid is a good candidate to be modified because it is not only the template of gene expression but also widely used for building well-organized nanostructures and nanodevices. Because the size and polarity distribution of the azobenzene molecule is similar to a nucleobase pair, the introduction of azobenzene into nucleic acids has been shown to be an ingenious molecular design for constructing light-switching biosystems or light-driven nanomachines. Here we review recent advances in azobenzene-modified nucleic acids and their applications for artificial regulation of gene expression and enzymatic reactions, construction of photoresponsive nanostructures and nanodevices, molecular beacons, as well as obtaining structural information using the introduced azobenzene as an internal probe. In particular, nucleic acids bearing multiple azobenzenes can be used as a novel artificial nanomaterial with merits of high sequence specificity, regular duplex structure, and high photoregulation efficiency. The combination of functional groups with biomolecules may further advance the development of chemical biotechnology and biomolecular engineering.

  15. Effect of tannic acid, resveratrol and its derivatives, on oxidative damage and apoptosis in human neutrophils.

    PubMed

    Zielińska-Przyjemska, Małgorzata; Ignatowicz, Ewa; Krajka-Kuźniak, Violetta; Baer-Dubowska, Wanda

    2015-10-01

    In this study we compared the antioxidant and DNA protective activity of tannic acid and stilbene derivatives, resveratrol, 3,5,4(')-trimethoxystilbene (TMS) and pterostilbene in human neutrophils stimulated to oxidative burst by 12-O-tetradecanoyl-phorbol-13-acetate (TPA) in relation to apoptosis induction. All polyphenols within the concentration range 1-100 μM reduced the intracellular ROS and H2O2 production in the TPA-stimulated cells. Tannic acid was the most effective polyphenol in protection against DNA damage induced by TPA. In the resting neutrophils resveratrol and to lesser extent other polyphenols increased DNA damage and increased the level of p53. Pretreatment of the TPA-stimulated cells with tannic acid or stilbenes led to the induction of apoptosis. The most significant effect was observed as a result of treatment with TMS and resveratrol. These compounds appeared the most effective inducers of p53 in the TPA-challenged neutrophils, what may suggest that pro-apoptotic activity of these stilbenes might be related to p53 activation. Overall, the results of our present study demonstrate that tannic acid and stilbenes modulate the ROS production, ultimately leading to cell apoptosis in human neutrophils stimulated to oxidative burst. In resting neutrophils they exhibit pro-oxidant activity, which is accompanied by p53 induction.

  16. Amino acid derivatives of cholesterol as "latent" organogelators with hydrogen chloride as a protonation reagent.

    PubMed

    Li, Yuangang; Liu, Kaiqiang; Liu, Jing; Peng, Junxia; Feng, Xuli; Fang, Yu

    2006-08-01

    A series of low molecular weight organic gelator (LMOG) gel systems sensitive to alkaline/acidic stimuli was established by employing amino acid derivatives of cholesterol as "latent" gelators, which are cholesteryl glycinate (1), cholesteryl L-alaninate, cholesteryl D-alaninate, cholesteryl L-phenyl alaninate, and cholesteryl D-phenyl alaninate. The hydrochloric salts are denoted as 2, 3, 4, 5, and 6, respectively. For the 18 solvents tested, one proved to be a weak gelator and gels only two of the solvents. Its gelation ability, however, was greatly improved by bubbling HCl gas, which was produced by reaction of concentrated sulfuric acid with NaCl, through its solution owing to protonation of its amino group. It was demonstrated that the protonated form of it gelled 14 of the solvents tested. Further investigation revealed that the gels changed into solution with addition of any of the amines, including triethylamine (TEA), diethylamine, ethylenediamine, and NH3. The phase transition could be reversed by further introduction of the acidic gas. SEM measurements showed that 1 self-assembled into different supramolecular structures in different gels. Salt effect studies proved that electrostatic interaction is one of the driving forces for formation of the gels.

  17. Production of fumaric acid from biodiesel-derived crude glycerol by Rhizopus arrhizus.

    PubMed

    Zhou, Yuqing; Nie, Kaili; Zhang, Xin; Liu, Shihong; Wang, Meng; Deng, Li; Wang, Fang; Tan, Tianwei

    2014-07-01

    This work investigated the capability of Rhizopus arrhizus to assimilate biodiesel-derived crude glycerol and convert it into fumaric acid. After optimizing the initial glycerol concentration, spore inoculum and yeast extract concentration, smaller pellets (0.7 mm) and higher biomass (3.11 g/L) were obtained when R. arrhizus grew on crude glycerol. It was found that crude glycerol was more suitable than glucose for smaller R. arrhizus pellet forming. When 80 g/L crude glycerol was used as carbon source, the fumaric acid production of 4.37 g/L was obtained at 192 h. With a highest concentration of 22.81 g/L achieved in the co-fermentation of crude glycerol (40 g/L) and glucose (40 g/L) at 144 h, the fumaric acid production was enhanced by 553.6%, compared to the fermentation using glycerol (80 g/L) as sole carbon source. Moreover, the production cost of fumaric acid in co-fermentation was reduced by approximately 14% compared to glucose fermentation.

  18. Recent progress in electrochemical biosensors based on phenylboronic acid and derivatives.

    PubMed

    Anzai, Jun-Ichi

    2016-10-01

    This review provides an overview of recent progress made in the development of electrochemical biosensors based on phenylboronic acid (PBA) and its derivatives. PBAs are known to selectively bind 1,2- and 1,3-diols to form negatively charged boronate esters in neutral aqueous media and have been used to construct electrochemical glucose sensors because of this selective binding. PBA-modified metal and carbon electrodes have been widely studied as voltammetric and potentiometric glucose sensors. In some cases, ferroceneboronic acid or ferrocene-modified phenylboronic acids are used as sugar-selective redox compounds. Another option for sensors using PBA-modified electrodes is potentiometric detection, in which the changes in surface potential of the electrodes are detected as an output signal. An ion-sensitive field effect transistor (FET) has been used as a signal transducer in potentiometric sensors. Glycoproteins, such as glycated hemoglobin (HbA1c), avidin, and serum albumin can also be detected by PBA-modified electrodes because they contain hydrocarbon chains on the surface. HbA1c sensors are promising alternatives to enzyme-based glucose sensors for monitoring blood glucose levels over the preceding 2-3months. In addition, PBA-modified electrodes can be used to detect a variety of compounds including hydroxy acids and fluoride (F(-)) ions. PBA-based F(-) ion sensors may be useful if reagentless sensors can be developed. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Antitumor Mechanisms of Amino Acid Hydroxyurea Derivatives in the Metastatic Colon Cancer Model

    PubMed Central

    Šaban, Nina; Stepanić, Višnja; Vučinić, Srđan; Horvatić, Anita; Cindrić, Mario; Perković, Ivana; Zorc, Branka; Oršolić, Nada; Mintas, Mladen; Pavelić, Krešimir; Pavelić, Sandra Kraljević

    2013-01-01

    The paper presents a detailed study of the biological effects of two amino acid hydroxyurea derivatives that showed selective antiproliferative effects in vitro on the growth of human tumor cell line SW620. Tested compounds induced cell cycle perturbations and apoptosis. Proteins were identified by proteomics analyses using two-dimensional gel electrophoresis coupled to mass spectrometry, which provided a complete insight into the most probable mechanism of action on the protein level. Molecular targets for tested compounds were analyzed by cheminformatics tools. Zinc-dependent histone deacetylases were identified as potential targets responsible for the observed antiproliferative effect. PMID:24304540

  20. The synthesis and antistaphylococcal activity of dehydroabietic acid derivatives: modifications at C12 and C7.

    PubMed

    Zhang, Wen-Ming; Yang, Teng; Pan, Xue-Ying; Liu, Xin-Lan; Lin, Hai-Xia; Gao, Zhao-Bing; Yang, Cai-Guang; Cui, Yong-Mei

    2017-02-15

    A series of 7-N-acylaminoethyl/propyloxime derivatives of dehydroabietic acid were synthesized and investigated for their antibacterial activity against Staphylococcus aureus Newman strain and multidrug-resistant strains (NRS-1, NRS-70, NRS-100, NRS-108 and NRS-271). Most of the target compounds having trifluoromethyl phenyl/benzyl, halogen-substituted thiophenyl, benzothiophenyl or pyrrolyl moiety exhibited potent in vitro antibacterial activity. Among which, compounds 4m, 4x and 7j showed high antibacterial activity with minimum inhibitory concentration (MIC) values of 1.25-3.13 μg/mL against five multidrug-resistant S. aureus.

  1. Thieno[3,2-b]thiophene-2-carboxylic acid derivatives as GPR35 agonists.

    PubMed

    Deng, Huayun; Hu, Jieyu; Hu, Haibei; He, Mingqian; Fang, Ye

    2012-06-15

    The optimization of a series of thieno[3,2-b]thiophene-2-carboxylic acid derivatives for agonist activity against the GPR35 is reported. Compounds were optimized to achieve β-arrestin-biased agonism for developing probe molecules that may be useful for elucidating the biology and physiology of GPR35. Compound 13 was identified to the most potent GPR35 agonist, and compounds 30 and 36 exhibited the highest efficacy to cause β-arrestin translocation. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. [Screening of new derivatives of arylheteroalkanecarboxylic acid on the immune system].

    PubMed

    Kolesnikova, O P; Kudaeva, O T; Sukhenko, T G; Lykov, A P; Gaĭdul', K V; Limonov, V L; Mirskova, A N; Lavskovskaia, G G; Voronkov, M G; Kozlov, V A

    2006-01-01

    The screening of 13 original compounds from the group of derivatives of arylheteroalkanecarboxylic acid on immunity were performed. The compounds exhibit strong myelostimulating/myelosuppressive property, increased or decreased influence on the: PFC (IgM and IgG), DTH at the sheep erythrocytes in CBF1 in vivo. In contrast, in vitro the compounds had no effect or inhibited the spontaneous, ConA or PWM induced proliferation of the splenocytes from normal mice. The problems of the universal methods of the screening of immunoactive properties of compounds are discussed.

  3. Synthesis of Gibberellic Acid Derivatives and Their Effects on Plant Growth.

    PubMed

    Tian, Hao; Xu, Yiren; Liu, Shaojin; Jin, Dingsha; Zhang, Jianjun; Duan, Liusheng; Tan, Weiming

    2017-04-26

    A series of novel C-3-OH substituted gibberellin derivatives bearing an amide group were designed and synthesized from the natural product gibberellic acid (GA₃). Their activities on the plant growth regulation of rice and Arabidopsis were evaluated in vivo. Among these compounds, 10d and 10f exhibited appreciable inhibitory activities on rice (48.6% at 100 μmol/L) and Arabidopsis (41.4% at 100 μmol/L), respectively. These results provide new insights into the design and synthesis of potential plant growth regulators.

  4. Pyridines and pyrazolines from salicylic acid derivatives with propenone residue and their antimicrobial properties.

    PubMed

    Grant, N; Mishriky, N; Asaad, F M; Fawzy, N G

    1998-08-01

    Reaction of the propenones 1c, d with chlorosulfonyl isocyanate followed by hydrolysis gave the corresponding carbamoyloxybenzoates 2a, b. While their reaction with ethyl isocyanate afforded the 1,3-benzoxazine-2,4-diones 3a, b. Reaction of 1a, b with aryl hydrazines gave the pyrazolines 4a, d, whereas, with hydrazine hydrate in acetic acid, the acetyl derivatives 4e, f were produced. 1c, d reacted with malononitrile and ethyl cyanoacetate affording the cyanopyridines 5 and cyanopyridones 6 respectively. The products show antimicrobial activities.

  5. Copper-catalyzed asymmetric conjugate reduction as a route to novel β-azaheterocyclic acid derivatives

    PubMed Central

    Rainka, Matthew P.; Aye, Yimon; Buchwald, Stephen L.

    2004-01-01

    A chiral copper-hydride catalyst for the asymmetric conjugate reduction of α,β-unsaturated carbonyl compounds has been used for the reduction of substrates containing β-nitrogen substituents. A new set of reaction conditions has allowed for a variety of β-azaheterocyclic acid derivatives to be synthesized in excellent yields and with high degrees of enantioselectivity. In addition, the effect that the nature of the nitrogen substituent has on the rate of the conjugate reduction reaction has been explored. PMID:15067136

  6. Synthesis and Biological Activity of Arylspiroborate Salts Derived from Caffeic Acid Phenethyl Ester

    PubMed Central

    Hébert, Martin J. G.; Flewelling, Andrew J.; Clark, Trevor N.; Jean-François, Jacques; Surette, Marc E.; Gray, Christopher A.; Vogels, Christopher M.; Touaibia, Mohamed; Westcott, Stephen A.

    2015-01-01

    Two novel boron compounds containing caffeic acid phenethyl ester (CAPE) derivatives have been prepared and characterized fully. These new compounds and CAPE have been investigated for potential antioxidant and antimicrobial properties and their ability to inhibit 5-lipoxygenase and whether chelation to boron improves their biological activity. Sodium salt 4 was generally more active than ammonium salt 5 in the biological assays and surpassed the radical scavenging ability of CAPE. Compounds 4 and 5 were more active than CAPE and Zileuton in human polymorphonuclear leukocytes. These results clearly show the effectiveness of the synthesized salts as transporter of CAPE. PMID:25834744

  7. Synthesis and biological activity of arylspiroborate salts derived from caffeic Acid phenethyl ester.

    PubMed

    Hébert, Martin J G; Flewelling, Andrew J; Clark, Trevor N; Levesque, Natalie A; Jean-François, Jacques; Surette, Marc E; Gray, Christopher A; Vogels, Christopher M; Touaibia, Mohamed; Westcott, Stephen A

    2015-01-01

    Two novel boron compounds containing caffeic acid phenethyl ester (CAPE) derivatives have been prepared and characterized fully. These new compounds and CAPE have been investigated for potential antioxidant and antimicrobial properties and their ability to inhibit 5-lipoxygenase and whether chelation to boron improves their biological activity. Sodium salt 4 was generally more active than ammonium salt 5 in the biological assays and surpassed the radical scavenging ability of CAPE. Compounds 4 and 5 were more active than CAPE and Zileuton in human polymorphonuclear leukocytes. These results clearly show the effectiveness of the synthesized salts as transporter of CAPE.

  8. Anti-MRSA cephems. Part 2: C-7 cinnamic acid derivatives.

    PubMed

    Springer, Dane M; Luh, Bing Yu; Goodrich, Jason; Bronson, Joanne J

    2003-01-17

    Forty-five novel cephalosporin derivatives with activity against methicillin-resistant Staphylococcus aureus (MRSA) are described. The compounds contain novel cinnamic acid moieties at C-7 that were synthesized using a key Heck reaction followed by nucleophilic aromatic substitution reactions. The most active compound (41) displayed an MIC(90) against MRSA of 1.0 microg/mL, and a PD(50) of 0.8 mg/kg. Compound 14 was found to be very safe in a mouse model of acute toxicity.

  9. Caffeic acid derivatives, analogs and applications: a patent review (2009-2013).

    PubMed

    Silva, Tiago; Oliveira, Catarina; Borges, Fernanda

    2014-11-01

    Caffeic acid (CA) is broadly distributed in several species of the plant kingdom and is widely consumed in human diet. CA and derivatives have been extensively studied in the past years, which unveiled a broad spectrum of biological activities and potential therapeutic applications. As a result, there has been an upsurge in the development of new chemical entities based on the CA scaffold. The scope of this review is to revisit the therapeutic potential of CA and derivatives. It provides an overview of patented processes and applications thereof between 2009 and 2013. The phenylpropanoid framework is currently considered a valid structure for drug discovery programs. Actually, CA has been widely used as a template for the development of new chemical entities with potential therapeutic interest in human diseases associated with oxidative stress. Additionally, the applicability of CA derivatives expands to the realms of cosmetic industry due to its stabilizing properties. The synthesis of esters, amides and hybrids with currently marketed drugs is a trending strategy for the development of derivatives with therapeutic application. It is our opinion that the innovative artwork currently being developed involving this chemical scaffold will yield new and effective therapeutic agents in a foreseeable future.

  10. Effectiveness of hyaluronic acid and its derivatives on chronic wounds: a systematic review.

    PubMed

    Shaharudin, A; Aziz, Z

    2016-10-02

    Hyaluronic acid (HA) and its derivatives are used for chronic wounds, but evidence of their effectiveness remains unclear. The aim of this study was to provide more updated evidence for the effectiveness of HA (or its derivatives) compared with placebo or other agents for promoting healing in chronic wounds. The Cochrane Central Register of Controlled Trials, MEDLINE via Ovid Online, CINAHL and the EMBASE via EBSCO host databases were searched. Drug companies and experts in wounds were also contacted. Randomised controlled trials of HA (or its derivatives) compared with control were eligible for inclusion. We identified nine randomised controlled trials involving 865 participants with chronic wounds were included in the review. The reporting for mixed arterial and venous ulcers seems to be better quality than that for venous leg ulcers (VLUs) and diabetic foot ulcers (DFUs). Studies provided little evidence regarding the claimed effects of HA or its derivaties on healing of chronic wounds. However, there is some evidence on their effectiveness for reducing pain intensity for mixed arterial and venous ulcers, which involved 255 patients (MD=-6.78 [95% CI: -11.10 to -2.46]). Evidence to guide decisions regarding the use of HA or its derivatives to promote wound healing is still limited. More good-quality randomised controlled trials are warranted.

  11. Aquatic predicted no-effect-concentration derivation for perfluorooctane sulfonic acid.

    PubMed

    Qi, Ping; Wang, Ying; Mu, Jingli; Wang, Juying

    2011-04-01

    Perfluorooctane sulfonic acid (PFOS), a representative perfluorinated surfactant, is an anthropogenic pollutant detected in various environmental and biological matrices. Some laboratory and field work has been conducted to assess the aquatic toxicity of PFOS, but little is known regarding its toxicity threshold to the aquatic ecosystem. In the present study, predicted no-effect concentrations (PNECs) were derived by four different approaches. The interspecies correlation estimation (ICE) program and final acute-to-chronic ratio (FACR) were applied to the development of PNEC based on the toxic mode of action (MOA) of PFOS. By comparison of the different PNECs, the recommended aquatic toxicity thresholds for PFOS are in the range of 0.61 to 6.66 µg/L. Based on comparison of PNEC values, microcosm results, and reported environmental concentrations, PFOS appears not to pose a serious threat to aquatic organisms. The present results demonstrate that MOA is an important consideration for the derivation of reliable PNECs; moreover, the ICE-based species sensitivity distribution (SSD) method can be used to derive PNECs when toxicological data are limited. The application of MOA and ICE for deriving PNEC values in the present study may facilitate studies on using a combination of quantitative structure-activity relationship (QSAR) models and ICE to estimate PNECs.

  12. Feasible protein aggregation of phosphorylated poly-γ-glutamic acid derivative from Bacillus subtilis (natto).

    PubMed

    Kurita, Osamu; Sago, Toru; Umetani, Kaori; Kokean, Yasushi; Yamaoka, Chizuru; Takahashi, Nobuyuki; Iwamoto, Hiroyuki

    2017-10-01

    Poly-γ-glutamic acid (PGA) was modified with phosphorylating agents such as sodium metaphosphate and potassium metaphosphate in the culture medium of Bacillus subtilis (natto). The highly phosphorylated PGA derivatives were prepared and investigated for their chemical and physicochemical properties. The PGA derivatives had approximately 7% (W/W) inorganic phosphorus and characteristic absorbance PO2(-) bands at 1082cm(-1) and 1260cm(-1) by Fourier Transform Infrared Spectroscopy. The derivative modified by sodium metaphosphate (J-5) was easily hydrated in water and had extremely low viscosity. The shear rate-induced transition leading to the decrease of viscosity was not observed in J-5 whereas the derivative modified by potassium metaphosphate (J-6) as well as unmodified PGA (J-1) showed the typical decrease of viscosity. In circular dichroism (CD) measurement of J-5, there was a significant loss of the negative chirality CD signal, implying that protein aggregation occured at decreasing pH from 6.2 to 4.4. The thioflavin T fluorescence intensity of the aqueous solution in the J-5 was extremely high despite the absence of heat-treatment. The results indicate that the J-5 is the likeliest type of aggregation by β-sheet cross-linking which is relevant to protein diseases like Alzheimer's disease. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Dehydroabietic Acid Derivative QC4 Induces Gastric Cancer Cell Death via Oncosis and Apoptosis

    PubMed Central

    Luo, Dongjun; Ni, Qing; Ji, Anlai; Gu, Wen; Wu, Junhua

    2016-01-01

    Aim. QC4 is the derivative of rosin's main components dehydroabietic acid (DHA). We investigated the cytotoxic effect of QC4 on gastric cancer cells and revealed the mechanisms beneath the induction of cell death. Methods. The cytotoxic effect of QC4 on gastric cancer cells was evaluated by CCK-8 assay and flow cytometry. The underlying mechanisms were tested by administration of cell death related inhibitors and detection of apoptotic and oncosis related proteins. Cytomembrane integrity and organelles damage were confirmed by lactate dehydrogenase (LDH) leakage assay, mitochondrial function test, and cytosolic free Ca2+ concentration detection. Results. QC4 inhibited cell proliferation dose- and time-dependently and destroyed cell membrane integrity, activated calpain-1 autolysis, and induced apoptotic protein cleavage in gastric cancer cells. The detection of decreased ATP and mitochondrial membrane potential, ROS accumulation, and cytosolic free Ca2+ elevation confirmed organelles damage in QC4-treated gastric cancer cells. Conclusions. DHA derivative QC4 induced the damage of cytomembrane and organelles which finally lead to oncosis and apoptosis in gastric cancer cells. Therefore, as a derivative of plant derived small molecule DHA, QC4 might become a promising agent in gastric cancer therapy. PMID:27057539

  14. Chemical and biological characterization of cinnamic acid derivatives from cell cultures of lavender (Lavandula officinalis) induced by stress and jasmonic acid.

    PubMed

    Nitzsche, Astrid; Tokalov, Sergey V; Gutzeit, Herwig O; Ludwig-Müller, Jutta

    2004-05-19

    Cell cultures of lavender (Lavandula officinalis) were analyzed for the metabolite profile under normal growth conditions and under stress as well as after jasmonic acid treatment. The main compound synthesized was rosmarinic acid, which was also secreted into the culture medium. Different solvent extraction methods at different pH values altered the profile slightly. Anoxic stress induced the synthesis of a cinnamic acid derivative, which was identified as caffeic acid by gas chromatography-mass spectrometry. Caffeic acid was also induced after treatment of the cell cultures with jasmonic acid. Although the antioxidative activity of both compounds, rosmarinic acid and caffeic acid, was confirmed in an assay using 2,2-diphenyl-1-picrylhydrazyl (DPPH), it was demonstrated that both substances have a low cytotoxic potential in vitro using acute myeloid leukemia (HL-60) cells. The potential of the system for finding new bioactive compounds is discussed.

  15. XAFS Studies of Cobalt(II) Binding by Solid Peat and Soil-derived Humic Acids and Plant-derived Humic Acid-like Substances

    SciTech Connect

    Ghabbour,E.; Scheinost, A.; Davies, G.

    2007-01-01

    This work has examined cobalt(II) binding by a variety of solid humic acids (HAs) isolated from peat, plant and soil sources at temperatures down to 60 K. The results confirm that X-ray absorption near-edge spectroscopy (XANES) measurements cannot distinguish between aquo and carboxylato ligands in the inner coordination sphere of Co(II). However, between 1 and 2 inner-sphere carboxylato ligands can be detected in all the peat, plant and soil-derived HA samples by extended X-ray absorption fine structure (EXAFS) measurements, indicating inner-sphere coordination of HA-bound Co(II). The precision of C(carboxylate) detection is limited by the extent and quality of the data and the contribution from inner-sphere O to the Fourier transformed peaks used to detect carbon. Putative chelate ring formation is consistent with a relatively negative entropy change in step A, the stronger Co(II) binding step by HA functional groups, and could relate to 'non-exchangeable' metal binding by HSs.

  16. XAFS studies of cobalt(II) binding by solid peat and soil-derived humic acids and plant-derived humic acid-like substances.

    PubMed

    Ghabbour, Elham A; Scheinost, Andreas C; Davies, Geoffrey

    2007-02-01

    This work has examined cobalt(II) binding by a variety of solid humic acids (HAs) isolated from peat, plant and soil sources at temperatures down to 60K. The results confirm that X-ray absorption near-edge spectroscopy (XANES) measurements cannot distinguish between aquo and carboxylato ligands in the inner coordination sphere of Co(II). However, between 1 and 2 inner-sphere carboxylato ligands can be detected in all the peat, plant and soil-derived HA samples by extended X-ray absorption fine structure (EXAFS) measurements, indicating inner-sphere coordination of HA-bound Co(II). The precision of C(carboxylate) detection is limited by the extent and quality of the data and the contribution from inner-sphere O to the Fourier transformed peaks used to detect carbon. Putative chelate ring formation is consistent with a relatively negative entropy change in step A, the stronger Co(II) binding step by HA functional groups, and could relate to 'non-exchangeable' metal binding by HSs.

  17. Insights into the spontaneity of hydrogen bond formation between formic acid and phthalimide derivatives.

    PubMed

    Júnior, Rogério V A; Moura, Gustavo L C; Lima, Nathalia B D

    2016-11-01

    We evaluated a group of phthalimide derivatives, which comprise a convenient test set for the study of the multiple factors involved in the energetics of hydrogen bond formation. Accordingly, we carried out quantum chemical calculations on the hydrogen bonded complexes formed between a sample of phthalimide derivatives with formic acid with the intent of identifying the most important electronic and structural factors related to how their strength and spontaneity vary across the series. The geometries of all species considered were fully optimized at DFT B3LYP/6-31++G(d,p), RM1, RM1-DH2, and RM1-D3H4 level, followed by frequency calculations to determine their Gibbs free energies of hydrogen bond formation using Gaussian 2009 and MOPAC 2012. Our results indicate that the phthalimide derivatives that form hydrogen bond complexes most favorably, have in their structures only one C=O group and at least one NH group. On the other hand, the phthalimide derivatives predicted to form hydrogen bonds least favorably, possess in their structures two carbonyl groups, C=O, and no NH group. The ability to donate electrons and simultaneously receive one acidic hydrogen is the most important property related to the spontaneity of hydrogen bond formation. We further chose two cyclic compounds, phthalimide and isoindolin-1-one, in which to study the main changes in molecular, structural and spectroscopic properties as related to the formation of hydrogen bonds. Thus, the greatest ability of the isoindolin-1-one compound in forming hydrogen bonds is evidenced by the larger effect on the structural, vibrational, and chemical shifts properties associated with the O-H group. In summary, the electron-donating ability of the hydrogen bond acceptor emerged as the most important property differentiating the spontaneity of hydrogen bond formation in this group of complexes.

  18. Effective synthesis of optically active trifluoromethyldiazirinyl homophenylalanine and aroylalanine derivatives with the Friedel-Crafts reaction in triflic acid.

    PubMed

    Murashige, Ryo; Murai, Yuta; Hatanaka, Yasumaru; Hashimoto, Makoto

    2009-06-01

    The Friedel-Crafts reaction with 3-(3-methoxyphenyl)-3-(trifluoromethyl)-3H-diazirine and optically active N-TFA-Asp(Cl)-OMe in triflic acid afforded homophenylalanine derivatives without any loss of the optical purity.

  19. The marine sponge-derived polyketide endoperoxide plakortide F acid mediates its antifungal activity by interfering with calcium homeostasis

    USDA-ARS?s Scientific Manuscript database

    Plakortide F acid (PFA) is a marine-derived polyketide endoperoxide exhibiting strong inhibitory activity against several clinically important fungal pathogens. In the present study, transcriptional profiling coupled with mutant and biochemical analyses were conducted using the model organism Sacch...

  20. An easy entry to optically active alpha-amino phosphonic acid derivatives using phase-transfer catalysis (PTC).

    PubMed

    Fini, Francesco; Micheletti, Gabriele; Bernardi, Luca; Pettersen, Daniel; Fochi, Mariafrancesca; Ricci, Alfredo

    2008-09-28

    The unprecedented use of phase-transfer catalysis (PTC) in an asymmetric hydrophosphonylation reaction allows the obtainment of a range of optically active alpha-amino phosphonic acid derivatives directly from alpha-amido sulfones.