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Sample records for alters l-a-amino-3-hydroxy-5-methyl-4-isoxazole propionic

  1. The glutamate receptor GluR5 agonist (S)-2-amino-3-(3-hydroxy-7,8-dihydro-6H-cyclohepta[d]isoxazol-4-yl)propionic acid and the 8-methyl analogue

    DEFF Research Database (Denmark)

    Clausen, Rasmus Prætorius; Naur, Peter; Kristensen, Anders Skov

    2009-01-01

    The design, synthesis, and pharmacological characterization of a highly potent and selective glutamate GluR5 agonist is reported. (S)-2-Amino-3-((RS)-3-hydroxy-8-methyl-7,8-dihydro-6H-cyclohepta[d]isoxazol-4-yl)propionic acid (5) is the 8-methyl analogue of (S)-2-amino-3-(3-hydroxy-7,8-dihydro-6H......-cyclohepta[d]isoxazol-4-yl)propionic acid ((S)-4-AHCP, 4). Compound 5 displays an improved selectivity profile compared to 4. A versatile stereoselective synthetic route for this class of compounds is presented along with the characterization of the binding affinity of 5 to ionotropic glutamate receptors (i......GluRs). Functional characterization of 5 at cloned iGluRs using a calcium imaging assay and voltage-clamp recordings show a different activation of GluR5 compared to (S)-glutamic acid (Glu), kainic acid (KA, 1), and (S)-2-amino-3-(3-hydroxy-5-tert-butyl-4-isoxazolyl)propionic acid ((S)-ATPA, 3) as previously...

  2. 2-Amino-3-(3-hydroxy-1,2,5-thiadiazol-4-yl)propionic acid

    DEFF Research Database (Denmark)

    Johansen, Tommy N; Janin, Yves L; Nielsen, Birgitte

    2002-01-01

    In order to identify new subtype-selective (S)-glutamate (Glu) receptor ligands we have synthesized (RS)-2-amino-3-(3-hydroxy-1,2,5-thiadiazol-4-yl)propionic acid [(RS)-TDPA]. Resolution of (RS)-TDPA by chiral chromatography was performed using a Crownpac CR(+) column affording (R)- and (S......)-TDPA of high enantiomeric purity (enantiomeric excess=99.9%). An X-ray crystallographic analysis revealed that the early eluting enantiomer has R-configuration. Both enantiomers showed high affinity as well as high agonist activity at (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA...... a remarkably low AMPA receptor stereoselectivity, (S)-TDPA showing the highest affinity and (R)-TDPA the most potent agonist activity. In addition, (S)-TDPA was shown to interact with synaptosomal Glu uptake sites displacing [(3)H](R)-aspartic acid (IC(50 ) approximately 390 microM). An enantiospecific...

  3. Resolution, configurational assignment, and enantiopharmacology at glutamate receptors of 2-amino-3-(3-carboxy-5-methyl-4-isoxazolyl)propionic acid (ACPA) and demethyl-ACPA

    DEFF Research Database (Denmark)

    Johansen, T N; Stensbøl, T B; Nielsen, B

    2001-01-01

    We have previously described (RS)-2-amino-3-(3-carboxy-5-methyl-4-isoxazolyl)propionic acid (ACPA) as a potent agonist at the (RS)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA) receptor subtype of (S)-glutamic acid (Glu) receptors. We now report the chromatographic resolution...... of ACPA and (RS)-2-amino-3-(3-carboxy-4-isoxazolyl)propionic acid (demethyl-ACPA) using a Sumichiral OA-5000 column. The configuration of the enantiomers of both compounds have been assigned based on X-ray crystallographic analyses, supported by circular dichroism spectra and elution orders on chiral HPLC...... columns. Furthermore, the enantiopharmacology of ACPA and demethyl-ACPA was investigated using radioligand binding and cortical wedge electrophysiological assay systems and cloned metabotropic Glu receptors. (S)-ACPA showed high affinity in AMPA binding (IC(50) = 0.025 microM), low affinity in kainic acid...

  4. Molecular pharmacology of the AMPA agonist, (S)-2-amino-3-(3-hydroxy-5-phenyl-4-isoxazolyl)propionic acid [(S)-APPA] and the AMPA antagonist, (R)-APPA

    DEFF Research Database (Denmark)

    Ebert, B; Madsen, U; Lund, Trine Meldgaard

    1994-01-01

    )-APPA, whereas (R)-APPA is a non-N-methyl-D-aspartic acid (non-NMDA) receptor antagonist showing preferential AMPA blocking effects. In agreement with classical theories for competitive interaction between agonists and antagonists, the efficacy of depolarizations produced by (S)-APPA in the rat cortical wedge......The heterocyclic analogue of (S)-glutamic acid, (S)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid [(S)-AMPA] is a potent and selective AMPA receptor agonist, whereas the enantiomeric compound, (R)-AMPA, is virtually inactive. We have previously characterized (RS)-2-amino-3-(3-hydroxy-5......-phenyl-4-isoxazolyl)propionic acid [(RS)-APPA] as a partial AMPA receptor agonist showing about 60% of the efficacy of (RS)-AMPA. This partial agonism produced by (RS)-APPA is, however, only apparent, since resolution of (RS)-APPA has now been shown to provide the full AMPA receptor agonist, (S...

  5. A new highly selective metabotropic excitatory amino acid agonist: 2-amino-4-(3-hydroxy-5-methylisoxazol-4-yl)butyric acid

    DEFF Research Database (Denmark)

    Bräuner-Osborne, Hans; Sløk, F A; Skjaerbaek, N

    1996-01-01

    The homologous series of acidic amino acids, ranging from aspartic acid (1) to 2-aminosuberic acid (5), and the corresponding series of 3-isoxazolol bioisosteres of these amino acids, ranging from (RS)-2-amino-2-(3-hydroxy-5-methylisoxazol-4-yl)acetic acid (AMAA, 6) to (RS)-2-amino-6-(3-hydroxy-5......-methylisoxazol-4-yl)hexanoic acid (10), were tested as ligands for metabotropic excitatory amino acid receptors (mGlu1 alpha, mGlu2, mGlu4a, and mGlu6). Whereas AMAA (6) and (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propinoic acid (AMPA, 7) are potent and highly selective agonists at N......-methyl-D-aspartic acid (NMDA) and AMPA receptors, respectively, the higher homologue of AMPA (7), (RS)-2-amino-4-(3-hydroxy-5-methylisoxazol-4-yl)butyric acid (homo-AMPA, 8), is inactive at ionotropic excitatory amino acid receptors. Homo-AMPA (8), which is a 3-isoxazolol bioisostere of 2-aminoadipic acid (3), was...

  6. Selective agonists at group II metabotropic glutamate receptors: synthesis, stereochemistry, and molecular pharmacology of (S)- and (R)-2-amino-4-(4-hydroxy[1,2,5]thiadiazol-3-yl)butyric acid

    DEFF Research Database (Denmark)

    Clausen, Rasmus P; Bräuner-Osborne, Hans; Greenwood, Jeremy R

    2002-01-01

    Homologation of analogues of the central excitatory neurotransmitter glutamic acid (Glu), in which the distal carboxy group has been bioisosterically replaced by acidic heterocyclic units, has previously provided subtype selective ligands for metabotropic Glu receptors (mGluRs). The (S......)-form of the 1,2,5-thiadiazol-3-ol Glu analogue, 2-amino-3-(4-hydroxy[1,2,5]thiadiazol-3-yl)propionic acid (TDPA, 6), is an 2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA) receptor agonist, which in addition stereospecifically activates group I mGluRs. We have now synthesized the (S)- and (R......)-forms of 2-amino-4-(4-hydroxy[1,2,5]thiadiazol-3-yl)butyric acid (homo-TDPA, 7) and shown that whereas neither enantiomer interacts with AMPA receptors, (S)- and (R)-7 appear to be selective and equipotent agonists at group II mGluRs as represented by the mGluR2 subtype. The activities of (S)- and (R)-7...

  7. Roles of fragile X mental retardation protein in dopaminergic stimulation-induced synapse-associated protein synthesis and subsequent alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-4-propionate (AMPA) receptor internalization.

    Science.gov (United States)

    Wang, Hansen; Kim, Susan S; Zhuo, Min

    2010-07-09

    Fragile X syndrome, the most common form of inherited mental retardation, is caused by the absence of the RNA-binding protein fragile X mental retardation protein (FMRP). FMRP regulates local protein synthesis in dendritic spines. Dopamine (DA) is involved in the modulation of synaptic plasticity. Activation of DA receptors can regulate higher brain functions in a protein synthesis-dependent manner. Our recent study has shown that FMRP acts as a key messenger for DA modulation in forebrain neurons. Here, we demonstrate that FMRP is critical for DA D1 receptor-mediated synthesis of synapse-associated protein 90/PSD-95-associated protein 3 (SAPAP3) in the prefrontal cortex (PFC). DA D1 receptor stimulation induced dynamic changes of FMRP phosphorylation. The changes in FMRP phosphorylation temporally correspond with the expression of SAPAP3 after D1 receptor stimulation. Protein phosphatase 2A, ribosomal protein S6 kinase, and mammalian target of rapamycin are the key signaling molecules for FMRP linking DA D1 receptors to SAPAP3. Knockdown of SAPAP3 did not affect surface expression of alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-4-propionate (AMPA) GluR1 receptors induced by D1 receptor activation but impaired their subsequent internalization in cultured PFC neurons; the subsequent internalization of GluR1 was also impaired in Fmr1 knock-out PFC neurons, suggesting that FMRP may be involved in subsequent internalization of GluR1 through regulating the abundance of SAPAP3 after DA D1 receptor stimulation. Our study thus provides further insights into FMRP involvement in DA modulation and may help to reveal the molecular mechanisms underlying impaired learning and memory in fragile X syndrome.

  8. Roles of Fragile X Mental Retardation Protein in Dopaminergic Stimulation-induced Synapse-associated Protein Synthesis and Subsequent α-Amino-3-hydroxyl-5-methyl-4-isoxazole-4-propionate (AMPA) Receptor Internalization*

    Science.gov (United States)

    Wang, Hansen; Kim, Susan S.; Zhuo, Min

    2010-01-01

    Fragile X syndrome, the most common form of inherited mental retardation, is caused by the absence of the RNA-binding protein fragile X mental retardation protein (FMRP). FMRP regulates local protein synthesis in dendritic spines. Dopamine (DA) is involved in the modulation of synaptic plasticity. Activation of DA receptors can regulate higher brain functions in a protein synthesis-dependent manner. Our recent study has shown that FMRP acts as a key messenger for DA modulation in forebrain neurons. Here, we demonstrate that FMRP is critical for DA D1 receptor-mediated synthesis of synapse-associated protein 90/PSD-95-associated protein 3 (SAPAP3) in the prefrontal cortex (PFC). DA D1 receptor stimulation induced dynamic changes of FMRP phosphorylation. The changes in FMRP phosphorylation temporally correspond with the expression of SAPAP3 after D1 receptor stimulation. Protein phosphatase 2A, ribosomal protein S6 kinase, and mammalian target of rapamycin are the key signaling molecules for FMRP linking DA D1 receptors to SAPAP3. Knockdown of SAPAP3 did not affect surface expression of α-amino-3-hydroxyl-5-methyl-4-isoxazole-4-propionate (AMPA) GluR1 receptors induced by D1 receptor activation but impaired their subsequent internalization in cultured PFC neurons; the subsequent internalization of GluR1 was also impaired in Fmr1 knock-out PFC neurons, suggesting that FMRP may be involved in subsequent internalization of GluR1 through regulating the abundance of SAPAP3 after DA D1 receptor stimulation. Our study thus provides further insights into FMRP involvement in DA modulation and may help to reveal the molecular mechanisms underlying impaired learning and memory in fragile X syndrome. PMID:20457613

  9. Excitatory amino acid receptor ligands: resolution, absolute stereochemistry, and enantiopharmacology of 2-amino-3-(4-butyl-3-hydroxyisoxazol-5-yl)propionic acid

    DEFF Research Database (Denmark)

    Johansen, T N; Ebert, B; Bräuner-Osborne, Hans

    1998-01-01

    (RS)-2-Amino-3-(4-butyl-3-hydroxyisoxazol-5-yl)propionic acid (Bu-HIBO, 6) has previously been shown to be an agonist at (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) receptors and an inhibitor of CaCl2-dependent [3H]-(S)-glutamic acid binding (J. Med. Chem. 1992, 35, 3512......-3519). To elucidate the pharmacological significance of this latter binding affinity, which is also shown by quisqualic acid (3) but not by AMPA, we have now resolved Bu-HIBO via diastereomeric salt formation using the diprotected Bu-HIBO derivative 11 and the enantiomers of 1-phenylethylamine (PEA). The absolute...... equipotent as inhibitors of CaCl2-dependent [3H]-(S)-glutamic acid binding, neither enantiomer showed significant affinity for the synaptosomal (S)-glutamic acid uptake system(s). AMPA receptor affinity (IC50 = 0.48 microM) and agonism (EC50 = 17 microM) were shown to reside exclusively in the S...

  10. Development of calcium-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors in cultured neocortical neurons visualized by cobalt staining

    DEFF Research Database (Denmark)

    Jensen, J B; Schousboe, A; Pickering, D S

    1998-01-01

    The developmental expression of calcium (Ca2+)-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate receptors in cultured neocortical neurons was evaluated by using cobalt uptake, a histochemical method that identifies cells expressing Ca2+-permeable, non-N-methyl-D-aspartate...

  11. Ketamine-induced inhibition of glycogen synthase kinase-3 contributes to the augmentation of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor signaling.

    Science.gov (United States)

    Beurel, Eléonore; Grieco, Steven F; Amadei, Celeste; Downey, Kimberlee; Jope, Richard S

    2016-09-01

    Sub-anesthetic doses of ketamine have been found to provide rapid antidepressant actions, indicating that the cellular signaling systems targeted by ketamine are potential sites for therapeutic intervention. Ketamine acts as an antagonist of N-methyl-D-aspartate (NMDA) receptors, and animal studies indicate that subsequent augmentation of signaling by α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors is critical for the antidepressant outcome. In this study, we tested if the inhibitory effect of ketamine on glycogen synthase kinase-3 (GSK3) affected hippocampal cell-surface AMPA receptors using immunoblotting of membrane and synaptosomal extracts from wild-type and GSK3 knockin mice. Treatment with an antidepressant dose of ketamine increased the hippocampal membrane level of the AMPA glutamate receptor (GluA)1 subunit, but did not alter the localization of GluA2, GluA3, or GluA4. This effect of ketamine was abrogated in GSK3 knockin mice expressing mutant GSK3 that cannot be inhibited by ketamine, demonstrating that ketamine-induced inhibition of GSK3 is necessary for up-regulation of cell surface AMPA GluA1 subunits. AMPA receptor trafficking is regulated by post-synaptic density-95 (PSD-95), a substrate for GSK3. Ketamine treatment decreased the hippocampal membrane level of phosphorylated PSD-95 on Thr-19, the target of GSK3 that promotes AMPA receptor internalization. These results demonstrate that ketamine-induced inhibition of GSK3 causes reduced phosphorylation of PSD-95, diminishing the internalization of AMPA GluA1 subunits to allow for augmented signaling through AMPA receptors following ketamine treatment. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. (S)-2-Amino-3-(3-hydroxy-7,8-dihydro-6H-cyclohepta[d]isoxazol-4-yl)propionic acid, a potent and selective agonist at the GluR5 subtype of ionotropic glutamate receptors. Synthesis, modeling, and molecular pharmacology

    DEFF Research Database (Denmark)

    Brehm, Lotte; Greenwood, Jeremy R; Hansen, Kasper B

    2003-01-01

    )propionic acid (AMPA) but inactive at NMDA receptors. However, 4-AHCP was found to be much weaker than AMPA as an inhibitor of [(3)H]AMPA binding and to have limited effect in a [(3)H]kainic acid binding assay using rat cortical membranes. To shed light on the mechanism(s) underlying this quite enigmatic......, activated cloned AMPA receptor subunits GluR1o, GluR3o, and GluR4o with EC(50) values in the range 4.5-15 microM and the coexpressed kainate-preferring subunits GluR6 + KA2 (EC(50) = 6.4 microM). Compound 6, but not 7, proved to be a very potent agonist (EC(50) = 0.13 microM) at the kainate-preferring GluR5...... subunit, equipotent with (S)-2-amino-3-(5-tert-butyl-3-hydroxyisothiazol-4-yl)propionic acid [(S)-Thio-ATPA, 4] and almost 4 times more potent than (S)-2-amino-3-(5-tert-butyl-3-hydroxyisoxazol-4-yl)propionic acid [(S)-ATPA, 3]. Compound 6 thus represents a new structural class of GluR5 agonists...

  13. Role of astrocytes in depolarization-coupled release of glutamate in cerebellar cultures

    DEFF Research Database (Denmark)

    Bak, Lasse K; Waagepetersen, Helle S; Schousboe, Arne

    2004-01-01

    Release of preloaded D-[3H]aspartate in response to depolarization induced by high potassium, N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) or the endogenous agonist glutamate was studied using cultured glutamatergic cerebellar granule neurons, cerebell...

  14. Ionotropic excitatory amino acid receptor ligands. Synthesis and pharmacology of a new amino acid AMPA antagonist

    DEFF Research Database (Denmark)

    Madsen, U; Sløk, F A; Stensbøl, T B

    2000-01-01

    We have previously described the potent and selective (RS)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA) receptor agonist, (RS)-2-amino-3-(3-carboxy-5-methyl-4-isoxazolyl)propionic acid (ACPA), and the AMPA receptor antagonist (RS)-2-amino-3-[3-(carboxymethoxy)-5-methyl-4...... excitatory amino acid (EAA) receptors using receptor binding and electrophysiological techniques, and for activity at metabotropic EAA receptors using second messenger assays. Compounds 1 and 4 were essentially inactive. (RS)-2-Amino-3-[3-(2-carboxyethyl)-5-methyl-4-isoxazolyl]propionic acid (ACMP, 2......-isoxazolyl]propionic acid (AMOA). Using these AMPA receptor ligands as leads, a series of compounds have been developed as tools for further elucidation of the structural requirements for activation and blockade of AMPA receptors. The synthesized compounds have been tested for activity at ionotropic...

  15. AMPA receptor ligands

    DEFF Research Database (Denmark)

    Strømgaard, Kristian; Mellor, Ian

    2004-01-01

    Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPAR), subtype of the ionotropic glutamate receptors (IGRs), mediate fast synaptic transmission in the central nervous system (CNS), and are involved in many neurological disorders, as well as being a key player in the f......Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPAR), subtype of the ionotropic glutamate receptors (IGRs), mediate fast synaptic transmission in the central nervous system (CNS), and are involved in many neurological disorders, as well as being a key player...... in the formation of memory. Hence, ligands affecting AMPARs are highly important for the study of the structure and function of this receptor, and in this regard polyamine-based ligands, particularly polyamine toxins, are unique as they selectively block Ca2+ -permeable AMPARs. Indeed, endogenous intracellular...

  16. 4-[(2-Hydroxy-4-pentadecyl-benzylidene-amino]-benzoic Acid Methyl Ester

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    Gadada Naganagowda

    2013-11-01

    Full Text Available A new Schiff base, 4-[(2-hydroxy-4-pentadecyl-benzylidene-amino]-benzoic acid methyl ester was synthesized and its UV, IR, 1H-NMR, 13C-NMR and ESI-MS spectroscopic data are presented.

  17. Crystal structure of 2-amino-4-methyl-pyridin-1-ium (2R,3R)-3-carb-oxy-2,3-di-hydroxy-propano-ate monohydrate.

    Science.gov (United States)

    Jovita, J V; Sathya, S; Usha, G; Vasanthi, R; Ramanand, A

    2014-09-01

    The title mol-ecular salt, C6H9N2 (+)·C4H5O6 (-)·H2O, crystallized with two 2-amino-4-methyl-pyridin-1-ium cations, two l-(+)-tartaric acid monoanions [systematic name: (2R,3R)-3-carb-oxy-2,3-di-hydroxy-propano-ate] and two water mol-ecules in the asymmetric unit. In the crystal, the cations, anions and water mol-ecules are linked via a number of O-H⋯O and N-H⋯O hydrogen bonds, and a C-H⋯O hydrogen bond, forming a three-dimensional structure.

  18. Role of spinal cord alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors in complete Freund's adjuvant-induced inflammatory pain

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    Shih Ming-Hung

    2008-12-01

    Full Text Available Abstract Spinal cord α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs mediate acute spinal processing of nociceptive and non-nociceptive information, but whether and how their activation contributes to the central sensitization that underlies persistent inflammatory pain are still unclear. Here, we examined the role of spinal AMPARs in the development and maintenance of complete Freund's adjuvant (CFA-induced persistent inflammatory pain. Intrathecal application of two selective non-competitive AMPAR antagonists, CFM-2 (25 and 50 μg and GYKI 52466 (50 μg, significantly attenuated mechanical and thermal hypersensitivities on the ipsilateral hind paw at 2 and 24 h post-CFA injection. Neither CFM-2 nor GYKI 52466 affected the contralateral basal responses to thermal and mechanical stimuli. Locomotor activity was not altered in any of the drug-treated animals. CFA-induced inflammation did not change total expression or distribution of AMPAR subunits GluR1 and GluR2 in dorsal horn but did alter their subcellular distribution. The amount of GluR2 was markedly increased in the crude cytosolic fraction and decreased in the crude membrane fraction from the ipsilateral L45 dorsal horn at 24 h (but not at 2 h post-CFA injection. Conversely, the level of GluR1 was significantly decreased in the crude cytosolic fraction and increased in the crude membrane fraction from the ipsilateral L45 dorsal horn at 24 h (but not at 2 h post-CFA injection. These findings suggest that spinal AMPARs might participate in the central spinal mechanism of persistent inflammatory pain.

  19. Synthesis, spectral and thermal studies of some dioxouranium(VI) coordination compounds of 4[N -( 4- hydroxy -3- methoxybenzalidene ) amino] antipyrine semicarbazone and 4[N-(3,4,5- trimethoxybenzalidene) amino] antipyrine semicarbazone

    International Nuclear Information System (INIS)

    Singh, Lakshman; Singh, U.P.; Chakraborti, Indranil

    2001-01-01

    In view of high coordination compounds formed by actinide metal ions, the present work describes the 8, 9 and 10-coordinated compounds of dioxouranium(IV) with 4[N-(4-hydroxy-3-methoxy-benzalidene) amino] antipyrine semicarbazone (HMBAAPS) and 4[N-(3,4,5-trimethoxybenzalidene) amino] antipyrine semicarbazone (TMBAAPS) with the general composition UO 2 X 2 .L (X = Br - , I - , NCS - or ClO 4 ) and UO 2 X 2 .L (X = NO 3 - or CH 3 COO - , and L HMBAAPS or TMBAAPS). All these complexes were characterized through elemental, spectral and thermal studies. (author)

  20. LOCALIZATION OF NMDA AND AMPA RECEPTORS IN RAT BARREL FIELD

    NARCIS (Netherlands)

    JAARSMA, D; SEBENS, JB; KORF, J

    1991-01-01

    The aim of this study was to asses the distribution of N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-S-methyl-4-isoxazole propionic acid (AMPA) receptors in the barrel field of rat primary somatosensory (SI) cortex using light-microscopic in vitro autoradiography. NMDA receptors were labeled

  1. Hippocampal GluA1-containing AMPA receptors mediate context-dependent sensitization to morphine

    OpenAIRE

    Xia, Yan; Portugal, George S.; Fakira, Amanda K.; Melyan, Zara; Neve, Rachael; Lee, H. Thomas; Russo, Scott J.; Liu, Jie; Morón, Jose A.

    2011-01-01

    Glutamatergic systems, including α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) are involved in opiate-induced neuronal and behavioral plasticity, although the mechanisms underlying these effects are not fully understood. In the present study, we investigated the effects of repeated morphine administration on AMPAR expression, synaptic plasticity, and context-dependent behavioral sensitization to morphine. We found that morphine treatment produced changes of synaptic...

  2. The respective N-hydroxypyrazole analogues of the classical glutamate receptor ligands ibotenic acid and (RS)-2-amino-2-(3-hydroxy-5-methyl-4-isoxazolyl)acetic acid

    DEFF Research Database (Denmark)

    Clausen, Rasmus P; Hansen, Kasper B; Calí, Patrizia

    2004-01-01

    We have determined the pharmacological activity of N-hydroxypyrazole analogues (3a and 4a) of the classical glutamate receptor ligands ibotenic acid and (RS)-2-amino-2-(3-hydroxy-5-methyl-4-isoxazolyl)acetic acid (AMAA), as well as substituted derivatives of these two compounds. The pharmacological...... partial agonism to antagonism with increasing substituent size, substitution abolishes affinity for mglu1 and mglu4 receptors. Ligand- and receptor-based modelling approaches assist in explaining these pharmacological trends among the metabotropic receptors and suggest a mechanism of partial agonism...

  3. Synthesis and pharmacology of 3-isoxazolol amino acids as selective antagonists at group I metabotropic glutamic acid receptors

    DEFF Research Database (Denmark)

    Madsen, U; Bräuner-Osborne, H; Frydenvang, Karla Andrea

    2001-01-01

    Using ibotenic acid (2) as a lead, two series of 3-isoxazolol amino acid ligands for (S)-glutamic acid (Glu, 1) receptors have been developed. Whereas analogues of (RS)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid [AMPA, (RS)-3] interact selectively with ionotropic Glu receptors (i......GluRs), the few analogues of (RS)-2-amino-3-(3-hydroxy-5-isoxazolyl)propionic acid [HIBO, (RS)-4] so far known typically interact with iGluRs as well as metabotropic Glu receptors (mGluRs). We here report the synthesis and pharmacology of a series of 4-substituted analogues of HIBO. The hexyl analogue 9 was shown...... to originate in (S)-11 (EC(50) = 395 microM, K(b) = 86 and 90 microM, respectively). Compound 9, administered icv, but not sc, was shown to protect mice against convulsions induced by N-methyl-D-aspartic acid (NMDA). Compounds 9 and 11 were resolved using chiral HPLC, and the configurational assignments...

  4. Amino acid derivatives are substrates or non-transported inhibitors of the amino acid transporter PAT2 (slc36a2).

    Science.gov (United States)

    Edwards, Noel; Anderson, Catriona M H; Gatfield, Kelly M; Jevons, Mark P; Ganapathy, Vadivel; Thwaites, David T

    2011-01-01

    The H(+)-coupled amino acid transporter PAT2 (SLC36A2) transports the amino acids proline, glycine, alanine and hydroxyproline. A physiological role played by PAT2 in amino acid reabsorption in the renal proximal tubule is demonstrated by mutations in SLC36A2 that lead to an iminoglycinuric phenotype (imino acid and glycine uria) in humans. A number of proline, GABA and tryptophan derivatives were examined to determine if they function either as transported substrates or non-transported inhibitors of PAT2. The compounds were investigated following heterologous expression of rat PAT2 in Xenopus laevis oocytes. PAT2 function was characterised by: radiotracer uptake and competition (cis-inhibition) studies; radiotracer efflux and trans-stimulation; and measurement of substrate-induced positive inward current by two-electrode voltage-clamp. In general, the proline derivatives appeared to be transported substrates and the relative ability to induce current flow was closely related to the inhibitory effects on PAT2-mediated l-[(3)H]proline uptake. In contrast, certain heterocyclic GABA derivatives (e.g. l-pipecolic acid) were translocated only slowly. Finally, the tryptophan derivatives inhibited PAT2 function but did not undergo transport. l-Proline uptake was inhibited by 5-hydroxy-l-tryptophan (IC(50) 1.6±0.4mM), α-methyl-d,l-tryptophan (3.5±1.5mM), l-tryptophan, 1-methyl-l-tryptophan and indole-3-propionic acid. Although neither 5-hydroxy-l-tryptophan nor α-methyl-d,l-tryptophan were able to elicit inward current in PAT2-expressing oocytes both reduced the current evoked by l-proline. 5-Hydroxy-l-tryptophan and α-methyl-d,l-tryptophan were unable to trans-stimulate l-proline efflux from PAT2-expressing oocytes, confirming that the two compounds act as non-transported blockers of PAT2. These two tryptophan derivatives should prove valuable experimental tools in future investigations of the physiological roles of PAT2. Copyright © 2010 Elsevier B.V. All rights

  5. 7-{[2-(4-Hydroxyphenylmethylidene]amino}-1,3-thiazol-4-yl-2-(methoxyiminoacetyl]amino}-3-{[(2-methyl-5,6-dioxo-1,2,5,6-tetrahydro-1,2,4-triazin-3-ylsulfanyl]methyl}-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic Acid

    Directory of Open Access Journals (Sweden)

    Ghulam Fareed

    2012-05-01

    Full Text Available Novel 7-{[2-(4-hydroxyphenylmethylidene]amino}-1,3-thiazol-4-yl-2-(methoxyiminoacetyl]amino}-3-{[(2-methyl-5,6-dioxo-1,2,5,6-tetrahydro-1,2,4-triazin-3-ylsulfanyl]methyl}-8-oxo-5-thia-1azabicyclo [4.2.0]oct-2-ene-2-carboxylic acid was prepared by condensation of ceftriaxone disodium (1 with 4-hydroxybenzaldehyde (2 in ethanol under reflux conditions for 34 h. The structure of synthesized compound was elucidated using LCMS, 1H-NMR, and CHN techniques.

  6. Synthesis and structure-activity studies on acidic amino acids and related diacids as NMDA receptor ligands

    DEFF Research Database (Denmark)

    Johansen, T N; Frydenvang, Karla Andrea; Ebert, B

    1994-01-01

    The 3-isoxazolol amino acids (S)-2-amino-3-(3-hydroxy-5-methyl-4- isoxazolyl)propionic acid [(S)-AMPA, 2] and (R,S)-2-amino-2-(3-hydroxy-5-methyl-4-isoxazolyl)acetic acid (AMAA, 5a) (Figure 1) are potent and specific agonists at the AMPA and N-methyl-D-aspartic acid (NMDA) subtypes, respectively......, of (S)-glutamic acid (1) receptors. A number of amino acids and diacids structurally related to AMAA were synthesized and tested electrophysiologically and in receptor-binding assays. The hydroxymethyl analogue 7c of AMAA was an NMDA agonist approximately equipotent with AMAA in the [3H...... by molecular mechanics calculations. Compound 7a possesses extra steric bulk and shows significant restriction of conformational flexibility compared to AMAA and 7c, which may be determining factors for the observed differences in biological activity. Although the nitrogen atom of quinolinic acid (6) has very...

  7. Stability constant for thorium(IV) complexes with aryl bis-(5-hydroxy-3-methyl-1-phenyl-4-pyrazolyl)-methane ligands

    Energy Technology Data Exchange (ETDEWEB)

    Stefan, L.S. [Ain Shams Univ., Cairo (Egypt)

    1995-09-01

    Chelate stability constants of aryl bis(5-hydroxy-3-methyl-1-phenyl-4-pyrazolyl)methane (ABPM) derivatives with thorium(IV) ion were determined by the potentiometric method at 30 C and 0.1 mol dm{sup -3} (KNO{sub 3}) in 75% (v/v) dioxane-water solvent. The computation of the titration data indicated that four kinds of complexes [ThL]{sup 2+}, [ThL(OH)]{sup +}, [ThL{sub 2}] and [ThL(OH){sub 2}] were formed. The appropriate formation constants for all of the 1:1 species and 2:1 complexes have been calculated are probable ligand-banding sites of the complexes were proposed. In addition, the applicability of the Hammett equation for correlation of the stability constants of [Th(IV)-ABPM] complexes was discussed. (author). 19 refs, 5 figs, 1 tab.

  8. Stability constant for thorium(IV) complexes with aryl bis-(5-hydroxy-3-methyl-1-phenyl-4-pyrazolyl)-methane ligands

    International Nuclear Information System (INIS)

    Stefan, L.S.

    1995-01-01

    Chelate stability constants of aryl bis(5-hydroxy-3-methyl-1-phenyl-4-pyrazolyl)methane (ABPM) derivatives with thorium(IV) ion were determined by the potentiometric method at 30 C and 0.1 mol dm -3 (KNO 3 ) in 75% (v/v) dioxane-water solvent. The computation of the titration data indicated that four kinds of complexes [ThL] 2+ , [ThL(OH)] + , [ThL 2 ] and [ThL(OH) 2 ] were formed. The appropriate formation constants for all of the 1:1 species and 2:1 complexes have been calculated are probable ligand-banding sites of the complexes were proposed. In addition, the applicability of the Hammett equation for correlation of the stability constants of [Th(IV)-ABPM] complexes was discussed. (author). 19 refs, 5 figs, 1 tab

  9. Distribution of radiolabeled 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride in rat brain tumor: intraarterial versus intravenous administration

    International Nuclear Information System (INIS)

    Yamada, K.; Ushio, Y.; Hayakawa, T.; Arita, N.; Huang, T.Y.; Nagatani, M.; Yamada, N.; Mogami, H.

    1987-01-01

    To assess the rationale of intraarterial (i.a.) 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea chemotherapy, distribution of 14 C-labeled 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea in rat glioma was studied after i.a. or i.v. infusion. Immediately after infusion, the tumor located in the hemisphere of intracarotid infusion received 4.6-fold higher radioactivity than the tumor located contralaterally to intracarotid infusion and 2.8-fold higher radioactivity than i.v. infusion. The difference was kept up to 30 min after i.a. infusion. Autoradiographic observation indicated rather uniform distribution of the tracer in the central portion of i.a. infusion. However, in the periphery of i.a. infusion, distribution of the tracer was nonhomogenous. The results indicate that i.a. 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea chemotherapy is useful when the tumor has high blood flow and is located in the center of an infused area

  10. Deoxyiminoalditols from Aldonic Acids - VI. - Preparation of the Four Stereoisomeric 4-Amino-3-hydroxypyrrolidines from Bromodeoxytetronic Acids. Discovery of a New alfa-Mannosidase Inhibitor

    DEFF Research Database (Denmark)

    Lundt, Inge; Limberg, Gerrit; Zavilla, John

    1999-01-01

    A convenient four step synthesis of amino hydroxy pyrrolidines is presented. From the readily available D- and L-tetronic acids the four possible stereoisomeric 4-amino-3-hydroxy pyrrolidines 14, 15, 17 and 19 could be accessed as crystalline compounds, avoiding any chromatographic purification....... The key step in the reactions was the regioselective formation of either the 2,4-diamino-2,4-dideoxy-D-threono-1,4-lactam (5) or the 3,4-diamino-3,4-dideoxy-L-erythrono-1,4-lactam (10) by treatment of the methyl 4-bromo-4-deoxy-2,3-cis- 3 or 2,3-trans- 9 epoxy tetronates, respectively, with liquid ammonia....... Thus, opposite regioselectivity for opening of the cis-configurated epoxide 3 (4 : 1, C-2 : C-3) and the trans-configurated epoxide 9 (3 : 7, C-2 : C-3) by ammonia was observed. - Initial testing as glycosidase inhibitors of the amino hydroxy pyrrolidines formed by reduction of the lactams showed...

  11. Positron emission tomographic studies on aromatic L-amino acid decarboxylase activity in vivo for L-dopa and 5-hydroxy-L-tryptophan in the monkey brain

    Energy Technology Data Exchange (ETDEWEB)

    Hartvig, P; Tedroff, J; Lindner, K J; Bjurling, P; Chang, C W; Laangstroem, B [Uppsala Univ. (Sweden); Tsukada, H [Central Research Lab., Hamamatsu Photonics Shizuoka, Osaka (Japan); Watanabe, Y [Dept. of Neuroscience, Osaka Bioscience Inst., Osaka (Japan)

    1993-01-01

    The regional brain kinetics following 5-hydroxy-L-([beta]-11 C)tryptophan and L-([beta]-11 C)DOPA intravenous injection was measured in twelve Rhesus monkeys using positron emission tomography (PET). The radiolabelled compounds were also injected together with various doses of unlabelled 5-hydroxy-L-tryptophan or L-DOPA. The radioactivity accumulated in the striatal region and the rate of increased utilization with time was calculated using a graphical method with back of the brain as a reference region. The rate constants for decarboxylation were 0.0070 [+-] 0.0007 (S. D) and 0.0121 [+-] 0.0010 min[sup -1] for 5-hydroxy-L-([beta]-11 C)tryptophan and L-([beta]-11 C)DOPA, respectively. After concomitant injection with unlabelled 5-hydroxy-L-tryptophan, the rate constant of 5-hydroxy-L-([beta]-11 C)tryptophan decreased dose-dependently and a 50 percent reduction was seen with a dose of about 4 mg/kg of unlabelled compound. A decreased utilization rate of L-([beta]-11 C)DOPA was seen only after simultaneous injection of 30 mg/kg of either L-DOPA or 5-hydroxy-L-tryptophan. This capacity limitation was most likely interpreted as different affinity of the striatal aromatic amino acid decarboxylase for L-DOPA and 5-hydroxy-L-tryptophan, respectively.

  12. Properties of GluR3 receptors tagged with GFP at the amino or carboxyl terminus.

    Science.gov (United States)

    Limon, Agenor; Reyes-Ruiz, Jorge Mauricio; Eusebi, Fabrizio; Miledi, Ricardo

    2007-09-25

    Anatomical visualization of neurotransmitter receptor localization is facilitated by tagging receptors, but this process can alter their functional properties. We have evaluated the distribution and properties of WT glutamate receptor 3 (GluR3) alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (WT GluR3) and two receptors in which GFP was tagged to the amino terminus (GFP-GluR3) or to the carboxyl terminus (GluR3-GFP). Although the fluorescence in Xenopus oocytes was stronger in the vegetal hemisphere because of localization of internal structures (probable sites of production, storage or recycling of receptors), the insertion of receptors into the plasma membrane was polarized to the animal hemisphere. The fluorescence intensity of oocytes injected with GluR3-GFP RNA was approximately double that of oocytes injected with GFP-GluR3 RNA. Accordingly, GluR3-GFP oocytes generated larger kainate-induced currents than GFP-GluR3 oocytes, with similar EC(50) values. Currents elicited by glutamate, or AMPA coapplied with cyclothiazide, were also larger in GluR3-GFP oocytes. The glutamate- to kainate-current amplitude ratios differed, with GluR3-GFP being activated more efficiently by glutamate than the WT or GFP-GluR3 receptors. This pattern correlates with the slower decay of glutamate-induced currents generated by GluR3-GFP receptors. These changes were not observed when GFP was tagged to the amino terminus, and these receptors behaved like the WT. The antagonistic effects of 6-nitro-7-sulfamoylbenzo[f]quinoxaline-2,3-dione (NBQX) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) were not altered in any of the tagged receptors. We conclude that GFP is a useful and convenient tag for visualizing these proteins. However, the effects of different sites of tag insertion on receptor characteristics must be taken into account in assessing the roles played by these receptor proteins.

  13. Measuring urinary N-acetyl-S-(4-hydroxy-2-methyl-2-buten-1-yl)-L-cysteine (IPMA3) as a potential biomarker of isoprene exposure.

    Science.gov (United States)

    Alwis, K Udeni; Bailey, T Liz; Patel, Dhrusti; Wang, Liqun; Blount, Benjamin C

    2016-10-19

    Isoprene, the 2-methyl analog of 1,3-butadiene, is identified as a possible human carcinogen by the International Agency for Research on Cancer (IARC). Isoprene is ubiquitous in the environment with numerous natural and anthropogenic sources. Tobacco smoke is the main exogenous source of isoprene exposure in indoor environments. Among smoke constituents, isoprene is thought to contribute significantly to cancer risk; however, no selective urinary biomarkers of isoprene exposure have been identified for humans. In this manuscript, we measured the minor isoprene metabolite IPMA1 (mixture of N-acetyl-S-(1-[hydroxymethyl]-2-methyl-2-propen-1-yl)-L-cysteine and N-acetyl-S-(2-hydroxy-3-methyl-3-buten-1-yl)-L-cysteine), and we identified IPMA3 (N-acetyl-S-(4-hydroxy-2-methyl-2-buten-1-yl)-L-cysteine) as a major isoprene metabolite and novel isoprene exposure biomarker for humans. Urinary isoprene metabolites were measured using ultra high performance liquid chromatography coupled with electrospray ionization triple quad tandem mass spectrometry (UPLC/ESI-MSMS). The detection rates of IPMA1 and IPMA3 are <20% and 82%, respectively. The selectivity and abundance of IPMA3 make it a useful urinary biomarker of isoprene exposure. The limit of detection of IPMA3 in urine was 0.5 ng mL -1 . IPMA3 was stable under different storage temperatures and following ten freeze-thaw cycles. The average recovery of urine spiked with IPMA3 at three different levels was 99%. IPMA3 was measured in urine samples received from 75 anonymous subjects; the median (25th percentile, 75th percentile) IPMA3 level in smokers was 36.2 (18.2, 56.8) ng mL -1 and non-smokers 2.31 (2.31, 4.38) ng mL -1 . Application of this method to large population studies will help to characterize isoprene exposure and assess potential health impact. Published by Elsevier B.V.

  14. Piracetam defines a new binding site for allosteric modulators of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors.

    Science.gov (United States)

    Ahmed, Ahmed H; Oswald, Robert E

    2010-03-11

    Glutamate receptors are the most prevalent excitatory neurotransmitter receptors in the vertebrate central nervous system and are important potential drug targets for cognitive enhancement and the treatment of schizophrenia. Allosteric modulators of AMPA receptors promote dimerization by binding to a dimer interface and reducing desensitization and deactivation. The pyrrolidine allosteric modulators, piracetam and aniracetam, were among the first of this class of drugs to be discovered. We have determined the structure of the ligand binding domain of the AMPA receptor subtypes GluA2 and GluA3 with piracetam and a corresponding structure of GluA3 with aniracetam. Both drugs bind to GluA2 and GluA3 in a very similar manner, suggesting little subunit specificity. However, the binding sites for piracetam and aniracetam differ considerably. Aniracetam binds to a symmetrical site at the center of the dimer interface. Piracetam binds to multiple sites along the dimer interface with low occupation, one of which is a unique binding site for potential allosteric modulators. This new site may be of importance in the design of new allosteric regulators.

  15. 1-[3-(2-Methyl-4-phenylquinolin-3-yl-5-phenyl-4,5-dihydro-1H-pyrazol-1-yl]-propane-1-one

    Directory of Open Access Journals (Sweden)

    Allaoua Kedjadja

    2015-06-01

    Full Text Available A novel compound, 1-[3-(2-methyl-4-phenylquinolin-3-yl-5-phenyl-4,5-dihydro-1H-pyrazol-1-yl]-propane-1-one (3 has been synthesized by cyclocondensation of (E-1-(2-methyl-4-phenylquinolin-3-yl-3-phenylprop-2-en-1-one (2 and hydrazine hydrate in propionic acid. The structure of this compound was established by elemental analysis, IR, 1H-NMR, 13C-NMR and MS data.

  16. Interactions of neurotoxins with non-NMDA glutamate receptors: an autoradiographic study

    International Nuclear Information System (INIS)

    Kuenig, G.; Niedermeyer, B.; Krause, F.; Hartmann, J.; Deckert, J.; Heinsen, H.; Beckmann, H.; Riederer, P.; Ransmayr, G.

    1994-01-01

    Neurotoxic substances are discussed to cause neurode-generation by acting as excitotoxins on glutamate receptors. We investigated the properties of L-beta-oxalyl-amino-alanine (L-BOAA) and 3,4,6-trihydroxyphenlyalanine (6-OH-Dopa) at the alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) glutamate receptor and that of L-BOAA and domoic acid at the kainate glutamate receptor in human hippocampus. (3 H)AMPA binding in hippocampal subfields was inhibited by L-BOAA and 6-OH-Dopa with mean IC50-values in the low micromolar range. (3H)Kainate binding was inhibited by L-BOAA with similar potency as (3H)AMPA binding and by domoic acid with mean IC50-values in the low nanomolar range. These results support the notion that symptoms like anterograde amnesia and epileptic seizures seen in domoic acid intoxication and limbic symptoms, e.g. cognitive and mood impairment observed in neurolathyrism may be caused by excitotoxic action on non-NMDA receptors. The potent interaction of 6-OH-Dopa with the AMPA-receptor may point to a possible dopaminergic-glutamatergic interaction in the development of neurodegenerative diseases like Parkinson's and Huntington's disease. (author)

  17. 5-Methyl-3,8-di-(2-amino-4-bromophenyl-4,9-dioxa-1,2,6,7-tetraaza-5λ5-phosphaspiro[4.4]nona-2,7-diene

    Directory of Open Access Journals (Sweden)

    Sławomir Kasperowicz

    2018-01-01

    Full Text Available 5-Methyl-3,8-di-(2-amino-4-bromophenyl-4,9-dioxa-1,2,6,7-tetraaza-5λ5-phosphaspiro[4.4]nona-2,7-diene was obtained by condensation of 2-amino-5-bromobenzohydrazide and methylphosphonyl dichloride in the presence of triethylamine. An initial biological screening was performed for the resulting product. The synthesized compound showed relatively strong cytotoxic activity, which was, however, similar for cancer and non-cancer cell lines.

  18. Piracetam Defines a New Binding Site for Allosteric Modulators of α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors§

    Science.gov (United States)

    Ahmed, Ahmed H.; Oswald, Robert E.

    2010-01-01

    Glutamate receptors are the most prevalent excitatory neurotransmitter receptors in the vertebrate central nervous system and are important potential drug targets for cognitive enhancement and the treatment of schizophrenia. Allosteric modulators of AMPA receptors promote dimerization by binding to a dimer interface and reducing desensitization and deactivation. The pyrrolidine allosteric modulators, piracetam and aniracetam, were among the first of this class of drugs to be discovered. We have determined the structure of the ligand binding domain of the AMPA receptor subtypes GluA2 and GluA3 with piracetam and a corresponding structure of GluA3 with aniracetam. Both drugs bind to both GluA2 and GluA3 in a very similar manner, suggesting little subunit specificity. However, the binding sites for piracetam and aniracetam differ considerably. Aniracetam binds to a symmetrical site at the center of the dimer interface. Piracetam binds to multiple sites along the dimer interface with low occupation, one of which is a unique binding site for potential allosteric modulators. This new site may be of importance in the design of new allosteric regulators. PMID:20163115

  19. The first 3':5'-cyclic nucleotide-amino acid complex: L-His-cIMP.

    Science.gov (United States)

    Slepokura, Katarzyna

    2012-08-01

    In the crystal structure of the L-His-cIMP complex, i.e. L-histidinium inosine 3':5'-cyclic phosphate [systematic name: 5-(2-amino-2-carboxyethyl)-1H-imidazol-3-ium 7-hydroxy-2-oxo-6-(6-oxo-6,9-dihydro-1H-purin-9-yl)-4a,6,7,7a-tetrahydro-4H-1,3,5,2λ(5)-furo[3,2-d][1,3,2λ(5)]dioxaphosphinin-2-olate], C(6)H(10)N(3)O(2)(+)·C(10)H(10)N(4)O(7)P(-), the Hoogsteen edge of the hypoxanthine (Hyp) base of cIMP and the Hyp face are engaged in specific amino acid-nucleotide (His···cIMP) recognition, i.e. by abutting edge-to-edge and by π-π stacking, respectively. The Watson-Crick edge of Hyp and the cIMP phosphate group play a role in nonspecific His···cIMP contacts. The interactions between the cIMP anions (anti/C3'-endo/trans-gauche/chair conformers) are realized mainly between riboses and phosphate groups. The results for this L-His-cIMP complex, compared with those for the previously reported solvated L-His-IMP crystal structure, indicate a different nature of amino acid-nucleotide recognition and interactions upon the 3':5'-cyclization of the nucleotide phosphate group.

  20. The antidepressant tianeptine reverts synaptic AMPA receptor defects caused by deficiency of CDKL5.

    Science.gov (United States)

    Tramarin, Marco; Rusconi, Laura; Pizzamiglio, Lara; Barbiero, Isabella; Peroni, Diana; Scaramuzza, Linda; Guilliams, Tim; Cavalla, David; Antonucci, Flavia; Kilstrup-Nielsen, Charlotte

    2018-06-15

    Mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene cause a complex neurological disorder, characterized by infantile seizures, impairment of cognitive and motor skills and autistic features. Loss of Cdkl5 in mice affects dendritic spine maturation and dynamics but the underlying molecular mechanisms are still far from fully understood. Here we show that Cdkl5 deficiency in primary hippocampal neurons leads to deranged expression of the alpha-amino-3-hydroxy-5-methyl-4-iso-xazole propionic acid receptors (AMPA-R). In particular, a dramatic reduction of expression of the GluA2 subunit occurs concomitantly with its hyper-phosphorylation on Serine 880 and increased ubiquitination. Consequently, Cdkl5 silencing skews the composition of membrane-inserted AMPA-Rs towards the GluA2-lacking calcium-permeable form. Such derangement is likely to contribute, at least in part, to the altered synaptic functions and cognitive impairment linked to loss of Cdkl5. Importantly, we find that tianeptine, a cognitive enhancer and antidepressant drug, known to recruit and stabilise AMPA-Rs at the synaptic sites, can normalise the expression of membrane inserted AMPA-Rs as well as the number of PSD-95 clusters, suggesting its therapeutic potential for patients with mutations in CDKL5.

  1. 2-Amino-1-methyl-6-(5-hydroxy-)phenylimidazo[4,5-b]pyridine (5-OH-PhIP), a biomarker for the genotoxic dose of the heterocyclic amine, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)

    DEFF Research Database (Denmark)

    Frandsen, H; Frederiksen, H; Alexander, J

    2002-01-01

    2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a mutagenic and carcinogenic heterocyclic amine formed during ordinary cooking. PhIP is metabolically activated by CYP P450 mediated N-hydroxylation followed by phase II esterification. The ultimate mutagenic metabolite reacts with DNA...

  2. β-N-oxalyl-L-α, β- diaminopropionic acid induces HRE expression by inhibiting HIF-prolyl hydroxylase-2 in normoxic conditions.

    Science.gov (United States)

    Eslavath, Ravi Kumar; Sharma, Deepshikha; Bin Omar, Nabil A M; Chikati, Rajasekhar; Teli, Mahesh Kumar; Rajanikant, G K; Singh, Surya S

    2016-11-15

    Hypoxia inducible factor (HIF)-1α, a subunit of HIF transcription factor, regulates cellular response to hypoxia. In normoxic conditions, it is hydroxylated by prolyl hydroxylase (PHD)-2 and targeted for proteosomal degradation. Drugs which inhibit PHD-2 have implications in conditions arising from insufficient blood supply. β-ODAP (β-N- oxalyl-L-α, β- diaminopropionic acid), a non-protein excitatory amino acid present in Lathyrus sativus, is an α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor agonist known to activate conventional protein kinase C and stabilize HIF-1α under normoxic conditions. However, the mechanism of HIF-1α stabilization by this compound is unknown. In silico approach was used to understand the mechanism of stabilization of HIF-1α which revealed β-ODAP interacts with key amino acid residues and Fe 2+ at the catalytic site of PHD-2. These results were further corroborated with luciferase HRE (hypoxia response element) reporter system in HeLa cells. Different chemical modulators of PHD-2 activity and HIF-1α levels were included in the study for comparison. Results obtained indicate that β-ODAP inhibits PHD-2 and facilitates HIF dependent HRE expression and hence, might be helpful in conditions arising from hypoxia. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. A new structural class of subtype-selective inhibitor of cloned excitatory amino acid transporter, EAAT2

    DEFF Research Database (Denmark)

    Bräuner-Osborne, Hans; Hermit, M B; Nielsen, B

    2000-01-01

    We have studied the pharmacological effects of (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) and the enantiomers of (RS)-2-amino-3-(3-hydroxy-1,2, 5-thiadiazol-4-yl)propionic acid (TDPA) on cloned human excitatory amino acid transporter subtypes 1, 2 and 3 (EAAT1......-3) expressed in Cos-7 cells. Whereas AMPA and (R)-TDPA were both inactive as inhibitors of [3H]-(R)-aspartic acid uptake on all three EAAT subtypes, (S)-TDPA was shown to selectively inhibit uptake by EAAT2 with a potency equal to that of the endogenous ligand (S)-glutamic acid. (S)-TDPA thus represents a new...

  4. Novel One-Pot Access to 3,3-bis(3-hydroxy-5-substituted-1H-pyrazol-4-yl) indolin-2-ones

    International Nuclear Information System (INIS)

    Lin, Y.; Fu, Z.; Song, Q.; Shen, T.

    2016-01-01

    Sodium bicarbonate was applied as catalyst for the synthesis of 3,3-bis(3-hydroxy-5-substituted-1H-pyrazol-4-yl)indolin-2-ones via the reaction of isatins, hydrazine hydrate and ethyl acetoacetate or ethyl benzoylacetate. This reaction was performed in ethanol at 78 degree C, giving 3,3-bis(3-hydroxy-5-substituted-1H-pyrazol-4-yl)indolin-2-one derivatives in good to excellent yields. The structure of 5-bromo-3,3-bis(3-hydroxy-5-methyl-1H-pyrazol-4-yl) indolin-2-one was unambiguously confirmed by X-ray single crystal structure analysis and a plausible reaction mechanism is also proposed. (author)

  5. N-acetyltransferase-dependent activation of 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine: formation of 2-amino-1-methyl-6-(5-hydroxy)phenylimidazo [4,5-b]pyridine, a possible biomarker for the reactive dose of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine

    DEFF Research Database (Denmark)

    Frandsen, Henrik Lauritz; Alexander, J.

    2000-01-01

    2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a mutagenic and carcinogenic heterocyclic amine formed during ordinary cooking. PhIP is metabolically activated to the ultimate mutagenic metabolite by CYP P450-mediated N-hydroxylation followed by phase II esterification, Incubation of N...

  6. Crystal and molecular structures of 3-amino-4-hydroxy benzenesulfonamide and its hydrochloride: Quantum-chemical study of their tautomerism

    Energy Technology Data Exchange (ETDEWEB)

    Kovalchukova, O. V., E-mail: okovalchukova@mail.ru; Strashnova, S. B.; Romashkina, E. P.; Strashnov, P. V.; Zaitsev, B. E. [Peoples' Friendship University of Russia (Russian Federation); Sergienko, V. S. [Russian Academy of Sciences, Kurnakov Institute of General and Inorganic Chemistry (Russian Federation)

    2013-03-15

    3-amino-4-hydroxy benzenesulfonamide and its hydrochloride have been isolated in the crystalline state. Their crystal and molecular structures are determined by X-ray diffraction. The equilibrium between neutral tautomeric forms of the 3-amino-4-hydroxy benzenesulfonamide molecule is studied within the approximation of density functional theory (B3LYP/aug-cc-pVDZ). The constants of acid-base equilibrium of 3-amino-4-hydroxy benzenesulfonamide are deter-mined using spectrophotometry.

  7. Biochemical characterization of an autoradiographic method for studying excitatory amino acid receptors using L-[3H]glutamate

    International Nuclear Information System (INIS)

    Cincotta, M.; Summers, R.J.; Beart, P.M.

    1989-01-01

    A method was developed for radiolabeling excitatory amino acid receptors of rat brain with L-[ 3 H]glutamate. Effective labeling of glutamate receptors in slide-mounted 10-microns sections was obtained using a low incubation volume (0.15 ml) and rapid washing: a procedure where high ligand concentrations were achieved with minimal waste. Saturation experiments using [ 3 H]glutamate revealed a single binding site of micromolar affinity. The Bmax was trebled in the presence of Ca2+ (2.5 mM) and Cl- (20 mM) with no change in the Kd. Binding was rapid, saturable, stereospecific, and sensitive to glutamate receptor agonists. The proportions of [ 3 H]glutamate binding sensitive to N-methyl-D-aspartate (NMDA), kainate, and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) were 34, 54, and 51%, respectively. NMDA inhibited binding at a distinct subset of L-[ 3 H]glutamate sites, whereas AMPA and kainate competed for some common sites. Labeling of sections with L-[ 3 H]glutamate in the presence of the selective agonists allowed autoradiographic visualization of glutamate receptor subtypes in brain tissue

  8. Synthesis of formazans from Mannich base of 5-(4-chlorophenyl amino-2-mercapto-1,3,4-thiadiazole as antimicrobial agents

    Directory of Open Access Journals (Sweden)

    Pramilla Sah

    2014-04-01

    Full Text Available 5-(4-Chlorophenyl amino-2-mercapto-1,3,4-thiadiazole (I was refluxed with formaldehyde and ammonium chloride in ethanol yielding the Mannich base 5-(4-chloro phenyl amino-3-aminomethyl-2-mercapto-1,3,4-thiadiazole (II. Esterification with 4-chloro-(2,6-dinitro phenoxy-ethyl acetate (III under anhydrous conditions gave the intermediate (IV. Subsequent hydrazinolysis with hydrazine hydrate gave the corresponding hydrazide 3-amino methyl-5-(4-chloro phenyl amino-2-mercapto-4′-(2′,6′-dinitro phenoxy-acetyl hydrazide (V. The hydrazide was converted into the Schiff bases (VIa–b by reacting with 2-chlorobenzaldehyde and 3-methoxy-4-hydroxy benzaldehyde in presence of methanol containing 2–3 drops of acetic acid. Diazotisation with aromatic amines, sulphanilic acid and sulphur drugs gave the formazans (VIIa–g respectively. Chemical structures have been established by elemental analysis and the spectral techniques of FTIR, 1H NMR and mass. Antimicrobial activity (in vitro was evaluated against the two pathogenic bacterial strains. Escherichia coli and Salmonella typhi, three fungal strains Aspergillus niger, Penicillium species and Candida albicans. The compounds have shown moderate activity.

  9. Concise and Straightforward Asymmetric Synthesis of a Cyclic Natural Hydroxy-Amino Acid

    Directory of Open Access Journals (Sweden)

    Mario J. Simirgiotis

    2014-11-01

    Full Text Available An enantioselective total synthesis of the natural amino acid (2S,4R,5R-4,5-di-hydroxy-pipecolic acid starting from D-glucoheptono-1, 4-lactone is presented. The best sequence employed as a key step the intramolecular nucleophilic displacement by an amino function of a 6-O-p-toluene-sulphonyl derivative of a methyl D-arabino-hexonate and involved only 12 steps with an overall yield of 19%. The structures of the compounds synthesized were elucidated on the basis of comprehensive spectroscopic (NMR and MS and computational analysis.

  10. Synthesis and antimicrobial evaluation of new 3-alkyl/aryl-2-[((alpha,alpha-diphenyl-alpha-hydroxy)acetyl)hydrazono]-5-methyl-4-thiazolidinones.

    Science.gov (United States)

    Güzeldemirci, Nuray Ulusoy; Ilhan, Eser; Küçükbasmaci, Omer; Satana, Dilek

    2010-01-01

    New 4-thiazolidinone derivatives of benzilic acid (alpha,alpha-diphenyl-alpha-hydroxyacetic acid) have been synthesized and evaluated for antibacterial and antifungal activities. The reaction of 1- (alpha,alpha-diphenyl-alpha-hydroxy)acetyl-4-alkyl/arylthiosemicarbazides with ethyl 2-bromopropionate gave 3-alkyl/aryl-2-[((alpha,alpha-diphenyl-alpha-hydroxy)acetyl)hydrazono]-5-methyl-4-thiazolidinone derivatives. Their antibacterial and antifungal activities were evaluated against S. aureus ATCC 29213, P. aeruginosa ATCC 27853, E. coli ATCC 25922, C. albicans ATCC 10231, C. parapsilosis ATCC 22019, C. krusei ATCC 6258, T. mentagrophytes var. erinacei NCPF 375, M. gypseum NCPF 580 and T. tonsurans NCPF 245. 3e, 3f, 3g and 3h showed the highest antibacterial activity. Particularly 3a and 3e showed the highest antifungal activities against C. parapsilosis ATCC 22019, T. tonsurans NCPF 245 and M. gypseum NCPF 580.

  11. 5-[(3-Fluorophenyl(2-hydroxy-6-oxocyclohex-1-en-1-ylmethyl]-6-hydroxy-1,3-dimethylpyrimidine-2,4(1H,3H-dione

    Directory of Open Access Journals (Sweden)

    Assem Barakat

    2016-09-01

    Full Text Available 5-[(3-Fluorophenyl(2-hydroxy-6-oxocyclohex-1-en-1-yl-methyl]-6-hydroxy-1,3-di-methylpyrimidine-2,4(1H,3H-dione 3 was synthesized via a multicomponent reaction. The Aldol–Michael addition reactions of N,N-dimethylbarbituric acid, cyclohexane-1,3-dione, and 3-fluorobenzaldehyde in aqueous solution gave the product in high yield. The molecular structure of the compound was confirmed by spectroscopic methods and X-ray crystallography. The title compound (C19H19FN2O5·H2O crystallizes in the Monoclinic form, P21/c, a = 7.8630 (5 Å, b = 20.0308 (13 Å, c = 11.3987 (8 Å, β = 104.274 (3°, V = 1739.9 (2° Å3, Z = 4, Rint = 0.117, wR(F2 = 0.124, T = 100 K.

  12. Natural 4-Hydroxy-2,5-dimethyl-3(2H)-furanone (Furaneol®)

    OpenAIRE

    Wilfried Schwab

    2013-01-01

    4-Hydroxy-2,5-dimethyl-3(2H)-furanone (HDMF, furaneol®) and its methyl ether 2,5-dimethyl-4-methoxy-3(2H)-furanone (DMMF) are import aroma chemicals and are considered key flavor compounds in many fruit. Due to their attractive sensory properties they are highly appreciated by the food industry. In fruits 2,5-dimethyl-3(2H)-furanones are synthesized by a series of enzymatic steps whereas HDMF is also a product of the Maillard reaction. Numerous methods for the synthetic preparation of these c...

  13. Synthesis and investigation of solvent effects on the ultraviolet absorption spectra of 5-substituted-4-methyl-3-cyano-6-hydroxy-2-pyridones

    Directory of Open Access Journals (Sweden)

    NATASA V. VALENTIC

    2001-08-01

    Full Text Available A number of 5-substituted-4-methyl-3-cyano-6-hydroxy-2-pyridones from cyanoacetamide and the corresponding alkyl ethyl acetoacetates were synthesized according to modified literature procedures. The alkyl ethyl acetoacetates were obtained by the reaction of C-alkylation of ethyl acetoacetate. An investigation of the reaction conditions for the synthesis of 4-methyl-3-cyano-6-hydroxy-2-pyridone from cyanoacetamide and ethyl acetoacetate in eight different solvents was also performed. The ultraviolet absorption spectra of synthesized pyridones were measured in nine different solvents in the range 200–400 nm. The effects of solvent polarity and hydrogen bonding on the absorption spectra are interpreted by means of linear solvation energy relationships using a general equation of the form n = n0 + sp* + aa + bb, where p* is a measure of the solvent polarity, a is the scale of the solvent hydrogen bond donor acidities and b is the scale of the solvent hydrogen bond acceptor basicities.

  14. Excitatory amino acid receptor antagonists

    DEFF Research Database (Denmark)

    Johansen, T N; Frydenvang, Karla Andrea; Ebert, B

    1997-01-01

    We have previously shown that (RS)-2-amino-2-(5-tert-butyl-3-hydroxyisoxazol-4-yl)acetic acid (ATAA) is an antagonist at N-methyl-D-aspartic acid (NMDA) and (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) receptors. We have now resolved ATAA via diastereomeric salt formation......)-phenylethylamine salt of N-BOC-(R)-ATAA. Like ATAA, neither (R)- nor (S)-ATAA significantly affected (IC50 > 100 microM) the receptor binding of tritiated AMPA, kainic acid, or (RS)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid, the latter being a competitive NMDA antagonist. Electrophysiological experiments......, using the rat cortical wedge preparation, showed the NMDA antagonist effect as well as the AMPA antagonist effect of ATAA to reside exclusively in the (R)-enantiomer (Ki = 75 +/- 5 microM and 57 +/- 1 microM, respectively). Neither (R)- nor (S)-ATAA significantly reduced kainic acid-induced excitation...

  15. 4-Hydroxy-3-methyl-6-phenylbenzofuran-2-carboxylic acid ethyl ester derivatives as potent anti-tumor agents.

    Science.gov (United States)

    Hayakawa, Ichiro; Shioya, Rieko; Agatsuma, Toshinori; Furukawa, Hidehiko; Naruto, Shunji; Sugano, Yuichi

    2004-01-19

    Based on the structure of 4-hydroxy-3-methyl-6-phenylbenzofuran-2-carboxylic acid ethyl ester (1), which exhibits selective cytotoxicity against a tumorigenic cell line, (2,4-dimethoxyphenyl)-(4-hydroxy-3-methyl-6-phenylbenzofuran-2-yl)-methanone (18m) was designed and synthesized as a biologically stable derivative containing no ester group. Although the potency of 18m was almost the same as our initial hit compound 1, 18m is expected to last longer in the human body as an anticancer agent.

  16. Potassium phthalimide as efficient basic organocatalyst for the synthesis of 3,4-disubstituted isoxazol-5(4H-ones in aqueous medium

    Directory of Open Access Journals (Sweden)

    Hamzeh Kiyani

    2017-01-01

    Full Text Available Potassium phthalimide (PPI is employed as an efficient and effective basic organocatalyst for the one-pot three-component reaction of β-oxoesters with hydroxylamine hydrochloride and various aromatic aldehydes. This cyclocondensation reaction was performed in water as an environmentally benign solvent at room temperature giving 3,4-disubstituted isoxazol-5(4H-ones in good to excellent yields. PPI was found to be an effective organocatalyst for the synthesis of isoxazol-5(4H-one system. The advantages of this method are efficiency, clean, easy work-up, high yields, shorter reaction times, inexpensive, and readily available catalyst.

  17. Electron impact ionization mass spectra of 3-substituted-2-hydroxy-4(3H)-quinazolinones

    International Nuclear Information System (INIS)

    El Deen, I. M.; Abd El Fattah, M. E.

    2003-01-01

    2-Amino-2-hydroxy-4(3H)-quinazolinone (3) was prepared via condensation of 1 with hydrazine hydrate. Treatment of 3 with appropriate acid in POCl 3 , ethyl chloroacetate and activated olefinic compounds in DMF yielded the corresponding 3-(substituted)amino-2-hydroxy-4(3H)-quinazolinones 4,5 and 6. The electron impact ionization mass spectra of compounds 3 and 4 show a weak molecular ion peak and a base peak of m/z 146 resulting from a cleavage fragmentation. The compounds 5 and 6 give a characteristics fragmentation pattern with a very stable fragment of benzopyrazolone (m/z 132)

  18. Motor Skills Training Enhances α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid Receptor Subunit mRNA Expression in the Ipsilateral Sensorimotor Cortex and Striatum of Rats Following Intracerebral Hemorrhage.

    Science.gov (United States)

    Tamakoshi, Keigo; Ishida, Kazuto; Kawanaka, Kentaro; Takamatsu, Yasuyuki; Tamaki, Hiroyuki

    2017-10-01

    We investigated the effects of acrobatic training (AT) on expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunits in the sensorimotor cortex and striatum after intracerebral hemorrhage (ICH). Male Wistar rats were divided into 4 groups: ICH without AT (ICH), ICH with AT (ICH + AT), sham operation without AT (SHAM), and sham operation with AT (SHAM + AT). ICH was induced by collagenase injection into the left striatum. The ICH + AT group performed 5 acrobatic tasks daily on days 4-28 post ICH. Forelimb sensorimotor function was evaluated using the forelimb placing test. On days 14 and 29, mRNA expression levels of AMPAR subunits GluR1-4 were measured by real-time reverse transcription-polymerase chain reaction. Forelimb placing test scores were significantly higher in the ICH + AT group than in the ICH group. Expression levels of all AMPAR subunit mRNAs were significantly higher in the ipsilateral sensorimotor cortex of rats in the ICH + AT group than in that of rats in the ICH group on day 29. GluR3 and GluR4 expression levels were reduced in the ipsilateral striatum of rats in the ICH group compared with that of rats in the SHAM group on day 14. These changes may play a critical role in motor skills training-induced recovery after ICH. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  19. Crystal structure of 4-[(5-methyl-isoxazol-3-yl)amino-sulfon-yl]anilinium 3,5-di-nitro-salicylate.

    Science.gov (United States)

    Malathy, Sevaiyan; Nirmalram, Jeyaraman Selvaraj; Muthiah, Packianathan Thomas

    2015-06-01

    The title mol-ecular salt, C10H12N3O3S(+)·C7H3N2O7 (-), protonation occurs at the amino N atom attached to the benzene ring of sulfamethoxazole. In the anion, there is an intra-molecular O-H⋯O hydrogen bond and the cation is linked to the anion by an N-H⋯O hydrogen bond. In the extended structure, the cations and anions are linked via N-H⋯O, N-H⋯N and C-H⋯O hydrogen bonds, forming a three-dimensional framework.

  20. Synthesis, characterization, and crystal structure of 2-amino-7-methyl-5-oxo-4-phenyl-4,5-dihydropyrano[3,2-c] pyran-3-carbonitrile

    Energy Technology Data Exchange (ETDEWEB)

    Sharma, S. [University of Jammu, X-ray Crystallography Laboratory, Post-Graduate Department of Physics and Electronics (India); Banerjee, B.; Brahmachari, G. [Visva-Bharati (a Central University), Laboratory of Natural Products & Organic Synthesis, Department of Chemistry (India); Kant, Rajni; Gupta, V. K., E-mail: vivek-gupta2k2@hotmail.com [University of Jammu, X-ray Crystallography Laboratory, Post-Graduate Department of Physics and Electronics (India)

    2015-12-15

    2-Amino-7-methyl-5-oxo-4-phenyl-4,5-dihydropyrano[3,2-c] pyran-3-carbonitrile, C{sub 16}H{sub 12}N{sub 2}O{sub 3} is synthesized via one-pot multi-component reaction at room temperature using commercially available urea as inexpensive and environmentally benign organo-catalyst. Its structure is determined by single-crystal X-ray diffraction technique The crystals are monoclinic, a = 10.7357(12), b = 8.7774(8), c = 15.0759(16) Å, β = 103.575(11)°, Z = 4, sp. gr. P2{sub 1}/n, R = 0.0551 for 1696 observed reflections. The crystal structure is stabilized by N–H···N, C–H···O, and C–H···π interactions.

  1. Non-Covalent Interactions in the Crystal Structure of Methyl 4-Hydroxy-3-Nitrobenzoate

    Directory of Open Access Journals (Sweden)

    Jim Simpson

    2012-06-01

    Full Text Available Methyl 4-hydroxy-3-nitrobenzoate, (I, C8H7NO5, crystallizes with two unique molecules, A and B, in the asymmetric unit of the triclinic unit cell. The space group was assigned as P-1, with lattice parameters a = 0.72831(15, b = 1.0522(2, c = 1.1410(2 nm, α = 83.38(3, β = 80.83(3, γ = 82.02(3°, Z = 4, V = 0.8510(3 nm3, Mr = 197.15, Dc = 1.539 g/m3, µ= 0.131 mm−1, F(000 = 408, R = 0.1002 and wR = 0.2519. In the crystal structure, 12 hydrogen bonding and two p-stacking interactions link the molecules into infinite stacked sheets parallel to (101.

  2. A library synthesis of 4-hydroxy-3-methyl-6-phenylbenzofuran-2-carboxylic acid ethyl ester derivatives as anti-tumor agents.

    Science.gov (United States)

    Hayakawa, Ichiro; Shioya, Rieko; Agatsuma, Toshinori; Furukawa, Hidehiko; Naruto, Shunji; Sugano, Yuichi

    2004-09-06

    As a result of a hit-to-lead program using a technique of solution-phase parallel synthesis, a highly potent (2,4-dimethoxyphenyl)-[6-(3-fluorophenyl)-4-hydroxy-3-methylbenzofuran-2-yl]methanone (15b) was synthesized as an optimized derivative of 4-hydroxy-3-methyl-6-phenylbenzofuran-2-carboxylic acid ethyl ester (1), which was discovered as a screening hit from small-molecule libraries and exhibited selective cytotoxicity against a tumorigenic cell line.

  3. Electrode Potentials of l-Tryptophan, l-Tyrosine, 3-Nitro-l-tyrosine, 2,3-Difluoro-l-tyrosine, and 2,3,5-Trifluoro-l-tyrosine.

    Science.gov (United States)

    Mahmoudi, Leila; Kissner, Reinhard; Nauser, Thomas; Koppenol, Willem H

    2016-05-24

    Electrode potentials for aromatic amino acid radical/amino acid couples were deduced from cyclic voltammograms and pulse radiolysis experiments. The amino acids investigated were l-tryptophan, l-tyrosine, N-acetyl-l-tyrosine methyl ester, N-acetyl-3-nitro-l-tyrosine ethyl ester, N-acetyl-2,3-difluoro-l-tyrosine methyl ester, and N-acetyl-2,3,5-trifluoro-l-tyrosine methyl ester. Conditional potentials were determined at pH 7.4 for all compounds listed; furthermore, Pourbaix diagrams for l-tryptophan, l-tyrosine, and N-acetyl-3-nitro-l-tyrosine ethyl ester were obtained. Electron transfer accompanied by proton transfer is reversible, as confirmed by detailed analysis of the current waves, and because the slopes of the Pourbaix diagrams obey Nernst's law. E°'(Trp(•),H(+)/TrpH) and E°'(TyrO(•),H(+)/TyrOH) at pH 7 are 0.99 ± 0.01 and 0.97 ± 0.01 V, respectively. Pulse radiolysis studies of two dipeptides that contain both amino acids indicate a difference in E°' of approximately 0.06 V. Thus, in small peptides, we recommend values of 1.00 and 0.96 V for E°'(Trp(•),H(+)/TrpH) and E°'(TyrO(•),H(+)/TyrOH), respectively. The electrode potential of N-acetyl-3-nitro-l-tyrosine ethyl ester is higher, while because of mesomeric stabilization of the radical, those of N-acetyl-2,3-difluoro-l-tyrosine methyl ester and N-acetyl-2,3,5-trifluoro-l-tyrosine methyl ester are lower than that of tyrosine. Given that the electrode potentials at pH 7 of E°'(Trp(•),H(+)/TrpH) and E°'(TyrO(•),H(+)/TyrOH) are nearly equal, they would be, in principle, interchangeable. Proton-coupled electron transfer pathways in proteins that use TrpH and TyrOH are thus nearly thermoneutral.

  4. Rational design, synthesis, and pharmacological evaluation of 2-azanorbornane-3-exo,5-endo-dicarboxylic acid

    DEFF Research Database (Denmark)

    Bunch, Lennart; Liljefors, Tommy; Greenwood, Jeremy R

    2003-01-01

    conformationally restricted (S)-glutamic acid (Glu) analogue intended as a mimic of the folded Glu conformation. The synthesis of 1 was completed in its racemic form in eight steps from commercially available starting materials. As a key step, the first facially selective hydroboration of a 5-methylidene[2......The design and synthesis of conformationally restricted analogues of alpha-amino acids is an often used strategy in medicinal chemistry research. Here we present the rational design, synthesis, and pharmacological evaluation of 2-azanorbornane-3-exo,5-endo-dicarboxylic acid (1), a novel...... studies on native 2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA) (IC(50) > 300 microM, [(3)H]AMPA) or kainic acid (IC(50) > 160 microM, [(3)H]kainic acid) receptors nor in binding studies on the cloned iGluR5,6 subtypes (IC(50) > 300 microM, [(3)H]kainic acid)....

  5. Easy method for the preparation of L (+) 2-amino 3-sulfino propionic acid (cysteine sulfinic acid)

    International Nuclear Information System (INIS)

    Emiliozzi, Romeo; Pichat, Louis

    1960-01-01

    Description of a new method of preparing cystine disulphoxide by oxidising cystine hydrochloride with a mixture of formic acid and hydrogen peroxide. Yield; 85 per cent. The disproportionation of cystine disulphoxide by ammonia gives 2-amino 3-sulfino propionic acid with a yield of 93 per cent. The method had been applied to the preparation of 35 S DL cysteine sulfinic acid. Reprint of a paper published in Bulletin de la Societe Chimique de France, no. 2653, 4. quarter 1959, p. 1887-1888 [fr

  6. Practical synthesis of methyl 7-(3-hydroxy-5-oxocyclopent-1-en-1-yl-heptanoate

    Directory of Open Access Journals (Sweden)

    Xinpeng Jiang

    2017-07-01

    Full Text Available The key intermediate of misoprostol, methyl 7-(3-hydroxy-5-oxocyclopent-1-en-1-yl-heptanoate was prepared from commercially available suberic acid in 40% yield over five steps. The key step involved a ZnCl2 catalyzed Friedel-Crafts reaction between furan and 2,9-oxonanedione. Sulfuric acid catalyzed methylation of 8-(furan-2-yl-8-oxooctanoic acid followed by sequential reduction and ZnCl2 catalyzed Piancatelli rearrangement resulted in the formation of the key intermediate of misoprostol.

  7. Selective antagonists at group I metabotropic glutamate receptors: synthesis and molecular pharmacology of 4-aryl-3-isoxazolol amino acids

    DEFF Research Database (Denmark)

    Kromann, Hasse; Sløk, Frank A; Stensbøl, Tine B

    2002-01-01

    Homologation of (S)-glutamic acid (Glu, 1) and Glu analogues has previously provided ligands with activity at metabotropic Glu receptors (mGluRs). The homologue of ibotenic acid (7), 2-amino-3-(3-hydroxy-5-isoxazolyl)propionic acid (HIBO, 8), and the 4-phenyl derivative of 8, compound 9a, are bot...... antagonists at group I mGluRs. Here we report the synthesis and molecular pharmacology of HIBO analogues 9b-h containing different 4-aryl substituents. All of these compounds possess antagonist activity at group I mGluRs but are inactive at group II and III mGluRs....

  8. [Study on the ultraviolet spectrum in a series of 2 (1H)-quinoxalin-2-one derivatives].

    Science.gov (United States)

    Yang, Xiao-bing; Ding, Song-tao; Wang, An-bang; Yang, Yu-sheng

    2003-02-01

    A series of 2 (1H)-quinoxalin-2-one derivatives: 1-alkyl-3-methyl-2 (1H)-quinoxalin-2-one (AMQ, alkyl = H, CH3, C2H5, n-C3H7, n-C5H11, n-C16H33) have been studied by ultraviolet spectrometry. They may be used as highly active fungicides, compounds inhibiting the growth of plants, neuroprotectant for cerebral ischemia, new fluorescent probes, selective antagonists to alpha-amino-3-hydroxy-5-methly-4-isoxazole propionic acid (AMPA) et al. Results show that as the length of the alky1 chain at the nitrogen on the 1-position increases, little changes have been found in the ultraviolet absorption spectra. All spectra have similar peak shape, a strong shoulder peak appears around 327 and 340 nm with a weaker peak around 280 nm. The peak about 340 nm in the UV spectrum is mainly due to the transition of n-->pi* and pi-->pi*, the intense absorption peak about 327 and 280 nm is as the result of the transition of pi-->pi*.

  9. Studies onthe behaviour of the insecticide 14C-Pirimiphos-Methyl in aquatic species: tilapia nilotica and potamogeton crispus plant

    International Nuclear Information System (INIS)

    Afifi, L.M.; Kamel, H.A.; Aly, M.A.S.

    2003-01-01

    The bioaccumulation and depletion of 1 4C-labelled pirimiphos-methyl (O-2- diethyl amino-6-methyl pyrimidine-4-gamma l O,O-dimethyl phosphorothioa) were monitored for 6 days following a single application at 7.5 ppm to 2 aquatic species: Bolti fish (Tilapia nilotica) and a rapid growing plant (Potamogeton crispus). The bioconcentration factor (BCF) for fish was relatively low with a maximum reached at 24 hours 122 and 55 in the absence and presence of the weed respectively. Depuration of the insecticide and/or its metabolites in clear water was readily fast. Feeding the treated dried fish to rat, the substance residues were found to be bioavailable where, 75.7% of the given amount was excreted in the urine and 15.3% in the feces. TLC analysis of the urine revealed the presence of 4 metabolites: Desethyl pirimiphos-methyl, 2-diethyl amino-4-hydroxy-6-methylpyrimidine, 2-ethyl amino-4-hydroxy-6-methyl-pyrimidine and 2-amino -4-hydroxy-6- methyl- pyrimidine

  10. Early continuous white noise exposure alters l-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor subunit glutamate receptor 2 and gamma-aminobutyric acid type a receptor subunit beta3 protein expression in rat auditory cortex.

    Science.gov (United States)

    Xu, Jinghong; Yu, Liping; Zhang, Jiping; Cai, Rui; Sun, Xinde

    2010-02-15

    Auditory experience during the postnatal critical period is essential for the normal maturation of auditory function. Previous studies have shown that rearing infant rat pups under conditions of continuous moderate-level noise delayed the emergence of adult-like topographic representational order and the refinement of response selectivity in the primary auditory cortex (A1) beyond normal developmental benchmarks and indefinitely blocked the closure of a brief, critical-period window. To gain insight into the molecular mechanisms of these physiological changes after noise rearing, we studied expression of the AMPA receptor subunit GluR2 and GABA(A) receptor subunit beta3 in the auditory cortex after noise rearing. Our results show that continuous moderate-level noise rearing during the early stages of development decreases the expression levels of GluR2 and GABA(A)beta3. Furthermore, noise rearing also induced a significant decrease in the level of GABA(A) receptors relative to AMPA receptors. However, in adult rats, noise rearing did not have significant effects on GluR2 and GABA(A)beta3 expression or the ratio between the two units. These changes could have a role in the cellular mechanisms involved in the delayed maturation of auditory receptive field structure and topographic organization of A1 after noise rearing. Copyright 2009 Wiley-Liss, Inc.

  11. Methylated DNMT1 and E2F1 are targeted for proteolysis by L3MBTL3 and CRL4DCAF5 ubiquitin ligase.

    Science.gov (United States)

    Leng, Feng; Yu, Jiekai; Zhang, Chunxiao; Alejo, Salvador; Hoang, Nam; Sun, Hong; Lu, Fei; Zhang, Hui

    2018-04-24

    Many non-histone proteins are lysine methylated and a novel function of this modification is to trigger the proteolysis of methylated proteins. Here, we report that the methylated lysine 142 of DNMT1, a major DNA methyltransferase that preserves epigenetic inheritance of DNA methylation patterns during DNA replication, is demethylated by LSD1. A novel methyl-binding protein, L3MBTL3, binds the K142-methylated DNMT1 and recruits a novel CRL4 DCAF5 ubiquitin ligase to degrade DNMT1. Both LSD1 and PHF20L1 act primarily in S phase to prevent DNMT1 degradation by L3MBTL3-CRL4 DCAF5 . Mouse L3MBTL3/MBT-1 deletion causes accumulation of DNMT1 protein, increased genomic DNA methylation, and late embryonic lethality. DNMT1 contains a consensus methylation motif shared by many non-histone proteins including E2F1, a key transcription factor for S phase. We show that the methylation-dependent E2F1 degradation is also controlled by L3MBTL3-CRL4 DCAF5 . Our studies elucidate for the first time a novel mechanism by which the stability of many methylated non-histone proteins are regulated.

  12. Synthesis and Herbicidal Activities of Novel 4-(4-(5-methyl-3-arylisoxazol-4-ylthiazol-2-ylpiperidyl Carboxamides and Thiocarboxamides

    Directory of Open Access Journals (Sweden)

    Ai-Dong Zhang

    2009-03-01

    Full Text Available A series of novel 4-(4-(5-methyl-3-arylisoxazol-4-ylthiazol-2-ylpiperidyl carboxamides and thiocarboxamides were synthesized as potential lead compounds of inhibitors targeting D1 protease in plants. These compounds were designed on the basis of a D1 protease inhibitor hit structure identified by homology modeling and virtual screening. The syntheses of these compounds were accomplished via a four-step procedure including the isoxazole ring formation, a-bromination of acetyl group, thiazole ring formation, and carboxamide/thiocarboxamide attachment. The in vivo herbicidal activity tests show that most compounds possess moderate to good herbicidal activities. The enzyme activity of one compound against the native spinach D1 protease exhibits a competitive inhibition. The results suggest that these compounds are indeed potential inhibitors for targeting D1 protease in plants.

  13. Synthesis of [14C]ABT-418, a cholinergic channel activator labeled at two sites on the isoxazole ring

    International Nuclear Information System (INIS)

    Surber, B.W.; Thomas, S.B.; Elliott, R.L.; Kopecka, Hana

    1996-01-01

    [ 14 C]ABT-418, (S)-3-[ 14 C]methyl-5-[N-methyl-2-pyrrolidinyl] [4- 14 C]isoxazole hydrochloride, was labeled in two positions at maximum specific activity. Starting with 100 mCi of sodium [2- 14 C]acetate, 14.6 mCi at 105 mCi/mmol was obtained in 8 steps including the formation of [1,3- 14 C]acetone in the pyrolysis of barium [2- 14 C]acetate. The key step was the formation of the dianion of [1,3- 14 C]acetone oxime and its condensation with L-proline methyl ester. (author)

  14. Synthesis, Immunosuppressive Properties, and Mechanism of Action of a New Isoxazole Derivative

    Directory of Open Access Journals (Sweden)

    Marcin Mączyński

    2018-06-01

    Full Text Available This work describes the synthesis of a new series of isoxazole derivatives, their immunosuppressive properties, and the mechanism of action of a representative compound. A new series of N′-substituted derivatives of 5-amino-N,3-dimethyl-1,2-oxazole-4-carbohydrazide (MM1–MM10 was synthesized in reaction of 5-amino-N,3-dimethyl-1,2-oxazole-4-carbohydrazide with relevant carbonyl compounds. The isoxazole derivatives were tested in several in vitro models using human cells. The compounds inhibited phytohemagglutinin A (PHA-induced proliferation of peripheral blood mononuclear cells (PBMCs to various degrees. The toxicity of the compounds with regard to a reference A549 cell line was also differential. 5-amino-N′-(2,4-dihydroxyphenylmethylidene-N,3-dimethyl-1,2-oxazole-4-carbohydrazide (MM3 compound was selected for further investigation because of its lack of toxicity and because it had the strongest antiproliferative activity. The compound was shown to inhibit lipopolysaccharide (LPS-induced tumor necrosis factor (TNF α production in human whole blood cell cultures. In the model of Jurkat cells, MM3 elicited strong increases in the expression of caspases, Fas, and NF-κB1, indicating that a proapoptotic action may account for its immunosuppressive action in the studied models.

  15. Enrichment of the Amino Acid L-Isovaline by Aqueous Alteration on CI and CM Meteorite Parent Bodies

    Science.gov (United States)

    Glavin, Daniel P.; Dworkin, Jason P.

    2009-01-01

    The distribution and enantiomeric composition of the 5-carbon (C(sub 5)) amino acids found in Cl-, CM-, and CR-type carbonaceous meteorites were investigated by using liquid chromatography fluorescence detection/TOF-MS coupled with o-phthaldialdehyde/Nacetyl- l-cysteine derivatization. A large L-enantiomeric excess (ee) of the a-methyl amino acid isovaline was found in the CM meteorite Murchison (L(sub ee) = 18.5 +/- 2.6%) and the Cl meteorite Orguell (L(sub ee) = 15.2 +/- 4.0%). The measured value for Murchison is the largest enantiomeric excess in any meteorite reported to date, and the Orgueil measurement of an isovaline excess has not been reported previously for this or any Cl meteorite. The L-isovaline enrichments in these two carbonaceous meteorites cannot be the result of interference from other C(sub 5) amino acid isomers present in the samples, analytical biases, or terrestrial amino acid contamination. We observed no L-isovaline enrichment for the most primitive unaltered Antarctic CR meteorites EET 92042 and QUE 99177. These results are inconsistent with UV circularly polarized light as the primary mechanism for L-isovaline enrichment and indicate that amplification of a small initial isovaline asymmetry in Murchison and Orgueil occurred during an extended aqueous alteration phase on the meteorite parent bodies. The large asymmetry in isovaline and other alpha-dialkyl amino acids found in altered Ct and CM meteorites suggests that amino acids delivered by asteroids, comets, and their fragments would have biased the Earth's prebiotic organic inventory with left-handed molecules before the origin of life.

  16. Growth and Characterization of Organic Marine Dye Compound: 6-Amino-8α-methoxy-5-methyl-4,7-dioxo-1,1a, 2,4,7,8,8a,8b-octahydroazireno[2',3':3,4] pyrrolo[1,2-α]indol- 8-yl]methyl Carbamate

    OpenAIRE

    Jayandran, M.; Balasubramanian, V.

    2011-01-01

    Single crystals of 6-amino-8α-methoxy-5-methyl-4,7-dioxo-1,1a, 2,4,7,8,8a,8b-octahydroazireno[2',3':3,4]pyrrolo[1,2-α]indol-8-yl]methyl carbamate (Mitomycin), an organic marine dye material has been grown from solution by slow evaporation at ambient temperature. The growth of crystals has been carried out at various pH values and the growth was confirmed at pH 6. The chemical composition of the grown crystals was determined by the FTIR spectra. The crystalline nature and its various planes of...

  17. Isoxazolium N-ylides and 1-oxa-5-azahexa-1,3,5-trienes on the way from isoxazoles to 2H-1,3-oxazines

    Directory of Open Access Journals (Sweden)

    Alexander F. Khlebnikov

    2014-08-01

    Full Text Available Theoretical and experimental studies of the reaction of isoxazoles with diazo compounds show that the formation of 2H-1,3-oxazines proceeds via the formation of (3Z-1-oxa-5-azahexa-1,3,5-trienes which undergo a 6π-cyclization. The stationary points corresponding to the probable reaction intermediates, isoxazolium N-ylides, were located by DFT calculations at the B3LYP/6-31G(d level only for derivatives without a substituent in position 3 of the isoxazole ring. These isoxazolium N-ylides are thermodynamically and kinetically very unstable. According to the calculations and experimental results 2H-1,3-oxazines are usually more thermodynamically stable than the corresponding open-chain isomers, (3Z-1-oxa-5-azahexa-1,3,5-trienes. The exception are oxaazahexatrienes derived from 5-alkoxyisoxazoles, which are thermodynamically more stable than the corresponding 2H-1,3-oxazines. Therefore, the reaction of diazo esters with 5-alkoxyisoxazoles is a good approach to 1,4-di(alkoxycarbonyl-2-azabuta-1,3-dienes. The reaction conditions for the preparation of aryl- and halogen-substituted 2H-1,3-oxazines and 1,4-di(alkoxycarbonyl-2-azabuta-1,3-dienes from isoxazoles were investigated.

  18. Natural 4-hydroxy-2,5-dimethyl-3(2H)-furanone (Furaneol®).

    Science.gov (United States)

    Schwab, Wilfried

    2013-06-13

    4-Hydroxy-2,5-dimethyl-3(2H)-furanone (HDMF, furaneol®) and its methyl ether 2,5-dimethyl-4-methoxy-3(2H)-furanone (DMMF) are import aroma chemicals and are considered key flavor compounds in many fruit. Due to their attractive sensory properties they are highly appreciated by the food industry. In fruits 2,5-dimethyl-3(2H)-furanones are synthesized by a series of enzymatic steps whereas HDMF is also a product of the Maillard reaction. Numerous methods for the synthetic preparation of these compounds have been published and are applied by industry, but for the development of a biotechnological process the knowledge and availability of biosynthetic enzymes are required. During the last years substantial progress has been made in the elucidation of the biological pathway leading to HDMF and DMMF. This review summarizes the latest advances in this field.

  19. Natural 4-Hydroxy-2,5-dimethyl-3(2H-furanone (Furaneol®

    Directory of Open Access Journals (Sweden)

    Wilfried Schwab

    2013-06-01

    Full Text Available 4-Hydroxy-2,5-dimethyl-3(2H-furanone (HDMF, furaneol® and its methyl ether 2,5-dimethyl-4-methoxy-3(2H-furanone (DMMF are import aroma chemicals and are considered key flavor compounds in many fruit. Due to their attractive sensory properties they are highly appreciated by the food industry. In fruits 2,5-dimethyl-3(2H-furanones are synthesized by a series of enzymatic steps whereas HDMF is also a product of the Maillard reaction. Numerous methods for the synthetic preparation of these compounds have been published and are applied by industry, but for the development of a biotechnological process the knowledge and availability of biosynthetic enzymes are required. During the last years substantial progress has been made in the elucidation of the biological pathway leading to HDMF and DMMF. This review summarizes the latest advances in this field.

  20. Synthesis of [{sup 14}C]ABT-418, a cholinergic channel activator labeled at two sites on the isoxazole ring

    Energy Technology Data Exchange (ETDEWEB)

    Surber, B.W.; Thomas, S.B. [Abbott Labs., Drug Metabolism, Abbott Park, IL (United States); Elliott, R.L.; Kopecka, Hana [Abbott Labs., Neuroscience Research, Abbott Park, IL (United States)

    1996-09-01

    [{sup 14}C]ABT-418, (S)-3-[{sup 14}C]methyl-5-[N-methyl-2-pyrrolidinyl] [4-{sup 14}C]isoxazole hydrochloride, was labeled in two positions at maximum specific activity. Starting with 100 mCi of sodium [2-{sup 14}C]acetate, 14.6 mCi at 105 mCi/mmol was obtained in 8 steps including the formation of [1,3-{sup 14}C]acetone in the pyrolysis of barium [2-{sup 14}C]acetate. The key step was the formation of the dianion of [1,3-{sup 14}C]acetone oxime and its condensation with L-proline methyl ester. (author).

  1. Synthesis of 2-hydroxy-3-(2-methyl-propenyl-1,4-naphthoquinone and related oxime derivatives

    Directory of Open Access Journals (Sweden)

    Patricia S. Oliveira

    2012-06-01

    Full Text Available The condensation reaction of commercial 2-hydroxy-1 ,4-naphthoquinone 1 (lawsone with isobutyraldehyde 2 furnishs norlapachol 3 (2-hydroxy-3-(2-methyl-propenyl -1,4-naphthoquinone with yields ranging from 66 to 93% depending on the different conditions tested, and a reaction temperature factor determinant for the formation of the desired product. It was treated with hydroxylamine hydrochloride in alkaline (NaOH to provide the oxime 4 from regioselective modification of the carbonyl C-1 with 91% yield. The regioselectivity of the reaction can be explained by analyzing the different resonance structures which can be seen that the carbonyl C-4 is less electrophilic than C-1. In this work was also obtained the oxime 5, 6 and 7 from lapachol, αlpha and β-lapachone, respectively, in yields of 64-85%. The oximes of αlpha and β-norlapachone, 8 and 9 are in obtention. All the products were analyzed by IR and NMR, and were observed that oximes of lapachol and norlapachol are isolated as E/Z mixtures. Two-dimensional NOE-type experiments of the corresponding acylated derivative will be made to help identify the proportion of the mixture.

  2. Structural basis for the enzymatic formation of the key strawberry flavor compound 4-hydroxy-2,5-dimethyl-3(2H)-furanone.

    Science.gov (United States)

    Schiefner, André; Sinz, Quirin; Neumaier, Irmgard; Schwab, Wilfried; Skerra, Arne

    2013-06-07

    The last step in the biosynthetic route to the key strawberry flavor compound 4-hydroxy-2,5-dimethyl-3(2H)-furanone (HDMF) is catalyzed by Fragaria x ananassa enone oxidoreductase (FaEO), earlier putatively assigned as quinone oxidoreductase (FaQR). The ripening-induced enzyme catalyzes the reduction of the exocyclic double bond of the highly reactive precursor 4-hydroxy-5-methyl-2-methylene-3(2H)-furanone (HMMF) in a NAD(P)H-dependent manner. To elucidate the molecular mechanism of this peculiar reaction, we determined the crystal structure of FaEO in six different states or complexes at resolutions of ≤1.6 Å, including those with HDMF as well as three distinct substrate analogs. Our crystallographic analysis revealed a monomeric enzyme whose active site is largely determined by the bound NAD(P)H cofactor, which is embedded in a Rossmann-fold. Considering that the quasi-symmetric enolic reaction product HDMF is prone to extensive tautomerization, whereas its precursor HMMF is chemically labile in aqueous solution, we used the asymmetric and more stable surrogate product 2-ethyl-4-hydroxy-5-methyl-3(2H)-furanone (EHMF) and the corresponding substrate (2E)-ethylidene-4-hydroxy-5-methyl-3(2H)-furanone (EDHMF) to study their enzyme complexes as well. Together with deuterium-labeling experiments of EDHMF reduction by [4R-(2)H]NADH and chiral-phase analysis of the reaction product EHMF, our data show that the 4R-hydride of NAD(P)H is transferred to the unsaturated exocyclic C6 carbon of HMMF, resulting in a cyclic achiral enolate intermediate that subsequently becomes protonated, eventually leading to HDMF. Apart from elucidating this important reaction of the plant secondary metabolism our study provides a foundation for protein engineering of enone oxidoreductases and their application in biocatalytic processes.

  3. Spectrophotometric determination of La (III) with sulphamethoxazole based hydroxy triazene

    International Nuclear Information System (INIS)

    Manwani, Sapana; Chauhan, R.S.; Goswami, A.K.

    2015-01-01

    In the present study, 3-hydroxy-3-p-chlorophenyll-1-(4-amino-N-(5-methyl-1,2-oxazole-3- yl) benzenesulphonamide-methane) triazene has been synthesized by coupling of hydroxylamine obtained by reduction of nitro compound with diazonium salt obtained from sulphamethoxazole taking hydroxylamine in excess at temperature between 0-5°C. Chemical structure of the synthesized compound was confirmed by IR, 1 H NMR, MASS and by elemental analysis. The complex of the reagent with La (III) has been studied. 3-hydroxy-3-p-chlorophenyll-1-(4-amino-N-(5-methyl-1,2-oxazole-3-yl) benzenesulphonamide-methane) triazene has been used for spectrophotometric determination of lanthanum (III) at 392 nm, keeping the pH between 8.5 to 8.9

  4. Stereoselective synthesis of 5-alkoxycarbonyl-4 alkyl-2-anino-3-cyano-6-methyl-4H-pyranes 3 via asymmetric Michael addition to aceptors-gamma-stereogenics; Sintesis esteroselective de 5-alcoxicarbonil-4-alquil-2-amino-3-ciano-6-metil-4H-piranos via adicion Michael sobre aceptores-gama-esterogenicos

    Energy Technology Data Exchange (ETDEWEB)

    Martinez-Grau, A.; Jimenez, B.; Martin, N.; Seoane, C.; Marco, J.L. [Departamento de Quimica Organica, Facultad de Quimica, Universidad Complutense, Madrid (Spain)

    1994-12-31

    The stereoselective synthesis of 5-alkoxycarbonyl-4-alkyl-2-amino-3-cyano-6-methyl-4H-pyrans 3 via asymmetric Michael addition of malononitrile to gamma-stereogenic alpha-acetylacrylates 2 obtained by Knoevenagel reaction of acetylacetates to quiral alpha-hydroxyaldehydes 1 is described. The resulting 2-amino-4H-pyrans 3 have been obtained in moderate yield and good diastereoselectivity. 15 refs.

  5. The effects of inferior olive lesion on strychnine seizure

    International Nuclear Information System (INIS)

    Anderson, M.C.; Chung, E.Y.; Van Woert, M.H.

    1990-01-01

    Bilateral inferior olive lesions, produced by systemic administration of the neurotoxin 3-acetylpyridine (3AP) produce a proconvulsant state specific for strychnine-induced seizures and myoclonus. We have proposed that these phenomena are mediated through increased excitation of cerebellar Purkinje cells, through activation of glutamate receptors, in response to climbing fiber deafferentation. An increase in quisqualic acid (QA)-displaceable [ 3 H]AMPA [(RS)-alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid] binding in cerebella from inferior olive-lesioned rats was observed, but no difference in [ 3 H]AMPA binding displaced by glutamate, kainic acid (KA) or glutamate diethylester (GDEE) was seen. The excitatory amino acid antagonists GDEE and MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclo-hepten-5,10 imine] were tested as anticonvulsants for strychnine-induced seizures in 3AP inferior olive-lesioned and control rats. Neither drug effected seizures in control rats, however, both GDEE and MK-801 produced a leftward shift in the strychnine-seizure dose-response curve in 3AP inferior olive-lesioned rats. GDEE also inhibited strychnine-induced myoclonus in the lesioned group, while MK-801 had no effect on myoclonus. The decreased threshold for strychnine-induced seizures and myoclonus in the 3AP-inferior olive-lesioned rats may be due to an increase in glutamate receptors as suggested by the [ 3 H]AMPA binding data

  6. 3-Hydroxy-2-[(4-hydroxy-3,5-dimethoxyphenyl(2-hydroxy-4,4-dimethyl-6-oxocyclohex-1-en-1-ylmethyl]-5,5-dimethylcyclohex-2-en-1-one

    Directory of Open Access Journals (Sweden)

    Xiao-Hui Yang

    2011-02-01

    Full Text Available In the title compound, C25H32O7, the 3-hydroxy-5,5-dimethylcyclohex-2-enone rings adopt slightly distorted envelope conformations with the two planes at the base of the envelope forming dihedral angles of 57.6 (4 and 53.9 (9° with the benzene ring. There is an intramolecular hydroxy–ketone O—H...O interaction between the two substituted cyclohexane rings as well as a short intramolecular phenol–methoxy O—H...O interaction.

  7. 2-[(4-Bromophenylimino)methyl]-5-pentadecylphenol

    OpenAIRE

    Basavaraj Padmashali; Patchanita Thamyongkit; Amorn Petsom; Gadada Naganagowda

    2012-01-01

    2-[(4-Bromophenylimino)methyl]-5-pentadecylphenol has been synthesized by reaction of 2-hydroxy-4-pentadecylbenzaldehyde with 4-bromoaniline in 1,4-dioxane and its IR, 1H-NMR, 13C-NMR and MS spectroscopic data are presented.

  8. Role of α-Dicarbonyl Compounds in the Inhibition Effect of Reducing Sugars on the Formation of 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine.

    Science.gov (United States)

    Han, Zhonghui; Liu, Bing; Niu, Zhiyan; Zhang, Yan; Gao, Jianxin; Shi, Lei; Wang, Shujun; Wang, Shuo

    2017-11-22

    The effect of reducing sugars on formation of PhIP in fried pork was investigated, and the underlying mechanisms were revealed by studying the reaction pathways between α-dicarbonyl compounds (α-DCs) and PhIP. The addition of reducing sugars (such as glucose) greatly reduced the amount of PhIP in fried pork from 15.5 ng/g to less than 1.0 ng/g. The amount of PhIP decreased significantly with an increasing level of added α-DCs in model systems. Similarly, the addition of methylglyoxal (MGO) decreased significantly the levels of phenylalanine (Phe) and creatinine (Crn) but increased significantly the level of phenylacetaldehyde (PEA). 2-Amino-1-methyl-5-(2-oxopropylidene)-imidazol-4-one and N-(1-methyl-4-oxoimidazolidin-2-ylidene) amino propionic acids were identified in MGO/Crn and MGO/Crn/Phe model systems and fried pork with glucose. These results revealed that the degradation products of reducing sugars-α-DCs-play an important role in inhibiting formation of PhIP by reacting with key precursors of PhIP and itself.

  9. (1S,3S,4S-tert-Butyl N-[1-benzyl-3-hydroxy-5-phenyl-4-(picolinamidopentyl]carbamate

    Directory of Open Access Journals (Sweden)

    Jian-Feng Zheng

    2008-07-01

    Full Text Available The title compound, C29H35N3O4, was obtained by the reaction of (2S,4S,5S-tert-butyl N-(4-amino-1-benzyl-3-hydroxy-5-phenylpentylcarbamate and picolinic acid using oxalyl chloride as a chlorinating reagent to activate the carboxyl group. In the crystal structure there are two molecules in the asymmetric unit, which are aligned edge-to-face. In one molecule, the pyridyl ring forms a dihedral angle of 22.0 (1° with the phenyl ring of the terminal benzyl group and 14.3 (1° with the other phenyl ring; in the other molecule, the corresponding angles are 12.1 (1 and 10.6 (1°, respectively. The packing is stabilized by intermolecular hydrogen bonds and C—H...π interactions.

  10. N-{(2S-3-Hydroxy-4-[(5-methyl-1,3,4-thiadiazol-2-ylsulfanyl]-1-phenyl-2-butyl}-4-methylbenzenesulfonamide

    Directory of Open Access Journals (Sweden)

    Claudia R. B. Gomes

    2011-09-01

    Full Text Available The thiadiazoyl and sulfonyl-benzene rings in the title compound, C20H23N3O3S3, are aligned to the same side of the molecule, forming a twisted `U' shape [dihedral angle = 77.6 (5°]. The benzyl-benzene ring is orientated in the opposite direction from the molecule but projects approximately along the same axis as the other rings [dihedral angle between benzene rings = 28.2 (5°] so that, overall, the molecule has a flattened shape. The hydroxy and amine groups are almost syn which enables the formation of intermolecular hydroxy-OH...N(thiadiazoyl and amine-H...O(sulfonyl hydrogen bonds leading to a supramolecular chain aligned along the a axis.

  11. Uptake of 3-[125I]iodo-α-methyl-L-tyrosine into colon cancer DLD-1 cells: characterization and inhibitory effect of natural amino acids and amino acid-like drugs

    International Nuclear Information System (INIS)

    Shikano, Naoto; Ogura, Masato; Okudaira, Hiroyuki; Nakajima, Syuichi; Kotani, Takashi; Kobayashi, Masato; Nakazawa, Shinya; Baba, Takeshi; Yamaguchi, Naoto; Kubota, Nobuo; Iwamura, Yukio; Kawai, Keiichi

    2010-01-01

    Introduction: We examined 3-[ 123 I]iodo-α-methyl-L-tyrosine ([ 123 I]IMT) uptake and inhibition by amino acids and amino acid-like drugs in the human DLD-1 colon cancer cell line, to discuss correlation between the inhibition effect and structure. Methods: Expression of relevant neutral amino acid transporters was examined by real-time PCR with DLD-1 cells. The time course of [ 125 I]IMT uptake, contributions of transport systems, concentration dependence and inhibition effects by amino acids and amino acid-like drugs (1 mM) on [ 125 I]IMT uptake were examined. Results: Expression of system L (4F2hc, LAT1 and LAT2), system A (ATA1, ATA2) and system ASC (ASCT1) was strongly detected; system L (LAT3, LAT4) and MCT8 were weakly detected; and B 0 AT was not detected. [ 125 I]IMT uptake in DLD-1 cells involved Na + -independent system L primarily and Na + -dependent system(s). Uptake of [ 125 I]IMT in Na + -free buffer followed Michaelis-Menten kinetics, with a K m of 78 μM and V max of 333 pmol/10 6 cells per minute. Neutral D- and L-amino acids with branched or aromatic large side chains inhibited [ 125 I]IMT uptake. Tyrosine analogues, tryptophan analogues, L-phenylalanine and p-halogeno-L-phenylalanines, and gamma amino acids [including 3,4-dihydroxy-L-phenylalanine (L-DOPA), DL-threo-β-(3,4-dihydroxyphenyl)serine (DOPS), 4-[bis(2-chloroethyl)amino]-L-phenylalanine and 1-(aminomethyl)-cyclohexaneacetic acid] strongly inhibited [ 125 I]IMT uptake, but L-tyrosine methyl ester and R(+)/S(-)-baclofen weakly inhibited uptake. The substrates of system ASC and A did not inhibit [ 125 I]IMT uptake except L-serine and D/L-cysteine. Conclusions: [ 125 I]IMT uptake in DLD-1 cells involves mostly LAT1 and its substrates' (including amino acid-like drugs derived from tyrosine, tryptophan and phenylalanine) affinity to transport via LAT1. Whether transport of gamma amino acid analogues is involved in LAT1 depends on the structure of the group corresponding to the amino acid

  12. Microwave-assisted rapid synthesis of methyl 2,4,5-trimethoxyphenylpropionate, a metabolite of Cordia alliodora.

    Science.gov (United States)

    Sinha, A K; Joshi, B P; Sharma, A; Kumar, J K; Kaul, V K

    2003-12-01

    Microwave assisted condensation of asaronaldehyde (2) with malonic acid in piperidine-AcOH provides 2,4,5-trimethoxycinnamic acid (3) in 87% yield within 4 min, which upon further reduction with PdCl2- HCOOH-aq. NaOH gives 3-(2,4,5-trimethoxy)phenyl propionic acid (4) in 88% yield within 3 min. Esterification of 4 with MeOH-H+ gives methyl 2,4,5-trimethoxyphenylpropionate (1), a metabolite of Cordia alliodora, in 94% yield within 3 min (overall 69% yield).

  13. Influence of degree of methyl methacrylate polymerization on spectroscopic properties of ethyl 5-(4-aminophenyl)- and 5-(4-dimethylaminophenyl)-3-amino-2,4-dicyanobenzoate

    International Nuclear Information System (INIS)

    Józefowicz, M.; Bajorek, A.; Pietrzak, M.; Jędrzejewska, B.; Heldt, J.R.; Heldt, J.

    2013-01-01

    The influence of degree of methyl methacrylate (MM) polymerization on the both emission modes (LE—locally excited and ICT—intramolecular charge transfer) of the fluorescence spectrum of ethyl 5-(4-aminophenyl)-3-amino-2,4-dicyanobenzoate (EAADCy) and ethyl 5-(4-dimethylaminophenyl)-3-amino-2,4-dicyanobenzoate (EDMAADCy) has been studied using steady-state and time-resolved spectroscopic technique. The purpose of these studies was to find a relationship between the changes in the spectroscopic characteristics (fluorescence intensity, wavelength of maximum intensity, fluorescence full-width at half maximum, emission anisotropy, fluorescence decay time) of the tested compounds and degree of monomer conversion into polymer. On the basis of the experimental results, it was shown that the ICT fluorescence full-width at half maximum for EDMAADCy shows a linear dependence on the time of MM polymerization. Our findings predestine the molecule EDMAADCy to be used as fluorescence probe for monitoring the polymerization process of MM. - Highlights: ► The fluorescence excitation and emission spectra in MM possess a complex nature. ► Fluorescence decay kinetics for different degrees of polymerization of MM were investigated. ► The ICT fluorescence FWHM for EDMAADCy shows a linear dependence on the time of polymerization. ► EDMAADCy can be used as fluorescence probe for monitoring the polymerization process of MM

  14. Synthesis, physical and chemical properties of 2-((5-(hydroxy(phenylmethyl-4R-4H-1,2,4-triazole-3-ylthioacetic acids and its salts

    Directory of Open Access Journals (Sweden)

    A. M. Rud

    2018-02-01

    Full Text Available Today’s a creation of new domestic medicines is very important problem for pharmacy and medicine. Therefore, it is relevant to synthesize new domestic biologically active compounds. It is known that a large number of new 3-thio and 4-amino derivatives on the basis of 1,2,4-triazole have recently been synthesized, among which compounds with high pharmacological activity have been found. Based on the experience of previous studies and with the aim of creating new original drugs, our goal was to synthesize 2-((5-(hydroxy(phenylmethyl-4-R-4H-1,2,4-triazole-3-ylthioacetic acids series and to obtain salts on its basis, which have high indicators of pharmacological activity based on the literature data. The goal of the work is a targeted synthesis of potential low-toxic and highly effective compounds with a wide spectrum of pharmacological activity among 5-(hydroxy(phenylmethyl-4-R-4H-1,2,4-triazole-3-thione derivatives, confirmation of their individuality and structure, as well as the study of physical-chemical properties, for the further pharmacological screening. Materials and methods. 2-((5-(hydroxy(phenylmethyl-4-R-4H-1,2,4-triazole-3-ylthioacetic acids were prepared by heating 5- (hydroxy(phenylmethyl-4-R-4H-1,2,4-triazol-3-thiones with chloroacetic acid. Subsequently, the synthesized thioacetic acids were subject for modification. Salts of 2-((5-(hydroxy(phenylmethyl-4-R-4H-1,2,4-triazole-3-ylthioacetic acids were obtained by reacting thioacetic acids with equivalents of sodium or potassium hydroxides. To obtain Iron(II, Copper(II or Zinc(II salts, half-molar amounts of the appropriate sulfates were added to the obtained solutions. Salts of 2-((5-(hydroxy(phenylmethyl-4-R-4H-1,2,4-triazole-3-ylthioacetic acids with organic bases were obtained by the reaction of acids with piperidine or morpholine in ethanol medium. Results. During the synthetic studies, 13 previously undescribed new compounds were obtained. The individuality of 2-((5-(hydroxy

  15. Synthesis of N,N,-didemethylzolpidem-N-{2-{3-(4-hydroxy-3-[125I] iodophenyl)}methyl propionate} for radioimmunoassay

    International Nuclear Information System (INIS)

    De Clerck, I.; Daenens, P.

    1997-01-01

    The 125 I-derivative of zolpidem was prepared by iodination of a L-tyrosine methyl ester conjugate of a zolpidem precursor. The iodinated compound has been used as a tracer molecule in the development of a radioimmunoassay for zolpidem. It was purified by normal phase HPLC, in combination with gamma counting detection. The structure was confirmed by high resolution L-SIMS. (UK)

  16. Synthesis of 5'-bromo-2'-hydroxy-4,4',6'-trimethoxychalcone from Garcinia nervosa and of its isomer 3'-bromo-2'-hydroxy-4,4',6'- trimethoxychalcone

    Digital Repository Service at National Institute of Oceanography (India)

    Parab, S.J.; Kapdi, S.G.; Naik, C.G.; Kamat, S.P.

    The unambiguous syntheses of the naturally occurring 5'-bromo-2'-hydroxy-4,4',6'-trimethoxychalcone 1, a constituent of Garcinia nervosa, and its positional isomer 3'-bromo-2'-hydroxy-4,4',6'-trimethoxychalcone 6 are described...

  17. Novel 1-hydroxyazole bioisosteres of glutamic acid. Synthesis, protolytic properties, and pharmacology

    DEFF Research Database (Denmark)

    Stensbøl, Tine B; Uhlmann, Peter; Morel, Sandrine

    2002-01-01

    A number of 1-hydroxyazole derivatives were synthesized as bioisosteres of (S)-glutamic acid (Glu) and as analogues of the AMPA receptor agonist (R,S)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA, 3b). All compounds were subjected to in vitro pharmacological studies, including ...

  18. Naturally Abundance Vanillin as Starting Material to Synthesizing 4-(4-Hydroxy-3-methoxyphenyl-6-methyl-3,4-dihydropyrimidin-2(1H-one

    Directory of Open Access Journals (Sweden)

    Masruri MASRURI

    2015-12-01

    Full Text Available Indonesia is the second biggest producer of natural vanillin. Traditionally it was isolated from the bean of vanilla (Vanilla planifolia Andrews. This paper reports on applying vanillin as starting material for synthesizing a biologically important chemical structure 3,4-dihydropyrimidinone. The reaction was undertaken in one step following multi component reaction (MCR. Products determination was undergone using FTIR and UV-Vis spectrophotometry, and also liquid chromatography-mass spectrometry (LCMS. After purification under flash column chromatography in ethyl acetate-hexane, it was found a white solid of 4-(4-hydroxy-3-methoxyphenyl-6-methyl-3,4-dihydropyrimidin-2(1H-one in 67% yield with a few amount of an unreacted vanillin.

  19. Distinct structural features of cyclothiazide are responsible for effects on peak current amplitude and desensitization kinetics at iGluR2

    DEFF Research Database (Denmark)

    Hald, Helle; Ahring, Philip Kiær; Timmermann, Daniel Brunicardi

    2009-01-01

    Ionotropic glutamate receptors (iGluRs) mediate fast excitatory neurotransmission. Upon glutamate application, 2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid receptors undergo rapid and almost complete desensitization that can be attenuated by positive allosteric modulators. The molecu......Ionotropic glutamate receptors (iGluRs) mediate fast excitatory neurotransmission. Upon glutamate application, 2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid receptors undergo rapid and almost complete desensitization that can be attenuated by positive allosteric modulators......) in micromolar: 10 (CTZ), 26 (NS1493), 43 (NS5206), and 48 (NS5217)]. The four modulators divide into three groups according to efficacy and desensitization kinetics: (1) CTZ increases the peak current efficacy twice as much as the three analogues and nearly completely blocks receptor desensitization; (2) NS5206...... and NS5217 have low efficacy and only attenuate desensitization partially; (3) NS1493 has low efficacy but nearly completely blocks receptor desensitization. A hydrophobic substituent at the 3-position of the 1,1-dioxo-3,4-dihydro-2H-benzo[e][1,2,4]thiadiazine ring system is important for compound...

  20. Analgesic Activity of Some 1,2,4-Triazole Heterocycles Clubbed with Pyrazole, Tetrazole, Isoxazole and Pyrimidine

    Directory of Open Access Journals (Sweden)

    Ramdas Bhanudas Pandhare

    2013-02-01

    Full Text Available Purpose: In the present study in vivo analgesic activity of some previously synthesized 1,2,4-triazole derivatives containing pyrazole, tetrazole, isoxazole and pyrimidine ring have been evaluated. Methods: Acetic acid induced writhing method and Hot plate method has been described to study analgesic activity of some 1,2,4-triazole derivatives containing pyrazole, tetrazole, isoxazole and pyrimidine as a pharmacological active lead. Results: Thirty six different derivatives containing 1,2,4-triazole ring were subjected to study their in vivo analgesic activity. Chloro, nitro and methoxy, hydroxy and bromo substituted derivatives showed excellent analgesic activity and dimethylamino, furan and phenyl substituted derivatives showed moderate analgesic activity in both of the methods. Compounds IIIa, IIId, IIIf, IIIi, IIIj, IVa, IVb, IVd, IVf, IVh, IVj IV3a and IIj were found to be superior analgesic agents after screening by Acetic acid induced writhing method. Compounds IIIb, IIId, IIIf, IIIh, IIIj, IVa, IVb, IVd, IVf, IVh, IVi, IV3c, IV3e and IIj were showed analgesic potential after screening of Hot plate method. Conclusion: All tested compounds containing 1,2,4-triazole were found to be promising analgesic agents, for this activity pyrazole, tetrazole, isoxazole and pyrimidine leads might be supported.

  1. Genetic inactivation of mGlu5 receptor improves motor coordination in the Grm1crv4 mouse model of SCAR13 ataxia.

    Science.gov (United States)

    Bossi, Simone; Musante, Ilaria; Bonfiglio, Tommaso; Bonifacino, Tiziana; Emionite, Laura; Cerminara, Maria; Cervetto, Chiara; Marcoli, Manuela; Bonanno, Giambattista; Ravazzolo, Roberto; Pittaluga, Anna; Puliti, Aldamaria

    2018-01-01

    Deleterious mutations in the glutamate receptor metabotropic 1 gene (GRM1) cause a recessive form of cerebellar ataxia, SCAR13. GRM1 and GRM5 code for the metabotropic glutamate type 1 (mGlu1) and type 5 (mGlu5) receptors, respectively. Their different expression profiles suggest they could have distinct functional roles. In a previous study, homozygous mice lacking mGlu1 receptors (Grm1 crv4/crv4 ) and exhibiting ataxia presented cerebellar overexpression of mGlu5 receptors, that was proposed to contribute to the mouse phenotype. To test this hypothesis, we here crossed Grm1 crv4 and Grm5 ko mice to generate double mutants (Grm1 crv4/crv4 Grm5 ko/ko ) lacking both mGlu1 and mGlu5 receptors. Double mutants and control mice were analyzed for spontaneous behavior and for motor activity by rotarod and footprint analyses. In the same mice, the release of glutamate from cerebellar nerve endings (synaptosomes) elicited by 12mM KCl or by α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) was also evaluated. Motor coordination resulted improved in double mutants when compared to Grm1 crv4/crv4 mice. Furthermore, in in vitro studies, glutamate release elicited by both KCl depolarization and activation of AMPA autoreceptors resulted reduced in Grm1 crv4/crv4 mice compared to wild type mice, while it presented normal levels in double mutants. Moreover, we found that Grm1 crv4/crv4 mice showed reduced expression of GluA2/3 AMPA receptor subunits in cerebellar synaptosomes, while it resulted restored to wild type level in double mutants. To conclude, blocking of mGlu5 receptor reduced the dysregulation of glutamate transmission and improved motor coordination in the Grm1 crv4 mouse model of SCAR13, thus suggesting the possible usefulness of pharmacological therapies based on modulation of mGlu5 receptor activity for the treatment of this type of ataxia. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Synthesis, antimicrobial, and anti-inflammatory activities of novel 2-[3-(1-adamantyl)-4-substituted-5-thioxo-1,2,4-triazolin-1-yl] acetic acids, 2-[3-(1-adamantyl)-4-substituted-5-thioxo-1,2,4-triazolin-1-yl]propionic acids and related derivatives.

    Science.gov (United States)

    Al-Deeb, Omar A; Al-Omar, Mohamed A; El-Brollosy, Nasser R; Habib, Elsayed E; Ibrahim, Tarek M; El-Emam, Ali A

    2006-01-01

    The reaction of 3-(1-adamantyl)-4-substituted-1,2,4-triazoline-5-thiones 3a-g with sodium chloroacetate, in ethanolic sodium hydroxide yielded the corresponding N1-acetic acid derivatives 4a-g. The interaction of 3a-g with ethyl 2-bromopropionate in acetone, in the presence of potassium carbonate, yielded the corresponding N1-ethyl propionate derivatives 5a-g, which upon hydrolysis with aqueous sodium hydroxide afforded the corresponding propionic acid derivatives 6a-g. Similarly, the reaction of 3-(1-adamantyl)-4-amino-1,2,4-triazoline-5-thione 7 with sodium chloroacetate in ethanolic sodium hydroxide yielded the corresponding N1-acetic acid derivative 8. On the other hand, the reaction of 2-(1-adamantyl)-1,3,4-oxadiazoline-5-thione 9 with sodium chloroacetate yielded the corresponding S-acetic acid derivative 10. Compounds 4a-g, 5b, 5c, 5g, 6a-g, 8 and 10 were tested for in vitro activities against a panel of Gram-positive and Gram-negative bacteria and the yeast-like pathogenic fungus Candida albicans. Several derivatives produced good or moderate activities particularly against Bacillus subtilis. In addition, the in vivo anti-inflammatory activities of these compounds were determined using the carrageenin-induced paw oedema method in rats. Compounds 4a, 4b, 4e, 4f, 6f, 6g and 10 produced good dose-dependent anti-inflammatory activities.

  3. Design and synthesis of new of 3-(benzo[d]isoxazol-3-yl)-1-substituted pyrrolidine-2, 5-dione derivatives as anticonvulsants.

    Science.gov (United States)

    Malik, Sachin; Ahuja, Priya; Sahu, Kapendra; Khan, Suroor Ahmad

    2014-09-12

    A series of 3-(benzo[d]isoxazol-3-yl)-N-substituted pyrrolidine-2, 5-dione (7a-7d, 8a-8d, 9a-9c) have been prepared and evaluated for their anticonvulsant activities. Preliminary anticonvulsant activity was performed using maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) tests after intraperitoneal (ip) injection into mice, which are the most widely employed models for early identification of anticonvulsant candidate. The acute neurological toxicity (NT) was determined applying rotorod test. The quantitative evaluation after oral administration in rats showed that the most active was 3-(benzo[d]isoxazol-3-yl)-1-(4-fluorophenyl) pyrrolidine-2, 5-dione (8a) with ED50 values of 14.90 mg/kg. Similarly the most potent in scPTZ was 3-(benzo[d]isoxazol-3-yl)-1-cyclohexylpyrrolidine-2, 5-dione (7d) with ED50 values of 42.30 mg/kg. These molecules were more potent and less neurotoxic than phenytoin and ethosuximide which were used as reference antiepileptic drugs. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  4. Synthesis of novel 2,5-disubstituted-1,3,4-selenadiazoles from fatty acid hydrazides

    Directory of Open Access Journals (Sweden)

    Himani Varshney

    2018-01-01

    Full Text Available A series of novel unsaturated hydroxy and non-hydroxy fatty acid residue substituted 1,3,4-selenadiazoles were described here. These derivatives were synthesized from the reaction of fatty acid hydrazide 1(a–d with acetyl chloride in the presence of anhydrous sodium carbonate in tetrahydrofuran and water at 0 °C, to form N′-acetyl undec-10-enoic hydrazide 2a, N′-acetyl-(9Z-octadec-9-enoic hydrazide 2b, N′-acetyl-(9Z, 12R-12-hydroxy-9-enoic hydrazide 2c, and N′-acetyl-(9R, 12Z-9-hydroxy-12-enoic hydrazide 2d. Then these hydrazines (dicarbonyl compound on reaction with Woollin’s reagent (WR in toluene led to the corresponding 2-(dec-9′-enyl-5-methyl-1,3,4-selenadiazole 3a, 2-[(8′Z-heptadec-8′-enyl]-5-methyl-1,3,4-selenadiazole 3b, 2-[(8′Z, 11′R-11′-hydroxy-octadec-8′-enyl]-5-methyl-1,3,4-selenadiazole 3c, and 2-[(8′R, 11′Z-8′-hydroxy-octadec-11′-enyl]-5-methyl-1,3,4-selenadiazole 3d, respectively. These synthesized compounds were characterized on the basis of IR, 1H NMR, 13C NMR, mass spectra and elemental analysis results.

  5. Effect of intrathecal non-NMDA EAA receptor antagonist LY293558 in rats: a new class of drugs for spinal anesthesia.

    Science.gov (United States)

    Von Bergen, Nicholas H; Subieta, Alberto; Brennan, Timothy J

    2002-07-01

    Excitatory amino acid receptors are important for both sensory and motor function in the spinal cord. We studied the effects of intrathecal LY293558, a competitive non-N-methyl-D-aspartate excitatory amino acid receptor antagonist, on motor and sensory function in rats to determine whether drugs blocking these receptors could potentially be used as alternative agents to local anesthetics for spinal anesthesia. Rats were tested before and 15-240 min after intrathecal injection of 5 nmol (in 10 microl) LY293558. Sensory function was tested at the hind paw using withdrawal response to pin prick and withdrawal to pinch with sharp forceps. Motor performance (ambulation, placing reflex, and Rotorod time), blood pressure, and heart rate were also evaluated. Some tests were repeated the next day. Responses after LY293558 were compared to injection of 40 microl bupivacaine, 0.75%. Pin-prick responses at the forepaw, chest, abdomen, hind leg, and hind paw were also examined after intrathecal LY293558. Intrathecal LY293558 blocked both sensory and motor responses through 180 min; complete recovery was present the following day. No change in blood pressure or heart rate occurred. The effects of LY293558 were more pronounced and sustained than those of bupivacaine. Segmental blockade of the response to pin prick was present after LY293558. Drugs like LY293558 that block alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)/kainate receptors may be an alternative to local anesthetics for spinal anesthesia in humans.

  6. Anatomical and pharmacological characterization of excitatory amino acid receptors

    International Nuclear Information System (INIS)

    Monaghan, D.T.

    1985-01-01

    The majority of the excitatory neurotransmission in the vertebrate Central Nervous System is thought to be mediated by acidic amino acid neurotransmitters. However, relatively little is known about the excitatory amino acid receptors and their distribution within the CNS. By analyzing radioligand binding to purified synaptic plasma membranes and to thin tissue sections processed for autoradiography, multiple distinct binding sites were found. These binding sites exhibited the pharmacological properties indicative of the excitatory amino acid receptors, which had been identified by electrophysiological techniques. Specifically, L-[ 3 H]-glutamate and D-[ 3 H]-amino-5-phosphonopentanoate appear to label N-methyl-D-aspartate receptors, L-[ 3 H]-glutamate and [ 3 H]-kainic acid appear to label kainic acid receptors, and L-[ 3 H]-glutamate and [ 3 H]-amino-3-hydroxy-5-methyl-4-isoxazolepropionate appear to label quisqualate receptors. Together, these results confirm the three receptor scheme proposed for excitatory amino acid neurotransmission. These results also show that these transmitter-receptor systems are differentially distributed in the brain, and that the total distribution is consistent with that found by other markers for excitatory amino acid-using neurons

  7. Solubility of ethylene in methyl propionate

    NARCIS (Netherlands)

    Shariati - Sarabi, A.; Florusse, L.J.; Peters, C.J.

    2015-01-01

    In this work, the solubility of ethylene in methyl propionate was measured within a temperature range of 283.5–464.8 K and pressures up to 10.7 MPa. Experiments were carried out using the Cailletet apparatus, which uses a synthetic method for the experiments. The critical points of several isopleths

  8. Synthesis, characterization and physiological activity of some novel isoxazoles.

    Directory of Open Access Journals (Sweden)

    NITIN G. GHODILE

    2012-07-01

    Full Text Available Hushare VJ, Rajput PR, Malpani MO, Ghodile NG. 2012. Synthesis, characterization and physiological activity of some novel isoxazoles. Nusantara Bioscience 4: 81-85. A series of chlorosubstituted 4-aroylisoxazoles have been synthesized by refluxing chlorosubstituted-3-aroylflavones and 3-alkoylchromone with hydroxylamine hydrochloride in dioxane medium containing 0.5 mL piperidine. Chlorosubstituted-3-aroylflavones and chlorosubstituted-3-alkoylchromone were prepared by refluxing them separately with iodine crystal in ethanol. Initially chlorosubstituted-3-aroylflavanones and 3-alkoylchromanone were prepared by the interaction of different aromatic and aliphatic aldehydes with 1-(2’-hydroxy-3’,5’-dichlorophenyl-3-phenyl-1,3-propanedione. Constitutions of synthesized compounds were confirmed on the basis of elemental analysis, molecular weight determination, UV-Visible, I.R. and 1H-NMR spectral data. The titled compounds were evaluated for their growth promoting activity on some flowering plants viz. Papaver rhoeas, Calendula officinalise, Gladiola tristis, Gaillardia aristata, Dianthus chinensis, and Iberis sp. (candytuft. The results indicate that applicated plants had higher shoots and more number of leaves.

  9. Regioselectively nucleus and/or side-chain fluorinated 2-(Phenanthryl)propionic acids by an effective combination of radical and organometallic chemistry.

    Science.gov (United States)

    Ricci, Giacomo; Ruzziconi, Renzo

    2005-01-21

    Regioselectively nucleus and/or side-chain fluorinated 2-(phenanthr-1-yl)- and 2-(phenanthr-2-yl)propionic acids 1-5 were prepared using phenanthren-1(2H)-ones 6a-c as key intermediates. Thus, ethyl 2-(fluorophenanthryl)propionates 11 were obtained in good yields by Reformatsky reaction of 6a-c with ethyl 2-bromopropionate followed by dehydratation and DDQ-promoted aromatization of the resulting beta-hydroxyesters. Side-chain alkyl 2-hydroxy-2-(phenanthr-1-yl)propionates 14 were obtained by bromine/lithium permutation of dihydrophenanthryl bromides 12a-c with butyllithium followed by quenching of the lithiated intermediates with methyl pyruvate or ethyl 3,3,3-trifluoropyruvate and subsequent DDQ-promoted aromatization. The alkyl 2-hydroxy-2-(phenanthr-1-yl)propionates 25 were prepared by reacting 8-bromo-1,3-difluorophenanthrene 24 with butyllithium for 10 seconds at -110 degrees C and subsequent addition of the suitable pyruvate to the lithiated intermediates. Alkyl 2-hydroxy-2-(phenanthr-2-yl)propionates 26 and 29 were suitably obtained by site-selective metalation of 1,3-difluorophenanthrene 28 and the bromophenanthrene 24, respectively, with LDA followed by quenching of the metalated intermediates with the suitable alkyl pyruvate. Fluorination of the above alpha-hydroxypropionates with DAST, followed by the alkaline hydrolysis, allowed the expected 2-(phenanthryl)propionic acids 1-5 to be obtained in satisfactory overall yields.

  10. Synthesis and Biological Evaluation of (S)-Amino-2-methyl-4-[(76)Br]bromo-3-(E)-butenoic Acid (BrVAIB) for Brain Tumor Imaging.

    Science.gov (United States)

    Burkemper, Jennifer L; Huang, Chaofeng; Li, Aixiao; Yuan, Liya; Rich, Keith; McConathy, Jonathan; Lapi, Suzanne E

    2015-11-12

    The novel compound, (S)-amino-2-methyl-4-[(76)Br]bromo-3-(E)-butenoic acid (BrVAIB, [(76)Br]5), was characterized against the known system A tracer, IVAIB ([(123)I]8). [(76)Br]5 was prepared in a 51% ± 19% radiochemical yield with high radiochemical purity (≥98%). The biological properties of [(76)Br]5 were compared with those of [(123)I]8. Results showed that [(76)Br]5 undergoes mixed amino acid transport by system A and system L transport, while [(123)I]8 had less uptake by system L. [(76)Br]5 demonstrated higher uptake than [(123)I]8 in DBT tumors 1 h after injection (3.7 ± 0.4% ID/g vs 1.5 ± 0.3% ID/g) and also showed higher uptake vs [(123)I]8 in normal brain. Small animal PET studies with [(76)Br]5 demonstrated good tumor visualization of intracranial DBTs up to 24 h with clearance from normal tissues. These results indicate that [(76)Br]5 is a promising PET tracer for brain tumor imaging and lead compound for a mixed system A and system L transport substrate.

  11. Structural, Optical, Electrical and Photoelectrical Properties of 2-Amino-4-(5-bromothiophen-2-yl)-5,6-dihydro-6-methyl-5-oxo-4 H-pyrano[3,2-c] quinoline-3-carbonitrile Films

    Science.gov (United States)

    Mansour, A. M.; El-Taweel, F. M. A.; Abu El-Enein, R. A. N.; El-Menyawy, E. M.

    2017-12-01

    2-Amino-4-(5-bromothiophen-2-yl)-5,6-dihydro-6-methyl-5-oxo-4 H-pyrano[3,2-c] quinoline-3-carbonitrile (ABDQC) powder was synthesized and showed thermal stability up to 535 K. ABDQC films were successfully prepared using thermal evaporation. X-ray diffraction showed that the prepared ABDQC powder had a polycrystalline structure, whereas the deposited film had an amorphous structure. The surface morphology of the films was characterized by using a transmission electron microscope. Optical absorption properties of ABDQC films were investigated by spectrophotometric measurements of the transmittance and reflectance in the wavelength range 200-2500 nm. The films were found to have indirect allowed optical band gap of 2.5 eV. Current-voltage characteristics of Au/ABDQC/ p-Si/Al were measured at different temperatures (300-420 K) in which the temperature dependence of the diode parameters has been discussed. Under illumination, the device showed open-circuit voltage and short-circuit current of 0.09 V and 3.26 × 10-4 A, respectively.

  12. Magnetic behavior of MnPS3 phases intercalated by [Zn2L]2+ (LH2: macrocyclic ligand obtained by condensation of 2-hydroxy-5-methyl-1,3-benzenedicarbaldehyde and 1,2-diaminobenzene)

    International Nuclear Information System (INIS)

    Spodine, E.; Valencia-Galvez, P.; Fuentealba, P.; Manzur, J.; Ruiz, D.; Venegas-Yazigi, D.; Paredes-Garcia, V.; Cardoso-Gil, R.; Schnelle, W.; Kniep, R.

    2011-01-01

    The intercalation of the cationic binuclear macrocyclic complex [Zn 2 L] 2+ (LH 2 : macrocyclic ligand obtained by the template condensation of 2-hydroxy-5-methyl-1,3-benzenedicarbaldehyde and 1,2-diaminobenzene) was achieved by a cationic exchange process, using K 0.4 Mn 0.8 PS 3 as a precursor. Three intercalated materials were obtained and characterized: (Zn 2 L) 0.05 K 0.3 Mn 0.8 PS 3 (1), (Zn 2 L) 0.1 K 0.2 Mn 0.8 PS 3 (2) and (Zn 2 L) 0.05 K 0.3 Mn 0.8 PS 3 (3), the latter phase being obtained by an assisted microwave radiation process. The magnetic data permit to estimate the Weiss temperature θ of ∼-130 K for (1); ∼-155 K for (2) and ∼-130 K for (3). The spin canting present in the potassium precursor remains unperturbed in composite (3), and spontaneous magnetization is observed under 50 K in both materials. However composites (1) and (2) do not present this spontaneous magnetization at low temperatures. The electronic properties of the intercalates do not appear to be significantly altered. The reflectance spectra of the intercalated phases (1), (2) and (3) show a gap value between 1.90 and 1.80 eV, lower than the value observed for the K 0.4 Mn 0.8 PS 3 precursor of 2.8 eV. -- Graphical Abstract: Microwave assisted synthesis was used to obtain an intercalated MnPS 3 phase with a binuclear Zn(II) macrocyclic complex. A comparative magnetic study of the composites obtained by assisted microwave and traditional synthetic methods is reported. Display Omitted Highlights: → A rapid and efficient preparation of intercalated MnPS 3 composites by assisted microwave synthesis is described. → The exchange of potassium ions of the precursor by the macrocyclic Zn(II) complex is partial. → The composite obtained by assisted microwave synthesis retains the spontaneous magnetization, observed in the low temperature range of the magnetic susceptibility of the potassium precursor. → The materials obtained by the conventional method loose the spontaneous

  13. Glufosinate ammonium induces convulsion through N-methyl-D-aspartate receptors in mice.

    Science.gov (United States)

    Matsumura, N; Takeuchi, C; Hishikawa, K; Fujii, T; Nakaki, T

    2001-05-18

    Glufosinate ammonium, a broad-spectrum herbicide, causes convulsion in rodents and humans. Because of the structural similarities between glufosinate and glutamate, the convulsion induced by glufosinate ammonium may be ascribed to glutamate receptor activation. Three N-methyl-D-asparate (NMDA) receptor antagonists, dizocilpine, LY235959, and Compound 40, and an alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate receptor antagonist, NBQX, were coadministrated with glufosinate ammonium (80 mg/kg, intraperitoneally) in mice. Statistical analyses showed that the NMDA receptor antagonists markedly inhibited the convulsions, while the AMPA/kainate receptor antagonist had no effect on the convulsion. These results suggest that the convulsion caused by glufosinate ammonium is mediated through NMDA receptors.

  14. Neuropharmacologic characterization of strychnine seizure potentiation in the inferior olive lesioned rat

    International Nuclear Information System (INIS)

    Anderson, M.C.

    1988-01-01

    Cerebellar stimulation is associated with anticonvulsant activity in several animal models. There are two afferent inputs to cerebellar Purkinje cells: (1) parallel fibers, which relay mossy fiber input, from brainstem, spinal cord, cerebral cortex and cerebellum, and (2) climbing fibers, arising from the inferior olive. Both climbing and parallel fibers release excitatory amino acid neurotransmitters, which stimulate Purkinje cells and cause GABA release in the deep cerebellar nuclei. Climbing fibers also exert tonic inhibition over Purkinje cell activity by producing an absolute refractory period following stimulation, rendering Purkinje cells unresponsive to parallel fibers. Climbing fiber deafferentation by bilateral inferior olive lesions produced a specific decrease in threshold for strychnine-seizures in the rat. Inferior olive lesions produced no change in threshold to seizures induced by picrotoxin, bicuculline or pentylenetetrazole. Inferior olive lesions also produced abnormal motor behavior including, myoclonus, backward locomotion and hyperextension, which was significantly aggravated by strychnine, brucine, picrotoxin, bicuculline and pentylenetetrazole. Inferior olive lesions produced a significant increase in quisqualate sensitive [ 3 H]AMPA ((Rs)-alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid) binding to cerebellar membranes. AMPA is a glutamate analog with high affinity for quisqualate sensitive receptors

  15. Determination of 5-hydroxy-N-methyl-2-pyrrolidone and 2-hydroxy-N-methylsuccinimide in human plasma and urine using liquid chromatography-electrospray tandem mass spectrometry.

    Science.gov (United States)

    Carnerup, M A; Akesson, B; Jönsson, B A

    2001-09-15

    A method for simultaneous determination of 5-hydroxy-N-methyl-2-pyrrolidone (5-HNMP) and 2-hydroxy-N-methylsuccinimide (2-HMSI) was developed. These compounds are metabolites from N-methyl-2-pyrrolidone (NMP), a powerful and widely used organic solvent. 5-HNMP and 2-HMSI were purified from plasma and urine by solid-phase extraction using Isolute ENV+ columns, and analysed by liquid chromatography coupled to a mass spectrometer fitted with an atmospheric pressure turbo ion spray ionisation interface in the positive ion mode. The method was validated for plasma and urine concentrations from 0.12 to 25 microg/ml. The recoveries for 5-HNMP and 2-HMSI in plasma were 99 and 98%, respectively, and in urine 111 and 106%, respectively. For 5-HNMP and 2-HMSI, the within-day precision in plasma was 1-4 and 3-6%, respectively, and in urine 2-12 and 3-10%, respectively. The corresponding data for the between-day precision was 5 and 3-6%, respectively, and 4-6 and 7-8%, respectively. The detection limit for 5-HNMP was 4 ng/ml in plasma and 120 ng/ml in urine. For 2-HMSI, it was 5 ng/ml in plasma and 85 ng/ml in urine. The method is applicable for analysis of plasma and urine samples from workers exposed to NMP.

  16. Synthesis, DNA binding and cytotoxic activity of pyrimido[4',5':4,5]thieno(2,3-b)quinoline with 9-hydroxy-4-(3-diethylaminopropylamino) and 8-methoxy-4-(3-diethylaminopropylamino) substitutions.

    Science.gov (United States)

    KiranKumar, Hulihalli N; RohitKumar, Heggodu G; Advirao, Gopal M

    2018-01-01

    Two new derivatives of pyrimido[4',5';4,5]thieno(2,3-b)quinoline (PTQ), 9-hydroxy-4-(3-diethylaminopropylamino)pyrimido[4',5';4,5]thieno(2,3-b)quinoline (Hydroxy-DPTQ) and 8-methoxy-4-(3-diethylaminopropylamino)pyrimido[4',5';4,5]thieno(2,3-b)quinoline (Methoxy-DPTQ) were synthesized and their DNA binding ability was analyzed using spectroscopy (UV-visible, fluorescence and circular dichroism), ethidium bromide dye displacement assay, melting temperature (T m ) analysis and computational docking studies. The hypochromism in UV-visible spectrum and increased fluorescence emission of Hydroxy-DPTQ and Methoxy-DPTQ in the presence of DNA suggested the molecule-DNA interaction. The association constants calculated from UV-visible and spectral titrations were of the order 10 4 to 10 6 M -1 . Circular dichroism studies corroborated the induced conformational changes in DNA upon addition of molecules. The change in the ellipticity was observed both in negative and positive peak of DNA, thus, suggesting the intercalation of molecules. The observed displacement of ethidium bromide from the DNA and increased T m , upon addition of DNA confirmed the intercalative mode of binding. This was further validated by computational docking, which showed clear intercalation of molecules into the d(GpC)-d(CpG) site of the receptor DNA. Anticancer activities of these molecules are evaluated by using MTT assay. Both molecules showed antiproliferative activity against all the three cancer cells studied, with Hydroxy-DPTQ being more potential molecule among the two. IC 50 value of Hydroxy-DPTQ and Methoxy-DPTQ were in the range of 3-5μM and 130-250μM, respectively. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Preparation of 3,5-disubstituted pyrazoles and isoxazoles from terminal alkynes, aldehydes, hydrazines, and hydroxylamine.

    Science.gov (United States)

    Harigae, Ryo; Moriyama, Katsuhiko; Togo, Hideo

    2014-03-07

    The reaction of terminal alkynes with n-BuLi, and then with aldehydes, followed by the treatment with molecular iodine, and subsequently hydrazines or hydroxylamine provided the corresponding 3,5-disubstituted pyrazoles or isoxazoles in good yields with high regioselectivity, through the formations of propargyl secondary alkoxides and α-alkynyl ketones. The present reactions are one-pot preparation of 3,5-disubstituted pyrazoles from terminal alkynes, aldehydes, molecular iodine, and hydrazines, and 3,5-disubstituted isoxazoles from terminal alkynes, aldehydes, molecular iodine, and hydroxylamine.

  18. Methyl 4′,5-dichloro-2-hydroxy-4,6-dimethylbiphenyl-3-carboxylate

    Directory of Open Access Journals (Sweden)

    Muhammad Adeel

    2012-04-01

    Full Text Available In the title compound, C16H14Cl2O3, the dihedral angle between the mean planes of the two benzene rings is 55.30 (5°. The methyl ester group lies within the ring plane due to an intramolecular O—H...O hydrogen bond [maximum deviation from the C8O2 mean plane is 0.0383 (13 Å]. In the crystal, molecules are held together by rather weak C—H...O hydrogen bonds.

  19. Prediction of allosteric sites on protein surfaces with an elastic-network-model-based thermodynamic method.

    Science.gov (United States)

    Su, Ji Guo; Qi, Li Sheng; Li, Chun Hua; Zhu, Yan Ying; Du, Hui Jing; Hou, Yan Xue; Hao, Rui; Wang, Ji Hua

    2014-08-01

    Allostery is a rapid and efficient way in many biological processes to regulate protein functions, where binding of an effector at the allosteric site alters the activity and function at a distant active site. Allosteric regulation of protein biological functions provides a promising strategy for novel drug design. However, how to effectively identify the allosteric sites remains one of the major challenges for allosteric drug design. In the present work, a thermodynamic method based on the elastic network model was proposed to predict the allosteric sites on the protein surface. In our method, the thermodynamic coupling between the allosteric and active sites was considered, and then the allosteric sites were identified as those where the binding of an effector molecule induces a large change in the binding free energy of the protein with its ligand. Using the proposed method, two proteins, i.e., the 70 kD heat shock protein (Hsp70) and GluA2 alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor, were studied and the allosteric sites on the protein surface were successfully identified. The predicted results are consistent with the available experimental data, which indicates that our method is a simple yet effective approach for the identification of allosteric sites on proteins.

  20. Short-term carcinogenicity testing of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3-methylimidazo[4,5-f] quinoline (IQ) in E mu-pim-1 transgenic mice

    DEFF Research Database (Denmark)

    Sørensen, Ilona Kryspin; Mortensen, Alicja; Kristiansen, E.

    1996-01-01

    The usefulness of transgenic E mu-pim-1 mice over-expressing the pim-1 oncogene in lymphoid tissues, as sensitive test organisms was studied in a short-term carcinogenicity study. The mice were fed standard diet Altromin 1314 supplemented either with 0.03% 2-amino-1-methyl-6-phenylimidazo[4,5-b......]pyridine (PhIP) for 7 months or with 0.03% 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) for 6 months, PhIP and IQ are heterocyclic amines formed during cooking of meat and fish and are mutagenic to bacteria and cultured mammalian cells, PhIP is a potent mouse lymphomagen, while IQ is a liver carcinogen...... to non-transgenic mice. Our results suggest that the transgenic E mu-pim-1 mouse may be a useful model for short-term carcinogenicity screening of potential genotoxic carcinogens having the lymphoid system as target tissue, The carcinogen IQ which does not have the lymphoid system as a target...

  1. Microwave Assisted Synthesis and Unusual Coupling of Some Novel Pyrido[3,2-f][1,4]thiazepines

    Directory of Open Access Journals (Sweden)

    Mohamed M. Youssef

    2011-05-01

    Full Text Available 3-Amino-3-thioxopropanamide (1 reacted with ethyl acetoacetate to form 6-hydroxy-4-methyl-2-thioxo-2,3-dihydropyridine-3-carboxamide (2, which reacted with α-haloketones 3 to produce 2,3-disubstituted-8-hydroxy-6-methyl-2H,5H-pyrido[3,2-f]-[1,4]thiazepin-5-ones 4a-c. Benzoylation of 4c led to the formation of the dibenzoate derivative 9. Compounds 4a-c could be prepared stepwise through the formation of S-alkylated derivatives 10a-c. Compounds 2, 4a-c, 9 and 10a-c were prepared using microwave as a source of heat, and gave better yields in shorter times than those achieved by traditional methods. Coupling of 4a-c with arenediazonium chlorides proceeded unusually to give the 6-hydroxy-4-methyl-2-(arylazothieno[2,3-b]pyridin-3(2H-one ring contraction products 14. Structures of the newly synthesized compounds were proven by spectral and chemical methods.

  2. Absorption of N-phenylpropenoyl-L-amino acids in healthy humans by oral administration of cocoa (Theobroma cacao).

    Science.gov (United States)

    Stark, Timo; Lang, Roman; Keller, Daniela; Hensel, Andreas; Hofmann, Thomas

    2008-10-01

    Besides flavan-3-ols, a family of N-phenylpropenoyl-L-amino acids (NPAs) has been recently identified as polyphenol/amino acid conjugates in the seeds of Theobroma cacao as well as in a variety of herbal drugs. Stimulated by reports on their biological activity, the purpose of this study was to investigate if these amides are absorbed by healthy volunteers after administration of a cocoa drink. For the first time, 12 NPAs were quantified in human urine by means of a stable isotope dilution analysis with LC-MS/MS (MRM) detection. A maximum amount was found in the urine taken 2 h after the cocoa consumption. The highest absolute amount of NPAs excreted with the urine was found for N-[4'-hydroxy-(E)-cinnamoyl]-L-aspartic acid (5), but the highest recovery rate (57.3 and 22.8%), that means the percentage amount of ingested amides excreted with the urine, were determined for N-[4'-hydroxy-(E)-cinnamoyl]-L-glutamic acid (6) and N-[4'-hydroxy-3'-methoxy-(E)-cinnamoyl]-L-tyrosine (13). In order to gain first insights into the NPA metabolism in vivo, urine samples were analyzed by LC-MS/MS before and after beta-glucuronidase/sulfatase treatment. As independent of the enzyme treatment the same NPA amounts were found in urine, there is strong evidence that these amides are metabolized neither via their O-glucuronides nor their O-sulfates. In order to screen for caffeic acid O-glucuronides as potential NPA metabolites, urine samples were screened by means of LC-MS/MS for caffeic acid 3-O-beta-D-glucuronide and 4-O-beta-D-glucuronide. But not even trace amounts of one of these glucuronides were detectable, thus excluding them as major NPA metabolites and underlining the importance of future investigations on a potential O-methylation or reduction of the N-phenylpropenoyl moiety in NPAs.

  3. 1-[(E-(3-Hydroxy-4-methoxybenzylideneamino]-3-methylthiourea

    Directory of Open Access Journals (Sweden)

    Md. Azharul Arafath

    2016-10-01

    Full Text Available In the title thiosemicarbazone Schiff base compound, C10H13N3O2S, the dihedral angle between the benzene ring and methyl carbothioamide side arm was found to be 17.4 (4°. The presence of two intramolecular hydrogen bonds is noted, namely hydroxy-O—H...O(methoxy and amine-N—H...N(imine. In the crystal, pairwise amine-N—H...S hydrogen bonds give rise to centrosymmetric {...HNCS}2 synthons, which lead to dimeric aggregates.

  4. Formation of 4-hydroxy-2,5-dimethyl-3[2H]-furanone by Zygosaccharomyces rouxii: identification of an intermediate.

    Science.gov (United States)

    Hauck, Tobias; Brühlmann, Fredi; Schwab, Wilfried

    2003-07-01

    The formation of the important flavor compound 4-hydroxy-2,5-dimethyl-3[2H]-furanone (HDMF; Furaneol) from D-fructose-1,6-bisphosphate by the yeast Zygosaccharomyces rouxii was studied with regard to the identification of intermediates present in the culture medium. Addition of o-phenylenediamine, a trapping reagent for alpha-dicarbonyls, to the culture medium and subsequent analysis by high-pressure liquid chromatography with diode array detection revealed the formation of three quinoxaline derivatives derived from D-fructose-1,6-bisphosphate under the applied growth conditions (30 degrees C; pH 4 to 5). Isolation and characterization of these compounds by tandem mass spectrometry and nuclear magnetic resonance spectroscopy led to the identification of phosphoric acid mono-(2,3,4-trihydroxy-4-quinoxaline-2-yl-butyl) ester (Q1), phosphoric acid mono-[2,3-dihydroxy-3-(3-methyl-quinoxaline-2-yl)-propyl] ester (Q2), and phosphoric acid mono-[2-hydroxy-3-(3-methyl-quinoxaline-2-yl)-propyl] ester (Q3). Q1 and Q2 were formed independently of Z. rouxii cells, whereas Q3 was detected only in incubation systems containing the yeast. Identification of Q2 demonstrated for the first time the chemical formation of 1-deoxy-2,3-hexodiulose-6-phosphate in the culture medium, a generally expected but never identified intermediate in the formation pathway of HDMF. Since HDMF was detected only in the presence of Z. rouxii cells, additional enzymatic steps were presumed. Incubation of periplasmic and cytosolic protein extracts obtained from yeast cells with D-fructose-1,6-bisphosphate led to the formation of HDMF, implying the presence of the required enzymes in both extracts.

  5. Comprehensive physicochemical studies of a new hybrid material: 2-Amino-4-methyl-3-nitropyridinium hydrogen oxalate

    Science.gov (United States)

    Bryndal, I.; Kucharska, E.; Wandas, M.; Lorenc, J.; Hermanowicz, K.; Mączka, M.; Lis, T.; Marchewka, M.; Hanuza, J.

    2014-01-01

    A new organic-organic salt, 2-amino-4-methyl-3-nitropyridinium hydrogen oxalate (AMNPO), and its deuterium analogue have been synthesized and characterized by means of FT-IR, FT-Raman, DSC and single crystal X-ray studies. The DSC measurements and temperature dependence of the IR and Raman spectra in the range 4-295 K show that it undergoes a reversible phase transition at ∼240 K. At room temperature it crystallizes in noncentrosymmetric space group P21. The unit-cell is built of the 2-amino-4-methyl-3-nitropyridinium cations and oxalate monoanions which are connected via the Nsbnd H⋯O and Osbnd H⋯O hydrogen bonds. The geometrical and hydrogen bond parameters are similar for non-deuterated (at 120 and 293 K) and deuterated compounds (at 90 K). The phase transition is probably a consequence of order-disorder transition inside of hydrogen network. The 6-311G(2d,2p) basis set with B3LYP functional have been used to discuss the structure and vibrational spectra of the studied compound.

  6. Polyketide family of novel antibacterial 7-O-methyl-5'-hydroxy-3'-heptenoate-macrolactin from seaweed-associated Bacillus subtilis MTCC 10403.

    Science.gov (United States)

    Chakraborty, Kajal; Thilakan, Bini; Raola, Vamshi Krishna

    2014-12-17

    Seaweed-associated heterotrophic bacterial communities were screened to isolate potentially useful antimicrobial strains, which were characterized by phylogenetic analysis. The bacteria were screened for the presence of metabolite genes involved in natural product biosynthetic pathway, and the structural properties of secondary metabolites were correlated with the genes. Bioactivity-guided isolation of polyene antibiotic 7-O-methyl-5'-hydroxy-3'-heptenoate-macrolactin from Bacillus subtilis MTCC10403 associated with seaweed Anthophycus longifolius using mass spectrometry and extensive 2D-NMR studies was carried out. The newly isolated macrolactin compound is a bactericidal antibiotic with broad spectrum activity against human opportunistic clinical pathogens. The biosynthetic pathway of 7-O-methyl-5'-hydroxy-3'-heptenoate-macrolactin by means of a stepwise, decarboxylative condensation pathway established the PKS-assisted biosynthesis of the parent macrolactin and the side-chain 5-hydroxyhept-3-enoate moiety attached to the macrolactin ring system at C-7. Antimicrobial activity analysis combined with the results of amplifying genes encoding for polyketide synthetase and nonribosomal peptide synthetase showed that seaweed-associated bacteria had broad-spectrum antimicrobial activity. The present work may have an impact on the exploitation of macrolactins for pharmaceutical and biotechnological applications.

  7. Synthesis of specifically 2H-labeled reserpines, 3,4,5-trimethoxybenzoic acids, and syringic acid

    International Nuclear Information System (INIS)

    Roth, R.W.; Fischer, D.L.; Pachta, J.M.; Althaus, J.F.

    1982-01-01

    3,4,5-Trimethoxy- 2 H 9 -, 4-methoxy-3,5-dimethoxy- 2 H 6 , and 4-hydroxyl-3,5-dimethoxy- 2 H 6 -benzoic acids were prepared from n-propyl 3,4,5-trihydroxybenzoate (n-propyl gallate) by means of appropriate alkylation-hydrolysis sequences employing iodomethane- 2 H 3 or dimethyl- 2 H 6 -sulfate as the deuterium source. 4-Methoxy- 2 H 3 -3,5-dimethoxybenzoic acid was similarly prepared from ethyl 4-hydroxy-3,5-dimethoxybenzoate. The labeled trimethoxybenzoic acids were converted to the corresponding 2 H-labeled reserpines by condensation of the acid chlorides with methyl reserpate in pyridine according to the classical procedure. The labeled reserpine analog methyl 18-0-(4-hydroxy-3,5-dimethoxy- 2 H 6 )benzoyl reserpate was likewise prepared from 4-hydroxy-3,5-dimethoxy- 2 H 6 -benzoic acid via the intermediate methyl 18-0-(4-ethoxycarbonyloxy-3,5-dimethoxy- 2 H 6 -benzoyl)reserpate (syrosingopine- 2 H 6 ). The isotopic purity of each compound exceeded 99 atom percent 2 H. (author)

  8. Acute cannabinoids impair working memory through astroglial CB1 receptor modulation of hippocampal LTD.

    Science.gov (United States)

    Han, Jing; Kesner, Philip; Metna-Laurent, Mathilde; Duan, Tingting; Xu, Lin; Georges, Francois; Koehl, Muriel; Abrous, Djoher Nora; Mendizabal-Zubiaga, Juan; Grandes, Pedro; Liu, Qingsong; Bai, Guang; Wang, Wei; Xiong, Lize; Ren, Wei; Marsicano, Giovanni; Zhang, Xia

    2012-03-02

    Impairment of working memory is one of the most important deleterious effects of marijuana intoxication in humans, but its underlying mechanisms are presently unknown. Here, we demonstrate that the impairment of spatial working memory (SWM) and in vivo long-term depression (LTD) of synaptic strength at hippocampal CA3-CA1 synapses, induced by an acute exposure of exogenous cannabinoids, is fully abolished in conditional mutant mice lacking type-1 cannabinoid receptors (CB(1)R) in brain astroglial cells but is conserved in mice lacking CB(1)R in glutamatergic or GABAergic neurons. Blockade of neuronal glutamate N-methyl-D-aspartate receptors (NMDAR) and of synaptic trafficking of glutamate α-amino-3-hydroxy-5-methyl-isoxazole propionic acid receptors (AMPAR) also abolishes cannabinoid effects on SWM and LTD induction and expression. We conclude that the impairment of working memory by marijuana and cannabinoids is due to the activation of astroglial CB(1)R and is associated with astroglia-dependent hippocampal LTD in vivo. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Longicalycinin A, a new cytotoxic cyclic peptide from Dianthus superbus var. longicalycinus (MAXIM.) WILL.

    Science.gov (United States)

    Hsieh, Pei-Wen; Chang, Fang-Rong; Wu, Ching-Chung; Li, Chien-Ming; Wu, Kuen-Yuh; Chen, Su-Li; Yen, Hsin-Fu; Wu, Yang-Chang

    2005-03-01

    A new cyclic peptide, longicalycinin A (1), and six known compounds, vaccaroside A, dianoside A, dianoside G, 3-(4-hydroxy-3-methoxy-phenyl)propionic acid methyl ester, p-hydroxybenzoic acid, and p-hydroxybenzaldehyde were isolated from the MeOH extract of Dianthus superbus var. longicalycinus. The amino acid sequences of 1 was elucidated as cyclo(Gly(1)-Phe(2)-Tyr(3)-Pro(4)-Phe(5)-) on the basis of ESI tandem mass fragmentation analysis, chemical evidence, and extensive 2D NMR methods. Furthermore, compound 1 showed cytotoxicity to Hep G2 cancer cell line.

  10. Synthesis and characterization of tritium labeled N-((R)-1-((S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl)-3-methyl-1-oxobutan-2-yl)-3-sulfamoylbenzamide.

    Science.gov (United States)

    Hong, Yang; Hynes, John; Tian, Yuan; Balasubramanian, Balu; Bonacorsi, Samuel

    2015-08-01

    N-((R)-1-((S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl)-3-methyl-1-oxobutan-2-yl)-3-sulfamoylbenzamide is a potent C-C chemokine receptor 1 (CCR1) antagonist. The compound, possessing benzamide functionality, successfully underwent tritium/hydrogen (T/H) exchange with an organoiridium catalyst (Crabtree's catalyst). The labeling pattern in the product was studied with liquid chromatography-mass spectrometry, time-of-flight mass spectrometry, and (3) H-NMR. Overall, multiple labeled species were identified. In addition to the anticipated incorporation of tritium in the benzamide moiety, tritium labeling was observed in the valine portion of the molecule including substitution at its chiral carbon. Using authentic standards, liquid chromatography analysis of the labeled compound showed complete retention of stereochemical configuration. Copyright © 2015 John Wiley & Sons, Ltd.

  11. Synthesis and in vivo evaluation of [O-methyl-11C](2R,4R)-4-hydroxy-2-[2-[2-[2-(3-methoxy)phenyl]ethyl]phenoxy] ethyl-1-methylpyrrolidine as a 5-HT2A receptor PET ligand

    International Nuclear Information System (INIS)

    Kumar, J.S. Dileep; Prabhakaran, Jaya; Erlandsson, Kjell; Majo, Vattoly J.; Simpson, Norman R.; Pratap, Mali; Heertum, Ronald L. van; Mann, J. John; Parsey, Ramin V.

    2006-01-01

    The serotonin 2A (5-HT 2A ) receptor is implicated in the pathophysiology of schizophrenia and mood disorders, and in vivo studies of this receptor would be of value in studying the pathophysiology of these disorders and in measuring the relationship of clinical response to receptor occupancy for 5-HT 2A antagonists such as atypical antipsychotics. Therefore, (2R,4R)-4-hydroxy-2-[2-[2-[2-(3-methoxy)-phenyl]ethyl] phenoxy]ethyl-1-methylpyrrolidine (MPM) (13), a selective and high-affinity (K i =0.79 nM) 5HT 2A antagonist, has been radiolabeled with carbon-11 by O-methylation of the corresponding desmethyl analogue (2R,4R)-4-hydroxy-2-[2-[2-[2-(3-hydroxy)phenyl]ethyl]phenoxy] ethyl-1-methylpyrrolidine (12) with [ 11 C]methyltriflate in order to determine the suitability of [ 11 C]MPM to quantify 5-HT 2A in living brain using PET. Desmethyl-MPM 12 and standard MPM were prepared, starting from 3-hydroxymethylphenol (2), in excellent yield. The yield obtained for radiolabeling was 40±5% (EOB), and the total synthesis time was 30 min at EOS. PET studies with [ 11 C]MPM in baboon showed a distribution in the brain consistent with the known distribution of 5-HT 2A receptors. The time-activity curves for the high-binding regions peaked at ∼45 min after injection. Blocking studies with M100907 demonstrated not only 38-57% blocking of tracer binding in brain regions known to have 5-HT 2A receptors but also 38% blocking in cerebellum, which has a low 5-HT 2A receptor concentration. Although [ 11 C]MPM exhibits appropriate kinetics in baboon for imaging 5-HT 2A receptors, its specific binding in cerebellum and higher proportion of nonspecific binding limit its usefulness for the in vivo quantification of 5-HT 2A receptors with PET

  12. The 1-hydroxy-2-methyl-butenyl 4-diphosphate reductase gene from ...

    African Journals Online (AJOL)

    The 1-hydroxy-2-methyl-butenyl 4-diphosphate reductase gene from Taxus media: Cloning, characterization and functional identification. Y Sun, M Chen, J Tang, W Liu, C Yang, Y Yang, X Lan, M Hsieh, Z Liao ...

  13. Simple assembly of polysubstituted pyrazoles and isoxazoles via ring closure-ring opening domino reaction of 3-acyl-4,5-dihydrofurans with hydrazines and hydroxylamine.

    Science.gov (United States)

    Chagarovskiy, Alexey O; Budynina, Ekaterina M; Ivanova, Olga A; Rybakov, Victor B; Trushkov, Igor V; Melnikov, Mikhail Ya

    2016-03-14

    A convenient general approach to 2-(pyrazol-4-yl)- and 2-(isoxazol-4-yl)ethanols based on the Brønsted acid-initiated reaction of 3-acyl-4,5-dihydrofurans with hydrazines or hydroxylamine was developed. Further transformation of the alcohol moiety in 2-(pyrazolyl)ethanols affording 2-(pyrazolyl)ethylamine as potent bioactive compounds as well as pyrazole-substituted derivatives of antitumor alkaloid crispine A was elaborated.

  14. Clinical study on antibody-associated limbic encephalitis

    Directory of Open Access Journals (Sweden)

    WANG Jia-wei

    2013-01-01

    Full Text Available In recent years, the antibody-associated limbic encephalitis (LE has attracted attentions of more and more clinicians. The associated antibodies mainly act on neuronal cell surface antigens, including the N-methyl-D-aspartate (NMDA receptor, the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA receptor, the γ-aminobutyric acid B (GABAB receptor, leucine-rich glioma-inactivated 1 (LGI1 and contactin-associated protein-like 2 (Caspr2 and so on. The clinical manifestation is primarily defined by the subacute onset of short-term memory loss, seizures, confusion and psychiatric symptoms suggesting the involvement of the limbic system. These severe and protracted disorders can affect children and young adults, occurring with or without tumor association. Routine detection of serum and cerebrospinal fluid (CSF and imaging tests show no specificity, but associated antibodies can be detected in serum and (or CSF. The patients respond well to tumor resection and immunotherapies, including corticosteroids, intravenous immunoglobulin (IVIg, plasma exchange or combination of them, but may relapse. This article aims to study the clinical features and treatment of antibody-associated limbic encephalitis and to improve the diagnosis and prognosis of these diseases.

  15. Synthesis, resolution and radioiodination of S(-)trans-5-hydroxy-2-[N-n-propyl-N-(3'-iodo-2'-propenyl)amino]tet ralin-S(-)trans-5-OH-PIPAT: a new dopamine D2-like receptor ligand

    International Nuclear Information System (INIS)

    Chumpradit, Sumalee; Meiping Kung; Vessotskie, Janet; Kung, H.F.

    1995-01-01

    A new dopamine D2-like receptor ligand, (R,S)trans-5-hydroxy-2-[N-n0propyl-N-(3'-iodo-2'-propeny)amino]tet ralin ((R,S)trans-5-OH-PIPAT,3), based on high affinity dopamine receptor agonist 5-hydroxy-2-[N,N-(di-n-propyl)-2-amino]tetralin (5-OH-DPAT,1), was prepared. The synthesis was achieved by a reductive amination of 5-methoxy-2-tetralone with n-propylamine, followed by N-alkylation, to afford 5-methoxy-N-propyl-N-2'-aminotetralin,7. Reduction of 7 with tributyltin hydride gave the tri-n-butyl tin derivative,8, which was converted to 9 by an iododemetalation reaction. Demethylation of 9 gave the desired compound, (R,S)trans-5-OH-PIPAT,3. The resolved (R) and (S)trans-5-OH-PIPAT,3 were also quantitatively prepared. (author)

  16. 4-Hydroxy-5-methoxy-N,1-dimethyl-2-oxo-N-[4-(trifluoromethylphenyl]-1,2-dihydroquinoline-3-carboxamide

    Directory of Open Access Journals (Sweden)

    Emmanuel S. Akinboye

    2014-03-01

    Full Text Available The title compound, C20H17F3N2O4, named tasquinimod, is a second-generation oral quinoline-3-carboxamide analogue, which is currently in phase III clinical trials for the treatment of metastatic prostate cancer. The quinoline unit is almost planar (r.m.s. deviation of fitted atoms = 0.0075 Å. The carboxamide side chain, substituted at position 3, is tilted by 88.07 (7° to the quinoline plane. Both the methyl and carbonyl groups of this carboxamide side chain are in a syn conformation. The 4-(trifluoromethylphenyl plane is inclined at 50.62 (17° to the plane of the carboxamide side chain, and at 87.14 (4° to the plane of the quinoline ring system. The 4-hydroxy H atom acts as a double proton donor in an intramolecular hydrogen bond to the 5-position methoxy O atom and in an intermolecular contact to the 2-oxo group, generating a chain along [010] in the crystal structure.

  17. FaQR, required for the biosynthesis of the strawberry flavor compound 4-hydroxy-2,5-dimethyl-3(2H)-furanone, encodes an enone oxidoreductase.

    Science.gov (United States)

    Raab, Thomas; López-Ráez, Juan Antonio; Klein, Dorothée; Caballero, Jose Luis; Moyano, Enriqueta; Schwab, Wilfried; Muñoz-Blanco, Juan

    2006-04-01

    The flavor of strawberry (Fragaria x ananassa) fruit is dominated by an uncommon group of aroma compounds with a 2,5-dimethyl-3(H)-furanone structure. We report the characterization of an enzyme involved in the biosynthesis of 4-hydroxy-2,5-dimethyl-3(2H)-furanone (HDMF; Furaneol), the key flavor compound in strawberries. Protein extracts were partially purified, and the observed distribution of enzymatic activity correlated with the presence of a single polypeptide of approximately 37 kD. Sequence analysis of two peptide fragments showed total identity with the protein sequence of a strongly ripening-induced, auxin-dependent putative quinone oxidoreductase, Fragaria x ananassa quinone oxidoreductase (FaQR). The open reading frame of the FaQR cDNA consists of 969 bp encoding a 322-amino acid protein with a calculated molecular mass of 34.3 kD. Laser capture microdissection followed by RNA extraction and amplification demonstrated the presence of FaQR mRNA in parenchyma tissue of the strawberry fruit. The FaQR protein was functionally expressed in Escherichia coli, and the monomer catalyzed the formation of HDMF. After chemical synthesis and liquid chromatography-tandem mass spectrometry analysis, 4-hydroxy-5-methyl-2-methylene-3(2H)-furanone was confirmed as a substrate of FaQR and the natural precursor of HDMF. This study demonstrates the function of the FaQR enzyme in the biosynthesis of HDMF as enone oxidoreductase and provides a foundation for the improvement of strawberry flavor and the biotechnological production of HDMF.

  18. Investigations on the synthesis and pharmacological properties of 4-alkoxy-2-[2-hydroxy-3-(4-aryl-1-piperazinyl)propyl]-6-methyl-1H-pyrrolo[3,4-c]pyridine-1,3(2H)-diones.

    Science.gov (United States)

    Sladowska, Helena; Filipek, Barbara; Szkatuła, Dominika; Sabiniarz, Aleksandra; Kardasz, Małgorzata; Potoczek, Joanna; Sieklucka-Dziuba, Maria; Rajtar, Grazyna; Kleinrok, Zdzisław; Lis, Tadeusz

    2002-11-01

    Synthesis of 2-[2-hydroxy-3-(4-aryl-1-piperazinyl)propyl] derivatives of 4-alkoxy-6-methyl-1H-pyrrolo[3,4-c]pyridine-1,3(2H)-diones (8-12) is described. The chlorides used in the above synthesis can exist in two isomeric forms: chain (18-20) and cyclic (19a, 20a). The compounds 8-12 exhibited potent analgesic activity which was superior than that of acetylsalicylic acid in two different tests. Most of the investigated imides suppressed significantly spontaneous locomotor activity in mice.

  19. Formation of the reduced form of furaneol® (2,5-dimethyl-4-hydroxy-tetrahydrofuran-3-one) during the Maillard reaction through catalysis of amino acid metal salts.

    Science.gov (United States)

    Nashalian, Ossanna; Wang, Xi; Yaylayan, Varoujan A

    2016-11-01

    Under pyrolytic conditions the acidity/basicity of Maillard reaction mixtures can be controlled through the use of hydrochloride or sodium salts of amino acids to generate a diversity of products. When the degradation of glucose was studied under pyrolytic conditions using excess sodium glycinate the reaction was found to generate a major unknown peak having a molecular ion at m/z 130. Subsequent in-depth isotope labelling studies indicated that acetol was an important precursor of this compound under pyrolytic and aqueous heating conditions. The dimerisation and cyclisation of acetol into 2,5-dimethyl-4-hydroxy-tetrahydrofuran-3-one was found to be catalysed by amino acid metal salts. Also, ESI/qTOF/MS studies indicated that the unknown peak has expected molecular formula of C6H10O3. Finally, a peak having the same retention time and mass spectrum was also generated pyrolytically when furaneol® was reduced with NaBH4 confirming the initial hypothesis regarding the unknown peak to be the reduced form of furaneol®. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. [Monograph for N-Methyl-pyrrolidone (NMP) and human biomonitoring values for the metabolites 5-Hydroxy-NMP and 2-Hydroxy-N-methylsuccinimide].

    Science.gov (United States)

    2015-10-01

    1-Methyl-pyrrolidone (NMP) is used as a solvent in many technical applications. The general population may be exposed to NMP from the use as ingredient in paint and graffiti remover, indoors also from use in paints and carpeting. Because of developmental toxic effects, the use of NMP in consumer products in the EU is regulated. The developmental effects accompanied by weak maternally toxic effects in animal experiments are considered as the critical effects by the German HBM Commission. Based on these effects, HBM-I values of 10 mg/l urine for children and of 15 mg/l for adults, respectively, were derived for the metabolites 5-Hydroxy-NMP and 2-Hydroxy-N-methylsuccinimide. HBM-II-values were set to 30 mg/l urine for children and 50 mg/l for adults, respectively. Because of similar effects of the structural analogue 1-ethyl-2-pyrrolidone (NEP), the possible mixed exposure to both compounds has to be taken into account when evaluating the total burden.

  1. Sleep-inducing N-alkyl-5-[m-(trifluoromethyl)phenyl]-5-hydroxy-2-pyrrolidinones and N-alkyl-3-(trifluoromethyl)cinnamamides.

    Science.gov (United States)

    Houlihan, W J; Gogerty, J H; Ryan, E A; Schmitt, G

    1985-01-01

    A series of N-alkyl-3-[m-(trifluoromethyl)phenyl]-5-hydroxy-2-pyrrolidinones and N-alkyl-3-(trifluoromethyl)-cinnamamides were prepared and screened in a series of tests designed to detect potential sleep inducers. The more active members of the series were evaluated for their ability to induce sleep in Cebus monkeys. The most active compound, N-methyl-5-[m-(trifluoromethyl)phenyl]-5-hydroxy-2-pyrrolidinone, was equal to methaqualone.

  2. Displacement of DL-[3H]-2-amino-4-phosphonobutanoic acid ( [3H]APB) binding with methyl-substituted APB analogues and glutamate agonists

    International Nuclear Information System (INIS)

    Robinson, M.B.; Crooks, S.L.; Johnson, R.L.; Koerner, J.F.

    1985-01-01

    The binding of the excitatory amino acid antagonist DL-2-amino-4-phosphonobutanoic acid (DL-APB) to rat brain synaptic plasma membranes was characterized. As determined by Scatchard analysis, the binding was saturable and homogeneous with a Kd = 6.0 microM and Bmax = 380 pmol/mg of protein. The binding was dependent on the presence of Ca 2+ and Cl - ions and was diminished upon freezing. The association rate constant was 6.8 X 10(-3) microM -1 min -1 , and the dissociation rate constant was 2.0 X 10(-2) min -1 . The L isomers of APB, glutamate, and aspartate were more potent as displacers of APB binding than the D isomers. With the exception of kynurenic acid, all compounds examined in both systems were more potent as displacers of APB binding than as inhibitors of synaptic transmission. This difference in potency was most pronounced for agonists at dentate granule cells. L-Glutamate, D-glutamate, and L-glutamate tetrazole were between 140- and 7500-fold more potent as displacers of DL-APB binding than as inhibitors of synaptic transmission. D-2-Amino-5-phosphonopentanoic acid and alpha-methyl-APB were between 10- and 20-fold more potent as displacers of binding

  3. Synthesis, antifungal evaluation and in silico study of novel Schiff bases derived from 4-amino-5(3,5-dimethoxy-phenyl-4H-1,2,4-triazol-3-thiol

    Directory of Open Access Journals (Sweden)

    N.S. Hari Narayana Moorthy

    2017-05-01

    Full Text Available A novel series of Schiff bases based on of 4-amino-5-(3,5-dimethoxy-phenyl-4H-1,2,4-triazol-3-thiol scaffold was prepared by heating thiocarbohydrazide and 3,5,-dimethoxy benzoic acid at the temperature above its meting point, and subsequently, treating with substituted benzaldehydes. The chemical constituents in the synthesized compounds were confirmed by IR, Mass, 1H NMR spectroscopy and elemental analysis and the antifungal activity was evaluated against Candida albicans. The structure activity relationship analysis shows that the chloride substituted derivatives possess promising activity in micromolar concentration and also the hydroxy phenyl derivatives exhibited considerable activity at 128 μg/ml. But other compounds with amino, furan and methoxy substitutions did not show antifungal activity till the concentration of 512 μg/ml. In silico pharmacokinetic prediction shows that all the compounds obeyed Lipinski rule of 5 and are free of toxicity and metabolically stable. Pharmacophore analysis revealed that the aromatic/hydrophobic and aromatic/acceptor/donor features in the compounds are essential for the activity. The predicted cardiotoxicity (hERG and lethal effect of the synthesized compounds will permit us to carry out further in vitro and in vivo toxicity studies.

  4. Synthesis and pharmacological properties of new derivatives of 4-alkoxy-6-methyl-1H-pyrrolo[3,4-c]pyridine-1,3(2H)-diones.

    Science.gov (United States)

    Sladowska, Helena; Sabiniarz, Aleksandra; Sapa, Jacek; Filipek, Barbara

    2009-01-01

    Synthesis of 2-(2-hydroxy-3-amino)propyl derivatives of 4-alkoxy-6-methyl-1H-pyrrolo[3,4-c]pyridine-1,3(2H)-diones (24-35) is described. The chlorides used in the above synthesis exist mainly in the cyclic forms (18, 20-23). Only chloride with benzhydryl substituent at the nitrogen atom of piperazine has the chain structure (19). Among the studied imides the most active analgesics in the "writhing" syndrome test proved to be compounds 30 and 31 (with LD50 > 2000 mg/kg) containing 4-benzylpiperidino group. Furthermore, all imides suppressed significantly spontaneous locomotor activity of mice.

  5. Isoxazole-type derivatives related to combretastatin A-4, synthesis and biological evaluation.

    Science.gov (United States)

    Kaffy, Julia; Pontikis, Renée; Carrez, Danièle; Croisy, Alain; Monneret, Claude; Florent, Jean-Claude

    2006-06-15

    Novel combretastatin analogues bearing various five-membered heterocycles with consecutive oxygen and nitrogen atoms, in place of the olefinic bridge of CA4, have been synthesized (isoxazole, isoxazoline, oxadiazole, etc). These compounds have been evaluated for cytotoxicity and their ability to inhibit the tubulin assembly. On the basis of the relative position of the aromatic A- and B-rings on the heterocyclic moiety, they could be split in two classes, the alpha,gamma- or alpha,beta-diaryl heterocyclic derivatives. In the first series, the 3,5-diaryloxadiazole 9a displayed comparable antitubulin activity to that of CA4, but was devoid of cytotoxic effects. Among the alpha,beta-diaryl heterocyclic derivatives, the 4,5-diarylisoxazole 35 exhibited greater antitubulin activity than that of CA4 (0.75 vs 1.2 microM), but modest antiproliferative activity. These data showed that minor alteration in the chemical structure of the heterocyclic ring and its relative orientation with regard to the two phenyl rings of CA4 could dramatically influence the tubulin binding properties.

  6. An Efficient One-Pot Synthesis of Pyrano[3,2-c]quinolin-2,5-dione Derivatives Catalyzed by L-Proline

    Directory of Open Access Journals (Sweden)

    Jing Wang

    2012-11-01

    Full Text Available A series of 4-aryl-6-methyl-3,4-dihydro-2H-pyrano[3,2-c]quinolin-2,5(6H-diones were synthesized via the three-component reactions of aromatic aldehydes, 4-hydroxy-1-methylquinolin-2(1H-one, and Meldrum’s acid catalyzed by L-proline. The structures of the products were identified by spectroscopic analysis. A mechanism for this three-component reaction catalyzed by L-proline was proposed.

  7. (S)-α-AMINO-3-HYDROXY-5-METHYL-4-ISOXAZOLEPROPANOIC ...

    African Journals Online (AJOL)

    a

    2003 Chemical Society of Ethiopia. ______ ... Chemistry Department, Kenyatta University, P.O. Box 43844, Nairobi 00100, Kenya. (Received June ... with {N,O} bonding which results in the formation of a stable five membered chelate ring. The.

  8. N-methyl-D-aspartic acid receptor agonists

    DEFF Research Database (Denmark)

    Madsen, U; Frydenvang, Karla Andrea; Ebert, B

    1996-01-01

    (R,S)-2-Amino-2-(3-hydroxy-5-methyl-4-isoxazolyl)acetic acid [(R,S)-AMAA, 4] is a potent and selective agonist at the N-methyl-D-aspartic acid (NMDA) subtype of excitatory amino acid receptors. Using the Ugi "four-component condensation" method, the two diastereomers (2R)- and (2S)-2-[3-(benzyloxy......) showed peak affinity for [3H]AMPA receptor sites (IC50 = 72 +/- 13 microM) and was shown to be a more potent inhibitor of [3H]CPP binding (IC50 = 3.7 +/- 1.5 microM) than (S)-AMAA (9) (IC50 = 61 +/- 6.4 microM). Neither enantiomer of AMAA affected [3H]kainic acid receptor binding significantly...

  9. Synthesis and in vivo evaluation of [O-methyl-{sup 11}C](2R,4R)-4-hydroxy-2-[2-[2-[2-(3-methoxy)phenyl]ethyl]phenoxy] ethyl-1-methylpyrrolidine as a 5-HT{sub 2A} receptor PET ligand

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, J.S. Dileep [Dept. of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States)]|[Div. of Brain Imaging, Dept. of Neuroscience, New York State Psychiatric Institute, New York, NY 10032 (United States)]. E-mail: dk2038@columbia.edu; Prabhakaran, Jaya [Dept. of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States); Erlandsson, Kjell [Dept. of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States)]|[Dept. of Radiology, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States); Majo, Vattoly J. [Dept. of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States); Simpson, Norman R. [Dept. of Radiology, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States); Pratap, Mali [Dept. of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States)]|[Div. of Brain Imaging, Dept. of Neuroscience, New York State Psychiatric Institute, New York, NY 10032 (United States); Heertum, Ronald L. van [Dept. of Radiology, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States); Mann, J. John [Dept. of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States)]|[Dept. of Radiology, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States)]|[Div. of Brain Imaging, Dept. of Neuroscience, New York State Psychiatric Institute, New York, NY 10032 (United States); Parsey, Ramin V. [Dept. of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States)]|[Div. of Brain Imaging, Dept. of Neuroscience, New York State Psychiatric Institute, New York, NY 10032 (United States)

    2006-05-15

    The serotonin{sub 2A} (5-HT{sub 2A}) receptor is implicated in the pathophysiology of schizophrenia and mood disorders, and in vivo studies of this receptor would be of value in studying the pathophysiology of these disorders and in measuring the relationship of clinical response to receptor occupancy for 5-HT{sub 2A} antagonists such as atypical antipsychotics. Therefore, (2R,4R)-4-hydroxy-2-[2-[2-[2-(3-methoxy)-phenyl]ethyl] phenoxy]ethyl-1-methylpyrrolidine (MPM) (13), a selective and high-affinity (K {sub i}=0.79 nM) 5HT{sub 2A} antagonist, has been radiolabeled with carbon-11 by O-methylation of the corresponding desmethyl analogue (2R,4R)-4-hydroxy-2-[2-[2-[2-(3-hydroxy)phenyl]ethyl]phenoxy] ethyl-1-methylpyrrolidine (12) with [{sup 11}C]methyltriflate in order to determine the suitability of [{sup 11}C]MPM to quantify 5-HT{sub 2A} in living brain using PET. Desmethyl-MPM 12 and standard MPM were prepared, starting from 3-hydroxymethylphenol (2), in excellent yield. The yield obtained for radiolabeling was 40{+-}5% (EOB), and the total synthesis time was 30 min at EOS. PET studies with [{sup 11}C]MPM in baboon showed a distribution in the brain consistent with the known distribution of 5-HT{sub 2A} receptors. The time-activity curves for the high-binding regions peaked at {approx}45 min after injection. Blocking studies with M100907 demonstrated not only 38-57% blocking of tracer binding in brain regions known to have 5-HT{sub 2A} receptors but also 38% blocking in cerebellum, which has a low 5-HT{sub 2A} receptor concentration. Although [{sup 11}C]MPM exhibits appropriate kinetics in baboon for imaging 5-HT{sub 2A} receptors, its specific binding in cerebellum and higher proportion of nonspecific binding limit its usefulness for the in vivo quantification of 5-HT{sub 2A} receptors with PET.

  10. Novel enaminones as non-cytotoxic compounds with mild antibacterial activity: Synthesis and structure-activity correlations

    Science.gov (United States)

    Cindrić, Marina; Rubčić, Mirta; Hrenar, Tomica; Pisk, Jana; Cvijanović, Danijela; Lovrić, Jasna; Vrdoljak, Višnja

    2018-02-01

    Six non-symmetric enaminones 4-[(2-hydroxy-5-methylphenyl)amino]pent-3-en-2-one (H2L1), 4-[(2-hydroxy-4-methylphenyl)amino]pent-3-en-2-one (H2L2), 4-[(4-hydroxy-2-methylphenyl)amino)]pent-3-en-2-one (H2L3), 3-[(2-hydroxy-5-methylphenyl)amino]-1-phenylbut-2-en-1-one (H2L4), 3-[(2-hydroxy-4-methylphenyl)amino]-1-phenylbut-2-en-1-one (H2L5) and 3-[(4-hydroxy-2-methylphenyl)amino]-1-phenylbut-2-en-1-one (H2L6) have been prepared by solution based method. The enaminones were characterized by elemental and DSC analysis, NMR and IR spectroscopy. Crystal and molecular structures of H2L1, H2L2, H2L4 and H2L6 were determined via single crystal X-ray analysis. The prepared enaminones were screened against THP-1 and HepG2 cells, and Staphylococcus aureus, Enterococcus faecalis, Escherichia coli and Moraxella catarrhalis bacteria to assess their cytotoxic and antibacterial activity, respectively. All compounds proved to be non-cytotoxic and showed mild or no antibacterial activity. Quantum mechanical calculations suggest that the presence of hydroxy group in ortho position, combined with the methyl group on the same aromatic ring, has a significant impact on the biological activities.

  11. 4-[4-(4-Fluorophenyl-2-methyl-5-oxo-2,5-dihydroisoxazol-3-yl]-1-methylpyridinium iodide–4-[3-(4-fluorophenyl-2-methyl-5-oxo-2,5-dihydroisoxazol-4-yl]-1-methylpyridinium iodide (0.6/0.4

    Directory of Open Access Journals (Sweden)

    Simona Margutti

    2008-01-01

    Full Text Available The crystal structure of the title compound, C16H16FN2O2+·I−, was determined as part of a study of the biological activity of isoxazolone derivatives as p38 mitogen-activated protein kinase (MAPK inhibitors. The X-ray crystal structure of 4-[4-(4-fluorophenyl-2-methyl-5-oxo-2,5-dihydroisoxazol-3-yl]-1-methylpyridinium iodide showed the presence of the regioisomer 4-[3-(4-fluorophenyl-2-methyl-5-oxo-2,5-dihydroisoxazol-4-yl]-1-methylpyridinium iodide. The synthesis of the former compound was achieved by reacting 4-(4-fluorophenyl-3-(4-pyridylisoxazol-5(2H-one after treatment with Et3N in dimethylformamide, with iodomethane. The unexpected formation of the regioisomer could be explained by a rearrangement occurring via aziridine of the isoxazolone compound. The regioisomers have site occupancies of 0.632 (4/0.368 (4. The two six members rings make a dihedral angle of 66.8 (2°.

  12. Design, synthesis and pharmacological evaluation of some novel derivatives of 1-{[3-(furan-2-yl-5-phenyl-4,5-dihydro-1,2-oxazol-4-yl]methyl}-4-methyl piperazine

    Directory of Open Access Journals (Sweden)

    Jagdish Kumar

    2017-01-01

    Full Text Available A novel series of 1-{[3-(furan-2-yl-5-substituted phenyl-4,5-dihydro-1,2-oxazol-4-yl]methyl}-4-methyl piperazine, compounds 3a–l have been synthesized. The synthetic work was carried out beginning from 2-acetylfuran through Claisen Schmidt condensation with different types of aromatic aldehyde, affording 1-(furan-2-yl-3-substitutedphenylprop-2-en-1-ones which on cyclization with hydroxylamine hydrochloride resulted in 3-(furan-2-yl-5-substitutedphenyl-4,5-dihydro-1,2-oxazole formation. The isoxazolines were subjected to Mannich’s reaction in the presence of N-methyl piperazine to produce the desired product. The chemical structures of the compounds were proved by IR, 1H NMR, 13C-NMR and Mass spectrometric data. The antidepressant activities of the compounds were investigated by Porsolt’s behavioral despair (forced swimming test on albino mice. Moreover, the antianxiety activity of the newly synthesized compounds was investigated by the plus maze method. Compounds 3a and 3k reduced the duration of immobility times of 152.00–152.33% at 10 mg/kg dose level and compounds 3a and 3k have also shown significant antianxiety activity.

  13. Improved Synthesis of 2',6'-Dihydroxy-3,4-dimethoxy Chalcone by Grinding Technique to Synthesize 5-Hydroxy-3',4'-dimethoxy Flavone

    Directory of Open Access Journals (Sweden)

    Elfi Susanti VH

    2014-07-01

    Full Text Available 5-hydroxy-3',4'-dimethoxy flavone can be efficiently synthesized in two steps via the formation of 2',6'-dihydroxy-3,4-dimethoxy chalcone with good results. 2',6'-dihydroxy-3,4-dimethoxy chalcone as reactants for synthesis of flavones was prepared through Claisen-Schmidt condensation reaction between 2,6-dihydroxyacetophenones,3,4-dimethoxybenzaldehyde and solid NaOH in mortar for 15 min. The yield of the product (70% is higher than conventional method (65%. This chalcone then oxidatively cyclized with iodine to form 5-hydroxy-3',4'-dimethoxy flavone (yield 62%. Compounds synthesized were characterized by spectroscopic (IR, 1H-NMR, and 13C-NMR.

  14. Ethyl 4-{1-[(2,4-dinitrophenylhydrazono]ethyl}-5-(2-naphthylmethoxymethylisoxazole-3-carboxylate

    Directory of Open Access Journals (Sweden)

    Nicholas R. Natale

    2009-01-01

    Full Text Available The title compound, C26H23N5O8, was prepared and its structure investigated to further develop a working hypothesis for the essential binding pharmacophore for ligands of the System Xc- transporter [Patel et al. (2004. Neuropharmacology, 46, 273–284]. The hydrazone group displays an E geometry and the isoxazole double bond and C=N group of the hydrazone are in an s-cis relationship. The secondary amino NH group forms an intramolecular N—H...O hydrogen bond to a ring nitro group. There is a dihedral angle of 44.27 (5° between the isoxazole plane and the hydrazone group plane.

  15. ANTI-ALLERGIC EFFECTS OF 1,5-BIS(4’-HYDROXY-3’-METHOXYPHENYL-1,4-PENTADIENE-3-ONE ON MAST CELL-MEDIATED ALLERGY MODEL

    Directory of Open Access Journals (Sweden)

    AGUNG ENDRO NUGROHO

    2009-01-01

    Full Text Available 1,5-bis(4’-hydroxy-3’-methoxyphenyl-1,4-pentadiene-3-one is a 1,5-diphenyl-1,4-pentadiene-3-one analogue of curcumin that is produced by modifying the middle site of curcumin leading to 1,4-pentadiene-3-ones to maintain the hydroxy moiety at the aromatic rings that are responsible for its biological activities. Curcumin has been reported to have anti-allergic effects and can inhibit the release of histamine from mast cells. In the present study, we evaluated the anti-allergic effects of 1,5-bis(4’-hydroxy-3’-methoxyphenyl-1,4-pentadiene-3-one in a mast cell-mediated allergy mode in order to provide information about a newly synthesised-compound for an alternative allergy drug. The study was performed using (1 a rat basophilic leukaemia (RBL-2H3 cell line, which is a tumour analogue of mast cells, with DNP24-BSA, thapsigargin and ionomycin as inducers for secretory markers from mast cells, and (2 an active cutaneous anaphylaxis (ACA reaction, with ovalbumin as an inductor of mast cell degranulation. Treatment with 1,5-bis(4’-hydroxy-3’-methoxyphenyl-1,4-pentadiene-3-one strongly inhibited the DNP24-BSA, thapsigargin and ionomycin-mediated release of histamine and β-hexosaminidase from the RBL-2H3 cell line. The results indicated that this compound influenced the activation processes of FcεRI by antigen and intracellular Ca2+ signalling events in mast cells. In type 1 allergy model, this compound also inhibited the active cutaneous anaphylactic reaction on rat dorsal skins generated by ovalbumin. We conclude that the compound 1,5-bis(4’-hydroxy-3’-methoxyphenyl-1,4-pentadiene-3-one showed anti-allergic activities mediated by mechanisms related to intracellular signalling events in mast cells.

  16. Insight into the theoretical and experimental studies of 1-phenyl-3-methyl-4-benzoyl-5-pyrazolone N(4)-methyl-N(4)- phenylthiosemicarbazone - A potential NLO material

    Science.gov (United States)

    Sangeetha, K. G.; Aravindakshan, K. K.; Safna Hussan, K. P.

    2017-12-01

    The synthesis, geometrical parameters, spectroscopic studies, optimised molecular structure, vibrational analysis, Mullikan population analysis, MEP, NBO, frontier molecular orbitals and NLO effects of 1-phenyl-3-methyl-4-benzoyl-5-pyrazolone N-(4)-methyl-N-(4)-phenylthiosemicarbazone, C25H23N5OS (L1) have been communicated in this paper. A combined experimental and theoretical approach was used to explore the structure and properties of the compound. For computational studies, Gaussian 09 program was used. Starting geometry of molecule was taken from X-ray refinement data and has been optimized by using DFT (B3LYP) method with the 6-31+G (d, p) basis sets. NBO analysis gave insight into the strongly delocalized structure, responsible for the nonlinearity and hence the stability of the molecule. Frontier molecular orbitals have been defined to forecast the global reactivity descriptors of L1. The computed first-order hyperpolarizability (β) of the compound is 2 times higher than that of urea and this account for its nonlinear optical property. Simultaneously, a molecular docking study of the compound was performed using GLIDE Program. For this, three biological enzymes, histone deacetylase, ribonucleotide reductase and DNA methyl transferase, were selected as receptor molecules.

  17. NMDAR inhibition-independent antidepressant actions of ketamine metabolites

    Science.gov (United States)

    Zanos, Panos; Moaddel, Ruin; Morris, Patrick J.; Georgiou, Polymnia; Fischell, Jonathan; Elmer, Greg I.; Alkondon, Manickavasagom; Yuan, Peixiong; Pribut, Heather J.; Singh, Nagendra S.; Dossou, Katina S.S.; Fang, Yuhong; Huang, Xi-Ping; Mayo, Cheryl L.; Wainer, Irving W.; Albuquerque, Edson X.; Thompson, Scott M.; Thomas, Craig J.; Zarate, Carlos A.; Gould, Todd D.

    2016-01-01

    Major depressive disorder afflicts ~16 percent of the world population at some point in their lives. Despite a number of available monoaminergic-based antidepressants, most patients require many weeks, if not months, to respond to these treatments, and many patients never attain sustained remission of their symptoms. The non-competitive glutamatergic N-methyl-D-aspartate receptor (NMDAR) antagonist, (R,S)-ketamine (ketamine), exerts rapid and sustained antidepressant effects following a single dose in depressed patients. Here we show that the metabolism of ketamine to (2S,6S;2R,6R)-hydroxynorketamine (HNK) is essential for its antidepressant effects, and that the (2R,6R)-HNK enantiomer exerts behavioural, electroencephalographic, electrophysiological and cellular antidepressant actions in vivo. Notably, we demonstrate that these antidepressant actions are NMDAR inhibition-independent but they involve early and sustained α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor activation. We also establish that (2R,6R)-HNK lacks ketamine-related side-effects. Our results indicate a novel mechanism underlying ketamine’s unique antidepressant properties, which involves the required activity of a distinct metabolite and is independent of NMDAR inhibition. These findings have relevance for the development of next generation, rapid-acting antidepressants. PMID:27144355

  18. Synthesis, electrochemical, spectrophotometric and potentiometric studies of two azo-compounds derived from 4-amino-2-methylquinoline in ethanolic-aqueous buffered solutions

    Energy Technology Data Exchange (ETDEWEB)

    El-Attar, Mona A.; Ghoneim, Mohamed M. [Analytical Chemistry Research Unit, Chemistry Department, Tanta University (Egypt); Ismail, Iqbal M., E-mail: maema.2011@yahoo.com [Chemistry Department, Faculty of Science, King Abdul Aziz University, Jeddah (Saudi Arabia)

    2012-08-15

    Two azo-compounds, 2-methyl-4-(5-amino-2-hydroxy-phenylazo)-quinoline (2) and 2-methyl-4-(2-hydroxy-5-nitrophenylazo)-quinoline, derived from 4-amino-2-methylquinoline were synthesized. Their chemical structures were characterized and confirmed by means of elemental chemical analysis, infrared (IR) spectroscopy, {sup 1}H nuclear magnetic resonance (NMR) and mass spectrometry (MS). The electrochemical behavior of the starting compound (4-amino-2-methylquinoline) and of the two synthesized azo-derivatives was studied at the mercury electrode in the B-R universal buffer at various pH values (2-11.5) containing 40% (v/v) ethanol using dc-polarography, cyclic voltammetry and controlled-potential coulometry. Their electrode reaction pathways were elucidated and discussed. The dissociation constants (pKa) of the examined compounds, stability constants and stoichiometry of their complexes in solution with some transition metal ions (Co(II), Ni(II), Cu(II), La(III) and UO{sup 2+}{sub 2}) were determined. (author)

  19. Dopamine D1-like receptor in lateral habenula nucleus affects contextual fear memory and long-term potentiation in hippocampal CA1 in rats.

    Science.gov (United States)

    Chan, Jiangping; Guan, Xin; Ni, Yiling; Luo, Lilu; Yang, Liqiang; Zhang, Pengyue; Zhang, Jichuan; Chen, Yanmei

    2017-03-15

    The Lateral Habenula (LHb) plays an important role in emotion and cognition. Recent experiments suggest that LHb has functional interaction with the hippocampus and plays an important role in spatial learning. LHb is reciprocally connected with midbrain monoaminergic brain areas such as the ventral tegmental area (VTA). However, the role of dopamine type 1 receptor (D1R) in LHb in learning and memory is not clear yet. In the present study, D1R agonist or antagonist were administered bilaterally into the LHb in rats. We found that both D1R agonist and antagonist impaired the acquisition of contextual fear memory in rats. D1R agonist or antagonist also impaired long term potentiation (LTP) in hippocampal CA3-CA1 synapses in freely moving rats and attenuated learning induced phosphorylation of α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR) subunit 1 (GluA1) at Ser831 and Ser845 in hippocampus. Taken together, our results suggested that dysfunction of D1R in LHb affected the function of hippocampus. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Molecularly imprinted poly(4-amino-5-hydroxy-2,7-naphthalenedisulfonic acid) modified glassy carbon electrode as an electrochemical theophylline sensor

    International Nuclear Information System (INIS)

    Aswini, K.K.; Vinu Mohan, A.M.; Biju, V.M.

    2016-01-01

    Theophylline is an inexpensive drug employed in asthma and chronic obstructive pulmonary disorder medications and is toxic at higher concentration. The development of a molecularly imprinted polymer based theophylline electrochemical sensor on glassy carbon electrode by the electropolymerization of 4-amino-5-hydroxy-2,7-naphthalenedisulfonic acid is being discussed in this work. The MIP modification enhances the theophylline recognition ability and the electron transfer kinetics of the bare electrode. The parameters, controlling the performance of the imprinted polymer based sensor, like number of electropolymerization cycles, composition of the pre-polymerization mixture, pH and immersion time were investigated and optimized. The interaction energy and the most stable conformation of the template–monomer complex in the pre-polymerization mixture were determined computationally using ab initio calculations based on density functional theory. The amperometric measurements showed that the developed sensor has a method detection limit of 0.32 μM for the dynamic range of 0.4 to 17 μM, at optimized conditions. The transducer possesses appreciable selectivity in the presence of structurally similar interferents such as theobromine, caffeine and doxofylline. The developed sensor showed remarkable stability and reproducibility and was also successfully employed in theophylline detection from commercially available tablets. - Highlights: • Molecularly imprinted polymer based theophylline sensor was developed. • Imprinted poly(4-amino-5-hydroxy-2,7-naphthalenedisulfonic acid) was electrodeposited. • Most stable template-monomer complex was assigned by computational analysis. • Possessed remarkable selectivity in the presence of structurally similar interferents • Employed for theophylline detection from commercially available tablets

  1. Molecularly imprinted poly(4-amino-5-hydroxy-2,7-naphthalenedisulfonic acid) modified glassy carbon electrode as an electrochemical theophylline sensor

    Energy Technology Data Exchange (ETDEWEB)

    Aswini, K.K., E-mail: aswinikk@ymail.com; Vinu Mohan, A.M.; Biju, V.M., E-mail: vmbiju@ymail.com

    2016-08-01

    Theophylline is an inexpensive drug employed in asthma and chronic obstructive pulmonary disorder medications and is toxic at higher concentration. The development of a molecularly imprinted polymer based theophylline electrochemical sensor on glassy carbon electrode by the electropolymerization of 4-amino-5-hydroxy-2,7-naphthalenedisulfonic acid is being discussed in this work. The MIP modification enhances the theophylline recognition ability and the electron transfer kinetics of the bare electrode. The parameters, controlling the performance of the imprinted polymer based sensor, like number of electropolymerization cycles, composition of the pre-polymerization mixture, pH and immersion time were investigated and optimized. The interaction energy and the most stable conformation of the template–monomer complex in the pre-polymerization mixture were determined computationally using ab initio calculations based on density functional theory. The amperometric measurements showed that the developed sensor has a method detection limit of 0.32 μM for the dynamic range of 0.4 to 17 μM, at optimized conditions. The transducer possesses appreciable selectivity in the presence of structurally similar interferents such as theobromine, caffeine and doxofylline. The developed sensor showed remarkable stability and reproducibility and was also successfully employed in theophylline detection from commercially available tablets. - Highlights: • Molecularly imprinted polymer based theophylline sensor was developed. • Imprinted poly(4-amino-5-hydroxy-2,7-naphthalenedisulfonic acid) was electrodeposited. • Most stable template-monomer complex was assigned by computational analysis. • Possessed remarkable selectivity in the presence of structurally similar interferents • Employed for theophylline detection from commercially available tablets.

  2. A sensitive progesterone enzyme immunoassay for cow, goat and llama plasma using a monoclonal antibody and Danazol (17-α-2,4-pregnadien-20-yno (2,3-D) isoxazol-17-ol) as a displacing agent

    International Nuclear Information System (INIS)

    Aba, M.A.; Carlsson, M.A.; Karlsson, A.; Forsberg, M.

    2001-01-01

    A sensitive progesterone enzyme immunoassay was developed for cow, goat and llama plasma using a monoclonal antibody and Danazol (17-α-2,4-pregnadien-20-yno (2,3-d) isoxazol-17-ol) as a displacing agent. The microtitration plates were first coated with progesterone 3 (o-carboxy-methyl) oxine: BSA conjugate. The immune reaction was performed by incubating overnight a mixture of 50 μL of plasma and 100 μL of first antibody. After washing, 100 μL of the second antibody (horse radish peroxidase conjugated anti-mouse IgG) were added. The plates were incubated for 1 hour and washed. Immediately the substrate solution was added and finally the reaction stopped and optical density measured. This assay allows accurate determination of progesterone in plasma from several species with good specificity, precision and accuracy, and is suitable for the rapid assessment of luteal function and reproductive status in both clinical and research situations. (author)

  3. Bubble point pressures of binary system of methanol and methyl propionate

    NARCIS (Netherlands)

    Shariati, A.; Florusse, L.J.; Kroon, M.C.; Peters, C.J.

    2016-01-01

    In this work, bubble point pressures of the system of methanol + methyl propionate were measured for several isopleths within temperature and pressure ranges of 382-444 K and 0.437-2.285 MPa, respectively. The vapor pressures of pure methanol and methyl propionate were also measured. The two-suffix

  4. Amino methylation of 2-R-6-R_1-imidazo-[2.1-B]-1.3.4-thiadiazole

    International Nuclear Information System (INIS)

    Saidov, D.K.; Rakhmonov, R.O.; Khodzhiboev, Yu.; Kukaniev, M.A.; Bandaev, S.

    2015-01-01

    Present article is devoted to amino methylation of 2-R-6-R_1-imidazo-[2.1-B]-1.3.4-thiadiazole. The reaction of new modifications of derivatives of imidazo-[2.1-B]-1.3.4-thiadiazoles-2-bromine-6-p-bromophenyl and 2-alkyl alkylene sulfonyl-6-phenyl imidazo--[2.1-B]-1.3.4-thiadiazole on Mannich with secondary and heterocyclic amines was studied.

  5. Novel 1,5,7-trihydroxy-3-hydroxy methyl anthraquinone isolated from terrestrial Streptomyces sp. (eri-26) with antimicrobial and molecular docking studies.

    Science.gov (United States)

    Duraipandiyan, V; Al-Dhabi, N A; Balachandran, C; Raj, M Karunai; Arasu, M Valan; Ignacimuthu, S

    2014-11-01

    Streptomyces sp. isolate ERI-26 was obtained from the Nilgiris forest soil of Western Ghats, Tamil Nadu, India. Novel anthraquinone compound was isolated from the active fraction 5; it was identified by spectroscopical data using UV, IR, NMR and MASS. The isolated compound 1,5,7-trihydroxy-3-hydroxy methyl anthraquinone was tested against bacteria and fungi at minimum inhibitory concentration level. The compound showed significant antimicrobial activity against bacteria, Staphylococcus aureus at 125 μg/ml, Staphylococcus epidermidis at 62.5 μg/m, Bacillus subtilis at 31.25 μg/ml, fungi; Epidermophyton floccosum at 62.5 μg/ml, Aspergillus niger at 31.25 μg/ml, Aspergiller flavus at 31.25 μg/ml, Trichophyton rubrum at 62.5 μg/ml and Botrytis cinerea at 62.5 μg/ml. The isolated compound was subjected to molecular docking studies for the inhibition of TtgR, topoisomerase IV and AmpC β-lactamase enzymes which are targets for antimicrobials. Docking studies of the compound showed low docking energy indicating its usefulness as antimicrobial agent. 1,5,7-Trihydroxy-3-hydroxy methyl anthraquinone is new, and its antimicrobial and molecular docking properties are reported for the first time.

  6. 5-hydroxy-2-methyl-1,4-naphthoquinone, a vitamin K3 analogue, suppresses STAT3 activation pathway through induction of protein tyrosine phosphatase, SHP-1: potential role in chemosensitization.

    Science.gov (United States)

    Sandur, Santosh K; Pandey, Manoj K; Sung, Bokyung; Aggarwal, Bharat B

    2010-01-01

    The activation of signal transducers and activators of transcription 3 (STAT3) has been linked with carcinogenesis through survival, proliferation, and angiogenesis of tumor cells. Agents that can suppress STAT3 activation have potential not only for prevention but also for treatment of cancer. In the present report, we investigated whether 5-hydroxy-2-methyl-1,4-naphthoquinone (plumbagin), an analogue of vitamin K, and isolated from chitrak (Plumbago zeylanica), an Ayurvedic medicinal plant, can modulate the STAT3 pathway. We found that plumbagin inhibited both constitutive and interleukin 6-inducible STAT3 phosphorylation in multiple myeloma (MM) cells and this correlated with the inhibition of c-Src, Janus-activated kinase (JAK)1, and JAK2 activation. Vanadate, however, reversed the plumbagin-induced downregulation of STAT3 activation, suggesting the involvement of a protein tyrosine phosphatase. Indeed, we found that plumbagin induced the expression of the protein tyrosine phosphatase, SHP-1, and silencing of the SHP-1 abolished the effect of plumbagin. This agent also downregulated the expression of STAT3-regulated cyclin D1, Bcl-xL, and vascular endothelial growth factor; activated caspase-3; induced poly (ADP ribose) polymerase cleavage; and increased the sub-G(1) population of MM cells. Consistent with these results, overexpression of constitutive active STAT3 significantly reduced the plumbagin-induced apoptosis. When compared with AG490, a rationally designed STAT3/JAK2 inhibitor, plumbagin was found more potent in suppressing the proliferation of cells. Plumbagin also significantly potentiated the apoptotic effects of thalidomide and bortezomib in MM cells. Overall, these results suggest that the plumbagin inhibits STAT3 activation pathway through the induction of SHP-1 and this may mediate the sensitization of STAT3 overexpressing cancers to chemotherapeutic agents.

  7. 2-[(2-{Bis[2-(2-hydroxy-5-nitrobenzylideneaminoethyl]amino}ethyliminomethyl]-4-nitrophenol acetonitrile monosolvate

    Directory of Open Access Journals (Sweden)

    Kwang Ha

    2010-12-01

    Full Text Available In the title compound, C27H27N7O9·CH3CN, the three nitro groups of the polydentate tripodal Schiff base are located approximately parallel to their respective carrier benzene rings, making dihedral angles of 3.9 (4, 5.0 (4 and 6.3 (4°. Intramolecular O—H...N hydrogen bonds between the hydroxy O atoms and the imine N atoms, with O...N distances in the range 2.607 (3–2.665 (3 Å, form nearly planar six-membered rings. In the crystal, weak intermolecular C—H...O and C—H...N hydrogen bonds occur and several intra- and intermolecular π–π interactions are present between adjacent benzene rings, with a shortest centroid–centroid distance of 3.507 (2 Å.

  8. Liquid chromatography-tandem mass spectrometry analysis of 2-amino-1-methyl-6-(4-hydroxyphenyl)imidazo[4,5-b]pyridine in cooked meats.

    Science.gov (United States)

    Busquets, R; Puignou, L; Galceran, M T; Wakabayashi, K; Skog, K

    2007-10-31

    Several cooked meats such as beef (fried, coated-fried), pork (fried, coated-fried), and chicken (fried, griddled, coated-fried, roasted) were analyzed for the heterocyclic amine 2-amino-1-methyl-6-(4-hydroxyphenyl)imidazo[4,5- b]pyridine (4'-OH-PhIP) not commonly determined in food and 2-amino-1-methyl-6-phenylimidazo[4,5- b]pyridine (PhIP). The highest content of 4'-OH-PhIP was found in fried and griddled chicken breast, the concentration being 43.7 and 13.4 ng/g, respectively, whereas the corresponding PhIP concentrations were 19.2 and 5.8 ng/g. The estimated concentration of both pyridines in fried pork loin, in fried pork sausages, and in coated-fried chicken was below 2.5 ng/g. In the rest of the samples, 4'-OH-PhIP was not detected. The analyses were performed by solid-phase extraction and LC-MS/MS. The fragmentation of 4'-OH-PhIP in an ion trap mass analyzer was studied in order to provide information for the identification of 4'-OH-PhIP. Additionally, the effect of red wine marinades on the formation of 4'-OH-PhIP in fried chicken was examined, finding a notable reduction (69%) in the amine's occurrence.

  9. Compatibility of nitrilotriacetic acid and 3-acetyl-4-hydroxy-6-methyl-2-pyrone in the coordination sphere of lanthanon ions

    International Nuclear Information System (INIS)

    Kadian, R.K.; Garg, B.S.; Singh, R.P.

    1982-01-01

    A study of the competetion of 3-acetyl-4-hydroxy-6-methyl-2-pyrone (dehydracetic acid, DHA) and nitrilotriacetic acid (NTA) in the coordination sphere of lanthanon ions has been carried out by calculating reproportionation constant which relates the stability of the mixed ligand complex to those of the parent complexes formed by the same ligands. It has been found that NTA and DHA are incompatible ligands and mixed ligand complexes formed are less stable than either of the parent complexes. The fact is also supported by the observed change in free energy occuring during mixed ligand complex formation. All these studies have been carried out at 30.0 +- 0.5 0 and μ-0.01 (NaClO 4 ) in 50 percent v/v aqueous dioxane medium. (author)

  10. Synthesis and anti-HIV activity of novel 3-substituted phenyl-6,7-dimethoxy-3a,4-dihydro-3H-indeno[1,2-c]isoxazole analogues.

    Science.gov (United States)

    Ali, Mohamed A; Ismail, Rusli; Choon, Tan S; Yoon, Yeong K; Wei, Ang C; Pandian, Suresh; Samy, Jeyabalan G; De Clercq, Eric; Pannecouque, Christophe

    2011-01-01

    A series of novel 3-(substituted phenyl)-6,7-dimethoxy-3a,4-dihydro-3H-indeno[1,2-c]isoxazole analogues were synthesized by the reaction of 5,6-dimethoxy-2-[(E)-1-phenylmethylidene]-1-indanone with hydroxylamine hydrochloride. The title compounds were tested for their in vitro anti-HIV activity. Among the compounds, (4g) showed a promising anti-HIV activity in the in vitro testing against IIIB and ROD strains. The IC50 of both IIIB and ROD were found to be 9.05 microM and > 125 microM, respectively.

  11. Candida Rugosa Lipase-catalyzed Kinetic Resolution of 3-(Isobutyryloxy)methyl 4-[2-(Difluoromethoxy)phenyl]-2-methyl-5,5-dioxo-1,4-dihydrobenzothieno[3,2-b]pyridine-3-carboxylate

    NARCIS (Netherlands)

    Sobolev, A.; Zhalubovskis, R.; Franssen, M.C.R.; Vigante, B.; Chekavichus, B.; Duburs, G.; Groot, de Æ.

    2004-01-01

    The lipase-catalyzed kinetic resolution of 3-(isobutyryloxy)methyl 4-[2-(difluoromethoxy)phenyl]-2-methyl-5,5-dioxo-1,4-dihydrobenzothieno[3,2-b]pyridine-3-carboxylate has been performed. The most enantioselective reaction (E = 28) was transesterification with n-butanol in water-saturated toluene at

  12. Kinetic tritium isotopic effects in the position 2 for 5'-hydroxy-L-tryptophane

    International Nuclear Information System (INIS)

    Boroda, E.; Kanska, M.

    2006-01-01

    Tryptophanase converts 5'-hydroxy-L-tryptophane to pyrogronic acid and ammonia, however there are known conditions for the reversed reaction. Mechanism of the processes are not known till now. Kinetic isotopic effect (KIE) permits finding the rate determining stage in the multistage process. In presented communication, 5'-hydroxy-[2- 3 H]-L-tryptophane was synthesized and the KIE in the room temperature determined for different reaction stages

  13. Opposite modulation of brain stimulation reward by NMDA and AMPA receptors in the ventral tegmental area.

    Science.gov (United States)

    Ducrot, Charles; Fortier, Emmanuel; Bouchard, Claude; Rompré, Pierre-Paul

    2013-01-01

    Previous studies have shown that blockade of ventral tegmental area (VTA) glutamate N-Methyl-D-Aspartate (NMDA) receptors induces reward, stimulates forward locomotion and enhances brain stimulation reward. Glutamate induces two types of excitatory response on VTA neurons, a fast and short lasting depolarization mediated by α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors and a longer lasting depolarization mediated by NMDA receptors. A role for the two glutamate receptors in modulation of VTA neuronal activity is evidenced by the functional change in AMPA and NMDA synaptic responses that result from repeated exposure to reward. Since both receptors contribute to the action of glutamate on VTA neuronal activity, we studied the effects of VTA AMPA and NMDA receptor blockade on reward induced by electrical brain stimulation. Experiments were performed on rats trained to self-administer electrical pulses in the medial posterior mesencephalon. Reward thresholds were measured with the curve-shift paradigm before and for 2 h after bilateral VTA microinjections of the AMPA antagonist, NBQX (2,3,-Dioxo-6-nitro-1,2,3,4-tetrahydrobenzo(f)quinoxaline-7-sulfonamide, 0, 80, and 800 pmol/0.5 μl/side) and of a single dose (0.825 nmol/0.5 μl/side) of the NMDA antagonist, PPPA (2R,4S)-4-(3-Phosphonopropyl)-2-piperidinecarboxylic acid). NBQX produced a dose-dependent increase in reward threshold with no significant change in maximum rate of responding. Whereas PPPA injected at the same VTA sites produced a significant time dependent decrease in reward threshold and increase in maximum rate of responding. We found a negative correlation between the magnitude of the attenuation effect of NBQX and the enhancement effect of PPPA; moreover, NBQX and PPPA were most effective when injected, respectively, into the anterior and posterior VTA. These results suggest that glutamate acts on different receptor sub-types, most likely located on different VTA neurons, to

  14. 4-Ferrocenylpyridine- and 4-Ferrocenyl-3-ferrocenylmethyl-3,4-dihydropyridine-3,5-dicarbonitriles: Multi-Component Synthesis, Structures and Electrochemistry

    Directory of Open Access Journals (Sweden)

    Luis Ortiz-Frade

    2012-08-01

    Full Text Available The reactions of 2-cyano-3-ferrocenylacrylonitrile (1 with malononitrile (2 in a MeOH/H2O or 2-PrOH/H2O medium in the presence of Na2CO3 afforded 6-alkoxy-2-amino-4-ferrocenylpyridine-3,5-dicarbonitriles 3a,b (multi-component condensation and 6-alkoxy-2-amino-4-ferrocenyl-3-ferrocenylmethyl-3,4-dihydropyridine-3,5-dicarbonitriles 4a,b (multi-component cyclodimerization. Analogous reactions of 1 with 2 in an MeOH/H2O medium in the presence of NaOH, piperidine, or morpholine gave compounds 3a, 4a and 2-amino-4-ferrocenyl-6-hydroxy-, 6-piperidino- and 6-morpholinopyridine-3,5-dicarbonitriles 3ce, respectively. The structures of the compounds 3b, 4a and 4b were established by the spectroscopic data and X-ray diffraction analysis. The electrochemical behaviour of compounds 3b, 3d and 4b was investigated by means of cyclic voltammetry.

  15. Mitochondrial localization of the mevalonate pathway enzyme 3-Hydroxy-3-methyl-glutaryl-CoA reductase in the Trypanosomatidae

    DEFF Research Database (Denmark)

    Pena Diaz, Javier; Montalvetti, Andrea; Flores, Carmen-Lisset

    2004-01-01

    3-Hydroxy-3-methyl-glutaryl-CoA reductase (HMGR) is a key enzyme in the sterol biosynthesis pathway, but its subcellular distribution in the Trypanosomatidae family is somewhat controversial. Trypanosoma cruzi and Leishmania HMGRs are closely related in their catalytic domains to bacterial and eu...

  16. Multicomponent hydrogen-bonding organic solids constructed from 6-hydroxy-2-naphthoic acid and N-heterocycles: Synthesis, structural characterization and synthon discussion

    Science.gov (United States)

    Zong, Yingxia; Shao, Hui; Pang, Yanyan; Wang, Debao; Liu, Kang; Wang, Lei

    2016-07-01

    Seven novel multicomponent crystals involving various substituted organic amine molecules and 6-hydroxy-2-naphthoic acid were prepared and characterized by using single crystal X-ray diffraction, infrared and thermogravimetric analyses (TGA). Crystal structures with 1,4-bis(imidazol) butane (L1) 1, 1,4-bis(imidazol-1-ylmethyl)benzene (L2) 2, 1-phenyl piperazine 3, 2-amino-4-hydroxy-6-methyl pyrimidine 4, 4,4'-bipyridine 5, 5,5'-dimethyl-2,2'-dipyridine 6, 2-amino-4,6-dimethyl pyrimidine 7 were determined. Among the seven molecular complexes, total proton transfer from 6-hydroxy-2-naphthoic acid to coformer has occurred in crystals 1-4, while the remaining were cocrystals. X-ray single-crystal structures of these complexes reveal that strong hydrogen bonding O-H···O/N-H···O/O-H···N and weak C-H···O/C-H···π/π···π intermolecular interactions direct the packing modes of molecular crystals together. The analysis of supramolecular synthons in the present structures shows that some classical supramolecular synthons like pyridine-carboxylic acid heterosynthon R22 (7) and aminopyridine-carboxylic acid heterosynthon R22 (8), are again observed in constructing the hydrogen-bonding networks in this paper. Besides, we noticed that water molecules act as a significant hydrogen-bonding connector in constructing supramolecular architectures of 3, 4, 6, and 7.

  17. Synthesis, spectral, thermal and biological studies of transition metal complexes of 4-hydroxy-3-[3-(4-hydroxyphenyl-acryloyl]-6-methyl-2H-pyran-2-one

    Directory of Open Access Journals (Sweden)

    BALASAHEB R. ARBAD

    2011-09-01

    Full Text Available The solid complexes of Mn(II, Fe(III, Co(II, Ni(II, and Cu(II with 4-hydroxy-3-[(2E-3-(4-hydroxyphenylprop-2-enoyl]-6-methyl-2H-pyran-2-one, derived from 3-acetyl-6-methyl-2H-pyran-2,4(3H-dione (dehydroacetic acid and 4-hydroxybenzaldehyde, were synthesized and characterized by elemental analysis, conductometry, thermal analysis, magnetic measurements, IR, 1H-NMR and UV–Vis spectroscopy and a biological study. From the analytical and spectral data, the stoichiometry of the complexes was found to be 1:2 (metal:ligand. The physico–chemical data suggest a distorted octahedral geometry for the Cu(II complexes and an octahedral geometry for all the other complexes. The thermal decomposition of all the complexes was studied by the TG–DTA method. The synthesized ligand and its metal complexes were screened for their in vitro antibacterial activity against Gram-negative (Escherichia coli and Gram-positive (Staphylococcus aureus bacterial strains and for in vitro antifungal activity against Aspergillus flavus, Curvularia lunata and Penicillium notatum. The results of these studies showed the metal complexes to be more antibacterial/antifungal against one or more species as compared with the non-complexed ligand.

  18. Studies on an (S)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA) receptor antagonist IKM-159

    DEFF Research Database (Denmark)

    Juknaite, Lina; Sugamata, Yutaro; Tokiwa, Kazuya

    2013-01-01

    IKM-159 was developed and identified as a member of a new class of heterotricyclic glutamate analogs that act as AMPA receptor-selective antagonists. However, it was not known which enantiomer of IKM-159 was responsible for its pharmacological activities. Here, we report in vivo and in vitro neur...

  19. Synthesis of 2-Amino-3-hydroxy-3H-indoles via Palladium-Catalyzed One-Pot Reaction of Isonitriles, Oxygen, and N-Tosylhydrazones Derived from 2-Acylanilines.

    Science.gov (United States)

    Chu, Haoke; Dai, Qiang; Jiang, Yan; Cheng, Jiang

    2017-08-04

    A cyanide-free one-pot procedure was developed to access 2-amino-3-hydroxy-3H-indoles, which involved: (1) in situ formation of ketenimines by the reaction of N'-(1-(2-aminophenyl)ethylidene)-p-tosylhydrazones with isonitriles; (2) the intramolecular nucleophilic attack of ketenimines by the amino in phenyl furnishing the ring closure leading to 2-aminoindoles; (3) the oxidation of 2-aminoindoles by O 2 leading to 2-amino-3-hydroxy-3H-indoles. This strategy represents not only a key compliment to the sporadic synthetic methods toward 2-amino-3-hydroxy-3H-indoles but also progress in N-tosylhydrazone, isonitrile, and ketenimine chemistry.

  20. N-(3-{[(Z-(3-Hydroxy-4-methylphenylimino]methyl}pyridin-2-ylpivalamide

    Directory of Open Access Journals (Sweden)

    Şehriman Atalay

    2016-03-01

    Full Text Available The molecular structure of the title compound, C18H21N3O2, contains pivalamide, pyridin and hydroxy-methylphenyl moieties. The whole molecule is not planar, the dihedral angle between the benzene rings being 34.84 (7°. The molecular conformation is stabilized by an intramolecular N—H...N hydrogen bond. In the crystal, molecules are linked by O—H...O, O—H...N and C—H...O hydrogen bonds. The C and H atoms of the tert-butyl group disordered over two sets of sites with an occupancy ratio of 0.692 (5:0.308 (5.

  1. Evidence that glutamate mediates axon-to-Schwann cell signaling in the squid.

    Science.gov (United States)

    Lieberman, E M; Abbott, N J; Hassan, S

    1989-01-01

    High-frequency stimulation (100 Hz) of isolated giant axons of the small squid Alloteuthis subulata and the large squid Loligo forbesi caused the periaxonal Schwann cell resting potential (Em = -40 mV) to hyperpolarize up to 11 mV in direct proportion to train duration and action potential amplitude. In both species, the Schwann cell also hyperpolarized up to 17 mV with the application of L-glutamate (10(-9) to 10(-6) M), in a dose-dependent manner. By contrast, in the presence of 10(-8) M d-tubocurarine (d-TC) to block the cholinergic component of the Schwann cell response, Schwann cells depolarized 8-9 mV during electrical stimulation of the axon or application of L-glutamate. In the presence of 10(-5) M 2-amino-4-phosphonobutyrate (2-APB), the hyperpolarization to glutamate and to axon stimulation was blocked, whereas the cholinergic (carbachol-induced) hyperpolarization was unaffected. In experiments with Alloteuthis, L-aspartate (10(-7) M) also caused a Schwann cell hyperpolarization, but this was not blocked by 2-APB. In tests with glutamate receptor agonists and antagonists, quisqualate (10(-5) M) produced a hyperpolarization blocked by 10(-4) M L-glutamic acid diethylester (GDEE), which also blocked the response to axonal stimulation. Kainic acid (10(-4) M) also caused a hyperpolarization, but n-methyl-D-aspartate (NMDA; 10(-4) M), ibotenate (10(-5) M), alpha-amino-3-hydroxy-5-methyl-isoxazole proprionate (AMPA; (10(-4) M), and isethionate (10(-5) M) had no effect.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. Synthesis of new trihalo methylated and non-symmetrical substituted 2-(1H-pyrazolyl)-5-(1H-pyrazolylcarbonyl)pyridines

    International Nuclear Information System (INIS)

    Bonacorso, Helio G.; Paim, Gisele R.; Guerra, Carolina Z.; Sehnem, Ronan C.; Cechinel, Cleber A.; Porte, Liliane M. F.; Martins, Marcos A. P.; Zanatta, Nilo

    2009-01-01

    This paper describes the synthesis of a new series of 2-[3-alkyl(aryl/heteroaryl)-5-trifluoro(chloro)methyl-5-hydroxy-4,5-dihydro -1H-pyrazol-1-yl]-5- [3-alkyl(aryl/heteroaryl)-5-trifluoro(chloro)methyl-5-hydroxy= -4,5-dihydro-1H-pyrazol-1-yl-1-carbonyl] pyridines by the cyclocondensation reaction of 4-alkoxy-4-alkyl(aryl/heteroaryl)-1,1,1- trifluoro(chloro) -3-alken- 2-ones [CX 3 C(O)CH=CR 1 OR, where R = Me, Et; R 1 = H, Me, Ph, 4-MeOPh, 4-NO 2 Ph, 4,4'-Biphenyl, 1-Naphthyl, Fur-2-yl, Thien-2-yl and X = F, Cl] with 6-hydrazinonicotinic hydrazide hydrate. Yields of 62 to 97% were obtained when the reactions were performed in ethanol as solvent at 78 deg C for 4 hours. In a subsequent step, the dehydration reactions of 2-(5-hydroxy-1H-pyrazol-1-yl)-5-(5-hydroxy-1H?pyrazol-1-yl-1-carbonyl) pyridines were carried out in pyridine/benzene in the presence of thionyl chloride and led to the isolation of a series of 2- [3-alkyl(aryl/heteroaryl)-5-trifluoro(chloro)methyl-1H-pyrazol-1-yl]-5- [3-alkyl(aryl/heteroaryl)-5 -trifluoro(chloro)methyl-1H-pyrazol-1-yl-1-carbonyl]pyridi= nes, in 64 to 86% yields. (author)

  3. Synthesis, spectral characterization and biological studies of some organotin(IV) complexes of L-proline, trans-hydroxy- L-proline and L-glutamine

    Science.gov (United States)

    Nath, Mala; Jairath, Ruchi; Eng, George; Song, Xueqing; Kumar, Ashok

    2005-12-01

    New organotin(IV) complexes of the general formula R 3Sn(L) (where R = Me, n-Bu and HL = L-proline; R = Me, Ph and HL = trans-hydroxy- L-proline and L-glutamine) and R 2Sn(L) 2 (where R = n-Bu, Ph and HL = L-proline; R = Ph, HL = trans-hydroxy- L-proline) have been synthesized by the reaction of R nSnCl 4- n (where n = 2 or 3) with sodium salt of the amino acid (HL). n-Bu 2Sn(Pro) 2 was synthesized by the reaction of n-Bu 2SnO with L-proline under azeotropic removal of water. The bonding and coordination behavior in these complexes have been discussed on the basis of IR and 119Sn Mössbauer spectroscopic studies in the solid-state. Their coordination behavior in solution has been discussed with the help of multinuclear ( 1H, 13C and 119Sn) NMR spectral studies. The 119Sn Mössbauer and IR studies indicate that L-proline and trans-hydroxy- L-proline show similar coordination behavior towards organotin(IV) compounds. Pentacoordinate trigonal-bipyramidal and hexacoordinate octahedral structures, respectively, have been proposed for the tri- and diorganotin(IV) complexes of L-proline and trans-hydroxy- L-proline, in which the carboxylate group acts as bidentate group. L-Glutamine shows different coordination behavior towards organotin(IV) compounds, it acts as monoanionic bidentate ligand coordinating through carboxylate and amino group. The triorganotin(IV) complexes of L-glutamine have been proposed to have trigonal-bipyramidal environment around tin. The newly synthesized complexes have been tested for their antiinflammatory and cardiovascular activities. Their LD 50 values are >1000 mg kg -1.

  4. 4-{3-[Hydroxy(phenylmethyl]-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-4-yl}benzenesulfonamide

    Directory of Open Access Journals (Sweden)

    Mehmet Akkurt

    2010-04-01

    Full Text Available In the title compound, C15H14N4O3S2, the hydroxy group is disordered over two positions with occupancies of 0.619 (5 and 0.381 (5. The benzene ring attached to the heterocycle makes a dihedral angle of 86.92 (9° with respect to the best plane through the five-membered ring. The crystal packing is stabilized by intermolecular O—H...O, N—H...S, N—H...N, C—H...O and C—H...N hydrogen bonds, and N—H...π and C—H...π interactions.

  5. Radiosynthesis of dimethyl-2-[{sup 18}F]-(fluoromethyl)-6-methyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate for L-type calcium channel imaging

    Energy Technology Data Exchange (ETDEWEB)

    Sadeghpour, H. [Nuclear Medicine Research Group, Agricultural, Medical and Industrial Research School (AMIRS), Karaj (Iran); Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran Univ. of Medical Sciences, Tehran (Iran); Jalilian, A.R.; Akhlaghi, M.; Mirzaei, M. [Nuclear Medicine Research Group, Agricultural, Medical and Industrial Research School (AMIRS), Karaj (Iran); Shafiee, A. [Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran Univ. of Medical Sciences, Tehran (Iran); Miri, R. [Medicinal and Natural Products Chemistry Research Center, Shiraz Univ. of Medical Sciences, Shiraz (Iran)

    2008-07-01

    Dimethyl 2-(fluoromethyl)-6-methyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate 4a, a fluorinated nifedipine analog, has been shown to elicit significant calcium channel blocker activity using a guinea pig ileal longitudinal smooth muscle model. In order to perform biological studies for detection of L-type calcium channel distribution, we decided to prepare the [{sup 18}F]-labeled compound. The latter compound was prepared in no-carrier-added (n.c.a.) form from dimethyl 2-(bromomethyl)-6-methyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate 2 in one step at 80 C in Kryptofix[222]/K[{sup 18}F]F and acetonitrile as a solvent in 15 min. Column chromatography afforded the radiochemically pure compound in 20 min. Radiochemical purity of the {sup 18}F-nifedipine was determined by RTLC and HPLC (> 98%) and specific activity of 21-48 GBq/{mu}mol (EOB). (orig.)

  6. Radioiodinated 4-iodo-L-meta-tyrosine, a system L selective artificial amino acid: molecular design and transport characterization in Chinese hamster ovary cells (CHO-K1 cells)

    Energy Technology Data Exchange (ETDEWEB)

    Shikano, Naoto, E-mail: sikano@ipu.ac.j [Department of Radiological Sciences, Ibaraki Prefectural University of Health Sciences, 4669-2 Ami, Ami-machi, Inashiki-gun, Ibaraki 300-0394 (Japan); Kotani, Takashi; Nakajima, Syuichi; Ogura, Masato; Nakazawa, Shinya [Department of Radiological Sciences, Ibaraki Prefectural University of Health Sciences, 4669-2 Ami, Ami-machi, Inashiki-gun, Ibaraki 300-0394 (Japan); Sagara, Jun-ichi [Center for Humanities and Sciences, Ibaraki Prefectural University of Health Sciences, 4669-2 Ami, Ami-machi, Inashiki-gun, Ibaraki 300-0394 (Japan); Kobayashi, Masato [Division of Health Science, Graduate School of Health Sciences, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa, Ishikawa 9200-942 (Japan); Baba, Takeshi; Yamaguchi, Naoto [Center for Medical Science, Ibaraki Prefectural University of Health Sciences, 4669-2 Ami, Ami-machi, Inashiki-gun, Ibaraki 300-0394 (Japan); Kubota, Nobuo [Department of Radiological Sciences, Ibaraki Prefectural University of Health Sciences, 4669-2 Ami, Ami-machi, Inashiki-gun, Ibaraki 300-0394 (Japan); Kawai, Keiichi [Division of Health Science, Graduate School of Health Sciences, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa, Ishikawa 9200-942 (Japan)

    2010-11-15

    Introduction: High expression of the system L amino acid transporter has been observed in clinically important tissues including tumors and the blood-brain barrier. We examined amino acid transport system L selectivity of {sup 14}C(U)-L-tyrosine ({sup 14}C-Tyr), {sup 125}I-4-iodo-L-meta-tyrosine (4-{sup 125}I-mTyr), {sup 125}I-6-iodo-L-meta-tyrosine (6-{sup 125}I-mTyr), {sup 125}I-3-iodo-{alpha}-methyl-L-tyrosine ({sup 125}I-IMT) and {sup 125}I-3-iodo-L-tyrosine (3-{sup 125}I-Tyr) using Chinese hamster ovary cells (CHO-K1). Methods: Cells in the exponential growth phase were incubated with 18.5 kBq of labeled amino acid in 2 mL of phosphate-buffered saline-based uptake solution and an uptake solution with/without Na{sup +} at 37{sup o}C or 4{sup o}C. We examined the effects of the following compounds (1.0 mM) on transport: 2-(methylamino)isobutyric acid (a specific inhibitor of system A, in Na{sup +}-containing uptake solution); 2-amino-bicyclo[2,2,1]heptane-2-carboxylic acid (a specific inhibitor of system L, in Na{sup +}-free uptake solution); sodium azide and 2,4-dinitrophenol (NaN{sub 3} and DNP, inhibitors of the generation of adenosine triphosphate); p-aminohippurate and tetraethylammonium (PAH and TEA, inhibitors of organic anion and cation transporters); and L- and D-isomers of natural amino acids. Results: {sup 14}C-Tyr exhibited affinity for systems L, A and ASC. 4-{sup 125}I-mTyr and 3-{sup 125}I-Tyr exhibited high specificity for system L, whereas 6-{sup 125}I-mTyr and {sup 125}I-IMT exhibited affinity for both systems L and ASC. Uptake of 4-{sup 125}I-mTyr was markedly reduced by incubation at 4 {sup o}C, and was not significantly inhibited by NaN{sub 3}, DNP, PAH or TEA. The inhibition profiles of the L- and D-isomers of natural amino acids indicated that system L mediates the transport of 4-{sup 125}I-mTyr. Conclusions: 4-{sup 125}I-mTyr exhibited the greatest system L specificity (93.46{+-}0.13%) of all of the tested amino acids.

  7. Molecular pharmacology of 4-substituted glutamic acid analogues at ionotropic and metabotropic excitatory amino acid receptors

    DEFF Research Database (Denmark)

    Bräuner-Osborne, Hans; Nielsen, B; Stensbøl, T B

    1997-01-01

    (subtypes 1alpha and 2), respectively, whereas (S)-4-methyleneglutamic acid showed high but rather non-selective affinity for the (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA), kainic acid, NMDA and mGlu receptors (subtypes 1alpha and 2). Although none of the compounds were specific......The pharmacology of (2S,4R)-4-methylglutamic acid, (2S,4S)-4-methylglutamic acid and (S)- and (R)-4-methyleneglutamic acids (obtained in high chemical and enantiomeric purity from racemic 4-methyleneglutamic acid by chiral HPLC using a Crownpak CR(+) column), was examined in binding experiments...... using rat brain ionotropic glutamate receptors, and in functional assays using cloned metabotropic glutamate (mGlu) receptors. As a notable result of these studies, (2S,4R)-4-methylglutamic acid and (2S,4S)-4-methylglutamic acid were shown to be selective for kainic acid receptors and mGlu receptors...

  8. Cell cycle-dependent regulation of kainate-induced inward currents in microglia

    International Nuclear Information System (INIS)

    Yamada, Jun; Sawada, Makoto; Nakanishi, Hiroshi

    2006-01-01

    Microglia are reported to have α-amino-hydroxy-5-methyl-isoxazole-4-propionate/kainate (KA) types. However, only small population of primary cultured rat microglia (approximately 20%) responded to KA. In the present study, we have attempted to elucidate the regulatory mechanism of responsiveness to KA in GMIR1 rat microglial cell line. When the GMIR1 cells were plated at a low density in the presence of granulocyte macrophage colony-stimulating factor, the proliferation rate increased and reached the peak after 2 days in culture and then gradually decreased because of density-dependent inhibition. At cell proliferation stage, approximately 80% of the GMIR1 cells exhibited glutamate (Glu)- and KA-induced inward currents at cell proliferation stage, whereas only 22.5% of the cells showed responsiveness to Glu and KA at cell quiescent stage. Furthermore, the mean amplitudes of inward currents induced by Glu and KA at cell proliferation stage (13.8 ± 3.0 and 8.4 ± 0.6 pA) were significantly larger than those obtained at cell quiescent stage (4.7 ± 0.8 and 6.2 ± 1.2 pA). In the GMIR1 cells, KA-induced inward currents were markedly inhibited by (RS)-3-(2-carboxybenzyl) willardiine (UBP296), a selective antagonist for KA receptors. The KA-responsive cells also responded to (RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl) propanoic acid (ATPA), a selective agonist for GluR5, in both GMIR1 cells and primary cultured rat microglia. Furthermore, mRNA levels of the KA receptor subunits, GluR5 and GluR6, at the cell proliferation stage were significantly higher than those at the cell quiescent stage. Furthermore, the immunoreactivity for GluR6/7 was found to increase in activated microglia in the post-ischemic hippocampus. These results strongly suggest that microglia have functional KA receptors mainly consisting of GluR5 and GluR6, and the expression levels of these subunits are closely regulated by the cell cycle mechanism

  9. Replacement of Oxygen by Sulfur in Small Organic Molecules. 3. Theoretical Studies on the Tautomeric Equilibria of the 2OH and 4OH-Substituted Oxazole and Thiazole and the 3OH and 4OH-Substituted Isoxazole and Isothiazole in the Isolated State and in Solution

    Directory of Open Access Journals (Sweden)

    Peter I. Nagy

    2016-07-01

    Full Text Available This follow-up paper completes the author’s investigations to explore the in-solution structural preferences and relative free energies of all OH-substituted oxazole, thiazole, isoxazole, and isothiazole systems. The polarizable continuum dielectric solvent method calculations in the integral-equation formalism (IEF-PCM were performed at the DFT/B97D/aug-cc-pv(q+(dz level for the stable neutral tautomers with geometries optimized in dichloromethane and aqueous solution. With the exception of the predictions for the predominant tautomers of the 3OH isoxazole and isothiazole, the results of the IEF-PCM calculations for identifying the most stable tautomer of the given species in the two selected solvents agreed with those from experimental investigations. The calculations predict that the hydroxy proton, with the exception for the 4OH isoxazole and 4OH isothiazole, moves preferentially to the ring nitrogen or to a ring carbon atom in parallel with the development of a C=O group. The remaining, low-fraction OH tautomers will not be observable in the equilibrium compositions. Relative solvation free energies obtained by the free energy perturbation method implemented in Monte Carlo simulations are in moderate accord with the IEF-PCM results, but consideration of the ΔGsolv/MC values in calculating ΔGstot maintains the tautomeric preferences. It was revealed from the Monte Carlo solution structure analyses that the S atom is not a hydrogen-bond acceptor in any OH-substituted thiazole or isothiazole, and the OH-substituted isoxazole and oxazole ring oxygens may act as a weak hydrogen-bond acceptor at most. The molecules form 1.0−3.4 solute−water hydrogen bonds in generally unexplored numbers at some specific solute sites. Nonetheless, hydrogen-bond formation is favorable with the NH, C=O and OH groups.

  10. Baker's yeast: production of D- and L-3-hydroxy esters

    DEFF Research Database (Denmark)

    Dahl, Allan Carsten; Madsen, Jørgen Øgaard

    1998-01-01

    harvested while growing. In contrast, the stereoselectivity was shifted towards L-hydroxy esters when the oxo esters were added slowly to ordinary baker's yeast supplied with gluconolactone as co-substrate. The reduction rate with gluconolactone was increased by active aeration. Ethyl L-(S)-3......Baker's yeast grown under oxygen limited conditions and used in the reduction of 3-oxo esters results in a shift of the stereoselectivity of the yeast towards D-hydroxy esters as compared with ordinary baker's yeast. The highest degree of stereoselectivity was obtained with growing yeast or yeast......-hydroxybutanoate was afforded in >99% ee. Both enantiomers of ethyl 3-hydroxypentanoate, D-(R) in 96% ee and L-(S) in 93% ee, and of ethyl 4-chloro-3-hydroxybutanoate, D-(S) in 98% ee and L-(R) in 94% ee, were obtained. The results demonstrate that the stereoselectivity of baker's yeast can be controlled...

  11. Radiochemical synthesis of 3-(4-[18F] Fluorophenyl)-8-hydroxy-1, 2, 3, 4-tetrahydrochromeno [3, 4-c] pyridin-5-one: A putative dopamine D$4 receptor PET imaging agent

    International Nuclear Information System (INIS)

    Li, G.C.; Yin, D.Z.; Wang, M.W.; Cheng, D.F.; Wang, Y.X.

    2005-01-01

    Introduction: The dopamine D 4 receptor has lately received increasing interest since it has been hypothesized to be involved in the pathology and pharmacotherapy of schizophrenia. While this receptor is expressed in lower density in various extrastriatal brain regions and its distribution is still unclear due to the lack of suitable imaging agent and its level change in schizophrenia is controversial. Herein, based on the structure-activity analysis of chromeno[3, 4-c]pyridine- 5-ones as potential dopamine D 4 receptor ligands, a putative D 4 subtype positron emission tomography (PET) radioligand, 3-(4-[ 18 F]fluorophenyl)-8-hydroxy-1, 2, 3, 4-tetrahydrochromeno [3, 4-c]pyridin-5-one ([ 18 F]FHTP), was designed and synthesized. Methods: The radiochemical synthesis route was shown in Figure 1. [ 18 F]Fluoride was produced with a Cyclone-30 (IBA, Belgium) by 18 O(p, n) 18 F reaction using enriched 18 O-H 2 O and eluted from a Dowex 1-X8 anion-exchange column with aqueous potassium carbonate (20 mg/mL). 4-[ 18 F]Fluorobenzaldehyde was prepared according to the method reported by Alan A. Wilson and et al.. Then, 8-hydroxy-1, 2, 3, 4-tetrahydrochromeno [3, 4-c]pyridin-5-one, sodium cyanoborohydride, methanol and acetic acid were added to the dry residue, The mixture was then sealed and heated at 120 degree C for 12 min. At the end of the reaction, the mixture was cooled, diluted with ethyl acetate and washed with water. The extracted organic layer was passed through a small anhydrous magnesium sulfate column. After removal of the solvents in the mixture at 50 degree C under a stream of nitrogen, the obtained residue was redissolved in methanol and purified with a semi-preparative HPLC system, then the desired product was collected. Results: The radiochemical synthesis of [ 18 F]FHTP took around 110 min at EOS with an overall radiochemical yield 19% (decay-corrected) and its radiochemical purity was higher than 95%. Conclusion: A presumed dopamine D 4 receptor PET

  12. 75 FR 78243 - Propionic Acid and Salts, Urea Sulfate, Methidathion, and Methyl Parathion; Registration Review...

    Science.gov (United States)

    2010-12-15

    ... ENVIRONMENTAL PROTECTION AGENCY [EPA-HQ-OPP-2010-0650; FRL-8855-5] Propionic Acid and Salts, Urea.... 4078, urea sulfate, case no. 7213, methidathion, case no. 0034, and methyl parathion, case no. 0153... pesticides in the table below--propionic acid and salts, case 4078, urea sulfate, case no. 7213, methidathion...

  13. Synthesis, Kinetic Study, and Biological Distribution of Iodine-125-N-[3-(4 morpholino) propyl] -N-methyl-2-hydroxy-5-iodo-3-methylbenzylamine (ERC-9): A Possible Melanoma Therapeutic Agent

    International Nuclear Information System (INIS)

    EL-Ghany, E.A.

    2008-01-01

    This study describe the labeling of N-[3-(4-morpholino) propyl] -N-methyl-2 hydroxy-5-iodo-3-methylbenzylamine (ERC-9) with iodine-125 in liquid and ill melt states .The labeling in liquid state was controlled by many factors such as the ratio of radioiodine to the molar concentration of ERC-9, This test was carried out using iodine-131 instead of iodine-125 due to high activity required, and the maximum yield of 131 I ERC-9 was obtained at 90 - 277 MBq NaI 131 to 19.9 m M of ERC-9. The labeling reaction was preceded well at ph 3,5. Acetic acid was the most suitable solvent for the labeling reaction. One mg of cuprous chloride was catalyzed the reaction and reduced the reaction time from 45 min to 20 min. The molarity of sodium hydroxide played an important role in the labeling reaction, as the labeling yield was maximum at 0,01 M NaOH. The labeling in melt state using ammonium acetate as catalyst produced 92 % radiochemical yield. The labeling in melt state was fast, easy, and done in one-step. The biological studies reflected that the tracer was lipophilic, as high liver uptake (39.4 ± 2,1 %) was observed at 1 h post injection. The tracer was excreted to some extent via the kidneys. Activation energy required for the reaction completion in the presence of cuprous chloride was 31.4 KJ/ mol when the reaction was preceded at 80 degree C for 80 min

  14. Chronic intermittent hypoxia impairs heart rate responses to AMPA and NMDA and induces loss of glutamate receptor neurons in nucleus ambiguous of F344 rats.

    Science.gov (United States)

    Yan, Binbin; Li, Lihua; Harden, Scott W; Gozal, David; Lin, Ying; Wead, William B; Wurster, Robert D; Cheng, Zixi Jack

    2009-02-01

    Chronic intermittent hypoxia (CIH), as occurs in sleep apnea, impairs baroreflex-mediated reductions in heart rate (HR) and enhances HR responses to electrical stimulation of vagal efferent. We tested the hypotheses that HR responses to activation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and N-methyl-D-aspartate (NMDA) receptors in the nucleus ambiguous (NA) are reduced in CIH-exposed rats and that this impairment is associated with degeneration of glutamate receptor (GluR)-immunoreactive NA neurons. Fischer 344 rats (3-4 mo) were exposed to room air (RA) or CIH for 35-50 days (n = 18/group). At the end of the exposures, AMPA (4 pmol, 20 nl) and NMDA (80 pmol, 20 nl) were microinjected into the same location of the left NA (-200 microm to +200 microm relative to caudal end of area postrema; n = 6/group), and HR and arterial blood pressure responses were measured. In addition, brain stem sections at the level of -800, -400, 0, +400, and +800 microm relative to obex were processed for AMPA and NMDA receptor immunohistochemistry. The number of NA neurons expressing AMPA receptors and NMDA receptors (NMDARs) was quantified. Compared with RA, we found that after CIH 1) HR responses to microinjection of AMPA into the left NA were reduced (RA -290 +/- 30 vs. CIH -227 +/- 15 beats/min, P neurons expressing GluRs contributes to impaired baroreflex control of HR in rats exposed to CIH.

  15. Acquisition of resistance to 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride in V79 cells through increased removal of O6-alkylguanine.

    Science.gov (United States)

    Satoh, M S; Huh, N H; Horie, Y; Thomale, J; Rajewsky, M F; Kuroki, T

    1987-10-01

    The molecular mechanism of acquisition of resistance to 1-(4-amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-chloroethyl)-3-nitroso ure a hydrochloride (ACNU) was investigated using ACNU-resistant clones (ACNUr-1-4) isolated from the V79 cell line. The binding level of alkyl cyanate, a decomposition product of ACNU, to protein in ACNUr-1 cells was not less than that in the parental V79 cells, indicating that the acquired resistance was not due to a reduced intracellular concentration of ACNU. Because O6-chloroethylguanine, an intermediate in cytotoxic interstrand cross-link formation by ACNU, is known to be repaired by the same mechanism as O6-ethyldeoxyguanosine (O6-EtdGuo), we quantitated O6-EtdGuo by radioimmunoassay at various times after exposure of cells to 100 micrograms/ml N-ethyl-N-nitrosourea for 20 min. In V79 cells, elimination of O6-EtdGuo was negligible, but in all four resistant clones, 30 to 59% of the O6-EtdGuo was removed within 24 hr after exposure. This increased removal of O6-EtdGuo among the resistant clones was associated with the activity of O6-alkylguanine DNA alkyltransferase (O6-AGT) determined using cell extracts. The present results indicate that increased removal of O6-chloroethylguanine in ACNU-resistant clones by O6-AGT is mechanistically linked to the acquisition of resistance to ACNU.

  16. Synthesis and Antitumor Activity of 3-Methyl-4-oxo-3,4-dihydroimidazo [5,1-d][1,2,3,5]tetrazine-8-carboxylates and -carboxamides

    Directory of Open Access Journals (Sweden)

    Lin-Xiang Zhao

    2010-12-01

    Full Text Available Seventeen novel 3-methyl-4-oxo-3,4-dihydroimidazo[5,1-d][1,2,3,5]tetrazine-8-carboxylate and -carboxamide derivatives were synthesized and evaluated for their growth inhibition in seven human solid tumor and a human leukemia HL-60 cell lines. Compound IVa showed more activity than the other compounds and the positive control temozolomide. In the presence of 40 mg/mL of IVa, the survival rate of all tested tumor cells was less than 10%. Esters displayed more potent antitumour activity than amides and temozolomide against HL-60 cells. These compounds also exhibited considerably enhanced water-solubility.

  17. Pharmacological characterization of LY233053: A structurally novel tetrazole-substituted competitive N-methyl-D-aspartic acid antagonist with a short duration of action

    International Nuclear Information System (INIS)

    Schoepp, D.D.; Ornstein, P.L.; Leander, J.D.; Lodge, D.; Salhoff, C.R.; Zeman, S.; Zimmerman, D.M.

    1990-01-01

    This study reports the activity of a structurally novel excitatory amino acid receptor antagonist, LY233053 [cis-(+-)-4-[(2H-tetrazol-5-yl)methyl]piperidine-2-carboxylic acid], the first tetrazole-containing competitive N-methyl-D-aspartic acid (NMDA) antagonist. LY233053 potently inhibited NMDA receptor binding to rat brain membranes as shown by the in vitro displacement of [3H] CGS19755 (IC50 = 107 +/- 7 nM). No appreciable affinity in [3H]alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) or [3H]kainate binding assays was observed (IC50 values greater than 10,000 nM). In vitro NMDA receptor antagonist activity was further demonstrated by selective inhibition of NMDA-induced depolarization in cortical wedges (IC50 = 4.2 +/- 0.4 microM vs. 40 microM NMDA). LY233053 was effective after in vivo systemic administration in a number of animal models. In neonatal rats, LY233053 selectively blocked NMDA-induced convulsions (ED50 = 14.5 mg/kg i.p.) with a relatively short duration of action (2-4 hr). In pigeons, LY233053 potently antagonized (ED50 = 1.3 mg/kg i.m.) the behavioral suppressant effects of 10 mg/kg of NMDA. However, a dose of 160 mg/kg, i.m., was required to produce phencyclidine-like catalepsy in pigeons. In mice, LY233053 protected against maximal electroshock-induced seizures at lower doses (ED50 = 19.9 mg/kg i.p.) than those that impaired horizontal screen performance (ED50 = 40.9 mg/kg i.p.). Cholinergic and GABAergic neuronal degenerations after striatal infusion of NMDA were prevented by single or multiple i.p. doses of LY233053. In summary, the antagonist activity of LY233053 after systemic administration demonstrates potential therapeutic value in conditions of neuronal cell loss due to NMDA receptor excitotoxicity

  18. NMDA receptors regulate nicotine-enhanced brain reward function and intravenous nicotine self-administration: role of the ventral tegmental area and central nucleus of the amygdala.

    Science.gov (United States)

    Kenny, Paul J; Chartoff, Elena; Roberto, Marisa; Carlezon, William A; Markou, Athina

    2009-01-01

    Nicotine is considered an important component of tobacco responsible for the smoking habit in humans. Nicotine increases glutamate-mediated transmission throughout brain reward circuitries. This action of nicotine could potentially contribute to its intrinsic rewarding and reward-enhancing properties, which motivate consumption of the drug. Here we show that the competitive N-methyl-D-aspartate (NMDA) receptor antagonist LY235959 (0.5-2.5 mg per kg) abolished nicotine-enhanced brain reward function, reflected in blockade of the lowering of intracranial self-stimulation (ICSS) thresholds usually observed after experimenter-administered (0.25 mg per kg) or intravenously self-administered (0.03 mg per kg per infusion) nicotine injections. The highest LY235959 dose (5 mg per kg) tested reversed the hedonic valence of nicotine from positive to negative, reflected in nicotine-induced elevations of ICSS thresholds. LY235959 doses that reversed nicotine-induced lowering of ICSS thresholds also markedly decreased nicotine self-administration without altering responding for food reinforcement, whereas the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor antagonist NBQX had no effects on nicotine intake. In addition, nicotine self-administration upregulated NMDA receptor subunit expression in the central nucleus of the amygdala (CeA) and ventral tegmental area (VTA), suggesting important interactions between nicotine and the NMDA receptor. Furthermore, nicotine (1 microM) increased NMDA receptor-mediated excitatory postsynaptic currents in rat CeA slices, similar to its previously described effects in the VTA. Finally, infusion of LY235959 (0.1-10 ng per side) into the CeA or VTA decreased nicotine self-administration. Taken together, these data suggest that NMDA receptors, including those in the CeA and VTA, gate the magnitude and valence of the effects of nicotine on brain reward systems, thereby regulating motivation to consume the drug.

  19. 5-Methyl-4-oxo-4,6-dihydro-3H-pyridazino[4,5-b]carbazole-1-carbonitrile

    Directory of Open Access Journals (Sweden)

    Norbert Haider

    2010-02-01

    Full Text Available The title compound was prepared in excellent yield from 5-methyl-4-oxo-4,6-dihydro-3H-pyridazino[4,5-b]carbazole-1-carbaldehyde by treatment with hydroxylamine hydrochloride in formic acid without isolation of the intermediate oxime.

  20. Synthesis, Molecular Structure and Characterization of Allylic Derivatives of 6-Amino-3-methyl-1,2,4-triazolo[3,4-f][1,2,4]-triazin-8(7H-one

    Directory of Open Access Journals (Sweden)

    Gene-Hsiang Lee

    2006-06-01

    Full Text Available 1-Allyl- (2 and 7-allyl-6-amino-3-methyl-1,2,4-triazolo[3,4-f][1,2,4]triazin-8(7H-one (3 were obtained via the 18-crown-6-ether catalyzed room temperature reactionof 6-amino-3-methyl-1,2,4-triazolo[3,4-f][1,2,4]triazin-8(7H-one (1 with potassiumcarbonate and allyl bromide in dry acetone. The structures of these two derivatives wereverified by 2D-NMR measurements, including gHSQC and gHMBC measurements. Theminor compound 2 may possess aromatic character. A single crystal X-ray diffractionexperiment indicated that the major compound 3 crystallizes from dimethyl sulfoxide in themonoclinic space group P21/n and its molecular structure includes an attached dimethylsulfoxide molecule, resulting in the molecular formula C10H16N6O2S. Molecular structuresof 3 are linked by extensive intermolecular N-H···N hydrogen bonding [graph set C 1 (7]. 1Each molecule is attached to the dimethyl sulfoxide oxygen via N-H···O intermolecularhydrogen bonding. The structure is further stabilized by π-π stacking interactions.

  1. 1,4-Dimethyl-3-phenyl-3H-pyrazolo[3,4-c]isoquinolin-5(4H-one

    Directory of Open Access Journals (Sweden)

    Giuseppe Daidone

    2008-05-01

    Full Text Available The title compound, C18H15N3O, is the product of the thermal decomposition of the diazonium salt derived from 2-amino-N-methyl-N-(3-methyl-1-phenyl-1H-pyrazol-5-ylbenzamide. It is characterized by a trans orientation of the methyl groups with respect to the tricyclic ring system. The molecule has a nearly planar phenylpyrazolo[3,4-c]isoquinolin-5-one system, the largest deviation from the mean plane being 0.066 (2 Å for the O atom. The dihedral angle between the phenyl substituent and the heterotricycle is 67 (1°. The packing is stabilized by C—H...N hydrogen-bond interactions, with the formation of molecular chains along the c axis.

  2. Synthesis of 7-[α-(2-amino-[2-14C]thiazol-4-yl)-α-(Z)-methoxyimin oacetamido]-3-(1-methylpyrrolidinio)methyl-3-cephem-4-carboxylate hydrochloride ([14C]cefepime hydrochloride)

    International Nuclear Information System (INIS)

    Standridge, R.T.; Swigor, J.E.

    1993-01-01

    The title compound ([ 14 C]cefepime hydrochloride) was prepared as follows:- [ 14 C]Thiourea was condensed with ethyl 4-bromo-3-oxo-2-methoxyimino-acetate providing ethyl 2-(2-amino-4-[2- 14 C] thiazolyl)-2-methoxyi-minoacetate as the pure Z-isomer. Saponification gave the amino acid this was reacted with 1-hydroxybenzotriazole to give the activated ester. Condensation in situ with 7-amino-3-(1-methylpyrrolidinio) methyl-3-cephem-4-carboxylate yielded the product as the pure sulfate salt. Treatment of the sulfate salt with base provided the zwitterion isolated as the stable N-methyl-2-pyrrolidinone adduct. An aqueous solution of the adduct was converted to the crystalline title compound, [ 14 C]Cefepime hydrochloride hydrate, with hydrochloric acid/acetone. Radiochemical purity was 99.0% and specific activity, 34.2 μCi/mg. Overall yield from [ 14 C]thiourea was 18%. (Author)

  3. 3’-Deoxyadenosine (Cordycepin) Produces a Rapid and Robust Antidepressant Effect via Enhancing Prefrontal AMPA Receptor Signaling Pathway

    Science.gov (United States)

    Li, Bai; Hou, Yangyang; Zhu, Ming; Bao, Hongkun; Nie, Jun; Zhang, Grace Y.; Shan, Liping; Yao, Yao; Du, Kai; Yang, Hongju; Li, Meizhang; Zheng, Bingrong; Xu, Xiufeng; Xiao, Chunjie; Du, Jing

    2016-01-01

    Background: The development of rapid and safe antidepressants for the treatment of major depression is in urgent demand. Converging evidence suggests that glutamatergic signaling seems to play important roles in the pathophysiology of depression. Methods: We studied the antidepressant effects of 3’-deoxyadenosine (3’-dA, Cordycepin) and the critical role of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor in male CD-1 mice via behavioral and biochemical experiments. After 3’-dA treatment, the phosphorylation and synaptic localization of the AMPA receptors GluR1 and GluR2 were determined in the prefrontal cortex (PFC) and hippocampus (HIP). The traditional antidepressant imipramine was applied as a positive control. Results: We found that an injection of 3’-dA led to a rapid and robust antidepressant effect, which was significantly faster and stronger than imipramine, after 45min in tail suspension and forced swim tests. This antidepressant effect remained after 5 days of treatment with 3’-dA. Unlike the psycho-stimulants, 3’-dA did not show a hyperactive effect in the open field test. After 45min or 5 days of treatment, 3’-dA enhanced GluR1 S845 phosphorylation in both the PFC and HIP. In addition, after 45min of treatment, 3’-dA significantly up-regulated GluR1 S845 phosphorylation and GluR1, but not GluR2 levels, at the synapses in the PFC. After 5 days of treatment, 3’-dA significantly enhanced GluR1 S845 phosphorylation and GluR1, but not GluR2, at the synapses in the PFC and HIP. Moreover, the AMPA-specific antagonist GYKI 52466 was able to block the rapid antidepressant effects of 3’-dA. Conclusion: This study identified 3’-dA as a novel rapid antidepressant with clinical potential and multiple beneficial mechanisms, particularly in regulating the prefrontal AMPA receptor signaling pathway. PMID:26443809

  4. Stimulation of {sup 125}I-3-iodo-{alpha}-methyl-L-tyrosine uptake in Chinese hamster ovary (CHO-K1) cells by tyrosine esters

    Energy Technology Data Exchange (ETDEWEB)

    Shikano, Naoto [Department of Radiological Sciences, Center for Medical Sciences and Center for Humanities and Sciences, Ibaraki Prefectural University of Health Sciences, Inashiki-gun, Ibaraki (Japan)], E-mail: sikano@ipu.ac.jp; Ogura, Masato; Sagara, Jun-ichi; Nakajima, Syuichi [Department of Radiological Sciences, Center for Medical Sciences and Center for Humanities and Sciences, Ibaraki Prefectural University of Health Sciences, Inashiki-gun, Ibaraki (Japan); Kobayashi, Masato [Division of Health Science, Graduate School of Health Sciences, Kanazawa University, Kanazawa, Ishikawa (Japan); Baba, Takeshi; Yamaguchi, Naoto; Iwamura, Yukio; Kubota, Nobuo [Department of Radiological Sciences, Center for Medical Sciences and Center for Humanities and Sciences, Ibaraki Prefectural University of Health Sciences, Inashiki-gun, Ibaraki (Japan); Kawai, Keiichi [Division of Health Science, Graduate School of Health Sciences, Kanazawa University, Kanazawa, Ishikawa (Japan)

    2010-02-15

    Introduction: Transport of the amino acid analog {sup 123}I-3-iodo-{alpha}-methyl-L-tyrosine, which is used in clinical SPECT imaging, occurs mainly via L-type amino acid transporter type 1 (LAT1; an amino acid exchanger). As LAT1 is highly expressed in actively proliferating tumors, we made a preliminary investigation of the effects of amino acid esters on enhancement of {sup 125}I-3-iodo-{alpha}-methyl-L-tyrosine (IMT) uptake via LAT1 in Chinese hamster ovary (CHO-K1) cells. Methods: Because the sequence of the CHO-K1 LAT1 gene is not available, we confirmed LAT1 expression through IMT (18.5 kBq) uptake mechanisms using specific inhibitors. L-Gly, L-Ser, L-Leu, L-Phe, L-Met, L-Tyr, D-Tyr, L-Val and L-Lys ethyl/methyl esters were tested in combination with IMT. Time-course studies over a 3-h period were conducted, and the concentration dependence of L-Tyr ethyl and methyl esters (0.001 to 10 mM) in combination with IMT was also examined. For a proof of de-esterification of L- and D-Tyr ethyl and methyl esters in the cells (by enzymatic attack or other cause), the concentration of L- and D-Tyr was analyzed by high-performance liquid chromatography of the esters in phosphate buffer (pH 7.4) and cell homogenates at 37 deg. C or under ice-cold conditions. Results: Inhibition tests suggested that LAT1 is involved in IMT uptake by CHO-K1 cells. Co-administration of 1 mM of L-Tyr ethyl or methyl ester with IMT produced the greatest enhancement. The de-esterification reaction was stereo selective and temperature dependent in the homogenate. De-esterification kinetics were very fast in the homogenate and very slow in the phosphate buffer. Conclusions: The L-Tyr ethyl or methyl esters were the most effective enhancers of IMT uptake into CHO-K1 cells and acted by trans-stimulation of the amino acid exchange function of LAT1. This result suggests that de-esterification in the cells may be caused by enzymatic attack. We will use IMT and L-Tyr ethyl or methyl esters to examine

  5. Synthesis of carboxylic acids, esters, alcohols and ethers containing a tetrahydropyran ring derived from 6-methyl-5-hepten-2-one.

    Science.gov (United States)

    Hanzawa, Yohko; Hashimoto, Kahoko; Kasashima, Yoshio; Takahashi, Yoshiko; Mino, Takashi; Sakamoto, Masami; Fujita, Tsutomu

    2012-01-01

    3-hydroxy acids, 3-hydroxy-3,7-dimethyloct-6-enoic acid (1) and 3-hydroxy-2,2,3,7-tetramethyloct-6-enoic acid (2), were prepared from 6-methyl-5-hepten-2-one, and they were subsequently used to prepare (2,6,6-trimethyltetrahydropyran-2-yl)acetic acid (3) and 2-methyl-2-(2,6,6-trimethyltetrahydropyran-2-yl)propanoic acid (4), respectively, via cyclization with an acidic catalyst such as boron trifluoride diethyl etherate or iodine. The reaction of carboxylic acids 3 and 4 with alcohols, including methanol, ethanol, and 1-propanol, produced the corresponding methyl, ethyl, and propyl esters, which all contained a tetrahydropyran ring. Reduction of carboxylic acids 3 and 4 afforded the corresponding alcohols. Subsequent reactions of these alcohols with several acyl chlorides produced novel esters. The alcohols also reacted with methyl iodide and sodium hydride to provide novel ethers. A one-pot cyclization-esterification of 1 to produce esters containing a tetrahydropyran ring, using iodine as a catalyst, was also investigated.

  6. 5-(2-18F-fluoroethoxy)-L-tryptophan as a substrate of system L transport for tumor imaging by PET.

    Science.gov (United States)

    Krämer, Stefanie D; Mu, Linjing; Müller, Adrienne; Keller, Claudia; Kuznetsova, Olga F; Schweinsberg, Christian; Franck, Dominic; Müller, Cristina; Ross, Tobias L; Schibli, Roger; Ametamey, Simon M

    2012-03-01

    Large neutral l-amino acids are substrates of system L amino acid transporters. The level of one of these, LAT1, is increased in many tumors. Aromatic l-amino acids may also be substrates of aromatic l-amino acid decarboxylase (AADC), the level of which is enhanced in endocrine tumors. Increased amino acid uptake and subsequent decarboxylation result in the intracellular accumulation of the amino acid and its decarboxylation product. (18)F- and (11)C-labeled neutral aromatic amino acids, such as l-3,4-dihydroxy-6-(18)F-fluorophenylalanine ((18)F-FDOPA) and 5-hydroxy-l-[β-(11)C]tryptophan, are thus successfully used in PET to image endocrine tumors. However, 5-hydroxy-l-[β-(11)C]tryptophan has a relatively short physical half-life (20 min). In this work, we evaluated the in vitro and in vivo characteristics of the (18)F-labeled tryptophan analog 5-(2-(18)F-fluoroethoxy)-l-tryptophan ((18)F-l-FEHTP) as a PET probe for tumor imaging. (18)F-l-FEHTP was synthesized by no-carrier-added (18)F fluorination of 5-hydroxy-l-tryptophan. In vitro cell uptake and efflux of (18)F-l-FEHTP and (18)F-FDOPA were studied with NCI-H69 endocrine small cell lung cancer cells, PC-3 pseudoendocrine prostate cancer cells, and MDA-MB-231 exocrine breast cancer cells. Small-animal PET was performed with the respective xenograft-bearing mice. Tissues were analyzed for potential metabolites. (18)F-l-FEHTP specific activity and radiochemical purity were 50-150 GBq/μmol and greater than 95%, respectively. In vitro cell uptake of (18)F-l-FEHTP was between 48% and 113% of added radioactivity per milligram of protein within 60 min at 37°C and was blocked by greater than 95% in all tested cell lines by the LAT1/2 inhibitor 2-amino-2-norboranecarboxylic acid. (18)F-FDOPA uptake ranged from 26% to 53%/mg. PET studies revealed similar xenograft-to-reference tissue ratios for (18)F-l-FEHTP and (18)F-FDOPA at 30-45 min after injection. In contrast to the (18)F-FDOPA PET results, pretreatment with the

  7. DNA methylation of amino acid transporter genes in the human placenta.

    Science.gov (United States)

    Simner, C; Novakovic, B; Lillycrop, K A; Bell, C G; Harvey, N C; Cooper, C; Saffery, R; Lewis, R M; Cleal, J K

    2017-12-01

    Placental transfer of amino acids via amino acid transporters is essential for fetal growth. Little is known about the epigenetic regulation of amino acid transporters in placenta. This study investigates the DNA methylation status of amino acid transporters and their expression across gestation in human placenta. BeWo cells were treated with 5-aza-2'-deoxycytidine to inhibit methylation and assess the effects on amino acid transporter gene expression. The DNA methylation levels of amino acid transporter genes in human placenta were determined across gestation using DNA methylation array data. Placental amino acid transporter gene expression across gestation was also analysed using data from publically available Gene Expression Omnibus data sets. The expression levels of these transporters at term were established using RNA sequencing data. Inhibition of DNA methylation in BeWo cells demonstrated that expression of specific amino acid transporters can be inversely associated with DNA methylation. Amino acid transporters expressed in term placenta generally showed low levels of promoter DNA methylation. Transporters with little or no expression in term placenta tended to be more highly methylated at gene promoter regions. The transporter genes SLC1A2, SLC1A3, SLC1A4, SLC7A5, SLC7A11 and SLC7A10 had significant changes in enhancer DNA methylation across gestation, as well as gene expression changes across gestation. This study implicates DNA methylation in the regulation of amino acid transporter gene expression. However, in human placenta, DNA methylation of these genes remains low across gestation and does not always play an obvious role in regulating gene expression, despite clear evidence for differential expression as gestation proceeds. Copyright © 2017. Published by Elsevier Ltd.

  8. Effects of volatile fatty acids on propionate metabolism and gluconeogenesis in caprine hepatocytes

    International Nuclear Information System (INIS)

    Aiello, R.J.; Armentano, L.E.

    1987-01-01

    Isolated caprine hepatocytes were incubated with fatty acids of various chain lengths. Short-chain fatty acids effects on rates of gluconeogenesis and oxidation from [2- 14 C] propionate were determined. Additions of glucose (2.5 mM) had no effect on hepatic [2- 14 C]-propionate metabolism in the presence and absence of amino acids. A complete mixture of amino acids increased label incorporation from [2- 14 C] propionate into [ 14 C] glucose by 22%. Butyrate inhibited [2- 14 C] propionate metabolism and increased the apparent Michaelis constant for [2- 14 C] propionate incorporation into [ 14 C] glucose from 2.4 +/- 1.5 to 5.6 +/- .9 mM. Butyrate's effects on propionate were similar in the presence and absence of L-carnitine (1 mM). Isobutyrate, 2-methylbutyrate, and valerate (1.25 mM) had no effect on [ 14 C] glucose production but decreased 14 CO 2 production to 57, 61, and 54% of the control [2- 14 C] propionate (1.25 mM). This inhibition on 14 CO 2 was not competitive. Isovalerate had no effect on either [2- 14 C] propionate incorporation into glucose of CO 2 . An increase in ratio of [ 14 C] glucose to 14 CO 2 from [2- 14 C]-propionate demonstrated that short-chain fatty acids other than butyrate do not inhibit gluconeogenesis from propionate. In addition, fatty acids that generate a net synthesis of intracellular oxaloacetate may partition propionate carbons toward gluconeogenic rather than oxidative pathways in goat hepatocytes

  9. Functional evidence for the critical amino-terminal conserved domain and key amino acids of Arabidopsis 4-HYDROXY-3-METHYLBUT-2-ENYL DIPHOSPHATE REDUCTASE.

    Science.gov (United States)

    Hsieh, Wei-Yu; Sung, Tzu-Ying; Wang, Hsin-Tzu; Hsieh, Ming-Hsiun

    2014-09-01

    The plant 4-HYDROXY-3-METHYLBUT-2-ENYL DIPHOSPHATE REDUCTASE (HDR) catalyzes the last step of the methylerythritol phosphate pathway to synthesize isopentenyl diphosphate and its allyl isomer dimethylallyl diphosphate, which are common precursors for the synthesis of plastid isoprenoids. The Arabidopsis (Arabidopsis thaliana) genomic HDR transgene-induced gene-silencing lines are albino, variegated, or pale green, confirming that HDR is essential for plants. We used Escherichia coli isoprenoid synthesis H (Protein Data Bank code 3F7T) as a template for homology modeling to identify key amino acids of Arabidopsis HDR. The predicted model reveals that cysteine (Cys)-122, Cys-213, and Cys-350 are involved in iron-sulfur cluster formation and that histidine (His)-152, His-241, glutamate (Glu)-242, Glu-243, threonine (Thr)-244, Thr-312, serine-379, and asparagine-381 are related to substrate binding or catalysis. Glu-242 and Thr-244 are conserved only in cyanobacteria, green algae, and land plants, whereas the other key amino acids are absolutely conserved from bacteria to plants. We used site-directed mutagenesis and complementation assay to confirm that these amino acids, except His-152 and His-241, were critical for Arabidopsis HDR function. Furthermore, the Arabidopsis HDR contains an extra amino-terminal domain following the transit peptide that is highly conserved from cyanobacteria, and green algae to land plants but not existing in the other bacteria. We demonstrated that the amino-terminal conserved domain was essential for Arabidopsis and cyanobacterial HDR function. Further analysis of conserved amino acids in the amino-terminal conserved domain revealed that the tyrosine-72 residue was critical for Arabidopsis HDR. These results suggest that the structure and reaction mechanism of HDR evolution have become specific for oxygen-evolving photosynthesis organisms and that HDR probably evolved independently in cyanobacteria versus other prokaryotes. © 2014

  10. 40 CFR 180.1281 - S-Abscisic Acid, (S)-5-(1-hydroxy-2,6,6-trimethyl-4-oxo-1-cyclohex-2-enyl)-3-methyl-penta-(2Z,4E...

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false S-Abscisic Acid, (S)-5-(1-hydroxy-2,6... Exemptions From Tolerances § 180.1281 S-Abscisic Acid, (S)-5-(1-hydroxy-2,6,6-trimethyl-4-oxo-1-cyclohex-2... from the requirement of a tolerance is established for residues of S-Abscisic Acid in or on all food...

  11. Deconjugation of N-glucuronide conjugated metabolites with hydrazine hydrate - Biomarkers for exposure to the food-borne carcinogen 2-amino-l-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)

    DEFF Research Database (Denmark)

    Frandsen, Henrik Lauritz

    2007-01-01

    The metabolism of the carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) has been investigated in rabbit liver S9. Two phase I metabolites, N-2-OH-PhIP and 4'-OH-PhIP were identified based on UV and mass spectra and co-elution with reference standards. Fortification of the incubation...

  12. Identification of epigallocatechin-3-O-(3-O-methyl)-gallate (EGCG3''Me) and amino acid profiles in various tea (Camellia sinensis L.) cultivars.

    Science.gov (United States)

    Ji, Hyang-Gi; Lee, Yeong-Ran; Lee, Min-Seuk; Hwang, Kyeng Hwan; Kim, Eun-Hee; Park, Jun Seong; Hong, Young-Shick

    2017-10-01

    This article includes experimental data on the identification of epigallocatechin-3-O-(3-O-methyl)-gallate (EGCG3''Me) by 2-dimensional (2D) proton ( 1 H) NMR analysis and on the information of amino acid and catechin compound profiles by HPLC analysis in leaf extracts of various tea cultivars. These data are related to the research article " Metabolic phenotyping of various tea (Camellia sinensis L.) cultivars and understanding of their intrinsic metabolism " (Ji et al., 2017) [1]. The assignment for EGCG3x''Me by 1 H NMR analysis was also confirmed with spiking experiment of its pure chemical.

  13. Development of a simple measurement method for GluR2 protein expression as an index of neuronal vulnerability

    Directory of Open Access Journals (Sweden)

    Chihiro Sugiyama

    2015-01-01

    Full Text Available In vitro estimating strategies for potential neurotoxicity are required to screen multiple substances. In a previous study, we showed that exposure to low-concentrations of some chemicals, such as organotin, decreased the expression of GluR2 protein, which is a subunit of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA-type glutamate receptors, and led to neuronal vulnerability. This result suggested that GluR2 decreases as an index of neuronal cell sensitivity and vulnerability to various toxic insults. Accordingly, we developed a versatile method that is a large scale determination of GluR2 protein expression in the presence of environmental chemicals by means of AlphaLISA technology. Various analytical conditions were optimized, and then GluR2 protein amount was measured by the method using AlphaLISA. The GluR2 amounts were strongly correlated with that of measured by western blotting, which is currently used to determine GluR2 expression. An ideal standard curve could be written with the authentic GluR2 protein from 0 ng to 100 ng. Subsequently, twenty environmental chemicals were screened and nitenpyram was identified as a chemical which lead to decrease in GluR2 protein expression. This assay may provide a tool for detecting neurotoxic chemicals according to decreases in GluR2 protein expression.

  14. Effects of L-cysteine and N-acetyl-L-cysteine on 4-hydroxy-2, 5-dimethyl-3(2H)-furanone (furaneol), 5-(hydroxymethyl)furfural, and 5-methylfurfural formation and browning in buffer solutions containing either rhamnose or glucose and arginine.

    Science.gov (United States)

    Haleva-Toledo, E; Naim, M; Zehavi, U; Rouseff, R L

    1999-10-01

    Solutions of L-cysteine (Cys) and N-acetyl-L-cysteine (AcCys), containing glucose or rhamnose, with or without arginine, were buffered to pH 3, 5, and 7 and incubated at 70 degrees C for 48 h. Cys and AcCys inhibited the formation of (hydroxymethyl)furfural (HMF) from glucose and methylfurfural (MF) from rhamnose under acidic conditions. AcCys inhibited the accumulation of 4-hydroxy-2, 5-dimethyl- 3(2H)-furanone (DMHF, Furaneol) from rhamnose, but Cys, under our experimental conditions, enhanced Furaneol accumulation from rhamnose. Cys and AcCys reacted directly with Furaneol but not with HMF or MF. Both Cys and AcCys inhibited nonenzymatic browning at pH 7. At pH 3, however, Cys reacted with both glucose and rhamnose to produce unidentified compounds that increased the visible absorbency.

  15. Syntheses of Novel 4-Substituted N-(5-amino-1H-1,2,4-triazol-3-ylpyridine-3-sulfonamide Derivatives with Potential Antifungal Activity

    Directory of Open Access Journals (Sweden)

    Krzysztof Szafrański

    2017-11-01

    Full Text Available Candidiasis represent a serious threat for patients with altered immune responses. Therefore, we have undertaken the synthesis of compounds comprising a pyridine-3-sulfonamide scaffold and known antifungally active 1,2,4-triazole substituents. Thus a series of novel 4-substituted N-(5-amino-1H-1,2,4-triazol-3-ylpyridine-3-sulfonamides have been synthesized by multistep reactions starting from 4-chloropyridine-3-sulfonamide via N′-cyano-N-[(4-substitutedpyridin-3-ylsulfonyl]carbamimidothioates which were further converted with hydrazine hydrate to the corresponding 1,2,4-triazole derivatives 26–36. The final compounds were evaluated for antifungal activity against strains of the genera Candida, Geotrichum, Rhodotorula, and Saccharomycess isolated from patients with mycosis. Many of them show greater efficacy than fluconazole, mostly towards Candida albicans and Rhodotorula mucilaginosa species, with MIC values ≤ 25 µg/mL. A docking study of the most active compounds 26, 34 and 35 was performed showing the potential mode of binding to Candida albicans lanosterol 14α-demethylase. Also in vitro cytotoxicity of selected compounds have been evaluated on the NCI-60 cell line panel.

  16. Order-disorder phase transitions and their influence on the structure and vibrational properties of new hybrid material: 2-Amino-4-methyl-3-nitropyridinium trifluoroacetate

    International Nuclear Information System (INIS)

    Lorenc, J.; Bryndal, I.; Syska, W.; Wandas, M.; Marchewka, M.; Pietraszko, A.; Lis, T.; Maczka, M.; Hermanowicz, K.; Hanuza, J.

    2010-01-01

    Graphical abstract: New organic-organic salt, 2-amino-4-methyl-3-nitropyridinium trifluoroacetate, has been synthesised and characterised by FT-IR, FT-Raman, DSC and single crystal X-ray crystallography. The 2-amino-4-methyl-3-nitropyridinium trifluoroacetate undergoes a reversible phase transition at ∼162 K. The X-ray structures, vibrational spectra and quantum chemical DFT calculations (B3LYP/6-31G(d,p) approach) have been analysed for high-temperature and low-temperature modifications of the compound, which both crystallize in orthorhombic space group Pbca with two non-equivalent cations and two anions in the asymmetric unit. Their crystal and molecular structures have been compared and the role of the intermolecular interactions in these crystals has been analysed. The mechanisms of the phase transition have been proposed. - Abstract: New organic-organic salt, 2-amino-4-methyl-3-nitropyridinium trifluoroacetate, has been synthesised and characterised by FT-IR, FT-Raman, DSC and single crystal X-ray crystallography. The 2-amino-4-methyl-3-nitropyridinium trifluoroacetate undergoes a reversible phase transition at ∼162 K. The X-ray structures, vibrational spectra and quantum chemical DFT calculations (B3LYP/6-31G(d,p) approach) have been analysed for high-temperature and low-temperature modifications of the compound, which both crystallize in orthorhombic space group Pbca with two non-equivalent cations and two anions in the asymmetric unit. Their crystal and molecular structures have been compared and the role of the intermolecular interactions in these crystals has been analysed. The mechanisms of the phase transition have been proposed.

  17. Order-disorder phase transitions and their influence on the structure and vibrational properties of new hybrid material: 2-Amino-4-methyl-3-nitropyridinium trifluoroacetate

    Energy Technology Data Exchange (ETDEWEB)

    Lorenc, J., E-mail: jadwiga.lorenc@ue.wroc.pl [Department of Bioorganic Chemistry, Institute of Chemistry and Food Technology, Faculty of Engineering and Economy, University of Economic, Wroclaw (Poland); Bryndal, I. [Department of Bioorganic Chemistry, Institute of Chemistry and Food Technology, Faculty of Engineering and Economy, University of Economic, Wroclaw (Poland); Faculty of Chemistry, University of Wroclaw (Poland); Syska, W.; Wandas, M. [Department of Bioorganic Chemistry, Institute of Chemistry and Food Technology, Faculty of Engineering and Economy, University of Economic, Wroclaw (Poland); Marchewka, M.; Pietraszko, A. [Institute of Low Temperature and Structure Research, Polish Academy of Sciences, Wroclaw (Poland); Lis, T. [Faculty of Chemistry, University of Wroclaw (Poland); Maczka, M.; Hermanowicz, K. [Institute of Low Temperature and Structure Research, Polish Academy of Sciences, Wroclaw (Poland); Hanuza, J. [Department of Bioorganic Chemistry, Institute of Chemistry and Food Technology, Faculty of Engineering and Economy, University of Economic, Wroclaw (Poland); Institute of Low Temperature and Structure Research, Polish Academy of Sciences, Wroclaw (Poland)

    2010-08-23

    Graphical abstract: New organic-organic salt, 2-amino-4-methyl-3-nitropyridinium trifluoroacetate, has been synthesised and characterised by FT-IR, FT-Raman, DSC and single crystal X-ray crystallography. The 2-amino-4-methyl-3-nitropyridinium trifluoroacetate undergoes a reversible phase transition at {approx}162 K. The X-ray structures, vibrational spectra and quantum chemical DFT calculations (B3LYP/6-31G(d,p) approach) have been analysed for high-temperature and low-temperature modifications of the compound, which both crystallize in orthorhombic space group Pbca with two non-equivalent cations and two anions in the asymmetric unit. Their crystal and molecular structures have been compared and the role of the intermolecular interactions in these crystals has been analysed. The mechanisms of the phase transition have been proposed. - Abstract: New organic-organic salt, 2-amino-4-methyl-3-nitropyridinium trifluoroacetate, has been synthesised and characterised by FT-IR, FT-Raman, DSC and single crystal X-ray crystallography. The 2-amino-4-methyl-3-nitropyridinium trifluoroacetate undergoes a reversible phase transition at {approx}162 K. The X-ray structures, vibrational spectra and quantum chemical DFT calculations (B3LYP/6-31G(d,p) approach) have been analysed for high-temperature and low-temperature modifications of the compound, which both crystallize in orthorhombic space group Pbca with two non-equivalent cations and two anions in the asymmetric unit. Their crystal and molecular structures have been compared and the role of the intermolecular interactions in these crystals has been analysed. The mechanisms of the phase transition have been proposed.

  18. Radiosynthesis of 7-chloro-N, N-dimethyl-5-[11C] methyl-4-oxo-3-phenyl-3, 5-dihydro-4H pyridazino [4, 5-b]indole-1-acetamide, [11C]SSR180575, a novel radioligand for imaging the TSPO (peripheral benzodiazepine receptor) with PET

    International Nuclear Information System (INIS)

    Thominiaux, C.; Damont, A.L.; Kuhnast, B.; Demphel, St.; Le Helleix, St.; Chauveau, F.; Boutin, H.; Van Camp, N.; Boisgard, R.; Tavitian, B.; Dolle, F.; Boisnard, S.; Rivron, L.; Roy, S.; Allen, J.; Chauveau, F.; Boutin, H.; Van Camp, N.; Boisgard, R.; Tavitian, B.; Rooney, T.; Benavides, J.; Hantraye, Ph.

    2010-01-01

    SSR180575 (7-chloro-N, N, 5-trimethyl-4-oxo-3-phenyl-3, 5-dihydro-4H-pyridazino [4, 5-b]indole-1-acetamide) is the lead compound of an original pyridazino-indole series of potent and highly selective TSPO (peripheral benzodiazepine receptor) ligands. Isotopic labeling of SSR180575 with the short-lived positron-emitter carbon-11 (T1/2: 20.38 min) at its 5-methyl-pyridazino[4, 5-b]indole moiety as well as at its N, N-dimethylacetamide function by methylation of the corresponding nor-analogues was investigated. Best results in terms of radiochemical yields and purities were obtained for the preparation of [indole-N-methyl- 11 C]SSR180575, where routine production batches of 4.5-5.0 GBq of radiochemically pure (499%) i.v. injectable solutions (specific radioactivities: 50-90 GBq/μmol) could be prepared within a total synthesis time of 25 min (HPLC purification included) starting from a 55 GBq [ 11 C]CO 2 cyclotron production batch (non decay-corrected overall radiochemical yields: 8-9%). The process comprises (1) trapping at -10 C of [ 11 C]methyl triflate in DMF (300 μl) containing 0.2-0.3 mg of the indole precursor for labeling and 4 mg of K 2 CO 3 (excess); (2) heating at 120 C for 3 min; (3) dilution of the residue with 0.5 ml of the HPLC mobile phase and (4) purification using semi-preparative reversed phase HPLC (Zorbax R SB-C-18). In vivo pharmacological properties of [indole-N-methyl- 11 C]SSR180575 as a candidate for imaging neuro-inflammation with positron emission tomography are currently evaluated. (authors)

  19. Differential alterations of cortical glutamatergic binding sites in senile dementia of the Alzheimer type

    International Nuclear Information System (INIS)

    Chalmers, D.T.; Dewar, D.; Graham, D.I.; Brooks, D.N.; McCulloch, J.

    1990-01-01

    Involvement of cortical glutamatergic mechanisms in senile dementia of the Alzheimer type (SDAT) has been investigated with quantitative ligand-binding autoradiography. The distribution and density of Na(+)-dependent glutamate uptake sites and glutamate receptor subtypes--kainate, quisqualate, and N-methyl-D-aspartate--were measured in adjacent sections of frontal cortex obtained postmortem from six patients with SDAT and six age-matched controls. The number of senile plaques was determined in the same brain region. Binding of D-[3H]aspartate to Na(+)-dependent uptake sites was reduced by approximately 40% throughout SDAT frontal cortex relative to controls, indicating a general loss of glutamatergic presynaptic terminals. [3H]Kainate receptor binding was significantly increased by approximately 70% in deep layers of SDAT frontal cortex compared with controls, whereas this binding was unaltered in superficial laminae. There was a positive correlation (r = 0.914) between kainate binding and senile plaque number in deep cortical layers. Quisqualate receptors, as assessed by 2-amino-3-hydroxy-5-[3H]methylisoxazole-4-propionic acid binding, were unaltered in SDAT frontal cortex compared with controls. There was a small reduction (25%) in N-methyl-D-aspartate-sensitive [3H]glutamate binding only in superficial cortical layers of SDAT brains relative to control subjects. [3H]Glutamate binding in SDAT subjects was unrelated to senile plaque number in superficial cortical layers (r = 0.104). These results indicate that in the presence of cortical glutamatergic terminal loss in SDAT plastic alterations occur in some glutamate receptor subtypes but not in others

  20. A hybrid non-ribosomal peptide/polyketide synthetase containing fatty-acyl ligase (FAAL synthesizes the β-amino fatty acid lipopeptides puwainaphycins in the Cyanobacterium Cylindrospermum alatosporum.

    Directory of Open Access Journals (Sweden)

    Jan Mareš

    Full Text Available A putative operon encoding the biosynthetic pathway for the cytotoxic cyanobacterial lipopeptides puwainphycins was identified in Cylindrospermum alatosporum. Bioinformatics analysis enabled sequential prediction of puwainaphycin biosynthesis; this process is initiated by the activation of a fatty acid residue via fatty acyl-AMP ligase and continued by a multidomain non-ribosomal peptide synthetase/polyketide synthetase. High-resolution mass spectrometry and nuclear magnetic resonance spectroscopy measurements proved the production of puwainaphycin F/G congeners differing in FA chain length formed by either 3-amino-2-hydroxy-4-methyl dodecanoic acid (4-methyl-Ahdoa or 3-amino-2-hydroxy-4-methyl tetradecanoic acid (4-methyl-Ahtea. Because only one puwainaphycin operon was recovered in the genome, we suggest that the fatty acyl-AMP ligase and one of the amino acid adenylation domains (Asn/Gln show extended substrate specificity. Our results provide the first insight into the biosynthesis of frequently occurring β-amino fatty acid lipopeptides in cyanobacteria, which may facilitate analytical assessment and development of monitoring tools for cytotoxic cyanobacterial lipopeptides.

  1. N-[11C]methyl-3,4-methylenedioxyamphetamine (Ecstasy) and 2-methyl-N-[11C]methyl-4,5-methylenedioxyamphetamine. Synthesis and biodistribution studies

    International Nuclear Information System (INIS)

    Patt, M.; Machulla, H.J.; Guendisch, D.; Kovar, K.A.; Wuellner, U.; Blocher, A.

    1999-01-01

    In order to evaluate the neurobiological mechanism causing the psychogenic effects of methylenedioxy-derivatives of amphetamine, the carbon-11 labeled analogues of 3,4-methylenedioxymethamphetamine (MDMA), 2 and 2,N-dimethyl-4,5-methylenedioxyamphetamine (MADAM-6) 4 were prepared for application in in-vivo PET studies by methylation of 3,4-methylenedioxyamphetamine (MDA) 1 and 2-methyl-4,5-methylenedioxyamphetamine 3 with [ 11 C]CH 3 I. The radiochemical yield was determined in dependence on time, temperature and amount of precursor. The best conditions for a fast labeling reaction with carbon-11 on a preparative scale were found to be a reaction time of 10 min using 1 mg of the corresponding dimethyl-precursors 1 or 3, thus obtaining radiochemical yields of 60% (based on produced [ 11 C]CH 3 I). Biodistribution studies were performed in rats, a high brain to blood ratio of 7.5 was observed for [ 11 C]MDMA in contrast to a ratio of 3.7 for [ 11 C]MADAM-6. (author)

  2. The role of hydrogen bonds in the crystals of 2-amino-4-methyl-5-nitropyridinium trifluoroacetate monohydrate and 4-hydroxybenzenesulfonate - X-ray and spectroscopic studies.

    Science.gov (United States)

    Bryndal, I; Marchewka, M; Wandas, M; Sąsiadek, W; Lorenc, J; Lis, T; Dymińska, L; Kucharska, E; Hanuza, J

    2014-04-05

    Two new organic-organic salts, 2-amino-4-methyl-5-nitropyridinium trifluoroacetate monohydrate (AMNP-TFA), and 2-amino-4-methyl-5-nitropyridinium 4-hydroxybenzenesulfonate (AMNP-HBS), were obtained and characterized by means of FT-IR, FT-Raman and single crystal X-ray crystallography. In the former crystal, the cations, anions and water molecules are linked into layers by three types of hydrogen bonds, NPH⋯O, NAH⋯O and OH⋯O. These layers are connected by weaker CH⋯O hydrogen bonds. In the latter crystal, the cations and anions form one-dimensional structure through a number of hydrogen-bonding interactions involving the OH, NH(+) and NH2 groups as donors. In this case the NPH⋯O and NAH⋯O hydrogen bonds are formed. The combination of interactions between cations and anions results in the formation of columns. Additionally, there are π-π stacking interactions between the columns. The obtained X-ray structural data are related to the vibrational spectra of the studied crystals. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Application of stable isotope ratio analysis explaining the bioformation of 2,5-dimethyl-4-hydroxy-3(2H)-furanone in plants by a biological Maillard reaction

    International Nuclear Information System (INIS)

    Schwab, W.

    1998-01-01

    [1-13C]-D-Fructose and [U-13C6]-D-fructose were applied to detached ripening strawberry fruits, and the incorporation into 2,5-dimethyl-4-hydroxy-3(2H)-furanone 1, 2,5-dimethyl-4-methoxy-3(2H)-furanone 2, 2,5-dimethyl-4-acetoxy-3(2H)-furanone 3, 2,5-dimethyl-4-hydroxy-3(2H)-furanone beta-D-glucopyranoside 4, and 2,5-dimethyl-4-hydroxy-3(2H)-furanone 6'-O-malonyl beta-D-glucopyranoside 5 was determined by HRGC-MS and HPLC-ESI MS-MS. The data clearly showed the direct conversion of D-fructose to the furanones without cleavage of the carbohydrate prior to the formation of 1-5, as expected for a biological Maillard reaction. Both, the furanone and the D-glucose moiety of 4 and 5 contained the labels. However, the label was primarily incorporated into the furanone moiety, indicating that D-fructose is a more efficient precursor of the furanones than D-glucose

  4. Acute toxicity of 5-(furan-2-yl, 2-metylfuran-3-yl-4-amino-1,2,4-triazole-3-thiol alkyl derivatives

    Directory of Open Access Journals (Sweden)

    D. M. Danilchenko

    2017-09-01

    Full Text Available The purpose of our work was the further exploration of the new 5-(furan-2-yl, 2-metylfuran-3-yl-4-amino-1,2,4-triazole-3-thiol alkyl derivatives’ acute toxicity, setting some patterns of alkyl substituents influence by the Sulfur atom on the acute toxicity. Research materials and methods. In this study we used first time synthesized 5-(furan-2-yl, 2-metylfuran-3-yl-4-amino-4H-1,2,4-triazole-3-thione derivatives. Acute toxicity was conducted on white rats weighing 160–250 g, which were injected once intraperitoneally with the investigated substances. The rats were received from the nursery of the Pharmacology and Toxicology Institute of Ukraine Medical Sciences Academy. The animals were kept on a standard diet with natural light mode "day-night". Results and their discussion. After the acute toxicity studies in a group of 5-(furan-2-yl, 2-metylfuran-3-yl-4-amino-4H-1,2,4-triazole 3-alkyl derivatives it was found that among all studied structures the most toxic was 2e, LD50 of which was 263 mg/kg, and the least toxic compound was 2a, LD50 of which was 1570 mg/kg, that belongs to the V toxicity class. After comparing the acute toxicity of well-known antimycotic agent fluconazole with the studied compounds it can be argued that most compounds are less toxic than the comparison drug fluconazole with the index of LD50 ˃320 mg/kg. It was found that the transition in a group from butyl to decyl, octyl, ventyl, propyl, nonyl and heptyl substituents in the molecule of 3-alkylthio 5-(furan-2-yl-4-amino-4H-1,2,4-triazole is accompanied by the toxicity increasing. Speaking about the 5-(2-metylfuran-3-yl-4-amino-4H-1,2,4-triazole 3-alkylthio derivatives we can find that this dependence is observed in a number from propyl, pentyl, nonil, butyl, heksyl, octyl and heptyl hydrocarbon chains. Conclusions. The investigated 3-alkylthio 5-(furan-2-yl, 2-metylfuran-3-yl-4-amino-4H-1,2,4-triazole derivatives belong to the IV-V toxicity class. The toxicity of 5

  5. Effect of (R)-2-(2-aminothiazol-4-yl)-4'-{2-[(2-hydroxy-2-phenylethyl)amino]ethyl} acetanilide (YM178), a novel selective beta3-adrenoceptor agonist, on bladder function.

    Science.gov (United States)

    Takasu, Toshiyuki; Ukai, Masashi; Sato, Shuichi; Matsui, Tetsuo; Nagase, Itsuro; Maruyama, Tatsuya; Sasamata, Masao; Miyata, Keiji; Uchida, Hisashi; Yamaguchi, Osamu

    2007-05-01

    We evaluated the pharmacological characteristics of (R)-2-(2-aminothiazol-4-yl)-4'-{2-[(2-hydroxy-2-phenylethyl)amino]-ethyl} acetanilide (YM178). YM178 increased cyclic AMP accumulation in Chinese hamster ovary (CHO) cells expressing human beta3-adrenoceptor (AR). The half-maximal effective concentration (EC50) value was 22.4 nM. EC50 values of YM178 for human beta1- and beta2-ARs were 10,000 nM or more, respectively. The ratio of intrinsic activities of YM178 versus maximal response induced by isoproterenol (nonselective beta-AR agonist) was 0.8 for human beta3-ARs, 0.1 for human beta1-ARs, and 0.1 for human beta2-ARs. The relaxant effects of YM178 were evaluated in rats and humans bladder strips precontracted with carbachol (CCh) and compared with those of isoproterenol and 4-[3-[(1,1-dimethylethyl)amino]-2-hydroxypropoxy]-1,3-dihydro-2H-benzimidazol-2-one hydrochloride (CGP-12177A) (beta3-AR agonist). EC50 values of YM178 and isoproterenol in rat bladder strips precontracted with 10(-6) M CCh were 5.1 and 1.4 microM, respectively, whereas those in human bladder strips precontracted with 10(-7) M CCh were 0.78 and 0.28 microM, respectively. In in vivo study, YM178 at a dose of 3 mg/kg i.v. decreased the frequency of rhythmic bladder contraction induced by intravesical filling with saline without suppressing its amplitude in anesthetized rats. These findings suggest the suitability of YM178 as a therapeutic drug for the treatment of symptoms of overactive bladder such as urinary frequency, urgency, and urge incontinence.

  6. Determination of the enthalpy of vaporization and prediction of surface tension for ionic liquid 1-alkyl-3-methylimidazolium propionate [C(n)mim][Pro](n = 4, 5, 6).

    Science.gov (United States)

    Tong, Jing; Yang, Hong-Xu; Liu, Ru-Jing; Li, Chi; Xia, Li-Xin; Yang, Jia-Zhen

    2014-11-13

    With the use of isothermogravimetrical analysis, the enthalpies of vaporization, Δ(g)lH(o)m(T(av)), at the average temperature, T(av) = 445.65 K, for the ionic liquids (ILs) 1-alkyl-3-methylimidazolium propionate [C(n)mim][Pro](n = 4, 5, 6) were determined. Using Verevkin's method, the difference of heat capacities between the vapor phase and the liquid phase, Δ(g)lC(p)(o)m, for [C(n)mim][Pro](n = 2, 3, 4, 5, 6), were calculated based on the statistical thermodynamics. Therefore, with the use of Δ(g)lC(p)(o)m, the values of Δ(g)lH(o)m(T(av)) were transformed into Δ(g)lH(o)m(298), 126.8, 130.3, and 136.5 for [C(n)mim][Pro](n = 4, 5, 6), respectively. In terms of the new scale of polarity for ILs, the order of the polarity of [C(n)mim][Pro](n = 2, 3, 4, 5, 6) was predicted, that is, the polarity decreases with increasing methylene. A new model of the relationship between the surface tension and the enthalpy of vaporization for aprotic ILs was put forward and used to predict the surface tension for [C(n)mim][Pro](n = 2, 3, 4, 5, 6) and others. The predicted surface tension for the ILs is in good agreement with the experimental one.

  7. Optically active antifungal azoles. XII. Synthesis and antifungal activity of the water-soluble prodrugs of 1-[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-3-[4-(1H-1-tetrazolyl)phenyl]-2-imidazolidinone.

    Science.gov (United States)

    Ichikawa, T; Kitazaki, T; Matsushita, Y; Yamada, M; Hayashi, R; Yamaguchi, M; Kiyota, Y; Okonogi, K; Itoh, K

    2001-09-01

    1-[(1R,2R)-2-(2,4-Difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-3-[4-(1H-1-tetrazolyl)phenyl]-2-imidazolidinone (1: TAK-456) was selected as a candidate for clinical trials, but since its water-solubility was insufficient for an injectable formulation, the quaternary triazolium salts 2 were designed as water-soluble prodrugs. Among the prodrugs prepared, 4-acetoxymethyl-1-[(2R,3R)-2-(2,4-difluorophenyl)-2-hydroxy-3-[2-oxo-3-[4-(1H-1-terazolyl)phenyl]-1-imidazolidinyl]butyl]-1H-1,2,4-triazolium chloride (2a: TAK-457) was selected as an injectable candidate for clinical trials based on the results of evaluations on solubility, stability, hemolytic effect and in vivo antifungal activities.

  8. Methyl 3′,4′,5′-trimethoxybiphenyl-4-carboxylate

    Directory of Open Access Journals (Sweden)

    Sami Nummelin

    2013-03-01

    Full Text Available In the title compound, C17H18O5, the dihedral angle between the benzene rings is 31.23 (16°. In the crystal, the molecules are packed in an antiparallel fashion in layers along the a axis. In each layer, very weak C—H...O hydrogen bonds occur between the methoxy and methyl ester groups. Weak C—H...π interactions between the 4′- and 5′-methoxy groups and neighbouring benzene rings [methoxy-C–ring centroid distances = 4.075 and 3.486 Å, respectively] connect the layers.

  9. Addiction-like Synaptic Impairments in Diet-Induced Obesity.

    Science.gov (United States)

    Brown, Robyn Mary; Kupchik, Yonatan Michael; Spencer, Sade; Garcia-Keller, Constanza; Spanswick, David C; Lawrence, Andrew John; Simonds, Stephanie Elise; Schwartz, Danielle Joy; Jordan, Kelsey Ann; Jhou, Thomas Clayton; Kalivas, Peter William

    2017-05-01

    There is increasing evidence that the pathological overeating underlying some forms of obesity is compulsive in nature and therefore contains elements of an addictive disorder. However, direct physiological evidence linking obesity to synaptic plasticity akin to that occurring in addiction is lacking. We sought to establish whether the propensity to diet-induced obesity (DIO) is associated with addictive-like behavior, as well as synaptic impairments in the nucleus accumbens core considered hallmarks of addiction. Sprague Dawley rats were allowed free access to a palatable diet for 8 weeks then separated by weight gain into DIO-prone and DIO-resistant subgroups. Access to palatable food was then restricted to daily operant self-administration sessions using fixed ratio 1, 3, and 5 and progressive ratio schedules. Subsequently, nucleus accumbens brain slices were prepared, and we tested for changes in the ratio between α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and N-methyl-D-aspartate currents and the ability to exhibit long-term depression. We found that propensity to develop DIO is linked to deficits in the ability to induce long-term depression in the nucleus accumbens, as well as increased potentiation at these synapses as measured by AMPA/N-methyl-D-aspartate currents. Consistent with these impairments, we observed addictive-like behavior in DIO-prone rats, including 1) heightened motivation for palatable food; 2) excessive intake; and 3) increased food seeking when food was unavailable. Our results show overlap between the propensity for DIO and the synaptic changes associated with facets of addictive behavior, supporting partial coincident neurological underpinnings for compulsive overeating and drug addiction. Copyright © 2016 Society of Biological Psychiatry. All rights reserved.

  10. 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) Is Selectively Toxic to Primary Dopaminergic Neurons In Vitro

    Science.gov (United States)

    Griggs, Amy M.; Agim, Zeynep S.; Mishra, Vartika R.; Tambe, Mitali A.; Director-Myska, Alison E.; Turteltaub, Kenneth W.; McCabe, George P.; Rochet, Jean-Christophe; Cannon, Jason R.

    2014-01-01

    Parkinson's disease (PD) is the second most common neurodegenerative disease. Much data has linked the etiology of PD to a variety of environmental factors. The majority of cases are thought to arise from a combination of genetic susceptibility and environmental factors. Chronic exposures to dietary factors, including meat, have been identified as potential risk factors. Although heterocyclic amines that are produced during high-temperature meat cooking are known to be carcinogenic, their effect on the nervous system has yet to be studied in depth. In this study, we investigated neurotoxic effects of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a highly abundant heterocyclic amine in cooked meat, in vitro. We tested toxicity of PhIP and the two major phase I metabolites, N-OH-PhIP and 4′-OH-PhIP, using primary mesencephalic cultures from rat embryos. This culture system contains both dopaminergic and nondopaminergic neurons, which allows specificity of neurotoxicity to be readily examined. We find that exposure to PhIP or N-OH-PhIP is selectively toxic to dopaminergic neurons in primary cultures, resulting in a decreased percentage of dopaminergic neurons. Neurite length is decreased in surviving dopaminergic neurons. Exposure to 4′-OH-PhIP did not produce significant neurotoxicity. PhIP treatment also increased formation of oxidative damage markers, 4-hydroxy-2-nonenal (HNE) and 3-nitrotyrosine in dopaminergic neurons. Pretreatment with N-acetylcysteine was protective. Finally, treatment with blueberry extract, a dietary factor with known antioxidant and other protective mechanisms, prevented PhIP-induced toxicity. Collectively, our study suggests, for the first time, that PhIP is selectively toxic to dopaminergic neurons likely through inducing oxidative stress. PMID:24718704

  11. Selective GABA transporter inhibitors tiagabine and EF1502 exhibit mechanistic differences in their ability to modulate the ataxia and anticonvulsant action of the extrasynaptic GABA(A) receptor agonist gaboxadol

    DEFF Research Database (Denmark)

    Madsen, Karsten Kirkegaard; Ebert, Bjarke; Clausen, Rasmus Prætorius

    2011-01-01

    seizures. Even though less is known about the therapeutic potential of other GABA transport inhibitors, previous investigations have demonstrated that N-[4,4-bis(3-methyl-2-thienyl)-3-butenyl]-3-hydroxy-4-(methylamino)-4,5,6,7-tetrahydrobenzo[d]isoxazol-3-ol (EF1502), which, like tiagabine, is inactive...... of gaboxadol (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol), which, at the doses used in this study (i.e., 1-5 mg/kg) selectively activates extrasynaptic a4-containing GABA(A) receptors, was determined alone and in combination with either tiagabine or EF1502 using Frings audiogenic seizure-susceptible and CF...

  12. The mechanism and kinetics of the electrochemical cleavage of azo bond of 2-hydroxy-5-sulfophenyl-azo-benzoic acids

    International Nuclear Information System (INIS)

    Mandic, Zoran; Nigovic, Biljana; Simunic, Branimir

    2004-01-01

    The electrochemical reduction of 2-hydroxy-5-[(4-sulfophenyl)azo]benzoic acid, 2-hydroxy-5-[(3-sulfophenyl)azo]benzoic acid, 2-hydroxy-5-[(2-sulfophenyl)azo]benzoic acid and 2-hydroxy-5-azo-benzoic acid has been carried out in aqueous solutions at glassy carbon electrode using cyclic voltammetry and chronoamperometry. The position of sulfo substituent relative to azo bridge as well as pH of the solution have significant impact on the electrochemical behavior of these compounds. It has been proposed that these compounds are reduced predominantly as hydrazone tautomers resulting in corresponding hydrazo compounds. The overall electrochemical reduction follows DISP2 mechanism, ultimately leading to the 5-amino salicylic acid and sulfanilic acid. The rate determining step is the homogenous redox reaction between intermediate hydrazo compound and 5-amino salicylic acid quinoneimine. The mechanism is proposed in which activated complex of 5-amino salicylic acid quinoneimine and intermediate hydrazo compound is formed with the simultaneous loss of one proton

  13. Selective removal mercury (Ⅱ) from aqueous solution using silica aerogel modified with 4-amino-5-methyl-1,2,4-triazole-3(4H)-thion

    Energy Technology Data Exchange (ETDEWEB)

    Tadayon, Fariba; Saber-Tehrani, Mohammad; Motahar, Shiva [Islamic Azad University, Tehran (Iran, Islamic Republic of)

    2013-03-15

    Silica aerogel surface modifications with chelating agents for adsorption/removal of metal ions have been reported in recent years. This investigation reported the preparation of silica aerogel (SA) adsorbent coupled with metal chelating ligands of 4-amino-5-methyl-1,2,4-triazole-3(4H)-thion (AMTT) and its application for selective adsorption of Hg(Ⅱ) ion. The adsorbent was characterized by Fourier transform infrared spectra (FTIR) and thermo gravimetric analysis (TGA) measurements, nitrogen physisorption and scanning electron microscope (SEM). Optimal experimental conditions including pH, temperature, adsorbent dosage and contact time have been established. Langmuir and Freundlich isotherm models were applied to analyze the experimental data. The best interpretation for the experimental data given by the Langmuir isotherm equation and the maximum adsorption capacity of the modified silica gel and silica aerogel was 142.85 and 17.24mgg⌃(-1), respectively. Thermodynamic parameters such as Gibbs free energy (ΔG{sup o}), standard enthalpy (ΔH{sup o}) and entropy change (ΔS{sup o}) were investigated. The adsorbed Hg(Ⅱ) on the SA-AMTT adsorbents could be completely eluted by 1.0M KBr solution and recycled at least four times without the loss of adsorption capacity. The results of the present investigation illustrate that modified silica aerogel with AMTT could be used as an adsorbent for the effective removal of Hg(Ⅱ) ions from aqueous solution.

  14. Facile synthesis of some novel 2-substituted-4,6-diarylpyrimidines using 4 ' -hydroxy-3 ' ,5 ' -dinitrochalcones and S-benzylthiouronium chloride

    Directory of Open Access Journals (Sweden)

    K. L. Ameta

    2012-01-01

    Full Text Available Various 4'-hydroxy-3',5'-dinitro substituted chalcones 1 and S-benzylthiouronium chloride (SBT 2 in the presence of DMF-organic bases (morpholine/ pyrrolidine/ piperidine gave 4,6-diaryl-2-(4-morpholinyl / 1-pyrrolidinyl /1-piperidinyl- pyrimidines 4, 5 and 6 in a facile one-pot conversion. In an another attempt reactants 1 and 2 yielded intermediate 2-benzylthiopyrimidines 3, in presence of DMF, which on treatment with heterocyclic secondary amines gave products 4, 5 and 6 in an alternate two-step process.

  15. Biosynthesis of 4-hydroxy-2,5-dimethyl-3(2H)-furanone and derivatives in in vitro grown strawberries.

    Science.gov (United States)

    Pérez, A G; Olías, R; Olías, J M; Sanz, C

    1999-02-01

    The biosynthesis of 2,5-dimethyl-4-hydroxy-3(2H)-furanone (Furaneol) and its methyl ether and glucoside derivatives has been studied in strawberries. An in vitro system was used for growing this fruit, showing that the presence in the incubation medium of sucrose or hydroxyquinoline hemisulfate has no effect on the bioformation of these compounds. Strawberries in vitro grown showed an increase in furanone content with time, especially between the second and fourth days, to the same extent as field-grown fruits but at a higher rate. Among the precursors added to the incubation medium, D-fructose gave rise to an increase in furaneol and its glucoside derivative of 42. 6% and 26.3%, respectively. D-fructose 6-phosphate seems to be the precursor of furaneol in strawberries since, when present in the incubation medium, it produced an average increase of 125% in all furanones contents with respect to control fruits.

  16. The Dnmt3L ADD Domain Controls Cytosine Methylation Establishment during Spermatogenesis

    Directory of Open Access Journals (Sweden)

    Georgios Vlachogiannis

    2015-02-01

    Full Text Available A critical aspect of mammalian gametogenesis is the reprogramming of genomic DNA methylation. The catalytically inactive adaptor Dnmt3L is essential to ensuring this occurs correctly, but the mechanism by which it functions is unclear. Using gene targeting to engineer a single-amino-acid mutation, we show that the Dnmt3L histone H3 binding domain (ADD is necessary for spermatogenesis. Genome-wide single-base-resolution DNA methylome analysis of mutant germ cells revealed overall reductions in CG methylation at repetitive sequences and non-promoter CpG islands. Strikingly, we also observe an even more severe loss of non-CG methylation, suggesting an unexpected role for the ADD in this process. These epigenetic deficiencies were coupled with defects in spermatogonia, with mutant cells displaying marked changes in gene expression and reactivation of retrotransposons. Our results demonstrate that the Dnmt3L ADD is necessary for Dnmt3L function and full reproductive fitness.

  17. (E-3-Methyl-6-(3-oxo-3-(3,4,5-trimethoxyphenylprop-1-en-1-yl-2(3H-benzothiazolone

    Directory of Open Access Journals (Sweden)

    Yordanka Ivanova

    2016-09-01

    Full Text Available The title compound, (E-3-methyl-6-(3-oxo-3-(3,4,5-trimethoxyphenylprop-1-en-1-yl-2(3H-benzothiazolone, was synthesized by both an acid- and base-catalyzed aldol condensation of 3-methyl-6-acetyl-2(3H-benzothiazolone and 3,4,5-trimethoxyacetophenone. The structure of the target compound was confirmed using 1H-NMR, 13C-NMR, IR, MS, and elemental analysis.

  18. A juvenile form of postsynaptic hippocampal long-term potentiation in mice deficient for the AMPA receptor subunit GluR-A

    NARCIS (Netherlands)

    Jensen, V.; Kaiser, K.M.M.; Borchardt, T.; Adelmann, G.; Rozov, A.; Burnashev, N.; Brix, C.; Frotscher, M.; Anderson, P.; Hvalby, O.; Sakmann, B.; Seeburg, P.H.; Sprengel, R.

    2003-01-01

    In adult mice, long-term potentiation (LTP) of synaptic transmission at CA3-to-CA1 synapses induced by tetanic stimulation requires L-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors containing GluR-A subunits. Here, we report a GluR-A-independent form of LTP, which is comparable in

  19. Transition metal complexes of 5-bromosalicylidene-4-amino-3-mercapto-1,2,4-triazine-5-one: Synthesis, characterization, catalytic and antibacterial studies

    Directory of Open Access Journals (Sweden)

    AYALOOR SUBRAMANIAN RAMASUBRAMANIAN

    2011-01-01

    Full Text Available Transition metal complexes of 5-bromosalicylidene-4-amino-3-mercapto-1,2,4-triazine-5-one with metal precursors, such as Cu(II, Ni(II, Co(II and Pd(II, were synthesized and characterized by physico–chemical and spectroscopic techniques. All the complexes are of the ML type. Based on analytical, spectral data and magnetic moments, the Co(II and Ni(II complexes were assigned octahedral geometries, while the Cu (II and Pd(II complexes square planar. A study on the catalytic oxidation of benzyl alcohol, cyclohexanol, cinnamyl alcohol, 2-propanol and 2-methyl-1-propanol was performed with N-methylmorpholine-N-oxide (NMO as co-oxidant. All the complexes and their parent organic moiety were screened for their biological activity on several pathogenic bacteria and were found to possess appreciable bactericidal properties.

  20. Radiotracer studies on the formation of 2,5-dimethyl-4-hydroxy-3(2H)-furanone in detached ripening strawberry fruits

    International Nuclear Information System (INIS)

    Roscher, R.; Bringmann, G.; Schreier, P.; Schwab, W.

    1998-01-01

    The transformation of 12 radioactively labeled compounds into 2,5-dimethyl-4-hydroxy-3(2H)-furanone (DMHF), glycosidically bound DMHF, and 2,5-dimethyl-4-methoxy-3(2H)-furanone (DMMF) was investigated in detached ripening strawberry fruits (Fragaria x ananassa) over a 3-day period. Radiochemical analysis of the different fruit parts revealed that major portions of the applied radioactivity (up to 66%) remained in the stems and calyx. Incorporation levels of [2- 14 C]-dihydroxyacetone, D-[1- 3 H]glucose, D-[U- 14 C]-glucose, D-[U- 14 C]glucose 6-phosphate, D-[U- 14 C]fructose, and D-[U- 14 C]fructose 1,6-bisphosphate into the total amount of furanone derivatives were 0.022, 0.032, 0.035, 0.147, 0.202, and 0.289% of the radioactivity entering the fruits, respectively. Minor amounts of radioactivity (0.001%) were detected in the furanone structures after the administration of [1- 14 C]acetate and [3- 14 C]pyruvate. L-[1- 14 C]Fucose, L-[6- 3 H]fucose, L-[1- 3 H]rhamnose, L-[U- 14 C]-threonine, L-[U- 14 C]lactaldehyde, and [2- 14 C]malonic acid were not transformed into DMHF or a derivative thereof. (author)

  1. New Synthesis and Antiparasitic Activity of Model 5-Aryl-1-methyl-4-nitroimidazoles

    Directory of Open Access Journals (Sweden)

    Mustafa M. El-Abadelah

    2009-07-01

    Full Text Available A number of 5-aryl-1-methyl-4-nitroimidazoles 5a-f have been synthesized in good yields by the Suzuki coupling reaction between 5-chloro-1-methyl-4-nitroimidazole (3 and arylboronic acids 4a-f, aided by dichlorobis-(triphenylphosphinepalladium(II, K2CO3, and tetrabutylammonium bromide in water at 70-80 °C. Compounds 5a-f were characterized by elemental analysis, NMR and MS spectral data. On the basis of in vitro screening data, 5-(3-chlorophenyl-1-methyl-4-nitro-1H-imidazole (5fexhibited potent lethal activity against Entamoeba histolytica and Giardia intestinalis with IC50 = 1.47 µM/mL, a value lower by a factor of two than that of the standard drug, metronidazole. The boosted activity of 5f was not accompanied by any increased cytotoxicity.The rest of the series also exhibited potent antiparasitic activity with IC50 valuesin the 1.72-4.43 µM/mL range. The cytotoxicity of the derivatives 5c and 5e was increased compared to the precursor compound, metronidazole, although they remain non-cytotoxic at concentrations much higher than the antiparasitic concentration of the two derivatives.

  2. New synthesis and antiparasitic activity of model 5-aryl-1-methyl-4-nitroimidazoles.

    Science.gov (United States)

    Saadeh, Haythem A; Mosleh, Ibrahim M; El-Abadelah, Mustafa M

    2009-07-27

    A number of 5-aryl-1-methyl-4-nitroimidazoles 5a-f have been synthesized in good yields by the Suzuki coupling reaction between 5-chloro-1-methyl-4-nitroimidazole (3) and arylboronic acids 4a-f, aided by dichlorobis-(triphenylphosphine)palladium(II), K(2)CO(3, )and tetrabutylammonium bromide in water at 70-80 degrees C. Compounds 5a-f were characterized by elemental analysis, NMR and MS spectral data. On the basis of in vitro screening data, 5-(3-chlorophenyl)-1-methyl-4-nitro-1H-imidazole (5f) exhibited potent lethal activity against Entamoeba histolytica and Giardia intestinalis with IC(50) = 1.47 microM/mL, a value lower by a factor of two than that of the standard drug, metronidazole. The boosted activity of 5f was not accompanied by any increased cytotoxicity.The rest of the series also exhibited potent antiparasitic activity with IC(50 ) values in the 1.72-4.43 microM/mL range. The cytotoxicity of the derivatives 5c and 5e was increased compared to the precursor compound, metronidazole, although they remain non-cytotoxic at concentrations much higher than the antiparasitic concentration of the two derivatives.

  3. Different hydrogen-bonded chains in the crystal structures of three alkyl N-[(E-1-(2-benzylidene-1-methylhydrazinyl-3-hydroxy-1-oxopropan-2-yl]carbamates

    Directory of Open Access Journals (Sweden)

    Thais C. M. Noguiera

    2015-07-01

    Full Text Available The crystal structures of three methylated hydrazine carbamate derivatives prepared by multi-step syntheses from l-serine are presented, namely benzyl N-{(E-1-[2-(4-cyanobenzylidene-1-methylhydrazinyl]-3-hydroxy-1-oxopropan-2-yl}carbamate, C20H20N4O4, tert-butyl N-{(E-1-[2-(4-cyanobenzylidene-1-methylhydrazinyl]-3-hydroxy-1-oxopropan-2-yl}carbamate, C17H22N4O4, and tert-butyl N-[(E-1-(2-benzylidene-1-methylhydrazinyl-3-hydroxy-1-oxopropan-2-yl]carbamate, C16H23N3O4. One of them shows that an unexpected racemization has occurred during the mild-condition methylation reaction. In each crystal structure, the molecules are linked into chains by O—H...O hydrogen bonds, but with significant differences between them.

  4. S3b amino acid substitutions and ancillary subunits alter the affinity of Heteropoda venatoria toxin 2 for Kv4.3.

    Science.gov (United States)

    DeSimone, Christopher V; Lu, YiChun; Bondarenko, Vladimir E; Morales, Michael J

    2009-07-01

    Heteropoda venatoria toxin 2 (HpTx2) is an inhibitor cystine knot (ICK)-gating modifier toxin that selectively inhibits Kv4 channels. To characterize the molecular determinants of interaction, we performed alanine scanning of the Kv4.3 S3b region. HpTx2-Kv4.3 interaction had an apparent K(d) value of 2.3 microM. Two alanine mutants in Kv4.3 increased K(d) values to 6.4 microM for V276A and 25 microM for L275A. Simultaneous mutation of both amino acids to alanine nearly eliminated toxin interaction. Unlike Hanatoxin and other well characterized ICK toxins, HpTx2 binding does not require a charged amino acid for interaction. To determine whether the identity of the S3b binding site amino acids altered HpTx2 specificity, we constructed Kv4.3 [LV275IF]. This mutation decreased the K(d) value to 0.54 microM, suggesting that the hydrophobic character of the putative binding site is the most important property for interaction with HpTx2. One mutant, N280A, caused stronger interaction of HpTx2 with Kv4.3; the K(d) value for Kv4.3 [N280A] was 0.26 microM. To understand Kv4.3-based transient outward currents in native tissues, we tested the affinity of HpTx2 for Kv4.3 coexpressed with KChIP2b. The toxin's K(d) value for Kv4.3 + KChIP2b was 0.95 microM. KChIP2b stabilizes the closed state of Kv4.3, suggesting that the increased toxin affinity is due to increased stabilization of the closed state. These data show that HpTx2 binding to Kv4.3 has aspects in common with other ICK gating modifier toxins but that the interventions that increase toxin affinity suggest flexibility toward channel binding that belies its unusual specificity for Kv4 channels.

  5. Pyridinium 5-[(1,3-diethyl-6-hydroxy-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidin-5-yl(2-methoxyphenylmethyl]-1,3-diethyl-4,6-dioxo-2-thioxopyrimidin-5-ide

    Directory of Open Access Journals (Sweden)

    Abdullah Mohamed Asiri

    2009-08-01

    Full Text Available 1,3-Diethyl-2-thiobarbituric acid reacts with 2-anisaldehyde to form the Michael addition product 2-anisylbis(1,3-diethyl-2-thiobarbitur-5-ylmethanate, which crystallizes as the title pyridinium salt, C5H6N+·C24H29N4O5S2−, when it reacts with the pyridine used to catalyse the reaction. There are two independent ion pairs in the crystal structure. The anion features a methine C atom connected to three six-membered rings; one of the rings carries a hydroxy group, which engages in hydrogen bonding with the carbonyl group belonging to another ring. The monoclinic unit cell emulates an orthorhombic unit cell, and is a twin with a minor twin component of 35%.

  6. Synthesis, binding affinity at glutamic acid receptors, neuroprotective effects, and molecular modeling investigation of novel dihydroisoxazole amino acids

    DEFF Research Database (Denmark)

    Conti, Paola; De Amici, Marco; Grazioso, Giovanni

    2005-01-01

    stereoisomers of the bicyclic analogue 5-amino-4,5,6,6a-tetrahydro-3aH-cyclopenta[d]isoxazole-3,5-dicarboxylic acid (+)-2, (-)-2, (+)-3, and (-)-3 were tested at ionotropic and metabotropic glutamate receptor subtypes. The most potent NMDA receptor antagonists [(+)-2, (-)-4, and (+)-5] showed a significant......The four stereoisomers of 5-(2-amino-2-carboxyethyl)-4,5-dihydroisoxazole-3-carboxylic acid(+)-4, (-)-4, (+)-5, and (-)-5 were prepared by stereoselective synthesis of two pairs of enantiomers, which were subsequently resolved by enzymatic procedures. These four stereoisomers and the four...

  7. Synthesis and characterization of 5-amino-2-((3-hydroxy-4-((3-hydroxyphenyl phenyl diazenyl phenol and its Cu(II complex – a strategy toward developing azo complexes for reduction of cytotoxicity

    Directory of Open Access Journals (Sweden)

    Durba Ganguly

    2014-12-01

    Full Text Available A major drawback of azo compounds is their associated toxicity, often carcinogenic, which is related to the reduction of the azo bond. This study intends to re-investigate this behavior by studying 5-amino-2-((3-hydroxy-4-((3-hydroxyphenyl phenyl diazenyl phenol (AHPD, a compound containing two azo bonds. Interaction of AHPD and its dimeric Cu(II complex with bacterial strains Escherichia coli and Staphylococcus aureus revealed the complex was less toxic. Reductive cleavage of the azo bond in AHPD and the complex followed using cytochrome c reductase (a model azo-reductase as well as azo-reductase enzymes obtained from bacterial cell extracts. Degradation of the azo bond was less in the complex allowing us to correlate the observed cytotoxicity. Cyclic voltammetry on AHPD and the complex support observations of enzyme assay experiments. These were particularly useful in realizing the formation of amines as an outcome of the reductive cleavage of azo bonds in AHPD that could not be identified through an enzyme assay. Results suggest that complex formation of azo compounds could be a means to control the formation of amines responsible for cytotoxicity. Studies carried out on bacterial cells for mere simplicity bear significance for multicellular organisms and could be important for human beings involved with the preparation and utilization of azo dyes.

  8. β-L-Arabinofuranosylation Conducted by 5-O-(2-pyridinecarbonyl)-L-arabinofuranosyl Trichloroacetimidate.

    Science.gov (United States)

    Li, Hong-Zhan; Ding, Jie; Cheng, Chun-Ru; Chen, Yue; Liang, Xing-Yong

    2018-05-02

    We describe a β-L-arabinofuranosylation method by employing the 5-O-(2-pyridinecarbonyl)-L-arabinofuranosyl trichloroacetimidate 10 as a donor. This approach allows a wide range of acceptor substrates, especially amino acid acceptors, to be used. Stereoselective synthesis of β-(1,4)-L-arabinofuranosyl-(2S, 4R)-4-hydroxy-L-proline (β-L-Araf-L-Hyp 4 ) and its dimer is achieved readily by this method. Both the stereoselectivities and yields of the reactions are excellent. To demonstrate the utility of this methodology, the preparation of a trisaccharide in a one-pot manner was carried out. Copyright © 2018 Elsevier Ltd. All rights reserved.

  9. Synthesis of Amino Acid Analogues of 5H-Dibenz[b,f]azepine and Evaluation of their Radical Scavenging Activity

    Directory of Open Access Journals (Sweden)

    H. Vijay Kumar

    2009-01-01

    Full Text Available A method for the synthesis of tyrosine, phenyl alanine, hydroxy proline and threonine free amino acid analogues of 5H-dibenz[b,f]azepine is proposed. 5H-dibenz[b,f]azepine was prepared by known method. The key intermediate 3-chloro-1-(5H-dibenz[b,f]azepine-5-ylpropan-1-one was obtained by N-acylation of 5H-dibenz[b,f]azepine with 3-chloro propionyl chloride. Further coupling of respective free amino acid to produce 2-(3-(5H-dibenz[b,f]azepine-5-yl-3-oxopropylamino3-(4 hydroxyphenyl propanoic acid, 2-(3-(5H-dibenz[b,f]azepine-5-yl-3-oxopropylamino-3-phenyl propanoicacid,1-(3-(5H-dibenz[b,f]azepine-5-yl-3-oxopropyl-3-hydroxypyrolidine-2-carboxylic acid and 2-(3-(5H-dibenz[b,f] azepine-yl-3-oxopropyl amino-3-hydroxy butanoic acid. The synthesized compounds were evaluated for their potential over 1,1-diphenyl-2-picryl hydrazyl (DPPH free radical scavenging activity. Butylated hydroxy anisole (BHA and ascorbic acid (AA were used as the reference antioxidant compounds and also the comparative study with synthesized compounds was done. Under our experimental conditions tyrosine, hydroxy proline and threonine analogues possess a direct scavenging effect on trapping the stable free radical DPPH. Hydroxy proline analogues showed a significant radical scavenging activity among the synthesized analogues

  10. Microwave assisted one-pot catalyst free green synthesis of new methyl-7-amino-4-oxo-5-phenyl-2-thioxo-2,3,4,5-tetrahydro-1H-pyrano[2,3-d]pyrimidine-6-carboxylates as potent in vitro antibacterial and antifungal activity

    Directory of Open Access Journals (Sweden)

    Ajmal R. Bhat

    2015-11-01

    Full Text Available An efficiently simple protocol for the synthesis of methyl 7 amino-4-oxo-5-phenyl-2-thioxo-2, 3, 4,5-tetrahydro-1H-pyrano[2,3-d]pyrimidine-6-carboxylates via one-pot three component condensation pathway is established via microwave irradiation using varied benzaldehyde derivatives, methylcyanoacetate and thio-barbituric acid in water as a green solvent. A variety of functionalized substrates were found to react under this methodology due to its easy operability and offers several advantages like, high yields (78–94%, short reaction time (3–6 min, safety and environment friendly without used any catalyst. The synthesized compounds (4a–4k showed comparatively good in vitro antimicrobial and antifungal activities against different strains. The Compounds 4a, 4b, 4c, 4d 4e and 4f showed maximum antimicrobial activity against Staphylococcus aureus, Bacillus cereus (gram-positive bacteria, Escherichia coli, Klebshiella pneumonia, Pseudomonas aeruginosa (gram-negative bacteria. The synthesized compound 4f showed maximum antifungal activity against Aspergillus Niger and Penicillium chrysogenum strains. Streptomycin is used as standard for bacterial studies and Mycostatin as standards for fungal studies. Structure of all newly synthesized products was characterized on the basis of IR, 1H NMR, 13C NMR and mass spectral analysis.

  11. Regulator of G-Protein Signaling 7 Regulates Reward Behavior by Controlling Opioid Signaling in the Striatum.

    Science.gov (United States)

    Sutton, Laurie P; Ostrovskaya, Olga; Dao, Maria; Xie, Keqiang; Orlandi, Cesare; Smith, Roy; Wee, Sunmee; Martemyanov, Kirill A

    2016-08-01

    Morphine mediates its euphoric and analgesic effects by acting on the μ-opioid receptor (MOR). MOR belongs to the family of G-protein coupled receptors whose signaling efficiency is controlled by the regulator of G-protein signaling (RGS) proteins. Our understanding of the molecular diversity of RGS proteins that control MOR signaling, their circuit specific actions, and underlying cellular mechanisms is very limited. We used genetic approaches to ablate regulator of G-protein signaling 7 (RGS7) both globally and in specific neuronal populations. We used conditioned place preference and self-administration paradigms to examine reward-related behavior and a battery of tests to assess analgesia, tolerance, and physical dependence to morphine. Electrophysiology approaches were applied to investigate the impact of RGS7 on morphine-induced alterations in neuronal excitability and plasticity of glutamatergic synapses. At least three animals were used for each assessment. Elimination of RGS7 enhanced reward, increased analgesia, delayed tolerance, and heightened withdrawal in response to morphine administration. RGS7 in striatal neurons was selectively responsible for determining the sensitivity of rewarding and reinforcing behaviors to morphine without affecting analgesia, tolerance, and withdrawal. In contrast, deletion of RGS7 in dopaminergic neurons did not influence morphine reward. RGS7 exerted its effects by controlling morphine-induced changes in excitability of medium spiny neurons in nucleus accumbens and gating the compositional plasticity of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid and N-methyl-D-aspartate receptors. This study identifies RGS7 as a novel regulator of MOR signaling by dissecting its circuit specific actions and pinpointing its role in regulating morphine reward by controlling the activity of nucleus accumbens neurons. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  12. Synthesis of a cleavable heterobifunctional photolabelling reagent: ring-labelled 3-((4-azidophenyl)dithio)propionic acid- sup 14 C

    Energy Technology Data Exchange (ETDEWEB)

    Ramaswami, Varadarajan (Carnegie-Mellon Univ., Pittsburgh, PA (USA). Dept. of Chemistry); Tirrell, D.A. (Massachusetts Univ., Amherst, MA (USA). Dept. of Polymer Science and Engineering)

    1989-08-01

    An efficient synthesis of ring-labelled 3-((4-azidophenyl)dithio)propionic acid-{sup 14}C is described. Chlorosulfonation of uniformly ring-labelled acetanilide-{sup 14}C followed by reductive dimerization of the sulfonyl chloride with HI afforded 4-acetamidophenyl disulfide. Hydrolysis and diazotization then gave 4-azidophenyl disulfide, which was converted to the title compound via the sulfur transfer reagent N-(4-azidophenylthio)phthalimide. The overall yield of 3-((4-azidophenyl)dithio)propionic acid-{sup 14}C was 22%. 3-((4-Azidophenyl)dithio)propionic acid-{sup 14}C is a cleavable heterobifunctional photolabelling reagent of potential utility in studies of biomembrane structure and intermacromolecular interaction. (author).

  13. Neuroprotective Properties of Compounds Extracted from Dianthus superbus L. against Glutamate-induced Cell Death in HT22 Cells.

    Science.gov (United States)

    Yun, Bo-Ra; Yang, Hye Jin; Weon, Jin Bae; Lee, Jiwoo; Eom, Min Rye; Ma, Choong Je

    2016-01-01

    Dianthus superbus L. has been used in Chinese herbal medicine as a diuretic and anti-inflammatory agent. In this study, we isolated ten bioactive compounds from D. superbus and evaluated their neuroprotective activity against glutamate-induced cell death in the hippocampal neuronal HT22 cells. New compound, (E)-methyl-4-hydroxy-4-(8a-methyl-3-oxodecahydronaphthalen-4a-yl) (1) and, nine known compounds, diosmetin-7-O (2'',6''-di-O-α-L-rhamnopyranosyl)-β-D-glucopyranoside (2), 4-hydroxy-3-methoxy-pentyl ester benzenepropanoic acid (3), vanillic acid (4), 4-hydroxy-benzeneacetic acid (5), 4-methoxybenzeneacetic acid (6), (E)-4-methoxycinnamic acid (7), 3-methoxy-4-hydroxyphenylethanol (8), hydroferulic acid (9), and methyl hydroferulate (10), were isolated by bioactivity-guided separation. Structures of the isolated compounds were identified on the basis of (1)H nuclear magnetic resonance (NMR), (13)C NMR, and two-dimensional NMR spectra, while their neuroprotective properties were evaluated by performing the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. D. superbus extract had a neuroprotective effect and isolated 10 compounds. Among the compounds, compounds 5 and 6 effectively protected HT22 cells against glutamate toxicity. In conclusion, the extract of D. superbus and compounds isolated from it exhibited neuroprotective properties, suggesting therapeutic potential for applications in neurotoxic diseases. D. superbus extract significantly protected on glutamate-induced cell death in HT22 cellsNew compound, (E)-methyl-4-hydroxy-4-(8a-methyl-3-oxodecahydronaphthalen-4a-yl) (1) and, nine known compounds, diosmetin-7-O(2'',6''-di-O-α-L-rhamnopyranosyl)-β-D-glucopyranoside (2), 4-hydroxy-3-methoxy-pentyl ester benzenepropanoic acid (3), vanillic acid (4), 4-hydroxy-benzeneacetic acid (5), 4-methoxybenzeneacetic acid (6), (E)-4-methoxycinnamic acid (7), 3-methoxy-4-hydroxyphenylethanol (8), hydroferulic acid (9), and methyl hydroferulate (10

  14. Spaceflight induces both transient and heritable alterations in DNA methylation and gene expression in rice (Oryza sativa L.)

    Energy Technology Data Exchange (ETDEWEB)

    Ou Xiufang [Key Laboratory of Molecular Epigenetic of MOE and Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024 (China); Long Likun [Inspection and Quarantine Technology Centre of Zhongshan Entry-Exit Inspection and Quarantine Bureau, Zhongshan 528400, Guangdong Province (China); Zhang Yunhong; Xue Yiqun; Liu Jingchun; Lin Xiuyun [Key Laboratory of Molecular Epigenetic of MOE and Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024 (China); Liu Bao [Key Laboratory of Molecular Epigenetic of MOE and Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024 (China)], E-mail: baoliu6677@yahoo.com.cn

    2009-03-09

    Spaceflight represents a complex environmental condition in which several interacting factors such as cosmic radiation, microgravity and space magnetic fields are involved, which may provoke stress responses and jeopardize genome integrity. Given the inherent property of epigenetic modifications to respond to intrinsic as well as external perturbations, it is conceivable that epigenetic markers like DNA methylation may undergo alterations in response to spaceflight. We report here that extensive alteration in both DNA methylation and gene expression occurred in rice plants subjected to a spaceflight, as revealed by a set of characterized sequences including 6 transposable elements (TEs) and 11 cellular genes. We found that several features characterize the alterations: (1) All detected alterations are hypermethylation events; (2) whereas alteration in both CG and CNG methylation occurred in the TEs, only alteration in CNG methylation occurred in the cellular genes; (3) alteration in expression includes both up- and down-regulations, which did not show a general correlation with alteration in methylation; (4) altered methylation patterns in both TEs and cellular genes are heritable to progenies at variable frequencies; however, stochastic reversion to wild-type patterns and further de novo changes in progenies are also apparent; and (5) the altered expression states in both TEs and cellular genes are also heritable to selfed progenies but with markedly lower transmission frequencies than altered DNA methylation states. Furthermore, we found that a set of genes encoding for the various putative DNA methyltransferases, 5-methylcytosine DNA glycosylases, the SWI/SNF chromatin remodeller (DDM1) and siRNA-related proteins are extremely sensitive to perturbation by spaceflight, which might be an underlying cause for the altered methylation patterns in the space-flown plants. We discuss implications of spaceflight-induced epigenetic variations with regard to health safety

  15. Spaceflight induces both transient and heritable alterations in DNA methylation and gene expression in rice (Oryza sativa L.)

    International Nuclear Information System (INIS)

    Ou Xiufang; Long Likun; Zhang Yunhong; Xue Yiqun; Liu Jingchun; Lin Xiuyun; Liu Bao

    2009-01-01

    Spaceflight represents a complex environmental condition in which several interacting factors such as cosmic radiation, microgravity and space magnetic fields are involved, which may provoke stress responses and jeopardize genome integrity. Given the inherent property of epigenetic modifications to respond to intrinsic as well as external perturbations, it is conceivable that epigenetic markers like DNA methylation may undergo alterations in response to spaceflight. We report here that extensive alteration in both DNA methylation and gene expression occurred in rice plants subjected to a spaceflight, as revealed by a set of characterized sequences including 6 transposable elements (TEs) and 11 cellular genes. We found that several features characterize the alterations: (1) All detected alterations are hypermethylation events; (2) whereas alteration in both CG and CNG methylation occurred in the TEs, only alteration in CNG methylation occurred in the cellular genes; (3) alteration in expression includes both up- and down-regulations, which did not show a general correlation with alteration in methylation; (4) altered methylation patterns in both TEs and cellular genes are heritable to progenies at variable frequencies; however, stochastic reversion to wild-type patterns and further de novo changes in progenies are also apparent; and (5) the altered expression states in both TEs and cellular genes are also heritable to selfed progenies but with markedly lower transmission frequencies than altered DNA methylation states. Furthermore, we found that a set of genes encoding for the various putative DNA methyltransferases, 5-methylcytosine DNA glycosylases, the SWI/SNF chromatin remodeller (DDM1) and siRNA-related proteins are extremely sensitive to perturbation by spaceflight, which might be an underlying cause for the altered methylation patterns in the space-flown plants. We discuss implications of spaceflight-induced epigenetic variations with regard to health safety

  16. Synthesis, Characterization, and Biological Activity of Novel Schiff and Mannich Bases of 4-Amino-3-(N-phthalimidomethyl-1,2,4-triazole-5-thione

    Directory of Open Access Journals (Sweden)

    Uzma Yunus

    2013-01-01

    Full Text Available The present work describes the syntheses and antimicrobial activity studies of a series of novel Schiff bases (4a–4i and their Mannich bases (5a–5h starting from 4-amino-3-(N-phthalimido-methyl-1,2,4-triazole-5-thione (3. All the synthesized compounds were characterized by IR, 1H-NMR, 13C-NMR, and MS. All the synthesized compounds were screened for four Gram-negative strains, one Gram-positive strain of bacteria, and one diploid fungal strain. In general the antimicrobial activity increased remarkably on the introduction of azomethine functionality in parent triazole (3. The antimicrobial activity further improved when morpholine group was added to them except for Enterobacter cloacae, where loss of activity was observed. The results are promising and show that the fine tuning of the structures (5a, 5b, 5e, 5f, and 5h can lead to some new antimicrobial compounds.

  17. Crystal structure of 5-hydroxy-5-propylbarbituric acid

    Directory of Open Access Journals (Sweden)

    Thomas Gelbrich

    2015-11-01

    Full Text Available Molecules of the title compound, C7H10N2O4, systematic name 5-hydroxy-5-propylpyrimidine-2,4,6(1H,3H,5H-trione, form a hydrogen-bonded framework which is based on three independent hydrogen bonds, N—H...O(carbonyl, N—H...O(hydroxy and O—H...O(carbonyl. This framework has the topology of the 5-connected nov net. Each molecule is linked to five other molecules via six hydrogen bonds, and the descriptor of the hydrogen-bonded structure is F65[44.66-nov]. The crystal packing is isostructural with that of the previously reported 5-hydroxy-5-ethyl analogue.

  18. 1-[3-(2-Benzyloxy-6-hydroxy-4-methylphenyl-5-[3,5-bis(trifluoromethylphenyl]-4,5-dihydro-1H-pyrazol-1-yl]propane-1-one

    Directory of Open Access Journals (Sweden)

    U. H. Patel

    2013-06-01

    Full Text Available In the title compound, C28H24F6N2O3, the mean plane of the central pyrazoline ring forms dihedral angles of 2.08 (9 and 69.02 (16° with the 2-benzyloxy-6-hydroxy-4-methylphenyl and 3,5-bis(trifluoromethylphenyl rings, respectively. The dihedral angle between the mean planes of the pyrazoline and 3,5-bis(trifluoromethylphenyl rings is 68.97 (9°. An intramolecular O—H...N hydrogen bond is observed, which forms an S(6 graph-set motif. In the crystal, pairs of weak C—H...F halogen interactions link the molecules into inversion dimers while molecular chains along [100] are formed by C—H...O contacts.

  19. A simplified one-pot synthesis of 9-[(3-[{sup 18}F]Fluoro-1-hydroxy-2-propoxy)methyl]guanine([{sup 18}F]FHPG) and 9-(4-[{sup 18}F]Fluoro-3-hydroxymethylbutyl)guanine ([{sup 18}F]FHBG) for gene therapy

    Energy Technology Data Exchange (ETDEWEB)

    Shiue, Grace G.; Shiue, Chyng-Yann E-mail: Shiue@rad.upenn.edu; Lee, Roland L.; MacDonald, Douglas; Hustinx, Roland; Eck, Stephen L.; Alavi, Abass A

    2001-10-01

    9-[(3-[{sup 18}F]Fluoro-1-hydroxy-2-propoxy)methyl]guanine ([{sup 18}F]FHPG, 2) has been synthesized by nucleophilic substitution of N{sup 2}-(p-anisyldiphenylmethyl)-9-{l_brace}[1-(p-anisyldiphenylmethoxy)-3 -toluenesulfonyloxy-2-propoxy]methyl{r_brace}guanine (1) with potassium [{sup 18}F]fluoride/Kryptofix 2.2.2 followed by deprotection with 1 N HCl and purification with different methods in variable yields. When both the nucleophilic substitution and deprotection were carried out at 90 deg. C and the product was purified by HPLC (method A), the yield of compound 2 was 5-10% and the synthesis time was 90 min from EOB. However, if both the nucleophilic substitution and deprotection were carried out at 120 deg. C and the product was purified by HPLC, the yield of compound 2 decreased to 2%. When compound 2 was synthesized at 90 deg. C and purified by Silica Sep-Pak (method B), the yield increased to 10-15% and the synthesis time was 60 min from EOB. Similarly, 9-(4-[{sup 18}F]fluoro-3-hydroxymethylbutyl)guanine ([{sup 18}F]FHBG, 4) was synthesized with method A and method B in 9% and 10-15% yield, respectively, in a synthesis time of 90 and 60 min, respectively, from EOB. Compound 2 was relatively unstable in acidic medium at 120 deg. C while compound 4 was stable under the same condition. Both compound 2 and compound 4 had low lipid/water partition coefficient (0.126{+-}0.022, n=5 and 0.165{+-}0.023, n=5, respectively). Although it contains non-radioactive ganciclovir ({approx}5-30 {mu}g) as a chemical by-product, compound 2 synthesized by method B has a similar uptake in 9L glioma cells as that synthesized by method A, and is a potential tracer for imaging herpes simplex virus thymidine kinase gene expression in tumors using PET. Similarly, compound 4 synthesized by method B contains {approx}10-25 {mu}g of penciclovir as a chemical by-product. Thus, the simplified one pot synthesis (method B) is a useful method for synthesizing both compound 2 and compound 4 in

  20. A simplified one-pot synthesis of 9-[(3-[18F]Fluoro-1-hydroxy-2-propoxy)methyl]guanine([18F]FHPG) and 9-(4-[18F]Fluoro-3-hydroxymethylbutyl)guanine ([18F]FHBG) for gene therapy

    International Nuclear Information System (INIS)

    Shiue, Grace G.; Shiue, Chyng-Yann; Lee, Roland L.; MacDonald, Douglas; Hustinx, Roland; Eck, Stephen L.; Alavi, Abass A.

    2001-01-01

    9-[(3-[ 18 F]Fluoro-1-hydroxy-2-propoxy)methyl]guanine ([ 18 F]FHPG, 2) has been synthesized by nucleophilic substitution of N 2 -(p-anisyldiphenylmethyl)-9-{[1-(p-anisyldiphenylmethoxy)-3 -toluenesulfonyloxy-2-propoxy]methyl}guanine (1) with potassium [ 18 F]fluoride/Kryptofix 2.2.2 followed by deprotection with 1 N HCl and purification with different methods in variable yields. When both the nucleophilic substitution and deprotection were carried out at 90 deg. C and the product was purified by HPLC (method A), the yield of compound 2 was 5-10% and the synthesis time was 90 min from EOB. However, if both the nucleophilic substitution and deprotection were carried out at 120 deg. C and the product was purified by HPLC, the yield of compound 2 decreased to 2%. When compound 2 was synthesized at 90 deg. C and purified by Silica Sep-Pak (method B), the yield increased to 10-15% and the synthesis time was 60 min from EOB. Similarly, 9-(4-[ 18 F]fluoro-3-hydroxymethylbutyl)guanine ([ 18 F]FHBG, 4) was synthesized with method A and method B in 9% and 10-15% yield, respectively, in a synthesis time of 90 and 60 min, respectively, from EOB. Compound 2 was relatively unstable in acidic medium at 120 deg. C while compound 4 was stable under the same condition. Both compound 2 and compound 4 had low lipid/water partition coefficient (0.126±0.022, n=5 and 0.165±0.023, n=5, respectively). Although it contains non-radioactive ganciclovir (∼5-30 μg) as a chemical by-product, compound 2 synthesized by method B has a similar uptake in 9L glioma cells as that synthesized by method A, and is a potential tracer for imaging herpes simplex virus thymidine kinase gene expression in tumors using PET. Similarly, compound 4 synthesized by method B contains ∼10-25 μg of penciclovir as a chemical by-product. Thus, the simplified one pot synthesis (method B) is a useful method for synthesizing both compound 2 and compound 4 in good yield for routine clinical use, and the method is

  1. On rates and mechanisms of OH and O3 reactions with isoprene-derived hydroxy nitrates.

    Science.gov (United States)

    Lee, Lance; Teng, Alex P; Wennberg, Paul O; Crounse, John D; Cohen, Ronald C

    2014-03-06

    Eight distinct hydroxy nitrates are stable products of the first step in the atmospheric oxidation of isoprene by OH. The subsequent chemical fate of these molecules affects global and regional production of ozone and aerosol as well as the location of nitrogen deposition. We synthesized and purified 3 of the 8 isoprene hydroxy nitrate isomers: (E/Z)-2-methyl-4-nitrooxybut-2-ene-1-ol and 3-methyl-2-nitrooxybut-3-ene-1-ol. Oxidation of these molecules by OH and ozone was studied using both chemical ionization mass spectrometry and thermo-dissociation laser induced fluorescence. The OH reaction rate constants at 300 K measured relative to propene at 745 Torr are (1.1 ± 0.2) × 10(-10) cm(3) molecule(-1) s(-1) for both the E and Z isomers and (4.2 ± 0.7) × 10(-11) cm(3) molecule(-1) s(-1) for the third isomer. The ozone reaction rate constants for (E/Z)-2-methyl-4-nitrooxybut-2-ene-1-ol are (2.7 ± 0.5) × 10(-17) and (2.9 ± 0.5) × 10(-17) cm(3) molecule(-1) s(-1), respectively. 3-Methyl-2-nitrooxybut-3-ene-1-ol reacts with ozone very slowly, within the range of (2.5-5) × 10(-19) cm(3) molecule(-1) s(-1). Reaction pathways, product yields, and implications for atmospheric chemistry are discussed. A condensed mechanism suitable for use in atmospheric chemistry models is presented.

  2. Involvement of AMPA receptors in the antidepressant-like effects of dextromethorphan in mice.

    Science.gov (United States)

    Nguyen, Linda; Matsumoto, Rae R

    2015-12-15

    Dextromethorphan (DM) is an antitussive with rapid acting antidepressant potential based on pharmacodynamic similarities to ketamine. Building upon our previous finding that DM produces antidepressant-like effects in the mouse forced swim test (FST), the present study aimed to establish the antidepressant-like actions of DM in the tail suspension test (TST), another well-established model predictive of antidepressant efficacy. Additionally, using the TST and FST, we investigated the role of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors in the antidepressant-like properties of DM because accumulating evidence suggests that AMPA receptors play an important role in the pathophysiology of depression and may contribute to the efficacy of antidepressant medications, including that of ketamine. We found that DM displays antidepressant-like effects in the TST similar to the conventional and fast acting antidepressants characterized by imipramine and ketamine, respectively. Moreover, decreasing the first-pass metabolism of DM by concomitant administration of quinidine (CYP2D6 inhibitor) potentiated antidepressant-like actions, implying DM itself has antidepressant efficacy. Finally, in both the TST and FST, pretreatment with the AMPA receptor antagonist NBQX (2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide) significantly attenuated the antidepressant-like behavior elicited by DM. Together, the data show that DM exerts antidepressant-like actions through AMPA receptors, further suggesting DM may act as a safe and effective fast acting antidepressant drug. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Identification and characterization of trans-3-hydroxy-l-proline dehydratase and Δ1-pyrroline-2-carboxylate reductase involved in trans-3-hydroxy-l-proline metabolism of bacteria

    Directory of Open Access Journals (Sweden)

    Seiya Watanabe

    2014-01-01

    Full Text Available trans-4-Hydroxy-l-proline (T4LHyp and trans-3-hydroxy-l-proline (T3LHyp occur mainly in collagen. A few bacteria can convert T4LHyp to α-ketoglutarate, and we previously revealed a hypothetical pathway consisting of four enzymes at the molecular level (J Biol Chem (2007 282, 6685–6695; J Biol Chem (2012 287, 32674–32688. Here, we first found that Azospirillum brasilense has the ability to grow not only on T4LHyp but also T3LHyp as a sole carbon source. In A. brasilense cells, T3LHyp dehydratase and NAD(PH-dependent Δ1-pyrroline-2-carboxylate (Pyr2C reductase activities were induced by T3LHyp (and d-proline and d-lysine but not T4LHyp, and no effect of T3LHyp was observed on the expression of T4LHyp metabolizing enzymes: a hypothetical pathway of T3LHyp → Pyr2C → l-proline was proposed. Bacterial T3LHyp dehydratase, encoded to LhpH gene, was homologous with the mammalian enzyme. On the other hand, Pyr2C reductase encoded to LhpI gene was a novel member of ornithine cyclodeaminase/μ-crystallin superfamily, differing from known bacterial protein. Furthermore, the LhpI enzymes of A. brasilense and another bacterium showed several different properties, including substrate and coenzyme specificities. T3LHyp was converted to proline by the purified LhpH and LhpI proteins. Furthermore, disruption of LhpI gene from A. brasilense led to loss of growth on T3LHyp, d-proline and d-lysine, indicating that this gene has dual metabolic functions as a reductase for Pyr2C and Δ1-piperidine-2-carboxylate in these pathways, and that the T3LHyp pathway is not linked to T4LHyp and l-proline metabolism.

  4. Synthesis and Biological Evaluation of 2-Hydroxy-3-[(2-aryloxyethylamino]propyl 4-[(Alkoxycarbonylamino]benzoates

    Directory of Open Access Journals (Sweden)

    Jan Tengler

    2013-01-01

    Full Text Available A series of twenty substituted 2-hydroxy-3-[(2-aryloxyethylamino]propyl 4-[(alkoxycarbonylamino]benzoates were prepared and characterized. As similar compounds have been described as potential antimycobacterials, primary in vitro screening of the synthesized carbamates was also performed against two mycobacterial species. 2-Hydroxy-3-[2-(2,6-dimethoxyphenoxyethylamino]-propyl 4-(butoxycarbonylaminobenzoate hydrochloride, 2-hydroxy-3-[2-(4-methoxyphenoxyethylamino]-propyl 4-(butoxycarbonylaminobenzoate hydrochloride, and 2-hydroxy-3-[2-(2-methoxyphenoxyethylamino]-propyl 4-(butoxycarbonylaminobenzoate hydrochloride showed higher activity against M. avium subsp. paratuberculosis and M. intracellulare than the standards ciprofloxacin, isoniazid, or pyrazinamide. Cytotoxicity assay of effective compounds was performed using the human monocytic leukaemia THP-1 cell line. Compounds with predicted amphiphilic properties were also tested for their effects on the rate of photosynthetic electron transport (PET in spinach (Spinacia oleracea L. chloroplasts. All butyl derivatives significantly stimulated the rate of PET, indicating that the compounds can induce conformational changes in thylakoid membranes resulting in an increase of their permeability and so causing uncoupling of phosphorylation from electron transport.

  5. Unusual Ring Contration by Substitution of 4-O-activated-pentono-1,5-lactams with cyanide. Stereospecific Synthesis of 6-Amino-1,4,5,6-tetradeoxy-1,4-imino-hexitols

    DEFF Research Database (Denmark)

    Godskesen, Michael Anders; Lundt, Inge; Søtofte, Inger

    2000-01-01

    Reaction of 4-O-sulfonylated 2,3-O-isopropylidene-D-ribo- or -D-lyxo-1,5-lactams with tetrabutylammonium cyanide gave 4-amino-5-C-cyano-4,5-dideoxy-2,3-O-isopropylidene-L-lyxo-5 or -L-ribo-15-1,4-lactams, respectively. A stereospecific ring contraction with inversion at C-4 had taken place in each...

  6. Synthesis, spectroscopic characterization, theoretical study and anti-hepatic cancer activity study of 4-(1E,3Z,6E)-3-hydroxy-7-(4-hydroxy-3-methoxyphenyl)-5-oxohepta-1,3,6-trien-1-yl)-2-methoxyphenyl 4-nitrobenzoate, a novel curcumin congener

    Science.gov (United States)

    Srivastava, Sangeeta; Gupta, Preeti; Singh, Ranvijay Pratap; Jafri, Asif; Arshad, M.; Banerjee, Monisha

    2017-08-01

    In the present work 4-(1E,3Z,6E)-3-hydroxy-7-(4-hydroxy-3-methoxyphenyl)-5-oxohepta-1,3,6-trien-1-yl)-2-methoxyphenyl 4-nitrobenzoate (2), a novel curcumin ester was synthesized. The molecular structure and spectroscopic analysis were performed using experimental techniques like FT-IR, 1H,13C NMR, mass and UV-visible as well as theoretical calculations. The theoretical calculations were done by DFT level of theory using B3LYP/6-31G (d,p) basis set. The vibrational wavenumbers were calculated using DFT method and assigned with the help of potential energy distribution (PED). The electronic properties such as frontier orbitals and band gap energies have been calculated using time dependent density functional theory (TD-DFT). The strength and nature of weak intramolecular interactions have been studied by AIM approach. Global and local reactivity descriptors have been computed to predict reactivity and reactive sites in the molecule. First hyperpolarizability values have been calculated to describe the nonlinear optical (NLO) property of the synthesized compounds. Molecular electrostatic potential (MEP) analysis has also been carried out. The anti-hepatic cancer activity of compound 2 was also carried out.

  7. Order-disorder phase transitions and their influence on the structure and vibrational properties of new hybrid material: 2-Amino-4-methyl-3-nitropyridinium trifluoroacetate

    Science.gov (United States)

    Lorenc, J.; Bryndal, I.; Syska, W.; Wandas, M.; Marchewka, M.; Pietraszko, A.; Lis, T.; Mączka, M.; Hermanowicz, K.; Hanuza, J.

    2010-08-01

    New organic-organic salt, 2-amino-4-methyl-3-nitropyridinium trifluoroacetate, has been synthesised and characterised by FT-IR, FT-Raman, DSC and single crystal X-ray crystallography. The 2-amino-4-methyl-3-nitropyridinium trifluoroacetate undergoes a reversible phase transition at ˜162 K. The X-ray structures, vibrational spectra and quantum chemical DFT calculations (B3LYP/6-31G(d,p) approach) have been analysed for high-temperature and low-temperature modifications of the compound, which both crystallize in orthorhombic space group Pbca with two non-equivalent cations and two anions in the asymmetric unit. Their crystal and molecular structures have been compared and the role of the intermolecular interactions in these crystals has been analysed. The mechanisms of the phase transition have been proposed.

  8. Synthesis and characterization of new 3-(4,5-dihydro-5-arylisoxazol-3-yl-4-hydroxyquinolin-2(1H-ones and 3-(4-styrylisoxazolo[4,5-c]quinolin-4(5H-one derivatives

    Directory of Open Access Journals (Sweden)

    S. Sarveswari

    2016-09-01

    Full Text Available The 4-hydroxy-3-(3-arylacryloylquinolin-2(1H-ones were synthesized from 3-acetyl-4-hydroxyquinolin-2(1H-one by microwave assisted synthesis, which in turn converted into their corresponding 3-(4,5-dihydro-5-arylisoxazol-3-yl-4-hydroxyquinolin-2(1H-ones and 3-(4-styrylisoxazolo[4,5-c]quinolin-4(5H-one derivatives.

  9. 1,1′-{1,4-Phenylene bis[3-(6-chloro-2-methyl-4-phenylquinolin-3-yl-4,5-dihydro-1H-pyrazole-5,1-diyl]}dibutan-1-one

    Directory of Open Access Journals (Sweden)

    Allaoua Kedjadja

    2015-10-01

    Full Text Available A new polycyclic compound, 1,1′-{1,4-phenylene bis[3-(6-chloro-2-methyl-4-phenylquinolin-3-yl-4,5-dihydro-1H-pyrazole-5,1-diyl]}dibutan-1-one (3 has been synthesized by cyclocondensation of (2E,2′E-1,1′-bis(6-chloro-2-methyl-4-phenylquinolin-3-yl-3,3′-(1,4-phenylenediprop-2-en-1-one (2 and hydrazine hydrate in butanoic acid. The structure of this compound was established by elemental analysis, 1H-NMR, 13C-NMR, mass and IR spectroscopy.

  10. Transmembrane and ubiquitin-like domain-containing protein 1 (Tmub1/HOPS facilitates surface expression of GluR2-containing AMPA receptors.

    Directory of Open Access Journals (Sweden)

    Hyunjeong Yang

    Full Text Available Some ubiquitin-like (UBL domain-containing proteins are known to play roles in receptor trafficking. Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs undergo constitutive cycling between the intracellular compartment and the cell surface in the central nervous system. However, the function of UBL domain-containing proteins in the recycling of the AMPARs to the synaptic surface has not yet been reported.Here, we report that the Transmembrane and ubiquitin-like domain-containing 1 (Tmub1 protein, formerly known as the Hepatocyte Odd Protein Shuttling (HOPS protein, which is abundantly expressed in the brain and which exists in a synaptosomal membrane fraction, facilitates the recycling of the AMPAR subunit GluR2 to the cell surface. Neurons transfected with Tmub1/HOPS-RNAi plasmids showed a significant reduction in the AMPAR current as compared to their control neurons. Consistently, the synaptic surface expression of GluR2, but not of GluR1, was significantly decreased in the neurons transfected with the Tmub1/HOPS-RNAi and increased in the neurons overexpressing EGFP-Tmub1/HOPS. The altered surface expression of GluR2 was speculated to be due to the altered surface-recycling of the internalized GluR2 in our recycling assay. Eventually, we found that GluR2 and glutamate receptor interacting protein (GRIP were coimmunoprecipitated by the anti-Tmub1/HOPS antibody from the mouse brain. Taken together, these observations show that the Tmub1/HOPS plays a role in regulating basal synaptic transmission; it contributes to maintain the synaptic surface number of the GluR2-containing AMPARs by facilitating the recycling of GluR2 to the plasma membrane.

  11. Spectroscopic study, antimicrobial activity and crystal structures of N-(2-hydroxy-5-nitrobenzalidene)4-aminomorpholine and N-(2-hydroxy-1-naphthylidene)4-aminomorpholine

    Science.gov (United States)

    Yıldız, Mustafa; Ünver, Hüseyin; Dülger, Başaran; Erdener, Diğdem; Ocak, Nazan; Erdönmez, Ahmet; Durlu, Tahsin Nuri

    2005-03-01

    Schiff bases N-(2-hydroxy-3-nitrobenzalidene)4-aminomorpholine ( 1) and N-(2-hydroxy-1-naphthylidene)4-aminomorpholine ( 2) were synthesized from the reaction of 4-aminomorpholine with 2-hydroxy-5-nitrobenzaldehyde and 2-hydroxy-1-naphthaldehyde. Compounds 1 and 2 were characterized by elemental analysis, IR, 1H NMR, 13C NMR and UV-Visible techniques. The UV-Visible spectra of the Schiff bases with OH group in ortho position to the imino group were studied in polar and nonpolar solvents in acidic and basic media. The structures of compounds 1 and 2 have been examined cyrstallographically, for two compounds exist as dominant form of enol-imines in both the solutions and solid state. The title compounds 1 and 2 crystallize in the monoclinic space group P2 1/ c and P2 1/ n with unit cell parameters: a=8.410(1) and 11.911(3), b=6.350(9) and 4.860(9), c=21.728(3) and 22.381(6) Å, β=90.190(1) and 95.6(2)°, V=1160.6(3) and 1289.5(5) Å 3, Dx=1.438 and 1.320 g cm -3, respectively. The crystal structures were solved by direct methods and refined by full-matrix least squares. The antimicrobial activities of compounds 1 and 2 have also been studied. The antimicrobial activities of the ligands have been screened in vitro against the organisms Escherichia coli ATCC 11230, Staphylococcus aureus ATCC 6538, Klebsiella pneumoniae UC57, Micrococcus luteus La 2971, Proteus vulgaris ATCC 8427, Pseudomonas aeruginosa ATCC 27853, Mycobacterium smegmatis CCM 2067, Bacillus cereus ATCC 7064, Listeria monocytogenes ATCC 15313, Candida albicans ATCC 10231, Kluyveromyces fragilis NRRL 2415, Rhodotorula rubra DSM 70403, Debaryomyces hansenii DSM 70238 and Hanseniaspora guilliermondii DSM 3432.

  12. A study of the possibility of using 3-(3'-5'Dinitro-4' - Hydroxy phenyl) phthalide as an indicator

    International Nuclear Information System (INIS)

    Khalil, A. R.; Al-Hamdany, R.

    1998-01-01

    This paper describes a ur-visible spectroscopic characterization and acid-base equilibrium studies of 3-(3 ' -5 ' -din tro-4 ' - hydroxy phenyl) phthalide (1) for its possible use as an indicator. The ionization constant (K 2 ) has been evaluated by potentiometric titration indicating that the reagent is a weak acid comparable to acetic acid. The (pK 2 ) has been attributed to deprotonation of the compound to give the corresponding anion, which possesses considerable resonance stabilization. The different colour shown by each species involved in equilibrium allows the use of this reagent as an acid-base indicator, placing the transition interval between ph 2.0 (colourless) and 3.0 (yellow). (authors). 11 refs., 1 fig., 2 tabs

  13. A urinary metabolite of {Delta}{sup 1}-tetrahydrocannabinol. The first synthesis of 4``-hydroxy-{Delta}{sup 1}-tetrahydrocannabinol-7-oic acid labelled with deuterium

    Energy Technology Data Exchange (ETDEWEB)

    Szirmai, Maria; Odqvist, Helena [Uppsala Univ. (Sweden). Dept. of Pharmacognosy; Halldin, M.M. [Karolinska Inst., Stockholm (Sweden). Dept. of Pharmacology

    1996-04-01

    The first synthesis of 4``-hydroxy-{Delta}-{sup 1}-THC-7-oic acid, one of the three major metabolites of {Delta}{sup 1}-THC identified in human urine is discussed. Methyl 4-(3,5-dihydroxyphenyl)butanoate was prepared from 3,5-diydroxybenzoic acid in an overall yield of 15% was condensed with a terpene synthon under acidic conditions followed by hydrolysis and conversion of the 4``-carboxylic acid function to the corresponding methyl ketone using methyllithium. Reduction with NaBH{sub 4} afforded the secondary alcohol in the side-chain. Acetylation and removal of the 1,3-dithiane masking group gave the aldehyde in C-7-position which was further oxidized using NaClO{sub 2} followed by deacetylation to give the desired metabolite. The same procedure may be used for the synthesis of unlabelled 4``-hydroxy-{Delta}{sup 1}-THC-7-oic acid. (author).

  14. Mechanisms of Action of Antiseizure Drugs and the Ketogenic Diet

    Science.gov (United States)

    Rogawski, Michael A.; Löscher, Wolfgang; Rho, Jong M.

    2016-01-01

    Antiseizure drugs (ASDs), also termed antiepileptic drugs, are the main form of symptomatic treatment for people with epilepsy, but not all patients become free of seizures. The ketogenic diet is one treatment option for drug-resistant patients. Both types of therapy exert their clinical effects through interactions with one or more of a diverse set of molecular targets in the brain. ASDs act by modulation of voltage-gated ion channels, including sodium, calcium, and potassium channels; by enhancement of γ-aminobutyric acid (GABA)-mediated inhibition through effects on GABAA receptors, the GABA transporter 1 (GAT1) GABA uptake transporter, or GABA transaminase; through interactions with elements of the synaptic release machinery, including synaptic vesicle 2A (SV2A) and α2δ; or by blockade of ionotropic glutamate receptors, including α-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) receptors. The ketogenic diet leads to increases in circulating ketones, which may contribute to the efficacy in treating pharmacoresistant seizures. Production in the brain of inhibitory mediators, such as adenosine, or ion channel modulators, such as polyunsaturated fatty acids, may also play a role. Metabolic effects, including diversion from glycolysis, are a further postulated mechanism. For some ASDs and the ketogenic diet, effects on multiple targets may contribute to activity. Better understanding of the ketogenic diet will inform the development of improved drug therapies to treat refractory seizures. PMID:26801895

  15. Synthesis and Antifungal Activities of 5-(o-Hydroxy phenyl-2-[4'aryl-3'chloro-2'azetidinon-1-yl]-1,3,4-thiadiazole

    Directory of Open Access Journals (Sweden)

    Shiv K. Gupta

    2011-01-01

    Full Text Available New series of 5-(o-hydroxy phenyl-2-[4'aryl-3'chloro-2'azetidinon-1-yl]-1,3,4-thiadiazole have been synthesized and the structures of the new compounds were established on the basis of IR, 1H NMR spectral data. In vitro antifungal activity (MIC activity was evaluated and compared with standard drugs of ketoconazole. Compounds 3c in the series has shown interesting antifungal activity against both C. albicans and A. niger fungus. In the gratifying result, most of the compounds were found to have moderate antifungal activity.

  16. Substituted 7-amino-5-thio-thiazolo[4,5-d]pyrimidines as potent and selective antagonists of the fractalkine receptor (CX3CR1).

    Science.gov (United States)

    Karlström, Sofia; Nordvall, Gunnar; Sohn, Daniel; Hettman, Andreas; Turek, Dominika; Åhlin, Kristofer; Kers, Annika; Claesson, Martina; Slivo, Can; Lo-Alfredsson, Yvonne; Petersson, Carl; Bessidskaia, Galina; Svensson, Per H; Rein, Tobias; Jerning, Eva; Malmberg, Åsa; Ahlgen, Charlotte; Ray, Colin; Vares, Lauri; Ivanov, Vladimir; Johansson, Rolf

    2013-04-25

    We have developed two parallel series, A and B, of CX3CR1 antagonists for the treatment of multiple sclerosis. By modifying the substituents on the 7-amino-5-thio-thiazolo[4,5-d]pyrimidine core structure, we were able to achieve compounds with high selectivity for CX3CR1 over the closely related CXCR2 receptor. The structure-activity relationships showed that a leucinol moiety attached to the core-structure in the 7-position together with α-methyl branched benzyl derivatives in the 5-position displayed promising affinity, and selectivity as well as physicochemical properties, as exemplified by compounds 18a and 24h. We show the preparation of the first potent and selective orally available CX3CR1 antagonists.

  17. Effect of Terbuthylazine-2-hydroxy at Environmental Concentrations on Early Life Stages of Common Carp (Cyprinus carpio L.

    Directory of Open Access Journals (Sweden)

    Josef Velisek

    2014-01-01

    Full Text Available The aim of the study was to investigate effects of the triazine’s herbicide terbuthylazine-2-hydroxy on early life stage of common carp (Cyprinus carpio L. through antioxidant indices, mortality, growth, development, and histopathology. Based on accumulated mortality in the experimental groups, lethal concentrations of terbuthylazine-2-hydroxy were estimated at 35-day LC50 = 10.9 mg/L terbuthylazine-2-hydroxy. By day 15, fish were exposed to 3.5 mg/L and by day 26, fish were exposed to 0.0029 mg/L; real environmental concentration in Czech rivers, 0.07 mg/L, 1.4 mg/L, and 3.5 mg/L terbuthylazine-2-hydroxy, showed significantly lower mass and total length compared with controls. Based on inhibition of growth in the experimental groups, lowest observed effect concentration (LOEC = 0.002 mg/L terbuthylazine-2-hydroxy and no observed effect concentration (NOEC = 0.0001 mg/L terbuthylazine-2-hydroxy. No significant negative effects on hatching or embryo viability were demonstrated at the concentrations tested, but significant differences in early ontogeny among groups were noted. Fish from the two highest tested concentrations showed a dose-related delay in development compared with the controls. Total superoxide dismutase (SOD activity was significant lower in all groups testedly for terbuthylazine-2-hydroxy compared with the control group. At concentrations of 1.4 and 3.5 mg/L damage to caudal kidney tubules when compared to control fish was found.

  18. Synthesis of 7-hydroxy-4'-methoxyflavanone and 7-hydroxy-4'-methoxyflavone as a candidate anticancer against cervical (HeLa) cancer cell and colon (WiDr) cancer cell by in vitro

    Science.gov (United States)

    Matsjeh, Sabirin; Anwar, Chairil; Solikhah, Eti Nurwening; Farah, Harra Ismi; Nurfitria, Kurnia

    2017-03-01

    The compound 7-hydroxy-4'-methoxyflavanone and 7-hydroxy-4'-methoxyflavone have been synthesized through cyclization reaction of 2 ', 4'-dihydroxy-4-methoxychalcone (1,3-diphenyl-2-propene-1-one). The 2 ', 4'-dihydroxy-4-methoxychalcone were synthesized through Claisen-Schmidt condensation from 2,4-dihydroxyacetophenone and 4-methoxybenzaldehyde (anisaldehyde) in aqueous KOH as a catalyst in ethanol. The 7-hydroxy-4'-methoxyflavanone has been synthesized through cyclization reaction of 2 ', 4'-dihydroxy-4-methoxychalcone by Oxa-Michael addition reaction with sulfuric acid as a catalyst in ethanol. The 7-hydroxy-4'-methoxyflavone has been synthesized through oxidative cyclization reaction of 2 ', 4'-dihydroxy-4-methoxychalcone using I2 in DMSO as a catalyst with a mole ratio (1: 1) mol. All these producets were characterized by FT-IR, GC-MS, and 1H-NMR and 13C-NMR spectrometer. Both of these compounds were tested citotoxycity activity as an anticancer against cervical and colon cancer cells (HeLa and WiDr cell lines) using MTT assay in vitro. Dose series given test solution concentration on HeLa and WiDr cells starting from 0,78; 1,56; 3,12; 6,25; 12,50; 25; 50 and 100 µg/mL with a long incubation treatment for 24 hours. The results study showed that the 7-hydroxy-4'-methoxyflavanone as bright yellow crystals with a melting point 172-174 ° C and a yield of 56.67% and the 7-hydroxy-4'-methoxyflavone as bright yellow crystals with a yield of 88, 31%, and a melting point of 263-265 ° C. The test results cytotoxic 7-hydroxy-4-methoxyflavone showed active against HeLa cells with IC50 value of 25.73 µg/mL and was quite active in the WiDr cells with IC50 value of 83.75 µg/mL. The result of the activity of 7-hydroxy-4-methoxyflavanone show active cytotoxic activity against HeLa and WiDr cell growth with IC50 value of 40.13 µg/mL and 37.85 µg/mL. IC50 value indicated that 7-hydroxy-4'-methoxyflavone and 7-hydroxy-4'-methoxyflavanone potential as inhibitors in HeLa and

  19. A short and facile synthesis of 2-(1Z)-(3-hydroxy-3,7-dimethylocta-1,6-dienyl)-1,4-benzenediol and 1-(3'-methoxypropanoyl)-2,4,5-trimethoxybenzene isolated from Cordia alliodora.

    Science.gov (United States)

    Kaur, Sukhbir; Singh, Vasundhara; Kumar, Gulshan; Kad, G L; Singh, Jasvinder

    2010-03-01

    A novel synthesis of 2-(1Z)-(3-hydroxy-3,7-dimethylocta-1,6-dienyl)-1,4-benzenediol and 1-(3'-methoxypropanoyl)-2,4,5-trimethoxybenzene has been carried out by making use of an easily available starting material, acceleration by MW irradiation and the use of water as a green solvent in the key steps.

  20. Radiosynthesis of 3-{l_brace}[4-(4-[{sup 18}F]fluorobenzyl)]piperazin-1-yl{r_brace}methyl-1H-pyrrolo[2,3-b]pyridine: A potential dopamine D{sub 4} receptor imaging agent

    Energy Technology Data Exchange (ETDEWEB)

    Haibin Tian; Duanzhi Yin; Junling Li; Lan Zhang; Cunfu Zhang; Yongxian Wang; Wei Zhou [Radiopharmaceutical Research Center, Shanghai Inst. of Nuclear Research, The Chinese Academy of Sciences, Shanghai, SH (China)

    2003-07-01

    The dopamine D{sub 4} receptor (D{sub 4}R) is expressed in low density in various extrastriatal brain regions. This receptor subtype is discussed in relation to the pathophysiology and treatment of schizophrenia but to date no selective positron emission tomography (PET) ligand is available to study its distribution in vivo. The 7-azaindole derivative 3-([4-(4-iodophenyl)piperazin-1-yl]-methyl)-1H-pyrrolo [2,3-b]pyridine (L-750,667) is a novel, high-affinity (K{sub i}=0.51nM) and selective D{sub 4}R ligand. L-750,667 analogue 3-[4-(4-[{sup 18}F]fluorobenzyl)]piperazin-1-yl methyl-1H-pyrrolo[2,3-b]-pyridine was prepared by reacting 3-(piperazin-1-yl)-methyl-1H-pyrrolo[2,3-b]pyridine with 4-[ 18F]fluorobenzaldehyde, which was labeled with no carrier added [ 18F]fluoride. The radiochemical yield of 3-[4-(4-[{sup 18}F]fluorobenzyl)]piperazin-1-yl methyl-1H-pyrrolo[2,3-b]pyridine was 12.0% at end of synthesis (EOS), and the synthesis time was 73min. The labeled benzaldehydes may be useful precursors for the radiosyntheses of other complex radiotracers for PET.

  1. Isolation of 3-amino-4-nitrobenzyl acetate: evidence of an undisclosed impurity in 5-amino-2-nitrobenzoic acid

    Directory of Open Access Journals (Sweden)

    Brandon Quillian

    2015-06-01

    Full Text Available Yellow crystals of the title compound 3-amino-4-nitrobenzyl acetate, C9H10N2O4, were isolated from the reaction of acetic anhydride with (5-amino-2-nitrophenylmethanol, prepared from reduction of commerically available 5-amino-2-nitrobenzoic acid with borane–THF. The molecule is essentially planar (r.m.s. deviation = 0.028 Å. The molecules are linked by intermolecular N—H...O hydrogen-bonding interactions between the carbonyl and amine groups, forming a zigzag chain along the b-axis direction lying in a plane parallel to (-102. The chains are stacked along the c axis by π–π interactions [centroid–centroid distances = 3.6240 (3 and 3.5855 (4 Å]. A strong intramolecular N—H...O hydrogen-bonding interaction is observed between the nitro group and the amine group [2.660 (2 Å].

  2. Silsesquioxane organofunctionalized with 4-amino-3-hydrazino-5-mercapto-1,2,4-triazole: Preparation and subsequent reaction with silver and potassium hexacyanoferrate(III) for detection of L-cysteine

    International Nuclear Information System (INIS)

    Carmo, Devaney R. do; Silvestrini, Daniela R.; Silveira, Tayla F.S. da; Cumba, Loanda R.; Dias Filho, Newton L.; Soares, Layciane A.

    2015-01-01

    The octakis(3-chloropropyl)octasilsesquioxane (SS) was organofunctionalized with 4-amino-3-hydrazino-5-mercapto-1,2,4-triazole (Purpald). The functionalized silsesquioxane with Purpald (SP) was characterized by Fourier transform infrared spectroscopy (FT-IR), and nuclear magnetic resonance (NMR). After functionalized, silsesquioxane can interact with silver nitrate and subsequently with potassium hexacyanoferrate (III) (AgHSP). The novel hybrid composite formed (AgHSP) was characterized by Fourier transform infrared spectra, scanning electron microscopy (SEM), and energy dispersive X-ray spectroscopy (EDX). AgHSP was electrochemically characterized by cyclic voltammetry (CV) using graphite paste electrode. The AgHSP incorporated into a graphite paste electrode (20% w/w) was tested for detection of L-cysteine. The modified electrode showed a linear response from 9.0 × 10 −5 to 5.0 × 10 −3 mol L −1 with the corresponding equation Y(A) = 0.01315 + 1.865 [L-cysteine], and a correlation coefficient of r 2 = 0.9995. The method showed a detection limit of 1.76 × 10 −4 mol L −1 with a relative standard deviation of ± 2% (n = 3) and amperometric sensitivity of 1.865 A/mol L −1 . - Highlights: • Functionalization of silsesquioxane with Purpald compound • Characterization of silsesquioxane was done with FT-IR, NMR, SEM, EDX and VC. • The modified silsesquioxane was interacted with AgNO 3 and K 3 [Fe(CN) 6 ]. • The composite was tested by cyclic voltammetry for detection of L-cysteine

  3. Silsesquioxane organofunctionalized with 4-amino-3-hydrazino-5-mercapto-1,2,4-triazole: Preparation and subsequent reaction with silver and potassium hexacyanoferrate(III) for detection of L-cysteine

    Energy Technology Data Exchange (ETDEWEB)

    Carmo, Devaney R. do, E-mail: docarmo@dfq.feis.unesp.br; Silvestrini, Daniela R.; Silveira, Tayla F.S. da; Cumba, Loanda R.; Dias Filho, Newton L.; Soares, Layciane A.

    2015-12-01

    The octakis(3-chloropropyl)octasilsesquioxane (SS) was organofunctionalized with 4-amino-3-hydrazino-5-mercapto-1,2,4-triazole (Purpald). The functionalized silsesquioxane with Purpald (SP) was characterized by Fourier transform infrared spectroscopy (FT-IR), and nuclear magnetic resonance (NMR). After functionalized, silsesquioxane can interact with silver nitrate and subsequently with potassium hexacyanoferrate (III) (AgHSP). The novel hybrid composite formed (AgHSP) was characterized by Fourier transform infrared spectra, scanning electron microscopy (SEM), and energy dispersive X-ray spectroscopy (EDX). AgHSP was electrochemically characterized by cyclic voltammetry (CV) using graphite paste electrode. The AgHSP incorporated into a graphite paste electrode (20% w/w) was tested for detection of L-cysteine. The modified electrode showed a linear response from 9.0 × 10{sup −5} to 5.0 × 10{sup −3} mol L{sup −1} with the corresponding equation Y(A) = 0.01315 + 1.865 [L-cysteine], and a correlation coefficient of r{sup 2} = 0.9995. The method showed a detection limit of 1.76 × 10{sup −4} mol L{sup −1} with a relative standard deviation of ± 2% (n = 3) and amperometric sensitivity of 1.865 A/mol L{sup −1}. - Highlights: • Functionalization of silsesquioxane with Purpald compound • Characterization of silsesquioxane was done with FT-IR, NMR, SEM, EDX and VC. • The modified silsesquioxane was interacted with AgNO{sub 3} and K{sub 3}[Fe(CN){sub 6}]. • The composite was tested by cyclic voltammetry for detection of L-cysteine.

  4. Growth and characterization of novel organic 3-Hydroxy Benzaldehyde-N-methyl 4 Stilbazolium Tosylate crystals for NLO applications.

    Science.gov (United States)

    Jagannathan, K; Umarani, P; Ratchagar, V; Ramesh, V; Kalainathan, S

    2016-01-15

    The 3-Hydroxy Benzaldehyde-N-methyl 4-Stilbazolium Tosylate (3- HBST) is a new organic NLO crystal and it is a new derivative in stilbazolium tosylate family. In this work we have synthesized 3-HBST and the single crystal was grown by conventional slow cooling method. The structure and lattice parameters of the grown crystal were determined by the single crystal X-ray diffraction (XRD) technique and it is exhibiting good crystalline nature which is observed from the powder XRD. In order to check the crystalline quality the rocking curve was recorded using multi crystal X-ray diffractometer. The functional groups were identified from both FTIR and NMR spectral analyses. The π-π* and n-π* optical transition energy levels were estimated from the absorption peaks. The NLO property was confirmed by measuring relative SHG efficiency by Kurtz powder test; it shows 24 times higher SHG efficiency than that of urea. In order to test the mechanical stability the Vickers and Knoop micro hardness measurement were carried out and found that the micro hardness number decreases with increasing load. The melting point was determined from Differential Scanning Colorimetry (DSC). Copyright © 2015 Elsevier B.V. All rights reserved.

  5. An unconditioned stimulus retrieval extinction procedure to prevent the return of fear memory.

    Science.gov (United States)

    Liu, Jianfeng; Zhao, Liyan; Xue, Yanxue; Shi, Jie; Suo, Lin; Luo, Yixiao; Chai, Baisheng; Yang, Chang; Fang, Qin; Zhang, Yan; Bao, Yanping; Pickens, Charles L; Lu, Lin

    2014-12-01

    Conditioned fear memories can be updated by extinction during reconsolidation, and this effect is specific to the reactivated conditioned stimulus (CS). However, a traumatic event can be associated with several cues, and each cue can potentially trigger recollection of the event. We introduced a technique to target all diverse cues associated with an aversive event that causes fear. In human experiments, 161 subjects underwent modified fear conditioning, in which they were exposed to an unconditioned stimulus (US) or unreinforced CS to reactivate the memory and then underwent extinction, spontaneous recovery, and reinstatement. In animal experiments, 343 rats underwent contextual fear conditioning under a similar protocol as that used in the human experiments. We also explored the molecular alterations after US reactivation in rats. Presentation of a lower intensity US before extinction disrupted the associations between the different CS and reactivated US in both humans and rats. This effect persisted for at least 6 months in humans and was selective to the reactivated US. This procedure was also effective for remote memories in both humans and rats. Compared with the CS, the US induced stronger endocytosis of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid glutamate receptors 1 and 2 and stronger activation of protein kinase A, p70S6 kinase, and cyclic adenosine monophosphate response element binding protein in the dorsal hippocampus in rats. These findings demonstrate that a modified US retrieval extinction strategy may have a potential impact on therapeutic approaches to prevent the return of fear. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  6. Matrix metalloproteinases regulate the formation of dendritic spine head protrusions during chemically induced long-term potentiation.

    Directory of Open Access Journals (Sweden)

    Zsuzsanna Szepesi

    Full Text Available Dendritic spines are are small membranous protrusions that extend from neuronal dendrites and harbor the majority of excitatory synapses. Increasing evidence has shown that matrix metalloproteinases (MMPs, a family of extracellularly acting and Zn(2+-dependent endopeptidases, are able to rapidly modulate dendritic spine morphology. Spine head protrusions (SHPs are filopodia-like processes that extend from the dendritic spine head, representing a form of postsynaptic structural remodeling in response to altered neuronal activity. Herein, we show that chemically induced long-term potentiation (cLTP in dissociated hippocampal cultures upregulates MMP-9 activity that controls the formation of SHPs. Blocking of MMPs activity or microtubule dynamics abolishes the emergence of SHPs. In addition, autoactive recombinant MMP-9, promotes the formation of SHPs in organotypic hippocampal slices. Furthermore, spines with SHPs gained postsynaptic α-amino-3-hydroxyl-5-methyl-4-isoxazole propionic acid (AMPA receptors upon cLTP and the synaptic delivery of AMPA receptors was controlled by MMPs. The present results strongly imply that MMP-9 is functionally involved in the formation of SHPs and the control of postsynaptic receptor distribution upon cLTP.

  7. Structure of dichloro(4-hydroxy-L-proline)cadmium(II)

    Energy Technology Data Exchange (ETDEWEB)

    Yukawa, Yasuhiko; Inomata, Yoshie; Takeuchi, Toshio [Jochi Univ., Tokyo (Japan). Faculty of Science and Technology; Shimoi, Mamoru; Ouchi, Akira

    1982-10-01

    An X-ray diffraction study of the title complex has been carried out. The crystal is monoclinic, with the space group P2/sub 1/; Z = 2; a = 8.196(4), b = 7.275(3), c = 7.740(4) A, beta = 103.73(4)/sup 0/. Full-matrix least-squares refinements have led to the final R value of 0.030. The structure consists of one-demensional polymers bridged by chlorine atoms and a carboxyl group. Four chlorine atoms coordinate to a cadmium atom and form a square plane. The planes extend in the direction of the b axis like an infinite folding screen, sharing opposite edges. From the trough positions in the zigzag structure, the carboxyl oxygen atoms of 4-hydroxy-L-proline coordinate forkedly to two cadmium atoms. The ligand is a switter ion in the complex.

  8. Isozyme-specific enzyme inhibitors. 14. 5'(R)-C-[(L-homocystein-S-yl)methyl]adenosine 5'-(beta,gamma-imidotriphosphate), a potent inhibitor of rat methionine adenosyltransferases.

    Science.gov (United States)

    Kappler, F; Vrudhula, V M; Hampton, A

    1987-09-01

    The title compound is a covalent adduct of L-methionine (Met) and beta,gamma-imido-ATP. In its synthesis the N-Boc derivative of 5'(R)-C-(aminomethyl)-N6-benzoyl-5'-O-tosyl-2',3'-O- isopropylidenadenosine was converted by the successive actions of CF3CO2H and HNO2 into the corresponding 5'(R)-C-hydroxymethyl derivative. Treatment of this with disodium L-homocysteinate led to attack of sulfur at C6', apparently via a 5',6'-epoxide, and to total stereoselective inversion at C5' to furnish, after debenzoylation, 5'(R)-C-(L-homocystein-S-ylmethyl)-2',3'-O-isopropylidene ade nosine. The 5' configuration was established by conversion of this into the known 5'(S)-C-methyl-2',3'-O-isopropylidene adenosine with Raney nickel. The alpha-amino acid residue was protected as an N-Boc methyl ester, after which the 5'-hydroxyl was phosphorylated with benzyl phosphate and dicyclohexylcarbodiimide. The phosphoanhydride bond with inorganic imidodiphosphate was then created by established methods. Finally, blocking groups were removed under conditions that gave the desired adduct with no racemization of its L-methionine residue. It was a potent inhibitor [KM(ATP)/Ki = 1080; KM(Met)/Ki = 7.7] of the M-2 (normal tissue) form of rat methionine adenosyltransferase and of the M-T (hepatoma tissue) form [KM(ATP)/Ki = 670; KM(Met)/Ki = 22]. Inhibitions were competitive with respect to ATP or to L-methionine, indicating a dual substrate site mode of binding to the enzyme forms.

  9. Autoinactivation of the stargazin-AMPA receptor complex: subunit-dependency and independence from physical dissociation.

    Directory of Open Access Journals (Sweden)

    Artur Semenov

    Full Text Available Agonist responses and channel kinetics of native α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA receptors are modulated by transmembrane accessory proteins. Stargazin, the prototypical accessory protein, decreases desensitization and increases agonist potency at AMPA receptors. Furthermore, in the presence of stargazin, the steady-state responses of AMPA receptors show a gradual decline at higher glutamate concentrations. This "autoinactivation" has been assigned to physical dissociation of the stargazin-AMPA receptor complex and suggested to serve as a protective mechanism against overactivation. Here, we analyzed autoinactivation of GluA1-A4 AMPA receptors (all flip isoform expressed in the presence of stargazin. Homomeric GluA1, GluA3, and GluA4 channels showed pronounced autoinactivation indicated by the bell-shaped steady-state dose response curves for glutamate. In contrast, homomeric GluA2i channels did not show significant autoinactivation. The resistance of GluA2 to autoinactivation showed striking dependence on the splice form as GluA2-flop receptors displayed clear autoinactivation. Interestingly, the resistance of GluA2-flip containing receptors to autoinactivation was transferred onto heteromeric receptors in a dominant fashion. To examine the relationship of autoinactivation to physical separation of stargazin from the AMPA receptor, we analyzed a GluA4-stargazin fusion protein. Notably, the covalently linked complex and separately expressed proteins expressed a similar level of autoinactivation. We conclude that autoinactivation is a subunit and splice form dependent property of AMPA receptor-stargazin complexes, which involves structural rearrangements within the complex rather than any physical dissociation.

  10. Blockade and enhancement of glutamate receptor responses in Xenopus oocytes by methylated arsenicals

    Energy Technology Data Exchange (ETDEWEB)

    Krueger, Katharina; Gruner, Janina; Madeja, Michael; Musshoff, Ulrich [Universitaetsklinikum Muenster, Institut fuer Physiologie I, Muenster (Germany); Hartmann, Louise M.; Hirner, Alfred V. [Universitaet Duisburg-Essen, Institut fuer Umweltanalytik, Essen (Germany); Binding, Norbert [Universitaetsklinikum Muenster, Institut fuer Arbeitsmedizin, Muenster (Germany)

    2006-08-15

    Pentavalent and trivalent organoarsenic compounds belong to the major metabolites of inorganic arsenicals detected in humans. Recently, the question was raised whether the organic arsenicals represent metabolites of a detoxification process or methylated species with deleterious biological effects. In this study, the effects of trivalent arsenite (AsO{sub 3} {sup 3-}; iA{sup III}), the pentavalent organoarsenic compounds monomethylarsonic acid (CH{sub 3}AsO(OH){sub 2}; MMA{sup V}) and dimethylarsinic acid ((CH{sub 3}){sub 2}AsO(OH); DMA{sup V}) and the trivalent compounds monomethylarsonous acid (CH{sub 3}As(OH){sub 2}, MMA{sup III}) and dimethylarsinous acid ((CH{sub 3}){sub 2}As(OH); DMA{sup III}) were tested on glutamate receptors and on voltage-operated potassium and sodium channels heterologously expressed in Xenopus oocytes. Membrane currents of ion channels were measured by conventional two-electrode voltage-clamp techniques. The effects of arsenite were tested in concentrations of 1-1,000 {mu}mol/l and the organic arsenical compounds were tested in concentrations of 0.1-100 {mu}mol/l. We found no significant effects on voltage-operated ion channels; however, the arsenicals exert different effects on glutamate receptors. While MMA{sup V} and MMA{sup III} significantly enhanced ion currents through N-methyl-d-aspartate (NMDA) receptor ion channels with threshold concentrations <10 {mu}mol/l, DMA{sup V} and DMA{sup III} significantly reduced NMDA-receptor mediated responses with threshold concentrations <0.1 {mu}mol/l; iA{sup III} had no effects on glutamate receptors of the NMDA type. MMA{sup III} and DMA{sup V} significantly reduced ion currents through {alpha}-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-receptor ion channels with threshold concentrations <10 {mu}mol/l (MMA{sup III}) and <1 {mu}mol/l (DMA{sup V}). MMA{sup V} and iA{sup III} had no significant effects on glutamate receptors of the AMPA type. The effects of MMA{sup V}, MMA

  11. 40 CFR 721.5252 - 2-Naphthalenecarboxylic acid, 4,4′-methylenebis [3-hydroxy-, zinc salt.

    Science.gov (United States)

    2010-07-01

    ...-methylenebis [3-hydroxy-, zinc salt. 721.5252 Section 721.5252 Protection of Environment ENVIRONMENTAL...′-methylenebis [3-hydroxy-, zinc salt. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as 2-Naphthalenecarboxylic acid, 4,4′-methylenebis [3-hydroxy-, zinc...

  12. Methyl 2-(1a,4a-dimethyl-2,8-dioxo-2,3,4,4a,5,6,7,8-octahydro-1aH-1-oxacyclopropa[d]naphthalen-7-ylacrylate

    Directory of Open Access Journals (Sweden)

    Mohamed Tebbaa

    2012-02-01

    Full Text Available The title compound, C16H20O5, was synthesized from ilicic acid [2-(8-hydroxy-4a,8-dimethyldecahydronaphthalen-2-ylacrylic acid], which was isolated from the chloroform extract of the aerial part of Inula viscose (L Aiton [or Dittrichia viscosa (L Greuter]. The molecule is built up from two fused six-membered rings, the epoxidized six-membered ring adopts a half-chair conformation while the other ring displays a perfect chair conformation. The crystal structure features C—H...O hydrogen bonds.

  13. Short-term carcinogenicity testing of a potent murine intestinal mutagen, 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP), in Apc1638N transgenic mice

    DEFF Research Database (Denmark)

    Sørensen, Ilona Kryspin; Kristiansen, E.; Mortensen, Alicja

    1997-01-01

    others, mammary tumors, We have studied these mice in a short-term carcinogenicity test with 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP), a potent murine small intestinal mutagen and lymphomagen. Upon dietary administration of 0.03% PhIP in a short-term (6 months) study, a significantly...

  14. Study of benzoate, propionate, and sorbate salts as mould spoilage inhibitors on intermediate moisture bakery products of low pH (4.5-5.5).

    Science.gov (United States)

    Guynot, M E; Ramos, A J; Sanchis, V; Marín, S

    2005-05-25

    A hurdle technology approach has been applied to control common mold species causing spoilage of intermediate moisture bakery products (Eurotium spp., Aspergillus spp., and Penicillium corylophilum), growing on a fermented bakery product analogue (FBPA). The factors studied included a combination of different levels of weak acid preservatives (potassium sorbate, calcium propionate, and sodium benzoate; 0-0.3%), pH (4.5-5.5), and water activity (a(w); 0.80-0.90). Potassium sorbate was found to be the most effective in preventing fungal spoilage of this kind of products at the maximum concentration tested (0.3%) regardless of a(w). The same concentration of calcium propionate and sodium benzoate was effective only at low a(w) levels. On the other hand, potassium sorbate activity was slightly reduced at pH 5.5, the 0.3% being only effective at 0.80 a(w). These findings indicate that potassium sorbate may be a suitable preserving agent to inhibit deterioration of a FBPA of slightly acidic pH (near 4.5) by xerophilic fungi. Further studies have to be done in order to adjust the minimal inhibitory concentration necessary to obtain a product with the required shelf life.

  15. Synthesis, Characterization and Chelating Properties of 4-Butyrylsemicarbazone-1-phenyl-3-methyl-2-pyrazolin-5-one

    Directory of Open Access Journals (Sweden)

    J. D. Patel

    2010-01-01

    Full Text Available 4-Butyrylsemicarbazone-1-phenyl-3-methyl-2-pyrazolin-5-one (BUMP-SC was prepared and its metal chelates of Cu2+, Ni2+, Co2+, Mn2+, Fe2+, Fe3+, Cr3+, UO2 and OV were prepared. The ligands and its chelates were characterized by elemental analysis, metal:ligand (M:L stoichiometry, IR-electronic spectral studies and magnetic properties. The compounds also were screened for their antimicrobial activity.

  16. (E,Z)-3-(3',5'-Dimethoxy-4'-hydroxy-benzylidene)-2-indolinone blocks mast cell degranulation.

    Science.gov (United States)

    Kiefer, S; Mertz, A C; Koryakina, A; Hamburger, M; Küenzi, P

    2010-05-12

    (E,Z)-3-(3',5'-Dimethoxy-4'-hydroxy-benzylidene)-2-indolinone (indolinone) is an alkaloid that has been identified as a pharmacologically active compound in extracts of the traditional anti-inflammatory herb Isatis tinctoria. Indolinone has been shown to inhibit compound 48/80-induced mast cell degranulation in vitro. Application of indolinone to bone marrow derived mast cells showed that it was uniformly distributed in the cytoplasm and that cellular uptake was terminated within minutes. Pre-treatment of IgE-sensitized mast cells with 100nM indolinone rendered them insensitive against FcvarepsilonRI-receptor dependent degranulation. However, upstream signalling induced by antigen such as activation of PI3-K and MAPK remained unaffected. We conclude that indolinone blocks mast cell degranulation at the level of granule exocitosis with an IC(50) of 54nm.

  17. Synthesis, characterization of some novel 1,3,4-oxadiazole compounds containing 8-hydroxy quinolone moiety as potential antibacterial and anticancer agents

    Directory of Open Access Journals (Sweden)

    Vinayak Mahadev Adimule

    2014-12-01

    Full Text Available In the present work a series of novel derivatives of 8-hydroxy quinolone substituted 1,3,4-oxadiazole compounds were synthesized by convergent synthetic method and studied for their antibacterial and anticancer properties. The cell lines used for cytotoxic evaluation were HeLa, Caco-2 and MCF7. The synthetic chemistry involved conversion of various substituted aromatic acids into ethyl ester 2a-e. The ethyl ester was converted into corresponding carbohydrazide 3a-e. Carbohydrazides are reacted with chloroacetic acid, phosphorous oxytrichloride and irradiated with microwave in order to obtain the various key intermediates 2-(chloromethyl-5-(substituted phenyl-1,3,4-oxadiazole 4a-e. The 2-(chloromethyl-5-(substituted phenyl-1,3,4-oxadiazole was reacted with 8-hydroxy quinolone in presence of sodium hydride and obtained a series of 8-hydroxy quinoline substituted 1,3,4-oxadiazoles 5a-e. Among the synthesised compounds, the cytotoxicity of the compound 5b i.e. 8-{[5-(2,4-dichlorophenyl-1,3,4-oxadiazol-2-yl]methoxy}quinoline against MCF7 with IC50 of 5.3µM and the compound 5e i.e. 8-{[5-(4-bromophenyl-1,3,4-oxadiazol-2-yl]methoxy}quinoline showed MIC of < 6.25µg/mL against Staphylococcus aureus which is comparable with the known standards. The standards used for cytotoxic evaluation was 5-fluorouracil and for antibacterial was nitrofurazone

  18. Lipase Catalyzed Kinetic Resolution of rac-2-(3-Methoxy-4-methylphenyl) propan-1-ol and rac-2-(3-Hydroxy-4-methylphenyl)propyl propanoate for S-(+)-Xanthorrhizol

    International Nuclear Information System (INIS)

    Shafioul, Azam Sharif Mohammed; Cheong, Chan Seong

    2012-01-01

    Xanthorrhizol is a bisabolane type of natural sesquiterpene, the major component of essential oils of Curcuma xanthorrhiza. 2-(3-Methoxy-4-methylphenyl)propan-1-ol and 2-(3-hydroxy-4-methyl phenyl)propan-1-ol could be essential building block for enantioselective synthesis of xanthorrhizol. Enantioselective (c = 53%, E = 80 ± 3) for R-(+)-2-(3-hydroxy-4-methylphenyl) propan-1-ol and (c = 58%, E = 27 ± 1) for R-(+)-2-(3- methoxy-4-methylphenyl) propan-1-ol resolution processes were developed via lipase-catalyzed reaction. We found lipase Aspergillus oryzae (AOL) and Porcine pancreas (PPL) are selective to transesterification and hydrolysis in organic and aqueous phase. Modified demethylated substrate is appropriate for enantioselective hydrolysis reaction without any additives. Enantiopure chiral alcohol was crystallized from ethyl acetate/ n-hexane co-solvent system. Gram scale resolved chiral intermediate will facilitate the synthesis of the unnatural S-(+)-xanthorrhizol, the corresponding isomer of the natural one

  19. Lipase Catalyzed Kinetic Resolution of rac-2-(3-Methoxy-4-methylphenyl) propan-1-ol and rac-2-(3-Hydroxy-4-methylphenyl)propyl propanoate for S-(+)-Xanthorrhizol

    Energy Technology Data Exchange (ETDEWEB)

    Shafioul, Azam Sharif Mohammed [University of Science and Technology, Daejeon (Korea, Republic of); Cheong, Chan Seong [Korea Institute of Science and Technology, Seoul (Korea, Republic of)

    2012-02-15

    Xanthorrhizol is a bisabolane type of natural sesquiterpene, the major component of essential oils of Curcuma xanthorrhiza. 2-(3-Methoxy-4-methylphenyl)propan-1-ol and 2-(3-hydroxy-4-methyl phenyl)propan-1-ol could be essential building block for enantioselective synthesis of xanthorrhizol. Enantioselective (c = 53%, E = 80 ± 3) for R-(+)-2-(3-hydroxy-4-methylphenyl) propan-1-ol and (c = 58%, E = 27 ± 1) for R-(+)-2-(3- methoxy-4-methylphenyl) propan-1-ol resolution processes were developed via lipase-catalyzed reaction. We found lipase Aspergillus oryzae (AOL) and Porcine pancreas (PPL) are selective to transesterification and hydrolysis in organic and aqueous phase. Modified demethylated substrate is appropriate for enantioselective hydrolysis reaction without any additives. Enantiopure chiral alcohol was crystallized from ethyl acetate/ n-hexane co-solvent system. Gram scale resolved chiral intermediate will facilitate the synthesis of the unnatural S-(+)-xanthorrhizol, the corresponding isomer of the natural one.

  20. N-Substituted 5-Amino-6-methylpyrazine-2,3-dicarbonitriles: Microwave-Assisted Synthesis and Biological Properties

    Directory of Open Access Journals (Sweden)

    Ondrej Jandourek

    2014-01-01

    Full Text Available In this work a series of 15 N-benzylamine substituted 5-amino-6-methyl-pyrazine-2,3-dicarbonitriles was prepared by the aminodehalogenation reactions using microwave assisted synthesis with experimentally set and proven conditions. This approach for the aminodehalogenation reaction was chosen due to its higher yields and shorter reaction times. The products of this reaction were characterized by IR, NMR and other analytical data. The compounds were evaluated for their antibacterial, antifungal and herbicidal activity. Compounds 3 (R = 3,4-Cl, 9 (R = 2-Cl and 11 (R = 4-CF3 showed good antimycobacterial activity against Mycobacterium tuberculosis (MIC = 6.25 µg/mL. It was found that the lipophilicity is important for antimycobacterial activity and the best substitution on the benzyl moiety of the compounds is a halogen or trifluoromethyl group according to Craig’s plot. The activities against bacteria or fungi were insignificant. The presented compounds also inhibited photosynthetic electron transport in spinach chloroplasts and the IC50 values of the active compounds varied in the range from 16.4 to 487.0 µmol/L. The most active substances were 2 (R = 3-CF3, 3 (R = 3,4-Cl and 11 (R = 4-CF3. A linear dependence between lipophilicity and herbicidal activity was observed.

  1. Facile synthesis of α-hydroxy carboxylic acids from the corresponding α-amino acids

    DEFF Research Database (Denmark)

    Stuhr-Hansen, Nicolai; Padrah, Shahrokh; Strømgaard, Kristian

    2014-01-01

    An effective and improved procedure is developed for the synthesis of α-hydroxy carboxylic acids by treatment of the corresponding protonated α-amino acid with tert-butyl nitrite in 1,4-dioxane-water. The amino moiety must be protonated and located α to a carboxylic acid function in order...

  2. Thalassospiramide G, a New γ-Amino-Acid-Bearing Peptide from the Marine Bacterium Thalassospira sp.

    Directory of Open Access Journals (Sweden)

    Sang Kook Lee

    2013-02-01

    Full Text Available In the chemical investigation of marine unicellular bacteria, a new peptide, thalassospiramide G (1, along with thalassospiramides A and D (2–3, was discovered from a large culture of Thalassospira sp. The structure of thalassospiramide G, bearing γ-amino acids, such as 4-amino-5-hydroxy-penta-2-enoic acid (AHPEA, 4-amino-3,5-dihydroxy-pentanoic acid (ADPA, and unique 2-amino-1-(1H-indol-3-yl ethanone (AIEN, was determined via extensive spectroscopic analysis. The absolute configuration of thalassospiramide D (3, including 4-amino-3-hydroxy-5-phenylpentanoic acid (AHPPA, was rigorously determined by 1H–1H coupling constant analysis and chemical derivatization. Thalassospiramides A and D (2–3 inhibited nitric oxide (NO production in lipopolysaccharide (LPS-stimulated mouse macrophage RAW 264.7 cells, with IC50 values of 16.4 and 4.8 μM, respectively.

  3. Synthesis and pharmacological evaluation of the individual stereoisomers of 3- [methyl(1,2,3,4-tetrahydro-2-naphthalenyl)amino]-1-indanone, a potent mast cell stabilising agent

    OpenAIRE

    WALSH, JOHN JARLATH

    2011-01-01

    PUBLISHED Each stereoisomer of 3-[methyl(1,2,3,4-tetrahydro-2-naphthalenyl)amino]-1-indanone, 1a-d, was prepared and evaluated in vitro for its ability to prevent mediator release induced by different degranulating agents from rodent mast cells and also in vivo against passive cutaneous anaphylaxis. The manner in which the stereoisomers prevented direct membrane activation was found to be highly dependent on the stereochemistry of the individual isomers. Stereoisomer 1b was the most active...

  4. Oxidation of propionic acid-3-14C with alkaline permanganate

    International Nuclear Information System (INIS)

    Zielinski, M.

    1981-01-01

    The mechanism of oxidation of propionic acid with permanganate in alkaline medium was reinvestigated using methyl- 14 C labelled propionate. The preferential rupture of the αC-βC bond in propionate in highly concentrated alkaline solutions of NaOH (and KOH) was confirmed and the appearance of 14 C-labelled oxalate explained by the formation of the symmetrical intermediate which decomposes in two different modes. (author)

  5. Opposite modulation of brain stimulation reward by NMDA and AMPA receptors in the ventral tegmental area.

    Directory of Open Access Journals (Sweden)

    Charles eDucrot

    2013-10-01

    Full Text Available Previous studies have shown that blockade of ventral midbrain (VM glutamate N-Methyl-D-Aspartate (NMDA receptors induces reward, stimulates forward locomotion and enhances brain stimulation reward. Glutamate induces two types of excitatory response on VM neurons, a fast and short lasting depolarisation mediated by a-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA receptors and a longer lasting depolarization mediated by NMDA receptors. A role for the two glutamate receptors in modulation of VM neuronal activity is evidenced by the functional change in AMPA and NMDA synaptic responses that result from repeated exposure to reward. Since both receptors contribute to the action of glutamate on VM neuronal activity, we studied the effects of VM AMPA and NMDA receptor blockade on reward induced by electrical brain stimulation. Experiments were performed on rats trained to self-administer electrical pulses in the medial posterior mesencephalon. Reward thresholds were measured with the curve-shift paradigm before and for two hours after bilateral VM microinjections of the AMPA antagonist, NBQX (2,3,-Dioxo-6-nitro-1,2,3,4-tetrahydrobenzo(fquinoxaline-7-sulfonamide, 0, 80, and 800 pmol/0.5ul/side and of a single dose (0.825 nmol/0.5ul/side of the NMDA antagonist, PPPA (2R,4S-4-(3-Phosphonopropyl-2-piperidinecarboxylic acid. NBQX produced a dose-dependent increase in reward threshold with no significant change in maximum rate of responding. Whereas PPPA injected at the same VM sites produced a significant time dependent decrease in reward threshold and increase in maximum rate of responding. We found a negative correlation between the magnitude of the attenuation effect of NBQX and the enhancement effect of PPPA; moreover, NBQX and PPPA were most effective when injected respectively into the anterior and posterior VM. These results suggest that glutamate acts on different receptor sub-types, most likely located on different VM neurons, to modulate

  6. Reversal of methylation silencing of Apo2L/TRAIL receptor 1 (DR4) expression overcomes resistance of SK-MEL-3 and SK-MEL-28 melanoma cells to interferons (IFNs) or Apo2L/TRAIL.

    Science.gov (United States)

    Bae, S I; Cheriyath, V; Jacobs, B S; Reu, F J; Borden, E C

    2008-01-17

    Human melanoma cell lines, SK-MEL-3 and SK-MEL-28, despite induction of the proapoptotic cytokine, Apo2L/TRAIL, did not undergo apoptosis in response to interferons (IFN-alpha2b or IFN-beta). Postulating that genes important for apoptosis induction by IFNs might be silenced by methylation, the DNA demethylating agent 5-aza-2'-deoxycytidine (5-AZAdC) was assessed. DR4 (TRAIL-R1) was identified as one of the genes reactivated by 5-AZAdC with a >3-fold increase in 8 of 10 melanoma cell lines. Pretreatment with 5-AZAdC sensitized SK-MEL-3 and SK-MEL-28 cells to apoptosis induced by IFN-alpha2b and IFN-beta; methylation-specific PCR and bisulfite sequencing confirmed demethylation of 5'CpG islands of DR4 and flow cytometry showed an increase in DR4 protein on the cell surface. In cells with reactivated DR4, neutralizing mAB to TRAIL reduced apoptosis in response to IFN-beta or Apo2L/TRAIL. To further confirm the role of DR4, it was expressed by retroviral vector in SK-MEL-3 and SK-MEL-28 cells with reversal of resistance to IFN-beta and Apo2L/TRAIL. Thus, reexpressing DR4 by 5-AZAdC or retroviral transfection in melanoma cell in which promoter methylation had suppressed its expression, potentiated apoptosis by IFN-alpha2b, IFN-beta and Apo2L/TRAIL. Reactivation of silenced proapoptotic genes by inhibitors of DNA methylation may enhance clinical response to IFNs or Apo2L/TRAIL.

  7. Isoxazole derivatives as new nitric oxide elicitors in plants

    Directory of Open Access Journals (Sweden)

    Anca Oancea

    2017-04-01

    Full Text Available Several 3,5-disubstituted isoxazoles were obtained in good yields by regiospecific 1,3-dipolar cycloaddition reactions between aromatic nitrile oxides, generated in situ from the corresponding hydroxyimidoyl chlorides, with non-symmetrical activated alkynes in the presence of catalytic amounts of copper(I iodide. Effects of 3,5-disubstituted isoxazoles on nitric oxide and reactive oxygen species generation in Arabidopsis tissues was studied using specific diaminofluoresceine dyes as fluorescence indicators.

  8. Effect of aromatization of the ring on intramolecular H-bond in 3-hydroxy-4-formylo derivatives of fulvene

    Science.gov (United States)

    Oziminski, Wojciech P.; Krygowski, Tadeusz M.

    2011-06-01

    DFT optimization of H-bonded 3-hydroxy-4-formylo derivatives of fulvene aromatized by amino substitution at C6 or by complexation with Li atom was performed using the B3LYP functional together with 6-311+G(d,p) basis set. Several aromaticity indicators (HOMA, NICS, pEDA and Shannon aromaticity) confirm an increase of aromaticity in the sequence: fulvene, 6-aminofulvene, Li-complex with fulvene and in the case of H-bonded 3-hydroxy-4-formylo derivatives, exhibited in the same sequence an increase of H-bond strength estimated by direct comparison of energy for H-bonded and open conformations, as well as by using AIM based electron densities at bond critical point.

  9. Inhibition of Listeria monocytogenes by propionic acid-based ingredients in cured deli-style Turkey.

    Science.gov (United States)

    Glass, Kathleen A; McDonnell, Lindsey M; Von Tayson, Roxanne; Wanless, Brandon; Badvela, Mani

    2013-12-01

    Listeria monocytogenes growth can be controlled on ready-to-eat meats through the incorporation of antimicrobial ingredients into the formulation or by postlethality kill steps. However, alternate approaches are needed to provide options that reduce sodium content but maintain protection against pathogen growth in meats after slicing. The objective of this study was to determine the inhibition of L. monocytogenes by propionic acid-based ingredients in high-moisture, cured turkey stored at 4 or 7°C. Six formulations of sliced, cured (120 ppm of NaNO2 ), deli-style turkey were tested, including control without antimicrobials, 3.2% lactate-diacetate blend (LD), 0.4% of a liquid propionate-benzoate-containing ingredient, or 0.3, 0.4, and 0.5% of a liquid propionate-containing ingredient. Products were inoculated with 5 log CFU L. monocytogenes per 100-g package (3 log CFU/ml rinsate), vacuum-sealed, and stored at 4 or 7°C for up to 12 weeks; and populations were enumerated by plating on modified Oxford agar. As expected, the control without antimicrobials supported rapid growth, with >2 log average per ml rinsate increase within 4 weeks of storage at 4°C, whereas growth was observed at 6 weeks for the LD treatment. For both replicate trials, all treatments that contained liquid propionate or propionate-benzoate limited L. monocytogenes growth to an increase of 1-log increase) was observed in individual samples for all propionate-containing treatments at weeks 10, 11, and 12. As expected, L. monocytogenes grew more rapidly when products were stored at 7°C, but trends in relative inhibition were similar to those observed at 4°C. These results verify that propionate-based ingredients inhibit growth of L. monocytogenes on sliced, high-moisture, cured turkey and can be considered as an alternative to reduce sodium-based salts while maintaining food safety.

  10. A click chemistry approach to glycomimetics: Michael addition of 2,3,4,6-tetra-O-acetyl-1-thio-beta-D-glucopyranose to 4-deoxy-1,2-O-isopropylidene-L-glycero-pent-4-enopyranos-3-ulose--a convenient route to novel 4-deoxy-(1-->5)-5-C-thiodisaccharides.

    Science.gov (United States)

    Witczak, Zbigniew J; Lorchak, David; Nguyen, Nguyen

    2007-09-03

    The base catalyzed conjugate Michael addition of the 1-thiosugar, 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranose, 1, to a new highly reactive enone 4-deoxy-1,2-O-isopropylidene-L-glycero-pent-4-enopyranos-3-ulose, 2, proceeds steroselectively with formation of adduct 3 in 94% yield. Convenient stereoselective reduction of the C-3 keto function of 3 with L-Selectride followed by in situ acetylation produces thiodisaccharide 4 in good 82% yield. Cleavage of the 1,2-O-isopropylidene protecting group with p-toluenesulfonic acid in methanol, followed by de-O-acetylation, produced an inseparable anomeric mixture of methyl 4-deoxy-5-C-(beta-D-glucopyranosyl)-thio-alpha/beta-L-ribo-pyranoside 5 in 72% overall yield. This approach constitutes a new general two-step click chemistry route to the previously unknown class of 4-deoxy-(1-->5)-5-C-thiodisaccharides as stable and biologically important glycomimetics.

  11. Prebiotics and age, but not probiotics affect the transformation of 2-amino-3-methyl-3H-imidazo[4,5-f]quinoline (IQ) by fecal microbiota - An in vitro study.

    Science.gov (United States)

    Nowak, Adriana; Czyżowska, Agata; Huben, Krzysztof; Sójka, Michał; Kuberski, Sławomir; Otlewska, Anna; Śliżewska, Katarzyna

    2016-06-01

    Heterocyclic aromatic amines (HAAs) are carcinogens which are formed in meat cooked using high-temperature methods. The human gastrointestinal (GI) microbiota plays a crucial role in maintaining health in humans of different ages, and especially in the elderly. However, the GI microbiota, whose metabolism and composition changes with age, may also be responsible for the activation of mutagenic substances reaching the colon with diet. Probiotics and prebiotics are promising in terms of reducing the destructive effects of HAAs. The aim of the study was to determine if fecal microbiota derived from the feces of 27 volunteers: infants (up to 18 months), adults (aged 23-39 years), the sub-elderly (aged 64-65 years), and the elderly (aged 76-87 years), and the presence of probiotics or prebiotics, affected the transformation of IQ (2-amino-3-methylimidazo[4,5-f]quinoline) to 7-OH-IQ (2-amino-3,6-dihydro-3-methyl-7H-imidazo[4,5-f]quinoline-7-one). The compounds were identified using LC-MS(n), NMR, and FTIR. Their genotoxicity was compared in the comet assay. Individual strains capable of IQ transformation were also identified. 7-OH-IQ was detected in six persons (two children and four elderly individuals). The degree of IQ conversion ranged from 26% (4-month-old girl) to 94% (81-year-old woman) of the initial quantity. Four Enterococcus isolates: two Enterococcus faecium and two Enterococcus faecalis strains, as well as one Clostridium difficile strain (LOCK 1030, from the culture collection) converted IQ to 7-OH-IQ. The genotoxicity of samples containing 7-OH-IQ was even three times higher (P < 0.05) than those with IQ and was correlated with the degree of IQ conversion and 7-OH-IQ concentration. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Structure-based discovery of antagonists for GluN3-containing N-methyl-D-aspartate receptors

    DEFF Research Database (Denmark)

    Kvist, Trine; Greenwood, Jeremy R; Hansen, Kasper B

    2013-01-01

    . In the subsequent pharmacological evaluation of 99 selected compounds, we identified 6-hydroxy-[1,2,5]oxadiazolo[3,4-b]pyrazin-5(4H)-one (TK80) a novel competitive antagonist with preference for the GluN3B subunit. Serendipitously, we also identified [2-hydroxy-5-((4-(pyridin-3-yl)thiazol-2-yl)amino]benzoic acid...... (TK13) and 4-(2,4-dichlorobenzoyl)-1H-pyrrole-2-carboxylic acid (TK30), two novel non-competitive GluN3 antagonists. These findings demonstrate that structural differences between the orthosteric binding site of GluN3 and GluN1 can be exploited to generate selective ligands....

  13. Methionine kinetics in adult men: effects of dietary betaine on L-[2H3-methyl-1-13C]methionine

    International Nuclear Information System (INIS)

    Storch, K.J.; Wagner, D.A.; Young, V.R.

    1991-01-01

    The effects of a daily 3-g supplement of betaine on kinetic aspects of L-[2H3-methyl-1-13C]methionine (MET) metabolism in healthy young adult men were explored. Four groups of four subjects each were given a control diet, based on an L-amino acid mixture supplying 29.5 and 21.9 mg.kg-1.d-1 of L-methionine and L-cystine for 4 d before the tracer study, conducted on day 5 during the fed state. Two groups received the control diet and two groups received the betaine supplement. Tracer was given intravenously (iv) or orally. The transmethylation rate of MET (TM), homocysteine remethylation (RM), and oxidation of methionine were estimated from plasma methionine labeling and 13C enrichment of expired air. RM tended to increase (P = 0.14) but the TM and methionine oxidation were significantly (P less than 0.05) higher after betaine supplementation when estimated with the oral tracer. No differences were detected with the intravenous tracer. Methionine concentration in plasma obtained from blood taken from subjects in the fed state was higher (P less than 0.01) with betaine supplementation. These results suggest that excess methyl-group intake may increase the dietary requirement for methionine

  14. 4-cyano-3-hydroxybutanoyl hydrazines, derivatives and process for the preparation thereof

    Energy Technology Data Exchange (ETDEWEB)

    Hollingsworth, Rawle I. (Haslett, MI); Wang, Guijun (East Lansing, MI)

    2000-01-01

    Novel 4-cyano-3-hydroxybutanoyl hydrazides (10), particularly R-chiral intermediates are described. The intermediates are useful in preparing (R)-3-hydroxy-4-trimethylaminobutyric acid (L-carnitine) and R-4-amino-3-hydroxybutyric acid (GABOB) and chiral chemical intermediates which are medically useful.

  15. Stereoselective synthesis of a-hydroxy-b-amino acids: the chiral pool approach

    Directory of Open Access Journals (Sweden)

    RADOMIR N. SAICIC

    2004-11-01

    Full Text Available A method for the stereoselective homologation of a-amino acids into syn-a-hydroxy-b-amino acids is described, based on the conversion of stereoisomeric cyanohydrins into trans-oxazolines. The synthetic potential of the method is illustrated in the enantioselective formal synthesis of Bestatin.

  16. Synthesis of the natural product building block 5-(3-bromophenyl)-4-hydroxy-5-methylhexan-2-one and its chiral characterization by using chiroptical spectroscopy.

    Science.gov (United States)

    De Gussem, Ewoud; Cornelus, Jelle; Pieters, Sam; Van den Bossche, Dries; Van der Eycken, Johan; Herrebout, Wouter; Bultinck, Patrick

    2013-10-07

    The absolute configuration of 5-(3-bromophenyl)-4-hydroxy-5-methylhexan-2-one, an intermediate in the synthesis of various natural products, is assigned by using vibrational circular dichroism (VCD), electronic circular dichroism (ECD), and optical rotatory dispersion (ORD). Experimental spectra were compared to density functional theory (DFT) calculations of the molecule with known configuration. These three techniques independently confirm that the absolute configuration is (S)-5-(3-bromophenyl)-4-hydroxy-5-methylhexan-2-one, thus enabling us to assign the absolute configuration with high reliability. The reliability of the VCD analysis was assessed quantitatively by using the CompareVOA program. We found that, in cases in which the agreement between theory and experiment was very good, a value of 10 cm(-1) for the triangular weighting function gave a more-realistic discriminative power between enantiomers than the default value of 20 cm(-1). Copyright © 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Preparation of polychlorinated isoxazoles and application to organic synthesis

    OpenAIRE

    Monasterolo, Claudio

    2016-01-01

    The work behind my doctoral thesis has been focused on the study of reactivity of 3,5-dimethyl-4-nitroisoxazole. This compound shows a peculiar reactivity compared to other isoxazole derivatives due to the presence of the nitro group in 4-position. The chemical behavior of 3,5-dimethyl-4-nitroisoxazole has been extensively studied in the last decade with the development of important applications in pharmaceutical chemistry in the preparation of valuable biologically active compounds. The i...

  18. Synthesis, Characterization and Antifungal Evaluation of 5-Substituted-4-Amino-1,2,4-Triazole-3-Thioesters

    Directory of Open Access Journals (Sweden)

    Aurangzeb Hasan

    2011-01-01

    Full Text Available A series of 5-substituted-4-amino-1,2,4-triazole-3-thioesters was synthesized by converting variously substituted organic acids successively into the corresponding esters, hydrazides, 5-substituted-1,3,4-oxadiazole-2-thiols, 5-substituted-1,2,4-triazole-2-thiols and 5-substituted-1,3,4-oxadiazole-2-thioesters. Finally the target compounds were obtained by refluxing 5-substituted-1,3,4-oxadiazole-2-thioesters in the presence of hydrazine hydrate and absolute alcohol. The structures of the synthesized compounds were established by physicochemical and spectroscopic methods. The synthesized compounds were evaluated for their in vitro antifungal activity. Some of the evaluated compounds possessed significant antifungal activity as compared to a terbinafine standard.

  19. Two new compounds from Helichrysum arenarium (L.).

    Science.gov (United States)

    Zhang, Yu-Wei; Sun, Wu-Xing; Li, Xian; Zhao, Chun-Chao; Meng, Da-Li; Li, Ning

    2009-01-01

    Two new compounds were isolated from the whole plant of Helichrysum arenarium (L.) Moench. By means of spectroscopic data (IR, UV, 1D and 2D NMR, HR-MS, ESI-MS, and NOESY) and chemical evidence, the structures were established as 6,7-dimethoxy-4-hydroxy-1-naphthoic acid (1) and (Z)-5-hydroxy-7-methoxy-4-[3-methyl-4-(O-beta-D-xylopyranosyl)but-2-enyl]isobenzofuran-1(3H)-one (2).

  20. Fatal intoxication with 3-methyl-N-methylcathinone (3-MMC) and 5-(2-aminopropyl)benzofuran (5-APB).

    Science.gov (United States)

    Adamowicz, Piotr; Zuba, Dariusz; Byrska, Bogumiła

    2014-12-01

    The emergence of a large number of new psychoactive substances (NPSs) in recent years poses a serious problem to clinical and forensic toxicologists. Here we report a patient who administrated ca. 500mg of 3-MMC (3-methyl-N-methylcathinone) and 400mg of 5-APB (5-(2-aminopropyl)benzofuran) in combination with 80g of ethyl alcohol. The clinical manifestations included agitation, seizures, hypertension, tachycardia, hyperthermia and bradycardia. The patient did not recover and died around 4h after the use of drugs. The cause of death was acute cardiovascular collapse that occurred following mixed intoxication with NPSs and alcohol. Toxicological analysis of post-mortem blood revealed 3-MMC and 5-APB in concentrations of 1.6μg/mL and 5.6μg/mL, respectively. Moreover, the serum alcohol concentration was 1.4g/L in ante-mortem sample collected 1h after admission to the hospital. This is the first report on blood concentration of 3-MMC and 5-APB in fatal intoxication. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  1. Radiosynthesis and biological evaluation of 5-(3-[18F]Fluoropropyloxy)-L-tryptophan for tumor PET imaging

    International Nuclear Information System (INIS)

    He, Shanzhen; Tang, Ganghua; Hu, Kongzhen; Wang, Hongliang; Wang, Shuxia; Huang, Tingting; Liang, Xiang; Tang, Xiaolan

    2013-01-01

    Introduction: [ 18 F]FDG PET has difficulty distinguishing tumor from inflammation in the clinic because of the same high uptake in nonmalignant and inflammatory tissue. In contrast, amino acid tracers do not accumulate in inflamed tissues and thus provide an excellent opportunity for their use in clinical cancer imaging. In this study, we developed a new amino acid tracer 5-(3-[ 18 F]Fluoropropyloxy)-L-tryptophan ([ 18 F]-L-FPTP) by two-step reactions and performed its biologic evaluation. Methods: [ 18 F]-L-FPTP was prepared by [ 18 F]fluoropropylation of 5-hydroxy-L-tryptophan disodium salt and purification on C18 cartridges. The biodistribution of [ 18 F]-L-FPTP was determined in normal mice and the incorporation of [ 18 F]-L-FPTP into tissue proteins was investigated. In vitro competitive inhibition experiments were performed with Hepa1-6 hepatoma cell lines. [ 18 F]-L-FPTP PET imaging was performed on tumor-bearing and inflammation mice and compared with [ 18 F]-L-FEHTP PET. Results: The overall uncorrected radiochemical yield of [ 18 F]-L-FPTP was 21.1 ± 4.4% with a synthesis time of 60 min, the radiochemical purity was more than 99%. Biodistribution studies demonstrate high uptake of [ 18 F]-L-FPTP in liver, kidney, pancreas, and blood at the early phase, and fast clearance in most tissues over the whole observed time. The uptake studies in Hepa1-6 cells suggest that [ 18 F]-L-FPTP is transported by the amino acid transport system B 0,+ , LAT2 and ASC. [ 18 F]-L-FPTP displays good stability and is not incorporated into proteins in vitro. PET imaging shows that [ 18 F]-L-FPTP can be a better potential PET tracer for differentiating tumor from inflammation than [ 18 F]FDG and 5-(3-[ 18 F]fluoroethyloxy)-L-tryptophan ([ 18 F]-L-FEHTP), with high [ 18 F]-L-FPTP uptake ratio (2.53) of tumor to inflammation at 60 min postinjection. Conclusions: Using [ 18 F]fluoropropyl derivatives as intermediates, the new tracer [ 18 F]-L-FPTP was achieved with good yield and

  2. Molecularly imprinted poly(4-amino-5-hydroxy-2,7-naphthalenedisulfonic acid) modified glassy carbon electrode as an electrochemical theophylline sensor.

    Science.gov (United States)

    Aswini, K K; Vinu Mohan, A M; Biju, V M

    2016-08-01

    Theophylline is an inexpensive drug employed in asthma and chronic obstructive pulmonary disorder medications and is toxic at higher concentration. The development of a molecularly imprinted polymer based theophylline electrochemical sensor on glassy carbon electrode by the electropolymerization of 4-amino-5-hydroxy-2,7-naphthalenedisulfonic acid is being discussed in this work. The MIP modification enhances the theophylline recognition ability and the electron transfer kinetics of the bare electrode. The parameters, controlling the performance of the imprinted polymer based sensor, like number of electropolymerization cycles, composition of the pre-polymerization mixture, pH and immersion time were investigated and optimized. The interaction energy and the most stable conformation of the template-monomer complex in the pre-polymerization mixture were determined computationally using ab initio calculations based on density functional theory. The amperometric measurements showed that the developed sensor has a method detection limit of 0.32μM for the dynamic range of 0.4 to 17μM, at optimized conditions. The transducer possesses appreciable selectivity in the presence of structurally similar interferents such as theobromine, caffeine and doxofylline. The developed sensor showed remarkable stability and reproducibility and was also successfully employed in theophylline detection from commercially available tablets. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. rac-1-[6-Hydroxy-4-(4-methoxyphenyl-3,6-dimethyl-4,5,6,7-tetrahydro-2H-indazol-5-yl]ethanone

    Directory of Open Access Journals (Sweden)

    Konstantin A. Potekhin

    2013-02-01

    Full Text Available The title compound, C18H22N2O3, represents a (4S,5R,6S-stereoisomer, crystallizing as a racemate in a centrosymmetric space group. The six-membered aliphatic ring adopts a half-chair conformation, with the hydroxy- and acetyl-substituted C atoms deviating by 0.458 (2 and −0.366 (2 Å, respectively, from the plane defined by other four ring atoms. The pyrazole ring is essentially planar [r.m.s deviation = 0.004 (2 Å]. In the crystal, the molecules are linked into chains along the b axis by N—H...N hydrogen bonds. The chains are linked by O—H...N hydrogen bonds into layers parallel to the bc plane.

  4. Prefrontal gamma-aminobutyric acid type A receptor insertion controls cue-induced relapse to nicotine seeking.

    Science.gov (United States)

    Lubbers, Bart R; van Mourik, Yvar; Schetters, Dustin; Smit, August B; De Vries, Taco J; Spijker, Sabine

    2014-11-01

    Current smoking cessation therapies offer limited success, as relapse rates remain high. Nicotine, which is the major component of tobacco smoke, is thought to be primarily responsible for the addictive properties of tobacco. However, little is known about the molecular mechanisms underlying nicotine relapse, hampering development of more effective therapies. The objective of this study was to elucidate the role of medial prefrontal cortex (mPFC) glutamatergic and gamma-aminobutyric acid (GABA)ergic receptors in controlling relapse to nicotine seeking. Using an intravenous self-administration model, we studied glutamate and gamma-aminobutyric acid receptor regulation in the synaptic membrane fraction of the rat mPFC following extinction and cue-induced relapse to nicotine seeking. Subsequently, we locally intervened at the level of GABAergic signaling by using a mimetic peptide of the GABA receptor associated protein-interacting domain of GABA type A (GABAA) receptor subunit γ2 (TAT-GABAγ2) and muscimol, a GABAA receptor agonist. Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid and N-methyl-D-aspartate receptors were not regulated after the 30-min relapse test. However, GABAA receptor subunits α1 and γ2 were upregulated, and interference with GABAA receptor insertion in the cell membrane using the TAT-GABAγ2 peptide in the dorsal mPFC, but not the ventral mPFC, significantly increased responding during relapse. Increasing GABAA transmission with muscimol in the dorsal and ventral mPFC attenuated relapse. These data indicate that cue-induced relapse entails a GABAergic plasticity mechanism that limits nicotine seeking by restoring inhibitory control in the dorsal mPFC. GABAA receptor-mediated neurotransmission in the dorsal mPFC constitutes a possible future therapeutic target for maintaining smoking abstinence. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  5. Antioxidant activity of salts of 2-(5-R-4-amino-1,2,4-triazole-3-ylthioacetic acid

    Directory of Open Access Journals (Sweden)

    Ye. S. Pruglo

    2017-12-01

    Full Text Available Antioxidants are chemical structures that prevent the oxidation of other chemicals. They protect key cell components by neutralizing the harmful effect of free radicals which are natural products of cell metabolism. Oxidative stress leads to serious cell damage which results in various human diseases such as Alzheimer's disease, Parkinson's disease, atherosclerosis, cancer, arthritis, neurodegenerative disorders etc. The deficiency of antioxidants in food also leads to oxidative stress, which indicates a lack of antioxidant substances consumed by humans. Therefore, the search of substances that could not only prevent but also increase the resistance of the human body to active forms of oxygen or nitrogen and interfere with the processes of oxidative stress is an important task of medicine and pharmacy. The purpose of this work was to study the antioxidant activity (AOA of salts of 2-(5-R-4-R-4H-1,2,4-triazole-3-ylthioacetic acids with non-enzymatic initiation of free radical oxidation and to establish laws concerning chemical structure and biological effects of the studied substances. Materials and methods. Original derivatives of 1,2,4-triazole were used in the series of screening studies. The antioxidant activity of the compounds in vitro was determined according to the methodical recommendations of the State Pharmacological Center MoH Ukraine using the method of non-enzymatic initiation of lipid peroxide oxidation. Results. Dimethylammonium salt of 2-(4-amino-5-(2-bromophenyl-1,2,4-triazole-3-ylthioacetic acid (3c possessed with a high AOA which reduced the content of TBK-AP by 54,95% ( р˂0,001. Derivatives of 4-amino-1,2,4-triazole had the most distinct AOA containing С5 carbon atoms 2-bromophenyl substituent. Thus, methylammonium salt 3b reduced the TBK-AP content by 80,31 (p˂0,001 which exceeds the reference ascorbic acid by 45,05% and the prototype thiotriazoline by 36,64%. Considering the data of experimental studies it was found

  6. Synthesis, antifungal activity and docking study of 2-amino-4H-benzochromene-3-carbonitrile derivatives

    Science.gov (United States)

    Mirjalili, BiBi Fatemeh; Zamani, Leila; Zomorodian, Kamiar; Khabnadideh, Soghra; Haghighijoo, Zahra; Malakotikhah, Zahra; Ayatollahi Mousavi, Seyyed Amin; Khojasteh, Shaghayegh

    2016-07-01

    Pathogenic fungi are associated with diseases ranging from simple dermatosis to life-threatening infections, particularly in immunocompromised patients. During the past two decades, resistance to established antifungal drugs has increased dramatically and has made it crucial to identify novel antimicrobial compounds. Here, we selected 12 new compounds of 2-amino-4H-benzochromene-3-carbonitrile drivetives (C1-C12) for synthesis by using nano-TiCl4.SiO2 as efficient and green catalyst, then nine of synthetic compounds were evaluated against different species of fungi, positive gram and negative gram of bacteria. Standard and clinical strains of antibiotics sensitive and resistant fungi and bacteria were cultured in appropriate media. Biological activity of the 2-amino-4H-benzochromene-3-carbonitrile derivatives against fungi and bacteries were estimated by the broth micro-dilution method as recommended by clinical and laboratory standard institute (CLSI). In addition minimal fangicidal and bactericial concenteration of the compounds were also determined. Considering our results showed that compound 2-amino-4-(4-methyl benzoate)-4H-benzo[f]chromen-3-carbonitrile (C9) had the most antifungal activity against Aspergillus clavatus, Candida glabarata, Candida dubliniensis, Candida albicans and Candida tropicalis at concentrations ranging from 8 to ≤128 μg/mL. Also compounds 2-amino-4-(3,4-dimethoxyphenyl)-4H-benzo[f]chromen-3-carbonitrile (C4) and 2-amino-4-(4-isopropylphenyl)-4H-benzo[f]chromen-3-carbonitrile (C3) had significant inhibitory activities against Epidermophyton floccosum following 2-amino-4-(4-methylbenzoate)-4H-benzo[f]chromen-3-carbonitrile (C9), respectively. Docking simulation was performed to insert compounds C3, C4 and C9 in to CYP51 active site to determine the probable binding model.

  7. Recent advances in isoxazole chemistry

    International Nuclear Information System (INIS)

    Galenko, A V; Khlebnikov, A F; Novikov, M S; Pakalnis, V V; Rostovskii, N V

    2015-01-01

    The preparation methods and reactions of isoxazoles are described and systematized on the basis of analysis of the literature published from 2005 to present. In the discussion of synthesis, major attention is focused on the most efficient approaches: condensation of hydroxylamine with 1,3-dielectrophiles and reactions of nitrile oxides with alkenes and alkynes. Five-membered ring opening reactions leading to acyclic functionalized or other heterocyclic compounds are considered. The transformations of isoxazole derivatives that occur without ring cleavage to form fused heterocyclic systems, as well as reactions that lead to the introduction of C-substituents into isoxazoles, are considered. Data on the biological activity of some isoxazole derivatives are reported. The bibliography includes 439 references

  8. Synthesis of carbasugars from aldonolactones, part III - A study on the allylic substitution of (1R,5R,8R)- and (1R,5R,8S)-8-hydroxy-2-oxabicyclo[3.3.0]oct-6-en-3-one derivatives - Preparation of (1S,2R,3R)-9-[2-hydroxy-3-(2-hydroxyethyl)cyclopent-4-en-1-yl]-9H-adenine

    DEFF Research Database (Denmark)

    Johansen, Steen Karsk; Lundt, Inge

    2001-01-01

    The palladium-catalyzed substitution of acylated (1R,5R,8R)- and (1R,SR,8S)-8-hydroxy-2-oxabicyclo[3.3.0] ones has been studied using a number of C- and N-nucleophiles, In all cases, the exo derivatives (8R) were found to be more reactive than the corresponding endo derivatives (8S). The reaction...... with these nucleophiles. Additionally, Mitsunobu substitution of (1R,5R,8R)-8-hydroxy-2-oxabicyclo[3.3.0]oct-B-en-3-one (3) with 6-chloropurine, followed by reduction of the lactone moiety and treatment with Liquid ammonia, gave the carbocyclic nucleoside (1S,2R,3R)-9-[2-hydroxy-3-(2-hydroxyethyl)cyclopent-4-en-1-yl]-9H...

  9. Effects of gamma radiation on the concentration of 5-hydroxy-L-tryptophan and 5-hydroxytryptamine in presence of radioprotector in Sprague Dawley rats

    International Nuclear Information System (INIS)

    Upadhyay, S.N.; Sharma, Ashok; Nagpal, K.K.; Saini, S.K.

    1997-01-01

    The result of variation of 5-hydroxy-L-tryptophan (HT) and 5-hydroxytryptamine (5-HT) in different tissues of control and gamma-irradiated Sprague Dawley rats with and without a radioprotector β-amino-ethylisothiuronium bromide hydrobromide (AET) combination e.g. (HT+AET) have been studied. The retention of HT, in the tissues studied, decreased after lethal dose (10.5 Gy) but for 5-HT, no such trend was observed after incorporation of HT+AET. A slight tendency of both metabolites to come back to control level was also observed for Sprague Dawley rats. In urine concentration of HT was less compared to 5-HT with a lethal dose (10.5 Gy). After incorporation of HT+AET the turnover rate of HT and 5-HT were found to be maximum when it was injected through intraperitoneal route. (author)

  10. Refined carbohydrate enhancement of aberrant crypt foci (ACF) in rat colon induced by the food-borne carcinogen 2-amino-3-methyl-imidazo[4,5-f]quinoline (IQ)

    DEFF Research Database (Denmark)

    Kristiansen, E.; Meyer, Otto A.; Thorup, I.

    1996-01-01

    ,2-dimethylhydrazine dihydrochloride (DMH) and azoxymethane (AOM), the use of a diet-related colon cancer initiator, such as the heterocyclic amine 2-amino-3-methyl-imidazo[4,5-f]quinoline (IQ) formed during meat cooking, would probably give a more relevant insight into diet-related colon carcinogenesis......The aberrant crypt foci (ACF) bioassay has been used extensively to study the early effects of different dietary components on the colonic mucosa of laboratory rodents. ACF are proposed to represent preneoplastic lesions of colon cancer. Compared to the normally used initiators 1....... In the present study it is shown that a feeding regimen with continuous low IQ doses (0.03% in the diet) throughout a study period of 10 weeks has a significant effect on the induction of ACF in the colon of male F344 rats. In addition, the study illustrates that the incidence of the IQ-induced ACF can...

  11. Scalable synthesis and isolation of the four stereoisomers of methyl 1-amino-3-(4-bromophenyl)cyclopentanecarboxylate, useful intermediates for the synthesis of S1P1 receptor agonists.

    Science.gov (United States)

    Wallace, Grier A; Gordon, Thomas D; Hayes, Martin E; Konopacki, Donald B; Fix-Stenzel, Shannon R; Zhang, Xiaolei; Grongsaard, Pintipa; Cusack, Kevin P; Schaffter, Lisa M; Henry, Rodger F; Stoffel, Robert H

    2009-07-03

    The individual isomers of methyl 1-amino-3-(4-bromophenyl)cyclopentanecarboxylate are useful intermediates for the synthesis of S1P1 receptor agonists. Herein we describe a scalable synthesis and isolation of each of the four stereoisomers of this compound in gram quantities with >98% ee and de. The utility of this approach is demonstrated by the synthesis of ((1R,3R)-1-amino-3-(4-octylphenyl)cyclopentyl)methanol in 7 steps, 11% overall yield, and >98% ee and de.

  12. Norepinephrine metabolism in man using deuterium labeling: turnover 4-hydroxy-3-methoxymandelic acid

    Energy Technology Data Exchange (ETDEWEB)

    Mardh, G.; Sjoequist, B.; Anggard, E.

    1982-06-01

    4-Hydroxy-3-methoxymandelic acid (HMMA; VMA) labeled with three deuterium atoms was used to study the turnover and fate of HMMA following intravenous injection. Five healthy men were given a pulse dose of 5.0 mumol of labeled HMMA. Plasma and urinary levels of both endogenous and labeled HMMA were subsequently followed by gas chromatography-mass spectrometry using selected ion detection. The kinetic parameters were determined both with and without compensation for the pool expansion caused by the injection of labeled HMMA. The urinary recovery of labeled HMMA was 85 +/- 10% (mean +/- SD). No conversion of HMMA to 4-hydroxy-3-methoxyphenyl glycol (HMPG) occurred. The biological half-life of HMMA was 0.54 +/- 0.22 h. The apparent volume of distribution was 0.36 +/- 0.11 L/kg. The production rate or body turnover was 1.27 +/- 0.51 mumol HMMA/h and urinary excretion rate was 0.82 +/- 0.22 mumol/h. These results show that HMMA is turnover over rapidly in a relatively small volume of distribution and that, unlike HMPG, it is an end metabolite of norepinephrine in man.

  13. Hexaaquabis[3,5-bis(hydroxyimino-1-methyl-2,4,6-trioxocyclohexanido-κ2N3,O4]barium tetrahydrate

    Directory of Open Access Journals (Sweden)

    Nguyen Dinh Do

    2013-11-01

    Full Text Available In the title compound, [Ba(C7H5N2O52(H2O6]·4H2O, the Ba2+ cation lies on a twofold rotation axis and is ten-coordinated by two 3,5-bis(hydroxyimino-1-methyl-2,4,6-trioxocyclohexanide oxo O atoms [Ba—O = 2.8715 (17 Å], two hydroxyimino N atoms [Ba—N = 3.036 (2 Å], and six water molecules [Ba—O = 2.847 (2, 2.848 (2, and 2.880 (2 Å]. The 3,5-bis(hydroxyimino-1-methyl-2,4,6-trioxocyclohexanide monoanions act in a bidentate chelating manner, coordinating through an N atom of the non-deprotonated hydroxyimino group and an O atom of the neighboring oxo group. Two lattice water molecules are located in the cavities of the framework and are involved in hydrogen bonding to O atoms of one of the coordinating water molecules and the O atom of a keto group of the ligand. As a result, a three-dimensional network is formed.

  14. Characterization of a Novel Nicotine Hydroxylase from Pseudomonas sp. ZZ-5 That Catalyzes the Conversion of 6-Hydroxy-3-Succinoylpyridine into 2,5-Dihydroxypyridine

    Directory of Open Access Journals (Sweden)

    Tao Wei

    2017-08-01

    Full Text Available A novel nicotine hydroxylase was isolated from Pseudomonas sp. ZZ-5 (HSPHZZ. The sequence encoding the enzyme was 1206 nucleotides long, and encoded a protein of 401 amino acids. Recombinant HSPHZZ was functionally overexpressed in Escherichia coli BL21-Codon Plus (DE3-RIL cells and purified to homogeneity after Ni-NTA affinity chromatography. Liquid chromatography-mass spectrometry (LC-MS analyses indicated that the enzyme could efficiently catalyze the conversion of 6-hydroxy-3-succinoylpyridine (HSP into 2,5-dihydroxypyridine (2,5-DHP and succinic acid in the presence of nicotinamide adenine dinucleotide (NADH and flavin adenine dinucleotide (FAD. The kinetic constants (Km, kcat, and kcat/Km of HSPHZZ toward HSP were 0.18 mM, 2.1 s−1, and 11.7 s−1 mM−1, respectively. The optimum temperature, pH, and optimum concentrations of substrate and enzyme for 2,5-DHP production were 30 °C, 8.5, 1.0 mM, and 1.0 μM, respectively. Under optimum conditions, 85.3 mg/L 2,5-DHP was produced in 40 min with a conversion of 74.9%. These results demonstrated that HSPHZZ could be used for the enzymatic production of 2,5-DHP in biotechnology applications.

  15. Effect of tibolone and its principal metabolites (3α- and 3β-hydroxy, 3α-sulfate, and 4-ene derivatives) on estrone sulfatase activity in normal and cancerous human breast tissue.

    Science.gov (United States)

    Chetrite, Gérard S; Cortes-Prieto, Joaquin; Pasqualini, Jorge R

    2011-12-01

    Tibolone (Org-OD14) is the active substance of Livial®, a synthetic steroid with the structure 7α,17α-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-yn-3-one, possessing weak tissue-specific estrogenic, progestogenic, and androgenic properties, used to treat menopausal complaints. After oral administration, tibolone is extensively metabolized into the 3α-(Org-4904) and 3β-(Org-30126) hydroxy derivatives with estrogenic properties, its 4-ene (Org-OM38) isomer with progestogenic/androgenic activities, and the 3α-sulfate (Org-34322) derivative, a major biologically inactive circulating form. We compared the dose response of tibolone and its metabolites on estrone sulfatase activity [conversion of estrone sulfate (E1S) to estrone (E1)] in normal and cancerous human breast tissues. Tissue minces were incubated with physiological concentrations of [3H]-E1S (5×10-9M) alone or in the presence of tibolone and its metabolites (concentration range: 5×10-7to 5×10-5M) for 4 h. Tritiated E1, estradiol (E2), and E1S were separated and evaluated quantitatively by thin-layer chromatography. The sulfatase activity was significantly higher in cancerous breast but strongly inhibited by tibolone and the different metabolites, whereas 3α- and 3β-hydroxy derivatives were the most potent inhibitors. This very significant inhibitory effect of tibolone and its principal metabolites on the enzyme involved in E2biosynthesis in the human breast provides interesting perspectives to study the biological responses of these compounds in trials with breast cancer patients.

  16. Synthesis and pharmacological evaluation of the individual stereoisomers of 3-[methyl(1,2,3,4-tetrahydro-2-naphthalenyl)amino]-1-indanone, a potent mast cell stabilising agent.

    Science.gov (United States)

    Byrne, Adam J; Barlow, James W; Walsh, John J

    2011-02-15

    Each stereoisomer of 3-[methyl(1,2,3,4-tetrahydro-2-naphthalenyl)amino]-1-indanone, 1a-d, was prepared and evaluated in vitro for its ability to prevent mediator release induced by different degranulating agents from rodent mast cells and also in vivo against passive cutaneous anaphylaxis. The manner in which the stereoisomers prevented direct membrane activation was found to be highly dependent on the stereochemistry of the individual isomers. Stereoisomer 1b was the most active isomer in vivo, exhibiting superior activity to disodium cromoglycate. Copyright © 2010 Elsevier Ltd. All rights reserved.

  17. Biomonitoring of urinary metabolites of 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) following human consumption of cooked chicken

    DEFF Research Database (Denmark)

    Frandsen, Henrik Lauritz

    2008-01-01

    Human risk assessment of exposure to 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) through the diet may be improved by conducting biomonitoring studies comparing metabolism in humans and rodents. Eleven volunteers ingested a meal of cooked chicken containing 4-OH-PhIP and PhIP in amounts...... for detoxification and the last a biomarker for activation. The eleven volunteers eliminated large amounts of 4'-OH-PhiP in the urine. The majority of which Could be accounted for by the presence of 4'-OH-PhIP in the fried chicken, showing that PhIP only to a small extent (11%) was metabolised to 4'-OH...

  18. Synthesis of 5α-Androstane-17-spiro-δ-lactones with a 3-Keto, 3-Hydroxy, 3-Spirocarbamate or 3-Spiromorpholinone as Inhibitors of 17β-Hydroxysteroid Dehydrogenases

    Directory of Open Access Journals (Sweden)

    Donald Poirier

    2013-01-01

    Full Text Available We synthesized two series of androstane derivatives as inhibitors of type 3 and type 5 17β-hydroxysteroid dehydrogenases (17β-HSDs. In the first series, four monospiro derivatives at position C17 were prepared from androsterone (ADT or epi-ADT. After the protection of the alcohol at C3, the C17-ketone was alkylated with the lithium acetylide of tetrahydro-2-(but-3-ynyl-2-H-pyran, the triple bond was hydrogenated, the protecting groups hydrolysed and the alcohols oxidized to give the corresponding 3-keto-17-spiro-lactone derivative. The other three compounds were generated from this keto-lactone by reducing the ketone at C3, or by introducing one or two methyl groups. In the second series, two dispiro derivatives at C3 and C17 were prepared from epi-ADT. After introducing a spiro-δ-lactone at C17 and an oxirane at C3, an aminolysis of the oxirane with L-isoleucine methyl ester provided an amino alcohol, which was treated with triphosgene or sodium methylate to afford a carbamate- or a morpholinone-androstane derivative, respectively. These steroid derivatives inhibited 17β-HSD3 (14–88% at 1 μM; 46–94% at 10 μM and 17β-HSD5 (54–73% at 0.3 μM; 91–92% at 3 μM. They did not produce any androgenic activity and did not bind steroid (androgen, estrogen, glucocorticoid and progestin receptors, suggesting a good profile for prostate cancer therapy.

  19. A General and Simple Diastereoselective Reduction by L-Selectride: Efficient Synthesis of Protected (4S,5S)-Dihydroxy Amides

    OpenAIRE

    Yin; Ye; Yu; Liu

    2010-01-01

    A general approach to (4S,5S)-4-benzyloxy-5-hydroxy-N-(4-methoxybenzyl) amides 10 based on a diastereoselective reduction of (5S,6RS)-6-alkyl-5-benzyloxy-6-hydroxy-2-piperidinones 6 and their tautomeric ring-opened keto amides 7 is described. The reduction with L-Selectride at -20 °C to room temperature afforded the products 10 in excellent yields and moderate to high syn-diastereoselectivities.

  20. A general and simple diastereoselective reduction by L-Selectride: efficient synthesis of protected (4S,5S)-dihydroxy amides.

    Science.gov (United States)

    Yin, Bo; Ye, Dong-Nai; Yu, Kai-Hui; Liu, Liang-Xian

    2010-04-16

    A general approach to (4S,5S)-4-benzyloxy-5-hydroxy-N-(4-methoxybenzyl) amides 10 based on a diastereoselective reduction of (5S,6RS)-6-alkyl-5-benzyloxy-6-hydroxy-2-piperidinones 6 and their tautomeric ring-opened keto amides 7 is described. The reduction with L-Selectride at -20 degrees C to room temperature afforded the products 10 in excellent yields and moderate to high syn-diastereoselectivities.

  1. 5,7-dihydroxy-2-(3-hydroxy-4, 5-dimethoxy-phenyl)-chromen-4-one-a flavone from Bruguiera gymnorrhiza displaying anti-inflammatory properties.

    Science.gov (United States)

    Barik, Rajib; Sarkar, Ratul; Biswas, Prova; Bera, Rammohan; Sharma, Soma; Nath, Suvadeep; Karmakar, Sanmoy; Sen, Tuhinadri

    2016-01-01

    Bruguiera gymnorrhiza (BRG) (L.) Lamk (Rhizophoraceae), a mangrove species, is widely distributed in the Pacific region, eastern Africa, Indian subcontinent, and subtropical Australia. The leaves of this plant are traditionally used for treating burns and inflammatory lesions. This study isolates the bioactive compound from the methanol extract of BRG leaves and evaluates the possible mechanisms of anti-inflammatory activity involved. Bioassay-guided fractionation of BRG was performed to identify the bioactive fraction (displaying inhibition of cyclooxygenase 2 [COX2] - 5-lipoxygenase (5-LOX) activities and tumor necrosis factor-alpha (TNF-α) production at the tested concentrations of 100 and 10 μg/ml). The fractionation was performed by solvent extraction and preparative high-performance liquid chromatography. The bioactive compound was characterized by ultraviolet-visible, liquid chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy. The antioxidant potential was evaluated by electron spin resonance spectrum of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical at 250 μM. The effect of the compound was also studied on TNF-α converting enzyme and nuclear factor kappa B (NF-κB) activities at the concentrations 100, 10 and 1 μg/ml. Bioassay-guided purification of BRG revealed the presence of a flavone (5,7-dihydroxy-2- [3-hydroxy-4,5-dimethoxy-phenyl]-chromen-4-one) of molecular weight 330Da. It demonstrated more than 80% inhibition against COX2, 5-LOX activities and TNF-α production at 100 μg/ml. It also displayed 40% inhibition against DPPH radical at the tested concentration along with 23.1% inhibition of NF-κB activity at 100 μg/ml. The isolated methoxy-flavone may play a predominant role in the anti-inflammatory properties displayed by BRG leaves. Such activity may involve multiple mechanisms, namely (a) modulation of oxidative stress (b) inhibition of arachidonic acid metabolism and (c) downregulation of pro-inflammatory cytokines

  2. Neurochemical and toxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 1-methyl-4-phenylpyridine to rat serotonin neurons in dissociated cell cultures

    International Nuclear Information System (INIS)

    Friedman, L.K.; Mytilineou, C.

    1990-01-01

    Dissociated cell cultures from the pontine area of embryonic rat brain were used to study the sensitivity of serotonin (5-hydroxy-tryptamine (5-HT)) neurons to the neurotoxins 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridine (MPP+). Treatment with MPTP (up to 100 microM) for 7 days did not cause degeneration of 5-HT neurons. A 50% inhibition of [3H]5-HT uptake caused by 100 microM MPTP was a direct effect on the 5-HT uptake carrier, reversed by washing for 7 days. Incubation of cultures with MPTP increased the intraneuronal levels of 5-HT and reduced the levels of 5-hydroxyindoleacetic acid, suggesting a reduction in 5-HT metabolism. MPTP reduced monoamine oxidase activity in the cultures, which probably led to the reduction in 5-HT metabolism. Exposure to MPP+ (0.5-10 microM) for 4 to 7 days decreased [3H]5-HT uptake and induced loss of neurons stained with antibodies against 5-HT. Comparison between 5-HT and dopamine (DA) neurons indicated a differential sensitivity to MPP+ toxicity with DA neurons being more susceptible. Analysis of the competition of MPP+ with the natural substrates for uptake sites of 5-HT and DA neurons demonstrated higher affinity of MPP+ for DA compared to 5-HT neurons. The lower affinity of MPP+ for 5-HT neurons could be responsible for the accumulation of lower MPP+ levels observed in pontine cultures and explain the resistance of 5-HT neurons to this toxin

  3. Diethylstilbestrol (DES)-stimulated hormonal toxicity is mediated by ERα alteration of target gene methylation patterns and epigenetic modifiers (DNMT3A, MBD2, and HDAC2) in the mouse seminal vesicle.

    Science.gov (United States)

    Li, Yin; Hamilton, Katherine J; Lai, Anne Y; Burns, Katherine A; Li, Leping; Wade, Paul A; Korach, Kenneth S

    2014-03-01

    Diethylstilbestrol (DES) is a synthetic estrogen associated with adverse effects on reproductive organs. DES-induced toxicity of the mouse seminal vesicle (SV) is mediated by estrogen receptor α (ERα), which alters expression of seminal vesicle secretory protein IV (Svs4) and lactoferrin (Ltf) genes. We examined a role for nuclear receptor activity in association with DNA methylation and altered gene expression. We used the neonatal DES exposure mouse model to examine DNA methylation patterns via bisulfite conversion sequencing in SVs of wild-type (WT) and ERα-knockout (αERKO) mice. The DNA methylation status at four specific CpGs (-160, -237, -306, and -367) in the Svs4 gene promoter changed during mouse development from methylated to unmethylated, and DES prevented this change at 10 weeks of age in WT SV. At two specific CpGs (-449 and -459) of the Ltf gene promoter, DES altered the methylation status from methylated to unmethylated. Alterations in DNA methylation of Svs4 and Ltf were not observed in αERKO SVs, suggesting that changes of methylation status at these CpGs are ERα dependent. The methylation status was associated with the level of gene expression. In addition, gene expression of three epigenetic modifiers-DNMT3A, MBD2, and HDAC2-increased in the SV of DES-exposed WT mice. DES-induced hormonal toxicity resulted from altered gene expression of Svs4 and Ltf associated with changes in DNA methylation that were mediated by ERα. Alterations in gene expression of DNMT3A, MBD2, and HDAC2 in DES-exposed male mice may be involved in mediating the changes in methylation status in the SV. Li Y, Hamilton KJ, Lai AY, Burns KA, Li L, Wade PA, Korach KS. 2014. Diethylstilbestrol (DES)-stimulated hormonal toxicity is mediated by ERα alteration of target gene methylation patterns and epigenetic modifiers (DNMT3A, MBD2, and HDAC2) in the mouse seminal vesicle. Environ Health Perspect 122:262-268; http://dx.doi.org/10.1289/ehp.1307351.

  4. Proton-transfer compounds of 8-hydroxy-7-iodoquinoline-5-sulfonic acid (ferron) with 4-chloroaniline and 4-bromoaniline.

    Science.gov (United States)

    Smith, Graham; Wermuth, Urs D; Healy, Peter C

    2007-07-01

    The crystal structures of the proton-transfer compounds of ferron (8-hydroxy-7-iodoquinoline-5-sulfonic acid) with 4-chloroaniline and 4-bromoaniline, namely 4-chloroanilinium 8-hydroxy-7-iodoquinoline-5-sulfonate monohydrate, C(6)H(7)ClN(+) x C(9)H(5)INO(4)S(-) x H(2)O, and 4-bromoanilinium 8-hydroxy-7-iodoquinoline-5-sulfonate monohydrate, C(6)H(7)BrN(+) x C(9)H(5)INO(4)S(-) x H(2)O, have been determined. The compounds are isomorphous and comprise sheets of hydrogen-bonded cations, anions and water molecules which are extended into a three-dimensional framework structure through centrosymmetric R(2)(2)(10) O-H...N hydrogen-bonded ferron dimer interactions.

  5. 4-(2,3-Dihydroxybenzylideneamino-3-methyl-1H-1,2,4-triazol-5(4H-one

    Directory of Open Access Journals (Sweden)

    Şamil Işık

    2009-12-01

    Full Text Available All the non-H atoms of the title compound, C10H10N4O3, are almost coplanar, the maximum deviation from planarity being 0.065 (3 Å. The dihedral angle between the aromatic rings is 1.66 (6°. The molecule adopts the enol–imine tautomeric form with an intramolecular hydrogen-bonding interaction between the Schiff base N atom and the hydroxy group. In the crystal, intermolecular N—H...O and O—H...O hydrogen bonds link the molecules into a three-dimensional network.

  6. Selective increases of AMPA, NMDA and kainate receptor subunit mRNAs in the hippocampus and orbitofrontal cortex but not in prefrontal cortex of human alcoholics

    Directory of Open Access Journals (Sweden)

    Zhe eJin

    2014-01-01

    Full Text Available Glutamate is the main excitatory transmitter in the human brain. Drugs that affect the glutamatergic signaling will alter neuronal excitability. Ethanol inhibits glutamate receptors. We examined the expression level of glutamate receptor subunit mRNAs in human post-mortem samples from alcoholics and compared the results to brain samples from control subjects. RNA from hippocampal dentate gyrus (HP-DG, orbitofrontal cortex (OFC, and dorso-lateral prefrontal cortex (DL-PFC samples from 21 controls and 19 individuals with chronic alcohol dependence were included in the study. Total RNA was assayed using quantitative RT-PCR. Out of the 16 glutamate receptor subunits, mRNAs encoding two AMPA (2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-ylpropanoic acid receptor subunits GluA2 and GluA3; three kainate receptor subunits GluK2, GluK3 and GluK5 and five NMDA (N-methyl-D-aspartate receptor subunits GluN1, GluN2A, GluN2C, GluN2D and GluN3A were significantly increased in the HP-DG region in alcoholics. In the OFC, mRNA encoding the NMDA receptor subunit GluN3A was increased, whereas in the DL-PFC, no differences in mRNA levels were observed. Our laboratory has previously shown that the expression of genes encoding inhibitory GABA-A receptors is altered in the HP-DG and OFC of alcoholics (Jin et al., 2011. Whether the changes in one neurotransmitter system drives changes in the other or if they change independently is currently not known. The results demonstrate that excessive long-term alcohol consumption is associated with altered expression of genes encoding glutamate receptors in a brain region-specific manner. It is an intriguing possibility that genetic predisposition to alcoholism may contribute to these gene expression changes.

  7. Extraction of hafnium by 1-phenyl-3-methyl-4-benzoyl-5-pyralozone from aqueous-alcoholic solutions

    International Nuclear Information System (INIS)

    Hala, J.; Prihoda, J.

    1975-01-01

    Extraction of hafnium by 1-phenyl-3-methyl-4-benzoyl-5-pyrazolone (HL) in benzene, toluene, chloroform and tetrachloromethane from aqueous-alcoholic solutions of the formal acidity of 2M-HClO 4 was studied. Methyl, ethyl, n- and isopropyl, tert-butyl and allyl alcohol as well as ethylene glycol monomethyl ether and propylene glycol were used as organic components of the mixed aqueous-organic phase. Their presence in some cases resulted in a synergic increase in the distribution ratio of hafnium. The increase is interpreted using the results of a slope analysis and measurements of the alcohol distribution and the relative permittivity of the organic phase. It is suggested that HfL 4 molecules were solvated by alcohol molecules in the organic phase. At high alcohol concentration synergism changed into antagonism. This was caused by changes in the distribution of HL and its interaction with the alcohol in the organic phase. (author)

  8. Synthesis, characterization and crystal structure of (2RS,4R)-2-(2-hydroxy-3-methoxyphenyl)thiazolidine-4-carboxylic acid

    Science.gov (United States)

    Muche, Simon; Müller, Matthias; Hołyńska, Małgorzata

    2018-03-01

    The condensation reaction of ortho-vanillin and L-cysteine leads to formation of a racemic mixture of (2RS,4R)-2-(2-hydroxy-3-methoxyphenyl)thiazolidine-4-carboxylic acid and not, as reported in the available literature, to a Schiff base. The racemic mixture was fully characterized by 1D and 2D NMR techniques, ESI-MS and X-ray diffraction. Addition of ZnCl2 led to formation of crystals in form of colorless needles, suitable for X-ray diffraction studies. The measured crystals were identified as the diastereomer (2R,4R)-2-(2-hydroxy-3-methoxyphenyl)thiazolidine-4-carboxylic acid 1. The bulk material is racemic. Thiazolidine exists as zwitterion in solid state, as indicated by the crystal structure.

  9. Permeability and toxicity characteristics of L-cysteine and 2-methyl-thiazolidine-4-carboxylic acid in Caco-2 cells.

    Science.gov (United States)

    Kartal-Hodzic, Alma; Marvola, Tuuli; Schmitt, Mechthild; Harju, Kirsi; Peltoniemi, Marikki; Sivén, Mia

    2013-01-01

    Acetaldehyde is a known mutagenic substance and has been classified as a group-one carcinogen by the WHO. It is possible to bind acetaldehyde locally in the gastrointestinal (GI) tract with the semi-essential amino acid l-cysteine, which reacts covalently with acetaldehyde and forms compound 2-methyl-thiozolidine-4-carboxylic acid (MTCA). The Caco-2 cell line was used to determine the permeation of l-cysteine and MTCA, as well as the possible cell toxicity of both substances. Neither of the substances permeated through the Caco-2 cells at the concentrations used in this study, and only the highest concentration of MTCA affected the viability of the cells in the MTT (3-[4,5-dimethylthiazol-2yl]-2,5-diphenyltetrazolium bromide) test. These results showed that when l-cysteine is administered in formulations releasing it locally in the lower parts of GI tract, it is not absorbed but can react with acetaldehyde, and that neither l-cysteine nor MTCA is harmful to the cells when present locally in the upper parts of GI tract. This study also shows that MTCA is sensitive at a lower pH of 5.5. Since stable MTCA is desired in different parts of the GI tract, this observation raises concern over the influence of lower pH on l-cysteine-containing product ability to bind and eliminate carcinogenic acetaldehyde.

  10. A General and Simple Diastereoselective Reduction by L-Selectride: Efficient Synthesis of Protected (4S,5S-Dihydroxy Amides

    Directory of Open Access Journals (Sweden)

    Bo Yin

    2010-04-01

    Full Text Available A general approach to (4S,5S-4-benzyloxy-5-hydroxy-N-(4-methoxybenzyl amides 10 based on a diastereoselective reduction of (5S,6RS-6-alkyl-5-benzyloxy-6-hydroxy-2-piperidinones 6 and their tautomeric ring-opened keto amides 7 is described. The reduction with L-Selectride at -20 °C to room temperature afforded the products 10 in excellent yields and moderate to high syn-diastereoselectivities.

  11. SSR240612 [(2R)-2-[((3R)-3-(1,3-benzodioxol-5-yl)-3-[[(6-methoxy-2-naphthyl)sulfonyl]amino]propanoyl)amino]-3-(4-[[2R,6S)-2,6-dimethylpiperidinyl]methyl]phenyl)-N-isopropyl-N-methylpropanamide hydrochloride], a new nonpeptide antagonist of the bradykinin B1 receptor: biochemical and pharmacological characterization.

    Science.gov (United States)

    Gougat, Jean; Ferrari, Bernard; Sarran, Lionel; Planchenault, Claudine; Poncelet, Martine; Maruani, Jeanne; Alonso, Richard; Cudennec, Annie; Croci, Tiziano; Guagnini, Fabio; Urban-Szabo, Katalin; Martinolle, Jean-Pierre; Soubrié, Philippe; Finance, Olivier; Le Fur, Gérard

    2004-05-01

    The biochemical and pharmacological properties of a novel non-peptide antagonist of the bradykinin (BK) B(1) receptor, SSR240612 [(2R)-2-[((3R)-3-(1,3-benzodioxol-5-yl)-3-[[(6-methoxy-2-naphthyl)sulfonyl]amino]propanoyl)amino]-3-(4-[[2R,6S)-2,6-dimethylpiperidinyl]methyl]phenyl)-N-isopropyl-N-methylpropanamide hydrochloride] were evaluated. SSR240612 inhibited the binding of [(3)H]Lys(0)-des-Arg(9)-BK to the B(1) receptor in human fibroblast MRC5 and to recombinant human B(1) receptor expressed in human embryonic kidney cells with inhibition constants (K(i)) of 0.48 and 0.73 nM, respectively. The compound selectivity for B(1) versus B(2) receptors was in the range of 500- to 1000-fold. SSR240612 inhibited Lys(0)-desAr(9)-BK (10 nM)-induced inositol monophosphate formation in human fibroblast MRC5, with an IC(50) of 1.9 nM. It also antagonized des-Arg(9)-BK-induced contractions of isolated rabbit aorta and mesenteric plexus of rat ileum with a pA(2) of 8.9 and 9.4, respectively. Antagonistic properties of SSR240612 were also demonstrated in vivo. SSR240612 inhibited des-Arg(9)-BK-induced paw edema in mice (3 and 10 mg/kg p.o. and 0.3 and 1 mg/kg i.p.). Moreover, SSR240612 reduced capsaicin-induced ear edema in mice (0.3, 3 and 30 mg/kg p.o.) and tissue destruction and neutrophil accumulation in the rat intestine following splanchnic artery occlusion/reperfusion (0.3 mg/kg i.v.). The compound also inhibited thermal hyperalgesia induced by UV irradiation (1 and 3 mg/kg p.o.) and the late phase of nociceptive response to formalin in rats (10 and 30 mg/kg p.o.). Finally, SSR240612 (20 and 30 mg/kg p.o.) prevented neuropathic thermal pain induced by sciatic nerve constriction in the rat. In conclusion, SSR240612 is a new, potent, and orally active specific non-peptide bradykinin B(1) receptor antagonist.

  12. Ethyl 4-chloro-2′-fluoro-3-hydroxy-5-methylbiphenyl-2-carboxylate

    Directory of Open Access Journals (Sweden)

    Muhammad Adeel

    2011-09-01

    Full Text Available In the title compound, C16H14ClFO3, the dihedral angle between the mean planes of the two benzene rings is 71.50 (5°. Due to an intramolecular O—H...O hydrogen bond between the hydroxy group and the carbonyl O atom of the ethyl ester group, the ethyl ester group lies within the ring plane. The crystal structure is consolidated by intermolecular C—H...O and C—H...F interactions.

  13. 2-[N-(3-Amino-4-nitrophenylcarboximidoyl]phenol

    Directory of Open Access Journals (Sweden)

    Gholam Hossein Shahverdizadeh

    2011-11-01

    Full Text Available The title compound, C13H11N3O3, is essentially planar (r.m.s. for the 19 non-H atoms = 0.031 Å, a conformation stabilized in part by intramolecular O—H...N and N—H...O hydrogen bonds. The configuration about the imine bond [1.2919 (12 Å] is E. The presence of N—H...O(nitro hydrogen bonds leads to the formation of supramolecular tapes in the crystal structure. These are connected into layers by π–π interactions [centroid–centroid distance = 3.6046 (6 Å] occurring between the hydroxy- and amino-substituted benzene rings.

  14. Wet, Carbonaceous Asteroids: Altering Minerals, Changing Amino Acids

    Science.gov (United States)

    Taylor, G. J.

    2011-04-01

    Many carbonaceous chondrites contain alteration products from water-rock interactions at low temperature and organic compounds. A fascinating fact known for decades is the presence in some of them of an assortment of organic compounds, including amino acids, sometimes called the building blocks of life. Murchison and other CM carbonaceous chondrites contain hundreds of amino acids. Early measurements indicated that the amino acids in carbonaceous chondrites had equal proportions of L- and D-structures, a situation called racemic. This was in sharp contrast to life on Earth, which heavily favors L- forms. However, beginning in 1997, John Cronin and Sandra Pizzarello (Arizona State University) found L- excesses in isovaline and several other amino acids in the Murchison carbonaceous chondrite. In 2009, Daniel Glavin and Jason Dworkin (Astrobiology Analytical Lab, Goddard Space Flight Center) reported the first independent confirmation of L-isovaline excesses in Murchison using a different analytical technique than employed by Cronin and Pizzarello. Inspired by this work, Daniel Glavin, Michael Callahan, Jason Dworkin, and Jamie Elsila (Astrobiology Analytical Lab, Goddard Space Flight Center), have done an extensive study of the abundance and symmetry of amino acids in carbonaceous chondrites that experienced a range of alteration by water in their parent asteroids. The results show that amino acids are more abundant in the less altered meteorites, implying that aqueous processing changes the mix of amino acids. They also confirmed the enrichment in L-structures of some amino acids, especially isovaline, confirming earlier work. The authors suggest that aqueously-altered planetesimals might have seeded the early Earth with nonracemic amino acids, perhaps explaining why life from microorganisms to people use only L- forms to make proteins. The initial imbalance caused by non-biologic processes in wet asteroids might have been amplified by life on Earth. Alternatively

  15. 3'-Hydroxy-3,4'-dimethoxyflavone blocks tubulin polymerization and is a potent apoptotic inducer in human SK-MEL-1 melanoma cells.

    Science.gov (United States)

    Estévez-Sarmiento, Francisco; Said, Mercedes; Brouard, Ignacio; León, Francisco; García, Celina; Quintana, José; Estévez, Francisco

    2017-11-01

    Flavonoids are naturally occurring polyphenolic compounds and are among the most promising anticancer agents. A series of flavonols and their 3-methyl ether derivatives were synthesized and assessed for cytotoxicity. It was found that 3'-hydroxy-3,4'-dimethoxyflavone (flavonoid 7a) displayed strong cytotoxicity against human SK-MEL-1 melanoma cells and blocked tubulin polymerization, but had no significant cytotoxic effects against quiescent or proliferating human peripheral blood mononuclear cells. Our analyses showed that flavonoid 7a induces G 2 -M cell cycle arrest and apoptosis in melanoma cells which is associated with cytochrome c release and activation of both extrinsic and intrinsic apoptotic pathways of cell death. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Nootropic agents enhance the recruitment of fast GABAA inhibition in rat neocortex.

    Science.gov (United States)

    Ling, Douglas S F; Benardo, Larry S

    2005-07-01

    It is widely believed that nootropic (cognition-enhancing) agents produce their therapeutic effects by augmenting excitatory synaptic transmission in cortical circuits, primarily through positive modulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate receptors (AMPARs). However, GABA-mediated inhibition is also critical for cognition, and enhanced GABA function may be likewise therapeutic for cognitive disorders. Could nootropics act through such a mechanism as well? To address this question, we examined the effects of nootropic agents on excitatory and inhibitory postsynaptic currents (EPSCs and IPSCs) recorded from layer V pyramidal cells in acute slices of somatosensory cortex. Aniracetam, a positive modulator of AMPA/kainate receptors, increased the peak amplitude of evoked EPSCs and the amplitude and duration of polysynaptic fast IPSCs, manifested as a greater total charge carried by IPSCs. As a result, the EPSC/IPSC ratio of total charge was decreased, representing a shift in the excitation-inhibition balance that favors inhibition. Aniracetam did not affect the magnitude of either monosynaptic IPSCs (mono-IPSCs) recorded in the presence of excitatory amino acid receptor antagonists, or miniature IPSCs (mIPSCs) recorded in the presence of tetrodotoxin. However, the duration of both mono-IPSCs and mIPSCs was prolonged, suggesting that aniracetam also directly modulates GABAergic transmission. Cyclothiazide, a preferential modulator of AMPAR function, enhanced the magnitude and duration of polysynaptic IPSCs, similar to aniracetam, but did not affect mono-IPSCs. Concanavalin A, a kainate receptor modulator, had little effect on EPSCs or IPSCs, suggesting there was no contribution from kainate receptor activity. These findings indicate that AMPAR modulators strengthen inhibition in neocortical pyramidal cells, most likely by altering the kinetics of AMPARs on synaptically connected interneurons and possibly by modulating GABA(A) receptor responses

  17. Solid-phase synthesis of isoxazoles using vinyl ethers as chameleon catches.

    Science.gov (United States)

    Barrett, A G; Procopiou, P A; Voigtmann, U

    2001-10-04

    [reaction: see text] Regioselective 1,3-dipolar cycloadditions of supported vinyl ethers R(1)C(=CH(2))O-CH(2)-polymer, prepared by the Tebbe olefination of R(1)CO(2)-CH(2)-polymer, with ethyl cyanoformate N-oxide gave supported isoxazoline derivatives. Release from the support under mild acidic conditions gave the isoxazoles ethyl 5-R(1)-isoxazole-3-carboxylates. Alternatively, further on-resin functionalization of the R(1) substituent using Suzuki coupling reactions and release from the support under acidic conditions gave more structurally diverse isoxazoles.

  18. Analgesic Activity of Some 1,2,4-Triazole Heterocycles Clubbed with Pyrazole, Tetrazole, Isoxazole and Pyrimidine

    OpenAIRE

    Gajanan Khanage, Shantaram; Raju, Appala; Baban Mohite, Popat; Bhanudas Pandhare, Ramdas

    2013-01-01

    Purpose: In the present study in vivo analgesic activity of some previously synthesized 1,2,4-triazole derivatives containing pyrazole, tetrazole, isoxazole and pyrimidine ring have been evaluated. Methods: Acetic acid induced writhing method and Hot plate method has been described to study analgesic activity of some 1,2,4-triazole derivatives containing pyrazole, tetrazole, isoxazole and pyrimidine as a pharmacological active lead. Results: Thirty six different derivatives con...

  19. Use of 3-(4-hydroxyphenyl)propionic acid as electron donating compound in a potentiometric aflatoxin M1-immunosensor

    International Nuclear Information System (INIS)

    Rameil, Steffen; Schubert, Peter; Grundmann, Peter; Dietrich, Richard; Maertlbauer, Erwin

    2010-01-01

    We developed a potentiometric aflatoxin M 1 -immunosensor which utilizes 3-(4-hydroxyphenyl)propionic acid (p-HPPA) as electron donating compound for horseradish peroxidase (HRP; EC 1.11.1.7). The assay system consists of a polypyrrole-surface-working electrode coated with a polyclonal anti-M 1 antibody (pAb-AFM 1 ), a Ag/AgCl reference electrode and a HRP-aflatoxin B 1 conjugate (HRP-AFB 1 conjugate). To optimize the potentiometric measuring system p-HPPA as well as related compounds serving as electron donating compounds were compared. Also the influence of different buffer systems, varying pH and substrate concentrations on signal intensity was investigated. Our results suggest that reaction conditions that favor the formation of Pummerer's type ketones lead to an increase in signal intensity rather than formation of fluorescent dye. Comparison with commercial ready-to-use HRP electron donating compounds such as 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS), o-phenylenediamine (OPD) or 3,3',5,5'-tetramethylbenzidine (TMB) showed that only 34%, 77% and 49% of the signal intensity of p-HPPA were reached, respectively. The optimized assay had a detection limit of 40 pg mL -1 and allowed detection of 500 pg mL -1 (FDA action limit) aflatoxin M 1 (AFM 1 ) in pasteurized milk and UHT-milk containing 0.3-3.8% fat within 10 min without any sample treatment. The working range was between 250 and 2000 pg mL -1 AFM 1 .

  20. Substituted 4-hydroxy-1,2,3-triazoles

    DEFF Research Database (Denmark)

    Pippione, Agnese C.; Dosio, Franco; Ducime, Alex

    2015-01-01

    the distal (S)-glutamic acid carboxyl group using the 4-hydroxy-1,2,3-triazole moiety is applied, to obtain two promising glutamate analogs. In the second example, a scaffold hopping approach is applied, replacing the phenolic moiety present in MDG-1-33A, a potent inhibitor of Onchocerca volvulus chitinase...

  1. Structural studies on Mannich bases of 2-Hydroxy-3,4,5,6-tetrachlorobenzene. An UV, IR, NMR and DFT study. A mini-review

    DEFF Research Database (Denmark)

    Hansen, Poul Erik; Spanget-Larsen, Jens

    2016-01-01

    Mannich bases of 2-Hydroxy-3,4,5,6-tetrachlorobenzene are chosen as an exemplary case for tautomeric Mannich bases. Molecular structures are calculated. OH stretching frequencies are rationalized based on DFT calculations. Intrinsic deuterium isotope effects on 13C chemical shifts in the M-form a...

  2. Cytotoxic, Antiproliferative and Pro-Apoptotic Effects of 5-Hydroxyl-6,7,3′,4′,5′-Pentamethoxyflavone Isolated from Lantana ukambensis

    Directory of Open Access Journals (Sweden)

    Wamtinga Richard Sawadogo

    2015-12-01

    Full Text Available Lantana ukambensis (Vatke Verdc. is an African food and medicinal plant. Its red fruits are eaten and highly appreciated by the rural population. This plant was extensively used in African folk medicinal traditions to treat chronic wounds but also as anti-leishmanial or cytotoxic remedies, especially in Burkina Faso, Tanzania, Kenya, or Ethiopia. This study investigates the in vitro bioactivity of polymethoxyflavones extracted from a L. ukambensis as anti-proliferative and pro-apoptotic agents. We isolated two known polymethoxyflavones, 5,6,7,3′,4′,5′-hexamethoxyflavone (1 and 5-hydroxy-6,7,3′,4′,5′-pentamethoxyflavone (2 from the whole plant of L. ukambensis. Their chemical structures were determined by spectroscopic analysis and comparison with published data. These molecules were tested for the anti-proliferative, cytotoxic and pro-apoptotic effects on human cancer cells. Among them, 5-hydroxy-6,7,3′,4′,5′-pentamethoxyflavone (2 was selectively cytotoxic against monocytic lymphoma (U937, acute T cell leukemia (Jurkat, and chronic myelogenous leukemia (K562 cell lines, but not against peripheral blood mononuclear cells (PBMCs from healthy donors, at all tested concentrations. Moreover, this compound exhibited significant anti-proliferative and pro-apoptotic effects against U937 acute myelogenous leukemia cells. This study highlights the anti-proliferative and pro-apoptotic effects of 5-hydroxy-6,7,3′,4′,5′-pentamethoxyflavone (2 and provides a scientific basis of traditional use of L. ukambensis.

  3. Association of Cognitive Impairment in Patients on 3-Hydroxy-3-Methyl-Glutaryl-CoA Reductase Inhibitors.

    Science.gov (United States)

    Roy, Satyajeet; Weinstock, Joshua Louis; Ishino, Allyse Sachiko; Benites, Jefferson Felix; Pop, Samantha Rachel; Perez, Christopher David; Gumbs, Edvard Adrian; Rosenbaum, Jennifer Ann; Roccato, Mary Kate; Shah, Hely; Contino, Gabriela; Hunter, Krystal

    2017-07-01

    Atherosclerotic cardiovascular diseases are the leading cause of death in the United States. A reduction in cholesterol with 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors (statin) significantly reduces mortality and morbidity. Statins may be associated with cognitive impairment or dementia. Our aim was to study the association of cognitive impairment or dementia in patients who were on a statin. Electronic medical records of 3,500 adult patients in our suburban internal medicine office were reviewed. There were 720 (20.6%) patients in the statin treatment group. Dementia or cognitive impairment was an associated comorbid condition in 7.9% patients in the statin treatment group compared to 3.1% patients in the non-statin group (P impairment or dementia showed that among the age ranges of 51 years through 100 years, the patients in the statin treatment group had a higher prevalence of cognitive impairment or dementia compared to the non-statin group. In the statin treatment group, we found significantly higher prevalence of hyperlipidemia (86.3%), hypertension (69.6%), diabetes mellitus (36.0%), osteoarthritis (31.5%), coronary artery disease (26.1%), hypothyroidism (21.5%) and depression (19.3%) compared to the non-statin group (P impairment were on statin therapy compared to 18.9% patients who had no dementia or cognitive impairment and were on statin therapy (P impairment with each year increase in age (1.3 times), in women (2.2 times), African American race (2.7 times), non-consumption of moderate amount of alcohol (two times), diabetes mellitus (1.6 times), hypothyroidism (1.7 times), cerebrovascular accident (3.2 times), and other rheumatological diseases (1.8 times). The association of dementia or cognitive impairment was significantly higher in the patients who were on statin therapy compared to the patients who were not on a statin.

  4. Synthesis of [[sup 123]I]tert-Butyl 8-iodo-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiaze pine 3-carboxylate, a potential SPECT imaging agent for diazepam-intensive (DI) benzodiazepine receptors

    Energy Technology Data Exchange (ETDEWEB)

    He, Xiaoshu; Matecka, Dorota; Gu, Ziqiang; Rice, K C; Costa, B.R. de [National Inst. of Diabetes and Digestive and Kidney Diseases, Bethesda, MD (United States); Lee, K S [National Inst. of Mental Health, Washington, DC (United States); Wong, Garry; Skolnick, Phil [National Inst. of Diabetes and Digestive and Kidney Diseases, Bethesda, MD (United States). Lab. of Neuroscience

    1994-01-01

    [[sup 123]I]tert-Butyl 8-iodo-5,6-dihydro-5-methyl-6-oxo-4H-imidazo [1,5-a] [1,4]benzodiazepine 3-carboxylate ([[sup 123]I]3), a high affinity and selective radioligand for the diazepam insensitive (DI) benzodiazepine receptor was synthesized in 2 steps from tert-butyl 8-bromo-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiaz epine 3-carboxylate. (Author).

  5. Crystal structure of ethyl (4R-2-amino-7-hydroxy-4-phenyl-4H-chromene-3-carboxylate

    Directory of Open Access Journals (Sweden)

    Joel T. Mague

    2015-07-01

    Full Text Available In the title compound, C18H17NO4, the dihedral angle between the phenyl ring and the fused six-membered ring is 77.65 (4°. The conformation of the molecule is determined in part by an intramolecular N—H...O hydrogen bond between the amino H atom and the carbonyl O atom, forming an S(6 motif. In the crystal, molecules are linked into N—H...O hydrogen-bonded inversion dimers which are then connected into chains along [001], forming a two-dimensional network parallel to (100 via O—H...O hydrogen bonds. C—H...O interactions further contribute to the crystal stability. The ethyl group is disordered over two sets of sites in a 0.801 (5:0.199 (5 ratio.

  6. Fermentable soluble fibres spare amino acids in healthy dogs fed a low-protein diet.

    Science.gov (United States)

    Wambacq, Wendy; Rybachuk, Galena; Jeusette, Isabelle; Rochus, Kristel; Wuyts, Brigitte; Fievez, Veerle; Nguyen, Patrick; Hesta, Myriam

    2016-06-28

    Research in cats has shown that increased fermentation-derived propionic acid and its metabolites can be used as alternative substrates for gluconeogenesis, thus sparing amino acids for other purposes. This amino acid sparing effect could be of particular interest in patients with kidney or liver disease, where this could reduce the kidneys'/liver's burden of N-waste removal. Since dogs are known to have a different metabolism than the obligatory carnivorous cat, the main objective of this study was to assess the possibility of altering amino acid metabolism through intestinal fermentation in healthy dogs. This was studied by supplementing a low-protein diet with fermentable fibres, hereby providing an initial model for future studies in dogs suffering from renal/liver disease. Eight healthy dogs were randomly assigned to one of two treatment groups: sugar beet pulp and guar gum mix (SF: soluble fibre, estimated to mainly stimulate propionic acid production) or cellulose (IF: insoluble fibre). Treatments were incorporated into a low-protein (17 %) extruded dry diet in amounts to obtain similar total dietary fibre (TDF) contents for both diets (9.4 % and 8.2 % for the SF and IF diet, respectively) and were tested in a 4-week crossover feeding trial. Apparent faecal nitrogen digestibility and post-prandial fermentation metabolites in faeces and plasma were evaluated. Dogs fed the SF diet showed significantly higher faecal excretion of acetic and propionic acid, resulting in a higher total SCFA excretion compared to IF. SF affected the three to six-hour postprandial plasma acylcarnitine profile by significantly increasing AUC of acetyl-, propionyl-, butyryl- + isobutyryl-, 3-OH-butyryl-, 3-OH-isovaleryl- and malonyl-L-carnitine. Moreover, the amino acid plasma profile at that time was modified as leucine + isoleucine concentrations were significantly increased by SF, and a similar trend for phenylalanine and tyrosine's AUC was found. These results indicate

  7. Pulse radiolytic one-electron reduction of 1,4-amino and hydroxy disubstituted 9,10-anthraquinones

    International Nuclear Information System (INIS)

    Pal, H.; Palit, D.K.; Mukherjee, T.; Mittal, J.P.

    1992-01-01

    The semiquinone radicals produced by one-electron reduction of 1-amino-4-hydroxy-9,10-anthraquinone and 1,4-diamino-9,10-anthraquinone have been studied in aqueous-organic mixed solvent using pulse radiolysis technique. Spectroscopic characteristics, kinetic characteristics of formation and decay, acid/base behaviour and redox characteristics of the semiquinones have been investigated and compared with those of some similar systems studied earlier. It has been shown that the variation of the disproportionation equilibria involving the reduced semiquinone radicals, the parent quinone and the fully reduced hydroquinone with pH of the solutions follow a similar trend as observed in the case of other dihydroxy quinones. Stability of the semiquinones over a broad pH range and their thermodynamic properties have been correlated. (Author)

  8. Methyl mercury uptake across bovine brain capillary endothelial cells in vitro: The role of amino acids

    International Nuclear Information System (INIS)

    Aschner, M.; Clarkson, T.W.

    1989-01-01

    Previous studies in the rat in vivo have demonstrated that co-injection of methyl mercury (MeHg) with L-cysteine into the common carotid artery enhances brain Hg levels folowing a single capillary pass through the CNS vasculature. In order to elucidate the relationship between MeHg transport and the neutral amino acid transport carrier system, regulatory aspects of MeHg transport across the bovine blood-brain barrier were investigated in isolated brain microvessel preparations. Following 1 hour co-incubations of 203 Hg-MeHgCl with 0.1 mM L-cysteine at 37 deg. C, 203 Hg uptake by suspended microvessels was significantly increased (P 203 Hg was abolished by co-incubations of microvessels with 0.1 mM L-cysteine-L-methionine, or 0.1 mM L-cysteine plus AT-125 (alpha S, 5S)-alpha-amino-3-chloro-4,5-dihydro-5-isoxazolacetic acid), an irreversible inhibitor of gamma-glutamyl-transpeptidase. One hr co-incubations of bovine capilaries with 203 Hg-MeHgCl and 0.1 mM D-cysteine at 37 deg. C or 0.1 mM L-cysteine at 0 deg. did not increase rat of 203 Hg uptake compared with controls. These results indicate that L-cysteine enhances the rate of capillary MeHg uptake. The accumulation of 203 Hg in the bovine microvessels appears to be a carrier-mediated process. It is inhibited by L-methionin, a competitive substrate for neutral amino acid transport, and by AT-125. Capillary uptake of 203 Hg is stereospecific to the L-enantiomorph of cystine, suggesting selective uptake of MeHg across the blood-brain barrier. The data emphasize the relationship between the L-enantiomorph neutral amino acid carrier system and MeHg transport across the capillaries. (author)

  9. Synthesis and Characterization of a New Coordinative Compound of Cu(II with 1-(3 Bromo, 2 Hydroxy, 4 Methylphenyl- 2-(4 Bromo-Phenyl-Sulphanyl- Etanone

    Directory of Open Access Journals (Sweden)

    Antighin Simona

    2015-07-01

    Full Text Available Continuing the research in the field of complex compounds, the authors present in this paper the synthesis and characterization of a new compound of Cu(II with the ligand 1-(3 bromo, 2 hydroxy, 4 methyl-phenyl-2-(4 bromophenyl- sulphanyl-etanone. Different methods were used, such as chemical elemental analysis, thermal-gravimetry, infrared absorption spectroscopy and electronic spin resonance (ESR. From chemical analysis resulted that the combination ratio ligand-central atom is 2:1. The new compound can also be used for gravimetric determination of Cu(II.

  10. Pharmacological properties of homomeric and heteromeric GluR1o and GluR3o receptors

    DEFF Research Database (Denmark)

    Nielsen, B S; Banke, T G; Schousboe, A

    1998-01-01

    Homomeric and heteromeric alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor subunits GluR1o and GluR3o were expressed in Spodoptera frugiperda (Sf9) insect cells. Membranes containing the recombinant receptors showed a doublet of bands of the expected size (99-109 kDa) after...

  11. Enzymatic methylation of band 3 anion transporter in intact human erythrocytes

    International Nuclear Information System (INIS)

    Lou, L.L.; Clarke, S.

    1987-01-01

    Band 3, the anion transport protein of erythrocyte membranes, is a major methyl-accepting substrate of the intracellular erythrocyte protein carboxyl methyltransferase (S-adenosyl-L-methionine: protein-D-aspartate O-methyltransferase; EC 2.1.1.77). The localization of methylation sites in intact cells by analysis of proteolytic fragments indicated that sites were present in the cytoplasmic N-terminal domain as well as the membranous C-terminal portion of the polypeptide. The amino acid residues that serve as carboxyl methylation sites of the erythrocyte anion transporter were also investigated. 3 H-Methylated band 3 was purified from intact erythrocytes incubated with L-[methyl- 3 H]methionine and from trypsinized and lysed erythrocytes incubated with S-adenosyl-L-[methyl- 3 H]methionine. After proteolytic digestion with carboxypeptidase Y, D-aspartic acid beta-[ 3 H]methyl ester was isolated in low yields (9% and 1%, respectively) from each preparation. The bulk of the radioactivity was recovered as [ 3 H]methanol, and the amino acid residue(s) originally associated with these methyl groups could not be determined. No L-aspartic acid beta-[ 3 H]methyl ester or glutamyl gamma-[ 3 H]methyl ester was detected. The formation of D-aspartic acid beta-[ 3 H]methyl esters in this protein in intact cells resulted from protein carboxyl methyltransferase activity since it was inhibited by adenosine and homocysteine thiolactone, which increases the intracellular concentration of the potent product inhibitor S-adenosylhomocysteine, and cycloleucine, which prevents the formation of the substrate S-adenosyl-L-[methyl- 3 H]methionine

  12. Synthesis of 5-Substituted 3-Amino-1H-Pyrazole-4-Carbonitriles as Precursors for Microwave Assisted Regiospecific Syntheses of Pyrazolo[1,5-a]Pyrimidines

    Directory of Open Access Journals (Sweden)

    Fawzia Al-Qalaf

    2008-12-01

    Full Text Available A simple route to 3-oxoalkanonitrile 5, aprecursor of the title compounds is described. Reaction of enaminones 2 with hydroxylamine hydrochloride in ethanol yielded aldoximes 3 that were converted readily into 5 in basic medium. This method has been successfully applied with a number of substrates and resulted in excellent yields of the products. Reacting 5 with trichloroacetonitrile afforded 3-amino-2-aroyl-4,4,4-trichloro-2-butenenitriles 6 that condensed with hydrazines to yield 3-amino-1H-pyrazole-4-carbonitrilederivatives 8. Substituted pyrazolo[1,5-a]pyridmidines have been prepared with regioselective condensation reactions of 8 with nonsymmetrical dielectrophiles. The structures of compounds obtained were deduced based on 1H-NMR, 1H-15N HMBC- measurements.

  13. Studies on synthesis, structural, luminescent and thermal properties of a new non-linear optical crystal: 4-amino-4H-1,2,4-triazol-1-ium-3-hydroxy-2,4,6-trinitrophenolate

    Energy Technology Data Exchange (ETDEWEB)

    Dhamodharan, P.; Sathya, K.; Dhandapani, M., E-mail: chemistrydhandapani@gmail.com

    2017-03-01

    A new organic proton transfer complex having NLO activity, 4-amino-4H-1,2,4-triazol-1-ium-3-hydroxy-2,4,6-trinitrophenolate (ATHTP), was crystallized to investigate the factors which stabilize the structure of the crystal. The compound crystallizes in triclinic system with space group P-1. Elemental analysis, thermal analysis, UV–Vis–NIR, FT-IR and NMR spectral analyses were carried out to characterize the crystal. Optical, spectral and thermal properties of the title crystal were analyzed to recommend the material for optical applications. Z-scan was used to measure the effective third-order nonlinear optical susceptibility and nonlinear refractive index. The crystal structure was determined using single crystal XRD method and the structure was optimized using Gaussian 09 program at B3LYP/6-311++G(d,p) level of basis set. This hydrogen bond interactions led to the increase in first-order hyperpolarizability of ATHTP and was 30 times greater than that of urea. Hirshfeld analyses surface analysis was carried out to explore intermolecular interactions in the crystalline state. - Highlights: • Single crystals were grown by slow evaporation solution growth technique. • N-H…O, O-H…O and C-H…O type of interactions lead to stable network. • The thermal stability of the compound was investigated by TG/DTA analyses. • The third-order nonlinear optical susceptibility is found to be 2.1×10{sup −7} esu. • Hirshfeld analyses explore covalent and non covalent interactions.

  14. Direct fluorination of melatonin and 5-hydroxy-L-tryptophan with [18F]F2

    International Nuclear Information System (INIS)

    Chirakal, R.; Firnau, G.; Garnett, E.S.

    1986-01-01

    In order that melatonin receptors may be studied in man with positron emission tomography, melatonin labelled with a positron emitting isotope is needed. The preparation of 6-fluoro-melatonin labelled with F-18 is described. Using the same fluorination method, 5-hydroxy-6-(F-18)fluorotryptophan and 4-(F-18)fluoro-5-hydroxy-tryptophan were also prepared. (UK)

  15. High Concentrations of Tranexamic Acid Inhibit Ionotropic Glutamate Receptors.

    Science.gov (United States)

    Lecker, Irene; Wang, Dian-Shi; Kaneshwaran, Kirusanthy; Mazer, C David; Orser, Beverley A

    2017-07-01

    The antifibrinolytic drug tranexamic acid is structurally similar to the amino acid glycine and may cause seizures and myoclonus by acting as a competitive antagonist of glycine receptors. Glycine is an obligatory co-agonist of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors. Thus, it is plausible that tranexamic acid inhibits NMDA receptors by acting as a competitive antagonist at the glycine binding site. The aim of this study was to determine whether tranexamic acid inhibits NMDA receptors, as well as α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and kainate subtypes of ionotropic glutamate receptors. Tranexamic acid modulation of NMDA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, and kainate receptors was studied using whole cell voltage-clamp recordings of current from cultured mouse hippocampal neurons. Tranexamic acid rapidly and reversibly inhibited NMDA receptors (half maximal inhibitory concentration = 241 ± 45 mM, mean ± SD; 95% CI, 200 to 281; n = 5) and shifted the glycine concentration-response curve for NMDA-evoked current to the right. Tranexamic acid also inhibited α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (half maximal inhibitory concentration = 231 ± 91 mM; 95% CI, 148 to 314; n = 5 to 6) and kainate receptors (half maximal inhibitory concentration = 90 ± 24 mM; 95% CI, 68 to 112; n = 5). Tranexamic acid inhibits NMDA receptors likely by reducing the binding of the co-agonist glycine and also inhibits α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and kainate receptors. Receptor blockade occurs at high millimolar concentrations of tranexamic acid, similar to the concentrations that occur after topical application to peripheral tissues. Glutamate receptors in tissues including bone, heart, and nerves play various physiologic roles, and tranexamic acid inhibition of these receptors may contribute to adverse drug effects.

  16. Ring rearrangements and reactivity of 3-((4-oxo-4H-chromen-3-ylmethylene-4-phenyl-1H-[1,5]benzodiazepin-2(3H-one toward some nucleophiles

    Directory of Open Access Journals (Sweden)

    Hanan Salah

    2017-05-01

    Full Text Available Condensation of 4-phenyl-1H-[1,5]benzodiazepin-2(3H-one (1 with 3-formylchromone (2 afforded a mixture of 3-(chromenylmethylene[1,5]benzodiazepinone 3 and 14-chromenylbenzodiazepino[2,3:6,5]pyrano[2,3-b]benzodiazepine 4. Ring rearrangements of compound 3 with different nucleophilic reagents, such as potassium hydroxide and/or ammonium acetate led to rearrangement into pyranobenzodiazepine 5 and pyridobenzodiazepine 6, respectively. Treatment of compound 3 with hydrazine hydrate, hydroxylamine hydrochloride, malononitrile, cyanothioacetamide, 2-cyano-3,3-disufanylacrylonitrile, and/or 2-cyano-3-phenylamino-3-sufanylacrylonitrile, has been carried out at different conditions, leading to versatile heterocyclic substituted benzodiazepines at position 3, viz. pyrazole 8, isoxazole 9, pyridines 10 and 11, 1,3-dithiine 12, and 1,3-thiazine 13 derivatives.

  17. X-ray investigations of sulfur-containing fungicides. IV. 4'-[[Benzoyl(4-chlorophenylhydrazono)methyl]sulfonyl]acetanilide and 4'-[[benzoyl(4-methoxyphenylhydrazono)methyl]sulfonyl]acetanilide.

    Science.gov (United States)

    Wolf, W M

    2001-09-01

    The conformations of the two approximately isomorphous structures 4'-[[benzoyl(4-chlorophenylhydrazono)methyl]sulfonyl]acetanilide, C(22)H(18)ClN(3)O(4)S, and 4'-[[benzoyl(4-methoxyphenylhydrazono)methyl]sulfonyl]acetanilide, C(23)H(21)N(3)O(5)S, are stabilized by resonance-assisted intramolecular hydrogen bonds linking the hydrazone moieties and sulfonyl groups. The stronger bond is observed in the former compound. The difference in electronic properties between the Cl atom and the methoxy group is too small to significantly alter the non-bonding interactions of the sulfonyl and beta-carbonyl groups.

  18. A synthetic coumarin (4-methyl-7 hydroxy coumarin) has anti-cancer potentials against DMBA-induced skin cancer in mice.

    Science.gov (United States)

    Bhattacharyya, Soumya S; Paul, Saili; Mandal, Sushil K; Banerjee, Antara; Boujedaini, Naoual; Khuda-Bukhsh, Anisur R

    2009-07-01

    Scopoletin, an alkaloid separated from ethanolic extract of the medicinal plant, Gelsemium sempervirens (Fam: Loganiaceae) has been reported to have anti-cancer potentials. The synthetic coumarin (4-Methyl-7 hydroxy coumarin) derived from resorcinol and ethyl aceto-acetate in presence of concentrated sulphuric acid is structurally close to scopoletin, being a coumarin derivative. Whether this synthetic compound also has anti-cancer potentials has been evaluated in vivo on DMBA (7,12-Dimethylbenz[a]anthracene) induced skin cancer in mice by analyzing results of several cytogenetic endpoints, Comet assay, and fluorescence activated cell sorting (FACS). Further, expressions of signal proteins like Aryl hydrocarbon receptor , p53, PCNA, Akt, Bcl-2, Bcl-xL, Bad, Bax, NF-kappaB Apaf, IL-6, Cytochrome-c, Caspase-3 and Caspase-9 were studied by immunoblot analysis along with histology of skin and immuno-histochemical localization of Aryl hydrocarbon receptor and PCNA in DMBA treated mice vis-a-vis carcinogen treated synthetic coumarin fed mice. Feeding of this synthetic coumarin induced positive modulations in expression of all biomarkers in DMBA administered mice, giving clues on its possible signaling pathway(s) - primarily through down-regulation of Aryl hydrocarbon receptor and PCNA and up-regulation of apoptotic proteins like Bax, Bad, Cytochrome c, Apaf, Caspase-3 and Caspase-9, resulting in an appreciable reduction in growth of papilloma in mice. Therefore, this synthetic coumarin shows promise for use in cancer therapy, particularly in skin cancer.

  19. Length and amino acid sequence of peptides substituted for the 5-HT3A receptor M3M4 loop may affect channel expression and desensitization.

    Directory of Open Access Journals (Sweden)

    Nicole K McKinnon

    Full Text Available 5-HT3A receptors are pentameric neurotransmitter-gated ion channels in the Cys-loop receptor family. Each subunit contains an extracellular domain, four transmembrane segments (M1, M2, M3, M4 and a 115 residue intracellular loop between M3 and M4. In contrast, the M3M4 loop in prokaryotic homologues is <15 residues. To investigate the limits of M3M4 loop length and composition on channel function we replaced the 5-HT3A M3M4 loop with two to seven alanine residues (5-HT3A-A(n = 2-7. Mutants were expressed in Xenopus laevis oocytes and characterized using two electrode voltage clamp recording. All mutants were functional. The 5-HT EC(50's were at most 5-fold greater than wild-type (WT. The desensitization rate differed significantly among the mutants. Desensitization rates for 5-HT3A-A(2, 5-HT3A-A(4, 5-HT3A-A(6, and 5-HT3A-A(7 were similar to WT. In contrast, 5-HT3A-A(3 and 5-HT3A-A(5 had desensitization rates at least an order of magnitude faster than WT. The one Ala loop construct, 5-HT3A-A(1, entered a non-functional state from which it did not recover after the first 5-HT application. These results suggest that the large M3M4 loop of eukaryotic Cys-loop channels is not required for receptor assembly or function. However, loop length and amino acid composition can effect channel expression and desensitization. We infer that the cytoplasmic ends of the M3 and M4 segments may undergo conformational changes during channel gating and desensitization and/or the loop may influence the position and mobility of these segments as they undergo gating-induced conformational changes. Altering structure or conformational mobility of the cytoplasmic ends of M3 and M4 may be the basis by which phosphorylation or protein binding to the cytoplasmic loop alters channel function.

  20. Amino Acids Inhibitory Effects and Mechanism on 2-Amino-1-Methyl-6-Phenylimidazo [4,5-b]Pyridine (PhIP) Formation in the Maillard Reaction Model Systems.

    Science.gov (United States)

    Linghu, Ziyi; Karim, Faris; Smith, J Scott

    2017-12-01

    This study was to investigate the inhibitory effects of amino acids (AAs) on the formation of 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) and to evaluate the inhibition mechanism of PhIP in Maillard model systems. Different AAs were individually added into model systems heat-treated at 180 °C/1 h. The PhIP, phenylacetaldehyde (PheAce), and pyrazines derivatives were determined using HPLC and GC-MS. AAs significantly reduced (P Pro > Leu > Met > Val > Ile > Thr > Phe > Asp, at the highest molar ratio. The PheAce content was gradually reduced with increasing AAs levels, suggesting that AAs may inhibit PhIP formation through scavenging the available PheAce. A correlation between PhIP inhibition and PheAce-scavenging activity of AAs was observed when PheAce and AAs were heated. The variety and quantity of pyrazines formed are highly depending on the type of AAs. © 2017 Institute of Food Technologists®.

  1. Synthesis of new series of 3-hydroxy/acetoxy-2-phenyl-4H-chromen ...

    Indian Academy of Sciences (India)

    Abstract. 3-Hydroxy-2-aryl/heteroaryl-4H-chromones 4(a–n) were synthesized from appropriate chalcones. 3(a–n) and acetylated to afford the corresponding acetoxy derivatives 5(a–n). All compounds were evalu- ated for antimicrobial activity against Staphylococus aureus, Bacillus subtillis, Escherichia coli and Pseu-.

  2. Synthesis, urease inhibition, antioxidant and antibacterial studies of some 4-amino-5-aryl-3H-1,2,4-triazole-3-thiones and their 3,6-disubstituted 1,2,4-triazolo[3,4-b]1,3,4-thiadiazole derivatives

    International Nuclear Information System (INIS)

    Hanif, Muhammad; Saleem, Muhammad; Rama, Nasim Hasan; Hussain, Muhammad Tahir; Zaib, Sumera; Aslam, Muhammad Adil M.; Iqbal, Jamshed; Jones, Peter G.

    2012-01-01

    A new series of 4-amino-5-aryl-3H-1,2,4-triazole-3-thiones, bearing various methoxybenzyl- and methoxyphenethyl groups, was synthesized by refluxing potassium hydrazinecarbodithioate salts in dilute aqueous solution of hydrazine hydrate. These salts were formed by the reaction of acid hydrazides and carbon disulfide in methanolic potassium hydroxide solution at 0-5 deg C. 4-Amino- 5-aryl-3H-1,2,4-triazole-3-thiones were condensed with different substituted aromatic acids to yield 3,6-disubstituted-1,2,4-triazolo[3,4-b]1,3,4-thiadiazoles. The structures of the synthesized compounds were characterized by infrared (IR), 1 H and 13 C nuclear magnetic resonance (NMR), elemental analysis and mass spectrometric (MS) studies. All the synthesized compounds were screened for their urease inhibition, antioxidant and antibacterial activities. Some compounds showed excellent urease inhibition activity, more than the standard drug. Others exhibited potent antioxidant activity. All the compounds showed significant antibacterial activities as compared to the standard drug. (author)

  3. Pulse radiolytic reduction of amino and hydroxy disubstituted anthraquinones (Preprint no. RC-15)

    International Nuclear Information System (INIS)

    Pal, H.; Palit, D.K.; Mukherjee, T.; Mittal, J.P.

    1991-01-01

    One-electron reduction of 1-amino-4-hydroxy-9, 10-anthraquinone (AHAQ) and 1,4-diamino-9, 10-anthraquinone (DAAQ) in various matrices has been investigated by electron pulse radiolysis. Spectroscopic and kinetic parameters, acid dissociation constants (pK a ) of the reduced semiquinone radicals and one-electron reduction potential for AHAQ have been measured. (author). 2 tabs

  4. Series of edge-sharing bi-triangle Ln4 clusters with a μ4-NO3- bridge: syntheses, structures, luminescence, and the SMM behavior of the Dy4 analogue.

    Science.gov (United States)

    Zou, Hua-Hong; Wang, Rong; Chen, Zi-Lu; Liu, Dong-Cheng; Liang, Fu-Pei

    2014-02-14

    A series of Ln4 clusters, [Ln4L2(μ3-OH)2(μ4-NO3)(NO3)4(OCH3)(H2O)]·xMeCN·yMeOH (Ln = Gd (1), Tb (2), Dy (3), Ho (4), Er (5), Yb (6), L = 2-{[2-(2-hydroxy-ethoxy)-ethylimino]-methyl}-6-methoxyphenol), have been synthesized by the reaction of Ln(NO)3 and a Schiff-base ligand formed in situ. The six complexes display similar structures, with an overall metal core comprising two edge-sharing triangular Ln3 units linked by a μ4-NO3(-) bridge. The luminescence spectrum of complex 2 shows the characteristic emission of the Tb(III) ions. The magnetic susceptibility studies reveal that the Ln(III) ions are very weakly interacting in all six compounds. Frequency dependence of the ac-susceptibility was found for 3, suggesting a typical single-molecule magnet (SMM) behavior with an anisotropic barrier of 28 K.

  5. Synthesis of 1- and 3-11C-labelled L-lactic acid using multi-enzyme catalysis

    International Nuclear Information System (INIS)

    Bjurling, P.; Laangstroem, B.

    1990-01-01

    The synthesis of 1- and 3- 11 C-labelled L-lactic acid from the corresponding racemic 1- or 3- 11 C-labelled alanine using a multi-enzymatic reaction route, is presented. DL-[1- 11 C]Alanine was synthesised by reacting sodium 1-hydroxy-ethyl sulfite with hydrogen [ 11 C]cyanide, obtained from [ 11 C]carbon dioxide, and ammonia followed by acid hydrolysis. DL-[3- 11 C]-Alanine was synthesised by a methylation of a glycine derivative, N-(diphenylmethylene)-glycine tert-butyl ester, with [ 11 C]methyl iodide, obtained from [ 11 C]carbon dioxide, and subsequent hydrolysis. The racemic 1- or 3- 11 C-labelled alanine was then converted to pyruvic acid, by D-amino acid oxidase/catalase and glutamic-pyruvic transaminase, which was directly reduced to L-lactic acid by L-lactic dehydrogenase in a one-pot procedure. The total synthesis time was 40 minutes, counted from release of [ 11 C]carbon dioxide. The decay corrected radiochemical yields were ca. 80% for L-[1- 11 C]lactic acid, based on hydrogen cyanide, and ca. 60% for L-[3- 11 C]lactic acid, based on carbon dioxide. The radiochemical purities were higher than 99% analysed by HPLC. (author)

  6. Reduction of nitro groups by ynamines; synthesis and x-ray crystal structure of n,n-diethyl-3,3a-dihydro-3-methylbenzofuro[3,2-c]isoxazole-3-carboxamide

    NARCIS (Netherlands)

    de Wit, A.D.; Trompenaars, W.P.; Reinhoudt, David; Harkema, Sybolt; van Hummel, G.J.

    1980-01-01

    3-Nitrobenzo[b]furan and 1-diethylaminopropyne react thermally at 5–10°C to give a 1:1 addition product ( ) in which one of the oxygen atoms of the nitro group is transferred to C-1 of the acetylene. The structure of the benzofuro[3,2-c]isoxazole ( ) has been determined by X-ray crystallography.

  7. 6-Hydroxy-5-[(2-hydroxy-4,4-dimethyl-6-oxocyclohex-1-enyl(4-nitrophenylmethyl]-1,3-dimethylpyrimidine-2,4(1H,3H-dione

    Directory of Open Access Journals (Sweden)

    N. Sureshbabu

    2013-11-01

    Full Text Available In the title compound, C21H23N3O7, the pyrimidinedione ring adopts a screw-boat conformation, whereas the cyclohexenone ring adopts an envelope conformation, with the C atom bearing the methyl groups as the flap atom. The dihedral angle between the mean planes of the pyrimidinedione and cyclohexenone rings is 58.78 (2°. The pyrimidinedione and cyclohexenone rings form dihedral angles of 59.94 (3 and 54.73 (2°, respectively, with the 4-nitrophenyl ring. Relatively strong intramolecular O—H...O hydrogen bonds are observed. In the crystal, molecules are linked by C—H...O hydrogen bonds, forming a chain along the c-axis direction.

  8. Synthesis and research of the physical-chemical properties of 5-((2-bromphenyl-4-amino-4H-1,2,4-triazole-3-ylthioacetic acid salts

    Directory of Open Access Journals (Sweden)

    Ye. S. Pruglo

    2018-03-01

    Full Text Available At this stage of the development of modern science the scientists get a lot of questions in the field of medicine and pharmacy, and one of the most important among them is the study and search of new ways of synthesis of high-performance and low-toxic substances. Special attention is paid to 1,2,4-triazole and xanthine. On their basis some medical drugs were made, which are widely used in medicine. The aim of this work was the synthesis and study of properties of salts of 5-(2-bromophenyl-4-amino-4H-1,2,4-triazole-3-ylthioacetic acid. Methods and results. As starting material theophylline was selected. Through a number of stages 5-(2-bromphenyl-4-amino-4H-1,2,4-triazole-3-thion was obtained. By the reaction of neutralization the salts with organic and inorganic bases were obtained. The physical-chemical properties of the compounds were determined. The structure of the substances was confirmed by elemental analysis on an Elementar Vario L cube (CHNS instrument; IR spectra (4000–400 cm-1 were taken on the ALPHA-T modules of the Bruker ALPHA FT-IR spectrometer. The 1H NMR spectra of the compounds were recorded using a Varian Mercury VX 200 spectrometer (solvent – DMSO-d6, internal standard: tetramethylsilane. The formation of salts was confirmed by the signals of the corresponding protonated amines. Chromato-mass spectral studies were carried out on the LC MS: Agilent 1260 Infinity HPLC System , ionization method – chemical ionization at atmospheric pressure (APCI. Conclusions. The interaction of the resulting thiol with monochloracetic acid in aqueous solution with double quantity of alkali and subsequent neutralization leads to corresponding carboxylic acid obtaining. It was confirmed that the greatest outputs of salts as the reaction products were observed when using water as the solvent with the subsequent replacement of acetone. the optimum conditions of obtaining salts of 5-(2-bromophenyl-4-amino-4H-1,2,4-triazole-3-ylthioacetic acid

  9. Glufosinate ammonium stimulates nitric oxide production through N-methyl D-aspartate receptors in rat cerebellum.

    Science.gov (United States)

    Nakaki, T; Mishima, A; Suzuki, E; Shintani, F; Fujii, T

    2000-09-01

    Glufosinate ammonium, a structural analogue of glutamate, is an active herbicidal ingredient. The neuronal activities of this compound were investigated by use of a microdialysis system that allowed us to measure nitric oxide production in the rat cerebellum in vivo. Kainate (0.3-30 nmol/10 microliter), N-methyl-D-aspartate (NMDA) (3-300 nmol/10 microliter) and glufosinate ammonium (30-3000 nmol/10 microliter), which were administered through the microdialysis probe at a rate of 1 microliter/min for 10 min, stimulated nitric oxide production. The glufosinate ammonium-elicited increase in nitric oxide production was suppressed by an inhibitor of nitric oxide synthase and was antagonized by NMDA receptor antagonists, but not by a kainate/(+/-)-alphaamino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor antagonist. These results suggest that glufosinate ammonium stimulates nitric oxide production through NMDA receptors.

  10. Xenon spectator and diagram L3-M4,5M4,5 Auger intensities near the L3 threshold

    International Nuclear Information System (INIS)

    Armen, G.B.; Levin, J.C.; Southworth, S.H.; LeBrun, T.; Arp, U.; MacDonald, M.A.

    1997-01-01

    Calculations based on the theory of radiationless resonant Raman scattering are employed in the interpretation of new XeL 3 -M 4,5 M 4,5 Auger spectra recorded using synchrotron radiation tuned to energies across the L 3 edge. Fits of theoretical line shapes to the spectra are employed in separating intensities due to nd spectator (resonant) and diagram Auger processes. Near-threshold Auger intensity, previously attributed to diagram decay, is found to be due to the large-n spectator lines that result from postcollision-interaction endash induced open-quotes recaptureclose quotes of threshold photoelectrons to nd orbitals. copyright 1997 The American Physical Society

  11. Magnetic nanoparticles grafted with β-cyclodextrin for solid-phase extraction of 5-hydroxy-3-indole acetic acid

    International Nuclear Information System (INIS)

    Ahmed, Gaber Hashem Gaber; Laíño, Rosana Badía; Calzón, Josefa Angela García; García, Marta Elena Díaz

    2014-01-01

    We describe the synthesis of β-cyclodextrin modified magnetic nanoparticles (CD-mNPs) as a material for solid-phase extraction of the cancer biomarker 5-hydroxy-indole-3-acetic acid (5-HIAA) from urine. The CD-mNPs were characterized by TEM, FTIR, and XRD, and the kinetics and adsorption isotherms were studied. The strong interaction between the CD-mNPs and 5-HIAA is the main driving force for recognition and extraction, while the magnetic core of the NPs allows their separation from the sample matrix. Recovery of 5-HIAA from the adsorbent using an adequate solvent regenerated the adsorbent for further use. 5-HIAA was then quantified by fluorometry of its complex with β-CD. The method works in the 1 × 10 −7 to 1 × 10 −5 mol L −1 (R 2 0.9982–0.9996) concentration range, and the limits of detection (3σ) and quantification (10 σ) of the method are 1.2 × 10 −8 mol L −1 and 4.01 × 10 −8 mol L −1 5-HIAA, respectively. The recovery of 5-HIAA from urine samples spiked with 5-HIAA in three concentrations (1.4 × 10 −6 , 4.50 × 10 −6 and 1.0 × 10 −5 mol L −1 ) are within 63 ± 3 %. (author)

  12. Stereochemistry of nitrogenous heterocycles. 61. Synthesis and configuration of an eighth isomer of 2-methyl-4-hydroxydecahydroquinoline

    International Nuclear Information System (INIS)

    Litvinenko, G.S.; Voronenko, L.A.

    1987-01-01

    Reduction of 1-benzoyl-2α-methyl-4-oxo-cis-decahydroquinoline with dodium borohydride and sodium in alcohol has given 1-benzoyl-2α-methyl-4β-hydroxy-cis-decahydroquinoline, which exists in the steroidal conformation with diaxial α, α'-substituents in the piperidine ring and with an equatorial hydroxy-group. Debenzoylation of this has given the last of the eight theoretically possible isomers of 2-methyl-4-hydroxydecahydroquinoline, namely 2α-methyl-4β-hydroxy-cis-decahydroquinoline, which exists in the nonsteroidal conformation with an axial hydroxy-group. IR spectra were obtained on a UR-20 spectrometer in KBr disks, and PMR spectra on a BS487 instrument (80 MHz), internal standard HMDS

  13. Preparation and biological evaluation of 2-amino-6-[{sup 18}F]fluoro-9-(4-hydroxy-3-hydroxy-methylbutyl) purine (6-[{sup 18}F]FPCV) as a novel PET probe for imaging HSV1-tk reporter gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Cai Hancheng [Research Center of Radiopharmaceuticals, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 (China); Graduate School of the Chinese Academy of Sciences, Beijing 100049 (China); Yin Duanzhi [Research Center of Radiopharmaceuticals, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 (China)], E-mail: chcbati@yahoo.com.cn; Zhang Lan [Research Center of Radiopharmaceuticals, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 (China); Zhejiang California International NanoSystems Institute, Hangzhou 310029 (China); Yang, Xiaofeng; Xu Xiaoyan; Liu Weiguo; Zheng Xuesheng [Institute of Brain Medical Science, Second affiliated Hospital, Medicine School of Zhejiang University, Hangzhou 310009 (China); Zhang Hong [Department of Nuclear Medicine, Second Affiliated Hospital, Zhejiang University Medical PET Center, Medicine School of Zhejiang University, Hangzhou 310009 (China); Wang Jing [Department of Nuclear Medicine, Second Affiliated Hospital, Zhejiang University Medical PET Center, Medicine School of Zhejiang University, Hangzhou 310009 (China); Zhejiang California International NanoSystems Institute, Hangzhou 310029 (China); Xu Yuhong [Zhejiang California International NanoSystems Institute, Hangzhou 310029 (China); Cheng Dengfeng; Zheng Mingqiang; Han Yanjiang; Wu Mingxing; Wang Yongxian [Research Center of Radiopharmaceuticals, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 (China)

    2007-08-15

    Introduction: 2-Amino-6-[{sup 18}F]fluoro-9-(4-hydroxy-3-hydroxy-methylbutyl) purine (6-[{sup 18}F]FPCV) was prepared via a one-step nucleophilic substitution and evaluated as a novel probe for imaging the expression of herpes simplex virus type 1 thymidine kinase (HSV1-tk) reporter gene. Methods: Log P of 6-[{sup 18}F]FPCV was calculated in octanol/phosphate-buffered saline (PBS). Stability studies were performed in PBS and bovine serum albumin (BSA). Cell uptake was performed at various time points in wild-type cells and transduced cells. For in vivo studies, tumors were grown in nude mice by inoculation with C6 cells, wild type and tk positive. The radiotracer was intravenously injected to animals, and micro-PET imaging was performed. Biodistribution of 6-[{sup 18}F]FPCV was performed on another group of animals at different time points. Results: Log P of 6-[{sup 18}F]FPCV was -0.517. 6-[{sup 18}F]FPCV was fairly stable in PBS and BSA at 6 h. The tracer uptake in C6-tk cells was 5.5-18.8 times higher than that in wild-type cells. The plasma half-life of 6-[{sup 18}F]FPCV was as follows: {alpha} t{sub 1/2}=1.2 min and {beta} t{sub 1/2}=73.7 min. The average ratio of tumor uptake between the transduced tumor and the wild-type tumor was 1.69 at 15 min. Conclusion: Biological evaluation showed that 6-[{sup 18}F]FPCV is a potential probe for imaging HSV1-tk gene expression. However, its in vivo defluorination may limit its application in PET imaging of gene expression.

  14. Synthesis, crystal structure determination and antiproliferative activity of novel 2-amino-4-aryl-4,10-dihydro[1,3,5]triazino[1,2- a]benzimidazoles

    Science.gov (United States)

    Hranjec, Marijana; Pavlović, Gordana; Karminski-Zamola, Grace

    2012-01-01

    This manuscript describes the synthesis of novel 2-amino-4-aryl-4,10-dihydro-[1,3,5]triazino[1,2- a]benzimidazoles as hydrochloride salts 4a-n and 5b which were prepared in the reaction of cyclocondensation between 2-guanidinobenzimidazole and versatile heteroaromatic aldehydes. Structures of all prepared compounds have been studied by using 1H and 13C NMR, IR and UV/Vis spectroscopy. The crystal and molecular structure of 4f was determined by X-ray diffraction on single crystals. The molecule of 2-amino-4-(4'-methylphenyl)-4,10-dihydro[1,3,5]triazino[1,2- a]benzimidazole hydrochloride 4f (C 16H 16N 5+·Cl -) exists in the solid state in one of the possible tautomeric forms, being protonated at the one of the nitrogen atoms of the 1,4-dihydrotriazine ring. The molecule is highly delocalized within the 4,10-dihydro[1,3,5]triazino[1,2- a]benzimidazole moiety with the highest deviation from the plane for the methine carbon atom and the protonated nitrogen atom of the 1,4-dihydrotriazine ring. The cations are joined via N-H⋯N hydrogen bonds into R22(8) centrosymmetric dimers. Cation dimers are further connected with Cl - ions via N-H⋯Cl and C-H⋯Cl hydrogen bonds into 2D chains spreading along the b axis. The obtained single-crystal X-ray structure determination unequivocally confirms tautomeric form of the compound present in the solid-state and can represent tantative pattern for other prepared compounds. All prepared compounds were tested on their antiproliferative activity in vitro on several human cancer cell lines. Compound 4m was the most active one (IC 50 ≈ 20 μM), while compounds 4d, 4f, 4k, 4l4m showed moderate, but non-selective, antiproliferative activity with IC 50 25-60 μM.

  15. Three-dimensional structure of the ligand-binding core of GluR2 in complex with the agonist (S)-ATPA

    DEFF Research Database (Denmark)

    Lunn, Marie-Louise; Hogner, Anders; Stensbøl, Tine B

    2003-01-01

    Two X-ray structures of the GluR2 ligand-binding core in complex with (S)-2-amino-3-(5-tert-butyl-3-hydroxy-4-isoxazolyl)propionic acid ((S)-ATPA) have been determined with and without Zn(2+) ions. (S)-ATPA induces a domain closure of ca. 21 degrees compared to the apo form. The tert-butyl moiety...

  16. Fumonisin FB1 treatment acts synergistically with methyl donor deficiency during rat pregnancy to produce alterations of H3- and H4-histone methylation patterns in fetuses.

    Science.gov (United States)

    Pellanda, Hélène; Forges, Thierry; Bressenot, Aude; Chango, Abalo; Bronowicki, Jean-Pierre; Guéant, Jean-Louis; Namour, Fares

    2012-06-01

    Prenatal folate and methyl donor malnutrition lead to epigenetic alterations that could enhance susceptibility to disease. Methyl-deficient diet (MDD) and fumonisin FB1 are risk factors for neural tube defects and cancers. Evidence indicates that FB1 impairs folate metabolism. Folate receptors and four heterochromatin markers were investigated in rat fetuses liver derived from dams exposed to MDD and/or FB1 administered at a dose twice higher than the provisional maximum tolerable daily intake (PMTDI = 2 μg/kg/day). Even though folate receptors transcription seemed up-regulated by methyl depletion regardless of FB1 treatment, combined MDD/FB1 exposure might reverse this up-regulation since folate receptors transcripts were lower in the MDD/FB1 versus MDD group. Methyl depletion decreased H4K20me3. Combined MDD/FB1 decreased H4K20me3 even more and increased H3K9me3. The elevated H3K9me3 can be viewed as a defense mechanism inciting the cell to resist heterochromatin disorganization. H3R2me2 and H4K16Ac varied according to this mechanism even though statistical significance was not consistent. Considering that humans are exposed to FB1 levels above the PMTDI, this study is relevant because it suggests that low doses of FB1 interact with MDD thus contributing to disrupt the epigenetic landscape. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Synthesis of new 3-(2-aminothiazol-4-yl-4-hydroxy-2H-chromen-2-one derivatives

    Directory of Open Access Journals (Sweden)

    S. SUKDOLAK

    2006-06-01

    Full Text Available Aminothiazole derivatives of 4-hydroxy-2H-chromen-2-one were prepared by the Hantzsch reaction1 using 3-(2-bromoacetyl-4-hydroxy-2H-chromen-2-one and thiourea derivatives. Starting compound for this synthesis 3-(2-bromoacetyl-4-hydroxy- 2H-chromen-2-one (1 was prepared previously.2 Also, for this synthesis we used thiourea derivatives (2a–j as compounds which possess groups with biological activity. Reactions are carried out in refluxing ethanol for a period of 30 – 45 min. Final products (3a–j are obtained in a high yield. Chemical structure of the obtained compounds was confirmed by elemental and structural analysis (IR and 1H NMR spectroscopy.

  18. Identification of 3-hydroxy-3-methylglutaric acid (HMG) as a hypoglycemic principle of Spanish moss (Tillandsia usneoides).

    Science.gov (United States)

    Witherup, K M; McLaughlin, J L; Judd, R L; Ziegler, M H; Medon, P J; Keller, W J

    1995-08-01

    Bioactivity-directed fractionation, using brine shrimp lethality and murine hypoglycemia, of an ethanol extract prepared from Tillandsia usneoides, led to the isolation of four apparently bioactive compounds from the water-soluble fraction. The compounds were identified as citric acid, succinic acid, 3-hydroxy-3-methylglutaric acid (HMG), and 3,6,3',5'-tetramethoxy-5,7,4'-trihydroxyflavone-7-O-beta-D-g lucoside. The brine shrimp lethality of the acids was simply due to acidity; however, HMG elicited significant hypoglycemic responses in fasting normal mice. Ethyl and methyl esters of citric acid were prepared and tested in the murine hypoglycemic assay. Five of the predominant sugars were identified by tlc. Free thymidine was also isolated. Further evaluation of HMG and other potential inhibitors of HMG CoA lyase, in the treatment of symptoms of diabetes mellitus, is suggested.

  19. Development of a fully automated sequential injection solid-phase extraction procedure coupled to liquid chromatography to determine free 2-hydroxy-4-methoxybenzophenone and 2-hydroxy-4-methoxybenzophenone-5-sulphonic acid in human urine.

    Science.gov (United States)

    León, Zacarías; Chisvert, Alberto; Balaguer, Angel; Salvador, Amparo

    2010-04-07

    2-Hydroxy-4-methoxybenzophenone and 2-hydroxy-4-methoxybenzophenone-5-sulphonic acid, commonly known as benzophenone-3 (BZ3) and benzophenone-4 (BZ4), respectively, are substances widely used as UV filters in cosmetic products in order to absorb UV radiation and protect human skin from direct exposure to the deleterious wavelengths of sunlight. As with other UV filters, there is evidence of their percutaneous absorption. This work describes an analytical method developed to determine trace levels of free BZ3 and BZ4 in human urine. The methodology is based on a solid-phase extraction (SPE) procedure for clean-up and pre-concentration, followed by the monitoring of the UV filters by liquid chromatography-ultraviolet spectrophotometry detection (LC-UV). In order to improve not only the sensitivity and selectivity, but also the precision of the method, the principle of sequential injection analysis was used to automate the SPE process and to transfer the eluates from the SPE to the LC system. The application of a six-channel valve as an interface for the switching arrangements successfully allowed the on-line connection of SPE sample processing with LC analysis. The SPE process for BZ3 and BZ4 was performed using octadecyl (C18) and diethylaminopropyl (DEA) modified silica microcolumns, respectively, in which the analytes were retained and eluted selectively. Due to the matrix effects, the determination was based on standard addition quantification and was fully validated. The relative standard deviations of the results were 13% and 6% for BZ3 and BZ4, respectively, whereas the limits of detection were 60 and 30 ng mL(-1), respectively. The method was satisfactorily applied to determine BZ3 and BZ4 in urine from volunteers that had applied a sunscreen cosmetic containing both UV filters. Copyright 2010 Elsevier B.V. All rights reserved.

  20. Development of a fully automated sequential injection solid-phase extraction procedure coupled to liquid chromatography to determine free 2-hydroxy-4-methoxybenzophenone and 2-hydroxy-4-methoxybenzophenone-5-sulphonic acid in human urine

    International Nuclear Information System (INIS)

    Leon, Zacarias; Chisvert, Alberto; Balaguer, Angel; Salvador, Amparo

    2010-01-01

    2-Hydroxy-4-methoxybenzophenone and 2-hydroxy-4-methoxybenzophenone-5-sulphonic acid, commonly known as benzophenone-3 (BZ3) and benzophenone-4 (BZ4), respectively, are substances widely used as UV filters in cosmetic products in order to absorb UV radiation and protect human skin from direct exposure to the deleterious wavelengths of sunlight. As with other UV filters, there is evidence of their percutaneous absorption. This work describes an analytical method developed to determine trace levels of free BZ3 and BZ4 in human urine. The methodology is based on a solid-phase extraction (SPE) procedure for clean-up and pre-concentration, followed by the monitoring of the UV filters by liquid chromatography-ultraviolet spectrophotometry detection (LC-UV). In order to improve not only the sensitivity and selectivity, but also the precision of the method, the principle of sequential injection analysis was used to automate the SPE process and to transfer the eluates from the SPE to the LC system. The application of a six-channel valve as an interface for the switching arrangements successfully allowed the on-line connection of SPE sample processing with LC analysis. The SPE process for BZ3 and BZ4 was performed using octadecyl (C18) and diethylaminopropyl (DEA) modified silica microcolumns, respectively, in which the analytes were retained and eluted selectively. Due to the matrix effects, the determination was based on standard addition quantification and was fully validated. The relative standard deviations of the results were 13% and 6% for BZ3 and BZ4, respectively, whereas the limits of detection were 60 and 30 ng mL -1 , respectively. The method was satisfactorily applied to determine BZ3 and BZ4 in urine from volunteers that had applied a sunscreen cosmetic containing both UV filters.

  1. Proton dynamics in the hydrogen bonds of 4-amino-3,5-dihalogenobenzoic acid

    Energy Technology Data Exchange (ETDEWEB)

    Asaji, Tetsuo, E-mail: asaji@chs.nihon-u.ac.jp [Department of Chemistry, College of Humanities and Sciences, Nihon University, 3-25-40 Sakurajosui, Setagaya-ku, Tokyo 156-8550 (Japan); Ueda, Kouhei; Oguni, Masaharu [Department of Chemistry, Graduate School of Science and Engineering, Tokyo Institute of Technology, 2-12-1 O-okayama, Meguro-ku, Tokyo 152-8551 (Japan)

    2015-08-18

    Highlights: • 4-Amino-3,5-dichlorobenzoic acid has a symmetric dimer structure. • The compound undergoes a phase transition at 138 K. • The symmetry breaking of the dimer was revealed by {sup 35}Cl NQR. • The proton dynamics was analyzed by coherent and incoherent tunneling models. - Abstract: On the polycrystalline sample of 4-amino-3,5-dihalogenobenzoic acid, 4-NH{sub 2}-3,5-X{sub 2}C{sub 6}H{sub 2}COOH, which has a symmetric dimer structure in the crystal, the proton tunneling in the hydrogen bonds has been investigated by NQR and NMR spin–lattice relaxation times T{sub 1} measurements. Two {sup 35}Cl NQR lines of the X = Cl derivative show the existence of two crystallographically inequivalent chlorine atoms in the high-temperature phase, in consistency with the reported crystal structure. Below 138 K, each splits into a doublet indicating the symmetry breaking of the benzoic acid dimer. The proton dynamics was analyzed by a coherent and incoherent tunneling models, for the high- and low-temperature phases, respectively. The temperature dependence of the correlation time of proton translation was estimated. As for the X = I derivative, the proton dynamics was discussed similarly by {sup 1}H NMR T{sub 1} data by assuming occurrence of a phase transition at low-temperature.

  2. Dynamic regulation of NMDAR function in the adult brain by the stress hormone corticosterone

    Directory of Open Access Journals (Sweden)

    Yiu Chung eTse

    2012-03-01

    Full Text Available Stress and corticosteroids dynamically modulate the expression of synaptic plasticity at glutamatergic synapses in the developed brain. Together with alpha-amino-3-hydroxy-methyl-4-isoxazole propionic acid receptors (AMPAR, N-methyl-D-aspartate receptors (NMDAR are critical mediators of synaptic function and are essential for the induction of many forms of synaptic plasticity. Regulation of NMDAR function by cortisol/corticosterone (CORT may be fundamental to the effects of stress on synaptic plasticity. Recent reports of the efficacy of NMDAR antagonists in treating certain stress-associated psychopathologies further highlight the importance of understanding the regulation of NMDAR function by CORT. Knowledge of how corticosteroids regulate NMDAR function within the adult brain is relatively sparse, perhaps due to a common belief that NMDAR function is relatively stable in the adult brain. We review recent results from our laboratory and others demonstrating dynamic regulation of NMDAR function by CORT in the adult brain. In addition, we consider the issue of how differences in the early life environment may program differential sensitivity to modulation of NMDAR function by CORT and how this may influence synaptic function during stress. Findings from these studies demonstrate that NMDAR function in the adult hippocampus remains sensitive to even brief exposures to CORT and that the capacity for modulation of NMDAR may be programmed, in part, by the early life environment. Modulation of NMDAR function may contribute to dynamic regulation of synaptic plasticity and adaptation in the face of stress, however enhanced NMDAR function may be implicated in mechanisms of stress related psychopathologies including depression.

  3. Synthesis of N-(5-(Substitutedphenyl-4,5-dihydro-1H-pyrazol-3-yl-4H-1,2,4-triazol-4-amine from 4-Amino-4H-1,2,4-triazole

    Directory of Open Access Journals (Sweden)

    Ashvin D. Panchal

    2011-01-01

    Full Text Available N-(4H-1,2,4-Triazol-4-ylacetamide (2 were prepared by reaction of 4-amino-4H-1,2,4-triazole (1 with acetyl chloride in dry benzene. It has been reacted with various aromatic aldehyde to afford 3-(substitutedphenyl-N-(4H-1,2,4-triazol-4-ylacrylamide (3a-e. The synthesis of N-(5-substitutedphenyl-4,5-dihydro-1H-pyrazol-3-yl-4H-1,2,4-triazol-4-amine (4a-e is achieved by the cyclisation of 3a-e with hydrazine hydrate in ethanol. The structures of synthesized compounds were characterized by 1H NMR and IR spectroscopic studies. The purity of the compounds was checked by thin layer chromatography.

  4. Responses of Blood Glucose, Insulin, Glucagon, and Fatty Acids to Intraruminal Infusion of Propionate in Hanwoo

    Directory of Open Access Journals (Sweden)

    Y. K. Oh

    2015-02-01

    Full Text Available This study was carried out to investigate the effects of intraruminal infusion of propionate on ruminal fermentation characteristics and blood hormones and metabolites in Hanwoo (Korean cattle steers. Four Hanwoo steers (average body wt. 270 kg, 13 month of age equipped with rumen cannula were infused into rumens with 0.0 M (Water, C, 0.5 M (37 g/L, T1, 1.0 M (74 g/L, T2 and 1.5 M (111 g/L, T3 of propionate for 1 hour per day and allotted by 4×4 Latin square design. On the 5th day of infusion, samples of rumen and blood were collected at 0, 60, 120, 180, and 300 min after intraruminal infusion of propionate. The concentrations of serum glucose and plasma glucagon were not affected (p>0.05 by intraruminal infusion of propionate. The serum insulin concentration at 60 min after infusion was significantly (p<0.05 higher in T3 than in C, while the concentration of non-esterified fatty acid (NEFA at 60 and 180 min after infusion was significantly (p<0.05 lower in the propionate treatments than in C. Hence, intraruminal infusion of propionate stimulates the secretion of insulin, and decreases serum NEFA concentration rather than the change of serum glucose concentration.

  5. Synthesis of 20-14C 3β-hydroxy-5β-pregnan-20-one

    International Nuclear Information System (INIS)

    Garraffo, H.M.; Gros, E.G.

    1982-01-01

    20 - 14 C 3β-hydroxy-5β-pregnan-20-one was synthesised by condensing 3β-acetoxy-5β-androstan-17-one with potassium 14 C cyanide to produce cyanohydrin. This was dehydrated and the resulting unsaturated nitrile treated with methylmagnesiumiodide to produce hydroxypregnenone. Hydrogenation of this gave 14 C 3β-hydroxy-5β-pregnan-20-one. (U.K.)

  6. Synthesis and characterization of tin(II) complexes of fluorinated Schiff bases derived from amino acids.

    Science.gov (United States)

    Singh, Har Lal

    2010-07-01

    New tin(II) complexes of general formula Sn(L)(2) (L=monoanion of 3-methyl-4-fluoro-acetophenone phenylalanine L(1)H, 3-methyl-4-fluoro-acetophenone alanine L(2)H, 3-methyl-4-fluoro acetophenone tryptophan L(3)H, 3-methyl-4-fluoro-acetophenone valine L(4)H, 3-methyl-4-fluoro-acetophenone isoleucine L(5)H and 3-methyl-4-fluoro-acetophenone glycine L(6)H) have been prepared. It is characterized by elemental analyses, molar conductance measurements and molecular weight determinations. Bonding of these complexes is discussed in terms of their UV-visible, infrared, and nuclear magnetic resonance ((1)H, (13)C, (19)F and (119)Sn NMR) spectral studies. The ligands act as bidentate towards metal ions, via the azomethine nitrogen and deprotonated oxygen of the respective amino acid. Elemental analyses and NMR spectral data of the ligands with their tin(II) complexes agree with their proposed square pyramidal structures. A few representative ligands and their tin complexes have been screened for their antibacterial activities and found to be quite active in this respect. Copyright 2010 Elsevier B.V. All rights reserved.

  7. Synthesis, physical and chemical properties of 2-((4-(R-amino-5-(thiophen-2-ylmethyl-4H-1,2,4-triazol-3-ylthioacetic acids salts

    Directory of Open Access Journals (Sweden)

    А.А. Safonov

    2017-12-01

    Full Text Available Thanks to the rapid development of science, humanity has achieved remarkable success in various fields. This also applies to the synthesis of biological compounds. Over the centuries, scientists have invented many methods and drugs that are being actively used to date. Derivatives of 1,2,4-triazole can be the foundation for the manufacture of new native drugs that will compete with foreign ones. The aim of work was synthesis and confirmation the structure of 2-((4-(R-amino-5-(thiophen-2-ylmethyl-4H-1,2,4-triazol-3-ylthioacetate acids salts. Materials and methods. As starting substances we used 2-((4-(R-amino-5-(thiophen-2-ylmethyl-4H-1,2,4-triazol-3-ylthioacetic acids, which were synthesized by previously described methods. The structure of synthesized compounds was confirmed by the complex use of modern physical-chemical methods of analysis: elemental analysis, 1H-NMR spectroscopy, HPLC-MS. Results. Salts of 2-((4-(R-amino-5-(thiophen-2-ylmethyl-4H-1,2,4-triazol-3-ylthioacetic acids were synthesized by the interaction of the appropriate acids with organic (morpholin, methanamin, 2-hydroxyethanamin, inorganic basics (aqueous ammonia solution, sodium hydroxide and salts (zinc sulfate, ferrum (III chloride, magnesium sulfate, copper (II sulfate in alcoholic or aqueous media. Conclusions. A series of novel 2-((4-(R-amino-5-(thiophen-2-ylmethyl-4H-1,2,4-triazol-3-ylthioacetic acids salts were synthesized. The structure of synthesized compounds is established using modern physical-chemical methods of analysis.

  8. Synthesis and antibacterial activity of bis-[2-hydroxy-3-(1,7,8,9,10-pentamethyl-3,5-dioxo-4-aza-tricyclo[5.2.1.0(2,6)]dec-8-en-4-yloxy)-propyl]-dimethyl-ammonium chloride.

    Science.gov (United States)

    Struga, Marta; Kossakowski, Jerzy; Stefańska, Joanna; Zimniak, Andrzej; Koziol, Anna E

    2008-06-01

    A new quaternary ammonium compound, bis-[2-hydroxy-3-(1,7,8,9,10-pentamethyl-3,5-dioxo-4-aza-tricyclo[5.2.1.0(2,6)]dec-8-en-4-yloxy)-propyl]-dimethyl-ammonium chloride (4), was synthesized. The compound was investigated for antibacterial activity, including Gram-positive cocci and Gram-negative rods, and antifungal activity. Compound 4 showed significant inhibition against Staphylococcus aureus. Research was carried out over 4 standard strains and 40 hospital strains. Elementary analysis and/or MS, (1)H NMR and (13)C NMR spectra confirmed the identity of the products. The molecular structure of 3 was determined by an X-ray analysis.

  9. Growth, structure, Hirshfeld surface and spectroscopic properties of 2-amino-4-hydroxy-6-methylpyrimidinium-2,3-pyrazinedicorboxylate single crystal

    Science.gov (United States)

    Faizan, Mohd; Alam, Mohammad Jane; Afroz, Ziya; Rodrigues, Vítor Hugo Nunes; Ahmad, Shabbir

    2018-03-01

    The present work is focused on the crystal structure, vibrational spectroscopy and DFT calculations of hydrogen bonded 2,3-pyrazinedicorboxylic acid and 2-amino-4-hydroxy-6-methylpyrimidine (PDCA-.AHMP+) crystal. The crystal structure has been determined using single crystal X-ray diffraction analysis which shows that the crystal belongs to monoclinic space group P21/n. The PDCA-.AHMP+ crystal has been characterized by FTIR, FT-Raman and FT-NMR spectroscopic techniques. The FTIR and FT-Raman spectra of the complex have unique spectroscopic feature as compared with those of the starting material to confirm salt formation. The theoretical vibrational studies have been performed to understand the modes of the vibrations of asymmetric unit of the complex by DFT methods. Hirschfeld surface and 2D fingerprint plots analyses were carried out to investigate the intermolecular interactions and its contribution in the building of PDCA-.AHMP+ crystal. The experimental and simulated 13C and 1H NMR studies have assisted in structural analysis of PDCA-.AHMP+ crystal. The electronic spectroscopic properties of the complex were explored by the experimental as well as theoretical electronic spectra simulated using TD-DFT/IEF-PCM method at B3LYP/6-311++G (d,p) level of theory. In addition, frontier molecular orbitals, molecular electrostatic potential map (MEP) and nonlinear optical (NLO) properties using DFT method have been also presented.

  10. Poly[bis­[μ4-N-(2-hydroxy­imino­propion­yl)-N′-(2-oxidoimino­propion­yl)propane-1,3-diaminato]dimethano­lcalciumdicopper(II)

    Science.gov (United States)

    Kalibabchuk, Valentina A.; Usenko, Natalia I.; Golenya, Irina A.; Iskenderov, Turganbay S.; Haukka, Matti

    2009-01-01

    In the title compound, [CaCu2(C9H13N4O4)2(CH3OH)2]n, the CaII atom lies on an inversion center and is situated in a moderately distorted octa­hedral environment. The CuII atom is in a distorted square-pyramidal geometry, defined by four N atoms belonging to the amide and oxime groups of the triply deprotonated residue of N,N′-bis­(2-hydroxy­imino­propano­yl)propane-1,3-diamine (H4pap) and one oxime O atom from a neighboring Hpap ligand at the apical site, forming a dimeric [Cu2(Hpap)2]2− unit. Each dimeric unit connects four Ca atoms and each Ca atom links four [Cu2(Hpap)2]2− units through Ca—O(amide) bonds, leading to a three-dimensional framework. The crystal structure involves intra- and inter­molecular O—H⋯O hydrogen bonds. PMID:21577475

  11. Use of 3-(4-hydroxyphenyl)propionic acid as electron donating compound in a potentiometric aflatoxin M{sub 1}-immunosensor

    Energy Technology Data Exchange (ETDEWEB)

    Rameil, Steffen, E-mail: s.rameil@r-biopharm.de [R-Biopharm AG, An der neuen Bergstrasse 17, 64297 Darmstadt (Germany); Schubert, Peter, E-mail: p.schubert@r-biopharm.de [R-Biopharm AG, An der neuen Bergstrasse 17, 64297 Darmstadt (Germany); Grundmann, Peter, E-mail: peter.grundmann@jennewein-biotech.de [R-Biopharm AG, An der neuen Bergstrasse 17, 64297 Darmstadt (Germany); Dietrich, Richard, E-mail: R.Dietrich@mh.vetmed.uni-muenchen.de [Department of Veterinary Sciences, University of Munich, Schoenleutner Str 8, 85764 Oberschleissheim (Germany); Maertlbauer, Erwin, E-mail: E.Maertlbauer@mh.vetmed.uni-muenchen.de [Department of Veterinary Sciences, University of Munich, Schoenleutner Str 8, 85764 Oberschleissheim (Germany)

    2010-02-19

    We developed a potentiometric aflatoxin M{sub 1}-immunosensor which utilizes 3-(4-hydroxyphenyl)propionic acid (p-HPPA) as electron donating compound for horseradish peroxidase (HRP; EC 1.11.1.7). The assay system consists of a polypyrrole-surface-working electrode coated with a polyclonal anti-M{sub 1} antibody (pAb-AFM{sub 1}), a Ag/AgCl reference electrode and a HRP-aflatoxin B{sub 1} conjugate (HRP-AFB{sub 1} conjugate). To optimize the potentiometric measuring system p-HPPA as well as related compounds serving as electron donating compounds were compared. Also the influence of different buffer systems, varying pH and substrate concentrations on signal intensity was investigated. Our results suggest that reaction conditions that favor the formation of Pummerer's type ketones lead to an increase in signal intensity rather than formation of fluorescent dye. Comparison with commercial ready-to-use HRP electron donating compounds such as 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS), o-phenylenediamine (OPD) or 3,3',5,5'-tetramethylbenzidine (TMB) showed that only 34%, 77% and 49% of the signal intensity of p-HPPA were reached, respectively. The optimized assay had a detection limit of 40 pg mL{sup -1} and allowed detection of 500 pg mL{sup -1} (FDA action limit) aflatoxin M{sub 1} (AFM{sub 1}) in pasteurized milk and UHT-milk containing 0.3-3.8% fat within 10 min without any sample treatment. The working range was between 250 and 2000 pg mL{sup -1} AFM{sub 1}.

  12. SYNTHESIS, CHARACTERIZATION AND ANTIOXIDANT ACTIVITY OF 7-HYDROXY-3',4'-DIMETHOXYFLAVONE

    Directory of Open Access Journals (Sweden)

    Elfi Susanti VH

    2012-03-01

    Full Text Available Synthesis of flavones and their derivatives has attracted considerable attention due to their significant pharmaceutical effects. 7-hydroxy-3',4'-dimethoxyflavone has been synthesized and its antioxidant activity has been investigated. Flavone was synthesized by oxidative cyclization of chalcone. 2',4'-dihydroxy-3,4-dimethoxychalcone was prepared by Claisen-Schmidt condensation of 2,4-dihydroxyacetophenones with 3,4-dimethoxybenzaldehydes in the presence of aqueous solution of sodium hydroxide and ethanol at room temperature. Oxidative cyclization of 2',4'-dihydroxy-3,4-dimethoxychalcone was done by using I2 catalyst in DMSO to form 7-hydroxy-3',4'-dimethoxyflavone. The synthesized compounds were characterized by means of their UV-Vis, IR, 1H-NMR and 13C-NMR spectral data. The compound was tested for their antioxidant activities by DPPH method.

  13. Synthesis, characterization, antioxidant and brine shrimp cytotoxic activity of novel 3-benzothioyl-1-(3-hydroxy-3-phenyl -3-propyl)-1-methylthiourea.

    Science.gov (United States)

    Shoaib, Mohammad; Ullah, Abid; Shah, Syed Wadood Ali; Tahir, Muhammad Nawaz

    2017-07-01

    In the present research work novel ephedrine based thiourea derivative, 3-benzothioyl-1-(3-hydroxy-3-phenyl -3-propyl)-1-methylthiourea 4is synthesized and then characterized elemental analyzed via various techniques i.e., Proton NMR, carbon13 NMR and fatherly confirmed via X-ray crystallography. Compound 4 was then screened for their possible antioxidant and cytotoxic potentials. Benzoyl chloride was treated with an equimolar potassium thiocyanate in acetone to achieve benzoyl isothiocyantes. It was then treated with an equimolar (1R, 2S)-(-)-Ephedrine to obtain the 3-benzothioyl-1-(3-hydroxy-3-phenyl-3-propyl)-1-methyl thiourea4. It was then screened for antioxidant and cytotoxic potentials. The compound 4 showed excellent antioxidant activity almost comparable to ascorbic acid (standard) and have significant cytotoxic activity with LC 50 value 05±0.58 ppm.

  14. Regioselective intramolecular ring closure of 2-amino-6-bromo-2,6-dideoxyhexono-1,4-lactones to 5- or 6-membered iminuronic acid analogues:synthesis of 1-deoxymannojirimycin and 2,5-dideoxy-2,5-imino-D-glucitol

    DEFF Research Database (Denmark)

    Malle, Birgitte Mølholm; Lundt, Inge; Wrodnigg, Tanja M.

    2008-01-01

    closure took place by 5-exo attack on the 5,6-epoxide leading to 2,5-dideoxy-2,5-imino-L-gulonic acid (9b), which was reduced to 2,5-dideoxy-2,5-imino-D-glucitol (9c). The method was further applied to 2-amino-6-bromo-2,6-dideoxy-D-galacto- as well as D-talo-1,4-lactones (14 and 15). However, only......-galacto- as well as L-talo-2-amino-6-bromo-2,6-dideoxy-1,4-lactones ent-14 and ent-15, reacted accordingly to give the D-galacto- and L-altro-1,5-iminuronic acid mimetics, (2S,3S,4R,5S)-3,4,5-trihydroxypipecolic acid (2,6-dideoxy-2,6-imino-L-galactonic acid, ent-16) and (2R,3S,4R,5S)-3,4,5-trihydroxypipecolic...

  15. Fabrication of a new samarium(III) ion-selective electrode based on 3-{l_brace}[2-oxo-1(2h)-acenaphthylenyliden]amino{r_brace}-2-thioxo -1,3-thiazolidin-4-one

    Energy Technology Data Exchange (ETDEWEB)

    Zamani, Hassan Ali [Islamic Azad University, Quchan (Iran, islamic Republic of). Quchan Branch. Dept. of Chemistry]. E-mail: haszamani@yahoo.com; Ganjali, Mohammad Reza [Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of). Endocrine and Metabolism Research Center; Adib, Mehdi [University of Tehran, Tehran (Iran, Islamic Republic of). Faculty of Chemistry. Center of Excellence in Electrochemistry

    2007-07-01

    This paper introduces the development of an original PVC membrane electrode, based on 3-{l_brace}[2-oxo-1(2H)-acenaphthylenyliden]amino{r_brace}-2-thioxo-1,3-thiazolidin-4-one (ATTO) which has revealed to be a suitable carrier for Sm{sup 3+} ions. The resulting data illustrated that the electrode shows a Nernstian slope of 19.3 {+-} 0.6 mV per decade for Sm{sup 3+} ions over a broad working concentration range of 1.0 X 10{sup -6} to 1.0 X 10{sup -1} mol L{sup -1}. The lower detection limit was found to be equal to (5.5{+-} 0.3) X 10{sup -7} mol L{sup -}'1 in the pH range of 3.5-7.5, and the response time was very short ({approx}10 s). The potentiometric sensor displayed good selectivities for a number of cations such as alkali, alkaline earth, transition and heavy metal ions. (author)

  16. Kinetics of metabolism of glucose, propionate and CO2 in steers as affected by injecting phlorizin and feeding propionate

    International Nuclear Information System (INIS)

    Veenhuizen, J.J.; Russell, R.W.; Young, J.W.

    1988-01-01

    Effects of injecting phlorizin subcutaneously and/or feeding propionate on metabolism of glucose, propionate and CO2 were determined for four steers used in a 4 x 4 Latin square design. Isotope dilution techniques were used to determine a four-pool kinetic solution for the flux of carbon among plasma glucose, rumen propionate, blood CO2 and rumen CO2. Injecting 1 g of phlorizin twice daily for 19 d resulted in 7.1 mol glucose C/d being excreted in urine. The basal glucose production of 13.4 mol C/d was increased to 17.9 mol C/d with phlorizin. There was no change in glucose oxidation or propionate production. The percentage of plasma glucose derived from propionate was unaffected by phlorizin, but 54 +/- 0.4% of total propionate was converted to plasma glucose during phlorizin treatment versus 40 +/- 0.6% during the basal treatment. When propionate was fed (18.3 mol C/d) glucose production increased to 21.2 mol C/d from the basal value of 13.4 mol C/d, and propionate oxidation to CO2 increased to 14.9 mol C/d from the basal value of 4.1 mol C/d. Glucose derived from propionate was 43 +/- 5% for the basal treatment and 67 +/- 3% during propionate feeding. The percentage of propionate converted to plasma glucose and blood and rumen CO2 was not affected by feeding propionate. An increased need for glucose, because of glucose excretion during phlorizin treatment, caused an increased utilization of propionate for gluconeogenesis, but an increased availability of propionate caused an increase in glucose production without affecting the relative distribution of carbon from propionate

  17. A practical and improved synthesis of (3S,5S)-3-[(tert-butyloxycarbonyl)methyl]- 5-[(methanesulfonyloxy)methyl]-2- pyrrolidinone.

    Science.gov (United States)

    Yee, Nathan K; Dong, Yong; Kapadia, Suresh R; Song, Jinhua J

    2002-11-29

    A practical and improved synthesis of (3S,5S)-3-[(tert-butyloxycarbonyl)methyl]-5-[(methanesulfonyloxy)methyl]-2-pyrrolidinone (1) is described. The key transformations involve a highly efficient reaction sequence consisting of ethoxycarbonylation, alkylation, hydrolysis, and decarboxylation to produce compound 10. The process described herein is practical, robust, and cost-effective, and it has been successfully implemented in a pilot plant to produce a multikilogram quantity of mesylate 1.

  18. New Synthesis, Structure and Analgesic Properties of Methyl 1-R-4-Methyl-2,2-Dioxo-1H-2λ6,1-Benzothiazine-3-Carboxylates

    Directory of Open Access Journals (Sweden)

    Liliana Azotla-Cruz

    2017-01-01

    Full Text Available According to the principles of the methodology of bioisosteric replacements a series of methyl 1-R-4-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxylates has been obtained as potential analgesics. In addition, a fundamentally new strategy for the synthesis of compounds of this chemical class involving the introduction of N-alkyl substituent at the final stage in 2,1-benzothiazine nucleus already formed has been proposed. Using nuclear magnetic resonance (NMR spectroscopy, mass spectrometry and X-ray diffraction analysis it has been proven that in the DMSO/K2CO3 system the reaction of methyl 4-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxylate and alkyl halides leads to formation of N-substituted derivatives with good yields regardless of the structure of the alkylating agent. The peculiarities of NMR (1Н and 13С spectra of the compounds synthesized, their mass spectrometric behavior and the spatial structure are discussed. In N-benzyl derivative the ability to form a monosolvate with methanol has been found. According to the results of the pharmacological testing conducted on the model of the thermal tail-flick it has been determined that replacement of 4-ОН-group in methyl 1-R-4-hydroxy-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxylates for the methyl group is actually bioisosteric since all methyl 1-R-4-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxylates synthesized demonstrated a statistically significant analgesic effect. The majority of the substances can inhibit the thermal pain response much more effective than piroxicam in the same dose. Under the same conditions as an analgesic the N-methyl-substituted analog exceeds not only piroxicam, but more active meloxicam as well. Therefore, it deserves in-depth biological studies on other experimental models.

  19. Syntheses of DNA adducts of two heterocyclic amines, 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeA alpha C) and 2-amino-9H-pyrido[2,3-b]indole (A alpha C) and identification of DNA adducts in organs from rats dosed with MeA alpha C

    DEFF Research Database (Denmark)

    Frederiksen, Hanne; Frandsen, Henrik Lauritz; Pfau, W.

    2004-01-01

    2-Amino-3-methyl-9H-pyrido[2,3-b]indole (MeAalphaC) and 2-amino-3-methyl-9H-pyrido[2,3-b]indole (AalphaC) are mutagenic and carcinogenic heterocyclic amines formed during ordinary cooking. MeAalphaC and AalphaC are activated to mutagenic metabolites by cytochrome P450-mediated N-oxidation...... by reaction of the parent amines with acetylated guanine N3-oxide. N-2-OH-MeAalphaC and N-2-OH-AalphaC reacted with calf thymus DNA after addition of acetic anhydride. P-32-postlabelling analysis of modified DNA showed one major adduct co-migrating with N-2-(3',5'-diphospho-2'-deoxyguanosin-8-yl...

  20. Synthetic, XRD, non-covalent interactions and solvent dependent nonlinear optical studies of Sulfadiazine-Ortho-Vanillin Schiff base: (E)-4-((2-hydroxy-3-methoxy- benzylidene) amino)-N-(pyrimidin-2-yl)benzene-sulfonamide

    Science.gov (United States)

    Shahid, Muhammad; Salim, Muhammad; Khalid, Muhammad; Tahir, Muhammad Nawaz; Khan, Muhammad Usman; Braga, Ataualpa Albert Carmo

    2018-06-01

    In this study, Sulfadiazine-Ortho-Vanillin Schiff base namely (E)-4-((2-hydroxy-3-methoxybenzylidene)amino)sbnd N-(pyrimidin-2-yl)benzene-sulfonamide (BS) was synthesized. Chemical characterization and computational studies using different techniques like XRD, FT-IR, UV-Vis, NBO, FMO, and MEP have been employed. Density functional theory (DFT) calculations have been performed at M06-2X/6-311 + G(d,p) level of theory to obtain optimized geometry and vibrational wave numbers for (E)-4-((2-hydroxy-3-methoxybenzylidene)amino)sbnd N-(pyrimidin-2-yl)benzene-sulfonamide (BS). The DFT optimized geometry supports the experimental XRD parameters. Frontier molecular orbital (FMO) energies and molecular electrostatic potential (MEP) surfaces have been executed at M06-2X/6-311 + G(d,p) level of theory. NBO analysis has been carried out at M06-2X/6-311 + G(d,p) level which not only discovered the hyper conjugative interactions and stability in title molecule but also reconfirmed the existence of Nsbnd H⋯N hydrogen bonds between the dimer. The findings of small EHOMO-ELUMO gap shows less hardness and larger softness values which suggested the bioactiveness of the title molecule. Finally, the effect of solvent on nonlinear optical (NLO) properties has been executed using M06-2X level of theory and 6-311 + G (d,p) basis set. The solvent polarity enhanced the NLO response from 3.62 × 10-30 esu to 4.66 × 10-30 esu indicating the considerable NLO character hence in general may have potential applications in the development of non-linear optical materials.

  1. Synthesis of certain fused pyrazoles derived from 2-methyl-3-amino-6-iodo-4(3 H) quinazolinone as possible insecticidal and radiosensitizing agents

    International Nuclear Information System (INIS)

    Abdel-Hamide, S.G.; Ghorab, M.M.; Ali, G.M.

    1996-01-01

    The Verisimilar reaction on 3-amino-2-methyl-6-4-quinazolone (1) using P O Cl 3 /DMF afforded 3-formyl pyrazole derivative (2). The condensation products (3 a,b) were obtained via reaction of (2) with malononitrile or ethyl cyano acetate. Heating the condensation products (3 a,b) with acetyl derivatives in the presence of ammonium acetate yielded the corresponding cyano pyridines (9 a-e) and (10 a-e), respectively. Compounds (9 c) and (10 c) were obtained also from the interaction of the chalcone derivative (11) with malononitrile or ethyl cyano acetate. Condensation of (2) with semicarbazide hydrochloride, thio semicarbazide or aromatic amines gave the corresponding (12 a), (12 b) and (13 a-c), respectively. Compound (12 a) could be cyclized to (14) in acid medium. Interaction of compound (12 b) with chloro acetyl chloride gave (15). The Verisimilar reaction on Schiff bass (16) using P O Cl 3 /DMF gave the amino acrolein derivates (17), which was converted into 2-pyrazole derivative (18) and 2-isoxazolinyl derivative (19), respectively. The obtained compounds have been characterized on the basis of their IR, 'H-NMR and Mass spectral data and elemental analysis. Among the synthesized compounds only the formyl pyrazole derivative (2) and the azetidinylthioured derivative (15) showed a remarkable adulticidal activity. In addition the formyl pyrazole derivative (2) acted as a potent radiosensitizer. 2 figs., 3 tabs

  2. Aldol Reactions of Axially Chiral 5-Methyl-2-(o-arylimino-3-(o-aryl-thiazolidine-4-ones

    Directory of Open Access Journals (Sweden)

    Sule Erol Gunal

    2016-06-01

    Full Text Available Axially chiral 5-methyl-2-(o-arylimino-3-(o-aryl-thiazolidine-4-ones have been subjected to aldol reactions with benzaldehyde to produce secondary carbinols which have been found to be separable by HPLC on a chiral stationary phase. Based on the reaction done on a single enantiomer resolved via a chromatographic separation from a racemic mixture of 5-methyl-2-(α-naphthylimino-3-(α-naphthyl-thiazolidine-4-one by HPLC on a chiral stationary phase, the aldol reaction was shown to proceed via an enolate intermediate. The axially chiral enolate of the thiazolidine-4-one was found to shield one face of the heterocyclic ring rendering face selectivity with respect to the enolate. The selectivities observed at C-5 of the ring varied from none to 11.5:1 depending on the size of the ortho substituent. Although the aldol reaction proceeded with a lack of face selectivity with respect to benzaldehyde, recrystallization returned highly diastereomerically enriched products.

  3. MMPs and soluble ICAM-5 increase neuronal excitability within in vitro networks of hippocampal neurons.

    Directory of Open Access Journals (Sweden)

    Mark Niedringhaus

    Full Text Available Matrix metalloproteinases (MMPs are zinc-dependent endopeptidases that are released from neurons in an activity dependent manner. Published studies suggest their activity is important to varied forms of learning and memory. At least one MMP can stimulate an increase in the size of dendritic spines, structures which represent the post synaptic component for a large number of glutamatergic synapses. This change may be associated with increased synaptic glutamate receptor incorporation, and an increased amplitude and/or frequency of α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA mini excitatory post-synaptic currents (EPSCs. An associated increase in the probability of action potential occurrence would be expected. While the mechanism(s by which MMPs may influence synaptic structure and function are not completely understood, MMP dependent shedding of specific cell adhesion molecules (CAMs could play an important role. CAMs are ideally positioned to be cleaved by synaptically released MMPs, and shed N terminal domains could potentially interact with previously unengaged integrins to stimulate dendritic actin polymerization with spine expansion. In the present study, we have used multielectrode arrays (MEAs to investigate MMP and soluble CAM dependent changes in neuronal activity recorded from hippocampal cultures. We have focused on intercellular adhesion molecule-5 (ICAM-5 in particular, as this CAM is expressed on glutamatergic dendrites and shed in an MMP dependent manner. We show that chemical long-term potentiation (cLTP evoked changes in recorded activity, and the dynamics of action potential bursts in particular, are altered by MMP inhibition. A blocking antibody to β(1 integrins has a similar effect. We also show that the ectodomain of ICAM-5 can stimulate β(1 integrin dependent increases in spike counts and burst number. These results support a growing body of literature suggesting that MMPs have important effects on neuronal

  4. Carbamoyl anion-initiated cascade reaction for stereoselective synthesis of substituted α-hydroxy-β-amino amides.

    Science.gov (United States)

    Lin, Chao-Yang; Ma, Peng-Ju; Sun, Zhao; Lu, Chong-Dao; Xu, Yan-Jun

    2016-01-18

    A carbamoyl anion-initiated cascade reaction with acylsilanes and imines has been used to rapidly construct substituted α-hydroxy-β-amino amides. The Brook rearrangement-mediated cascade allows the formation of two C-C bonds and one O-Si bond in a single pot. Using this approach, a range of α-aryl α-hydroxy-β-amino amides has been synthesized in high yields with excellent diastereoselectivities.

  5. Two Zinc(II) metal-organic frameworks with mixed ligands of 5-amino-tetrazolate and l,2,4,5-benzenetetracarboxylate: Synthesis, structural diversity and photoluminescent properties

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xiao-Bing [Department of Chemistry, Shaoguan University, Shaoguan, Guangdong 512005 (China); Lu, Wen-Guan, E-mail: lwg@sgu.edu.cn [Department of Chemistry, Shaoguan University, Shaoguan, Guangdong 512005 (China); Zhong, Di-Chang [School of Chemistry and Chemical Engineering, Gannan Normal University, Ganzhou 341000 (China)

    2017-06-15

    The reactions of Zn(NO{sub 3}){sub 2}·6H{sub 2}O with mixed ligands of 5-amino-tetrazole (Hatz) and l,2,4,5-benzenetetracarboxylic acid (H{sub 4}btec) under hydro(solvo)thermal conditions, gave two three-dimensional (3D) porous metal-organic frameworks (MOFs) of ([Zn{sub 3}(atz){sub 2}(btec)(DMF){sub 2}]·DMF·2H{sub 2}O){sub n} (1) and [Zn{sub 2}(Hprz)(atz)(btec)(H{sub 2}O)]{sub n} (2) in the absence and presence of piperazine (prz), respectively. 1 and 2 were characterized by infrared spectra (IR), elemental analyses (EA) and single-crystal/powder X-ray diffraction. In 1, the adjacent 1D [Zn{sub 3}(btec)]{sub n}{sup 2n+} chains are linked together by atz{sup −} ligands to form a 3D porous MOF with 1D tetragonal channels filled with coordinated and guest DMF, and lattice water molecules. In 2, the adjacent 2D [Zn{sub 2}(btec)]{sub n} wavelike sheets are pillared through atz{sup −} ligands to generate a 3D layered-pillared porous MOF with 1D open channels, which are occupied by coordinated Hprz{sup +} cations and coordinated water molecules. Additionally, thermal stabilities and photoluminescent properties of both compounds in the solid-state at room temperature have been investigated and discussed in detail. - Graphical abstract: Two new MOFs constructed from Zn(II) salts with mixed ligands of 5-amino-tetrazole and l,2,4,5-benzenetetracarboxylic acid were synthesized under different reaction conditions. Structural diversities indicate that the reaction solvent system or the presence of organic base play crucial roles in modulating structures of these compounds. And more, their thermal stability and luminescence are also discussed. - Highlights: • Two new Zn(II) MOFs based on mixed ligands were synthesized. • The two Zn(II) MOFs exhibit different structural motifs. • The two Zn(II) MOFs are photoluminscent in the solid state at room temperature.

  6. Enhanced Bio-hydrogen Production from Protein Wastewater by Altering Protein Structure and Amino Acids Acidification Type

    Science.gov (United States)

    Xiao, Naidong; Chen, Yinguang; Chen, Aihui; Feng, Leiyu

    2014-01-01

    Enhanced bio-hydrogen production from protein wastewater by altering protein structure and amino acids acidification type via pH control was investigated. The hydrogen production reached 205.2 mL/g-protein when protein wastewater was pretreated at pH 12 and then fermented at pH 10. The mechanism studies showed that pH 12 pretreatment significantly enhanced protein bio-hydrolysis during the subsequent fermentation stage as it caused the unfolding of protein, damaged the protein hydrogen bonding networks, and destroyed the disulfide bridges, which increased the susceptibility of protein to protease. Moreover, pH 10 fermentation produced more acetic but less propionic acid during the anaerobic fermentation of amino acids, which was consistent with the theory of fermentation type affecting hydrogen production. Further analyses of the critical enzymes, genes, and microorganisms indicated that the activity and abundance of hydrogen producing bacteria in the pH 10 fermentation reactor were greater than those in the control. PMID:24495932

  7. Enhanced bio-hydrogen production from protein wastewater by altering protein structure and amino acids acidification type.

    Science.gov (United States)

    Xiao, Naidong; Chen, Yinguang; Chen, Aihui; Feng, Leiyu

    2014-02-05

    Enhanced bio-hydrogen production from protein wastewater by altering protein structure and amino acids acidification type via pH control was investigated. The hydrogen production reached 205.2 mL/g-protein when protein wastewater was pretreated at pH 12 and then fermented at pH 10. The mechanism studies showed that pH 12 pretreatment significantly enhanced protein bio-hydrolysis during the subsequent fermentation stage as it caused the unfolding of protein, damaged the protein hydrogen bonding networks, and destroyed the disulfide bridges, which increased the susceptibility of protein to protease. Moreover, pH 10 fermentation produced more acetic but less propionic acid during the anaerobic fermentation of amino acids, which was consistent with the theory of fermentation type affecting hydrogen production. Further analyses of the critical enzymes, genes, and microorganisms indicated that the activity and abundance of hydrogen producing bacteria in the pH 10 fermentation reactor were greater than those in the control.

  8. Synthesis and structure of new 4-amino-5-(2-R1-phenyl-1,2,4-triazole-3-thiol alkilderivatives

    Directory of Open Access Journals (Sweden)

    Ye. S. Pruglo

    2017-08-01

    Full Text Available Chemistry of heterocyclic systems is a separate branch of organic chemistry with a long history and future prospects. The ring system of 1,2,4-triazole continuously attracts the interest of chemists, pharmacologists and pharmacists in finding medicinal compounds through its universal potential interactions with biological systems. Today it is known that 1,2,4-triazole derivatives have antibacterial, antifungal, antiinflammatory, anticonvulsant, antiviral, antituberculosis, antioxidant, anticancer and antitumor activities. They also have analgesic, local anesthetic, antimalarial, antiproliferative effects, antihypertensive, antidepressant, sedative, antihistamine, hepatoprotective, hypoglycemic, diuretic, antipyretic and countless number of action types. Therefore, the search of biologically active remedies and creating of new drugs on its base is highly efficient topical issue of medical and pharmaceutical work. The purpose of these studies is the synthesis, establishment of physical-chemical parameters of new 4-amino-5-(2-R1-phenyl-1,2,4-triazole-3-thiol alkylderivatives. Materials and methods. The studying of physical and chemical properties of compounds was made in accordance with the methods described in the State Pharmacopoeia of Ukraine 2.0. The melting point was determined on an automatic gear MPA100. The elemental composition of the compounds was set on the analyzer Elementar Vario EL cube. 1H NMR spectra were recorded using the spectrometer Varian Mercury VX-200 (1H, 200 MHz and decrypted by a computer program SpinWorks 3.1.8. Chromatography-mass spectral studies were carried out in the gas-liquid chromatograph Agilent 1260 Infinity HPLC equipped with a mass spectrometer Agilent 6120 (in electrospray ionization (ESI. Results. 4-amino-5-phenyl-4H-1,2,4-triazole-3-thiol and 4-amino-5-(2-bromophenyl-4H-1,2,4-triazol-3-thiol were used as the initial materials. These compounds were obtained by reaction of benzoic acid hydrazide and 2

  9. A functional (E)-4-hydroxy-3-methylbut-2-enyl diphosphate reductase exhibits diurnal regulation of expression in Stevia rebaudiana (Bertoni).

    Science.gov (United States)

    Kumar, Hitesh; Kumar, Sanjay

    2013-09-15

    The leaves of stevia [Stevia rebaudiana (Bertoni)] are a rich source of steviol glycosides that are used as non-calorific sweetener in many countries around the world. Steviol moiety of steviol glycosides is synthesized via plastidial 2C-methyl-D-erythritol 4-phosphate pathway, where (E)-4-hydroxy-3-methylbut-2-enyl diphosphate reductase (HDR) is the key enzyme. HDR catalyzes the simultaneous conversion of (E)-4-hydroxy-3-methylbut-2-enyl diphosphate into five carbon isoprenoid units, isopentenyl diphosphate and dimethylallyl diphosphate. Stevia HDR (SrHDR) successfully rescued HDR lethal mutant strain MG1655 araispH upon genetic complementation, suggesting SrHDR to encode a functional protein. The gene exhibited diurnal variation in expression. To identify the possible regulatory elements, upstream region of the gene was cloned and putative cis-acting elements were detected by in silico analysis. Electrophoretic mobility shift assay, using a putative light responsive element GATA showed the binding of nuclear proteins (NP) isolated from leaves during light period of the day, but not with the NP from leaves during the dark period. Data suggested the involvement of GATA box in light mediated gene regulation of SrHDR in stevia. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Synthesis of 25-hydroxyvitamin D3 3β-3'-[N-(4-azido-2-nitrophenyl)amino]propyl ether, a second-generation photoaffinity analogue of 25-hydroxyvitamin D3: Photoaffinity labeling of rat serum vitamin D binding protein

    International Nuclear Information System (INIS)

    Ray, R.; Holick, M.F.; Bouillon, R.; Van Baelen, H.

    1991-01-01

    Vulnerability of 25-hydroxy-[26,27- 3 H]vitamin D 3 3β-N-(4-azido-2-nitrophenyl)glycinate, a photoaffinity analogue of 25-hydroxyvitamin D 3 (25-OH-D 3 ) toward standard conditions of carboxymethylationin promoted the authors to synthesize 25-hydroxyvitamin D 3 3β-3'-[N-(4-azido-2-nitrophenyl)amino]propyl ether (25-ANE), a hydrolytically stable photoaffinity analogue of 25-OH-D 3 , and 25-hydroxyvitamin D 3 3β-3'-[N-(4-azido-2-nitro-[3,5- 3 H]phenyl)amino]propyl ether ( 3 H-25-ANE), the radiolabeled counterpart of 25-ANE competes for the 25-OH-D 3 binding site in rat serum vitamin D binding protein (rDBP). On the other hand, UV exposure of a sample of purified rat DBP (rDBP), preincubated in the dark with 3 H-25-ANE, covalently labeled the protein. However, very little covalent labeling was observed in the absence of UV light or in the presence of a large excess of 25-OH-D 3 . These results provide strong evidence for the covalent labeling of the 25-OH-D 3 binding site in rDPB by 3 H-25-ANE

  11. Description of analytical method and clinical utility of measuring serum 7-alpha-hydroxy-4-cholesten-3-one (7aC4) by mass spectrometry.

    Science.gov (United States)

    Donato, Leslie J; Lueke, Alan; Kenyon, Stacy M; Meeusen, Jeffrey W; Camilleri, Michael

    2018-02-01

    Imbalance of bile acids (BA) homeostasis in the gastrointestinal tract can lead to chronic diarrhea or constipation when BA in the colon are in excess or low, respectively. Since both disturbances of bowel function can result from other etiologies, identifying BA imbalance is important to tailor treatment strategies. Serum concentrations of 7-alpha-hydroxy-4-cholesten-3-one (7aC4), a precursor in bile acid synthesis, reflect BA homeostasis. Here we describe a method to accurately measure serum 7aC4 and evaluate the clinical utility in patients with diarrhea or constipation phenotypes. Serum 7aC4 is measured after acetonitrile protein precipitation using C18 liquid chromatography, tandem mass spectrometry, and deuterium-labeled 7aC4 internal standard. Assay performance including linearity, precision, and accuracy was assessed using waste serum samples. The reference interval was established in healthy individuals without BA-altering conditions or medications. Clinical performance was assessed in patients with irritable bowel syndrome. The method precisely and accurately measured 7aC4 in human serum from 1.4-338ng/mL with no ion suppression or interference from related 7-keto-cholesterol. Central 95th percentile reference interval was 2.5-63.2ng/mL. Lower serum 7aC4 was found in patients with constipation with sensitivity/specificity of 79%/55% compared to healthy controls. Higher 7aC4 was found in patients with bile acid diarrhea (BAD) compared to those without BAD with sensitivity/specificity of 82%/53%. We have developed a sensitive and precise assay for measuring the concentration of 7aC4 in serum. The assay can be used to screen for diarrhea caused by bile acid malabsorption. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  12. Design, Synthesis and the Biological Evaluation of New 1,3-Thiazolidine-4-ones Based on the 4-Amino-2,3-dimethyl-1-phenyl-3-pyrazolin-5-one Scaffold

    Directory of Open Access Journals (Sweden)

    Maria Apotrosoaei

    2014-09-01

    Full Text Available New thiazolidine-4-one derivatives based on the 4-aminophenazone (4-amino-2,3-dimethyl-1-phenyl-3-pyrazolin-5-one scaffold have been synthesized as potential anti-inflammatory drugs. The pyrazoline derivatives are known especially for their antipyretic, analgesic and anti-inflammatory effects, but recently there were synthesized new compounds with important antioxidant, antiproliferative, anticancer and antidiabetic activities. The beneficial effects of these compounds are explained by nonselective inhibition of cyclooxygenase izoenzymes, but also by their potential scavenging ability for reactive oxygen and nitrogen species. The structure of the new compounds was proved using spectroscopic methods (FR-IR, 1H-NMR, 13C-NMR, MS. The in vitro antioxidant potential of the synthesized compounds was evaluated according to the ferric reducing antioxidant power, phosphomolydenum reducing antioxidant power, DPPH and ABTS radical scavenging assays. The chemical modulation of 4-aminophenazone (6 through linkage to thiazolidine-propanoic acid derivatives 5a–l led to improved antioxidant potential, all derivatives 7a–l being more active than phenazone. The most active compounds are the derivatives 7e, and 7k, which showed the higher antioxidant effect depending on the antioxidant assay considered.

  13. Roles of Fragile X Mental Retardation Protein in Dopaminergic Stimulation-induced Synapse-associated Protein Synthesis and Subsequent α-Amino-3-hydroxyl-5-methyl-4-isoxazole-4-propionate (AMPA) Receptor Internalization*

    OpenAIRE

    Wang, Hansen; Kim, Susan S.; Zhuo, Min

    2010-01-01

    Fragile X syndrome, the most common form of inherited mental retardation, is caused by the absence of the RNA-binding protein fragile X mental retardation protein (FMRP). FMRP regulates local protein synthesis in dendritic spines. Dopamine (DA) is involved in the modulation of synaptic plasticity. Activation of DA receptors can regulate higher brain functions in a protein synthesis-dependent manner. Our recent study has shown that FMRP acts as a key messenger for DA modulation in forebrain ne...

  14. Metabolism of carbon-14 labelled l-tryptophan, l-kynerenine and hydroxy-l-kynerenine in miners with scleroderma

    International Nuclear Information System (INIS)

    Hankes, L.V.; De Bruin, E.; Jansen, C.R.; Voster, L.; Schmaeler, M.

    1977-01-01

    Six South African white miners were studied with the 2-g l-tryptophan load test and tracer doses of L-tryptophan-7a-carbon-14, L-kynurenine-keto-carbon-14 and hydroxy-L-kynerenine-keto-carbon-14. The breath 14 CO 2 and 14 urinary metabolites were measured. When they were compared with a previous study of American women with scleroderma, similar 14 CO 2 and tryptophan metabolite excretion patterns were observed in the data from the miners. The labelled quinolinic acid excretion was more significantly elevated in the South African miners' urine than in the urine of the American women. The data from both studies suggest that some patients with scleroderma have an altered step in the tryptophan metabolic pathway after hydroxy-anthranilic acid. What relationship exists between the induction of pulmonary silicosis and the subsequent development of scleroderma, requires additional human studies

  15. Potentiation of insulin release in response to amino acid methyl esters correlates to activation of islet glutamate dehydrogenase activity

    DEFF Research Database (Denmark)

    Kofod, Hans; Lernmark, A; Hedeskov, C J

    1986-01-01

    Column perifusion of mouse pancreatic islets was used to study the ability of amino acids and their methyl esters to influence insulin release and activate islet glutamate dehydrogenase activity. In the absence of L-glutamine, L-serine and the methyl ester of L-phenylalanine, but neither L...... glutamate dehydrogenase activity showed that only the two methyl esters of L-phenylalanine and L-serine activated the enzyme. It is concluded that the mechanism by which methyl esters of amino acids potentiate insulin release is most likely to be mediated by the activation of pancreatic beta-cell glutamate...

  16. A new diarylheptanoid from Alpinia officinarum promotes the differentiation of 3T3-L1 preadipocytes.

    Science.gov (United States)

    Zhang, Xuguang; Zhang, Xiaopo; Wang, Yong; Chen, Feng; Li, Youbin; Li, Yonghui; Tan, Yinfeng; Gong, Jingwen; Zhong, Xia; Li, Hailong; Zhang, Junqing

    2018-03-01

    A new diarylheptanoid, namely trans-(4R,5S)-epoxy-1,7-diphenyl-3-heptanone (1), and a new natural product, 7-(4″-hydroxy-3″-methoxyphenyl)-1-phenyl-hepta-4E,6E-dien-3-one (2), were obtained from the aqueous extract of Alpinia officinarum Hance, together with three other diarylheptanoids, 5-hydroxy-1,7-diphenyl-3-heptanone (3), 1,7-diphenyl-4E-en-3-heptanone (4) and 5-methoxy-1,7-diphenyl-3-heptanone (5). The structures were characterised mainly by analysing their physical data including IR, NMR and HRMS. This study highlights that the 4,5-epoxy moiety in 1 is rarely seen in diarylheptanoids. In addition, the five isolates were tested for their differentiation activity of 3T3-L1 preadipocytes. The results showed that these compounds could dose-dependently promote adipocyte differentiation without cytotoxicity (IC 50  > 100 μM).

  17. Different structural requirements for functional ion pore transplantation suggest different gating mechanisms of NMDA and kainate receptors.

    Science.gov (United States)

    Villmann, Carmen; Hoffmann, Jutta; Werner, Markus; Kott, Sabine; Strutz-Seebohm, Nathalie; Nilsson, Tanja; Hollmann, Michael

    2008-10-01

    Although considerable progress has been made in characterizing the physiological function of the high-affinity kainate (KA) receptor subunits KA1 and KA2, no homomeric ion channel function has been shown. An ion channel transplantation approach was employed in this study to directly test if homomerically expressed KA1 and KA2 pore domains are capable of conducting currents. Transplantation of the ion pore of KA1 or KA2 into GluR6 generated perfectly functional ion channels that allowed characterization of those electrophysiological and pharmacological properties that are determined exclusively by the ion pore of KA1 or KA2. This demonstrates for the first time that KA1 and KA2 ion pore domains are intrinsically capable of conducting ions even in homomeric pore assemblies. NMDA receptors, similar to KA1- or KA2-containing receptors, function only as heteromeric complexes. They are composed of NR1 and NR2 subunits, which both are non-functional when expressed homomerically. In contrast to NR1, the homomeric NR2B ion pore failed to translate ligand binding into pore opening when transplanted into GluR6. Similarly, heteromeric coexpression of the ion channel domains of both NR1 and NR2 inserted into GluR6 failed to produce functional channels. Therefore, we conclude that the mechanism underlying the ion channel opening in the obligatorily heterotetrameric NMDA receptors differs significantly from that in the facultatively heterotetrameric alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate and KA receptors.

  18. Synthesis, crystal structure, DFT studies, acid dissociation constant, and antimicrobial activity of methyl 2-(4-chlorophenyl)-7a-((4-chlorophenyl)carbamothioyl)-1-oxo-5,5-diphenyl-3-thioxo-hexahydro-1H-pyrrolo[1,2-e]imidazole-6-carboxylate

    Science.gov (United States)

    Nural, Yahya; Gemili, Muge; Seferoglu, Nurgul; Sahin, Ertan; Ulger, Mahmut; Sari, Hayati

    2018-05-01

    A novel bicyclic thiohydantoin fused to pyrrolidine compound, methyl 2-(4-chlorophenyl)-7a-((4-chlorophenyl)carbamothioyl)-1-oxo-5,5-diphenyl-3-thioxo-hexahydro-1H-pyrrolo[1,2-e]imidazole-6-carboxylate, was synthesized by the cyclization reaction of dimethyl 5,5-diphenylpyrrolidine-2,4-dicarboxylate and 4-chlorophenyl isothiocyanate in the presence of 4-(dimethylamino)pyridine to form methyl 2-(4-chlorophenyl)-1-oxo-5,5-diphenyl-3-thioxo-hexahydro-1H-pyrrolo[1,2-e]imidazole-6-carboxylate with concomitant addition reaction of the 4-chlorophenyl isothiocyanate in 79% yield. The structural characterization was performed by NMR, FT-IR, MS and HRMS techniques, and the stereochemistry of the compound was determined by single crystal X-ray diffraction study. In addition, the molecular structure and 1H and 13C NMR chemical shifts of the compound were obtained with the density functional theory and Hartree-Fock calculations. Acid dissociation constants of the compound were determined using potentiometric titration method in 25% (v/v) dimethyl sulfoxide-water hydroorganic solvent at 25 ± 0.1 °C, at an ionic background of 0.1 mol/L of NaCl using the HYPERQUAD computer program. Four acid dissociation constants were obtained for the compound, and we suggest that these acid dissociation constants are related to the NH, for two groups of enthiols and enol groups. Antimicrobial activity study was performed against S. aureus, B. subtilis, A. hydrophila, E. coli and A. baumannii as bacterial standard strains, and against M. tuberculosis H37Rv as mycobacterial strain. The compound exhibited antibacterial activity in the range of 31.25-62.5 μg/mL, and antimycobacterial activity with a MIC value of 40 μg/mL against the indicated strains.

  19. Technetium(V)-nitrido complexes of dithiocarbazic acid derivatives. Reactivity of [Tc≡N]2+ core towards Schiff bases derived from S-methyl dithiocarbazate. Crystal structures of [S-methyl 3-(2-hydroxyphenyl-methylene) dithiocarbazato]intrido(triphenylphosphine)technetium(V) and bis(S-methyl 3-isopropylidenedithiocarbazato)nitridotechnetium(V)

    International Nuclear Information System (INIS)

    Marchi, A.; Duatti, A.; Rossi, R.; Magon, L.; Bertolasi, V.; Ferretti, V.; Gilli, G.; Pasqualini, R.

    1988-01-01

    As a potential alternative approach to lipophilic square-pyramidal technetium complexes, we investigate here the synthesis of new Tcsup(V) complexes, containing the [Tc''ident to''N] 2+ core, with bi- and tri-dentate Schiff bases derived from S-methyl dithiocarbazate, NH 2 NHC(=S)SCH 3 . Square-pyramidal complexes having an apical Tcsup(V) ≡ N group, with bis(quinoline-8-thiolato), [TcN(C 9 H 6 NS) 2 ], and bis(diethyldithiocarbamate), [TcN(S 2 CNEt 2 ) 2 ], have been reported. In this paper, we report the synthesis and characterization of a series of technetium(V)-nitrido complexes with the ligands illustrated, obtained by reduction of the technetium(VI) complex [TcNCl 4 ] - or by ligand substitution of the Tcsup(V) complex [TcNCl 2 (PPh 3 ) 2 ]. We discuss also the crystal structures of the complexes [TcNL 1 (PPh 3 )] [H 2 L 1 = S-methyl 3-(2-hydroxy-phenylmethylene)dithiocarbazate] and [TcN(L 12 ) 2 ] (HL 12 S-methyl 3-isopropylidenedithiocarbazate. (author)

  20. 2,4-Diamino-6-methyl-1,3,5-triazin-1-ium hydrogen oxalate

    Directory of Open Access Journals (Sweden)

    Bohari M. Yamin

    2012-05-01

    Full Text Available The title compound, C4H8N5+·C2HO4−, was obtained from the reaction of oxalic acid and 2,4-diamino-6-methyl-1,3,5-triazine. The protonated triazine ring is essentially planar with a maximum deviation of 0.035 (1 Å, but the hydrogen oxalate anion is less planar, with a maximum deviation of 0.131 (1 Å for both carbonyl O atoms. In the crystal, the ions are linked by intermolecular N—H...O, N—H...N, O—H...O and C—H...O hydrogen bonds, forming a three-dimensional network. Weak π–π [centroid–centroid distance = 3.763 Å] and C—O...π interactions [O...centroid = 3.5300 (16 Å, C—O...centroid = 132.19 (10°] are also present.

  1. Design, synthesis, and pharmacology of a highly subtype-selective GluR1/2 agonist, (RS)-2-amino-3-(4-chloro-3-hydroxy-5-isoxazolyl)propionic acid (Cl-HIBO)

    DEFF Research Database (Denmark)

    Bjerrum, Esben J; Kristensen, Anders S; Pickering, Darryl S

    2003-01-01

    On the basis of structural studies, chloro-homoibotenic acid (Cl-HIBO) was designed and synthesized. Cl-HIBO was characterized in binding and electrophysiology experiments on native and cloned subtypes of GluRs. Electrophysiological selectivities ranged from 275 to 1600 for GluR1/2 over GluR3/4. ...

  2. Ketamine-induced inhibition of glycogen synthase kinase-3 contributes to the augmentation of AMPA receptor signaling

    Science.gov (United States)

    Beurel, Eléonore; Grieco, Steven F; Amadei, Celeste; Downey, Kimberlee; Jope, Richard S

    2016-01-01

    Objectives Sub-anesthetic doses of ketamine have been found to provide rapid antidepressant actions, indicating that the cellular signaling systems targeted by ketamine are potential sites for therapeutic intervention. Ketamine acts as an antagonist of N-methyl-D-aspartate (NMDA) receptors, and animal studies indicate that subsequent augmentation of signaling by α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors is critical for the antidepressant outcome. Methods In this study, we tested if the inhibitory effect of ketamine on glycogen synthase kinase-3 (GSK3) affected hippocampal cell-surface AMPA receptors using immunoblotting of membrane and synaptosomal extracts from wild-type and GSK3 knockin mice. Results Treatment with an antidepressant dose of ketamine increased the hippocampal membrane level of the AMPA glutamate receptor (GluA)1 subunit, but did not alter the localization of GluA2, GluA3, or GluA4. This effect of ketamine was abrogated in GSK3 knockin mice expressing mutant GSK3 that cannot be inhibited by ketamine, demonstrating that ketamine-induced inhibition of GSK3 is necessary for up-regulation of cell surface AMPA GluA1 subunits. AMPA receptor trafficking is regulated by post-synaptic density-95 (PSD-95), a substrate for GSK3. Ketamine treatment decreased the hippocampal membrane level of phosphorylated PSD-95 on Thr-19, the target of GSK3 that promotes AMPA receptor internalization. Conclusions These results demonstrate that ketamine-induced inhibition of GSK3 causes reduced phosphorylation of PSD-95, diminishing the internalization of AMPA GluA1 subunits to allow for augmented signaling through AMPA receptors following ketamine treatment. PMID:27687706

  3. 4,4-Dimethyl- and diastereomeric 4-hydroxy-4-methyl-(2S)-glutamate analogues display distinct pharmacological profiles at ionotropic glutamate receptors and excitatory amino acid transporters

    DEFF Research Database (Denmark)

    Bunch, Lennart; Pickering, Darryl S; Gefflaut, Thierry

    2009-01-01

    this approach has provided important insight into the structure-activity relationships (SAR) for ionotropic and metabotropic glutamate receptors (iGluRs and mGluRs), as well as the excitatory amino acid transporters (EAATs). In this work, three 4,4-disubstituted Glu analogues 1-3, which are hybrid structures......Subtype-selective ligands are of great interest to the scientific community, as they provide a tool for investigating the function of one receptor or transporter subtype when functioning in its native environment. Several 4-substituted (S)-glutamate (Glu) analogues were synthesized, and altogether...

  4. Five new prenylated p-hydroxybenzoic acid derivatives with antimicrobial and molluscicidal activity from Piper aduncum leaves.

    Science.gov (United States)

    Orjala, J; Erdelmeier, C A; Wright, A D; Rali, T; Sticher, O

    1993-12-01

    Five new prenylated benzoic acid derivatives, methyl 3-(3,7-dimethyl-2,6-octadienyl)-4-methoxybenzoate (1), 1-(1-methylethyl)-4-methyl-3-cyclohexenyl 3,5-bis(3-methyl-2-butenyl)-4-hydroxybenzoate (2), 1-(1-methylethyl)-4-methyl-3-cyclohexenyl 3,5-bis(3-methyl-2-butenyl)-4-methoxybenzoate (3), methyl 3,5-bis(3-methyl-2-butenyl)-4-methoxybenzoate (4), and 4-hydroxy-3-(3-methyl-2-butenyl)-5-(3-methyl-2-butenyl)-benzoic acid (5) were isolated from the dried leaves of Piper aduncum L. (Piperaceae). Together with the new metabolites, four known prenylated benzoic acid derivatives, 3,5-bis(3-methyl-2-butenyl)-4-methoxybenzoic acid (6), 4-hydroxy-3,5-bis(3-methyl-2-butenyl)-benzoic acid (nervogenic acid, 7), methyl 4-hydroxy-3,5-bis(3-methyl-2-butenyl)-benzoate (8), and methyl 4-hydroxy-3-(3-methyl-2-butenyl)-benzoate (9) as well as, dillapiol (10), myristicin, and the three sesquiterpenes humulene, caryophyllene epoxide, and humulene epoxide were isolated. Compounds 7, 8, and 9 are reported as natural products for the first time. The structures of the isolates were elucidated by spectroscopic methods, mainly 1D-and 2D-NMR spectroscopy. Isolates 4-7, 9, and 10 were molluscicidal while 2, 5-7, and 9 displayed significant antibacterial activities.

  5. Chiral separation of dansyl amino acids in capillary electrophoresis using mono-(3-methyl-imidazolium)-beta-cyclodextrin chloride as selector.

    Science.gov (United States)

    Tang, Weihua; Ong, Teng Teng; Ng, Siu-Choon

    2007-06-01

    Enantioseparations of fourteen dansyl amino acids were achieved by using a positively-charged single-isomer beta-cyclodextrin, mono-(3-methyl-imidazolium)-beta-cyclodextrin chloride, as a chiral selector. Separation parameters such as buffer pH, selector concentration, separation temperature, and organic modifier were investigated for the enantioseparation in order to achieve the maximum possible resolution. Chiral separation of dansyl amino acids was found to be highly dependent on pH since the degree of protonation of these amino acids can alter the strength of electrostatic interaction and/or inclusion complexation between each enantiomer and chiral selector. In general, the chiral resolution of dansyl amino acids was enhanced at higher pH, which indicates that the carboxylate group on the analytes may interact with the imidazolium group of cationic cyclodextrin. For most analytes, a distinct maximum in enantioresolution was obtained at pH 8.0. Moreover, the chiral separation can be further improved by careful tuning of the separation parameters such as higher selector concentration (e.g. 10 mM), lower temperature, and addition of methanol. Enantioseparation of a standard mixture of these dansyl amino acids was further achieved in a single run within 30 min.

  6. Positive allosteric modulation of the human metabotropic glutamate receptor 4 (hmGluR4) by SIB-1893 and MPEP

    DEFF Research Database (Denmark)

    Mathiesen, Jesper Mosolff; Svendsen, Nannette; Bräuner-Osborne, Hans

    2003-01-01

    We have identified 2-methyl-6-(2-phenylethenyl)pyridine (SIB-1893) and 2-methyl-6-phenylethynyl pyridine hydrochloride (MPEP) as positive allosteric modulators for the hmGluR4. SIB-1893 and MPEP enhanced the potency and efficacy of L-2-amino-4-phophonobutyrate (L-AP4) in guanosine 5'-O-(3-[(35)S...

  7. SYNTHESIS, CHARACTERIZATION AND ANTIOXIDANT ACTIVITIES OF NOVEL 1-(MORPHOLINE-4-YL-METHYL-3-ALKYL(ARYL-4-[4-(DIMETHYLAMINO-BENZYLIDENAMINO]-4,5-DIHYDRO-1H-1,2,4-TRIAZOL-5-ONES

    Directory of Open Access Journals (Sweden)

    Özlem Gürsoy Kol

    2016-08-01

    Full Text Available In this paper, eight novel 1-(morpholine-4-yl-methyl-3-alkyl(aryl-4-[4-(dimethylamino-benzylidenamino]-4,5-dihydro-1H-1,2,4-triazol-5-ones (2 were obtained by the reactions of 3-alkyl(aryl-4-[4-(dimethylamino-benzylidenamino]-4,5-dihydro-1H-1,2,4-triazol-5-ones (1 with formaldehyde and morpholine. The novel synthesized compounds were identified by IR, 1H NMR and 13C NMR spectral data. Besides, the newly synthesized compounds were analysed for their in vitro potential antioxidant capacities in three different assays. All of the compounds demonstrated significant activity for metal chelating effect.

  8. Synthesis of methyl-2 O-tolyl-3 quinazolone-4 {sup 14}C-2; Synthese de la methyl-2 O-tolyl-3 quinazolone-4 {sup 14}C-2

    Energy Technology Data Exchange (ETDEWEB)

    Herbert, M; Pichat, L [Commissariat a l' Energie Atomique, Saclay (France).Centre d' Etudes Nucleaires

    1959-07-01

    Description of the preparation of methyl-2 O-tolyl-3 quinazolone-4 {sup 14}C-2 (abbreviated to M.T.Q.), using N-acetyl {sup 14}C-1 anthranilic acid. The overall yield reaches 72 per cent with respect to acetyl chloride {sup 14}C-1. By applying the same method to acetyl chloride {sup 14}C-2, M.T.Q. labelled on the methyl group could be obtained. (author) [French] Description de la preparation de la methyl-2 O-tolyl-3 quinazolone-4 {sup 14}C-2 (abregee en M.T.Q.) par l'intermediaire de l'acide N-acetyl {sup 14}C-1 anthranilique. Le rendement global atteint 72 pour cent par rapport au chlorure d'acetyle {sup 14}C-1. La meme methode appliquee au chlorure d'acetyle {sup 14}C-2 permettrait d'obtenir la M.T.Q. marquee sur le groupement methyle. (auteur)

  9. HISTOPATHOLOGICAL EFFECTS OF (4S)-2-(4-HYDROXY-3-METHOXYPHENYL) THIAZOLIDINE-4-CARBOXYLIC ACID ON ZEBRAFISH (Danio rerio) HEART TISSUE

    OpenAIRE

    YÖN, Nazan Deniz; ÖZTÜRK, Burcu; ZENGİN, Mustafa; AKBULUT, Cansu

    2018-01-01

    Examination thehistopathological effects of (4s)-2-(4-hydroxy-3-methoxyphenyl) thiazolidine-4-carboxylicacid on heart tissue of zebrafish were aimed.Introduction:(4S)-2-(4-hydroxy-3-methoxyphenyl) thiazolidine-4-carboxylic acid is newsynthesized substance which obtained from cysteine and valine. Because ofthiazolidine derivates have important biological responses scientist workintensively on these compounds recent years. It is obvious that thiazolidinecontained compounds will be used in futur...

  10. Effects of β-hydroxy β-methyl butyrate supplementation to sows in late gestation on absorption and hepatic metabolism of glucose and amino acids during transition

    DEFF Research Database (Denmark)

    Flummer, Christine; Lyby, H; Storli, K S

    2012-01-01

    A multicatheter sow model was established to study the effects of dietary β-hydroxy β-methyl butyrate (HMB) supplementation on net portal flux (NPF) and net hepatic flux (NHF) of HMB, glucose, and the AA Ala, Gly, Ile, Leu, Phe, Tyr, and Val. Eight second parity sows were fitted with permanent...... the experiment, and 4 HMB sows were fed the control diet supplemented with 15 mg Ca(HMB)2/kg BW mixed in one third of the morning meal from day –10 until parturition. Net portal flux of HMB was affected by treatment (Trt; P HMB sows at 6.9 mmol/h 30 min after the morning meal...... and then decreased towards preprandial level (0.0 mmol/h) 3.5 h after the meal, revealing that dietary HMB was rapidly absorbed from the intestine. The NHF of HMB tended to be affected by Trt (P = 0.06) showing a small hepatic uptake of HMB (1.1 mmol/h) in HMB sows. Net portal flux of glucose and all measured AA...

  11. Synthesis and biological evaluation of (3-arylisoxazol-5-yl methyl 6-fluoro-4-oxo-4H-chromene-2-carboxylates as antioxidant and antimicrobial agents

    Directory of Open Access Journals (Sweden)

    Battula Kumaraswamy

    2017-01-01

    Full Text Available A series of novel (3-aryl-1,2-oxazol-5-yl methyl 6-fluoro-4-oxo-4H- -chromene-2-carboxylate derivatives (C1-C12 were synthesized by Cu (I catalyzed reaction of in situ generated nitrile oxides with prop-2-yn-1-yl 6-fluoro-4-oxo-4H-chromene-2-carboxylate in good yields and investigated their antioxidant and antimicrobial activities. Among all the synthesized compounds, C1 (IC50: 16.43 ± 0.57 μM and C12 (IC50:15.98 ± 0.72 μM have registered good antioxidant activity as compared to the standard drug Trolox. Compound-C1, C3, and C6 have registered very good inhibition against all gram-positive and gram-negative bacterial strains with MIC values ranging from 9.375 to 37.5 (μg mL-1. Compound-C7, C8, C9, C10, and C11 have registered good inhibition against B. subtilis and S. aureus with MIC values ranging from 18.75 to 37.5 (μg mL-1. Compound-C10 and C11 against P. aero-ginosa have shown prominent activity than the standard drug Penicillin (MIC: 12.5 μg mL-1 with MIC 9.375 μg mL-1 (~ 1.33 fold potent than Penicillin. Compound-C7, C8, and C9 have registered good to moderate antifungal activity against four tested fungal strains with MIC values ranging from 18.75 and 37.5 μg mL-1

  12. LC-MS/MS quantification of 7α-hydroxy-4-cholesten-3-one (C4) in rat and monkey plasma.

    Science.gov (United States)

    Kang, Lijuan; Connolly, Thomas M; Weng, Naidong; Jian, Wenying

    2017-10-01

    7α-hydroxy-4-cholesten-3-one (C4) is an oxidative enzymatic product of cholesterol metabolism via cholesterol 7α-hydroxylase, an enzyme also known as cholesterol 7-alpha-monooxygenase or cytochrome P450 7A1 (CYP7A1). C4 is a stable intermediate in the rate limiting pathway of bile acid biosynthesis. Previous studies showed that plasma C4 levels correlated with CYP7A1 enzymatic activity and could serve as a biomarker for bile acid synthesis. Here we developed and qualified a simple and robust high-throughput method using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) to quantify C4 in rat and monkey plasma. As C4 being an endogenous compound, this method used calibration standards in 50/50: acetonitrile/water (v/v). In order to mimic the incurred samples, quality control samples were prepared in the authentic plasma. Stable isotope labeled C4 (C4-d 7 ) was used as the internal standard. The sample volume for analysis was 20μL and the sample preparation method was protein precipitation with acetonitrile. The average endogenous C4 concentrations, from 10 different lots of rat and monkey plasma, were 53.0±16.5ng/mL and 6.8±5.6ng/mL, respectively. Based on these observed endogenous C4 levels, the calibration curve ranges were established at 1-200ng/mL and 0.5-100ng/mL for rat assay and monkey assay, respectively. The method was qualified with acceptable accuracy, precision, linearity, and specificity. Matrix effect, recovery, and plasma stability of bench-top, freeze-thaw, and long-term frozen storage were also evaluated. The method has been successfully applied to pre-clinical studies. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. SYNTHESIS AND STUDY OF ANTIOXIDANT ACTIVITY OF [(1-ARYL-5-FORMYL-1H-IMIDAZOLE-4-ILTHIO]PROPIONIC ACIDS

    Directory of Open Access Journals (Sweden)

    A. O. Palamar

    2014-12-01

    -yellow color, well soluble in solutions of alkali and in organic solvents. Their composition and structure has been reliably confirmed by elemental analysis and by results of IR-, 1H, 13C NMR and chromatography mass-spectra measurements. The results of in vitro antioxidant activity screening of synthesized compounds show pronounced antioxidant effect of all of the studied compounds. It has been determined that the thiopropionic acid’s derivatives show much higher in vitro activity than the derivatives of the thioacetic acid. The maximum inhibition level of Fe2+-ascorbate initiated FROL in the rats’ liver in vitro under the action of these compounds varies in the range between 67-72% in comparison with the control samples. The produced results indicate that with the growth of the carbon chain length of the thioalkanecarboxylic acids’ fragment the antioxidant activity of the studied compounds grows. Conclusions. 1. By interaction of 4-chloro-5-formylimidazoles with thiopropionic acid in the presence of potassium hydroxide the new [(1-aryl-4-chloro-1H-imidazole-5-ilmethyl]thiopropionic acids have been synthesized with high yields. 2. All studied derivatives of imidazole in the range of concentrations of 10-3-10-1М show high antioxidant activity in the in vitro system. 3. The comparison of antioxidant activity of [(1-aryl-5-formylimidazole-4-ilthio]acetic and propionic acids has shown that the increasing of methylene groups’ quantity in the carboxyalkylthiol fragment leads to increasing of the antioxidant effect of the synthesized compounds.

  14. Microbial Propionic Acid Production

    Directory of Open Access Journals (Sweden)

    R. Axayacatl Gonzalez-Garcia

    2017-05-01

    Full Text Available Propionic acid (propionate is a commercially valuable carboxylic acid produced through microbial fermentation. Propionic acid is mainly used in the food industry but has recently found applications in the cosmetic, plastics and pharmaceutical industries. Propionate can be produced via various metabolic pathways, which can be classified into three major groups: fermentative pathways, biosynthetic pathways, and amino acid catabolic pathways. The current review provides an in-depth description of the major metabolic routes for propionate production from an energy optimization perspective. Biological propionate production is limited by high downstream purification costs which can be addressed if the target yield, productivity and titre can be achieved. Genome shuffling combined with high throughput omics and metabolic engineering is providing new opportunities, and biological propionate production is likely to enter the market in the not so distant future. In order to realise the full potential of metabolic engineering and heterologous expression, however, a greater understanding of metabolic capabilities of the native producers, the fittest producers, is required.

  15. Response of Syntrophic Propionate Degradation to pH Decrease and Microbial Community Shifts in an UASB Reactor.

    Science.gov (United States)

    Zhang, Liguo; Ban, Qiaoying; Li, Jianzheng; Jha, Ajay Kumar

    2016-08-28

    The effect of pH on propionate degradation in an upflow anaerobic sludge blanket (UASB) reactor containing propionate as a sole carbon source was studied. Under influent propionate of 2,000 mg/l and 35ºC, propionate removal at pH 7.5-6.8 was above 93.6%. Propionate conversion was significantly inhibited with stepwise pH decrease from pH 6.8 to 6.5, 6.0, 5.5, 5.0, 4.5, and then to 4.0. After long-term operation, the propionate removal at pH 6.5-4.5 maintained an efficiency of 88.5%-70.1%, whereas propionate was hardly decomposed at pH 4.0. Microbial composition analysis showed that propionate-oxidizing bacteria from the genera Pelotomaculum and Smithella likely existed in this system. They were significantly reduced at pH ≤5.5. The methanogens in this UASB reactor belonged to four genera: Methanobacterium, Methanospirillum, Methanofollis, and Methanosaeta. Most detectable hydrogenotrophic methanogens were able to grow at low pH conditions (pH 6.0-4.0), but the acetotrophic methanogens were reduced as pH decreased. These results indicated that propionate-oxidizing bacteria and acetotrophic methanogens were more sensitive to low pH (5.5-4.0) than hydrogenotrophic methanogens.

  16. 3-{(E-[4-(4-Hydroxy-3-methoxyphenylbutan-2-ylidene]amino}-1-phenylurea: crystal structure and Hirshfeld surface analysis

    Directory of Open Access Journals (Sweden)

    Ming Yueh Tan

    2018-01-01

    Full Text Available Two independent molecules (A and B comprise the asymmetric unit of the title compound, C18H21N3O3. The urea moiety is disubstituted with one amine being linked to a phenyl ring, which is twisted out of the plane of the CN2O urea core [dihedral angles = 25.57 (11 (A and 29.13 (10° (B]. The second amine is connected to an imine (E conformation, which is linked in turn to an ethane bridge that links a disubstituted benzene ring. Intramolecular amine-N—H...N(imine and hydroxyl-O—H...O(methoxy hydrogen bonds close S(5 loops in each case. The molecules have twisted conformations with the dihedral angles between the outer rings being 38.64 (81 (A and 48.55 (7° (B. In the crystal, amide-N—H...O(amide hydrogen bonds link the molecules A and B via an eight-membered {...HNCO}2 synthon. Further associations between molecules, leading to supramolecular layers in the ac plane, are hydrogen bonds of the type hydroxyl-O—H...N(imine and phenylamine-N—H...O(methoxy. Connections between layers, leading to a three-dimensional architecture, comprise benzene-C—H...O(hydroxy interactions. A detailed analysis of the calculated Hirshfeld surfaces shows molecules A and B participate in very similar intermolecular interactions and that any variations relate to conformational differences between the molecules.

  17. Cloning, Expression Profiling and Functional Analysis of CnHMGS, a Gene Encoding 3-hydroxy-3-Methylglutaryl Coenzyme A Synthase from Chamaemelum nobile

    Directory of Open Access Journals (Sweden)

    Shuiyuan Cheng

    2016-03-01

    Full Text Available Roman chamomile (Chamaemelum nobile L. is renowned for its production of essential oils, which major components are sesquiterpenoids. As the important enzyme in the sesquiterpenoid biosynthesis pathway, 3-hydroxy-3-methylglutaryl coenzyme A synthase (HMGS catalyze the crucial step in the mevalonate pathway in plants. To isolate and identify the functional genes involved in the sesquiterpene biosynthesis of C. nobile L., a HMGS gene designated as CnHMGS (GenBank Accession No. KU529969 was cloned from C. nobile. The cDNA sequence of CnHMGS contained a 1377 bp open reading frame encoding a 458-amino-acid protein. The sequence of the CnHMGS protein was highly homologous to those of HMGS proteins from other plant species. Phylogenetic tree analysis revealed that CnHMGS clustered with the HMGS of Asteraceae in the dicotyledon clade. Further functional complementation of CnHMGS in the mutant yeast strain YSC6274 lacking HMGS activity demonstrated that the cloned CnHMGS cDNA encodes a functional HMGS. Transcript profile analysis indicated that CnHMGS was preferentially expressed in flowers and roots of C. nobile. The expression of CnHMGS could be upregulated by exogenous elicitors, including methyl jasmonate and salicylic acid, suggesting that CnHMGS was elicitor-responsive. The characterization and expression analysis of CnHMGS is helpful to understand the biosynthesis of sesquiterpenoid in C. nobile at the molecular level and also provides molecular wealth for the biotechnological improvement of this important medicinal plant.

  18. Cloning, Expression Profiling and Functional Analysis of CnHMGS, a Gene Encoding 3-hydroxy-3-Methylglutaryl Coenzyme A Synthase from Chamaemelum nobile.

    Science.gov (United States)

    Cheng, Shuiyuan; Wang, Xiaohui; Xu, Feng; Chen, Qiangwen; Tao, Tingting; Lei, Jing; Zhang, Weiwei; Liao, Yongling; Chang, Jie; Li, Xingxiang

    2016-03-08

    Roman chamomile (Chamaemelum nobile L.) is renowned for its production of essential oils, which major components are sesquiterpenoids. As the important enzyme in the sesquiterpenoid biosynthesis pathway, 3-hydroxy-3-methylglutaryl coenzyme A synthase (HMGS) catalyze the crucial step in the mevalonate pathway in plants. To isolate and identify the functional genes involved in the sesquiterpene biosynthesis of C. nobile L., a HMGS gene designated as CnHMGS (GenBank Accession No. KU529969) was cloned from C. nobile. The cDNA sequence of CnHMGS contained a 1377 bp open reading frame encoding a 458-amino-acid protein. The sequence of the CnHMGS protein was highly homologous to those of HMGS proteins from other plant species. Phylogenetic tree analysis revealed that CnHMGS clustered with the HMGS of Asteraceae in the dicotyledon clade. Further functional complementation of CnHMGS in the mutant yeast strain YSC6274 lacking HMGS activity demonstrated that the cloned CnHMGS cDNA encodes a functional HMGS. Transcript profile analysis indicated that CnHMGS was preferentially expressed in flowers and roots of C. nobile. The expression of CnHMGS could be upregulated by exogenous elicitors, including methyl jasmonate and salicylic acid, suggesting that CnHMGS was elicitor-responsive. The characterization and expression analysis of CnHMGS is helpful to understand the biosynthesis of sesquiterpenoid in C. nobile at the molecular level and also provides molecular wealth for the biotechnological improvement of this important medicinal plant.

  19. Use of 3H-muscimol for GABA receptor studies

    International Nuclear Information System (INIS)

    Snodgrass, S.R.

    1978-01-01

    It is stated that gamma aminobutyric acid (GABA) is a major transmitter in the mammalian central nervous system and studies of synaptic receptors for neurotransmitters have been useful in many areas of neuropharmacology. Although GABA receptors can be studied using 3 H-GABA itself, a ligand which does not bind to GABA uptake sites would be valuable for autoradiography and for other studies of receptor function. Muscimol (3-hydroxy-5-aminomethly-isoxazole) is a naturally occurring GABA analogue found in Amanita muscaria. It seems to enter the brain after peripheral injection. Evidence is here presented of the binding of 3 H-muscimol by brain tissue. The ability of muscimol to alter evoked release of GABA by synaptosomes was also of muscimol to alter evoked release of GABA by synaptosomes was also used to verify the ability of muscimol to alter the function of GABA neurones. (author)

  20. Selective Screening for Organic Acidurias and Amino Acidopathies in Pakistani Children

    International Nuclear Information System (INIS)

    Sherazi, N. A.; Khan, A. H.; Jafri, L.; Jamil, A.; Khan, N. A.; Afroze, B.

    2017-01-01

    Objective: To determine the frequency of organic acidurais (OA) and amino acidopathies (AA) in selected high-risk patients screened in two years. Study Design: Retrospective Observational study. Place and Duration of Study: The Aga Khan University Hospital (AKUH), Karachi, from January 2013 to December 2014. Methodology: Patients with OA and AA were included in the study and patients with IMDs other than OA and AA were excluded. Amino acids and organic acids were analyzed on high performance liquid chromatography and gas chromatography-mass spectrometry respectively. Clinical data and chromatograms of patients screened for IMDs were reviewed by chemical pathologist and metabolic physician. Results: Eighty-eight cases (4.7 percent) were diagnosed including 41 OA (46.5 percent), 28 AA (31.8 percent) and 19 others (21.5 percent) from 1,866 specimens analyzed. Median age of the patients was 1.1 years, with high consanguinity rate (64.8 percent). Among OA, methyl CoA mutase deficiency was diagnosed in 9 (10.2 percent) and was suspected in 2 (2.3 percent) cases. Five (5.7 percent) cases of MHBD (2-methyl-3-hydroxybutyryl-CoA), 4 (4.5 percent) each of PPA (propionic aciduria) and HMG-CoA lyase deficiency, 3 (3.4 percent) cases each of IVA (isovaleric aciduria), multiple carboxylase deficiency, fructose-1, 6-biphosphatase deficiency, fumarase deficiency, GA-1 (glutaric aciduria type 1) and 2 (2.3 percent) cases of EMA (ethyl-malonic aciduria). AA included 8 (9.1 percent) cases of MSUD (maple syrup urine disease), 6 (6.8 percent) cases of CBS (cystathionine beta-synthetase) and UCDs (urea cycle disorders) each, 5 (5.7 percent) cases of hyperphenylalaninemia and 3 (3.4 percent) cases of hyperprolinemia were reported. Other inherited metabolic disorders included: 9 (10.2 percent) cases of intracellular cobalamin defects, 2 (2.3 percent) cases each of alkaptonuria, Canavan's disease, SUCL (succinate CoA ligase) deficiency, and 1 (1.1 percent) case each of DPD

  1. The occurrence of 2-hydroxy-6-methoxybenzoic acid methyl ester in Securidaca longepedunculata Fresen root bark

    Directory of Open Access Journals (Sweden)

    Lognay G.

    2000-01-01

    Full Text Available As part of our ongoing search for natural fumigants from Senegalese plants, we have investigated Securicicidaca longepedunculata root barks and demonstrated that 2-hydroxy-benzoic acid methyl ester (methyl salicylate, I is responsible of their biocide effect against stored grain insects. A second unknown apparented product, II has been systematically observed in all analyzed samples. The present paper describes the identification of this molecule. The analytical investigations including GCMS, GLC and 1H-NMR. spectrometry led to the conclusion that II corresponds to the 2-hydroxy-6-methoxybenzoic acid methyl ester.

  2. Synthesis of carbasugars from aldonolactones. Part II. Preparation of polyhydroxy/aminocyclopentanes functionalised at all five carbons

    DEFF Research Database (Denmark)

    Lundt, Inge; Johansen, Steen Karsk

    1999-01-01

    Starting from (1R,5R,8R)-8-acetoxy-2-oxabicyclo[3.3.0]oct-6-en-3-one (4) the syntheses of 4a(R)-hydroxy-5-deoxycarba--L-xylo-hexofuranose (17), 4a(S)-hydroxy-5-deoxycarba--L-xylo-hexofuranose (21), 4a(S)-hydroxy-5-deoxycarba--L-xylo-hexofuranose (23) and 4a(R)-hydroxy-1-amino-1,5-dideoxycarba-......--L-xylo-hexofur anose (1) have been achieved. The methodology included OsO4 catalysed dihydroxylation as well as regioselective epoxide opening followed by calcium borohydride reduction of the lactone moiety....

  3. Xanthohumol, a prenylated flavonoid contained in beer, prevents the induction of preneoplastic lesions and DNA damage in liver and colon induced by the heterocyclic aromatic amine amino-3-methyl-imidazo[4,5-f]quinoline (IQ)

    International Nuclear Information System (INIS)

    Ferk, Franziska; Huber, Wolfgang W.; Filipic, Metka; Bichler, Julia; Haslinger, Elisabeth; Misik, Miroslav; Nersesyan, Armen; Grasl-Kraupp, Bettina; Zegura, Bojana; Knasmueller, Siegfried

    2010-01-01

    Xanthohumol (XN) is a hop derived prenylated flavonoid contained in beer. Earlier findings indicated that it has promising chemopreventive properties and protects cells against DNA damage by carcinogens via inhibition of their activation. Furthermore, it was found that XN inhibits DNA synthesis and proliferation of cancer cells in vitro, inactivates oxygen radicals and induces apoptosis. Since evidence for its chemoprotective properties is restricted to results from in vitro experiments, we monitored the impact of XN on the formation of amino-3-methyl-imidazo[4,5-f]quinoline (IQ)-induced preneoplastic foci in livers and colons of rats (9/group). Additionally, we studied its effects on IQ-induced DNA damage in colonocytes and hepatocytes in single cell gel electrophoresis assays and on the activities of a panel of drug metabolising enzymes. Consumption of the drinking water supplemented with XN (71 μg/kg b.w.) before and during carcinogen treatment led to a significant reduction of the number of GST-p + foci in the liver by 50% and also to a decrease of the foci area by 44%. DNA migration was decreased significantly in both, colon mucosa and liver cells, but no alterations of the activities of different phases I and II enzymes were found in hepatic tissue. Our findings indicate that XN protects against DNA damage and cancer induced by the cooked food mutagen. Since the effects were observed with low doses of XN which are reached after consumption of brews with high XN levels, our findings may be relevant for humans.

  4. A Silsesquioxane Organically Modified with 4-Amino-5-(4-pyridyl-4H-1,2,4-triazole-3-thiol: Thermal Behavior and Its Electrochemical Detection of Sulfhydryl Compounds

    Directory of Open Access Journals (Sweden)

    D. R. Do Carmo

    2014-01-01

    Full Text Available The octakis(3-chloropropylsilsesquioxane (SS was organofunctionalized with 4-amino-5-4(pyridyl-4H-1,2,4-triazole-3-thiol. The product formed (SA was undergo another reactions in two steps, first with copper and so hexacyanoferrate (III to form CuHSA. The organofunctionalized silsesquioxane was characterized by the following techniques: scanning electron microscopy (SEM, Fourier transform infrared (FTIR, nuclear magnetic resonance (NMR in solid state, and thermogravimetric analysis in air and nitrogen atmosphere. The composite CuHSA was incorporated into a graphite paste electrode and the electrochemical behavior studies were conducted with cyclic voltammetry. The cyclic voltammogram of the modified graphite paste electrode with CuHSA showed one redox couple with formal potential Eθ′=0.75 V versus Ag/AgCl(sat (KCl 1.0 mol L−1; v = 20 mV s−1 attributed to the redox process Fe(II(CN6/Fe(III(CN6 of the binuclear complex formed. The redox couple presents an electrocatalytic response of sulfhydryl compounds such as n-acetylcysteine and l-cysteine. For determination of n-acetylcysteine and l-cysteine the modified graphite paste electrode showed a linear region in the concentration range of 2 to 20 mmol L−1. The modified electrode was chemically and electrochemically stable and showed good reproducibility.

  5. Structural studies on Mannich bases of 2-Hydroxy-3,4,5,6-tetrachlorobenzene. An UV, IR, NMR and DFT study. A mini-review

    DEFF Research Database (Denmark)

    Hansen, Poul Erik; Spanget-Larsen, Jens

    2016-01-01

    Mannich bases of 2-Hydroxy-3,4,5,6-tetrachlorobenzene are chosen as an exemplary case for tautomeric Mannich bases. Molecular structures are calculated. OH stretching frequencies are rationalized based on DFT calculations. Intrinsic deuterium isotope effects on 13C chemical shifts in the M-form a......-form are estimated based on OH bond lengths. The observed deuterium isotope effects on 13C chemical shifts are demonstrated to be largely of equilibrium type except at ambient temperatures....

  6. A systematic review on aromatic L-amino acid decarboxylase (5-hydroxytryptophan decarboxylase)

    International Nuclear Information System (INIS)

    Rahman, M.K.; Nagatsu, T.

    1988-11-01

    Aromatic L-amino acid decarboxylase (AADC, EC. 4.1.1.28) with L-5-hydroxytryptophan as a substrate (also called L-5-hydroxytryptophan decarboxylase, 5-HTPDC) decarboxylates L-5-hydroxytryptophan to serotonin (5-HT), an important neurotransmitter that involved in the regulation of neuronal functions, behaviour and emotion of higher animals. As it is an important enzyme, many researchers are now working on its physiological functions and properties and also on its isolation, purification and characterization from mammalian tissues. But up to now no systematic review studies have been done on this enzyme. We made systematic studies on this enzyme in tissues and brains of rats, and human subjects. We also developed highly sensitive assay methods of the enzyme. This new method led us to discover the enzyme in the sera of various animals. We examined the developmental changes of 5-HTPDC in the sera of animals. We discovered an endogenous inhibitor of the enzyme in the monkey blood. The purification of the enzyme were performed by us and other researches from the sera, brains, adrenals, liver and kidneys of mammals. These and other results of up to date research papers on 5-HTPDC have been reviewed in this paper. (author). 71 refs, 10 figs, 14 tabs

  7. L-leucine methyl ester stimulates insulin secretion and islet glutamate dehydrogenase

    DEFF Research Database (Denmark)

    Knudsen, P; Kofod, Hans; Lernmark, A

    1983-01-01

    Column perifusion of collagenase-isolated mouse pancreatic islets was used to study the dynamics of insulin release in experiments lasting for several hours. The methyl esters of L-leucine and L-arginine were synthesized. Whereas L-arginine methyl ester (L-arginine OMe) had no effect, L-leucine OMe...... stimulated the release of insulin. The effect of L-leucine OMe was maximal at 5 mmol/liter. Whereas the Km for glucose-stimulated insulin release was unaffected by 1 mmol/liter L-leucine OMe, the maximal release of D-glucose was increased by the amino acid derivative that appeared more effective than L......-leucine. L-Leucine OMe was also a potent stimulus of insulin release from the perfused mouse pancreas. In the presence of 10 mmol/liter L-glutamine, 1 mmol/liter L-leucine OMe induced a 50- to 75-fold increase in insulin release. A similar stimulatory effect was also observed in column-perifused RIN 5F cells...

  8. Solution-phase synthesis of a hindered N-methylated tetrapeptide using Bts-protected amino acid chlorides: efficient coupling and methylation steps allow purification by extraction.

    Science.gov (United States)

    Vedejs, E; Kongkittingam, C

    2000-04-21

    N-Benzothiazole-2-sulfonyl (Bts)-protected amino acid chlorides were used to prepare the hindered cyclosporin 8-11 tetrapeptide subunit 1. The synthesis was performed via 3a and the deprotected amines 5a, 13, and 19, including three repeated cycles involving N-methylation using iodomethane/potassium carbonate, deprotection of the Bts group, and N-acylation with a N-Bts-amino acid chloride such as 9b or 9c. Among three Bts cleavage methods compared (H3PO2/THF; NaBH4/EtOH; PhSH/K2CO3), the third gave somewhat higher overall yields. N-Acylation of 5a with the Bts-protected N-methylamino acid chloride 10b followed by deprotection was also highly efficient and could be used as an alternative route to 11. Each of the deprotected amines was isolated without chromatography using simple extraction methods to remove neutral byproducts. The tetrapeptide 1 was obtained in analytically pure form as the monohydrate.

  9. The effects of conformational constraints and steric bulk in the amino acid moiety of philanthotoxins on AMPAR antagonism

    DEFF Research Database (Denmark)

    Jørgensen, Malene; Olsen, Christian A; Mellor, Ian R

    2005-01-01

    , establishing general protocols for philanthotoxin solution- and solid-phase synthesis (39-90% and 42-54% overall yields, respectively). The analogues were tested for their ability to antagonize kainate-induced currents of 2-amino-3-(3-hydroxy-5-methyl-4-isoxazoyl)propanoic acid receptors (AMPAR) expressed...... in Xenopus oocytes from rat brain mRNA. This showed that steric bulk in the amino acid moiety is well tolerated and suggests that binding to AMPAR does not involve the alpha-NHCO group as a donor in hydrogen bonding.......Philanthotoxin-343 (PhTX-343), a synthetic analogue of wasp toxin PhTX-433, is a noncompetitive antagonist at ionotropic receptors (e.g., AChR or iGluR). To determine possible effects of variations of the amino acid side chain, a library consisting of seventeen PhTX-343 analogues was prepared. Thus...

  10. On the inhibition of mild steel corrosion by 4-amino-5-phenyl-4H-1, 2, 4-trizole-3-thiol

    International Nuclear Information System (INIS)

    Musa, Ahmed Y.; Kadhum, Abdul Amir H.; Mohamad, Abu Bakar; Takriff, Mohd Sobri; Daud, Abdul Razak; Kamarudin, Siti Kartom

    2010-01-01

    The corrosion inhibition of mild steel in a 2.5 M H 2 SO 4 solution by 4-amino-5-phenyl-4H-1, 2, 4-trizole-3-thiol (APTT) was studied at different temperatures, utilising open circuit potential, potentiodynamic and impedance measurements. The results indicate that APTT performed as an excellent mixed-type inhibitor for mild steel corrosion in a 2.5 M H 2 SO 4 solution and that the inhibition efficiencies increased with the inhibitor concentration but decreased proportionally with temperature. The kinetic and thermodynamic parameters for adsorption of APTT on the mild steel surface were calculated. A chemisorption mechanism of APTT molecules on the mild steel surface was proposed based on the thermodynamic adsorption parameters.

  11. Developmental Toxicity of (4S-2- (4-hydroxy-3-methoxyphenyl thiazolidine-4-carboxylic acid in Zebrafish ( Danio rerio

    Directory of Open Access Journals (Sweden)

    Cansu Akbulut

    2017-08-01

    Full Text Available ABSTRACT (4S-2-(4-hydroxy-3-methoxyphenylthiazolidine-4-carboxylic acid is new synthesized substance obtained from cysteine and valine. Thiazolidine derivates have important biological responses so scientists work intensively on these compounds in recent years. It is obvious that thiazolidine contained compounds will be used in future in the pharmaceutical industry to treat important diseases. Median lethal concentrations (LC50 for 48 h and 96 h were found as 1.106±0.052 mM and 0.804mM ± 0.102 respectively. According to LC50, exposure doses were determined as control, 0.4 mM, 0.2 mM and 0.1 mM (4S-2-(4-hydroxy-3-methoxyphenylthiazolidine-4-carboxylic acid. Developmental toxicity and apoptotic features on zebrafish development were evaluated in this study. The results of this study indicate that (4S-2-(4-hydroxy-3-methoxyphenylthiazolidine-4-carboxylic acid exposure cause developmental defects like pericardial edema, bent spine, tail malformation, blood accumulation, yolk sac edema but on the other hand concentration-dependent decrease in apoptotic rate. Likewise, concentration-dependent decrease in hatching and increase in mortality of embryos were also detected.

  12. Synthesis and crystal structures of 2-methyl-4-aryl-5-oxo-5H-indeno [1,2-b] pyridine carboxylate derivatives

    DEFF Research Database (Denmark)

    Pandian, Ramesh; Naushad, Edayadulla; Vijayakumar, Vinodhkumar

    2014-01-01

    pyridine derivatives through oxidation. Consequently, the interest in this aromatization reaction, investigation of a wide range of 1, 4-DHPs continues to attract the attention of researchers. Herein, we report the preparation of pyridine derivatives and the crystal structures determined by X......-ray crystallographic methods.Results: The crystal structures and conformational studies of two organic compounds, namely ethyl 2-methyl-4-phenyl-5-oxo-5H-indeno [1,2-b] pyridine-3-carboxylate (I) and ethyl 2-methyl-4-(4 chlorophenyl)-5-oxo-5H-indeno [1,2-b] pyridine-3-carboxylate (II) are reported. The terminal ethyl......) dimer running along 011 direction.Conclusion: The crystal structures ethyl 2-methyl-4-phenyl-5-oxo-5H-indeno [1,2-b] pyridine-3-carboxylate and ethyl 2-methyl-4-(4 chlorophenyl)-5-oxo-5H-indeno [1,2-b] pyridine-3-carboxylate have been investigated in detail. The terminal ethyl group of compound I...

  13. Method of preparing [methyl-3H]thymine and 5-hydroxy[3H]methyluracil mixture of high molar activity

    International Nuclear Information System (INIS)

    Filip, J.; Bohacek, L.

    1981-01-01

    Non-active 5-formyluracil dissolved in 0.01 N to 1.0 N of hydrochloric acid is acted upon by gaseous carrier-free tritium at room temperature in the presence of a heterogeneous palladium/carrier catalyst, with advantage palladium on barium sulfate. The described procedure allows the preparation of [methyl- 3 H]thymine on a microscale, with a high molar activity in a single reaction stage with a high chemical (50-70%) and radiochemical (15-25%) yield. (J.P.)

  14. Deficiency of Lipoprotein Lipase in Neurons Decreases AMPA Receptor Phosphorylation and Leads to Neurobehavioral Abnormalities in Mice.

    Directory of Open Access Journals (Sweden)

    Tian Yu

    Full Text Available Alterations in lipid metabolism have been found in several neurodegenerative disorders, including Alzheimer's disease. Lipoprotein lipase (LPL hydrolyzes triacylglycerides in lipoproteins and regulates lipid metabolism in multiple organs and tissues, including the central nervous system (CNS. Though many brain regions express LPL, the functions of this lipase in the CNS remain largely unknown. We developed mice with neuron-specific LPL deficiency that became obese on chow by 16 wks in homozygous mutant mice (NEXLPL-/- and 10 mo in heterozygous mice (NEXLPL+/-. In the present study, we show that 21 mo NEXLPL+/- mice display substantial cognitive function decline including poorer learning and memory, and increased anxiety with no difference in general motor activities and exploratory behavior. These neurobehavioral abnormalities are associated with a reduction in the 2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl propanoic acid (AMPA receptor subunit GluA1 and its phosphorylation, without any alterations in amyloid β accumulation. Importantly, a marked deficit in omega-3 and omega-6 polyunsaturated fatty acids (PUFA in the hippocampus precedes the development of the neurobehavioral phenotype of NEXLPL+/- mice. And, a diet supplemented with n-3 PUFA can improve the learning and memory of NEXLPL+/- mice at both 10 mo and 21 mo of age. We interpret these findings to indicate that LPL regulates the availability of PUFA in the CNS and, this in turn, impacts the strength of synaptic plasticity in the brain of aging mice through the modification of AMPA receptor and its phosphorylation.

  15. PRMT1-mediated arginine methylation controls ATXN2L localization

    Energy Technology Data Exchange (ETDEWEB)

    Kaehler, Christian; Guenther, Anika; Uhlich, Anja; Krobitsch, Sylvia, E-mail: krobitsc@molgen.mpg.de

    2015-05-15

    Arginine methylation is a posttranslational modification that is of importance in diverse cellular processes. Recent proteomic mass spectrometry studies reported arginine methylation of ataxin-2-like (ATXN2L), the paralog of ataxin-2, a protein that is implicated in the neurodegenerative disorder spinocerebellar ataxia type 2. Here, we investigated the methylation state of ATXN2L and its significance for ATXN2L localization. We first confirmed that ATXN2L is asymmetrically dimethylated in vivo, and observed that the nuclear localization of ATXN2L is altered under methylation inhibition. We further discovered that ATXN2L associates with the protein arginine-N-methyltransferase 1 (PRMT1). Finally, we showed that neither mutation of the arginine–glycine-rich motifs of ATXN2L nor methylation inhibition alters ATXN2L localization to stress granules, suggesting that methylation of ATXN2L is probably not mandatory. - Highlights: • ATXN2L is asymmetrically dimethylated in vivo. • ATXN2L interacts with PRMT1 under normal and stress conditions. • PRMT1-mediated dimethylation of ATXN2L controls its nuclear localization. • ATXN2L localization to stress granules appears independent of its methylation state.

  16. Selective solid phase extraction and pre-concentration of heavy metals from seawater by physically and chemically immobilized 4-amino-3-hydroxy-2-(2-chlorobenzene)-azo-1-naphtalene sulfonic acid silica gel

    International Nuclear Information System (INIS)

    Mahmoud, M.E.; Soayed, A.A.; Hafez, O.F.

    2003-01-01

    4-Amino-3-hydroxy-2 - (2-chlorobenzene)-azo-l-naphthalene sulfonic acid (AHCANSA) was used as a chelating modifier to improve the reactivity of the silica gel surface in terms of selective binding and extraction of heavy metal ions. The surface cover-age values were found to be 0.488 and 0.473 mmol g -1 for the newly modified physically adsorbed silica gel phase (I) and chemically immobilized-AHCANSA phase (II), respectively. The modified silica gel phases (I, II) were tested for stability in different acidic buffer solutions (pH 1-6) and found to be highly resistant to hydrolysis and leaching by buffer solutions above pH 2. The application of these two phases as solid extractors for a series of mono-, di-, and tri-valent metal ions from aqueous solutions was also performed with different controlling factors such as the pH value of metal ion solutions and equilibrium shaking time. The mmol g -1 metal capacity values determined by silica gel phases (I, II) were found to confirm high affinity and selectivity characters for binding with heavy metal ions such as Cr 3+ , Ni 2+ , Cu 2+ , Zn 2+ , Cd 2+ and Pb 2+ in a range of 0.250-0.483. The tested alkali and alkaline earth metals, Na + , K + , Mg 2+ and Ca 2+ , were found to exhibit little interaction and binding ability with the modified silica gel phases. The selectivity characters incorporated into the modified silica gel phases were further utilized and applied in solid phase extraction and pre-concentration of trace concentration levels (∼1.0 μg mL -1 and 2.00-2.50 ng mL -1 ) from real seawater samples. The percentage recovery values determined for Cr 3+ , Cu 2+ , Zn 2+ , Cd 2+ and Pb 2+ were found to be in the range of 95.2-98.1 ± 2.0-5.0 %, and the pre-concentration recovery values for the same tested heavy metal ions were found to be in the range of 92.5-97.1 ± 3.0-6.0 % for the two newly modified silica gel phases with a pre-concentration factor of 500. Refs. 25 (author)

  17. Green synthesis of monodisperse silver nanoparticles using hydroxy propyl methyl cellulose

    Energy Technology Data Exchange (ETDEWEB)

    Dong, Chunfa; Zhang, Xianglin, E-mail: hust_zxl@mail.hust.edu.cn; Cai, Hao

    2014-01-15

    Graphical abstract: -- Highlights: • Synthesis of silver nanoparticles using hydroxy propyl methyl cellulose is reported. • HPMC and glucose are used as capping agent and reducing agent respectively. • It is the first time to use HPMC for synthesis of silver nanoparticles. • The small, spherical and well-dispersed particle is observed in the range of 3–17 nm. • The green method can be extended to other noble metals. -- Abstract: A simple and environmentally friendly method for the synthesis of highly stable and small sized silver nanoparticles with narrow distribution from 3 nm to 17 nm is reported. Silver nitrate, hydroxy propyl methyl cellulose (HPMC) and glucose, were used as silver precursor, capping agents and reducing agents respectively. The formation of silver nanoparticles was observed by change of color from colorless to wine red. The silver nanoparticles were characterized by transmission electron microscopy (TEM), UV–visible spectroscopy (UV–vis), X-ray diffraction (XRD) and Fourier-transform infrared spectroscopy (FT-IR). The results demonstrated that the obtained metallic nanoparticles were single crystalline silver nanoparticles capped with HPMC. The effects of the reaction time, reaction temperature and the concentration of silver ion and reducing agents on the particle size were investigated. A possible formation mechanism was proposed. The method may be extended to other noble metal for other technological applications such as additional medicinal, industrial applications.

  18. Green synthesis of monodisperse silver nanoparticles using hydroxy propyl methyl cellulose

    International Nuclear Information System (INIS)

    Dong, Chunfa; Zhang, Xianglin; Cai, Hao

    2014-01-01

    Graphical abstract: -- Highlights: • Synthesis of silver nanoparticles using hydroxy propyl methyl cellulose is reported. • HPMC and glucose are used as capping agent and reducing agent respectively. • It is the first time to use HPMC for synthesis of silver nanoparticles. • The small, spherical and well-dispersed particle is observed in the range of 3–17 nm. • The green method can be extended to other noble metals. -- Abstract: A simple and environmentally friendly method for the synthesis of highly stable and small sized silver nanoparticles with narrow distribution from 3 nm to 17 nm is reported. Silver nitrate, hydroxy propyl methyl cellulose (HPMC) and glucose, were used as silver precursor, capping agents and reducing agents respectively. The formation of silver nanoparticles was observed by change of color from colorless to wine red. The silver nanoparticles were characterized by transmission electron microscopy (TEM), UV–visible spectroscopy (UV–vis), X-ray diffraction (XRD) and Fourier-transform infrared spectroscopy (FT-IR). The results demonstrated that the obtained metallic nanoparticles were single crystalline silver nanoparticles capped with HPMC. The effects of the reaction time, reaction temperature and the concentration of silver ion and reducing agents on the particle size were investigated. A possible formation mechanism was proposed. The method may be extended to other noble metal for other technological applications such as additional medicinal, industrial applications

  19. Metabolism of /sup 14/C-labelled L-tryptophan, L-kynurenine, and hydroxy-L-kynurenine in miners with scleroderma

    Energy Technology Data Exchange (ETDEWEB)

    Hankes, L.V.; De Bruin, E.; Jansen, C.R.; Vorster, L.; Schmaeler, M.

    1977-03-19

    Six South African white miners were studied with the 2-g L-tryptophan load test and tracer doses of L-tryptophan-7a-/sup 14/C, L-kynurenine-keto-/sup 14/C and hydroxy-L-kynurenine-keto-/sup 14/C. The breath /sup 14/CO/sub 2/ and 14 urinary metabolites were measured. When they were compared with a previous study of American women with scleroderma, similar /sup 14/CO/sub 2/ and tryptophan metabolite excretion patterns were observed in the data from the miners. The labelled quinolinic acid excretion was more significantly elevated in the South African miners' urine than in the urine of the American women. The data from both studies suggest that some patients with scleroderma have an altered step in the tryptophan metabolic pathway after hydroxy-anthranilic acid. What relationship exists between the induction of pulmonary silicosis and the subsequent development of scleroderma, requires additional human studies.

  20. Design of Novel 4-Hydroxy-chromene-2-one Derivatives as Antimicrobial Agents

    Directory of Open Access Journals (Sweden)

    Milan Mladenović

    2010-06-01

    Full Text Available This paper presents the design of novel 4-hydroxy-chromene-2 one derivatives, based on previously obtained minimal inhibitory concentration values (MICs, against twenty four microorganism cultures, Gram positive and negative bacteria and fungi. Two of our compounds, 3b (MIC range 130–500 μg/mL and 9c (31.25–62.5 μg/mL, presented high potential antimicrobial activity. The compound 9c had equal activity to the standard ketoconazole (31.25 μg/mL against M. mucedo. Enlarged resistance of S. aureus, E. coli and C. albicans on the effect of potential drugs and known toxicity of coumarin antibiotics, motivated us to establish SAR and QSAR models of activity against these cultures and correlate biological activity, molecular descriptors and partial charges of functional groups to explain activity and use for the design of new compounds. The QSAR study presents essential relation of antimicrobial activity and dominant substituents, 4-hydroxy, 3-acetyl and thiazole functional groups, also confirmed through molecular docking. The result was ten new designed compounds with much improved predicted inhibition constants and average biological activity.

  1. Development of a Widely Usable Amino Acid Tracer: ⁷⁶Br-α-Methyl-Phenylalanine for Tumor PET Imaging.

    Science.gov (United States)

    Hanaoka, Hirofumi; Ohshima, Yasuhiro; Suzuki, Yurika; Yamaguchi, Aiko; Watanabe, Shigeki; Uehara, Tomoya; Nagamori, Shushi; Kanai, Yoshikatsu; Ishioka, Noriko S; Tsushima, Yoshito; Endo, Keigo; Arano, Yasushi

    2015-05-01

    Radiolabeled amino acids are superior PET tracers for the imaging of malignant tumors, and amino acids labeled with (76)Br, an attractive positron emitter because of its relatively long half-life (16.2 h), could potentially be a widely usable tumor imaging tracer. In this study, in consideration of its stability and tumor specificity, we designed two (76)Br-labeled amino acid derivatives, 2-(76)Br-bromo-α-methyl-l-phenylalanine (2-(76)Br-BAMP) and 4-(76)Br-bromo-α-methyl-l-phenylalanine (4-(76)Br-BAMP), and investigated their potential as tumor imaging agents. Both (76)Br- and (77)Br-labeled amino acid derivatives were prepared. We performed in vitro and in vivo stability studies and cellular uptake studies using the LS180 colon adenocarcinoma cell line. Biodistribution studies in normal mice and in LS180 tumor-bearing mice were performed, and the tumors were imaged with a small-animal PET scanner. Both (77)Br-BAMPs were stable in the plasma and in the murine body. Although both (77)Br-BAMPs were taken up by LS180 cells and the uptake was inhibited by L-type amino acid transporter 1 inhibitors, 2-(77)Br-BAMP exhibited higher uptake than 4-(77)Br-BAMP. In the biodistribution studies, 2-(77)Br-BAMP showed more rapid blood clearance and lower renal accumulation than 4-(77)Br-BAMP. More than 90% of the injected radioactivity was excreted in the urine by 6 h after the injection of 2-(77)Br-BAMP. High tumor accumulation of 2-(77)Br-BAMP was observed in tumor-bearing mice, and PET imaging with 2-(76)Br-BAMP enabled clear visualization of the tumors. 2-(77)Br-BAMP exhibited preferred pharmacokinetics and high LS180 tumor accumulation, and 2-(76)Br-BAMP enabled clear visualization of the tumors by PET imaging. These findings suggest that 2-(76)Br-BAMP could constitute a potential new PET tracer for tumor imaging and may eventually enable the wider use of amino acid tracers. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  2. 4-[(5-Hydroxy-3-methyl-1-phenyl-1H-pyrazol-4-ylphenylmethyl]-5-methyl-2-phenyl-1H-pyrazol-3(2H-one ethanol hemisolvate

    Directory of Open Access Journals (Sweden)

    Hoong-Kun Fun

    2009-01-01

    Full Text Available The asymmetric unit of the title compound, C27H24N4O2·0.5C2H6O, comprises two crystallographically independent molecules (A and B with slightly different conformations, and one ethanol molecule of crystallization. Intramolecular C—H...O and O—H...O hydrogen bonds generate six- and eight-membered rings, producing S(6 and S(8 ring motifs, respectively. In molecule A, one of the benzene rings is disordered over two positions, with site-occupancy factors of 0.542 (11 and 0.458 (11. The dihedral angles between the central benzene ring and the two outer benzene rings are 73.88 (9 and 82.6 (2/88.9 (2° in molecule A, and 80.81 (8 and 79.38 (8° in molecule B. In the crystal structure, molecules form infinite one-dimensional chains in the (101 plane. The crystal structure is stabilized by intermolecular O—H...N, N—H...N, N—H...O and C—H...O hydrogen bonds, weak C—H...π and π–π [centroid–centroid = 3.5496 (1 Å] interactions.

  3. Synthesis of tritium or deuterium labelled 19-nor-3. cap alpha. -hydroxy-5. cap alpha. -androstan-17-one from nortestosterone

    Energy Technology Data Exchange (ETDEWEB)

    Protiva, J; Klinotova, E [Karlova Univ., Prague (Czechoslovakia). Prirodovedecka Fakulta; Filip, J [Ustav pro Vyzkum, Vyrobu a Vyuziti Radioisotopu, Prague (Czechoslovakia); Hampl, R [Research Inst. of Endocrinology, Praha (Czechoslovakia)

    1982-10-20

    Tritium and/or deuterium (5-H) labelled 19-nor-3..cap alpha..-hydroxy-5..cap alpha..-androstan-17-one (norandrosterone) was prepared from nortestosterone in view to use it as a radioligand for radioimmunoassay of the main nortestosterone metabolites. Based upon model experiments using testosterone and deuterium labelling, the following four step procedure was established: nortestosterone was oxidized with pyridine chlorochromate and the resulting 19-nor-4-androsten-3,17-dione was tritiated with tritium gas under catalysis with tris(triphenylphosphine)rhodium chloride to give (4,5..cap alpha..-/sup 3/H)19-nor-5..cap alpha..-androstan-3,17-dione. A selective reduction of the latter compound yielded (5-/sup 3/H)19-nor-3..cap alpha..-hydroxy-5..cap alpha..-androstan-17-one of the molar radioactivity 0.3 TBq (8.15 Ci)/mmol.

  4. Soluble ICAM-5, a product of activity dependent proteolysis, increases mEPSC frequency and dendritic expression of GluA1.

    Directory of Open Access Journals (Sweden)

    Irina Lonskaya

    Full Text Available Matrix metalloproteinases (MMPs are zinc dependent endopeptidases that can be released from neurons in an activity dependent manner to play a role in varied forms of learning and memory. MMP inhibitors impair hippocampal long term potentiation (LTP, spatial memory, and behavioral correlates of drug addiction. Since MMPs are thought to influence LTP through a β1 integrin dependent mechanism, it has been suggested that these enzymes cleave specific substrates to generate integrin binding ligands. In previously published work, we have shown that neuronal activity stimulates rapid MMP dependent shedding of intercellular adhesion molecule-5 (ICAM-5, a synaptic adhesion molecule expressed on dendrites of the telencephalon. We have also shown that the ICAM-5 ectodomain can interact with β1 integrins to stimulate integrin dependent phosphorylation of cofilin, an event that occurs with dendritic spine maturation and LTP. In the current study, we investigate the potential for the ICAM-5 ectodomain to stimulate changes in α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor (AMPAR dependent glutamatergic transmission. Single cell recordings show that the ICAM-5 ectodomain stimulates an increase in the frequency, but not the amplitude, of AMPA mini excitatory post synaptic currents (mEPSCs. With biotinylation and precipitation assays, we also show that the ICAM-5 ectodomain stimulates an increase in membrane levels of GluA1, but not GluA2, AMPAR subunits. In addition, we observe an ICAM-5 associated increase in GluA1 phosphorylation at serine 845. Concomitantly, ICAM-5 affects an increase in GluA1 surface staining along dendrites without affecting an increase in dendritic spine number. Together these data are consistent with the possibility that soluble ICAM-5 increases glutamatergic transmission and that post-synaptic changes, including increased phosphorylation and dendritic insertion of GluA1, could contribute. We suggest that future studies

  5. Synthesis and Antitumor Molecular Mechanism of Agents Based on Amino 2-(3′,4′,5′-Trimethoxybenzoyl)-benzo[b]furan: Inhibition of Tubulin and Induction of Apoptosis

    Science.gov (United States)

    Baraldi, Pier Giovanni; Lopez-Cara, Carlota; Cruz-Lopez, Olga; Carrion, Maria Dora; Salvador, Maria Kimatrai; Bermejo, Jaime; Estévez, Sara; Estévez, Francisco; Balzarini, Jan; Brancale, Andrea; Ricci, Antonio; Chen, Longchuan; Kim, Jae Gwan; Hamel, Ernest

    2011-01-01

    Induction of apoptosis is a promising strategy that could lead to the discovery of new molecules active in cancer chemotherapy. This property is generally observed when cells are treated with agents that target microtubules, dynamic structures that play a crucial role in cell division. Small molecules such as benzo[b]furans are attractive as inhibitors of tubulin polymerization. A new class of inhibitors of tubulin polymerization based on the 2-(3′,4′,5′-trimethoxybenzoyl)benzo[b]furan molecular skeleton, with the amino group placed at different positions on the benzene ring, were synthesized and evaluated for antiproliferative activity, inhibition of tubulin polymerization, and cell-cycle effects. The methoxy substitution pattern on the benzene portion of the benzo[b]furan moiety played an important role in affecting antiproliferative activity. In the series of 5-amino derivatives, the greatest inhibition of cell growth oc curred if the methoxy substituent is placed at the C6 position, whereas C7 substitution decreases potency. The most promising compound in this series is 2-(3′,4′,5′-trimethoxybenzoyl)-3-methyl-5-amino-6-methoxybenzo[b]furan (3h), which inhibits cancer cell growth at nanomolar concentrations (IC50=16–24 nm), and interacts strongly with tubulin by binding to the colchicine site. Sub-G1 apoptotic cells in cultures of HL-60 and U937 cells were observed by flow cytometric analysis after treatment with 3h in a concentration-dependent manner. We also show that compound 3h induces apoptosis by activation of caspase-3, -8, and -9, and this is associated with cytochrome c release from mitochondria. The introduction of an α-bromoacryloyl group increased antiproliferative activity with respect to the parent amino derivatives. PMID:21805646

  6. Recovery of plutonium from oxalate supernatant using 1-phenyl-3-methyl-4-benzoyl-5-pyrazolone

    International Nuclear Information System (INIS)

    Mohapatra, P.K.; Manchanda, V.K.; Gupta, K.K.; Singh, R.K.

    1997-01-01

    Extraction of Pu(IV) from oxalate supernatant was carried out employing varying concentrations of 1-phenyl-3-methyl-4-benzoyl-5-pyrazolone (PMBP). Near quantitative extraction of Pu(IV) from an aqueous solution of 0.2M oxalic acid and 3M HNO 3 was possible employing 0.05M PMBP solution in xylene. Extraction studies at different uranium loading conditions were carried out and conditions for quantitative stripping were arrived at. (author). 2 refs., 4 tabs

  7. The average effective dose of 4-amino-5-(furan-2-yl-4H-1 ,2,4-triazole-3-thiol in experimental hepatitis

    Directory of Open Access Journals (Sweden)

    I. M. Belay

    2014-04-01

    Full Text Available The work presents the research of the average effective dose of 4-amino-5-(furan-2-yl-4H-1,2,4-triazole-3-thiol in experimental hepatitis. Recalculations conducted for the human with the sensitivity coefficient, average effective dose for human is 13,87 mg/kg.

  8. Features of the behavior of 4-amino-5-carboxamido-1,2,3-triazole in multicomponent heterocyclizations with carbonyl compounds

    Directory of Open Access Journals (Sweden)

    Eugene S. Gladkov

    2012-11-01

    Full Text Available Multicomponent reactions involving polyfunctional 4-amino-5-carboxamido-1,2,3-triazole and cyclic carbonyl-containing CH-acids were studied under conventional thermal heating, microwave and ultrasonic irradiation. The features of the reactions studied were discussed and the optimized procedures for the synthesis of final triazolopyrimidines were elaborated. In contrast to the similar MCRs of numerous other aminoazoles, a change of direction of the heterocyclizations in the case of 4-amino-5-carboxamido-1,2,3-triazole was not observed when microwave or thermal heating was substituted by ultrasonication at ambient temperature.

  9. Determination of 4-Chloroindole-3-Acetic Acid Methyl Ester in Lathyrus Vicia and Pisum by Gas Chromatography - Mass Spectrometry

    DEFF Research Database (Denmark)

    Engvild, Kjeld Christensen; Egsgaard, Helge; Larsen, Elfinn

    1980-01-01

    4-Chloroindole-3-acetic acid methyl ester was identified unequivocally in Lathyrus latifolius L., Vicia faba L. and Pisum sativum L. by thin layer chromatography, gas chromatography and mass spectrometry. The gas chromatographic system was able to separate underivatized chloroindole-3-acetic acid...... methyl ester isomers. The quantitative determination of 4-chloroindole-3-acetic acid methyl ester in immature seeds of these three species was performed by gas chromatography – mass spectrometry using deuterium labelled 4-chloro-indole-3-acetic acid methyl ester as an internal standard. P. sativum...

  10. 2-Hydroxy-5-nitrobenzaldehyde

    Directory of Open Access Journals (Sweden)

    Şamil Işık

    2009-12-01

    Full Text Available The title compound, C7H5NO4, is essentially planar, with a maximum deviation from the mean plane of 0.0116 (11 Å for the hydroxy O atom. The molecular and crystal structure are stabilized by intra- and intermolecular interactions. An intramolecular O—H...O hydrogen bond generates a six-membered ring, producing an S(6 ring motif. The C—H...O interactions result in the formation of C(5 chains and R22(8 rings forming an approximately planar network parallel to (10overline{1}. These planes are interconnected through π–π interactions [centroid–centroid distance 3.582 (2 Å].

  11. O-Alkylated heavy atom carbohydrate probes for protein X-ray crystallography: Studies towards the synthesis of methyl 2-O-methyl-L-selenofucopyranoside

    Directory of Open Access Journals (Sweden)

    Roman Sommer

    2016-12-01

    Full Text Available Selenoglycosides are used as reactive glycosyl donors in the syntheses of oligosaccharides. In addition, such heavy atom analogs of natural glycosides are useful tools for structure determination of their lectin receptors using X-ray crystallography. Some lectins, e.g., members of the tectonin family, only bind to carbohydrate epitopes with O-alkylated ring hydroxy groups. In this context, we report the first synthesis of an O-methylated selenoglycoside, specifically methyl 2-O-methyl-L-selenofucopyranoside, a ligand of the lectin tectonin-2 from the mushroom Laccaria bicolor. The synthetic route required a strategic revision and further optimization due to the intrinsic lability of alkyl selenoglycosides, in particular for the labile fucose. Here, we describe a successful synthetic access to methyl 2-O-methyl-L-selenofucopyranoside in 9 linear steps and 26% overall yield starting from allyl L-fucopyranoside.

  12. O-Alkylated heavy atom carbohydrate probes for protein X-ray crystallography: Studies towards the synthesis of methyl 2-O-methyl-L-selenofucopyranoside.

    Science.gov (United States)

    Sommer, Roman; Hauck, Dirk; Varrot, Annabelle; Imberty, Anne; Künzler, Markus; Titz, Alexander

    2016-01-01

    Selenoglycosides are used as reactive glycosyl donors in the syntheses of oligosaccharides. In addition, such heavy atom analogs of natural glycosides are useful tools for structure determination of their lectin receptors using X-ray crystallography. Some lectins, e.g., members of the tectonin family, only bind to carbohydrate epitopes with O-alkylated ring hydroxy groups. In this context, we report the first synthesis of an O -methylated selenoglycoside, specifically methyl 2- O -methyl-L-selenofucopyranoside, a ligand of the lectin tectonin-2 from the mushroom Laccaria bicolor . The synthetic route required a strategic revision and further optimization due to the intrinsic lability of alkyl selenoglycosides, in particular for the labile fucose. Here, we describe a successful synthetic access to methyl 2- O -methyl-L-selenofucopyranoside in 9 linear steps and 26% overall yield starting from allyl L-fucopyranoside.

  13. A Novel Schiff Base of 3-acetyl-4-hydroxy-6-methyl-(2Hpyran-2-one and 2,2'-(ethylenedioxydiethylamine as Potential Corrosion Inhibitor for Mild Steel in Acidic Medium

    Directory of Open Access Journals (Sweden)

    Jonnie N. Asegbeloyin

    2015-05-01

    Full Text Available The corrosion inhibition activity of a newly synthesized Schiff base (SB from 3-acetyl-4-hydroxy-6-methyl-(2H-pyran-2-one and 2,2'-(ethylenedioxydiethylamine was investigated on the corrosion of mild steel in 1 M HCl solution using potentiodynamic polarization and electrochemical impedance spectroscopic techniques. Ultraviolet-visible (UV-vis and Raman spectroscopic techniques were used to study the chemical interactions between SB and mild steel surface. SB was found to be a relatively good inhibitor of mild steel corrosion in 1 M HCl. The inhibition efficiency increases with increase in concentration of SB. The inhibition activity of SB was ascribed to its adsorption onto mild steel surface, through physisorption and chemisorption, and described by the Langmuir adsorption model. Quantum chemical calculations indicated the presence of atomic sites with potential nucleophilic and electrophilic characteristics with which SB can establish electronic interactions with the charged mild steel surface.

  14. 2-[3-Furyl(hydroxy)methyl]-2,3-dimethylcyclohexanone.

    Science.gov (United States)

    García, Esther; Mendoza, Virgilio; Guzmán, José Agustín; Maldonado Graniel, Luis Angel; Hernández-Ortega, Simón

    2002-06-01

    Contribution No. 1750 of the Instituto de Quimica, UNAM, Mexico. In the molecule of the title compound, C(13)H(18)O(3), there is a syn relationship between the two vicinal methyl groups. The six-membered ring adopts a chair conformation, with one equatorial and two axial groups, and the furyl group is almost parallel to the ketone group. Intermolecular hydrogen bonds [O[bond]H...O[double bond]C 2.814 (3) A] form chains along [100].

  15. The structure of carbon nanotubes formed of graphene layers L4-8, L5-7, L3-12, L4-6-12

    Science.gov (United States)

    Shapovalova, K. E.; Belenkov, E. A.

    2017-11-01

    We geometrically calculate the optimized structure of nanotubes based on the graphene layers, using the method of molecular mechanics MM+. It was found that only the nanotubes, based on the graphene layers L4-8, L5-7, L3-12, L4-6-12, have a cylindrical form. Calculations of the sublimation energy, carried out using the semi-empirical quantum-mechanic method PM3, show that energy increases with the increase of nanotube diameters.

  16. Synthesis, NMR spectral and antimicrobial studies of some [N-methyl-3t-alkyl-2r,6c-diarylpiperidin-4-ylidine]-5‧-methylthiazolidine-4-ones

    Science.gov (United States)

    Prakash, S. M.; Pandiarajan, K.; Kumar, S.

    2013-06-01

    Four new [N-methyl-3t-alkyl-2r,6c-diaryl-4-ylidine]-5'-methylthiozolidin-4-ones 9-12 have been synthesized by the condensation of N-methyl-3t-alkyl-2r,6c-diarylpiperidin-4-one thiosemicarbazones with ethyl 2-bromopropionate. These compounds have been characterized using FT-IR, 1H NMR, 13C NMR spectral techniques. HOMOCOSY, HSQC and HMBC spectral study have been done for [N-methyl-3,3-dimethyl-2r,6c-bis(p-methoxyphenyl)piperidin-4-ylidine]-5'-methylthiazolidine-4-one (12). Two geometrical isomers are formed in this reaction. In all these compounds piperidin rings adopt chair conformation. The rotation of the aryl group at C-2 is rather slow in 10-12. Antimicrobial activities have also been studied for 9-12. These compounds are active against all the tested bacterial and fungal strains.

  17. Base induced chemical conversion of 3-carbamoyl-2-isoxazolines.

    Science.gov (United States)

    Nishiwaki, Nagatoshi; Maki, Asaka; Ariga, Masahiro

    2009-01-01

    3-Carbamoyl-2-isoxazolines, prepared by cycloaddition of functionalized nitrile oxide, serve as masked 3-unsubstituted isoxazolines to afford 2-isoxazoline-3-carboxylic acid, beta-cyanoalcohol, alpha,beta-unsaturated nitrile, and alpha,beta-unsaturated amide upon heating in the alkaline solution. The present reaction is also applicable to synthesis of 3,4-difunctionalized isoxazoles and beta-hydroxy-gamma-lactone.

  18. Methionine kinetics and balance at the 1985 FAO/WHO/UNU intake requirement in adult men studied with L-[2H3-methyl-1-13C]methionine as a tracer

    International Nuclear Information System (INIS)

    Young, V.R.; Wagner, D.A.; Burini, R.; Storch, K.J.

    1991-01-01

    The upper range of the requirement for methionine plus cystine in healthy adults was proposed in 1985 by FAO/WHO/UNU to be 13 mg.kg body wt-1.d-1. To explore the validity of this estimate, five healthy, young adult men were given for 7 d a diet based on an L-amino acid mixture supplying 13 mg methionine.kg-1.d-1 (87 mumol.kg-1.d-1) without cystine. Constant intravenous infusions of L-[2H3-methyl-1-13C]methionine were given on days 5 and 7 while subjects were in the fed and postabsorptive states, respectively. Estimates were made of methionine oxidation, and daily methionine balance was derived from the intake-oxidation data. For the five subjects, methionine balances were -0.9, +0.7, +3.5, -3.1, and -3.8 mg kg-1.d-1, or -6, +5, +23, -21, and -26 mumol.kg-1.d-1. These findings lead to the conclusion that the upper range of the requirement for methionine plus cystine probably exceeds 13 mg.kg-1.d-1 in healthy young adults. The implications of this conclusion for establishing an appropriate amount of sulfur amino acids in an amino acid requirement pattern for adults is discussed

  19. Searching for Extraterrestrial Amino Acids in a Contaminated Meteorite: Amino Acid Analyses of the Canakkale L6 Chondrite

    Science.gov (United States)

    Burton, A. S.; Elsila, J. E.; Glavin, D. P.; Dworkin, J. P.; Ornek, C. Y.; Esenoglu, H. H.; Unsalan, O.; Ozturk, B.

    2016-01-01

    Amino acids can serve as important markers of cosmochemistry, as their abundances and isomeric and isotopic compositions have been found to vary predictably with changes in parent body chemistry and alteration processes. Amino acids are also of astrobiological interest because they are essential for life on Earth. Analyses of a range of meteorites, including all groups of carbonaceous chondrites, along with H, R, and LL chondrites, ureilites, and a martian shergottite, have revealed that amino acids of plausible extraterrestrial origin can be formed in and persist after a wide range of parent body conditions. However, amino acid analyses of L6 chondrites to date have not provided evidence for indigenous amino acids. In the present study, we performed amino acid analysis on larger samples of a different L6 chondite, Canakkale, to determine whether or not trace levels of indigenous amino acids could be found. The Canakkale meteor was an observed fall in late July, 1964, near Canakkale, Turkey. The meteorite samples (1.36 and 1.09 g) analyzed in this study were allocated by C. Y. Ornek, along with a soil sample (1.5 g) collected near the Canakkale recovery site.

  20. Synthesis of novel pyrazolo[3,4-d]pyrimidinone derivatives as cytotoxic inhibitors

    Directory of Open Access Journals (Sweden)

    Ameur Rahmouni

    2014-02-01

    Full Text Available Various α-fonctionalized iminoethers 2 were easily prepared from ethyl 5-amino-3-substituted-1-phenyl-1H-pyrazole-4-carboxylate 1. The reaction of iminoethers 2 with ammonia afforded 3-substitued-1-phenyl-1H-pyrazolo[3,4-d] pyrimidin-4(5H-ones 3 which were also synthesized by the addition of formamide to ethyl 5-amino-3-substituted-1-phenyl-1H-pyrazole-4-carboxylate 1. The 5-amino-3-substitued-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H-ones 4 were obtained from hydrazonolysis of iminoethers 2. Otherwise, the condensation of these intermediates 2 with a series of some primary amines and hydroxylamine led respectively, to the corresponding 3,5-disubstitued-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H-ones 5 and the 3-substitued-5-hydroxy-1-phenyl-1H-pyrazolo[3,4-d] pyrimidin-4-(5H-ones 6. The synthesized compounds 1-6 were completely characterized by 1H NMR, 13C NMR, IR and HRMS. Some synthesized compounds were evaluated for their cytotoxic effect using the Human cervical adenocarcinoma Hela cell line.