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Sample records for acid transaminase inhibitor

  1. Effects of the gamma-aminobutyrate transaminase inhibitors gabaculine and gamma-vinyl GABA on gamma-aminobutyric acid release from slices of rat cerebral cortex

    The release of [3H]gamma-aminobutyric acid (GABA) from pre-loaded slices of rat cerebral cortex was investigated in the presence and absence of the GABA-transaminase inhibitors gabaculine and gamma-vinyl GABA. In the experiments carried out without an inhibitor, an ion-exchange column chromatographic technique was used to separate [3H]GABA from tritiated metabolites released with it into the superfusate. The presence of gabaculine (5 microM) substantially reduced the Ca2+-dependence of the release of [3H]GABA evoked by a 4 min 30 mM K+ pulse, whereas this was not appreciably reduced by the presence of gamma-vinyl GABA (2 mM or 10 mM). Nevertheless, the characteristics of [3H]GABA release were not identical in the presence and absence of either inhibitor

  2. Genotoxic and mutagenic effects of vigabatrin, a γ-aminobutyric acid transaminase inhibitor, in Wistar rats submitted to rotarod task.

    Coelho, V R; Sousa, K; Pires, T R; Papke, Dkm; Vieira, C G; de Souza, L P; Leal, M B; Schunck, Rva; Picada, J N; Pereira, P

    2016-09-01

    Vigabatrin (VGB) is an antiepileptic drug thatincreases brain γ-aminobutyric acid (GABA) levels through irreversible inhibition of GABA transaminase. The aim of this study was to evaluate neurotoxicological effects of VGB measuring motor activity and genotoxic and mutagenic effects after a single and repeated administration. Male Wistar rats received saline, VGB 50, 100, or 250 mg/kg by gavage for acute and subchronic (14 days) treatments and evaluated in the rotarod task. Genotoxicity was evaluated using the alkaline version of the comet assay in samples of blood, liver, hippocampus, and brain cortex after both treatments. Mutagenicity was evaluated using the micronucleus test in bone marrow of the same animals that received subchronic treatment. The groups treated with VGB showed similar performance in rotarod compared with the saline group. Regarding the acute treatment, it was observed that only higher VGB doses induced DNA damage in blood and hippocampus. After the subchronic treatment, VGB did not show genotoxic or mutagenic effects. In brief, VGB did not impair motor activities in rats after acute and subchronic treatments. It showed a repairable genotoxic potential in the central nervous system since genotoxicity was observed in the acute treatment group. PMID:26500220

  3. Effects of Vigabatrin, an Irreversible GABA Transaminase Inhibitor, on Ethanol Reinforcement and Ethanol Discriminative Stimuli in Mice

    Griffin, William C.; Nguyen, Shaun A.; Deleon, Christopher P.; Middaugh, Lawrence D.

    2012-01-01

    We tested the hypothesis that the irreversible gamma-amino butyric acid (GABA) transaminase inhibitor, γ-vinyl GABA (Vigabatrin; VGB) would reduce ethanol reinforcement and enhance the discriminative stimulus effect of ethanol, effectively reducing ethanol intake. The present studies used adult C57BL/6J (B6) mice in well-established operant, two-bottle choice consumption, locomotor activity and ethanol discrimination procedures, to examine comprehensively the effects of VGB on ethanol-support...

  4. Bacillus anthracis ω-amino acid:pyruvate transaminase employs a different mechanism for dual substrate recognition than other amine transaminases.

    Steffen-Munsberg, Fabian; Matzel, Philipp; Sowa, Miriam A; Berglund, Per; Bornscheuer, Uwe T; Höhne, Matthias

    2016-05-01

    Understanding the metabolic potential of organisms or a bacterial community based on their (meta) genome requires the reliable prediction of an enzyme's function from its amino acid sequence. Besides a remarkable development in prediction algorithms, the substrate scope of sequences with low identity to well-characterized enzymes remains often very elusive. From a recently conducted structure function analysis study of PLP-dependent enzymes, we identified a putative transaminase from Bacillus anthracis (Ban-TA) with the crystal structure 3N5M (deposited in the protein data bank in 2011, but not yet published). The active site residues of Ban-TA differ from those in related (class III) transaminases, which thereby have prevented function predictions. By investigating 50 substrate combinations its amine and ω-amino acid:pyruvate transaminase activity was revealed. Even though Ban-TA showed a relatively narrow amine substrate scope within the tested substrates, it accepts 2-propylamine, which is a prerequisite for industrial asymmetric amine synthesis. Structural information implied that the so-called dual substrate recognition of chemically different substrates (i.e. amines and amino acids) differs from that in formerly known enzymes. It lacks the normally conserved 'flipping' arginine, which enables dual substrate recognition by its side chain flexibility in other ω-amino acid:pyruvate transaminases. Molecular dynamics studies suggested that another arginine (R162) binds ω-amino acids in Ban-TA, but no side chain movements are required for amine and amino acid binding. These results, supported by mutagenesis studies, provide functional insights for the B. anthracis enzyme, enable function predictions of related proteins, and broadened the knowledge regarding ω-amino acid and amine converting transaminases. PMID:26795966

  5. Effect of chronic treatment with the GABA transaminase inhibitors γ-vinyl GABA and ethanolamine O-sulphate on the in vitro GABA release from rat hippocampus

    Qume, M; Fowler, L. J.

    1997-01-01

    The effects of 2, 8 and 21 day oral treatment with the specific γ-aminobutyric acid transaminase (GABA-T) inhibitors γ-vinyl GABA (GVG) and ethanolamine O-sulphate (EOS) on brain GABA levels, GABA-T activity, and basal and stimulated GABA release from rat cross-chopped brain hippocampal slices was investigated.Treatment with GABA-T inhibitors lead to a reduction in brain GABA-T activity by 65–80% compared with control values, with a concomitant increase in brain GABA content of 40–100%.Basal ...

  6. Two previously undetected variants of glutamic-pyruvic transaminase found by acidic polyacrylamide gel electrophoresis.

    McLellan, T

    1982-01-01

    Two new electrophoretic variants of glutamic-pyruvic transaminase (GPT) have been found by polyacrylamide gel electrophoresis at acidic pH. They appeared to represent a single allele, GPT 2, by the standard method of starch gel electrophoresis. Studies in families show that they are inherited as codominant alleles at the GPT locus. Population frequencies are about the same as those of other rare GPT variants. Their behavior on gels is consistent with both of them having substitutions of histi...

  7. Ursodeoxycholic Acid Can Improve Liver Transaminase Quantities in Children with Anticonvulsant Drugs Hepatotoxicity: a Pilot Study.

    Masoumeh Asgarshirazi

    2015-06-01

    Full Text Available The present study has been directed to investigate Ursodeoxycholic Acid (UDCA effect in children, to reduce the high Liver transaminases induced by Anticonvulsant drugs (drug induced hepatitis. This idea has been driven from Cytoprotective and antioxidant properties of UDCA to be used in drug induced inflammation in Liver. Twenty two epileptic patients aged between 4 mo - 3 yr whom were under anticonvulsant therapy with drugs such as valperoic acid, primidone, levetiracetam, Phenobarbital or any combination of them and had shown Liver transaminases rise , after rule out of Viral-Autoimmune, Metabolic and Anatomic causes, have been prescribed UDCA in dose of 10-15 mg/kg/day, at least for 6 months. Any patient who have shown confusing factors such as genetic disorders with liver involvement or spontaneous decline in enzymes or had not treatment compliance has been excluded from the study. Transaminases range changes as well as Probable side effects of the drug have been monitored. The results indicated that UDCA is effective and well tolerable in the children with drug induced hyper transaminasemia. No side effect has been seen and recorded in this study. Based on this study and its results, we recommend UDCA as a safe and effective choice in drug induced hepatotoxicities.

  8. Nucleic acids encoding plant glutamine phenylpyruvate transaminase (GPT) and uses thereof

    Unkefer, Pat J.; Anderson, Penelope S.; Knight, Thomas J.

    2016-03-29

    Glutamine phenylpyruvate transaminase (GPT) proteins, nucleic acid molecules encoding GPT proteins, and uses thereof are disclosed. Provided herein are various GPT proteins and GPT gene coding sequences isolated from a number of plant species. As disclosed herein, GPT proteins share remarkable structural similarity within plant species, and are active in catalyzing the synthesis of 2-hydroxy-5-oxoproline (2-oxoglutaramate), a powerful signal metabolite which regulates the function of a large number of genes involved in the photosynthesis apparatus, carbon fixation and nitrogen metabolism.

  9. Effect of organophosphorus pesticide on plasma transaminases and amino acids in rats

    Pesticides are added to the environment for killing or injuring some of life. Most of the chemicals that are used as pesticides are not highly selective but are generally toxic to man, and other desirable form of life. in case of organophosphorus pesticides, the problem of accumulated residual physiological effects of these pesticides has lead to some studies on their effects on animals. the present investigation was undertaken to show the effect of repeated administered doses of organophosphorus pesticide, curacron, for different periods on brain and liver free amino acids. the toxic effects of repeated oral doses of curacron were evaluated by measuring serum alkaline phosphatase, glutamic pyruvic and glutamic oxaloacetic transaminases. also radioimmunoassay technique was used to study the effect of different repeated doses of curacron at different periods on triiodothyronine (T3) and tetraiodothyronine (T4) hormones using 125I labelled triiodothyronine and 125I labelled thyroxine

  10. Crystallization and preliminary X-ray diffraction analysis of ω-amino acid:pyruvate transaminase from Chromobacterium violaceum

    An ω-amino acid:pyruvate transaminase from C. violaceum has been purified and crystallized in two crystal forms. The structure has been solved using molecular replacement. The enzyme ω-transaminase catalyses the conversion of chiral ω-amines to ketones. The recombinant enzyme from Chromobacterium violaceum has been purified to homogeneity. The enzyme was crystallized from PEG 4000 using the microbatch method. Data were collected to 1.7 Å resolution from a crystal belonging to the triclinic space group P1, with unit-cell parameters a = 58.9, b = 61.9, c = 63.9 Å, α = 71.9, β = 87.0, γ = 74.6°. Data were also collected to 1.95 Å from a second triclinic crystal form. The structure has been solved using the molecular-replacement method

  11. Deletion of the Saccharomyces cerevisiae ARO8 gene, encoding an aromatic amino acid transaminase, enhances phenylethanol production from glucose.

    Romagnoli, Gabriele; Knijnenburg, Theo A; Liti, Gianni; Louis, Edward J; Pronk, Jack T; Daran, Jean-Marc

    2015-01-01

    Phenylethanol has a characteristic rose-like aroma that makes it a popular ingredient in foods, beverages and cosmetics. Microbial production of phenylethanol currently relies on whole-cell bioconversion of phenylalanine with yeasts that harbour an Ehrlich pathway for phenylalanine catabolism. Complete biosynthesis of phenylethanol from a cheap carbon source, such as glucose, provides an economically attractive alternative for phenylalanine bioconversion. In this study, synthetic genetic array (SGA) screening was applied to identify genes involved in regulation of phenylethanol synthesis in Saccharomyces cerevisiae. The screen focused on transcriptional regulation of ARO10, which encodes the major decarboxylase involved in conversion of phenylpyruvate to phenylethanol. A deletion in ARO8, which encodes an aromatic amino acid transaminase, was found to underlie the transcriptional upregulation of ARO10 during growth, with ammonium sulphate as the sole nitrogen source. Physiological characterization revealed that the aro8Δ mutation led to substantial changes in the absolute and relative intracellular concentrations of amino acids. Moreover, deletion of ARO8 led to de novo production of phenylethanol during growth on a glucose synthetic medium with ammonium as the sole nitrogen source. The aro8Δ mutation also stimulated phenylethanol production when combined with other, previously documented, mutations that deregulate aromatic amino acid biosynthesis in S. cerevisiae. The resulting engineered S. cerevisiae strain produced >3 mm phenylethanol from glucose during growth on a simple synthetic medium. The strong impact of a transaminase deletion on intracellular amino acid concentrations opens new possibilities for yeast-based production of amino acid-derived products. PMID:24733517

  12. Plasma membrane fatty acid-binding protein and mitochondrial glutamic-oxaloacetic transaminase of rat liver are related

    The hepatic plasma membrane fatty acid-binding protein (h-FABPPM) and the mitochondrial isoenzyme of glutamic-oxaloacetic transaminase (mGOT) of rat liver have similar amino acid compositions and identical amino acid sequences for residues 3-24. Both proteins migrate with an apparent molecular mass of 43 kDa on SDS/polyacrylamide gel electrophoresis, have a similar pattern of basic charge isomers on isoelectric focusing, are eluted similarly from four different high-performance liquid chromatographic columns, have absorption maxima at 435 nm under acid conditions and 354 nm at pH 8.3, and bind oleate. Sinusoidally enriched liver plasma membranes and purified h-FABPPM have GOT enzymatic activity. Monospecific rabbit antiserum against h-FABPPM reacts on Western blotting with mGOT, and vice versa. Antisera against both proteins produce plasma membrane immunofluorescence in rat hepatocytes and selectively inhibit the hepatocellular uptake of [3H]oleate but not that of [35S]sulfobromophthalein or [14C]taurocholate. The inhibition of oleate uptake produced by anti-h-FABPPM can be eliminated by preincubation of the antiserum with mGOT; similarly, the plasma membrane immunofluorescence produced by either antiserum can be eliminated by preincubation with the other antigen. These data suggest that h-FABPPM and mGOT are closely related

  13. The use of 15N-labelled amino acids in vivo and in vitro for transamination studies: tryptophan transaminase in maize plants

    Besides conventional methods, transaminase activity can also be followed by an isotopically labelled substrate, i.e. by an amino acid with a 15N labelled amino group. The application of the labelled substrate enables their study in vitro as well as in vivo. This method was applied for following the tryptophan transaminase activity in germinating maize plants. The enzym preparations used for in vitro analysis were purified on a Sephadex G 100 column. For in vivo experiments the 15N substrate was introduced by vacuum infiltration into the plants leaves. The amino acids originated by transamination are chromatographically separated and after purifying by paper electrophoresis, the atom excess 15N is determined. In maize tissue originated glutamic acid (from infiltrated α-ketoglutarate substrate), which in the course of further reactions was transformed into aspartic acid and asparagine. The results found so far by studying the low activity of tryptophan-transaminase in vivo entitle us to improve our method of transaminase activity determination by using 15N labelled-substrate. (author)

  14. Complete amino acid sequence of branched-chain amino acid aminotransferase (transaminase B) of Salmonella typhimurium, identification of the coenzyme-binding site and sequence comparison analysis

    The complete amino acid sequence of the subunit of branched-chain amino acid aminotransferase of Salmonella typhimurium was determined by automated Edman degradation of peptide fragments generated by chemical and enzymatic digestion of S-carboxymethylated and S-pyridylethylated transaminase B. Peptide fragments of transaminase B were generated by treatment of the enzyme with trypsin, Staphylococcus aureus V8 protease, endoproteinase Lys-C, and cyanogen bromide. Protocols were developed for separation of the peptide fragments by reverse-phase high performance liquid chromatography (HPLC), ion-exchange HPLC, and SDS-urea gel electrophoresis. The enzyme subunit contains 308 amino acid residues and has a molecular weight of 33,920 daltons. The coenzyme-binding site was determined by treatment of the enzyme, containing bound pyridoxal 5-phosphate, with tritiated sodium borohydride prior to trypsin digestion. Monitoring radioactivity incorporation and peptide map comparisons with an apoenzyme tryptic digest, allowed identification of the pyridoxylated-peptide which was isolated by reverse-phase HPLC and sequenced. The coenzyme-binding site is a lysyl residue at position 159. Some peptides were further characterized by fast atom bombardment mass spectrometry

  15. Suppression of γ-Aminobutyric Acid (GABA) Transaminases Induces Prominent GABA Accumulation, Dwarfism and Infertility in the Tomato (Solanum lycopersicum L.)

    Koike, Satoshi; Matsukura, Chiaki; Takayama, Mariko; Asamizu, Erika; Ezura, Hiroshi

    2013-01-01

    Tomatoes accumulate γ-aminobutyric acid (GABA) at high levels in the immature fruits. GABA is rapidly converted to succinate during fruit ripening through the activities of GABA transaminase (GABA-T) and succinate semialdehyde dehydrogenase (SSADH). Although three genes encoding GABA-T and both pyruvate- and α-ketoglutarate-dependent GABA-T activities have been detected in tomato fruits, the mechanism underlying the GABA-T-mediated conversion of GABA has not been fully understood. In this wor...

  16. Branched chain amino acid transaminase and branched chain alpha-ketoacid dehydrogenase activity in the brain, liver and skele­tal muscle of acute hepatic failure rats

    Takei,Nobuyuki

    1985-02-01

    Full Text Available Branched chain amino acid (BCAA transaminase activity increased in both the mitochondrial and supernatant fractions of brain from hepatic failure rats, in which a partial hepatectomy was performed 24h following carbon tetrachloride (CCl4 administration, although the activity of liver and skeletal muscle was the same as in control rats. The elevation of mitochondrial BCAA transaminase activity in liver-injured rats was partly due to increased activity of brain specific Type III isozyme. Branched chain alpha-ketoacid (BCKA dehydrogenase in the brain homogenates was not significantly altered in acute hepatic failure rats, while the liver enzyme activity was markedly diminished. BCKA dehydrogenase activity in the brain homogenates was inhibited by adding ATP to the assay system, and was activated in vitro by preincubating the brain homogenate at 37 degrees C for 15 min. These findings suggest that brain BCAA catabolism is accelerated in acute hepatic failure rats.

  17. Chemical protection against radiation effects on Serum transaminase and the levels of glutamic and pyruvic acids following gamma irradiation of rats

    The present study been carried out to evaluate the radioprotective efficiency of urea and vitamin E for protecting certain enzymatic systems from deleterious radiation effects. The activities of serum transaminase; aspartate aminotransferase (A S T) and alanine aminotransferase (A L T); as well as their relative substrates; glutamic and pyruvic acid levels; were selected for this study. The results indicated that whole body gamma irradiation at the dose of 7 Gy caused an evident elevation in the activities of both A S T and A L T and in the level of pyruvic acid at the experiment period (first,third,seventh and tenth days post irradiation). On the other hand the free glutamic acid level decreased at all post irradiation days. The variation in both enzymatic activities, pyruvic and glutamic acid levels became less pronounced in rats treated with either urea or vitamin E as chemical radioprotectors before whole body gamma irradiation. The results showed that the two agents are good radioprotectors, with respect to these parameters under investigation

  18. Mutations in γ-aminobutyric acid (GABA) transaminase genes in plants or Pseudomonas syringae reduce bacterial virulence

    D.H. Park; R. Mirabella; P.A. Bronstein; G.M. Preston; M.A. Haring; C.K. Lim; A. Collmer; R.C. Schuurink

    2010-01-01

    Pseudomonas syringae pv. tomato DC3000 is a bacterial pathogen of Arabidopsis and tomato that grows in the apoplast. The non-protein amino acid γ-amino butyric acid (GABA) is produced by Arabidopsis and tomato and is the most abundant amino acid in the apoplastic fluid of tomato. The DC3000 genome h

  19. Analysis of an avtA::Mu d1(Ap lac) mutant: metabolic role of transaminase C.

    Whalen, W A; Berg, C M

    1982-01-01

    Escherichia coli can synthesize alpha-ketoisovalerate, the precursor of valine, leucine, and pantothenate, by three routes: anabolically via dihydroxyacid dehydrase and catabolically via both the branched-chain amino acid transaminase (transaminase B) and the alanine-valine transaminase (transaminase C). An E. coli K-12 mutant devoid of transaminase C (avtA) was isolated by mutagenizing an isoleucine-requiring strain devoid of transaminase B (ilvE::Tn5) with Mu d1(Ap lac) and selecting for va...

  20. Substitution of glutamine for lysine at the pyridoxal phosphate binding site of bacterial D-amino acid transaminase. Effects of exogenous amines on the slow formation of intermediates.

    Futaki, S; Ueno, H; Martinez del Pozo, A; Pospischil, M A; Manning, J M; Ringe, D; Stoddard, B; Tanizawa, K; Yoshimura, T; Soda, K

    1990-12-25

    In bacterial D-amino acid transaminase, Lys-145, which binds the coenzyme pyridoxal 5'-phosphate in Schiff base linkage, was changed to Gln-145 by site-directed mutagenesis (K145Q). The mutant enzyme had 0.015% the activity of the wild-type enzyme and was capable of forming a Schiff base with D-alanine; this external aldimine was formed over a period of minutes depending upon the D-alanine concentration. The transformation of the pyridoxal-5'-phosphate form of the enzyme to the pyridoxamine-5'-phosphate form (i.e. the half-reaction of transamination) occurred over a period of hours with this mutant enzyme. Thus, information on these two steps in the reaction and on the factors that influence them can readily be obtained with this mutant enzyme. In contrast, these reactions with the wild-type enzyme occur at much faster rates and are not easily studied separately. The mutant enzyme shows distinct preference for D- over L-alanine as substrates but it does so about 50-fold less effectively than the wild-type enzyme. Thus, Lys-145 probably acts in concert with the coenzyme and other functional side chain(s) to lead to efficient and stereochemically precise transamination in the wild-type enzyme. The addition of exogenous amines, ethanolamine or methyl amine, increased the rate of external aldimine formation with D-alanine and the mutant enzyme but the subsequent transformation to the pyridoxamine-5'-phosphate form of the enzyme was unaffected by exogenous amines. The wild-type enzyme displayed a large negative trough in the circular dichroic spectrum at 420 nm, which was practically absent in the mutant enzyme. However, addition of D-alanine to the mutant enzyme generated this negative Cotton effect (due to formation of the external aldimine with D-alanine). This circular dichroism band gradually collapsed in parallel with the transformation to the pyridoxamine-5'-phosphate enzyme. Further studies on this mutant enzyme, which displays the characteristics of the wild

  1. beta-Chloro-L-alanine inhibition of the Escherichia coli alanine-valine transaminase.

    Whalen, W A; Wang, M D; Berg, C M

    1985-01-01

    beta-Chloro-L-alanine, an amino acid analog which inhibits a number of enzymes, reversibly inhibited the Escherichia coli K-12 alanine-valine transaminase, transaminase C. This inhibition, along with the inhibition of transaminase B, accounted for the isoleucine-plus-valine requirement of E. coli in the presence of beta-chloro-L-alanine.

  2. Simultaneous synthesis of 2-phenylethanol and L-homophenylalanine using aromatic transaminase with yeast Ehrlich pathway.

    Hwang, Joon-Young; Park, Jihyang; Seo, Joo-Hyun; Cha, Minho; Cho, Byung-Kwan; Kim, Juhan; Kim, Byung-Gee

    2009-04-01

    2-Phenylethanol is a widely used aroma compound with rose-like fragrance and L-homophenylalanine is a building block of angiotensin-converting enzyme (ACE) inhibitor. 2-phenylethanol and L-homophenylalanine were synthesized simultaneously with high yield from 2-oxo-4-phenylbutyric acid and L-phenylalanine, respectively. A recombinant Escherichia coli harboring a coupled reaction pathway comprising of aromatic transaminase, phenylpyruvate decarboxylase, carbonyl reductase, and glucose dehydrogenase (GDH) was constructed. In the coupled reaction pathway, the transaminase reaction was coupled with the Ehrlich pathway of yeast; (1) a phenylpyruvate decarboxylase (YDR380W) as the enzyme to generate the substrate for the carbonyl reductase from phenylpyruvate (i.e., byproduct of the transaminase reaction) and to shift the reaction equilibrium of the transaminase reaction, and (2) a carbonyl reductase (YGL157W) to produce the 2-phenylethanol. Selecting the right carbonyl reductase showing the highest activity on phenylacetaldehyde with narrow substrate specificity was the key to success of the constructing the coupling reaction. In addition, NADPH regeneration was achieved by incorporating the GDH from Bacillus subtilis in the coupled reaction pathway. Based on 40 mM of L-phenylalanine used, about 96% final product conversion yield of 2-phenylethanol was achieved using the recombinant E. coli. PMID:19016485

  3. Hexamine as Corrosion Inhibitors forZinc in Phosphoric Acid

    R. T. Vashi; Diksha Naik

    2010-01-01

    The corrosion of zinc in phosphoric acid containing hexamine has been studied at different acid concentrations, inhibitor concentration and temperatures. Corrosion increases with the concentration of acid and the temperature. The inhibition efficiency (IE) of hexamine increases with the concentration of inhibitor. The IE decreases with the increase in concentration of acid. As temperature increases, percentage of inhibition decreases. The plot of log (Θ/1-Θ) versus log C results in a straight...

  4. Selective cell adhesion inhibitors: Barbituric acid based alpha4beta7--MAdCAM inhibitors.

    Harriman, Geraldine C; Brewer, Matthias; Bennett, Robert; Kuhn, Cyrille; Bazin, Marc; Larosa, Greg; Skerker, Paul; Cochran, Nancy; Gallant, Debra; Baxter, Deborah; Picarella, Dominic; Jaffee, Bruce; Luly, Jay R; Briskin, Michael J

    2008-04-01

    A novel series of barbituric acid derivatives were identified as selective inhibitors of alpha4beta7 MAdCAM (mucosal addressin cell adhesion molecule-1) interactions via a high throughput screening exercise. These inhibitors were optimized to submicromolar potencies in whole cell adhesion assays, retaining their selectivity over alpha4beta1 VCAM. PMID:18331794

  5. Disorders of GABA metabolism: SSADH and GABA-transaminase deficiencies

    Parviz, Mahsa; Vogel, Kara; Gibson, K Michael; Pearl, Phillip L.

    2014-01-01

    Clinical disorders known to affect inherited gamma-amino butyric acid (GABA) metabolism are autosomal recessively inherited succinic semialdehyde dehydrogenase and GABA-transaminase deficiency. The clinical presentation of succinic semialdehyde dehydrogenase deficiency includes intellectual disability, ataxia, obsessive-compulsive disorder and epilepsy with a nonprogressive course in typical cases, although a progressive form in early childhood as well as deterioration in adulthood with worse...

  6. Anacardic acid derived salicylates are inhibitors or activators of lipoxygenases

    Wisastra, Rosalina; Ghizzoni, Massimo; Boltjes, Andre; Haisma, Hidde J.; Dekker, Frank J.

    2012-01-01

    Lipoxygenases catalyze the oxidation of unsaturated fatty acids, such as linoleic acid, which play a crucial role in inflammatory responses. Selective inhibitors may provide a new therapeutic approach for inflammatory diseases. In this study, we describe the identification of a novel soybean lipoxyg

  7. Identification of Novel Functional Inhibitors of Acid Sphingomyelinase

    Kornhuber, Johannes; Muehlbacher, Markus; Trapp, Stefan;

    2011-01-01

    We describe a hitherto unknown feature for 27 small drug-like molecules, namely functional inhibition of acid sphingomyelinase (ASM). These entities named FIASMAs (Functional Inhibitors of Acid SphingoMyelinAse), therefore, can be potentially used to treat diseases associated with enhanced activity...

  8. Amino acids as corrosion inhibitors for copper in acidic medium: Experimental and theoretical study

    Milošev Ingrid; Pavlinac Jasminka; Hodošček Milan; Lesar Antonija

    2013-01-01

    Experimental electrochemical methods combined with quantum chemical calculations and molecular dynamics simulations were used to investigate the possibility of use various amino acids as “green” corrosion inhibitors for copper in 0.5 M HCl solution. Among eleven amino acids studied, cysteine achieved the highest inhibitor effectiveness reaching 52% at 10 mM concentration. Other amino acids reached achieved effectiveness less than 25%, some of them even acte...

  9. Corrosion Inhibition of a Green Scale Inhibitor Polyepoxysuccinic Acid

    Rong Chun XIONG; Qing ZHOU; Gang WEI

    2003-01-01

    The corrosion inhibition of a green scale inhibitor, polyepoxysuccinic acid (PESA) wasstudied based on dynamic tests. It is found that when PESA is used alone, it had good corrosioninhibition. So, PESA should be included in the category of corrosion inhibitors. It is not only akind of green scale inhibitor, but also a green corrosion inhibitor. The synergistic effect betweenPESA and Zn2+ or sodium gluconate is poor. However, the synergistic effect among PESA, Zn2+and sodium gluconate is excellent, and the corrosion inhibition efficiency for carbon steel is higherthan 99%. Further study of corrosion inhibition mechanism reveals that corrosion inhibition ofPESA is not affected by carboxyl group, but by the oxygen atom inserted The existence ofoxygen atom in PESA molecular structure makes it easy to form stable chelate with pentacyclicstructure.

  10. SERUM PROTEINS, TRANSAMINASES AND PHOSPHATASES IN MALNUTRITION

    H. Mohammadiha

    1976-07-01

    Full Text Available The levels of serum tota1 protein, albumin, transaminases and phosphatases were estimated in a group of children with severe Marasmus or mild malnutrition in order to identify some of the associated deficiencies in these syndromes. The biochemical pattern was similar in the normal and malnourished children.

  11. Regulation of transaminase C synthesis in Escherichia coli: conditional leucine auxotrophy.

    McGilvray, D; Umbarger, H E

    1974-11-01

    The regulation of synthesis of the valine-alanine-alpha-aminobutyrate transaminase (transaminase C) was studied in Escherichia coli mutants lacking the branched-chain amino acid transaminase (transaminase B). An investigation was made of two strains, CU2 and CU2002, each carrying the same transaminase B lesion but exhibiting different growth responses on a medium supplemented with branched-chain amino acids. Both had the absolute isoleucine requirement characteristic of ilvE auxotrophs, but growth of strain CU2 was stimulated by valine, whereas that of strain CU2002 was markedly inhibited by valine. Strain CU2002 behaved like a conditional leucine auxotroph in that the inhibition by valine was reversed by leucine. Results of enzymatic studies showed that synthesis of transaminase C was repressed by valine in strain CU2002 but not in strain CU2. Inhibition by valine in strain CU2002 appears to be the combined effect of repression on transaminase C synthesis and valine-dependent feedback inhibition of alpha-acetohydroxy acid synthase activity, causing alpha-ketoisovalerate (and hence leucine) limitation. The ilvE markers of strains CU2 and CU2002 were each transferred by transduction to a wild-type genetical background. All ilvE recombinants from both crosses resembled strain CU2002 and were inhibited by valine in the presence of isoleucine. Thus, strain CU2 carries an additional lesion that allows it to grow on a medium containing isoleucine plus valine. It is concluded that conditional leucine auxotrophy is characteristic of mutants carrying an ilvE lesion alone. PMID:4616947

  12. Hybridization of glutamate aspartate transaminase. Investigation of subunit interaction.

    Boettcher, B; Martinez-Carrion, M

    1975-10-01

    Glutamate aspartate transaminase (EC 2.6.1.1) is a dimeric enzyme with identical subunits with each active site containing pyridoxal 5'-phosphate linked via an internal Shiff's base to a lysine residue. It is not known if these sites interact during catalysis but negative cooperativity has been reported for binding of the coenzyme (Arrio-Dupont, M. (1972), Eur. J. Biochem. 30, 307). Also nonequivalence of its subunits in binding 8-anilinonaphthalene-1-sulfonate (Harris, H.E., and Bayley, P. M. (1975), Biochem. J. 145, 125), in modification of only a single tyrosine with full loss of activity (Christen, P., and Riordan, J.F. (1970), Biochemistry 9, 3025), and following modification with 5,5'-dithiobis(2-nitrobenzoic acid) (Cournil, I., and Arrio-Dupont, M. (1973), Biochemie 55, 103) has been reported. However, steady-state and transient kinetic methods as well as direct titration of the active site chromophore with substrates and substrate analogs have not revealed any cooperative phenomena (Braunstein, A. E. (1973), Enzymes, 3rd Ed. 9, 379). It was therefore decided that a more direct approach should be used to clarify the quistion of subunit interaction during the covalent phase of catalysis. To this end a hybrid method was devised in which a hybrid transaminase was prepared which contained one subunit with a functional active site while the other subunit has the internal Shiff's base reduced with NaBH4. The specific activities and amount of "actively bound" pyridoxal 5'-phosphate are both in a 2:1 ratio for the native and hybrid forms. Comparison of the steady-state kinetic properties of the hybrid and native enzyme forms shows that both forms gave parallel double reciprocal plots which is characteristic of the Ping-Pong Bi-Bi mechanism of transamination. The Km values for the substrates L-aspartic acid and alpha-ketoglutaric acid are nearly identical while the Vmax value for the hybrid is one-half the value of the native transaminase. It therefore appears that

  13. STUDY OF SERUM TRANSAMINASES IN HYPOTHYROIDISM

    Manjula

    2013-01-01

    Full Text Available ABSTRACT: BACKGROUND: Thyroid hormones regulate Basal Metabolic Rate (BM R and calorigenesis in tissues, including hepatocytes and thereby modulate hepatic function. The liver in turn metabolizes the thyroid hormones and regula tes their systemic endocrine effect. Raised serum transaminase activities in absence of any ove rt liver dysfunction can therefore be attributed to primary thyroid dysfunction. The aim o f this study is to assess the impairment in liver function by estimating serum Aspartate Transam inase (AST and Alanine Transaminase (ALT in patients with hypothyroidism. MATERIALS AND METHODS: 50 patients diagnosed with thyroid disorders irrespective of duration of t he disease and treatment were taken as cases and 50 healthy adults were taken as control. Estim ation of T3, T4, TSH, serum AST and serum ALT were carried out. RESULTS: Serum AST and serum ALT were within reference rang e in both cases and controls. CONCLUSION: The likelihood of abnormal serum transaminases lev els in hypothyroid patients is minimal. Early detection and better management of the thyroid diseases in recent times might be attributed as one of the factors for the same

  14. Tanzawaic Acids, a Chemically Novel Set of Bacterial Conjugation Inhibitors

    Getino, María; Fernández-López, Raúl; Palencia-Gándara, Carolina; Campos-Gómez, Javier; Sánchez-López, Jose M.; Martínez, Marta; Fernández, Antonio; de la Cruz, Fernando

    2016-01-01

    Bacterial conjugation is the main mechanism for the dissemination of multiple antibiotic resistance in human pathogens. This dissemination could be controlled by molecules that interfere with the conjugation process. A search for conjugation inhibitors among a collection of 1,632 natural compounds, identified tanzawaic acids A and B as best hits. They specially inhibited IncW and IncFII conjugative systems, including plasmids mobilized by them. Plasmids belonging to IncFI, IncI, IncL/M, IncX and IncH incompatibility groups were targeted to a lesser extent, whereas IncN and IncP plasmids were unaffected. Tanzawaic acids showed reduced toxicity in bacterial, fungal or human cells, when compared to synthetic conjugation inhibitors, opening the possibility of their deployment in complex environments, including natural settings relevant for antibiotic resistance dissemination. PMID:26812051

  15. Factors associated with mortality in human immunodeficiency virus type 1-infected adults initiating protease inhibitor-containing therapy: role of education level and of early transaminase level elevation (APROCO-ANRS EP11 study). The Antiprotéases Cohorte Agence Nationale de Recherches sur le SIDA EP 11 study.

    Lewden, Charlotte; Raffi, François; Cuzin, Lise; Cailleton, Valérie; Vildé, Jean-Louis; Chêne, Geneviève; Allavena, Clotilde; Salamon, Roger; Leport, Catherine

    2002-09-01

    This study attempted to identify factors associated with mortality among human immunodeficiency virus (HIV)-infected adults starting a protease inhibitor (PI)-containing therapy. Among 1155 patients consecutively enrolled in the APROCO study between May 1997 and June 1998, clinical characteristics were as follows: median age, 36 years; median baseline CD4 cell count, 288 cells/mm(3); and median baseline plasma HIV RNA load, 4.4 log(10) copies/mL. After a median follow-up of 27 months, 48 deaths had occurred, of which 44% were related to acquired immune deficiency syndrome. The mortality rate was 2.9% at 12 months. When both data at baseline and data at 4 months after the start of PI therapy were considered, factors independently associated with mortality were (Cox model) low baseline plasma creatinine level, low school education level, low CD4 cell count at 4 months, low hemoglobin level, and elevated hepatic transaminase levels. Thus, social context plus clinical and biologic data, including the 4-month response to treatment, must be considered in treatment of HIV-infected patients. PMID:12195361

  16. Fatty acid synthase inhibitors isolated from Punica granatum L

    Jiang, He-Zhong [School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, (China); Ma, Qing-Yun; Liang, Wen-Juan; Huang, Sheng-Zhuo; Dai, Hao-Fu; Wang, Peng-Cheng; Zhao, You-Xing, E-mail: zhaoyx1011@163.com [Institute of Tropical Bioscience and Biotechnology, Chinese Academy of Tropical Agricultural Sciences, Haikou (China); Fan, Hui-Jin; Ma, Xiao-Feng, E-mail: maxiaofeng@gucas.ac.cn [College of Life Sciences, Graduate University of Chinese Academy of Sciences, Beijing (China)

    2012-05-15

    The aim of this work is the isolation of fatty acid synthase (FAS) inhibitors from the ethyl acetate extracts of fruit peels of Punica granatum L. Bioassay-guided chemical investigation of the fruit peels resulted in the isolation of seventeen compounds mainly including triterpenoids and phenolic compounds, from which one new oleanane-type triterpene (punicaone) along with fourteen known compounds were isolated for the first time from this plant. Seven isolates were evaluated for inhibitory activities of FAS and two compounds showed to be active. Particularly, flavogallonic acid exhibited strong FAS inhibitory activity with IC{sub 50} value of 10.3 {mu}mol L{sup -1}. (author)

  17. Fatty acid synthase inhibitors isolated from Punica granatum L

    The aim of this work is the isolation of fatty acid synthase (FAS) inhibitors from the ethyl acetate extracts of fruit peels of Punica granatum L. Bioassay-guided chemical investigation of the fruit peels resulted in the isolation of seventeen compounds mainly including triterpenoids and phenolic compounds, from which one new oleanane-type triterpene (punicaone) along with fourteen known compounds were isolated for the first time from this plant. Seven isolates were evaluated for inhibitory activities of FAS and two compounds showed to be active. Particularly, flavogallonic acid exhibited strong FAS inhibitory activity with IC50 value of 10.3 μmol L-1. (author)

  18. Purification, characterization, and molecular cloning of a novel amine:pyruvate transaminase from Vibrio fluvialis JS17.

    Shin, J-S; Yun, H; Jang, J-W; Park, I; Kim, B-G

    2003-06-01

    A transaminase from Vibrio fluvialis JS17 showing activity toward chiral amines was purified to homogeneity and its enzymatic properties were characterized. The transaminase showed an apparent molecular mass of 100 kDa as determined by gel filtration chromatography and a subunit mass of 50 kDa by MALDI-TOF mass spectrometry, suggesting a dimeric structure. The enzyme had an isoelectric point of 5.4 and its absorption spectrum exhibited maxima at 320 and 405 nm. The optimal pH and temperature for enzyme activity were 9.2 and 37 degrees C, respectively. Pyruvate and pyridoxal 5'-phosphate increased enzyme stability whereas (S)-alpha-methylbenzylamine reversibly inactivated the enzyme. The transaminase gene was cloned from a V. fluvialis JS17 genomic library. The deduced amino acid sequence (453 residues) showed significant homology with omega-amino acid:pyruvate transaminases (omega-APT) from various bacterial strains (80 identical residues with four omega-APTs). However, of 159 conserved residues in the four omega-APTs, 79 were not conserved in the transaminase from V. fluvialis JS17. Taken together with the sequence homology results, and the lack of activity toward beta-alanine (a typical amino donor for the omega-APT), the results suggest that the transaminase is a novel amine:pyruvate transaminase that has not been reported to date. PMID:12687298

  19. Role of alanine-valine transaminase in Salmonella typhimurium and analysis of an avtA::Tn5 mutant.

    Berg, C M; Whalen, W A; Archambault, L B

    1983-01-01

    In Salmonella typhimurium, as in Escherichia coli, mutations in avtA, the gene encoding the alanine-valine transaminase (transaminase C), are silent unless they are combined with mutations involved in isoleucine-valine biosynthesis. avtA is repressed by leucine or alanine but not by valine. Transaminase C is found at reduced levels upon starvation for any one of several amino acids. We hypothesize that this is due to repression of avtA by the elevated alanine and leucine pools found in amino ...

  20. cis-Cinnamic acid selective suppressors distinct from auxin inhibitors.

    Okuda, Katsuhiro; Nishikawa, Keisuke; Fukuda, Hiroshi; Fujii, Yoshiharu; Shindo, Mitsuru

    2014-01-01

    The activity of cis-cinnamic acid (cis-CA), one of the allelochemicals, in plants is very similar to that of indole-3-acetic acid (IAA), a natural auxin, and thus cis-CA has long been believed to be an analog of auxin. We have reported some structure-activity relationships studies by synthesizing over 250 cis-CA derivatives and estimating their inhibitory activities on root growth inhibition in lettuce. In this study, the compounds that showed low- or no-activity on root growth inhibition were recruited as candidates suppressors against cis-CA and/or auxin and tested for their activity. In the presence of cis-CA, lettuce root growth was inhibited; however, the addition of some cis-CA derivatives restored control-level root growth. Four compounds, (Z)-3-(4-isopropylphenyl)acrylic acid, (Z)-3-(3-butoxyphenyl)acrylic acid, (Z)-3-[3-(pentyloxy)phenyl]acrylic acid, and (Z)-3-(naphthalen-1-yl)acrylic acid were selected as candidates for a cis-CA selective suppressor they allowed the recovery of root growth from inhibition by cis-CA treatment without any effects on the IAA-induced effect or elongating activity by themselves. Three candidates significantly ameliorated the root shortening by the potent inhibitor derived from cis-CA. In brief, we have found some cis-CA selective suppressors which have never been reported from inactive cis-CA derivatives for root growth inhibition. cis-CA selective suppressors will play an important role in elucidating the mechanism of plant growth regulation. PMID:24881667

  1. Sulfonyl fluoride inhibitors of fatty acid amide hydrolase.

    Alapafuja, Shakiru O; Nikas, Spyros P; Bharathan, Indu T; Shukla, Vidyanand G; Nasr, Mahmoud L; Bowman, Anna L; Zvonok, Nikolai; Li, Jing; Shi, Xiaomeng; Engen, John R; Makriyannis, Alexandros

    2012-11-26

    Sulfonyl fluorides are known to inhibit esterases. Early work from our laboratory has identified hexadecyl sulfonylfluoride (AM374) as a potent in vitro and in vivo inhibitor of fatty acid amide hydrolase (FAAH). We now report on later generation sulfonyl fluoride analogs that exhibit potent and selective inhibition of FAAH. Using recombinant rat and human FAAH, we show that 5-(4-hydroxyphenyl)pentanesulfonyl fluoride (AM3506) has similar inhibitory activity for both the rat and the human enzyme, while rapid dilution assays and mass spectrometry analysis suggest that the compound is a covalent modifier for FAAH and inhibits its action in an irreversible manner. Our SAR results are highlighted by molecular docking of key analogs. PMID:23083016

  2. Serum Glutamic-Oxaloacetic Transaminase (GOT) and Glutamic-Pyruvic Transaminase (GPT) Levels in Children and Adolescents with Intellectual Disabilities

    Lin, Jin-Ding; Lin, Pei-Ying; Chen, Li-Mei; Fang, Wen-Hui; Lin, Lan-Ping; Loh, Ching-Hui

    2010-01-01

    The elevated serum glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) rate among people with intellectual disabilities (ID) is unknown and have not been sufficiently studies. The present paper aims to provide the profile of GOT and GPT, and their associated relationship with other biochemical levels of children or…

  3. Effect of deoxyribonucleic acid replication inhibitors on bacterial recombination

    Two inhibitors of replicative deoxyribonucleic acid (DNA) synthesis, nalidixic acid (NAL) and 6-(p-hydroxyphenylazo)-uracil (HPUra), showed different effects on genetic recombination and DNA repair in Bacillus subtilis. Previous work (Pedrini et al., 1972) showed that NAL does not interfere with the transformation process of B. subtilis. The results reported in this work demonstrated that the drug was also without effect on the transfection SPP1 or SPO-1 phage DNA (a process that requires a recombination event). The drug was also ineffective on the host cell reactivation of ultraviolet-irradiated SPP1 phage, as well as on transfection with ultraviolet-irradiated DNA of the same phage. HPUra instead markedly reduced the transformation process, as well as transfection, by SPO-1 DNA, but it did not affect the host cell reactivation of SPO-1 phage. In conclusion, whereas the NAL target seems to be specific for replicative DNA synthesis, the HPUra target (i.e., the DNA polymerase III of B. subtilis) seems to be involved also in recombination, but not in the excision repair process. The mutations conferring NAL and HPUra resistance used in this work were mapped by PBS-1 transduction

  4. Corrosion Inhibition of Aluminum in Acidic Solution by Aqueous Extract of Ajowan Plant as Green Inhibitor

    Aisha M. Al-Turkustani; Mona M. Al-Solmi

    2011-01-01

    The inhibition of aluminum corrosion in 0.5 M hydrochloric acid by Ajowan plant was studied using chemical (weight loss) and ectrochemical (impedance and polarization) methods. The Ajowan plant extract was found to be good inhibitor for aluminum corrosion in 0.5 M hydrochloric acid in the studied concentration range of inhibitor. Corrosion inhibition could be explained by considering an interaction between metal surface and the inhibitor molecules. Electrochemical measurements showed that Ajo...

  5. Antineoplastic effects of the DNA methylation inhibitor hydralazine and the histone deacetylase inhibitor valproic acid in cancer cell lines

    Chavez-Blanco, Alma; Perez-Plasencia, Carlos; Perez-Cardenas, Enrique; Carrasco-Legleu, Claudia; Rangel-Lopez, Edgar; Segura-Pacheco, Blanca; Taja-Chayeb, Lucia; Trejo-Becerril, Catalina; Gonzalez-Fierro, Aurora; Candelaria, Myrna; Cabrera, Gustavo; Duenas-Gonzalez, Alfonso

    2006-01-01

    Background Among the epigenetic alterations occurring in cancer, DNA hypermethylation and histone hypoacetylation are the focus of intense research because their pharmacological inhibition has shown to produce antineoplastic activity in a variety of experimental models. The objective of this study was to evaluate the combined antineoplastic effect of the DNA methylation inhibitor hydralazine and the histone deacetylase inhibitor valproic acid in a panel of cancer cell lines. Results Hydralazi...

  6. Antineoplastic effects of the DNA methylation inhibitor hydralazine and the histone deacetylase inhibitor valproic acid in cancer cell lines

    Candelaria Myrna; Gonzalez-Fierro Aurora; Trejo-Becerril Catalina; Taja-Chayeb Lucia; Segura-Pacheco Blanca; Rangel-Lopez Edgar; Carrasco-Legleu Claudia; Perez-Cardenas Enrique; Perez-Plasencia Carlos; Chavez-Blanco Alma; Cabrera Gustavo; Duenas-Gonzalez Alfonso

    2006-01-01

    Abstract Background Among the epigenetic alterations occurring in cancer, DNA hypermethylation and histone hypoacetylation are the focus of intense research because their pharmacological inhibition has shown to produce antineoplastic activity in a variety of experimental models. The objective of this study was to evaluate the combined antineoplastic effect of the DNA methylation inhibitor hydralazine and the histone deacetylase inhibitor valproic acid in a panel of cancer cell lines. Results ...

  7. A β-Alanine Catabolism Pathway Containing a Highly Promiscuous ω-Transaminase in the 12-Aminododecanate-Degrading Pseudomonas sp. Strain AAC

    Wilding, Matthew; Thomas S Peat; Newman, Janet; Scott, Colin

    2016-01-01

    ABSTRACT We previously isolated the transaminase KES23458 from Pseudomonas sp. strain AAC as a promising biocatalyst for the production of 12-aminododecanoic acid, a constituent building block of nylon-12. Here, we report the subsequent characterization of this transaminase. It exhibits activity with a broad substrate range which includes α-, β-, and ω-amino acids, as well as α,ω-diamines and a number of other industrially relevant compounds. It is therefore a prospective candidate for the bi...

  8. Amino acids as corrosion inhibitors for copper in acidic medium: Experimental and theoretical study

    Milošev Ingrid

    2013-01-01

    Full Text Available Experimental electrochemical methods combined with quantum chemical calculations and molecular dynamics simulations were used to investigate the possibility of use various amino acids as “green” corrosion inhibitors for copper in 0.5 M HCl solution. Among eleven amino acids studied, cysteine achieved the highest inhibitor effectiveness reaching 52% at 10 mM concentration. Other amino acids reached achieved effectiveness less than 25%, some of them even acted as corrosion accelerators. Based on the experimental results, theoretical calculations and simulations were focused on cysteine and alanine. The electronic and reactivity parameters of their protonated forms in electrical double layer were evaluated by density functional calculations. In addition, molecular dynamic simulations were introduced to follow the adsorption behaviour of these two amino acids at the Cu(111 surface in the electrolyte solution. The results indicate that the orientation of both molecules is nearly parallel to the surface except of ammonium group which is directed away from the surface. Therefore, as the orientation of the cysteine and alanine molecules at the surface is similar, thiol functional group is responsible for superior inhibition efficiency of cysteine.

  9. TRANSAMINASES ACTIVITY IN THE SAND LIZARD’S SERUM UNDER INFLUENCE OF INDUSTRIAL POLLUTION

    O. Y. Klymenko; V. Y. Gasso

    2009-01-01

    Influence of the environmental pollution on the alanine aminotransferase and aspartate aminotransferase activity in the blood serum of the sand lizard has been studied. Aminotransferases (ALT and AST) are similar by the mechanism of action. These enzymes take part in the amino acids metabolism. The increase of the transaminases activities under conditions of the pollution is found. It may be a proof of a damage of relevant organs: namely, the liver.

  10. Applying Enzymatic Cascades for ISCPR in ω-transaminase Systems

    Janes, Kresimir; Woodley, John; Tufvesson, Pär; Gernaey, Krist

    , esterases, ketoreductases and proteases and many more emerging biocatalysts such are monoamine oxidases, transaminases and P450 monooxygenases to name a few. The focus of this thesis is the biocatalytic synthesis of small molecule pharmaceuticals (Mw<1000), and in particular the production of optically pure...... amines via ω-transaminases, which is an interesting class of reactions for the pharmaceutical industry. There are many challenges related to the realization and implementation of these technologies, and attempts of tackling them have been numerous. In some cases ω-transaminase catalyzed reactions are...... enzymatic cascades often provides the only viable option as equilibrium shifting strategy. In the literature several enzymatic cascades have been reported as an ISCPR for the ω-transaminase systems, however in most cases no process considerations have been made and the consequences of using a givens cascade...

  11. Characterization of a novel amine transaminase from Halomonas elongata

    Cerioli, Lorenzo; Planchestainer, Matteo; Cassidy, Jennifer; Tessaro, Davide; Paradisi, Francesca

    2015-01-01

    Chiral amines are indispensable building blocks in the production of biologically active compounds. They are fundamental for the pharmaceutical industry, both as active molecules themselves and as chiral auxiliaries in asymmetric synthesis; however, the available synthetic strategies often present disadvantages. ω-Transaminases (ω-TAs) appear as an attractive alternative by driving the stereoselective amination of prochiral ketones. HEWT is a novel amine transaminase from the moderate halophi...

  12. A rational approach for ω-transaminase-catalyzed process design

    T. Gundersen, Maria; Lloyd, Richard; Tufvesson, Pär; Woodley, John

    Herein we describe a novel rational approach to the design of a ω-transaminase process such that it will fulfill criteria necessary for industrial use. By first determining the fundamental properties of the reaction system, it is possible to suggest appropriate process strategies that may be used...... to overcome any unfavorable parameters. The ω-transaminase is used as a model system because it is an important enzyme class and developing a systematic methodology would have significant value....

  13. Proteasome inhibitors: Their effects on arachidonic acid release from cells in culture and arachidonic acid metabolism in rat liver cells

    Levine Lawrence

    2004-01-01

    Abstract Background I have postulated that arachidonic acid release from rat liver cells is associated with cancer chemoprevention. Since it has been reported that inhibition of proteasome activities may prevent cancer, the effects of proteasome inhibitors on arachidonic acid release from cells and on prostaglandin I2 production in rat liver cells were studied. Results The proteasome inhibitors, epoxomicin, lactacystin and carbobenzoxy-leucyl-leucyl-leucinal, stimulate the release of arachido...

  14. GREWIA TILIAEFOLIA BARK EXTRACT AS GREEN INHIBITOR OF MILD STEEL C ORROSION IN SULPHURIC ACID MEDIUM

    V.N. Sheeja; S. Subhashini

    2015-01-01

    This paper presents the inhibitory properties of Grewia tiliaefolia bark extract on the corrosion of mild steel in sulphuric acid medium. The corrosion rates and inhibition efficiencies were evaluated by weight loss measurements. The adsorption of inhibitor obeyed Langmuir isotherm and the negative values of Gibbs energy indicate the nature of interactions between inhibitor molecules and metal surface. Further...

  15. Use of Hydrazone Derivates as Inhibitors for the Corrosion of Nickel in Hydrochloric Acid Solution

    A.S. Fouda, H. A. Mostafa, S. E. Ghazy and S. A. El- Farah

    2007-01-01

    The influence of hydrazone derivatives on the corrosion of nickel in 2 mol L-1 hydrochloric acid solution has been studied using weight loss and galvanostatic polarization techniques. In general, at constant acid concentration, the inhibition efficiency increases with increasing the inhibitor concentration and decreases with increasing temperature. Polarization studies indicate that the compounds act as mixed- type inhibitors. The addition of iodide ions enhances the inhibition efficiency to ...

  16. [Effect of proteolysis inhibitors on the incorporation of labelled amino acids into proteins].

    Konikova, A S; Korotkina, R N

    1975-01-01

    Role of peptide bond breaks in the incorporation of amino acids into proteins in a "protein--amino acid" system is investigated. For this purpose the incorporation of labelled amino acids into trypsin under the inhibition of its autolysis by a specific inhibitor from soybean and epsilon-amino-caproic acid is studied. The trypsin inhibitor from soybean is found to suppress considerably the incorporation of 14C-glycine, 14C-lysine and 14C-methionine into crystal trypsin and not to affect the incorporation of labelled amino acids into chomotrypsin, papain and carboxypeptidase. Epsilon-Aminocaproic acid inhibited 14C-glycine incorporation into crystal trypsin by 40% and did not change its incorporation level into serum albumin. The dependency of amino acid incorporation level into trypsin on the activity of autolysis in the "protein--amino acid" system is demonstrated. PMID:1212456

  17. Benzoxazolone carboxamides as potent acid ceramidase inhibitors: Synthesis and structure-activity relationship (SAR) studies

    Bach, Anders

    2015-01-01

    Ceramides are lipid-derived intracellular messengers involved in the control of senescence, inflammation, and apoptosis. The cysteine amidase, acid ceramidase (AC), hydrolyzes these substances into sphingosine and fatty acid and, by doing so, regulates their signaling activity. AC inhibitors may...... be useful in the treatment of pathological conditions, such as cancer, in which ceramide levels are abnormally reduced. Here, we present a systematic SAR investigation of the benzoxazolone carboxamides, a recently described class of AC inhibitors that display high potency and systemic activity in mice. We...... administration. The results expand our arsenal of AC inhibitors, thereby facilitating the use of these compounds as pharmacological tools and their potential development as drug leads....

  18. 2-Aminoimidazole Amino Acids as Inhibitors of the Binuclear Manganese Metalloenzyme Human Arginase I

    Ilies, M.; Di Costanzo, L; North, M; Scott, J; Christianson, D

    2010-01-01

    Arginase, a key metalloenzyme of the urea cycle that converts L-arginine into L-ornithine and urea, is presently considered a pharmaceutical target for the management of diseases associated with aberrant L-arginine homeostasis, such as asthma, cardiovascular diseases, and erectile dysfunction. We now report the design, synthesis, and evaluation of a series of 2-aminoimidazole amino acid inhibitors in which the 2-aminoimidazole moiety serves as a guanidine mimetic. These compounds represent a new class of arginase inhibitors. The most potent inhibitor identified in this study, 2-(S)-amino-5-(2-aminoimidazol-1-yl)pentanoic acid (A1P, 10), binds to human arginase I with K{sub d} = 2 {micro}M and significantly attenuates airways hyperresponsiveness in a murine model of allergic airways inflammation. These findings suggest that 2-aminoimidazole amino acids represent new leads for the development of arginase inhibitors with promising pharmacological profiles.

  19. Serum transaminase levels and dengue shock syndrome in children

    Yoga Putra

    2014-05-01

    Full Text Available Background Clinical and biochemical impacts on liver dysfunction, as manifested by an increase in serum transaminase levels, are common in dengue infection. However, an association of elevated serum transaminase and dengue shock syndrome (DSS has not been well-established. Objective To assess for an association between serum transaminase levels and the presence of DSS in children. Methods A nested, case control study was conducted on children aged 1 month to 12 years admitted to Sanglah Hospital who were diagnosed with dengue infection. Baseline characteristics and serum transaminase levels were recorded. Patients who were included in the study were observed for the presence of DSS. Those who had DSS were selected as cases, and those who did not develop DSS were selected as controls. Data was analyzed using bivariate and multivariate methods with 95% confidence intervals and P value <0.05 was considered as statistically significant. Results Ninety-four children were involeved, 47 children in the case group and the other 47 were in the control group. Baseline characteristics of the subjects were similar between the case and control groups. Serum aspartate transaminase (AST level of ≥128 U/L and alanine transaminase (ALT of ≥40 U/L were associated with DSS (OR 10; 95%CI 2.3 to 44.4; P=0.002 and (OR 7.3; 95%CI 1.6 to 32.9; P=0.009, respectively. Conclusion Elevated AST and ALT levels were associated with an increased risk of DSS in children with dengue infection

  20. Inhibitors of Fatty Acid Amide Hydrolase and Monoacylglycerol Lipase: New Targets for Future Antidepressants.

    Ogawa, Shintaro; Kunugi, Hiroshi

    2015-01-01

    Cannabis and analogs of Δ9-tetrahydrocannabinol have been used for therapeutic purposes, but their therapeutic use remains limited because of various adverse effects. Endogenous cannabinoids have been discovered, and dysregulation of endocannabinoid signaling is implicated in the pathophysiology of major depressive disorder (MDD). Recently, endocannabinoid hydrolytic enzymes such as fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) have become new therapeutic targets in the treatment of MDD. Several FAAH or MAGL inhibitors are reported to have no cannabimimetic side effects and, therefore, are new potential therapeutic options for patients with MDD who are resistant to first-line antidepressants (selective serotonin and serotonin-norepinephrine reuptake inhibitors). In this review, we focus on the possible relationships between MDD and the endocannabinoid system as well as the inhibitors' therapeutic potential. MAGL inhibitors may reduce inflammatory responses through activation of cannabinoid receptor type 2. In the hypothalamic-pituitary-adrenal axis, repeated FAAH inhibitor administration may be beneficial for reducing circulating glucocorticoid levels. Both FAAH and MAGL inhibitors may contribute to dopaminergic system regulation. Recently, several new inhibitors have been developed with strong potency and selectivity. FAAH inhibitor, MAGL inhibitor, or dual blocker use would be promising new treatments for MDD. Further pre-clinical studies and clinical trials using these inhibitors are warranted. PMID:26630956

  1. Process considerations for protein engineering of ω-Transaminase

    Lima Afonso Neto, Watson; Schwarze, Daniel; Tufvesson, Pär; Vogel, Andreas; Woodley, John

    enantio specificity (e.e). However, it is critical that this is done in parallel process development to make sure that the properties developed also fit the process requirements. As an example, ω -transaminases (EC 2.6.1.18) can be used to produce optyically pure chiral amines (with 100% theoretical yield...... how changes to a wild type transaminase through protein engineering changed the characteristics of the biocatalyst and the implications this would have on a process. A methodology for characterizing the biocatalyst was developed which was subsequently applied to the wild type and 5 mutants selected...

  2. Unsaturated fatty acids are inhibitors of bacterial conjugation

    Fernandez-Lopez, R.; Machón, C.; Longshaw, C.; Martin, S.; Molin, S; E. Zechner; Espinosa, M; Lanka, E; de la Cruz, F

    2005-01-01

    This report describes a high-throughput assay to identify substances that reduce the frequency of conjugation in Gram-negative bacteria. Bacterial conjugation is largely responsible for the spread of multiple antibiotic resistances in human pathogens. Conjugation inhibitors may provide a means to control the spread of antibiotic resistance. An automated conjugation assay was developed that used plasmid R388 and a laboratory strain of Escherichia coli as a model system, and bioluminescence as ...

  3. Chitosan as a green inhibitor for copper corrosion in acidic medium.

    El-Haddad, Mahmoud N

    2013-04-01

    The behavior of copper in 0.5 M HCl acid containing different concentrations of chitosan has been studied by weight loss, potentiodynamic polarization, electrochemical impedance spectroscopy (EIS) and electrochemical frequency modulation (EFM) measurements. Potentiodynamic polarization measurements show that the chitosan acts essentially as a mixed-type inhibitor. EFM can be used as a rapid and non destructive technique for corrosion rate measurements without prior knowledge of Tafel constants. The results of EIS indicate that the value of CPEs tends to decrease and both charge transfer resistance and inhibition efficiency tend to increase by increasing the inhibitor concentration. The investigated inhibitor has shown good inhibition efficiency in 0.5 M HCl. The adsorption of inhibitor on the copper surface obeys Langmuir's isotherm. Metal surface characterization was performed using scanning electron microscope (SEM) and Fourier transform infrared spectroscopy (FT-IR). Also, the relationship between quantum chemical calculations and experimental inhibition efficiency of the inhibitor was discussed. PMID:23298849

  4. Natural fatty acid synthase inhibitors as potent therapeutic agents for cancers: A review.

    Zhang, Jia-Sui; Lei, Jie-Ping; Wei, Guo-Qing; Chen, Hui; Ma, Chao-Ying; Jiang, He-Zhong

    2016-09-01

    Context Fatty acid synthase (FAS) is the only mammalian enzyme to catalyse the synthesis of fatty acid. The expression level of FAS is related to cancer progression, aggressiveness and metastasis. In recent years, research on natural FAS inhibitors with significant bioactivities and low side effects has increasingly become a new trend. Herein, we present recent research progress on natural fatty acid synthase inhibitors as potent therapeutic agents. Objective This paper is a mini overview of the typical natural FAS inhibitors and their possible mechanism of action in the past 10 years (2004-2014). Method The information was collected and compiled through major databases including Web of Science, PubMed, and CNKI. Results Many natural products induce cancer cells apoptosis by inhibiting FAS expression, with fewer side effects than synthetic inhibitors. Conclusion Natural FAS inhibitors are widely distributed in plants (especially in herbs and foods). Some natural products (mainly phenolics) possessing potent biological activities and stable structures are available as lead compounds to synthesise promising FAS inhibitors. PMID:26864638

  5. Inhibitors of fatty acid biosynthesis in sunflower seeds.

    Pleite, Rafael; Martínez-Force, Enrique; Garcés, Rafael

    2006-09-01

    During de novo fatty acid synthesis in sunflower seeds, saturated fatty acid production is influenced by the competition between the enzymes of the principal pathways and the saturated acyl-ACP thioesterases. Genetic backgrounds with more efficient saturated acyl-ACP thioesterase alleles only express their phenotypic effects when the alleles for the enzymes in the main pathway are less efficient. For this reason, we studied the incorporation of [2-(14)C]acetate into the lipids of developing sunflower seeds (Helianthus annuus L.) from several mutant lines in vivo. The labelling of different triacylglycerol fatty acids in different oilseed mutants reflects the fatty acid composition of the seed and supports the channelling theory of fatty acid biosynthesis. Incubation with methyl viologen diminished the conversion of stearoyl-ACP to oleoyl-ACP in vivo through a decrease in the available reductant power. In turn, this led to the accumulation of stearoyl-ACP to the levels detected in seeds from high stearic acid mutants. The concomitant reduction of oleoyl-ACP content inside the plastid allowed us to study the activity of acyl-ACP thioesterases on saturated fatty acids. In these mutants, we verified that the accumulation of saturated fatty acids requires efficient thioesterase activity on saturated-ACPs. By studying the effects of cerulenin on the in vivo incorporation of [2-(14)C]acetate into lipids and on the in vitro activity of beta-ketoacyl-ACP synthase II, we found that elongation to very long chain fatty acids can occur both inside and outside of the plastid in sunflower seeds. PMID:16500723

  6. Acid violet 6B as a novel corrosion inhibitor for cold rolled steel in hydrochloric acid solution

    Research highlights: → Acid violet 6B (AV6B) is found to be a good inhibitor for the corrosion of CRS in 1.0 M HCl. → Effects of hydrochloric acid concentration (1.0 - 5.0 M) and immersion time (2 - 144 h) are discussed in detail. → The corrosion inhibition is satisfactorily discussed by both thermodynamic and kinetic parameters. → AV6B acts as a mixed-type inhibitor. → The adsorption of AV6B obeys Langmuir adsorption isotherm. - Abstract: The inhibition effect of acid violet 6B (AV6B) on the corrosion of cold rolled steel (CRS) in 1.0-5.0 M HCl solution was studied for the first time by weight loss, potentiodynamic polarization, and electrochemical impedance spectroscopy (EIS) methods. The results show that AV6B is a very good inhibitor in 1.0 M HCl, and the adsorption of AV6B on CRS surface obeys Langmuir adsorption isotherm. Polarization curves reveal that AV6B behaves as a mixed-type inhibitor. EIS spectra exhibit one capacitive loop and confirm the inhibitive ability. Effects of immersion time and acid concentration on inhibition performance were also discussed.

  7. Use of Hydrazone Derivates as Inhibitors for the Corrosion of Nickel in Hydrochloric Acid Solution

    A.S. Fouda, H. A. Mostafa, S. E. Ghazy and S. A. El- Farah

    2007-02-01

    Full Text Available The influence of hydrazone derivatives on the corrosion of nickel in 2 mol L-1 hydrochloric acid solution has been studied using weight loss and galvanostatic polarization techniques. In general, at constant acid concentration, the inhibition efficiency increases with increasing the inhibitor concentration and decreases with increasing temperature. Polarization studies indicate that the compounds act as mixed- type inhibitors. The addition of iodide ions enhances the inhibition efficiency to a considerable extent .The effect of temperature on corrosion inhibition has been studied and activation energy has been calculated. Some thermodynamic parameters are calculated and discussed.

  8. Inhibitors

    ... wrong place in the body. Immune Tolerance Induction (ITI) Therapy: The goal of ITI therapy is to stop the inhibitor reaction from ... body to accept clotting factor concentrate treatments. With ITI therapy, people receive large amounts of clotting factor ...

  9. Advances in the discovery of N-acylethanolamine acid amidase inhibitors.

    Bandiera, Tiziano; Ponzano, Stefano; Piomelli, Daniele

    2014-08-01

    N-Acylethanolamine acid amidase (NAAA) is a cysteine amidase that hydrolyzes saturated or monounsaturated fatty acid ethanolamides, such as palmitoylethanolamide (PEA) and oleoylethanolamide (OEA). PEA has been shown to exert analgesic and anti-inflammatory effects by engaging peroxisome proliferator-activated receptor-α. Like other fatty acid ethanolamides, PEA is not stored in cells, but produced on demand from cell membrane precursors, and its actions are terminated by intracellular hydrolysis by either fatty acid amide hydrolase or NAAA. Endogenous levels of PEA and OEA have been shown to decrease during inflammation. Modulation of the tissue levels of PEA by inhibition of enzymes responsible for the breakdown of this lipid mediator may represent therefore a new therapeutic strategy for the treatment of pain and inflammation. While a large number of inhibitors of fatty acid amide hydrolase have been discovered, few compounds have been reported to inhibit NAAA activity. Here, we describe the most representative NAAA inhibitors and briefly highlight their pharmacological profile. A recent study has shown that a NAAA inhibitor attenuated heat hyperalgesia and mechanical allodynia caused by local inflammation or nerve damage in animal models of pain and inflammation. This finding encourages further exploration of the pharmacology of NAAA inhibitors. PMID:24798679

  10. Fatty Acid Synthase Inhibitor C75 Ameliorates Experimental Colitis

    Matsuo, Shingo; Yang, Weng-Lang; Aziz, Monowar; Kameoka, Shingo; Wang, Ping

    2013-01-01

    Abnormalities of lipid metabolism through overexpression of fatty acid synthase (FASN), which catalyzes the formation of long-chain fatty acids, are associated with the development of inflammatory bowel disease (IBD). C75 is a synthetic α-methylene-γ-butyrolactone compound that inhibits FASN activity. We hypothesized that C75 treatment could effectively reduce the severity of experimental colitis. Male C57BL/6 mice were fed 4% dextran sodium sulfate (DSS) for 7 d. C75 (5 mg/kg body weight) or...

  11. Impacts of lignocellulose-derived inhibitors on L-lactic acid fermentation by Rhizopus oryzae.

    Zhang, Li; Li, Xin; Yong, Qiang; Yang, Shang-Tian; Ouyang, Jia; Yu, Shiyuan

    2016-03-01

    Inhibitors generated in the pretreatment and hydrolysis of corn stover and corn cob were identified. In general, they inhibited cell growth, lactate dehydrogenase, and lactic acid production but with less or no adverse effect on alcohol dehydrogenase and ethanol production in batch fermentation by Rhizopus oryzae. Furfural and 5-hydroxymethyl furfural (HMF) were highly toxic at 0.5-1 g L(-1), while formic and acetic acids at less than 4 g L(-1) and levulinic acid at 10 g L(-1) were not toxic. Among the phenolic compounds at 1 g L(-1), trans-cinnamic acid and syringaldehyde had the highest toxicity while syringic, ferulic and p-coumaric acids were not toxic. Although these inhibitors were present at concentrations much lower than their separately identified toxic levels, lactic acid fermentation with the hydrolysates showed much inferior performance compared to the control without inhibitor, suggesting synergistic or compounded effects of the lignocellulose-degraded compounds on inhibiting lactic acid fermentation. PMID:26724548

  12. Sodium phthalamates as corrosion inhibitors for carbon steel in aqueous hydrochloric acid solution

    Highlights: → N-Alkyl-sodium phthalamates as corrosion inhibitors for industry in acidic medium. → Compounds behaved as mixed type inhibitors and followed Langmuir adsorption isotherm. → Efficiencies were proportional to aliphatic chain length and inhibitor concentration. → Iron complexes and chelates with phthalamates contributed to carbon steel protection. - Abstract: Three compounds of N-alkyl-sodium phthalamates were synthesized and tested as corrosion inhibitors for carbon steel in 0.5 M aqueous hydrochloric acid. Tests showed that inhibitor efficiencies were related to aliphatic chain length and dependent on concentration. N-1-n-tetradecyl-sodium phthalamate displayed moderate efficiency against uniform corrosion, 42-86% at 25 deg. C and 25-60% at 40 oC. Tests indicated that compounds behave as mixed type inhibitors where molecular adsorption on steel followed Langmuir isotherm, whereas thermodynamic suggested that a physisorption process occurred. XPS analysis confirmed film formation on surface, where Fe+2 complexes and Fe+2 chelates with phthalamates prevented steel from further corrosion.

  13. Binding of [alpha, alpha]-Disubstituted Amino Acids to Arginase Suggests New Avenues for Inhibitor Design

    Ilies, Monica; Di Costanzo, Luigi; Dowling, Daniel P.; Thorn, Katherine J.; Christianson, David W. (MIT); (Episcopal U); (Rutgers); (Drexel); (Penn)

    2011-10-21

    Arginase is a binuclear manganese metalloenzyme that hydrolyzes L-arginine to form L-ornithine and urea, and aberrant arginase activity is implicated in various diseases such as erectile dysfunction, asthma, atherosclerosis, and cerebral malaria. Accordingly, arginase inhibitors may be therapeutically useful. Continuing our efforts to expand the chemical space of arginase inhibitor design and inspired by the binding of 2-(difluoromethyl)-L-ornithine to human arginase I, we now report the first study of the binding of {alpha},{alpha}-disubstituted amino acids to arginase. Specifically, we report the design, synthesis, and assay of racemic 2-amino-6-borono-2-methylhexanoic acid and racemic 2-amino-6-borono-2-(difluoromethyl)hexanoic acid. X-ray crystal structures of human arginase I and Plasmodium falciparum arginase complexed with these inhibitors reveal the exclusive binding of the L-stereoisomer; the additional {alpha}-substituent of each inhibitor is readily accommodated and makes new intermolecular interactions in the outer active site of each enzyme. Therefore, this work highlights a new region of the protein surface that can be targeted for additional affinity interactions, as well as the first comparative structural insights on inhibitor discrimination between a human and a parasitic arginase.

  14. Curcumin Derivatives as Green Corrosion Inhibitors for α-Brass in Nitric Acid Solution

    Fouda, A. S.; Elattar, K. M.

    2012-11-01

    1,7- Bis-(4-hydroxy-3-methoxy-phenyl)-hepta-1,6-diene-4-arylazo-3,5-dione I-V have been investigated as corrosion inhibitors for α-brass in 2 M nitric acid solution using weight-loss and galvanostatic polarization techniques. The efficiency of the inhibitors increases with the increase in the inhibitor concentration but decreases with a rise in temperature. The conjoint effect of the curcumin derivatives and KSCN has also been studied. The apparent activation energy ( E a*) and other thermodynamic parameters for the corrosion process have also been calculated. The galvanostatic polarization data indicated that the inhibitors were of mixed-type, but the cathode is more polarized than the anode. The slopes of the cathodic and anodic Tafel lines ( b c and b a) are maintained approximately equal for various inhibitor concentrations. However, the value of the Tafel slopes increases together as inhibitor concentration increases. The adsorption of these compounds on α-brass surface has been found to obey the Frumkin's adsorption isotherm. The mechanism of inhibition was discussed in the light of the chemical structure of the undertaken inhibitors.

  15. THE STUDY OF HENNA LEAVES EXTRACT AS GREEN CORROSION INHIBITOR FOR MILD STEEL IN ACETIC ACID.

    H. G. Chaudhari; R. T. Vashi

    2016-01-01

    The inhibitive action of henna leaves extract on mild steel in acetic acid solution have been investigated by weight-loss, A C impedence and potentiodynamic polarization measurements. The study indicates that as acid concentration increases corrosion rate increases. The corrosion inhibition efficiency increases with increase in concentration of extract. The result obtained revealed that henna leaves extract act as efficient inhibitor. The adsorption of the henna leaves extract obeyed Langmuir...

  16. The effect of gamma irradiation on fish transaminase and rhodanese

    Investigations on glutamic oxaloacetic transaminase (GOT), glutamic pyruvate transaminase (GPT) and rhodanese of both unirradiated and irradiated chub mackerel (Rastrelliger neglectus) have been carried out. Fish were irradiated with doses varied from 0 to 5 kGy, at a dose rate of 2 kGy/hr. Fish extracts prepared in 0.01 M phosphate-buffer of pH 7 were used throughout the enzyme experiments. The conclusion drawn from five replicates showed a significant decrease (P<=0.01) in fish G0T, GPT and rhodanese specific activities after irradiation. It is proved that GOT and GPT were more susceptible towards irradiation as compared to rhodanese. An irradiation dose of 4 kGy was able to inactivate G0T, GPT and rhodanese for ca 50, 44 and 36% respectively. Evidently transaminase as well as rhodanese specific activities to spoiled fish were significantly lower (P<=0.01) than those of fresh fish. The residual GOT, GPT and rhodanese specific activities in spoiled fish was found to be about 35, 41 and 22% respectively. (author)

  17. Impact of plasma transaminase levels on the peripheral blood glutamate levels and memory functions in healthy subjects☆

    Kamada, Yoshihiro; Hashimoto, Ryota; Yamamori, Hidenaga; Yasuda, Yuka; Takehara, Tetsuo; Fujita, Yuko; Hashimoto, Kenji; Miyoshi, Eiji

    2016-01-01

    Background & aims Blood aspartate aminotransferase (AST) and alanine transaminase (ALT) levels are the most frequently reliable biomarkers of liver injury. Although AST and ALT play central roles in glutamate production as transaminases, peripheral blood levels of AST and ALT have been regarded only as liver injury biomarkers. Glutamate is a principal excitatory neurotransmitter, which affects memory functions in the brain. In this study, we investigated the impact of blood transaminase levels on blood glutamate concentration and memory. Methods Psychiatrically, medically, and neurologically healthy subjects (n = 514, female/male: 268/246) were enrolled in this study through local advertisements. Plasma amino acids (glutamate, glutamine, glycine, d-serine, and l-serine) were measured using a high performance liquid chromatography system. The five indices, verbal memory, visual memory, general memory, attention/concentration, and delayed recall of the Wechsler Memory Scale-Revised were used to measure memory functions. Results Both plasma AST and ALT had a significant positive correlation with plasma glutamate levels. Plasma AST and ALT levels were significantly negatively correlated with four of five memory functions, and plasma glutamate was significantly negatively correlated with three of five memory functions. Multivariate analyses demonstrated that plasma AST, ALT, and glutamate levels were significantly correlated with memory functions even after adjustment for gender and education. Conclusions As far as we know, this is the first report which could demonstrate the impact of blood transaminase levels on blood glutamate concentration and memory functions in human. These findings are important for the interpretation of obesity-induced metabolic syndrome with elevated transaminases and cognitive dysfunction. PMID:27051595

  18. Bis(aminomethyl)phosphinic Acid, a Highly Promising Scaffold for the Development of Bacterial Urease Inhibitors.

    Macegoniuk, Katarzyna; Dziełak, Anna; Mucha, Artur; Berlicki, Łukasz

    2015-02-12

    Inhibitors of bacterial ureases are considered to be promising compounds in the treatment of infections caused by Helicobacter pylori in the gastric tract and/or by urealytic bacteria (e.g., Proteus species) in the urinary tract. A new, extended transition state scaffold, bis(aminomethyl)phosphinic acid, was successfully explored for the construction of effective enzyme inhibitors. A reliable methodology for the synthesis of phosphinate analogues in a three-component Mannich-type reaction was elaborated. The obtained molecules were assayed against ureases purified from Sporosarcina pasteurii and Proteus mirabilis, and aminomethyl(N-n-hexylaminomethyl)phosphinic acid was found to be the most potent inhibitor, with a K i = 108 nM against the S. pasteurii enzyme. PMID:25699141

  19. N-heterocyclic Amine Derivatives as Efficient Corrosion Inhibitors for Carbon Steel in Acidic Medium

    A novel heterocyclic amine derivatives, namely N, N'-substituted pyridinyl ethylene diamine tetra acetic acid sodium salt (A) and ethylene diamine N, N'-diacetic acid di (2-methylene tetra hydro furfuryl) acetate (B) were synthesized and their structure confirmations were performed by FTIR, HNMR and CNMR spectra. The inhibition effectiveness was evaluated against the corrosion of carbon steel in 1 M HCl by weight loss and polarization techniques. The results showed that the synthesized derivatives are good corrosion inhibitors for carbon steel in 1 M HCl medium, their inhibition efficiency, increased with inhibitor concentration, and (A) is slightly more effective than (B). The potentiostatic polarization study showed that (A) and (B) are mixed-type inhibitors in 1 M HCl. These compounds prevent carbon steel from corrosion by adsorption to the steel surface and forming insoluble complexes with ferrous species. The weight loss results and potentiostatic polarization studies were in reasonable agreement. (author)

  20. Benzoxazolone Carboxamides as Potent Acid Ceramidase Inhibitors: Synthesis and Structure-Activity Relationship (SAR) Studies.

    Bach, Anders; Pizzirani, Daniela; Realini, Natalia; Vozella, Valentina; Russo, Debora; Penna, Ilaria; Melzig, Laurin; Scarpelli, Rita; Piomelli, Daniele

    2015-12-10

    Ceramides are lipid-derived intracellular messengers involved in the control of senescence, inflammation, and apoptosis. The cysteine amidase, acid ceramidase (AC), hydrolyzes these substances into sphingosine and fatty acid and, by doing so, regulates their signaling activity. AC inhibitors may be useful in the treatment of pathological conditions, such as cancer, in which ceramide levels are abnormally reduced. Here, we present a systematic SAR investigation of the benzoxazolone carboxamides, a recently described class of AC inhibitors that display high potency and systemic activity in mice. We examined a diverse series of substitutions on both benzoxazolone ring and carboxamide side chain. Several modifications enhanced potency and stability, and one key compound with a balanced activity-stability profile (14) was found to inhibit AC activity in mouse lungs and cerebral cortex after systemic administration. The results expand our arsenal of AC inhibitors, thereby facilitating the use of these compounds as pharmacological tools and their potential development as drug leads. PMID:26560855

  1. Beyond gastric acid reduction: Proton pump inhibitors induce heme oxygenase-1 in gastric and endothelial cells

    Proton pump inhibitors (PPIs) have been demonstrated to prevent gastric mucosal injury by mechanisms independent of acid inhibition. Here we demonstrate that both omeprazole and lansoprazole protect human gastric epithelial and endothelial cells against oxidative stress. This effect was abrogated in the presence of the heme oxygenase-1 (HO-1) inhibitor ZnBG. Exposure to either PPI resulted in a strong induction of HO-1 expression on mRNA and protein level, and led to an increased activity of this enzyme. Expression of cyclooxygenase isoforms 1 and 2 remained unaffected, and COX-inhibitors did not antagonize HO-1 induction by PPIs. Our results suggest that the antioxidant defense protein HO-1 is a target of PPIs in both endothelial and gastric epithelial cells. HO-1 induction might account for the gastroprotective effects of PPIs independently of acid inhibition, especially in NSAID gastropathy. Moreover, our findings provide additional perspectives for a possible but yet unexplored use of PPIs in vasoprotection

  2. Inhibitors of Fatty Acid Synthesis Induce PPAR α -Regulated Fatty Acid β -Oxidative Genes: Synergistic Roles of L-FABP and Glucose

    Huan Huang; McIntosh, Avery L.; Martin, Gregory G.; Petrescu, Anca D.; Landrock, Kerstin K.; Danilo Landrock; Kier, Ann B.; Friedhelm Schroeder

    2013-01-01

    While TOFA (acetyl CoA carboxylase inhibitor) and C75 (fatty acid synthase inhibitor) prevent lipid accumulation by inhibiting fatty acid synthesis, the mechanism of action is not simply accounted for by inhibition of the enzymes alone. Liver fatty acid binding protein (L-FABP), a mediator of long chain fatty acid signaling to peroxisome proliferator-activated receptor-α (PPARα) in the nucleus, was found to bind TOFA and its activated CoA th...

  3. Trypsin inhibitors from ridged gourd (Luffa acutangula Linn.) seeds: purification, properties, and amino acid sequences.

    Haldar, U C; Saha, S K; Beavis, R C; Sinha, N K

    1996-02-01

    Two trypsin inhibitors, LA-1 and LA-2, have been isolated from ridged gourd (Luffa acutangula Linn.) seeds and purified to homogeneity by gel filtration followed by ion-exchange chromatography. The isoelectric point is at pH 4.55 for LA-1 and at pH 5.85 for LA-2. The Stokes radius of each inhibitor is 11.4 A. The fluorescence emission spectrum of each inhibitor is similar to that of the free tyrosine. The biomolecular rate constant of acrylamide quenching is 1.0 x 10(9) M-1 sec-1 for LA-1 and 0.8 x 10(9) M-1 sec-1 for LA-2 and that of K2HPO4 quenching is 1.6 x 10(11) M-1 sec-1 for LA-1 and 1.2 x 10(11) M-1 sec-1 for LA-2. Analysis of the circular dichroic spectra yields 40% alpha-helix and 60% beta-turn for La-1 and 45% alpha-helix and 55% beta-turn for LA-2. Inhibitors LA-1 and LA-2 consist of 28 and 29 amino acid residues, respectively. They lack threonine, alanine, valine, and tryptophan. Both inhibitors strongly inhibit trypsin by forming enzyme-inhibitor complexes at a molar ratio of unity. A chemical modification study suggests the involvement of arginine of LA-1 and lysine of LA-2 in their reactive sites. The inhibitors are very similar in their amino acid sequences, and show sequence homology with other squash family inhibitors. PMID:8924202

  4. The identification and optimization of 2,4-diketobutyric acids as flap endonuclease 1 inhibitors.

    Tumey, L Nathan; Huck, Bayard; Gleason, Elizabeth; Wang, Jianmin; Silver, Daniel; Brunden, Kurt; Boozer, Sherry; Rundlett, Stephen; Sherf, Bruce; Murphy, Steven; Bailey, Andrew; Dent, Tom; Leventhal, Christina; Harrington, John; Bennani, Youssef L

    2004-10-01

    There have been several recent reports of chemopotentiation via inhibition of DNA repair processes. Flap endonuclease 1 (FEN1) is a key enzyme involved in base excision repair (BER), a primary pathway utilized by mammalian cells to repair DNA damage. In this report, we describe the identification and SAR of a series of 2,4-diketobutyric acid FEN1 inhibitors. PMID:15341951

  5. Synthesis of corrosion inhibitors from corn oil fatty acids and study of their adsorption properties

    The imidazoline derivatives were synthesized from corn oil fatty acids and triethylenetetramine. The corrosion inhibition efficiency studies of these imidazolines were performed in H2S solutions by gravimetric method. The adsorption behaviour of the compounds obeys the Langmuir isotherm and the interaction between the inhibitor molecule and the metal surface is a strong chemical reaction with high Gibbs free adsorption energy

  6. Crystallization and preliminary X-ray crystallographic studies of β-transaminase from Mesorhizobium sp. strain LUK

    β-Transaminase from Mesorhizobium sp. strain LUK was crystallized. The crystals were found to belong to the orthorhombic space group C2221, with unit-cell parameters a = 90.91, b = 192.17, c = 52.75 Å. The crystals were obtained at 293 K and diffracted to a resolution of 2.5 Å. β-Transaminase (β-TA) catalyzes the transamination reaction between β-aminocarboxylic acids and keto acids. This enzyme is a particularly suitable candidate for use as a biocatalyst for the asymmetric synthesis of enantiochemically pure β-amino acids for pharmaceutical purposes. The β-TA from Mesorhizobium sp. strain LUK (β-TAMs) belongs to a novel class in that it shows β-transaminase activity with a broad and unique substrate specificity. In this study, β-TAMs was overexpressed in Escherichia coli with an engineered C-terminal His tag. β-TAMs was then purified to homogeneity and crystallized at 293 K. X-ray diffraction data were collected to a resolution of 2.5 Å from a crystal that belonged to the orthorhombic space group C2221, with unit-cell parameters a = 90.91, b = 192.17, c = 52.75 Å

  7. Penta- and hexadienoic acid derivatives: a novel series of 5-lipoxygenase inhibitors.

    Malleron, J L; Roussel, G; Gueremy, G; Ponsinet, G; Robin, J L; Terlain, B; Tissieres, J M

    1990-10-01

    The synthesis of a series of pentadienoic and hexadienoic acid derivatives is reported. These compounds were tested as inhibitors of 5-lipoxygenase (5 LO) and cyclooxygenase (CO) in vitro and as inhibitors of arachidonic acid (AA) induced ear edema in mice in vivo. Their potency is compared with that of the standard inhibitors nafazatrom, BW 755C, NDGA, KME4, quercetine, and L 652,243. The most potent compound in vivo, diethyl 2-hydroxy-5-(ethylthio)-2(Z),4(Z)-hexadienedioate (20) inhibited AA-induced ear edema when administered topically or orally, with an ED50 value of 0.01 mg/ear and 20 mg/kg, respectively. Among the standard compounds tested, L 652,243 was the most active compound in this test with an ED50 value of 0.01 mg/ear and 1 mg/kg po, but unlike this compound, 20 is a selective inhibitor of 5-LO (IC50 = 2 microM) without any significant activity against CO (IC50 greater than 50 microM). Most of the other compounds in this series are also selective 5-LO inhibitors. PMID:2213827

  8. Structure-based design of non-natural amino-acid inhibitors of amyloid fibril formation

    Sievers, Stuart A.; Karanicolas, John; Chang, Howard W.; Zhao, Anni; Jiang, Lin; Zirafi, Onofrio; Stevens, Jason T.; Münch, Jan; Baker, David; Eisenberg, David (UCLA); (UWASH); (UL); (Kansas); (Ulm)

    2011-09-20

    Many globular and natively disordered proteins can convert into amyloid fibrils. These fibrils are associated with numerous pathologies as well as with normal cellular functions, and frequently form during protein denaturation. Inhibitors of pathological amyloid fibril formation could be useful in the development of therapeutics, provided that the inhibitors were specific enough to avoid interfering with normal processes. Here we show that computer-aided, structure-based design can yield highly specific peptide inhibitors of amyloid formation. Using known atomic structures of segments of amyloid fibrils as templates, we have designed and characterized an all-D-amino-acid inhibitor of the fibril formation of the tau protein associated with Alzheimer's disease, and a non-natural L-amino-acid inhibitor of an amyloid fibril that enhances sexual transmission of human immunodeficiency virus. Our results indicate that peptides from structure-based designs can disrupt the fibril formation of full-length proteins, including those, such as tau protein, that lack fully ordered native structures. Because the inhibiting peptides have been designed on structures of dual-{beta}-sheet 'steric zippers', the successful inhibition of amyloid fibril formation strengthens the hypothesis that amyloid spines contain steric zippers.

  9. Peroxisomal fatty acid oxidation and inhibitors of the mitochondrial carnitine palmitoyltransferase I in isolated rat hepatocytes.

    Skorin, C; Necochea, C; Johow, V; Soto, U; Grau, A M; Bremer, J; Leighton, F

    1992-01-01

    Fatty acid oxidation was studied in the presence of inhibitors of carnitine palmitoyltransferase I (CPT I), in normal and in peroxisome-proliferated rat hepatocytes. The oxidation decreased in mitochondria, as expected, but in peroxisomes it increased. These two effects were seen, in variable proportions, with (+)-decanoylcarnitine, 2-tetradecylglycidic acid (TDGA) and etomoxir. The decrease in mitochondrial oxidation (ketogenesis) affected saturated fatty acids with 12 or more carbon atoms, whereas the increase in peroxisomal oxidation (H2O2 production) affected saturated fatty acids with 8 or more carbon atoms. The peroxisomal increase was sensitive to chlorpromazine, a peroxisomal inhibitor. To study possible mechanisms, palmitoyl-, octanoyl- and acetyl-carnitine acyltransferase activities were measured, in homogenates and in subcellular fractions from control and TDGA-treated cells. The palmitoylcarnitine acyltransferase was inhibited, as expected, but the octanoyltransferase activity also decreased. The CoA derivative of TDGA was synthesized and tentatively identified as being responsible for inhibition of the octanoylcarnitine acyltransferase. These results show that inhibitors of the mitochondrial CPT I may also inhibit the peroxisomal octanoyl transferase; they also support the hypothesis that the octanoyltransferase has the capacity to control or regulate peroxisomal fatty acid oxidation. PMID:1736904

  10. Cathepsin D-mediated yolk protein degradation is blocked by acid phosphatase inhibitors.

    Fialho, Eliane; Nakamura, Angelica; Juliano, Luiz; Masuda, Hatisaburo; Silva-Neto, Mário A C

    2005-04-15

    Vitellin (VT) is a lipoglycophosphoprotein stored inside the eggs of every oviparous organism during oogenesis. In the blood-sucking bug Rhodnius prolixus, VT is deposited inside growing oocytes together with two acid hydrolases: acid phosphatase (AP) and cathepsin D (CD). Egg fertilization triggers AP activity and VT proteolysis in vivo [Insect Biochem. Mol. Biol. 2002 (32) 847]. Here, we show that CD is the main protease targeting VT proteolysis during egg development. CD activity in total egg homogenates is blocked by the classical aspartyl protease inhibitor, pepstatin A. Surprisingly, AP inhibitors such as NaF, Na+/K+ tartrate, and inorganic phosphate also block VT proteolysis, whereas this effect is not observed when tyrosine phosphatase inhibitors such as vanadate and phenylarsine oxide or an inhibitor of alkaline phosphatases such as levamisole are used in a VT proteolysis assay. NaF concentrations that block isolated AP activity do not affect the activity of partially purified CD. Therefore, a specific repressor of VT proteolysis must be dephosphorylated by AP in vivo. In conclusion, these results demonstrate for the first time that acid hydrolases act cooperatively to promote yolk degradation during egg development in arthropods. PMID:15797237

  11. Identification of new quinic acid derivatives as histone deacetylase inhibitors by fluorescence-based cellular assay.

    Son, Dohyun; Kim, Chung Sub; Lee, Kang Ro; Park, Hyun-Ju

    2016-05-01

    A fluorescence-based cellular assay system was established to identify potential epigenetic modulator ligands. This assay method is to detect the de-repression of an EGFP reporter in cancer cells by the treatment of HDAC (histone deacetylase) or DNMT (DNA methyltransferase) inhibitor. Using this system, we conducted a preliminary screening of in-house natural product library containing extracts and pure compounds, and identified several active compounds. Among them, novel quinic acid derivatives were recognized as excellent HDAC inhibitors by both enzymatic and cell-based HDAC assays. PMID:26996372

  12. Molecular design, synthesis and biological activities of amidines as new ketol-acid reductoisomerase inhibitors

    Bao Lei Wang; Yong Hong Li; Jian Guo Wang; Yi Ma; Zheng Ming Li

    2008-01-01

    Diamidine (A) was identified in our in vitro bio-assay as a possible inhibitor of ketol-acid reductoisomerase (KARI) from the ACD database search based on the known three-dimensional crystal structure of KARI. An investigation on interaction of A on KARI active sites, led to the design and synthesis of 15 novel monoamidines. Some of those showed better biological activity than A on rice KARI (in vitro) and in greenhouse herbicidal tests (in vivo). The structure-biological activity relationship was investigated, which provides valuable information to further study of potential KARI inhibitors.

  13. Alteration of the Donor/Acceptor Spectrum of the (S-Amine Transaminase from Vibrio fluvialis

    Maika Genz

    2015-11-01

    Full Text Available To alter the amine donor/acceptor spectrum of an (S-selective amine transaminase (ATA, a library based on the Vibrio fluvialis ATA targeting four residues close to the active site (L56, W57, R415 and L417 was created. A 3DM-derived alignment comprising fold class I pyridoxal-5′-phosphate (PLP-dependent enzymes allowed identification of positions, which were assumed to determine substrate specificity. These positions were targeted for mutagenesis with a focused alphabet of hydrophobic amino acids to convert an amine:α-keto acid transferase into an amine:aldehyde transferase. Screening of 1200 variants revealed three hits, which showed a shifted amine donor/acceptor spectrum towards aliphatic aldehydes (mainly pentanal, as well as an altered pH profile. Interestingly, all three hits, although found independently, contained the same mutation R415L and additional W57F and L417V substitutions.

  14. A dual inhibitor of cyclooxygenase and 5-lipoxygenase protects against kainic acid-induced brain injury.

    Minutoli, Letteria; Marini, Herbert; Rinaldi, Mariagrazia; Bitto, Alessandra; Irrera, Natasha; Pizzino, Gabriele; Pallio, Giovanni; Calò, Margherita; Adamo, Elena Bianca; Trichilo, Vincenzo; Interdonato, Monica; Galfo, Federica; Squadrito, Francesco; Altavilla, Domenica

    2015-06-01

    Systemic administration of kainic acid causes inflammation and apoptosis in the brain, resulting in neuronal loss. Dual cyclooxygenase/5-lipoxygenase (COX/5-LOX) inhibitors could represent a possible neuroprotective approach in preventing glutamate excitotoxicity. Consequently, we investigated the effects of a dual inhibitor of COX/5-LOX following intraperitoneal administration of kainic acid (KA, 10 mg/kg) in rats. Animals were randomized to receive either the dual inhibitor of COX/5-LOX (flavocoxid, 20 mg/kg i.p.) or its vehicle (1 ml/kg i.p.) 30 min after KA administration. Sham brain injury rats were used as controls. We evaluated protein expression of phosphorylated extracellular signal-regulated kinase (p-ERK1/2) and tumor necrosis factor alpha (TNF-α) as well as levels of malondialdehyde (MDA), prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) in the hippocampus. Animals were also observed for monitoring behavioral changes according to Racine Scale. Finally, histological analysis and brain edema evaluation were carried out. Treatment with the dual inhibitor of COX/5-LOX decreased protein expression of p-ERK1/2 and TNF-α in hippocampus, markedly reduced MDA, LTB4 and PGE2 hippocampal levels, and also ameliorated brain edema. Histological analysis showed a reduction in cell damage in rats treated with the dual inhibitor of COX/5-LOX, particularly in hippocampal subregion CA3c. Moreover, flavocoxid significantly improved behavioral signs following kainic acid administration. Our results suggest that dual inhibition of COX/5-LOX by flavocoxid has neuroprotective effects during kainic acid-induced excitotoxicity. PMID:25893744

  15. EFFECT OF INHIBITORS ON ENZYMATIC HYDROLYSIS AND SIMULTANEOUS SACCHARIFICATION FERMENTATION FOR LACTIC ACID PRODUCTION FROM STEAM EXPLOSION PRETREATED LESPEDEZA STALKS

    Yue Feng; Xiang Qi,; Hong-lei Jian,; Run-cang Sun; Jian-xin Jiang

    2012-01-01

    The effects on both cellulose conversion rate and lactic acid yield were studied by adding inhibitors, including formic acid, acetic acid, furfural, and vanillin into the hydrolysate of steam-pretreated Lespedeza stalks. The results suggest that formic acid has a significant influence on the enzyme activity and poisoned bacterial cells, resulting in the reduction of cellulose conversion rate and lactic acid yield by 21% and 16.4%, respectively. Acetic acid showed a strong inhibition on simult...

  16. Identification of ellagic acid as potent inhibitor of protein kinase CK2: a successful example of a virtual screening application.

    Cozza, Giorgio; Bonvini, Paolo; Zorzi, Elisa; Poletto, Giorgia; Pagano, Mario A; Sarno, Stefania; Donella-Deana, Arianna; Zagotto, Giuseppe; Rosolen, Angelo; Pinna, Lorenzo A; Meggio, Flavio; Moro, Stefano

    2006-04-20

    Casein kinase 2 (CK2) is a ubiquitous, essential, and highly pleiotropic protein kinase whose abnormally high constitutive activity is suspected to underlie its pathogenic potential in neoplasia and other diseases. Using a virtual screening approach, we have identified the ellagic acid, a naturally occurring tannic acid derivative, as a novel potent CK2 inhibitor. At present, ellagic acid represents the most potent known CK2 inhibitor (K(i) = 20 nM). PMID:16610779

  17. Lichen secondary metabolite evernic acid as potential quorum sensing inhibitor against Pseudomonas aeruginosa.

    Gökalsın, Barış; Sesal, Nüzhet Cenk

    2016-09-01

    Cystic Fibrosis is a genetic disease and it affects the respiratory and digestive systems. Pseudomonas aeruginosa infections in Cystic Fibrosis are presented as the main cause for high mortality and morbidity rates. Pseudomonas aeruginosa populations can regulate their virulence gene expressions via the bacterial communication system: quorum sensing. Inhibition of quorum sensing by employing quorum sensing inhibitors can leave the bacteria vulnerable. Therefore, determining natural sources to obtain potential quorum sensing inhibitors is essential. Lichens have ethnobotanical value for their medicinal properties and it is possible that their secondary metabolites have quorum sensing inhibitor properties. This study aims to investigate an alternative treatment approach by utilizing lichen secondary metabolite evernic acid to reduce the expressions of Pseudomonas aeruginosa virulence factors by inhibiting quorum sensing. For this purpose, fluorescent monitor strains were utilized for quorum sensing inhibitor screens and quantitative reverse-transcriptase PCR analyses were conducted for comparison. Results indicate that evernic acid is capable of inhibiting Pseudomonas aeruginosa quorum sensing systems. PMID:27465850

  18. Inhibition of deoxyribonucleic acid replication in Bacillus brevis by ribonucleic acid polymerase inhibitors.

    Bhattacharya, S.; Sarkar, N.

    1981-01-01

    The incorporation of [3H]thymidine into deoxyribonucleic acid by exponentially growing cells of Bacillus brevis was inhibited by streptolydigin and rifampin in the same concentration range in which these drugs inhibit ribonucleic acid synthesis. Complete inhibition occurred within one-third generation time after drug addition, suggesting an effect on deoxyribonucleic acid chain elongation.

  19. Some novel antimicrobial therapeutic agents for acetylcholinesterase inhibitors; synthesis of hydroxyquinoline ester involving amino acid

    Şakıyan, İffet; Aynacı, Elif; Arslan, Fatma; Öğütcü, Hatice; Sarı, Nurşen

    2015-01-01

    The aim of this work was to investigate the new effective agents candidate for treatment of the Alzheimer’s disease. So, a series of new and highly active acetylcholinesterase inhibitors derived from hydroxyquinoline ester containing amino acid were synthesized. Antibacterial activities of the molecules were studied by the well-diffusion method against Listeria monocytogenes 4b, Staphylococcus aureus, Escherichia coli, Salmonella typhi H, Brucella abortus, Staphylococcus epidermis sp., ...

  20. Synthesis and Application of Phenyl Nitrone Derivatives as Acidic and Microbial Corrosion Inhibitors

    Shijun Chen; Kang Zhao; Gang Chen

    2015-01-01

    Nitrone has drawn great attention due to its wide applications as a 1,3-dipole in heterocyclic compounds synthesis and the bioactivities. With the special structure, nitrone can also be used as ligand in inorganic chemistry. Based on the current research, the nitrones are anticipated to be effective inhibitors against acidic and microbial corrosion. The aim of this work is to investigate the inhibitory action of nitrones. In this work, a series of phenyl nitrone derivatives (PN) was synthesiz...

  1. Predictive QSPR analysis of corrosion inhibitors for super 13% Cr steel in hydrochloric acid

    S. P. Cardoso; J. A. C. P. Gomes; L. E. P. Borges; E. Hollauer

    2007-01-01

    An experimental and theoretical study on the inhibition corrosion efficiencies of twenty three compounds in hydrochloric acid (15% w/v) on 13% Cr modified stainless steel (martensitic) has been carried out. This inhibitor set includes amines, thiourea derivatives and acetylenic alcohols. Experimental weight losses at 60ºC were correlated with group and quantum AM1 descriptors obtained from QSPR analysis. Such data, for a large set of molecules, offer a unique opportunity for searching for cor...

  2. INHIBITIVE EFFECT OF WRIGHTIA TINCTORIA LEAVES AS GREEN INHIBITOR FOR MILD STEEL IN ACID MEDIUM

    P. Deivanayagam*; I. Malarvizhi; Selvaraj, S

    2016-01-01

    The inhibition efficacy of Wrightia tinctoria leaves (WTL) extract on mild steel in 1.0N hydrochloric acid with various exposure time (24 to 360hrs) and temperature (313 to 333K) are investigated by mass loss measurements. The value of inhibition efficiency is increased with increase of inhibitor concentration and gradually decreased with rise in temperature is suggestive of physisorption. The adsorption of WTL onto the mild steel surface is found to follow the Langmuir adsorption isotherm. B...

  3. Study of Plant Cordia Dichotoma as Green Corrosion Inhibitor for Mild Steel in Different Acid Media

    Khandelwal, R; Arora, S. K.; Mathur, S P

    2011-01-01

    The corrosion inhibition of mild steel using extracts of Cordia dichotoma in different acid media was investigated by mass loss and thermometric methods. The experiments were carried out at 299±0.2 K in presence of different concentrations of dry fruit, leaves and stem extracts of Cordia dichotoma. The results reveal that the alcoholic extracts of Cordia dichotoma is a better corrosion inhibitor than that of toxic chemicals. The fruit extract is more potent than leaves and stem extracts to in...

  4. Pyrrolidinobenzoic Acid Inhibitors of Influenza Virus Neuraminidase: the Hydrophobic Side Chain Influences Type A Subtype Selectivity

    Li, Yanwu; Silamkoti, Arundutt; Kolavi, Gundurao; Mou, Liyuan; Gulati, Shelly; Air, Gillian M; Brouillette, Wayne J.

    2012-01-01

    Neuraminidase (NA) plays a critical role in the life cycle of influenza virus and is a target for new therapeutic agents. A series of influenza neuraminidase inhibitors with the pyrrolidinobenzoic acid scaffold containing lipophilic side chains at the C3 position have been synthesized and evaluated for influenza neuraminidase inhibitory activity. The size and geometry of the C3 side chains have been modified in order to investigate structure-activity relationships. The results indicated that ...

  5. Sulfonate salts of amino acids: novel inhibitors of the serine proteinases.

    Groutas, W C; Brubaker, M J; Zandler, M E; Stanga, M A; Huang, T L; Castrisos, J C; Crowley, J P

    1985-04-16

    A series of amino acid-derived sulfonate salts have been synthesized. They were found to inactivate efficiently and selectively human leukocyte elastase. The sulfonate salts of the methyl esters of L-norleucine, L-norvaline and L-valine were the most potent. The enzyme is inactivated irreversibly with concomitant release of bisulfite ion. The results demonstrate for the first time that ionic compounds can indeed function as novel inhibitors for the serine proteinases. PMID:3885950

  6. Corrosion inhibitor binding in an acidic medium: Interaction of 2-mercaptobenizmidazole with carbon-steel in hydrochloric acid

    Highlights: • Carbon-steel inhibited by 2-mercaptobenzimidazole in 1 M HCl is examined with XPS. • Data reveal surface termination as a function of corrosion inhibitor concentration. • N 1s spectra suggest that 2-mercaptobenzimidazole adsorbs in two tautomeric forms. • For well-inhibited substrates, adsorption is on film-free carbon-steel. • 2-Mercaptobenzimidazole apparently binds preferentially to active corrosion sites. - Abstract: Mechanistic understanding of the functionality of organic corrosion inhibitors in acidic media is essential to knowledge-based performance optimization. In this study, we address a key issue hindering progress in this area, namely the chemical nature of the corrosion inhibitor/substrate interface. X-ray photoelectron spectroscopy (XPS) is employed to reveal the surface termination of carbon-steel, following immersion in 1 M hydrochloric acid inhibited with 2-mercaptobenzimidazole (MBI). Core level spectra indicate that the termination varies as a function of MBI concentration, with the interface consisting of MBI bound to film-free carbon-steel on highly inhibited substrates

  7. THE EFFECT OF METHANOGENIC INHIBITOR FEED ON PROPIONIC ACID AND LAMB MEAT CHEMICAL QUALITY

    E. Suryanto

    2012-09-01

    Full Text Available This study aimed to determine the effect of medium chain fatty acids (MCFA on propionic acids and lamb meat chemical quality. The treatment given was R1: feed without medium chain fatty acids (MCFA, while R2 dan R3 were the feed contained 1.0% and 1.5% of MCFA, respectively. The twelve heads of lambs yearling weight of 16-17 kg were used as materials. Biological trial was done for three months and then was slaughtered. Before being slaughtered, the animal was taken rumen fluid to be analyzed for propionic acid. The carcass was sampled to be analyzed for chemical composition, cholesterol and fatty acids content. This study showed that methanogenic inhibitor feed with 1.0-1.5% MCFA could be used as sheep feed, and the results: the propionic acid content in rumen increased 29.59 – 36.11%. The cholesterol content decreased 7.14-10.06%. For the meat fatty acids composition, unsaturated fatty acids increased 9.05 – 17.96%. while saturated fatty acid decreased 6.59 – 11.88%.

  8. Garcinia indica as an Environmentally Safe Corrosion Inhibitor for Aluminium in 0.5 M Phosphoric Acid

    Deepa Prabhu; Padmalatha Rao

    2013-01-01

    The Inhibitive and adsorption properties of aqueous extract of seeds of Garcinia indica extract (GIE) have been studied for corrosion control of aluminium in 0.5 M phosphoric acid solution using potentiodynamic polarization and electrochemical impedance spectroscopy (EIS) techniques at 30∘C to 50∘C. The effects of inhibitor concentration on the inhibition action were investigated. Polarization measurements showed that the GIE acted as mixed inhibitor and the inhibitor molecules followed chemi...

  9. Comparative Study of Elaeis Guiniensis Exudates (Palm Wine as a Corrosion Inhibitor for Mild Steel in Acidic and Basic Solutions

    S.C. Nwigbo

    2012-01-01

    Full Text Available This study has explored the possibility of using a typical plant extract other than the use of conventional materials as corrosion inhibitor. Elaeis guinensis exudates (Palm wine, which contains carbonyl groups, double bonds and triple bonds as shown by the FTIR, Gas chromatography-mass spectrometry and phytochemical tests is a one of good natural materials as corrosion inhibitor. This paper was focused on the behaviour of palm wine as corrosion inhibitor for mild steel in (0.1 and 0.5 M H2SO4 and NaOH solutions at 303 and 333 K temperatures and inhibitor concentrations using weight loss measurement. Results showed that weight loss decreases as concentration of both solutions studied increase. The inhibitor performs better under the basic solution compared to the acidic solution. The kinetics results showed that activation energy increases as temperature and inhibitors concentration increase. Palm wine inhibitor adsorbed on the surface of mild steel through physical adsorption.

  10. Crystallization and preliminary X-ray crystallographic studies of omega-transaminase from Vibrio fluvialis JS17

    The omega-transaminase from V. fluvialis JS17 was crystallized. Crystals were found to belong to the orthorhombic space group P212121, with unit-cell parameters a = 78.43, b = 95.95, c = 122.89 Å. The crystals were obtained at 293 K and diffracted to a resolution of 2.5 Å. Omega-transaminase (ω-TA) catalyzes the transfer of an amino group from a non-α-position amino acid or an amine compound with no carboxylic group to an amino acceptor. ω-TA from Vibrio fluvialis JS17 (ω-TAVf) is a novel amine:pyruvate transaminase that is capable of stereoselective transamination of aryl chiral amines. In this study, ω-TAVf was overexpressed in Escherichia coli with engineered C-terminal His tags. ω-TAVf was then purified to homogeneity and crystallized at 292 K. X-ray diffraction data were collected to a resolution of 2.5 Å from a crystal belonging to the orthorhombic space group P212121, with unit-cell parameters a = 78.43, b = 95.95, c = 122.89 Å

  11. Suppression of asymmetric acid efflux and gravitropism in maize roots treated with auxin transport inhibitors of sodium orthovanadate

    Mulkey, T. J.; Evans, M. L.

    1982-01-01

    In gravitropically stimulated roots of maize (Zea mays L., hybrid WF9 x 38MS), there is more acid efflux on the rapidly growing upper side than on the slowly growing lower side. In light of the Cholodny/Went hypothesis of gravitropism which states that gravitropic curvature results from lateral redistribution of auxin, the effects of auxin transport inhibitors on the development of acid efflux asymmetry and curvature in gravistimulated roots were examined. All the transport inhibitors tested prevented both gravitropism and the development of asymmetric acid efflux in gravistimulated roots. The results indicate that auxin redistribution may cause the asymmetry of acid efflux, a finding consistent with the Cholodny/Went hypothesis of gravitropism. As further evidence that auxin-induced acid efflux asymmetry may mediate gravitropic curvature, sodium orthovanadate, an inhibitor of auxin-induced H+ efflux was found to prevent both gravitropism and the development of asymmetric acid efflux in gravistimulated roots.

  12. Steel Corrosion Inhibition by Acid Garlic Essential Oil as a Green Corrosion Inhibitor a nd Sorption Behavior

    Afia, L.; Benali, O.; Salghi, R.; Ebenso, Eno E.; Jodeh, S.; Zougagh, M.; Hammouti, B.

    2014-01-01

    The aim of this work was to investigate the inhibition effect of acid garlic essential oil (GO oil) as an inhibitor on the corrosion of carbon steel in a 1M HCl solution at different temperatures by weight loss,electrochemical impedance spectroscopy (EIS) and potentiodynamic polarization methods. The GO oil acts as an effective corrosion inhibitor for carbon steel in a hydrochloric acid medium. The inhibition process is attributed to the formatio...

  13. Aminocarnitine and acylaminocarnitines: Carnitine acyltransferase inhibitors affecting long-chain fatty acid and glucose metabolism

    DL-Aminocarnitine (DL-3-amino-4-trimethylaminobutyrate) and the acylaminocarnitines acetyl-, decanoyl- and palmitoyl-DL-aminocarnitine have been synthesized and tested as inhibitors of carnitine palmitoyl-transferase and carnitine acetyltransferase in vitro and in vivo. Acetyl-DL-aaminocarnitine is the most potent reversible inhibitor of carnitine acetyltransferase reported to date, and is competitive with respect to acetyl-L-carnitine. Mice given acetyl-DL-aminocarnitine metabolize [U-14C]acetyl-L-carnitine at about 60% of the rate of control mice. Palmitoyl-DL-aminocarnitine is the most potent reversible inhibitor of carnitine palmitoyltransferase reported to date. Decanoyl-DL-aminocarnitine and DL-aminocarnitine are also very potent inhibitors; all compounds inhibit the catabolism of [14C]palmitate to 14CO2 in intact mice by at least 50%. Carnitine palmitoyltransferase controls the entry of long-chain fatty acids into the mitochondrial matrix for β-oxidation. The inhibition of carnitine palmitoyltransferase by aminocarnitine or acylaminocarnitines in vivo prevents or reverses ketogenesis in fasted mice, and causes the reversible accumulation of triglycerides in liver, kidney and plasma. Administration of DL-aminocarnitine to streptozotocindiabetic mice lowers plasma glucose levels and improves the glucose tolerance test

  14. Chemical Genetics Uncovers Novel Inhibitors of Lignification, Including p-Iodobenzoic Acid Targeting CINNAMATE-4-HYDROXYLASE.

    Van de Wouwer, Dorien; Vanholme, Ruben; Decou, Raphaël; Goeminne, Geert; Audenaert, Dominique; Nguyen, Long; Höfer, René; Pesquet, Edouard; Vanholme, Bartel; Boerjan, Wout

    2016-09-01

    Plant secondary-thickened cell walls are characterized by the presence of lignin, a recalcitrant and hydrophobic polymer that provides mechanical strength and ensures long-distance water transport. Exactly the recalcitrance and hydrophobicity of lignin put a burden on the industrial processing efficiency of lignocellulosic biomass. Both forward and reverse genetic strategies have been used intensively to unravel the molecular mechanism of lignin deposition. As an alternative strategy, we introduce here a forward chemical genetic approach to find candidate inhibitors of lignification. A high-throughput assay to assess lignification in Arabidopsis (Arabidopsis thaliana) seedlings was developed and used to screen a 10-k library of structurally diverse, synthetic molecules. Of the 73 compounds that reduced lignin deposition, 39 that had a major impact were retained and classified into five clusters based on the shift they induced in the phenolic profile of Arabidopsis seedlings. One representative compound of each cluster was selected for further lignin-specific assays, leading to the identification of an aromatic compound that is processed in the plant into two fragments, both having inhibitory activity against lignification. One fragment, p-iodobenzoic acid, was further characterized as a new inhibitor of CINNAMATE 4-HYDROXYLASE, a key enzyme of the phenylpropanoid pathway synthesizing the building blocks of the lignin polymer. As such, we provide proof of concept of this chemical biology approach to screen for inhibitors of lignification and present a broad array of putative inhibitors of lignin deposition for further characterization. PMID:27485881

  15. Synergism of Antifungal Activity between Mitochondrial Respiration Inhibitors and Kojic Acid

    Ronald P. Haff

    2013-01-01

    Full Text Available Co-application of certain types of compounds to conventional antimicrobial drugs can enhance the efficacy of the drugs through a process termed chemosensitization. We show that kojic acid (KA, a natural pyrone, is a potent chemosensitizing agent of complex III inhibitors disrupting the mitochondrial respiratory chain in fungi. Addition of KA greatly lowered the minimum inhibitory concentrations of complex III inhibitors tested against certain filamentous fungi. Efficacy of KA synergism in decreasing order was pyraclostrobin > kresoxim-methyl > antimycin A. KA was also found to be a chemosensitizer of cells to hydrogen peroxide (H2O2, tested as a mimic of reactive oxygen species involved in host defense during infection, against several human fungal pathogens and Penicillium strains infecting crops. In comparison, KA-mediated chemosensitization to complex III inhibitors/H2O2 was undetectable in other types of fungi, including Aspergillus flavus, A. parasiticus, and P. griseofulvum, among others. Of note, KA was found to function as an antioxidant, but not as an antifungal chemosensitizer in yeasts. In summary, KA could serve as an antifungal chemosensitizer to complex III inhibitors or H2O2 against selected human pathogens or Penicillium species. KA-mediated chemosensitization to H2O2 seemed specific for filamentous fungi. Thus, results indicate strain- and/or drug-specificity exist during KA chemosensitization.

  16. Aminocarnitine and acylaminocarnitines: Carnitine acyltransferase inhibitors affecting long-chain fatty acid and glucose metabolism

    Clark, D.J.

    1989-01-01

    DL-Aminocarnitine (DL-3-amino-4-trimethylaminobutyrate) and the acylaminocarnitines acetyl-, decanoyl- and palmitoyl-DL-aminocarnitine have been synthesized and tested as inhibitors of carnitine palmitoyl-transferase and carnitine acetyltransferase in vitro and in vivo. Acetyl-DL-aaminocarnitine is the most potent reversible inhibitor of carnitine acetyltransferase reported to date, and is competitive with respect to acetyl-L-carnitine. Mice given acetyl-DL-aminocarnitine metabolize (U-{sup 14}C)acetyl-L-carnitine at about 60% of the rate of control mice. Palmitoyl-DL-aminocarnitine is the most potent reversible inhibitor of carnitine palmitoyltransferase reported to date. Decanoyl-DL-aminocarnitine and DL-aminocarnitine are also very potent inhibitors; all compounds inhibit the catabolism of ({sup 14}C)palmitate to {sup 14}CO{sub 2} in intact mice by at least 50%. Carnitine palmitoyltransferase controls the entry of long-chain fatty acids into the mitochondrial matrix for {beta}-oxidation. The inhibition of carnitine palmitoyltransferase by aminocarnitine or acylaminocarnitines in vivo prevents or reverses ketogenesis in fasted mice, and causes the reversible accumulation of triglycerides in liver, kidney and plasma. Administration of DL-aminocarnitine to streptozotocindiabetic mice lowers plasma glucose levels and improves the glucose tolerance test.

  17. Pronounced radiosensitization of cultured human cancer cells by COX inhibitor under acidic microenvironment

    Purpose: To demonstrate the influence of pH on the cytotoxicity and radiosensitization by COX (cyclooxygenase) -1 and -2 inhibitors using established human cancer cells in culture. Methods and Materials: Nonselective COX inhibitor, ibuprofen (IB), and selective COX-2 inhibitor, SC-236, were used to determine the cytotoxicity and radiosensitization at varying pH of culture media. Human colon carcinoma cell line (HT-29) was exposed to the drug alone and in combination with radiation at different pH of the cell culture media. The end point was clonogenic ability of the single-plated cells after the treatment. Results: Cytotoxicity and radiosensitization of IB increased with higher drug concentration and longer exposure time. The most significant radiosensitization was seen with IB (1.5 mM) for 2-h treatment at pH 6.7 before irradiation. The dose-modifying factor as defined by the ratio of radiation doses required to achieve the same effect on cell survival was 1.8 at 10% survival level. In contrast, SC-236 (50 μM for 2-8 h) showed no pH-dependent cytotoxicity. There was modest increase in the cell killing at lower doses of radiation. Conclusion: An acidic pH was an important factor affecting the increased cytotoxicity and radiosensitization by ibuprofen. Radiation response was enhanced at shoulder portion of the cell survival curve by selective COX-2 inhibitor

  18. Effect of carbonyl inhibitors and their H₂O₂ detoxification on lactic acid fermentation.

    Li, Jing; Zhu, Caiqing; Tu, Maobing; Han, Pingping; Wu, Yonnie

    2015-04-01

    Biomass degradation compounds significantly inhibit biochemical conversion of biomass prehydrolysates to biofuels and chemicals, such as lactic acid. To characterize the structure-activity relationship of carbonyl inhibition on lactic acid fermentation, we examined effects of eight carbonyl compounds (furfural, 5-hydroxymethyl furfural, vanillin, syringaldehyde, 4-hydroxybenzaldehyde, phthalaldehyde, benzoic acid, and pyrogallol aldehyde) and creosol on lactic acid production by Lactobacillus delbrueckii. Pyrogallol aldehyde reduced the cell growth rate by 35 % at 1.0 mM and inhibited lactic acid production completely at 2.0 mM. By correlating the molecular descriptors to the inhibition constants in lactic acid fermentation, we found a good relationship between the hydrophobicity (Log P) of aldehydes and their inhibition constants in fermentation. The inhibitory effect of carbonyl inhibitors appeared to correlate with their thiol reactivity as well. In addition, we found that H2O2 detoxified pyrogallol aldehyde and phthalaldehyde inhibitory activity. H2O2 detoxification was applied to real biomass prehydrolysates in lactic acid fermentation. PMID:25666370

  19. N-substituted aminomethanephosphonic and aminomethane-P-methylphosphinic acids as inhibitors of ureases.

    Berlicki, Lukasz; Bochno, Marta; Grabowiecka, Agnieszka; Białas, Arkadiusz; Kosikowska, Paulina; Kafarski, Paweł

    2012-05-01

    Small unextended molecules based on the diamidophosphate structure with a covalent carbon-to-phosphorus bond to improve hydrolytic stability were developed as a novel group of inhibitors to control microbial urea decomposition. Applying a structure-based inhibitor design approach using available crystal structures of bacterial urease, N-substituted derivatives of aminomethylphosphonic and P-methyl-aminomethylphosphinic acids were designed and synthesized. In inhibition studies using urease from Bacillus pasteurii and Canavalia ensiformis, the N,N-dimethyl derivatives of both lead structures were most effective with dissociation constants in the low micromolar range (Ki=13±0.8 and 0.62±0.09 μM, respectively). Whole-cell studies on a ureolytic strain of Proteus mirabilis showed the high efficiency of N,N-dimethyl and N-methyl derivatives of aminomethane-P-methylphosphinic acids for urease inhibition in pathogenic bacteria. The high hydrolytic stability of selected inhibitors was confirmed over a period of 30 days using NMR technique. PMID:21559954

  20. Valproic Acid Antagonizes the Capacity of Other Histone Deacetylase Inhibitors To Activate the Epstein-Barr Virus Lytic Cycle▿

    Daigle, Derek; Gradoville, Lyn; Tuck, David; Schulz, Vince; Wang'ondu, Ruth; Ye, Jianjiang; Gorres, Kelly; Miller, George

    2011-01-01

    Diverse stimuli reactivate the Epstein-Barr virus (EBV) lytic cycle in Burkitt lymphoma (BL) cells. In HH514-16 BL cells, two histone deacetylase (HDAC) inhibitors, sodium butyrate (NaB) and trichostatin A (TSA), and the DNA methyltransferase inhibitor azacytidine (AzaCdR) promote lytic reactivation. Valproic acid (VPA), which, like NaB, belongs to the short-chain fatty acid class of HDAC inhibitors, fails to induce the EBV lytic cycle in these cells. Nonetheless, VPA behaves as an HDAC inhib...

  1. Discovery of arjunolic acid as a novel non-zinc binding carbonic anhydrase II inhibitor.

    Kalyanavenkataraman, Subhalakshmi; Nanjan, Pandurangan; Banerji, Asoke; Nair, Bipin G; Kumar, Geetha B

    2016-06-01

    Elevated levels of carbonic anhydrase II (CA II) have been shown to be associated with cardiac hypertrophy and heart failure. Although arjunolic acid (AA) has a diverse range of therapeutic applications including cardio-protection, there have been no reports on the effect of AA on CA II. The present study describes for the first time, the novel zinc independent inhibition of CA II by AA. The molecular docking studies of AA indicated that the hydroxyl group at C2 of the A-ring, which hydrogen bonds with the catalytic site residues (His64, Asn62 and Asn67), along with the gem-dimethyl group at C20 of the E-ring, greatly influences the inhibitory activity, independent of the catalytic zinc, unlike the inhibition observed with most CA II inhibitors. Among the triterpenoids tested viz. arjunolic acid, arjunic acid, asiatic acid, oleanolic acid and ursolic acid, AA was the most potent in inhibiting CA II in vitro with an IC50 of 9μM. It was interesting to note, that in spite of exhibiting very little differences in their structures, these triterpenoids exhibited vast differences in their inhibitory activities, with IC50 values ranging from 9μM to as high as 333μM. Furthermore, AA also inhibited the cytosolic activity of CA in H9c2 cardiomyocytes, as reflected by the decrease in acidification of the intracellular pH (pHi). The decreased acidification reduced the intracellular calcium levels, which further prevented the mitochondrial membrane depolarization. Thus, these studies provide a better understanding for establishing the novel molecular mechanism involved in CA II inhibition by the non-zinc binding inhibitor AA. PMID:27038848

  2. Synthesis, activity evaluation, and docking analysis of barbituric acid aryl hydrazone derivatives as RSK2 inhibitors.

    Xue, Mengzhu; Xu, Minghao; Lu, Weiqiang; Huang, Jin; Li, Honglin; Xu, Yufang; Liu, Xiaofeng; Zhao, Zhenjiang

    2013-08-01

    The 90 kDa ribosomal S6 kinases (RSKs), especially RSK2, have attracted attention for the development of new anticancer agents. Through structural optimization of the hit compound 1 from our previous study, a series of barbituric acid aryl hydrazone analogues were designed and synthesized as potential RSK2 inhibitors. The most potent one, compound 9, showed a higher activity against RSK2 with an IC50 value of 1.95 μM. To analyze and elucidate their structure-activity relationship, the homology model of RSK2 N-terminal kinase domain was built and molecular docking simulations were performed, which provide helpful clues to design new inhibitors with desired activities. PMID:22545939

  3. Molecular Structure of Phenylthiourea as a Corrosion Inhibitor for Mild Steel in Hydrochloric Acid

    Anees A, Khadom

    2011-01-01

    The application of statistical analysis and quantum chemical models on the corrosion inhibition of mild steel in hydrochloric acid in presence of phenylthiourea (PTU) as corrosion inhibitor have been investigated. Two mathematical models were used, second order polynomial model and Arrhenius type equation model. STATISTICA software based on Levenberg-Marquardt estimation method was used to evaluate the coefficients of two Models. It follows that the two models were suitable to represent the corrosion rate data at different conditions. The correlation coefficient of second order polynomial model was 0.973, while for the Arrhenius type model was 0.919. The structure of inhibitor was optimized by ArgusLab 4.0.1 package. The quantum chemical parameters (EHoMO, ELUMO, AE, and dipole moment μ) were estimated by PM3-SCF method.

  4. Mangrove tannins and their flavanoid monomers as alternative steel corrosion inhibitors in acidic medium

    Rahim, Afidah A. [School of Chemical Sciences, University Sains Malaysia, 11800 Penang (Malaysia)]. E-mail: afidah@usm.my; Rocca, E. [Laboratoire de Chimie du Solide Mineral, Universite Henri Poincare, Nancy I BP 239, 54506 Vandoeuvre Les Nancy (France); Steinmetz, J. [Laboratoire de Chimie du Solide Mineral, Universite Henri Poincare, Nancy I BP 239, 54506 Vandoeuvre Les Nancy (France); Kassim, M.J. [School of Chemical Sciences, University Sains Malaysia, 11800 Penang (Malaysia); Adnan, R. [School of Chemical Sciences, University Sains Malaysia, 11800 Penang (Malaysia); Sani Ibrahim, M. [School of Chemical Sciences, University Sains Malaysia, 11800 Penang (Malaysia)

    2007-02-15

    The inhibitive behaviour on steel of flavanoid monomers that constitute mangrove tannins namely catechin, epicatechin, epigallocatechin and epicatechingallate was investigated in an aerated HCl solution via electrochemical methods. The monomers were found to be mainly cathodic inhibitors and the inhibition efficiency was dependent on concentration. To explain the adsorptive behaviour of the molecules on the steel surface, a semiempirical approach involving quantum chemical calculations using HyperChem 6.0 was undertaken. The HOMO electronic density of the molecule was used to explain the inhibiting mechanism. The most probable adsorption centers were found in the vicinity of the phenolic groups. In a second part, the use of mangrove tannin, extracted from the mangrove barks as steel corrosion inhibitors in acidic media was investigated and its inhibitive efficiency was compared with that of commercial mimosa, quebracho and chestnut tannins. The inhibitive performance of mangrove tannins was comparable to the other tannins investigated, indicating their potential in corrosion protection.

  5. Mangrove tannins and their flavanoid monomers as alternative steel corrosion inhibitors in acidic medium

    The inhibitive behaviour on steel of flavanoid monomers that constitute mangrove tannins namely catechin, epicatechin, epigallocatechin and epicatechingallate was investigated in an aerated HCl solution via electrochemical methods. The monomers were found to be mainly cathodic inhibitors and the inhibition efficiency was dependent on concentration. To explain the adsorptive behaviour of the molecules on the steel surface, a semiempirical approach involving quantum chemical calculations using HyperChem 6.0 was undertaken. The HOMO electronic density of the molecule was used to explain the inhibiting mechanism. The most probable adsorption centers were found in the vicinity of the phenolic groups. In a second part, the use of mangrove tannin, extracted from the mangrove barks as steel corrosion inhibitors in acidic media was investigated and its inhibitive efficiency was compared with that of commercial mimosa, quebracho and chestnut tannins. The inhibitive performance of mangrove tannins was comparable to the other tannins investigated, indicating their potential in corrosion protection

  6. Punica granatum leave extract as green corrosion inhibitor for mild steel in Hydrochloric acid

    Abboud Y.

    2013-09-01

    Full Text Available Leave of Punica granatum extract (LPGE as green inhibitor for the corrosion of mild steel in 1M HCl solution was studied using weight-loss and potentiodynamic polarization measurements. The results obtained revealed that LPGE has fairly good inhibiting properties for mild steel corrosion in 1M HCl solution, with efficiency of around 94 % at a concentration of 1 g/l. The inhibition was of a mixed anodic–cathodic nature. The film which is formed over the metal surface was analysed by FT-IR spectroscopy. Further examination using X-ray diffraction confirms the role of LPGE as an effective corrosion inhibitor for mild steel in acid media.

  7. Synthesis and characterization of phosphocitric acid, a potent inhibitor of hydroxylapatite crystal growth.

    Tew, W P; Mahle, C; Benavides, J; Howard, J E; Lehninger, A L

    1980-04-29

    Human urine and extracts of rat liver mitochondria contain apparently identical agents capable of inhibiting the precipitation or crystallization of calcium phosphate. Its general properties, as well as 1H NMR and mass spectra, have suggested that the agent is phosphocitric acid. This paper reports the synthesis of phosphocitric acid via the phosphorylation of triethyl citrate with o-phenylene phosphochloridate, hydrogenolysis of the product to yield triethyl phosphocitrate, hydrolytic removal of the blocking ethyl groups and also chromatographic purification. An enzymatic assay of phosphocitrate is described. Synthetic phosphocitrate was found to be an exceedingly potent inhibitor of the growth of hydroxylapatite seed crystals in a medium supersaturated with respect to Ca2+ and phosphate. Comparative assays showed phosphocitrate to be much more potent than the most active precipitation-crystallization inhibitors previously reported, which include pyrophosphate and ATP. 14C-Labeled phosphocitrate was bound very tightly to hydroxylapatite crystals. Such binding appeared to be essential for its inhibitory activity on crystal growth. Citrate added before but not after, phosphocitrate greatly enhanced the inhibitory potency of the latter. This enhancement effect was not given by other tricarboxylic acids. The monoethyl ester of phosphocitrate had no inhibitory effect on hydroxylapatite crystal growth. PMID:7378389

  8. C-3 benzoic acid derivatives of C-3 deoxybetulinic acid and deoxybetulin as HIV-1 maturation inhibitors.

    Liu, Zheng; Swidorski, Jacob J; Nowicka-Sans, Beata; Terry, Brian; Protack, Tricia; Lin, Zeyu; Samanta, Himadri; Zhang, Sharon; Li, Zhufang; Parker, Dawn D; Rahematpura, Sandhya; Jenkins, Susan; Beno, Brett R; Krystal, Mark; Meanwell, Nicholas A; Dicker, Ira B; Regueiro-Ren, Alicia

    2016-04-15

    A series of C-3 phenyl- and heterocycle-substituted derivatives of C-3 deoxybetulinic acid and C-3 deoxybetulin was designed and synthesized as HIV-1 maturation inhibitors (MIs) and evaluated for their antiviral activity and cytotoxicity in cell culture. A 4-subsituted benzoic acid moiety was identified as an advantageous replacement for the 3'3'-dimethylsuccinate moiety present in previously disclosed MIs that illuminates new aspects of the topography of the pharmacophore. The new analogs exhibit excellent in vitro antiviral activity against wild-type (wt) virus and a lower serum shift when compared with the prototypical HIV-1 MI bevirimat (1, BVM), the first MI to be evaluated in clinical studies. Compound 9a exhibits comparable cell culture potency toward wt virus as 1 (WT EC50=16nM for 9a compared to 10nM for 1). However, the potency of 9a is less affected by the presence of human serum, while the compound displays a similar pharmacokinetic profile in rats to 1. Hence 9a, the 4-benzoic acid derivative of deoxybetulinic acid, represents a new starting point from which to explore the design of a 2nd generation MI. PMID:26968652

  9. Benzimidazole as corrosion inhibitor for heat treated 6061 Al- SiCp composite in acetic acid

    Chacko, Melby; Nayak, Jagannath

    2015-06-01

    6061 Al-SiCpcomposite was solutionizedat 350 °C for 30 minutes and water quenched. It was then underaged at 140 °C (T6 treatment). The aging behaviour of the composite was studied using Rockwell B hardness measurement. Corrosion behaviour of the underaged sample was studied in different concentrations of acetic acid and at different temperatures. Benzimidazole at different concentrations was used for the inhibition studies. Inhibition efficiency of benzimidazole was calculated for different experimental conditions. Thermodynamic parameters were found out which suggested benzimidazole is an efficient inhibitor and it adsorbed on to the surface of composite by mixed adsorption where chemisorption is predominant.

  10. Integrase Inhibitor Prodrugs: Approaches to Enhancing the Anti-HIV Activity of β-Diketo Acids

    Vasu Nair; Maurice Okello

    2015-01-01

    HIV integrase, encoded at the 3′-end of the HIV pol gene, is essential for HIV replication. This enzyme catalyzes the incorporation of HIV DNA into human DNA, which represents the point of “no-return” in HIV infection. Integrase is a significant target in anti-HIV drug discovery. This review article focuses largely on the design of integrase inhibitors that are β-diketo acids constructed on pyridinone scaffolds. Methodologies for synthesis of these compounds are discussed. Integrase inhibiti...

  11. Myrsinoic A acid and its derivative: in vitro inhibitors of photosynthesis

    Myrsinoic A acid, isolated from Myrsine cuneifolia and its hydrogenated derivative had their effect on photosynthesis tested. The compounds inhibited the electron flow (basal, phosphorylating and uncoupled) from water to methyl viologen; therefore, they act as Hill reaction inhibitors in spinach thylakoids. They inhibited partial reactions of PSII electron flow from water to 2,5-dichloro-1,4-benzoquinone, from water to sodium silicomolybdate, and partially electron flow from diphenylcarbazide to 2,6-dichloroindophenol. Their inhibition sites were at the donor and acceptor sides of PSII, between P680 and QA. Chlorophyll α fluorescence measurements confirmed the behavior of the compounds (pool of quinones). (author)

  12. THE STUDY OF HENNA LEAVES EXTRACT AS GREEN CORROSION INHIBITOR FOR MILD STEEL IN ACETIC ACID.

    H. G. Chaudhari

    2016-05-01

    Full Text Available The inhibitive action of henna leaves extract on mild steel in acetic acid solution have been investigated by weight-loss, A C impedence and potentiodynamic polarization measurements. The study indicates that as acid concentration increases corrosion rate increases. The corrosion inhibition efficiency increases with increase in concentration of extract. The result obtained revealed that henna leaves extract act as efficient inhibitor. The adsorption of the henna leaves extract obeyed Langmuir adsorption isotherm. The calculated thermodynamic parameters indicated that the adsorption was a spontaneous, exothermic process accompanied by an increase in entropy. Cathodic and anodic polarization curves show that henna leaves extract is a mixed-type inhibitor. Normal 0 false false false EN-IN X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin-top:0cm; mso-para-margin-right:0cm; mso-para-margin-bottom:10.0pt; mso-para-margin-left:0cm; line-height:115%; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;}   ABSTRACT:    The inhibitive action of henna leaves extract on mild steel in acetic acid solution have been investigated by weight-loss, A C impedence and potentiodynamic polarization measurements. The study indicates that as acid concentration increases corrosion rate increases. The corrosion inhibition efficiency increases with increase in concentration of extract. The result obtained revealed that henna leaves extract act as efficient inhibitor. The adsorption of the henna leaves

  13. Synthesis of water soluble glycosides of pentacyclic dihydroxytriterpene carboxylic acids as inhibitors of α-glucosidase.

    Xu, Jiancong; Nie, Xuliang; Hong, Yanping; Jiang, Yan; Wu, Guoqiang; Yin, Xiaoli; Wang, Chunrong; Wang, Xiaoqiang

    2016-04-01

    A series of compounds were synthesized by glycosylation of maslinic acid (MA) and corosolic acid (CA) with monosaccharides and disaccharides, and the structures of the derivatives were elucidated by standard spectroscopic methods including (1)H NMR, (13)C NMR and HRMS. The α-glucosidase inhibitory activities of all the novel compounds were evaluated in vitro. The solubility and inhibitory activity of α-glucosidase assays showed that the bis-disaccharide glycosides of triterpene acids possessed higher water solubility and α-glucosidase inhibitory activities than the bis-monosaccharide glycosides. Among these compounds, maslinic acid bis-lactoside (8e, IC50 = 684 µM) and corosolic acid bis-lactoside (9e, IC50 = 428 µM) had the best water solubility, and 9e exhibited a better inhibitory activity than acarbose (IC50 = 478 µM). However, most of glycosylated derivatives possessed lower inhibitory activities than the parent compounds, although their water solubility was enhanced obviously. Moreover, the kinetic inhibition studies indicated that 9e was a non-competitive inhibitor, and structure-activity relationships of the derivatives are also discussed. PMID:26974355

  14. Antibacterial drugs as corrosion inhibitors for bronze surfaces in acidic solutions

    Graphical abstract: - Highlights: • All four investigated antibacterial drugs act as corrosion inhibitors for bronze surface. • In the presence of antibiotics, a 3RC electric circuit simulates the corrosion system. • The electrochemical results indicate as best inhibitors Doxy, followed by Strepto. • HOMO–LUMO energy gap increases in the order: Doxy > Strepto > Cipro > Amoxi. • The thin protective film on bronze is reinforced by the presence of the antibiotics. - Abstract: The present study is aiming to investigate the effect of four antibiotics (amoxicillin, ciprofloxacin, doxycycline and streptomycin,) belonging to different classes of antibacterial drugs on bronze corrosion in a solution simulating an acid rain (pH 4). Due to their ability to form protective films on the metal surface, the tested antibiotics act as corrosion inhibitors for bronze. The antibiotics were tested at various concentrations in order to determine the optimal concentration range for the best corrosion inhibiting effect. In evaluating the inhibition efficiency, polarization curves, electrochemical impedance spectroscopy, SEM and XPS measurements were used. Moreover, a correlation between the inhibition efficiency of some antibacterial drugs and certain molecular parameters was determined by quantum chemical computations. Parameters like energies EHOMO and ELUMO and HOMO–LUMO energy gap were used for correlation with the corrosion data

  15. Epigenetic suppression of the antitumor cytotoxicity of NK cells by histone deacetylase inhibitor valproic acid

    Shi, Xiumin; Li, Min; Cui, Meizi; Niu, Chao; Xu, Jianting; Zhou, Lei; Li, Wei; Gao, Yushun; Kong, Weisheng; Cui, Jiuwei; Hu, Jifan; Jin, Haofan

    2016-01-01

    Natural killer (NK) cells play an essential role in the fight against tumor development. The therapeutic use of autologous NK cells has been exploited to treat human malignancies, yet only limited antitumor activity is observed in cancer patients. In this study, we sought to augment the antitumor activity of NK cells using epigenetic approaches. Four small molecules that have been known to promote epigenetic reprogramming were tested for their ability to enhance the activity of NK cells. Using a tumor cell lysis assay, we found that the DNA demethylating agent 5-azacytidine and vitamin C did not significantly affect the tumor killing ability of NK cells. The thyroid hormone triiodothyronine (T3) slightly increased the activity of NK cells. The histone deacetylase inhibitor valproic acid (VPA), however, inhibited NK cell lytic activity against leukemic cells in a dose-dependent manner. Pretreatment using VPA reduced IFNγ secretion, impaired CD107a degranulation, and induced apoptosis by activating the PD-1/PD-L1 pathway. VPA downregulated the expression of the activating receptor NKG2D (natural-killer group 2, member D) by inducing histone K9 hypermethylation and DNA methylation in the gene promoter. Histone deacetylase inhibitors have been developed as anticancer agents for use as monotherapies or in combination with other anticancer therapies. Our data suggest that the activity of histone deacetylase inhibitors on NK cell activity should be considered in drug development.

  16. A pharmaceutical product as corrosion inhibitor for carbon steel in acidic environments.

    Samide, Adriana

    2013-01-01

    A pharmaceutical product, Trimethoprim (TMP), IUPAC name: 5-(3,4,5-trimethoxybenzyl)pyrimidine-2,4-diamine was investigated, as inhibitor to prevent carbon steel corrosion in acidic environments. The study was performed using weight loss and electrochemical measurements, in temperatures ranging between 25-55°C. The surface morphology before and after corrosion of carbon steel in 1.0 M HCl solution in the presence and absence of TMP was evaluated using scanning electron microscopy (SEM). The inhibition efficiency (IE) increased with the increasing of the inhibitor concentration, reaching a maximum value of 92% at 25°C and 0.9 mM TMP, and decreased with increasing temperature. The inhibition of carbon steel corrosion by TMP can be attributed to the adsorption ability of inhibitor molecules onto the reactive sites of the metal surface. The adsorption is spontaneous and it is best described by the Langmuir isotherm. The apparent activation energy (E(a)) for the corrosion process in the absence and presence of TMP was evaluated from Arrhenius equation, to elucidate its inhibitive properties. PMID:23043337

  17. Antibacterial drugs as corrosion inhibitors for bronze surfaces in acidic solutions

    Rotaru, Ileana [Department of Chemical Engineering, “Babes-Bolyai” University, 11 Arany-Janos St., 400028 Cluj-Napoca (Romania); Varvara, Simona, E-mail: svarvara@uab.ro [Department of Exact Sciences and Engineering, “1 Decembrie 1918” University, 11-13 Nicolae Iorga St., 510009 Alba Iulia (Romania); Gaina, Luiza [Department of Chemical Engineering, “Babes-Bolyai” University, 11 Arany-Janos St., 400028 Cluj-Napoca (Romania); Muresan, Liana Maria, E-mail: limur@chem.ubbcluj.ro [Department of Chemical Engineering, “Babes-Bolyai” University, 11 Arany-Janos St., 400028 Cluj-Napoca (Romania)

    2014-12-01

    Graphical abstract: - Highlights: • All four investigated antibacterial drugs act as corrosion inhibitors for bronze surface. • In the presence of antibiotics, a 3RC electric circuit simulates the corrosion system. • The electrochemical results indicate as best inhibitors Doxy, followed by Strepto. • HOMO–LUMO energy gap increases in the order: Doxy > Strepto > Cipro > Amoxi. • The thin protective film on bronze is reinforced by the presence of the antibiotics. - Abstract: The present study is aiming to investigate the effect of four antibiotics (amoxicillin, ciprofloxacin, doxycycline and streptomycin,) belonging to different classes of antibacterial drugs on bronze corrosion in a solution simulating an acid rain (pH 4). Due to their ability to form protective films on the metal surface, the tested antibiotics act as corrosion inhibitors for bronze. The antibiotics were tested at various concentrations in order to determine the optimal concentration range for the best corrosion inhibiting effect. In evaluating the inhibition efficiency, polarization curves, electrochemical impedance spectroscopy, SEM and XPS measurements were used. Moreover, a correlation between the inhibition efficiency of some antibacterial drugs and certain molecular parameters was determined by quantum chemical computations. Parameters like energies E{sub HOMO} and E{sub LUMO} and HOMO–LUMO energy gap were used for correlation with the corrosion data.

  18. Adsorptive removal of fermentation inhibitors from concentrated acid hydrolyzates of lignocellulosic biomass.

    Sainio, Tuomo; Turku, Irina; Heinonen, Jari

    2011-05-01

    Adsorptive purification of concentrated acid hydrolyzate of lignocellulose was investigated. Cation exchange resin (CS16GC), neutral polymer adsorbent (XAD-16), and granulated activated carbon (GAC) were studied to remove furfural, HMF, and acetic acid from a synthetic hydrolyzate containing 20 wt.% H(2)SO(4). Adsorption isotherms were determined experimentally. Loading and regeneration were investigated in a laboratory scale column. GAC has the highest adsorption capacity, but regeneration with water was not feasible. XAD-16 and CS16GC had lower adsorption capacities but also shorter cycle times due to easier regeneration. Productivity increased when regenerating with 50 wt.% EtOH(aq) solution. To compare adsorbents, process performance was quantified by productivity and fraction of inhibitors removed. GAC yields highest performance when high purity is required and ethanol can be used in regeneration. For lower purities, XAD-16 and GAC yield approximately equal performance. When using ethanol must be avoided, CS16GC offers highest productivity. PMID:21441022

  19. Hydrophobic amino acids as a new class of kinetic inhibitors for gas hydrate formation

    Sa, Jeong-Hoon; Kwak, Gye-Hoon; Lee, Bo Ram; Park, Da-Hye; Han, Kunwoo; Lee, Kun-Hong

    2013-08-01

    As the foundation of energy industry moves towards gas, flow assurance technology preventing pipelines from hydrate blockages becomes increasingly significant. However, the principle of hydrate inhibition is still poorly understood. Here, we examined natural hydrophobic amino acids as novel kinetic hydrate inhibitors (KHIs), and investigated hydrate inhibition phenomena by using them as a model system. Amino acids with lower hydrophobicity were found to be better KHIs to delay nucleation and retard growth, working by disrupting the water hydrogen bond network, while those with higher hydrophobicity strengthened the local water structure. It was found that perturbation of the water structure around KHIs plays a critical role in hydrate inhibition. This suggestion of a new class of KHIs will aid development of KHIs with enhanced biodegradability, and the present findings will accelerate the improved control of hydrate formation for natural gas exploitation and the utilization of hydrates as next-generation gas capture media.

  20. Proton pump inhibitor-responsive chronic cough without acid reflux: a case report

    Nobata Kouichi

    2007-08-01

    Full Text Available Abstract Background Because 24-h esophageal pH monitoring is quite invasive, the diagnosis of gastroesophageal reflux disease (GERD-associated cough has usually been made based merely on the clinical efficacy of treatment with proton pump inhibitor (PPI. Case presentation We recently encountered two patients with PPI-responsive chronic non-productive cough for whom switching from bronchodilators and glucocorticosteroids to PPI resulted in improvement of cough. The cough returned nearly to pre-administration level a few weeks after discontinuation of PPI. Though GERD-associated cough was suspected, 24-h esophageal pH monitoring revealed that the cough rarely involved gastric acid reflux. Following re-initiation of PPI, the cough disappeared again. Conclusion PPI may improve cough unrelated to gastric acid reflux.

  1. Potent human uric acid transporter 1 inhibitors: in vitro and in vivo metabolism and pharmacokinetic studies

    Wempe MF

    2012-11-01

    Full Text Available Michael F Wempe,1 Janet W Lightner,2 Bettina Miller,1 Timothy J Iwen,1 Peter J Rice,1 Shin Wakui,3 Naohiko Anzai,4 Promsuk Jutabha,4 Hitoshi Endou51Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA; 2Department of Pharmacology, East Tennessee State University, Johnson City, TN, USA; 3Department of Toxicology, Azabu University School of Veterinary Medicine, Chuo Sagamihara, Kanagawa, Japan; 4Department of Pharmacology and Toxicology, Dokkyo Medical University School of Medicine, Mibu, Shimotsuga, Tochigi, Japan; 5Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Mitaka, Tokyo, JapanAbstract: Human uric acid transporter 1 (hURAT1; SLC22A12 is a very important urate anion exchanger. Elevated urate levels are known to play a pivotal role in cardiovascular diseases, chronic renal disease, diabetes, and hypertension. Therefore, the development of potent uric acid transport inhibitors may lead to novel therapeutic agents to combat these human diseases. The current study investigates small molecular weight compounds and their ability to inhibit 14C-urate uptake in oocytes expressing hURAT1. Using the most promising drug candidates generated from our structure–activity relationship findings, we subsequently conducted in vitro hepatic metabolism and pharmacokinetic (PK studies in male Sprague-Dawley rats. Compounds were incubated with rat liver microsomes containing cofactors nicotinamide adenine dinucleotide phosphate and uridine 5'-diphosphoglucuronic acid. In vitro metabolism and PK samples were analyzed using liquid chromatography/mass spectrometry-mass spectrometry methods. Independently, six different inhibitors were orally (capsule dosing or intravenously (orbital sinus administered to fasting male Sprague-Dawley rats. Blood samples were collected and analyzed; these data were used to compare in vitro and in vivo metabolism and to

  2. Synthesis and Application of Phenyl Nitrone Derivatives as Acidic and Microbial Corrosion Inhibitors

    Shijun Chen

    2015-01-01

    Full Text Available Nitrone has drawn great attention due to its wide applications as a 1,3-dipole in heterocyclic compounds synthesis and the bioactivities. With the special structure, nitrone can also be used as ligand in inorganic chemistry. Based on the current research, the nitrones are anticipated to be effective inhibitors against acidic and microbial corrosion. The aim of this work is to investigate the inhibitory action of nitrones. In this work, a series of phenyl nitrone derivatives (PN was synthesized and used as acidic and microbial corrosion inhibitors. The results indicate that several compounds show moderate to high inhibition efficiency (IE in 3% HCl. Accompanied with HMTA or BOZ, the IEs greatly increase, and the highest efficiency of 98.5% was obtained by using PN4 + BOZ. Investigation of the antibacterial activity against oilfield microorganism shows that the nitrone derivatives can inhibit SRB, IB, and TGB with moderate to high efficiency under 1,000 mg/L, which makes them potential to be used as bifunctional oilfield chemicals.

  3. Integrase Inhibitor Prodrugs: Approaches to Enhancing the Anti-HIV Activity of β-Diketo Acids

    Vasu Nair

    2015-07-01

    Full Text Available HIV integrase, encoded at the 3′-end of the HIV pol gene, is essential for HIV replication. This enzyme catalyzes the incorporation of HIV DNA into human DNA, which represents the point of “no-return” in HIV infection. Integrase is a significant target in anti-HIV drug discovery. This review article focuses largely on the design of integrase inhibitors that are β-diketo acids constructed on pyridinone scaffolds. Methodologies for synthesis of these compounds are discussed. Integrase inhibition data for the strand transfer (ST step are compared with in vitro anti-HIV data. The review also examines the issue of the lack of correlation between the ST enzymology data and anti-HIV assay results. Because this disconnect appeared to be a problem associated with permeability, prodrugs of these inhibitors were designed and synthesized. Prodrugs dramatically improved the anti-HIV activity data. For example, for compound, 96, the anti-HIV activity (EC50 improved from 500 nM for this diketo acid to 9 nM for its prodrug 116. In addition, there was excellent correlation between the IC50 and IC90 ST enzymology data for 96 (6 nM and 97 nM, respectively and the EC50 and EC90 anti-HIV data for its prodrug 116 (9 nM and 94 nM, respectively. Finally, it was confirmed that the prodrug 116 was rapidly hydrolyzed in cells to the active compound 96.

  4. Integrase Inhibitor Prodrugs: Approaches to Enhancing the Anti-HIV Activity of β-Diketo Acids.

    Nair, Vasu; Okello, Maurice

    2015-01-01

    HIV integrase, encoded at the 3'-end of the HIV pol gene, is essential for HIV replication. This enzyme catalyzes the incorporation of HIV DNA into human DNA, which represents the point of "no-return" in HIV infection. Integrase is a significant target in anti-HIV drug discovery. This review article focuses largely on the design of integrase inhibitors that are β-diketo acids constructed on pyridinone scaffolds. Methodologies for synthesis of these compounds are discussed. Integrase inhibition data for the strand transfer (ST) step are compared with in vitro anti-HIV data. The review also examines the issue of the lack of correlation between the ST enzymology data and anti-HIV assay results. Because this disconnect appeared to be a problem associated with permeability, prodrugs of these inhibitors were designed and synthesized. Prodrugs dramatically improved the anti-HIV activity data. For example, for compound, 96, the anti-HIV activity (EC50) improved from 500 nM for this diketo acid to 9 nM for its prodrug 116. In addition, there was excellent correlation between the IC50 and IC90 ST enzymology data for 96 (6 nM and 97 nM, respectively) and the EC50 and EC90 anti-HIV data for its prodrug 116 (9 nM and 94 nM, respectively). Finally, it was confirmed that the prodrug 116 was rapidly hydrolyzed in cells to the active compound 96. PMID:26184144

  5. Amino acid amides of piperic acid (PA) and 4-ethylpiperic acid (EPA) as NorA efflux pump inhibitors of Staphylococcus aureus.

    Wani, Naiem Ahmad; Singh, Samsher; Farooq, Saleem; Shankar, Sudha; Koul, Surrinder; Khan, Inshad Ali; Rai, Rajkishor

    2016-09-01

    A total of eighteen piperic acid (PA) and 4-ethylpiperic acid (EPA) amides (C1-C18) with α-, β- and γ-amino acids were synthesized, characterized and evaluated for their efflux pump inhibitory activity against ciprofloxacin resistant Staphylococcus aureus. The amides were screened against NorA overexpressing S. aureus SA-1199B and wild type S. aureus SA-1199 using ethidium bromide as NorA efflux pump substrate. EPI C6 was found to be most potent and reduced the MIC of ciprofloxacin by 16 fold followed by C18 which showed 4 fold reduction of MIC. Ethidium bromide efflux inhibition and accumulation assay proved these compounds as NorA inhibitors. PMID:27503686

  6. Theoretical study of inhibition efficiencies of some amino acids on corrosion of carbon steel in acidic media: green corrosion inhibitors.

    Dehdab, Maryam; Shahraki, Mehdi; Habibi-Khorassani, Sayyed Mostafa

    2016-01-01

    Inhibition efficiencies of three amino acids [tryptophan (B), tyrosine (c), and serine (A)] have been studied as green corrosion inhibitors on corrosion of carbon steel using density functional theory (DFT) method in gas and aqueous phases. Quantum chemical parameters such as EH OMO (highest occupied molecular orbital energy), E LUMO (lowest unoccupied molecular orbital energy), hardness (η), polarizability ([Formula: see text]), total negative charges on atoms (TNC), molecular volume (MV) and total energy (TE) have been calculated at the B3LYP level of theory with 6-311++G** basis set. Consistent with experimental data, theoretical results showed that the order of inhibition efficiency is tryptophan (B) > tyrosine (C) > serine (A). In order to determine the possible sites of nucleophilic and electrophilic attacks, local reactivity has been evaluated through Fukui indices. PMID:26347374

  7. Identification of a mutation affecting an alanine-alpha-ketoisovalerate transaminase activity in Escherichia coli K-12.

    Falkinham, J O

    1979-10-01

    A mutation affecting alanine-alpha-ketoisovalerate transaminase activity has been shown to be cotransducible with ilv gene cluster. The transaminase deficiency results in conditional isoleucine auxotrophy in the presence of alanine. PMID:396446

  8. In silico modification of suberoylanilide hydroxamic acid (SAHA) as potential inhibitor for class II histone deacetylase (HDAC)

    Tambunan Usman SF; Bramantya N; Parikesit Arli A

    2011-01-01

    Abstract Background The cervical cancer is the second most prevalent cancer for the woman in the world. It is caused by the oncogenic human papilloma virus (HPV). The inhibition activity of histone deacetylase (HDAC) is a potential strategy for cancer therapy. Suberoylanilide hydroxamic acid (SAHA) is widely known as a low toxicity HDAC inhibitor. This research presents in silico SAHA modification by utilizing triazole, in order to obtain a better inhibitor. We conducted docking of the SAHA i...

  9. Inhibition of leukemic cells by valproic acid, an HDAC inhibitor, in xenograft tumors

    Zhang Z

    2013-06-01

    Full Text Available Zhihua Zhang,1 Changlai Hao,1 Lihong Wang,1 Peng Liu,2 Lei Zhao,1 Cuimin Zhu,1 Xia Tian31Hematology Department, Affiliated Hospital of Chengde Medical College, Chengde, Hebei Province, 2Department of Medical Oncology, Shijiazhuang Municipal No 1 Hospital, Hebei Province, 3Department of Medical Oncology, Rizhao Municipal People’s Hospital, Shandong Province, People's Republic of ChinaAbstract: The chimeric fusion protein, AML1-ETO, generated by translocation of t(8;21, abnormally recruits histone deacetylase (HDAC to the promoters of AML1 target genes, resulting in transcriptional repression of the target genes and development of t(8;21 acute myeloid leukemia. Abnormal expression of cyclin-dependent kinase inhibitors, especially p21, is considered a possible mechanism of the arrested maturation and differentiation seen in leukemia cells. A new generation of HDAC inhibitors is becoming an increasing focus of attention for their ability to induce differentiation and apoptosis in tumor cells and to block the cell cycle. Our previous research had demonstrated that valproic acid induces G0/G1 arrest of Kasumi-1 cells in t(8;21 acute myeloid leukemia. In this study, we further confirmed that valproic acid inhibits the growth of Kasumi-1 cells in a murine xenograft tumor model, and that this occurs via upregulation of histone acetylation in the p21 promoter region, enhancement of p21 expression, suppression of phosphorylation of retinoblastoma protein, blocking of transcription activated by E2F, and induction of G0/G1 arrest.Keywords: valproic acid, acute myeloid leukemia, AML1-ETO, p21, E2F

  10. Valproic Acid as a Potential Inhibitor of Plasmodium falciparum Histone Deacetylase 1 (PfHDAC1: An in Silico Approach

    Mohamed A. Abdallah Elbadawi

    2015-02-01

    Full Text Available A new Plasmodium falciparum histone deacetylase1 (PfHDAC1 homology model was built based on the highest sequence identity available template human histone deacetylase 2 structure. The generated model was carefully evaluated for stereochemical accuracy, folding correctness and overall structure quality. All evaluations were acceptable and consistent. Docking a group of hydroxamic acid histone deacetylase inhibitors and valproic acid has shown binding poses that agree well with inhibitor-bound histone deacetylase-solved structural interactions. Docking affinity dG scores were in agreement with available experimental binding affinities. Further, enzyme-ligand complex stability and reliability were investigated by running 5-nanosecond molecular dynamics simulations. Thorough analysis of the simulation trajectories has shown that enzyme-ligand complexes were stable during the simulation period. Interestingly, the calculated theoretical binding energies of the docked hydroxamic acid inhibitors have shown that the model can discriminate between strong and weaker inhibitors and agrees well with the experimental affinities reported in the literature. The model and the docking methodology can be used in screening virtual libraries for PfHDAC1 inhibitors, since the docking scores have ranked ligands in accordance with experimental binding affinities. Valproic acid calculated theoretical binding energy suggests that it may inhibit PfHDAC1.

  11. Inhibiting properties and adsorption of an amine based fatty acid corrosion inhibitor on carbon steel in aqueous carbon dioxide solutions

    Buchweishaija, Joseph

    1997-12-31

    Carbon dioxide corrosion is a major corrosion problem in oil and gas production systems and many organic inhibitors have been tested and used to protect the substrate from corrosion. This thesis studies the mechanism of interaction of the inhibitor molecule with the metallic substrate and how this affects the dissolution rate of the metal. The performance of a commercial amine based fatty acid corrosion inhibitor has been investigated using rotating cylinder electrodes and carbon steel electrodes in CO{sub 2} saturated formation water in the temperature range between 35 to 80{sup o}C. The corrosion process was monitored by electrochemical impedance measurements, and at the end of each experiment full polarization curves were recorded. When the inhibitor was applied on noncorroded electrodes, high inhibitor performance, over 99.7%, was observed independent of temperature. On precorroded electrodes inhibitor performance was found to depend on temperature and time of precorrosion. Above 60{sup o}C, the inhibitor performance decreased with increasing time of precorrosion, presumably because of the formation of a corrosion film of either iron carbonate or a combination of iron carbonate and iron carbide which prevent the inhibitor from reaching the surface. The inhibitor protection efficiency was assumed to be associated with the degree of inhibitor coverage at the material surface, and adsorption isotherms have been calculated in the concentration range between 0.1 ppm and 100 ppm. A Langmuir isotherm was found to give the best fit. The inhibitor performance on a 2 days precorroded rotating electrode was investigated at different solution pH ranging between 4.5 and 6.5 at 35{sup o}C. 130 refs., 80 figs., 22 tabs.

  12. Structure Activity Relationship of Phenolic Acid inhibitors of α-Synuclein Fibril Formation and Toxicity

    Mustafa eArdah

    2014-08-01

    Full Text Available The aggregation of α-synuclein (α-syn is considered the key pathogenic event in many neurological disorders such as Parkinson’s disease (PD, dementia with Lewy bodies and multiple system atrophy, giving rise to a whole category of neurodegenerative diseases known as synucleinopathies. Although the molecular basis of α-syn toxicity has not been precisely elucidated, a great deal of effort has been put into identifying compounds that could inhibit or even reverse the aggregation process. Previous reports indicated that many phenolic compounds are potent inhibitors of α-syn aggregation. The aim of the present study was to assess the anti-aggregating effect of gallic acid (GA (3,4,5-trihydroxybenzoic acid, a benzoic acid derivative that belongs to a group of phenolic compounds known as phenolic acids. By employing an array of biophysical and biochemical techniques and a cell-viability assay, GA was shown not only to inhibit α-syn fibrillation and toxicity but also to disaggregate preformed α-syn amyloid fibrils. Interestingly, GA was found to bind to soluble, non-toxic oligomers with no β-sheet content, and to stabilize their structure. The binding of GA to the oligomers may represent a potential mechanism of action. Additionally, by using structure activity relationship data obtained from fourteen structurally similar benzoic acid derivatives, it was determined that the inhibition of α-syn fibrillation by GA is related to the number of hydroxyl moieties and their position on the phenyl ring. GA may represent the starting point for designing new molecules that could be used for the treatment of PD and related disorders.

  13. New metabolically stabilized analogues of lysophosphatidic acid: agonists, antagonists and enzyme inhibitors.

    Prestwich, G D; Xu, Y; Qian, L; Gajewiak, J; Jiang, G

    2005-12-01

    Lysophosphatidic acid (LPA) is a metabolically labile natural phospholipid with a bewildering array of physiological effects. We describe herein a variety of long-lived receptor-specific agonists and antagonists for LPA receptors. Several LPA and PA (phosphatidic acid) analogues also inhibit LPP (lipid phosphate phosphatase). The sn-1 or sn-2 hydroxy groups have been replaced by fluorine, difluoromethyl, difluoroethyl, O-methyl or O-hydroxyethoxy groups to give non-migrating LPA analogues that resist acyltransferases. Alkyl ether replacement of acyl esters produced lipase and acyltransferase-resistant analogues. Replacement of the bridging oxygen in the monophosphate by an alpha-monofluoromethylene-, alpha-bromomethylene- or alpha,alpha-difluoromethylenephosphonate gave phosphatase-resistant analogues. Phosphorothioate analogues with O-acyl and O-alkyl chains are potent, long-lived agonists for LPA1 and LPA3 receptors. Most recently, we have (i) prepared stabilized O-alkyl analogues of lysobisphosphatidic acid, (ii) explored the structure-activity relationship of stabilized cyclic LPA analogues and (iii) synthesized neutral head group trifluoromethylsulphonamide analogues of LPA. Through collaborative studies, we have collected data for these stabilized analogues as selective LPA receptor (ant)agonists, LPP inhibitors, TREK (transmembrane calcium channel) K+ channel agonists, activators of the nuclear transcription factor PPAR-gamma (peroxisome-proliferator-activated receptor-gamma), promoters of cell motility and survival, and radioprotectants for human B-cells. PMID:16246118

  14. EFFECT OF INHIBITORS ON ENZYMATIC HYDROLYSIS AND SIMULTANEOUS SACCHARIFICATION FERMENTATION FOR LACTIC ACID PRODUCTION FROM STEAM EXPLOSION PRETREATED LESPEDEZA STALKS

    Yue Feng,

    2012-06-01

    Full Text Available The effects on both cellulose conversion rate and lactic acid yield were studied by adding inhibitors, including formic acid, acetic acid, furfural, and vanillin into the hydrolysate of steam-pretreated Lespedeza stalks. The results suggest that formic acid has a significant influence on the enzyme activity and poisoned bacterial cells, resulting in the reduction of cellulose conversion rate and lactic acid yield by 21% and 16.4%, respectively. Acetic acid showed a strong inhibition on simultaneous saccharification fermentation (SSF process, but little effect on enzymatic hydrolysis. Hydrolysis and SSF were less affected by furfural and vanillin compared with weak acids. The lactic acid yield of Lespedeza stalks rinsed with water increased from 64.0% to 89.4%, and the time to reach the maximum concentration was shortened from 96 hours to 48 hours when compared with the unwashed materials.

  15. Study of Ellagic Acid as a Natural Elastase Inhibitor by Spectroscopic Methods

    Xing, X.; Yang, X.; Cao, Yu.

    2016-03-01

    A new natural inhibitor, ellagic acid (EA), was developed, and its inhibition efficiency on elastase was studied by spectroscopic methods. The experimental results proved that EA is a potent elastase inhibitor with an IC50 value of 1.44 mg/mL by UV-vis spectroscopy, and the inhibition mechanism of elastase was confirmed by fluorescence quenching. The interacting between EA and elastase was mainly based on the static quenching owing to the complex formation when the concentration of EA was ≤40 μM. Fluorescence quenching mainly occurred via dynamic quenching with increasing EA concentration. The thermodynamic parameters such as ΔH and ΔS were calculated to be -86.35 kJ/mol and -165.88 J/mol · K, respectively, indicating that the interactions between EA and elastase were mainly due to van der Waals forces or hydrogen bonding. The synchronous fl uorescence spectra showed that binding of EA to elastase can induce conformational changes in elastase.

  16. Combined Kinetic Studies and Computational Analysis on Kojic Acid Analogs as Tyrosinase Inhibitors

    Carlyle Ribeiro Lima

    2014-07-01

    Full Text Available Tyrosinase is a key enzyme in melanin synthesis and widely distributed in plants and animals tissues. In mammals, this enzyme is related to pigment production, involved in wound healing, primary immune response and it can also contribute to catecholamines synthesis in the brain. Consequently, tyrosinase enzyme represents an attractive and selective target in the field of the medicine, cosmetics and bio-insecticides. In this paper, experimental kinetics and computational analysis were used to study the inhibition of tyrosinase by analogous of Kojic acid. The main interactions occurring between inhibitors-tyrosinase complexes and the influence of divalent cation (Cu2+ in enzymatic inhibition were investigated by using molecular docking, molecular dynamic simulations and electrostatic binding free energy by using the Linear Interaction Energy (LIE method. The results showed that the electrostatic binding free energy are correlated with values of constant inhibition (r2 = 0.97.Thus, the model obtained here could contribute to future studies of this important system and, therefore, eventually facilitate development of tyrosinase inhibitors.

  17. Identification of a D-amino acid decapeptide HIV-1 entry inhibitor

    Entry of human immunodeficiency virus type 1 (HIV-1) virion into host cells involves three major steps, each being a potential target for the development of entry inhibitors: gp120 binding to CD4, gp120-CD4 complex interacting with a coreceptor, and gp41 refolding to form a six-helix bundle. Using a D-amino acid decapeptide combinatorial library, we identified peptide DC13 as having potent HIV-1 fusion inhibitory activity, and effectively inhibiting infection by several laboratory-adapted and primary HIV-1 strains. While DC13 did not block binding of gp120 to CD4, nor disrupt the gp41 six-helix bundle formation, it effectively blocked the binding of an anti-CXCR4 monoclonal antibody and chemokine SDF-1α to CXCR4-expressing cells. However, because R5-using primary viruses were also neutralized, the antiviral activity of DC13 implies additional mode(s) of action. These results suggest that DC13 is a useful HIV-1 coreceptor antagonist for CXCR4 and, due to its biostability and simplicity, may be of value for developing a new class of HIV-1 entry inhibitors

  18. Development of Cholinesterase Inhibitors Using (a)-Lipoic Acid-benzyl Piperazine Hybrid Molecules

    Kim, Beomcheol; Lee, Seunghwan; Jang, Mi; Shon, Min Young; Park, Jeong Ho [Hanbat National Univ., Daejeon (Korea, Republic of)

    2013-11-15

    A series of hybrid molecules between (α)-lipoic acid (ALA) and benzyl piperazines were synthesized and their in vitro cholinesterase [acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE)] inhibitory activities were evaluated. Even though the parent compounds did not show any inhibitory activity against cholinesterase (ChE), all hybrid molecules showed BuChE inhibitory activity. Some hybrid compounds also displayed AChE inhibitory activity. Specifically, ALA-1-(3-methylbenzyl)piperazine (15) was shown to be an effective inhibitor of both BuChE (IC{sub 50} = 2.3 ± 0.7 μM) and AChE (IC{sub 50} = 30.31 ± 0.64 μM). An inhibition kinetic study using compound 15 indicated a mixed inhibition type. Its binding affinity (K{sub i}) value to BuChE is 2.91 ± 0.15 μM.

  19. Pyrrolidinobenzoic acid inhibitors of influenza virus neuraminidase: the hydrophobic side chain influences type A subtype selectivity.

    Li, Yanwu; Silamkoti, Arundutt; Kolavi, Gundurao; Mou, Liyuan; Gulati, Shelly; Air, Gillian M; Brouillette, Wayne J

    2012-07-15

    Neuraminidase (NA) plays a critical role in the life cycle of influenza virus and is a target for new therapeutic agents. A series of influenza neuraminidase inhibitors with the pyrrolidinobenzoic acid scaffold containing lipophilic side chains at the C3 position have been synthesized and evaluated for influenza neuraminidase inhibitory activity. The size and geometry of the C3 side chains have been modified in order to investigate structure-activity relationships. The results indicated that size and geometry of the C3-side chain are important for selectivity of inhibition against N1 versus N2 NA, important type A influenza variants that infect man, including the highly lethal avian influenza. PMID:22677529

  20. Synthesis and dynamics studies of barbituric acid derivatives as urease inhibitors

    Barakat, Assem; Al-Majid, Abdullah Mohammed; Lotfy, Gehad; Arshad, Fiza; Yousuf, Sammer; Choudhary, M Iqbal; Ashraf, Sajda; Ul-Haq, Zaheer

    2015-01-01

    Background Discovery of potent inhibitors of urease (jack bean) enzyme is the first step in the development of drugs against diseases caused by ureolytic enzyme. Results Thirty-two derivatives of barbituric acid as zwitterionic adducts of diethyl ammonium salts were synthesized. All synthesized compounds (4a–z and 5a–s) were screened for their in vitro inhibition potential against urease enzyme (jack bean urease). The compounds 4i (IC50 = 17.6 ± 0.23 µM) and 5l (IC50 = 17.2 ± 0.44 µM) were fo...

  1. Benzoxazolone Carboxamides: Potent and Systemically Active Inhibitors of Intracellular Acid Ceramidase

    Pizzirani, Daniela*; Bach, Anders*; Realini, Natalia;

    2015-01-01

    cells. Because of its central role in the ceramide metabolism, AC may offer a novel molecular target in disorders with dysfunctional ceramide-mediated signaling. Here, a class of benzoxazolone carboxamides is identified as the first potent and systemically active inhibitors of AC. Prototype members......The ceramides are a family of bioactive lipid-derived messengers involved in the control of cellular senescence, inflammation, and apoptosis. Ceramide hydrolysis by acid ceramidase (AC) stops the biological activity of these substances and influences survival and function of normal and neoplastic...... of this class inhibit AC with low nanomolar potency by covalent binding to the catalytic cysteine. Their metabolic stability and high in vivo efficacy suggest that these compounds may be used as probes to investigate the roles of ceramide in health and disease, and that this scaffold may represent a promising...

  2. Physical Nature of Fatty Acid Amide Hydrolase Interactions with Its Inhibitors: Testing a Simple Nonempirical Scoring Model.

    Giedroyć-Piasecka, Wiktoria; Dyguda-Kazimierowicz, Edyta; Beker, Wiktor; Mor, Marco; Lodola, Alessio; Sokalski, W Andrzej

    2014-12-26

    Fatty acid amide hydrolase (FAAH) is an enzyme responsible for the deactivating hydrolysis of fatty acid ethanolamide neuromodulators. FAAH inhibitors have gained considerable interest due to their possible application in the treatment of anxiety, inflammation, and pain. In the context of inhibitor design, the availability of reliable computational tools for predicting binding affinity is still a challenging task, and it is now well understood that empirical scoring functions have several limitations that in principle could be overcome by quantum mechanics. Herein, systematic ab initio analyses of FAAH interactions with a series of inhibitors belonging to the class of the N-alkylcarbamic acid aryl esters have been performed. In contrast to our earlier studies of other classes of enzyme-inhibitor complexes, reasonable correlation with experimental results required us to consider correlation effects along with electrostatic term. Therefore, the simplest comprehensive nonempirical model allowing for qualitative predictions of binding affinities for FAAH ligands consists of electrostatic multipole and second-order dispersion terms. Such a model has been validated against the relative stabilities of the benchmark S66 set of biomolecular complexes. As it does not involve parameters fitted to experimentally derived data, this model offers a unique opportunity for generally applicable inhibitor design and virtual screening. PMID:25420234

  3. The effect of gamma rays on the total protein content of aldolase, glutamic acid transaminase and glutamic acid-pyruvic acid transaminase in the rabbit lens

    The author subjected rabbit eyes to gamma rays using the Stallard applicators which are also employed in the treatment of intraocular tumors in human eyes. In the radiated eyes there was a reduction of activity of aldolase and GOT in the lenses which was indirectly proportional to the applied dose of ionized rays. The lens of the fellow eye which was not directly subjected to radiation showed also a lowering of enzyme activity which was however of only a low degree. In the material examined there were no changes in total protein content. There were however slight changes in the activity of GPT. In the discussion special attention is paid to radiation damage to the fellow eyes which were not subjected to direct radiation. (orig.)

  4. Development of Better Analogs of Valproic Acid for the Treatment of Epilepsy by CADD

    Manoj Kumar Mahto

    2012-01-01

    Full Text Available Epilepsy is one of the major neurological disorders occurring due to the abnormal functioning of the various receptors and enzymes in the central nervous system. Many potentials drugs were developed in recent times which act on ion channels like sodium (Na+, calcium (Ca2+, chloride (Cl-, and receptors like GABA receptor and enzymes like GABA transaminase. Some drugs act as enzyme, ion channel inhibitors or blockers, and some drugs as receptor agonist like barbiturates, benzodiazepines acting on GABA receptors. In the present study performed computational techniques in order to develop better inhibitors for the enzyme GABA transaminase by modifying the terminal ‘methyl’ group of the Valproic acid structure with electrophilic, nucleophile and neutral pharmacophoric features. Molecular mechanics studies has been carried out for the analogs and protein – ligand interactions of these analogs was identified through docking studies using GOLD 4.1 software against the enzyme 4-aminobutyrate-aminotransferase(GABA transaminase. From the docking studies we found that replacement of methyl with amine, hydrogen and hydroxyl groups (hydrophilic groups, are showing better fitness than that of the valproic acid.

  5. Tranexamic acid, an inhibitor of plasminogen activation, reduces urinary collagen cross-link excretion in both experimental and rheumatoid arthritis

    Ronday, H.K.; TeKoppele, J.M.; Greenwald, R.A.; Moak, S.A.; Roos, J.A.D.M. de; Dijkmans, B.A.C.; Breedveld, F.C.; Verheijen, J.H.

    1998-01-01

    The plasminogen activation system is one of the enzyme systems held responsible for bone and cartilage degradation in rheumatoid arthritis (RA). In this study, we evaluated the effect of tranexamic acid (TEA), an inhibitor of plasminogen activation, on urinary collagen cross-link excretion and radio

  6. Urolithin as a converging scaffold linking ellagic acid and coumarin analogues: design of potent protein kinase CK2 inhibitors.

    Cozza, Giorgio; Gianoncelli, Alessandra; Bonvini, Paolo; Zorzi, Elisa; Pasquale, Riccardo; Rosolen, Angelo; Pinna, Lorenzo A; Meggio, Flavio; Zagotto, Giuseppe; Moro, Stefano

    2011-12-01

    Casein kinase 2 (CK2) is a ubiquitous, essential, and highly pleiotropic protein kinase; its abnormally high constitutive activity is suspected to underlie its pathogenic potential in neoplasia and other relevant diseases. Previously, using different in silico screening approaches, two potent and selective CK2 inhibitors were identified by our group: ellagic acid, a naturally occurring tannic acid derivative (K(i)=20 nM) and 3,8-dibromo-7-hydroxy-4-methylchromen-2-one (DBC, K(i)=60 nM). Comparing the crystallographic binding modes of both ellagic acid and DBC, an X-ray structure-driven merging approach was taken to design novel CK2 inhibitors with improved target affinity. A urolithin moiety is proposed as a possible bridging scaffold between the two known CK2 inhibitors, ellagic acid and DBC. Optimization of urolithin A as the bridging moiety led to the identification of 4-bromo-3,8-dihydroxy-benzo[c]chromen-6-one as a novel, potent and selective CK2 inhibitor, which shows a K(i) value of 7 nM against the protein kinase, representing a significant improvement in affinity for the target compared with the two parent fragments. PMID:21972104

  7. Treatment with the Hyaluronic Acid Synthesis Inhibitor 4-Methylumbelliferone Suppresses SEB-Induced Lung Inflammation

    Olga N. Uchakina

    2013-10-01

    Full Text Available Exposure to bacterial superantigens, such as staphylococcal enterotoxin B (SEB, can lead to the induction of acute lung injury/acute respiratory distress syndrome (ALI/ARDS. To date, there are no known effective treatments for SEB-induced inflammation. In the current study we investigated the potential use of the hyaluronic acid synthase inhibitor 4-methylumbelliferone (4-MU on staphylococcal enterotoxin B (SEB induced acute lung inflammation. Culturing SEB-activated immune cells with 4-MU led to reduced proliferation, reduced cytokine production as well as an increase in apoptosis when compared to untreated cells. Treatment of mice with 4-MU led to protection from SEB-induced lung injury. Specifically, 4-MU treatment led to a reduction in SEB-induced HA levels, reduction in lung permeability, and reduced pro-inflammatory cytokine production. Taken together, these results suggest that use of 4-MU to target hyaluronic acid production may be an effective treatment for the inflammatory response following exposure to SEB.

  8. Two Distinctive Binding Modes of Endonuclease Inhibitors to the N-Terminal Region of Influenza Virus Polymerase Acidic Subunit.

    Fudo, Satoshi; Yamamoto, Norio; Nukaga, Michiyoshi; Odagiri, Takato; Tashiro, Masato; Hoshino, Tyuji

    2016-05-10

    Influenza viruses are global threat to humans, and the development of new antiviral agents are still demanded to prepare for pandemics and to overcome the emerging resistance to the current drugs. Influenza polymerase acidic protein N-terminal domain (PAN) has endonuclease activity and is one of the appropriate targets for novel antiviral agents. First, we performed X-ray cocrystal analysis on the complex structures of PAN with two endonuclease inhibitors. The protein crystallization and the inhibitor soaking were done at pH 5.8. The binding modes of the two inhibitors were different from a common binding mode previously reported for the other influenza virus endonuclease inhibitors. We additionally clarified the complex structures of PAN with the same two endonuclease inhibitors at pH 7.0. In one of the crystal structures, an additional inhibitor molecule, which chelated to the two metal ions in the active site, was observed. On the basis of the crystal structures at pH 7.0, we carried out 100 ns molecular dynamics (MD) simulations for both of the complexes. The analysis of simulation results suggested that the binding mode of each inhibitor to PAN was stable in spite of the partial deviation of the simulation structure from the crystal one. Furthermore, crystal structure analysis and MD simulation were performed for PAN in complex with an inhibitor, which was already reported to have a high compound potency for comparison. The findings on the presence of multiple binding sites at around the PAN substrate-binding pocket will provide a hint for enhancing the binding affinity of inhibitors. PMID:27088785

  9. Choosing a Proton Pump Inhibitor (PPI) to Treat Heartburn, Acid Reflux & GERD

    ... You probably need a medicine called a proton pump inhibitor (PPI). • Talk with your doctor about the ... a PPI for GERD We compared seven proton pump inhibitors (PPIs). This is what we found: All ...

  10. Aqueous Extract of Kalmegh (Andrographis paniculata Leaves as Green Inhibitor for Mild Steel in Hydrochloric Acid Solution

    Ambrish Singh

    2010-01-01

    Full Text Available The inhibition of the corrosion of mild steel in hydrochloric acid solution by the extract of Kalmegh (Andrographis paniculata leaves extract has been studied using weight loss, electrochemical impedance spectroscopy, linear polarization, and potentiodynamic polarization techniques. Inhibition was found to increase with increasing concentration of the extract. The effect of temperature, immersion time, and acid concentration on the corrosion behavior of mild steel in 1 M HCl with addition of extract was also studied. The inhibition was assumed to occur via adsorption of the inhibitor molecules on the metal surface. The adsorption of the molecules of the extract on the mild steel surface obeyed the Langmuir adsorption isotherm. The protective film formed on the metal surface was analyzed by FTIR spectroscopy. The results obtained showed that the extract of Kalmegh (Andrographis paniculata leaves extract could serve as an effective inhibitor of the corrosion of mild steel in hydrochloric acid media.

  11. Proton-pump inhibitor therapy induces acid-related symptoms in healthy volunteers after withdrawal of therapy

    Reimer, Christina; Søndergaard, Bo; Hilsted, Linda;

    2009-01-01

    BACKGROUND & AIMS: Rebound acid hypersecretion (RAHS) has been demonstrated after 8 weeks of treatment with a proton-pump inhibitor (PPI). If RAHS induces acid-related symptoms, this might lead to PPI dependency and thus have important implications. METHODS: A randomized, double-blind, placebo...... dyspepsia, heartburn, or acid regurgitation in the PPI group was 13 of 59 (22%) at week 10, 13 of 59 (22%) at week 11, and 12 of 58 (21%) at week 12. Corresponding figures in the placebo group were 7% at week 10 (P = .034), 5% at week 11 (P = .013), and 2% at week 12 (P = .001). CONCLUSIONS: PPI therapy for...

  12. Sargassum Wightii Extract as a Green Inhibitor for Corrosion of Brass in 0.1 N Phosphoric Acid Solution

    R. Selva Kumar

    2015-06-01

    Full Text Available The effect of marine algae Sargassum wightii extract on corrosion inhibition of brass in phosphoric acid was investigated by weight-loss method, potentiodynamic polarization and electrochemical impedance spectroscopy studies. The inhibition efficiency is found to increase with increasing concentration of extract and decreases with rise in temperature. The inhibitive effect could be attributed to the phytochemical constituents present in the inhibitor containing N, S, O atoms. The activation energy, thermodynamic parameters (free energy, enthalpy and entropy change and kinetic parameters (rate constant and half-life for inhibition process were calculated. These thermodynamic and kinetic parameters indicate a strong interaction between the inhibitor and the brass surface. The inhibition is assumed to occur via adsorption of inhibitor molecules on the brass surface, which obeys Temkin adsorption isotherm. The adsorption of inhibitor on the brass surface is exothermic, physical, and spontaneous, follows first order kinetics. The polarization measurements showed that the inhibitor behaves as a mixed type inhibitor. Inhibition efficiency values were found to show good trend with weight-loss method, potentiodynamic polarization and electrochemical impedance spectroscopy studies. Surface study techniques (FT-IR and SEM were carried out to ascertain the inhibitive nature of the algal extract on the brass surface.

  13. In silico analysis for predicting fatty acids of black cumin oil as inhibitors of P-glycoprotein

    Babar Ali

    2015-01-01

    Full Text Available Background: Black cumin oil is obtained from the seeds of Nigella sativa L. which belongs to family Ranunculaceae. The seed oil has been reported to possess antitumor, antioxidant, antibacterial, anti-inflammatory, hypoglycemic, central nervous system depressant, antioxidant, and immunostimulatory activities. These bioactivities have been attributed to the fixed oil, volatile oil, or their components. Seed oil consisted of 15 saturated fatty acids (17% and 17 unsaturated fatty acids (82.9%. Long chain fatty acids and medium chain fatty acids have been reported to increase oral bioavailability of peptides, antibiotics, and other important therapeutic agents. In earlier studies, permeation enhancement and bioenhancement of drugs has been done with black cumin oil. Objective: In order to recognize the mechanism of binding of fatty acids to P-glycoprotein (P-gp, linoleic acid, oleic acid, margaric acid, cis-11, 14-eicosadienoic acid, and stearic acid were selected for in silico studies, which were carried out using AutoDock 4.2, based on the Lamarckian genetic algorithm principle. Materials and Methods: Template search with BLAST and HHblits has been performed against the SWISS-MODEL template library. The target sequence was searched with BLAST against the primary amino acid sequence of P-gp from Rattus norvegicus. Results: The amount of energy needed by linoleic acid, oleic acid, eicosadienoic acid, margaric acid, and stearic acid to bind with P-gp were found to be − 10.60, −10.48, −9.95, −11.92, and − 10.37 kcal/mol, respectively. The obtained data support that all the selected fatty acids have contributed to inhibit P-gp activity thereby enhances the bioavailability of drugs. Conclusion: This study plays a significant role in finding hot spots in P-gp and may offer the further scope of designing potent and specific inhibitors of P-gp.

  14. 4-Substituted anilinomethylpropionate: New and efficient corrosion inhibitors for mild steel in hydrochloric acid solution

    4-substituted anilinomethylpropionate namely 3-anilinomethylpropionate (Inh-1), 3-(4-methylanilino)methylpropionate (Inh-2) and 3-(4-chloroanilino) methylpropionate (Inh-3) were synthesized and investigated as corrosion inhibitors of mild steel in 1 N HCl solution using weight loss, polarization resistance, Tafel polarization and electrochemical Impedance spectroscopy techniques. The inhibition efficiency of the synthesized inhibitors followed the order Inh3 > Inh2 > Inh1. The inhibiting action of the all inhibitors was found to depend on electronic nature of functional groups present in inhibitors. Potentiodynamic polarizations suggest that all inhibitors are mixed type in nature. Electrochemical impedance spectroscopy was also used to investigate the mechanism of corrosion inhibition.

  15. Baphia nitida Leaves Extract as a Green Corrosion Inhibitor for the Corrosion of Mild Steel in Acidic Media

    Njoku, V. O.; E. E. Oguzie; Obi, C.; Ayuk, A. A.

    2014-01-01

    The inhibiting effect of Baphia nitida (BN) leaves extract on the corrosion of mild steel in 1 M H2SO4 and 2 M HCl was studied at different temperatures using gasometric and weight loss techniques. The results showed that the leaves extract is a good inhibitor for mild steel corrosion in both acid media and better performances were obtained in 2 M HCl solutions. Inhibition efficiency was found to increase with increasing inhibitor concentration and decreasing temperature. The addition of hali...

  16. Characterization of the corrosion products formed on mild steel in acidic medium with N-octadecylpyridinium bromide as corrosion inhibitor

    The characterization of the corrosion products formed on mild steel SAE 1018 after 2 months exposure in aqueous sulfuric acid with and without corrosion inhibitor N-octadecylpyridinium bromide has been carried out by means of transmission 57Fe Mössbauer spectroscopy and X-ray powder diffraction (XRD). The major constituent of the rust formed in this environment without corrosion inhibitor is goethite (α-FeOOH). The samples with N-octadecylpyridinium bromide contain rozenite and large amounts of melanterite in the corrosion layers.

  17. Characterization of the corrosion products formed on mild steel in acidic medium with N-octadecylpyridinium bromide as corrosion inhibitor

    Nava, N., E-mail: tnava@imp.mx; Likhanova, N. V. [Direccion de Investigacion y Posgrado, Instituto Mexicano del Petroleo (Mexico); Olivares-Xometl, O. [Benemerita Universidad Autonoma de Puebla, Facultad de Ingenieria Quimica (Mexico); Flores, E. A. [Direccion de Investigacion y Posgrado, Instituto Mexicano del Petroleo (Mexico); Lijanova, I. V. [CIITEC, Instituto Politecnico Nacional (Mexico)

    2011-11-15

    The characterization of the corrosion products formed on mild steel SAE 1018 after 2 months exposure in aqueous sulfuric acid with and without corrosion inhibitor N-octadecylpyridinium bromide has been carried out by means of transmission {sup 57}Fe Moessbauer spectroscopy and X-ray powder diffraction (XRD). The major constituent of the rust formed in this environment without corrosion inhibitor is goethite ({alpha}-FeOOH). The samples with N-octadecylpyridinium bromide contain rozenite and large amounts of melanterite in the corrosion layers.

  18. Novel 2-oxoimidazolidine-4-carboxylic acid derivatives as Hepatitis C virus NS3-4A serine protease inhibitors: synthesis, activity, and X-ray crystal structure of an enzyme inhibitor complex

    Arasappan, Ashok; Njoroge, F. George; Parekh, Tejal N.; Yang, Xiaozheng; Pichardo, John; Butkiewicz, Nancy; Prongay, Andrew; Yao, Nanhua; Girijavallabhan, Viyyoor (SPRI)

    2008-06-30

    Synthesis and HCV NS3 serine protease inhibitory activity of some novel 2-oxoimidazolidine-4-carboxylic acid derivatives are reported. Inhibitors derived from this new P2 core exhibited activity in the low {micro}M range. X-ray structure of an inhibitor, 15c bound to the protease is presented.

  19. Fatty acid transport protein-2 inhibitor Grassofermata/CB5 protects cells against lipid accumulation and toxicity

    The inhibition of the fatty acid uptake into non-adipose tissues provides an attractive target for prevention of lipotoxicity leading to obesity-associated non-alcoholic fatty liver disease and type 2 diabetes. Fatty acid transport proteins (FATPs) are bifunctional proteins involved in the uptake and activation of fatty acids by esterification with coenzyme A. Here we characterize Grassofermata/CB5, previously identified as a fatty acid uptake inhibitor directed against HsFATP2. The compound was effective in inhibiting the uptake of fatty acids in the low micro-molar range (IC50 8–11 μM) and prevented palmitate-mediated lipid accumulation and cell death in cell lines that are models for intestines, liver, muscle and pancreas. In adipocytes, uptake inhibition was less effective (IC50 58 μM). Inhibition was specific for long chain fatty acids and was ineffective toward medium chain fatty acids, which are transported by diffusion. Kinetic analysis of Grassofermata-dependent FA transport inhibition verified a non-competitive mechanism. By comparison with Grassofermata, several atypical antipsychotic drugs previously implicated as inhibitors of FA uptake were ineffectual. In mice Grassofermata decreased absorption of 13C-oleate demonstrating its potential as a therapeutic agent. - Highlights: • Grassofermata is a small compound inhibitor of FATP2. • Uptake inhibition is specific for long chain fatty acids. • Uptake kinetics shows low specificity for adipocytes compared to other cell types. • Inhibition is by a non-competitive mechanism. • Atypical antipsychotics do not inhibit FA uptake by comparison with Grassofermata

  20. Fatty acid transport protein-2 inhibitor Grassofermata/CB5 protects cells against lipid accumulation and toxicity

    Saini, Nipun; Black, Paul N.; Montefusco, David; DiRusso, Concetta C., E-mail: cdirusso2@unl.edu

    2015-09-25

    The inhibition of the fatty acid uptake into non-adipose tissues provides an attractive target for prevention of lipotoxicity leading to obesity-associated non-alcoholic fatty liver disease and type 2 diabetes. Fatty acid transport proteins (FATPs) are bifunctional proteins involved in the uptake and activation of fatty acids by esterification with coenzyme A. Here we characterize Grassofermata/CB5, previously identified as a fatty acid uptake inhibitor directed against HsFATP2. The compound was effective in inhibiting the uptake of fatty acids in the low micro-molar range (IC{sub 50} 8–11 μM) and prevented palmitate-mediated lipid accumulation and cell death in cell lines that are models for intestines, liver, muscle and pancreas. In adipocytes, uptake inhibition was less effective (IC{sub 50} 58 μM). Inhibition was specific for long chain fatty acids and was ineffective toward medium chain fatty acids, which are transported by diffusion. Kinetic analysis of Grassofermata-dependent FA transport inhibition verified a non-competitive mechanism. By comparison with Grassofermata, several atypical antipsychotic drugs previously implicated as inhibitors of FA uptake were ineffectual. In mice Grassofermata decreased absorption of {sup 13}C-oleate demonstrating its potential as a therapeutic agent. - Highlights: • Grassofermata is a small compound inhibitor of FATP2. • Uptake inhibition is specific for long chain fatty acids. • Uptake kinetics shows low specificity for adipocytes compared to other cell types. • Inhibition is by a non-competitive mechanism. • Atypical antipsychotics do not inhibit FA uptake by comparison with Grassofermata.

  1. Nicotinic acid as a nontoxic corrosion inhibitor for hot dipped Zn and Zn-Al alloy coatings on steels in diluted hydrochloric acid

    The inhibition effect of nicotinic acid for corrosion of hot dipped Zn and Zn-Al alloy coatings in diluted hydrochloric acid was investigated using quantum chemistry analysis, weight loss test, electrochemical measurement, and scanning electronic microscope (SEM) analysis. Quantum chemistry calculation results showed that nicotinic acid possessed planar structure with a number of active centers, and the populations of the Mulliken charge, the highest occupied molecular orbital (HOMO), and the lowest unoccupied molecular orbital (LUMO) were found mainly focused around oxygen and nitrogen atoms, and the cyclic of the benzene as well. The results of weight loss test and electrochemical measurement indicated that inhibition efficiency (IE%) increased with inhibitor concentration, and the highest inhibition efficiency was up to 96.7%. The corrosion inhibition of these coatings was discussed in terms of blocking the electrode reaction by adsorption of the molecules at the active centers on the electrode surface. It was found that the adsorption of nicotinic acid on coating surface followed Langmuir adsorption isotherm with single molecular layer, and nicotinic acid adsorbed on the coating surface probably by chemisorption. Nicotinic acid, therefore, can act as a good nontoxic corrosion inhibitor for hot dipped Zn and Zn-Al alloy coatings in diluted hydrochloric acid solution

  2. Examination of the Addictive and Behavioral Properties of Fatty Acid-Binding Protein Inhibitor SBFI26

    Thanos, Panayotis K.; Clavin, Brendan H.; Hamilton, John; O’Rourke, Joseph R.; Maher, Thomas; Koumas, Christopher; Miao, Erick; Lankop, Jessenia; Elhage, Aya; Haj-Dahmane, Samir; Deutsch, Dale; Kaczocha, Martin

    2016-01-01

    The therapeutic properties of cannabinoids have been well demonstrated but are overshadowed by such adverse effects as cognitive and motor dysfunction, as well as their potential for addiction. Recent research on the natural lipid ligands of cannabinoid receptors, also known as endocannabinoids, has shed light on the mechanisms of intracellular transport of the endocannabinoid anandamide by fatty acid-binding proteins (FABPs) and subsequent catabolism by fatty acid amide hydrolase. These findings facilitated the recent development of SBFI26, a pharmacological inhibitor of epidermal- and brain-specific FABP5 and FABP7, which effectively increases anandamide signaling. The goal of this study was to examine this compound for any possible rewarding and addictive properties as well as effects on locomotor activity, working/recognition memory, and propensity for sociability and preference for social novelty (SN) given its recently reported anti-inflammatory and analgesic properties. Male C57BL mice were split into four treatment groups and conditioned with 5.0, 20.0, 40.0 mg/kg SBFI26, or vehicle during a conditioned place preference (CPP) paradigm. Following CPP, mice underwent a battery of behavioral tests [open field, novel object recognition (NOR), social interaction (SI), and SN] paired with acute SBFI26 administration. Results showed that SBFI26 did not produce CPP or conditioned place aversion regardless of dose and did not induce any differences in locomotor and exploratory activity during CPP- or SBFI26-paired open field activity. We also observed no differences between treatment groups in NOR, SI, and SN. In conclusion, as SBFI26 was shown previously by our group to have significant analgesic and anti-inflammatory properties, here we show that it does not pose a risk of dependence or motor and cognitive impairment under the conditions tested. PMID:27092087

  3. Examination of the Addictive and Behavioral Properties of Fatty Acid-Binding Protein Inhibitor SBFI26.

    Thanos, Panayotis K; Clavin, Brendan H; Hamilton, John; O'Rourke, Joseph R; Maher, Thomas; Koumas, Christopher; Miao, Erick; Lankop, Jessenia; Elhage, Aya; Haj-Dahmane, Samir; Deutsch, Dale; Kaczocha, Martin

    2016-01-01

    The therapeutic properties of cannabinoids have been well demonstrated but are overshadowed by such adverse effects as cognitive and motor dysfunction, as well as their potential for addiction. Recent research on the natural lipid ligands of cannabinoid receptors, also known as endocannabinoids, has shed light on the mechanisms of intracellular transport of the endocannabinoid anandamide by fatty acid-binding proteins (FABPs) and subsequent catabolism by fatty acid amide hydrolase. These findings facilitated the recent development of SBFI26, a pharmacological inhibitor of epidermal- and brain-specific FABP5 and FABP7, which effectively increases anandamide signaling. The goal of this study was to examine this compound for any possible rewarding and addictive properties as well as effects on locomotor activity, working/recognition memory, and propensity for sociability and preference for social novelty (SN) given its recently reported anti-inflammatory and analgesic properties. Male C57BL mice were split into four treatment groups and conditioned with 5.0, 20.0, 40.0 mg/kg SBFI26, or vehicle during a conditioned place preference (CPP) paradigm. Following CPP, mice underwent a battery of behavioral tests [open field, novel object recognition (NOR), social interaction (SI), and SN] paired with acute SBFI26 administration. Results showed that SBFI26 did not produce CPP or conditioned place aversion regardless of dose and did not induce any differences in locomotor and exploratory activity during CPP- or SBFI26-paired open field activity. We also observed no differences between treatment groups in NOR, SI, and SN. In conclusion, as SBFI26 was shown previously by our group to have significant analgesic and anti-inflammatory properties, here we show that it does not pose a risk of dependence or motor and cognitive impairment under the conditions tested. PMID:27092087

  4. The histone deacetylase inhibitor suberoylanilide hydroxamic acid attenuates human astrocyte neurotoxicity induced by interferon-γ

    Hashioka Sadayuki

    2012-05-01

    Full Text Available Abstract Backgrounds Increasing evidence shows that the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA possesses potent anti-inflammatory and immunomodulatory properties. It is tempting to evaluate the potential of SAHA as a therapeutic agent in various neuroinflammatory and neurodegenerative disorders. Methods We examined the effects of SAHA on interferon (IFN-γ-induced neurotoxicity of human astrocytes and on IFN-γ-induced phosphorylation of signal transducer and activator of transcription (STAT 3 in human astrocytes. We also studied the effects of SAHA on the astrocytic production of two representative IFN-γ-inducible inflammatory molecules, namely IFN-γ-inducible T cell α chemoattractant (I-TAC and intercellular adhesion molecule-1 (ICAM-1. Results SAHA significantly attenuated the toxicity of astrocytes activated by IFN-γ towards SH-SY5Y human neuronal cells. In the IFN-γ-activated astrocytes, SAHA reduced the STAT3 phosphorylation. SAHA also inhibited the IFN-γ-induced astrocytic production of I-TAC, but not ICAM-1. These results indicate that SAHA suppresses IFN-γ-induced neurotoxicity of human astrocytes through inhibition of the STAT3 signaling pathway. Conclusion Due to its anti-neurotoxic and anti-inflammatory properties, SAHA appears to have the therapeutic or preventive potential for a wide range of neuroinflammatory disorders associated with activated astrocytes.

  5. Theoretical studies of three triazole derivatives as corrosion inhibitors for mild steel in acidic medium

    Highlights: • Three triazole derivatives as corrosion inhibitors were theoretically investigated. • Quantum chemical calculations and Monte Carlo simulations were performed. • Quantitative structure activity relationship (QSAR) approach has been used. • Theoretical conclusions are validated by the consistency with experimental findings. - Abstract: Corrosion inhibitive performance of 4-chloro-acetophenone-O-1′-(1′.3′.4′-triazolyl)-metheneoxime (CATM), 4-fluoro-acetophenone-O-1′-(1′.3′.4′-triazolyl)-metheneoxime (FATM), and 3,4-dichloro-acetophenone-O-1′-(1′.3′.4′-triazolyl)-metheneoxime (DATM) during the acidic corrosion of mild steel surface was investigated using density functional theory (DFT). Quantum chemical parameters such as the highest occupied molecular orbital energy (EHOMO), the lowest unoccupied molecular orbital energy (ELUMO), energy gap (ΔE), Mulliken charges, hardness (ξ), dipole moment (μ), and the fraction of electrons transferred (ΔN), were calculated. Quantitative structure activity relationship (QSAR) approach has been used, and a composite index of above-mentioned descriptors was performed to characterize the inhibition performance of the studied molecules. Furthermore, Monte Carlo simulation studies were applied to search for the best configurational space of iron/triazole derivative system

  6. Mechanism for release of arachidonic acid during guinea pig platelet aggregation: a role for the diacylglycerol lipase inhibitor RHC 80267

    The mechanism of the release of arachidonic acid from phospholipids after the stimulation of guinea pig platelets with collagen, thrombin and platelet activating factor (PAF) was studied. RHC 80267, a diacylglycerol lipase inhibitor, and indomethacin, a cyclooxygenase inhibitor, were used. Various in vitro assays for enzymes involved in arachidonic acid release and metabolism were conducted. Platelet aggregation and simultaneous release of ADP from platelets were monitored using a Chrono-log Lumiaggregometer. Platelets were labeled with (14C)arachidonic acid to facilitate sensitive determination of small changes in platelet phospholipids during platelet aggregation. In the present investigation it is shown that collagen, thrombin and PAF increased phospholipase C activity. It was also discovered that cyclooxygenase products were responsible for further stimulation (a positive feed-back) of phospholipase C activity, while diacylglycerol provided a negative feed-back control over receptor-stimulated phospholipase C activity and inhibited ADP release. The guinea pig platelet is an ideal model to study phospholipase C-diacylglycerol lipase pathway for the release of arachidonic acid from platelet phospholipids because it does not have any phospholipase A2 activity. It was observed that cyclooxygenase products were responsible for collagen-induced guinea pig platelet aggregation. Indomethacin completely inhibited collagen-induced platelet aggregation, was less effective against thrombin, and had no effect on PAF-induced platelet aggregation. On the other hand, RHC 80267 was a powerful inhibitor of aggregation and ADP release induced by all three of these potent aggregating agents

  7. Amino Acid Composition, Urease Activity and Trypsin Inhibitor Activity after Toasting of Soybean in Thick and Thin Layer

    Tajana Krička

    2009-12-01

    Full Text Available The objective of this study was to determine amino acid content, urease activity and trypsin inhibitor activity in soybean grain for polygastric animals’ feed aft er toasting with the aim to introduce thick layer in toasting technology. Hence, soybean was toasted both in thick and thin layer at 130 oC during 10 minutes. In order to properly monitor the technological process of soybean thermal processing, it was necessary to study crude protein content, urease activity, trypsin inhibitor activity and amino acid composition of soybean in natural and toasted samples. Results demonstrate that protein content in soybean toasted in thick and thin layer was found to be slightly increased while urease activity was reduced in relation to non-treated sample. Study also established a significant reduction of trypsin inhibitor activity aft er toasting, at higher extent in thin layer toasting. Amino acid content of soybean was slightly increased in relation to natural sample, as well as difference between amino acid content in samples toasted in thick and thin layers.

  8. Impact of plasma transaminase levels on the peripheral blood glutamate levels and memory functions in healthy subjects ☆

    Kamada, Yoshihiro; Hashimoto, Ryota; Yamamori, Hidenaga; Yasuda, Yuka; Takehara, Tetsuo; Fujita, Yuko; Hashimoto, Kenji; Miyoshi, Eiji

    2016-01-01

    Background & aims Blood aspartate aminotransferase (AST) and alanine transaminase (ALT) levels are the most frequently reliable biomarkers of liver injury. Although AST and ALT play central roles in glutamate production as transaminases, peripheral blood levels of AST and ALT have been regarded only as liver injury biomarkers. Glutamate is a principal excitatory neurotransmitter, which affects memory functions in the brain. In this study, we investigated the impact of blood transaminase level...

  9. Catalytic Promiscuity of Transaminases: Preparation of Enantioenriched β-Fluoroamines by Formal Tandem Hydrodefluorination/Deamination.

    Cuetos, Aníbal; García-Ramos, Marina; Fischereder, Eva-Maria; Díaz-Rodríguez, Alba; Grogan, Gideon; Gotor, Vicente; Kroutil, Wolfgang; Lavandera, Iván

    2016-02-01

    Transaminases are valuable enzymes for industrial biocatalysis and enable the preparation of optically pure amines. For these transformations they require either an amine donor (amination of ketones) or an amine acceptor (deamination of racemic amines). Herein transaminases are shown to react with aromatic β-fluoroamines, thus leading to simultaneous enantioselective dehalogenation and deamination to form the corresponding acetophenone derivatives in the absence of an amine acceptor. A series of racemic β-fluoroamines was resolved in a kinetic resolution by tandem hydrodefluorination/deamination, thus giving the corresponding amines with up to greater than 99 % ee. This protocol is the first example of exploiting the catalytic promiscuity of transaminases as a tool for novel transformations. PMID:26836037

  10. Valoniopsis pachynema Extract as a Green Inhibitor for Corrosion of Brass in 0.1 N Phosphoric Acid Solution

    Selva Kumar, R.; Chandrasekaran, V.

    2016-04-01

    The effect of marine alga Valoniopsis pachynema extract on corrosion inhibition of brass in phosphoric acid was investigated by weight-loss method, potentiodynamic polarization, and electrochemical impedance spectroscopy studies. The inhibition efficiency is found to increase with increasing concentration of extract and decreases with rise in temperature. The activation energy, thermodynamic parameters (free energy, enthalpy, and entropy change) and kinetic parameters (rate constant and half-life) for inhibition process were calculated. These thermodynamic and kinetic parameters indicate a strong interaction between the inhibitor and the brass surface. The inhibition is assumed to occur via adsorption of inhibitor molecules on brass surface, which obeys Temkin adsorption isotherm. The adsorption of inhibitor on the brass surface is exothermic, physical, and spontaneous, and follows first-order kinetics. The polarization measurements showed that the inhibitor behaves as a mixed type inhibitor and the higher inhibition surface coverage on the brass was predicted. Inhibition efficiency values were found to show good trend with weight-loss method, potentiodynamic polarization, and electrochemical impedance spectroscopy studies. Surface study techniques (FT-IR and SEM) were carried out to ascertain the inhibitive nature of the algal extract on the brass surface.

  11. A Novel Strategy to Assemble the β-Diketo Acid Pharmacophore of HIV Integrase Inhibitors on Purine Nucleobase Scaffolds

    Uchil, Vinod; Seo, Byung; Nair, Vasu

    2007-01-01

    Claisen condensation, the key step in constructing the pharmacophore of aryl β-diketo acids (DKA) as integrase inhibitors, fails in certain cases of highly electron-deficient heterocycles such as purines. A general synthetic strategy to assemble the DKA motif on the purine scaffold has been accomplished. The synthetic sequence entails a palladium-catalyzed cross-coupling, a C-acylation involving a tandem addition/elimination reaction and a novel ferric ion-catalyzed selective hydrolysis of an...

  12. Sargassum Wightii Extract as a Green Inhibitor for Corrosion of Brass in 0.1 N Phosphoric Acid Solution

    R. Selva Kumar; Chandrasekaran, V.

    2015-01-01

    The effect of marine algae Sargassum wightii extract on corrosion inhibition of brass in phosphoric acid was investigated by weight-loss method, potentiodynamic polarization and electrochemical impedance spectroscopy studies. The inhibition efficiency is found to increase with increasing concentration of extract and decreases with rise in temperature. The inhibitive effect could be attributed to the phytochemical constituents present in the inhibitor containing N, S, O atoms. The activation e...

  13. Diketo acid inhibitor mechanism and HIV-1 integrase: Implications for metal binding in the active site of phosphotransferase enzymes

    Grobler, Jay A.; Stillmock, Kara; Hu, Binghua; Witmer, Marc; Felock, Peter; Espeseth, Amy S.; Wolfe, Abigail; Egbertson, Melissa; Bourgeois, Michele; Melamed, Jeffrey; Wai, John S.; Young, Steve; Vacca, Joseph; Hazuda, Daria J.

    2002-01-01

    The process of integrating the reverse-transcribed HIV-1 DNA into the host chromosomal DNA is catalyzed by the virally encoded enzyme integrase (IN). Integration requires two metal-dependent reactions, 3′ end processing and strand transfer. Compounds that contain a diketo acid moiety have been shown to selectively inhibit the strand transfer reaction of IN in vitro and in infected cells and are effective as inhibitors of HIV-1 replication. To characterize the molecular basis of inhibition, we...

  14. Pomegranate (Punica granatum) Peel Extract as a Green Corrosion Inhibitor for Mild Steel in Hydrochloric Acid Solution

    Habib Ashassi-Sorkhabi; Shoja Mirzaee; Taghi Rostamikia; Robabeh Bagheri

    2015-01-01

    The inhibition effect of pomegranate peel extract (PPE) on the corrosion of mild steel in hydrochloric acid (HCl) solution was investigated. The polarization, mass loss, and electrochemical impendence techniques were used to evaluate the corrosion inhibition performance of the pomegranate peel extract. The results revealed that PPE acts as a corrosion inhibitor in HCl solution. The inhibition efficiency increased with the increase of extract concentration. The inhibition action was attributed...

  15. A methodology for cascade selection for co-product removal in the ω-transaminase system

    Janes, Kresimir; Gernaey, Krist; Tufvesson, Pär; Woodley, John

    Production of chiral amines using transaminases has indeed been proposed recently as an interesting alternative to conventional methods to help in the synthesis of many new pharmaceuticals. Two reaction strategies have been demonstrated: kinetic resolution and asymmetric synthesis. The latter...... methodology has been applied to an ω-transaminase system which is thermodynamically challenged and enzymatic ISCPR is deployed to shift the equilibrium. The enzymes proposed for co-product removal are dehydrogenases: lactate dehydrogenase (EC 1.1.1.27), alanine dehydrogenase (EC 1.4.1.1), yeast alcohol...

  16. Emulgin as an inhibitor of corrosion and hydrogenation of carbon steel in weakly acidic H2S-containing solutions

    Protective efficiency of emulgin (technological mixture of primary and secondary aliphatic amines) as an inhibitor (0.078-0.625 mmol/l) of acidic, acid carbonate and hydrogen sulfide corrosion and hydrogenation of the St.3 carbon steel is studied. Protection degree of 97% and complete absence of local damages were obtained in the 5-50 mM HCl, saturated by hydrogen sulfide. The anode reaction retardation increases the simultaneous presence of HCl and H2S also does not noticeably decreases it. Hydrogenation of steel under optimal conditions is practically completely removed, what is facilitated by increase in the HCl and H2S concentration and solution temperature

  17. Nitrogen-15 NMR spectroscopy of the catalytic-triad histidine of a serine protease in peptide boronic acid inhibitor complexes

    15N NMR spectroscopy was used to examine the active-site histidyl residue of α-lytic protease in peptide boronic acid inhibitor complexes. Two distinct types of complexes were observed: (1) Boronic acids that are analogues of substrates form complexes in which the active-site imidazole ring is protonated and both imidazole N-H protons are strongly hydrogen bonded. (2) Boronic acids that are not substrate analogues form complexes in which Nε2 of the active-site histidine is covalently bonded to the boron atom of the inhibitor. The proton bound to Nδ1 of the histidine in these histidine-boronate adducts remains strongly hydrogen bonded, presumably to the active-site aspartate. In both types of complexes the N-H protons of His-57 exchange unusually slowly as evidenced by the room temperature visibility of the low-field 1H resonances and the 15N-H spin couplings. These results indicate that occupancy of the specificity subsites may be required to fully form the transition-state binding site. The significance of these findings for understanding inhibitor binding and the catalytic mechanism of serine proteases is discussed

  18. Biological inhibitor abatement and ethanol fermentation of sugars from dilute acid-pretreated rice hulls

    Fermentation inhibitors arise from lignin, hemicellulose, and degraded sugar during pretreatment of lignocellulosic biomass. Use of a microbe has been explored for abatement of pretreated biomass in which fermentation inhibitors, if left untreated, can complicate microbial conversion of biomass to f...

  19. Role of bile acids, prostaglandins and COX inhibitors in chronic esophagitis in a mouse model

    C Poplawski; D Sosnowski; A Szaflarska-Poplawska; J Sarosiek; R McCallum; Z Bartuzi

    2006-01-01

    AIM: To develop a new experimental model of esophagitis that serves a complementary tool to clinical investigation in an insight into the mechanism of the damage to the esophagus mucosa by aggressive factors, and role of COX inhibitors in this process.METHODS: The study was conducted in 56 male mice.Animals were divided into seven groups: (1) perfused with HCl, (2) perfused with HCl and physiologic concentration of pepsin (HCl/P), (3) perfused with similar HCl/P solution enriched with conjugated bile acids (glycho- and tauro-sodium salts) designated esophageal infusion catheter under the general anesthesia, (4) perfused as in group 2 treated with indometacin, (5) perfused as in group 2 treated with NS-398, (6) perfused as in group 3 treated with indometacin, and (7) perfused as in group 3 treated with NS-398.The esophagus was divided into 3 parts: upper, middle and lower. The PGE2 concentration was measured in all parts of esophagus using RIA method. Esophagus of sacrificed animals was macroscopically evaluated using a low power dissecting microscope (20x). Specimeris, representing the most frequently seen changes were fixed,stained with H&E and assessed microscopically using the damage score, and inflammatory score.RESULTS: The macroscopic changes were significantly severer in HCl/P than those in HCl animals (77%) and in HCl/P/BA group (43%). In HCl/P NS-398 group we noticed significantly less changes than those in not treated group (42%) and in analogical group treated with indometacine (45%). In HCl/P/BA INDO group we observed significantly severer changes than that in not treated group (52%). We noticed less changes in HCl/P NS-398 than that in group with indometacine (46%). In HCl/P/BA NS-398 group we had less changes than that in indometacin group (34%). The microscopic changes observed in HCl/P/BA INDO group were severer than that in not treated group (48%). Esophagitis index in HCl group was significantly lower than in HCl/P and also HCl/P/BA group (32% and

  20. Histone deacetylase inhibitor valproic acid promotes the induction of pluripotency in mouse fibroblasts by suppressing reprogramming-induced senescence stress

    Histone deacetylase inhibitor valproic acid (VPA) has been used to increase the reprogramming efficiency of induced pluripotent stem cell (iPSC) from somatic cells, yet the specific molecular mechanisms underlying this effect is unknown. Here, we demonstrate that reprogramming with lentiviruses carrying the iPSC-inducing factors (Oct4-Sox2-Klf4-cMyc, OSKM) caused senescence in mouse fibroblasts, establishing a stress barrier for cell reprogramming. Administration of VPA protected cells from reprogramming-induced senescent stress. Using an in vitro pre-mature senescence model, we found that VPA treatment increased cell proliferation and inhibited apoptosis through the suppression of the p16/p21 pathway. In addition, VPA also inhibited the G2/M phase blockage derived from the senescence stress. These findings highlight the role of VPA in breaking the cell senescence barrier required for the induction of pluripotency. - Highlights: • Histone deacetylase inhibitor valproic acid enhances iPSC induction. • Valproic acid suppresses reprogramming-induced senescence stress. • Valproic acid downregulates the p16/p21 pathway in reprogramming. • This study demonstrates a new mechanistic role of valproic acid in enhancing reprogramming

  1. Histone deacetylase inhibitor valproic acid promotes the induction of pluripotency in mouse fibroblasts by suppressing reprogramming-induced senescence stress

    Zhai, Yingying; Chen, Xi; Yu, Dehai [Stem Cell and Cancer Center, First Affiliated Hospital, Jilin University, Changchun, Jilin 130061 (China); Stanford University Medical School, Palo Alto Veterans Institute for Research, Palo Alto, CA 94304 (United States); Li, Tao [Stanford University Medical School, Palo Alto Veterans Institute for Research, Palo Alto, CA 94304 (United States); Cui, Jiuwei; Wang, Guanjun [Stem Cell and Cancer Center, First Affiliated Hospital, Jilin University, Changchun, Jilin 130061 (China); Hu, Ji-Fan, E-mail: jifan@stanford.edu [Stem Cell and Cancer Center, First Affiliated Hospital, Jilin University, Changchun, Jilin 130061 (China); Stanford University Medical School, Palo Alto Veterans Institute for Research, Palo Alto, CA 94304 (United States); Li, Wei, E-mail: jdyylw@163.com [Stem Cell and Cancer Center, First Affiliated Hospital, Jilin University, Changchun, Jilin 130061 (China)

    2015-09-10

    Histone deacetylase inhibitor valproic acid (VPA) has been used to increase the reprogramming efficiency of induced pluripotent stem cell (iPSC) from somatic cells, yet the specific molecular mechanisms underlying this effect is unknown. Here, we demonstrate that reprogramming with lentiviruses carrying the iPSC-inducing factors (Oct4-Sox2-Klf4-cMyc, OSKM) caused senescence in mouse fibroblasts, establishing a stress barrier for cell reprogramming. Administration of VPA protected cells from reprogramming-induced senescent stress. Using an in vitro pre-mature senescence model, we found that VPA treatment increased cell proliferation and inhibited apoptosis through the suppression of the p16/p21 pathway. In addition, VPA also inhibited the G2/M phase blockage derived from the senescence stress. These findings highlight the role of VPA in breaking the cell senescence barrier required for the induction of pluripotency. - Highlights: • Histone deacetylase inhibitor valproic acid enhances iPSC induction. • Valproic acid suppresses reprogramming-induced senescence stress. • Valproic acid downregulates the p16/p21 pathway in reprogramming. • This study demonstrates a new mechanistic role of valproic acid in enhancing reprogramming.

  2. Experimental studies of 2-pyridinecarbonitrile as corrosion inhibitor for mild steel in hydrochloric acid solution

    Highlights: • The corrosion effect of inhibitor was studied in 0.1 mol L−1 HCl on mild steel. • The inhibitor efficiency increases with increase in the concentration of inhibitor. • SEM micrographs showed that the inhibitor has a good protective film on the metal surface. - Abstract: The effect of 2-Pyridinecarbonitrile (2-PCN) was studied on mild steel (MS) corrosion in 0.1 mol L−1 HCl by electrochemical impedance spectroscopy (EIS), linear polarization resistance (LPR) and potentiodynamic polarization measurements. The surface morphologies of the MS were investigated in the inhibitor-free and in the presence of 10 mmol L−1 2-PCN containing corrosive media, at 120 h exposure period by scanning electron microscopy (SEM). The mechanism of adsorption was determined from the potential of zero charge (Epzc). 2-PCN adsorption on the MS surface obeyed the isotherm of Langmuir and the thermodynamic parameters Kads; ΔGads° were also calculated and discussed

  3. Inhibitors of monoacylglycerol lipase, fatty-acid amide hydrolase and endocannabinoid transport differentially suppress capsaicin-induced behavioral sensitization through peripheral endocannabinoid mechanisms

    Spradley, Jessica M.; Guindon, Josée; Hohmann, Andrea G.

    2010-01-01

    Monoacylglycerol lipase (MGL) and fatty acid amide hydrolase (FAAH) degrade the endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide (AEA), respectively. Pharmacological inhibition of these enzymes in the periphery may elucidate the role of endocannabinoids in controlling nociceptive transmission. We compared effects of the MGL inhibitor JZL184, the FAAH inhibitor URB597, and the endocannabinoid uptake inhibitor VDM11, administered locally in the paw, on behavioral hypersensitivities...

  4. Proton pump inhibitors

    Proton pump inhibitors (PPIs) are medicines that work by reducing the amount of stomach acid made by glands in ... Proton pump inhibitors are used to: Relieve symptoms of acid reflux, or gastroesophageal reflux disease (GERD). This is a ...

  5. Proton pump inhibitors

    Proton pump inhibitors (PPIs) are medicines that work by reducing the amount of stomach acid made by ... Proton pump inhibitors are used to: Relieve symptoms of acid reflux, or gastroesophageal reflux disease (GERD). This ...

  6. Cefalexin drug: A new and efficient corrosion inhibitor for mild steel in hydrochloric acid solution

    Corrosion inhibition of mild steel in 1N HCl by cefalexin has been studied by electrochemical and weight loss measurements. The inhibitor showed increase in inhibition efficiency with increase in inhibitor concentration up to optimum concentration 400 ppm. Potentiodynamic polarization suggests that it is a mixed type of inhibitor. Electrochemical impedance spectroscopy was used to investigate the mechanism of corrosion inhibition. Thermodynamic parameters were calculated to investigate mechanism of inhibition. AFM is used to investigate the surface morphology of the uninhibited and inhibited mild steel.

  7. Eco-Friendly Inhibitors for Copper Corrosion in Nitric Acid: Experimental and Theoretical Evaluation

    Savita; Mourya, Punita; Chaubey, Namrata; Singh, V. K.; Singh, M. M.

    2016-02-01

    The inhibitive performance of Vitex negundo, Adhatoda vasica, and Saraka asoka leaf extracts on corrosion of copper in 3M HNO3 solution was investigated using gravimetric, potentiodynamic polarization, and electrochemical impedance spectroscopic techniques. Potentiodynamic polarization studies indicated that these extracts act as efficient and predominantly cathodic mixed inhibitor. Thermodynamic parameters revealed that the adsorption of these inhibitors on copper surface was spontaneous, controlled by physiochemical processes and occurred according to the Langmuir adsorption isotherm. AFM examination of copper surface confirmed that the inhibitor prevented corrosion by forming protective layer on its surface. The correlation between inhibitive effect and molecular structure was ascertained by density functional theory data.

  8. Cefalexin drug: A new and efficient corrosion inhibitor for mild steel in hydrochloric acid solution

    Shukla, Sudhish Kumar [Department of Applied Chemistry, Institute of Technology, Banaras Hindu University, Varanasi 221 005 (India); Quraishi, M.A., E-mail: maquraishi.apc@itbhu.ac.in [Department of Applied Chemistry, Institute of Technology, Banaras Hindu University, Varanasi 221 005 (India)

    2010-03-15

    Corrosion inhibition of mild steel in 1N HCl by cefalexin has been studied by electrochemical and weight loss measurements. The inhibitor showed increase in inhibition efficiency with increase in inhibitor concentration up to optimum concentration 400 ppm. Potentiodynamic polarization suggests that it is a mixed type of inhibitor. Electrochemical impedance spectroscopy was used to investigate the mechanism of corrosion inhibition. Thermodynamic parameters were calculated to investigate mechanism of inhibition. AFM is used to investigate the surface morphology of the uninhibited and inhibited mild steel.

  9. Discovery of a Potent, Selective, and Efficacious Class of Reversible α-Ketoheterocycle Inhibitors of Fatty Acid Amide Hydrolase Effective as Analgesicsa

    Boger, Dale L.; Miyauchi, Hiroshi; Du, Wu; Hardouin, Christophe; Fecik, Robert A.; Cheng, Heng; Hwang, Inkyu; Hedrick, Michael P.; Leung, Donmienne; Acevedo, Orlando; Guimarães, Cristiano R. W.; Jorgensen, William L.; Cravatt, Benjamin F.

    2005-01-01

    Fatty acid amide hydrolase (FAAH) degrades neuromodulating fatty acid amides including anandamide (endogenous cannabinoid agonist) and oleamide (sleep-inducing lipid) at their sites of action and is intimately involved in their regulation. Herein we report the discovery of a potent, selective, and efficacious class of reversible FAAH inhibitors that produce analgesia in animal models validating a new therapeutic target for pain intervention. Key to the useful inhibitor discovery was the routi...

  10. Disproportional exaggerated aspartate transaminase is a useful prognostic parameter in late leptospirosis

    Ming-Ling Chang; Chih-Wei Yang; Jeng-Chang Chen; Yu-Pin Ho; Ming-Jeng Pan; Cheng-Hui Lin; Deng-Yn Lin

    2005-01-01

    AIM: To evaluate the hepatic dysfunction in leptospirosis is usually mild and resolved eventually. However,sequential follow-up of liver biochemical data remained lacking..METHODS: The biochemistry data and clinical symptoms of 11 sporadic patients were collected and analyzed, focusing on the impacts of leptospirosis upon liver biochemistry tests.RESULTS: The results disclosed that of the 11 cases, 5 or 45% died. The liver biochemistry data in the beginning of the disease course were only mildly elevated.Nevertheless, late exaggerated aspartate transaminase (AST)elevations were noted in three cases who finally died when compared with the typical course. Besides, significant higher AST/alanine transaminase (ALT) ratios (AARs) of the peak levels for transaminase were also noted in the cases who eventually succumbed. The mean±SD of AARs for the survival group and dead group were 5.65±2.27 (n = 5)and 1.86±0.64 (n = 6) respectively (P= 0.006). The ratios of the cases who finally died were all more than 3.0.Conversely, the survival group's ratios were less than 3.0.CONCLUSION: Serial follow-up of transaminase might provide evidence to predict some rare evolutions in leptospirosis. If AST elevated progressively without a concomitant change of ALT, it might indicate an acute disease course with ensuing death. Additionally, AAR is another prognostic parameter for leptospirosis. Once the value was higher than 3.0, a grave prognosis is inevitable.

  11. Amine donor and acceptor influence on the thermodynamics of ω-transaminase reactions

    Gundersen, Maria T.; Abu, Rohana; Schürmann, Martin; Woodley, John

    2015-01-01

    In recent years biocatalytic transamination using ω-transaminase has become established as one of the most interesting routes to synthesize chiral amines with a high enantiomeric purity, especially in the pharmaceutical sector where the demand for such compounds is high. Nevertheless, one limitat...

  12. A Practical and Fast Method To Predict the Thermodynamic Preference of ω-Transaminase-Based Transformations

    Meier, Robert J.; Gundersen, Maria T.; Woodley, John; Schürmann, Martin

    2015-01-01

    A simple, easy-to-use, and fast approach method is proposed and validated that can predict whether a transaminase reaction is thermodynamically unfavourable. This allowed us to de-select, in the present case, at least 50% of the reactions because they were thermodynamically unfavourable as confir...

  13. Indian patients with nonalcoholic fatty liver disease presenting with raised transaminases are different at presentation

    Ajay Duseja; Naveen Kaita; Ashim Das; Radha Krishan Dhiman; Yogesh Kumar Chawla; Reena Das; Sanjay Bhadada; Ravinder Sialy; Kiran Kumar Thumburu; Anil Bhansali

    2007-01-01

    @@ TO THE EDITOR We read with great interest the article, "Non-alcoholic fatty liver disease may not be a severe disease at presentation among Asian Indians" by Madan et al in the recent issue of WJG. Twenty-eight (55%) out of 51 patients with nonalcoholic fatty liver disease (NAFLD) who presented with abnormal transaminases had histological evidence of nonalcoholic steatohepatitis (NASH).

  14. A Rapid Selection Procedure for Simple Commercial Implementation of omega-Transaminase Reactions

    Gundersen Deslauriers, Maria; Tufvesson, Pär; Rackham, Emma J.; Lloyd, Richard C.; Woodley, John

    2016-01-01

    A stepwise selection procedure is presented to quickly evaluate whether a given omega-transaminase reaction is suitable for a so-called "simple" scale-up for fast industrial implementation. Here "simple" is defined as a system without the need for extensive process development or specialized...

  15. Immobilization of Escherichia coli containing ω‐transaminase activity in LentiKats®

    Cárdenas‐Fernández, Max; Lima Afonso Neto, Watson; López, Carmen; Álvaro, Gregorio; Tufvesson, Pär; Woodley, John M.

    2012-01-01

    Whole Escherichia coli cells overexpressing ω‐transaminase (ω‐TA) and immobilized cells entrapped in LentiKats® were used as biocatalysts in the asymmetric synthesis of the aromatic chiral amines 1‐phenylethylamine (PEA) and 3‐amino‐1‐phenylbutane (APB). Whole cells were permeabilized with...

  16. Selections of minimal conditions for a simple intensification and scale up of w-transaminase reactions

    Gundersen, Maria T.; Lloyd, Richard C; Woodley, John

    A step wise decision matrix is presented to quickly evaluate w - transaminase for a ‘simple scale up’ in the synthetic direction . Here a ‘simple scale up’ is defined as a system without specialized equipment or process development, thus a rapid implementation . The three step method consists of...

  17. A new dioxime corrosion inhibitor for the protection and conservation of copper: synthesis, characterization and evaluation in acidic chloride solution

    Abu-Baker, Ahmad N.; Al-Qudah, Mahmoud A.

    2016-08-01

    This study aimed to investigate a new dioxime compound as a corrosion inhibitor for copper. The compound (4,6-dihydroxy benzene-1,3-dicarbaldehyde dioxime) was synthesized and characterized by nuclear magnetic resonance spectroscopy. Electrochemical impedance spectroscopy and potentiodynamic polarization measurements were used to compare the dioxime compound with benzotriazole for their effectiveness as corrosion inhibitors for copper in 0.1 M HCl solution. Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM) were used to investigate the bonding mechanisms and morphological changes of the two inhibitors on the copper surface. The electrochemical techniques showed that the new dioxime compound was more effective than benzotriazole in inhibiting copper corrosion in the acidic chloride medium. The FTIR and SEM results indicated that the dioxime compound was able to coordinate with copper ions and formed a protective film on the copper surface. It was concluded that the new dioxime compound proved effectiveness to be used as a corrosion inhibitor for the protection and conservation of copper.

  18. Corrosion inhibitor activity of 1,3-diketone malonates for mild steel in aqueous hydrochloric acid solution

    Highlights: ► 1,3-Diketone malonates displayed relatively high corrosion inhibition efficiency. ► Inhibition efficiency is improved when temperature is increased within 25–55 °C. ► Corrosion inhibitor efficiency of diketone malonates is dependent on diketo population tautomer. ► Diketone malonates act as mixed corrosion inhibitors with a Langmuir isotherm. - Abstract: Four 1,3-diketone malonates compounds were synthesized and tested as corrosion inhibitors for mild steel in 1.0 M aqueous hydrochloric acid. Gravimetric and polarization tests showed that inhibitor efficiencies were related to molecular moiety and depended on tautomer concentration, i.e. enol–keto and diketo. Both tautomers displayed relatively high corrosion inhibition efficiency (75–96%) at 100 mg L−1, which increased with temperature (25–55 °C) and dependent on diketo population. Improvement in corrosion resistance was related to the presence of different substituent groups, from which hydrogen substituent contributed the most, apparently due to easiness of electron acceptance as confirmed by quantum chemical calculations.

  19. New coumarin derivative as an eco-friendly inhibitor of corrosion of mild steel in Acid medium.

    Al-Amiery, Ahmed A; Al-Majedy, Yasameen K; Kadhum, Abdul Amir H; Mohamad, Abu Bakar

    2015-01-01

    The anticorrosion ability of a synthesized coumarin, namely 2-(coumarin-4-yloxy)acetohydrazide (EFCI), for mild steel (MS) in 1 M hydrochloric acid solution has been studied using a weight loss method. The effect of temperature on the corrosion rate was investigated, and some thermodynamic parameters were calculated. The results indicated that inhibition efficiencies were enhanced with an increase in concentration of inhibitor and decreased with a rise in temperature. The IE value reaches 94.7% at the highest used concentration of the new eco-friendly inhibitor. The adsorption of inhibitor on MS surface was found to obey a Langmuir adsorption isotherm. Scanning electron microscopy (SEM) was performed on inhibited and uninhibited mild steel samples to characterize the surface. The Density Function theory (DFT) was employed for quantum-chemical calculations such as EHOMO (highest occupied molecular orbital energy), ELUMO (lowest unoccupied molecular orbital energy) and μ (dipole moment), and the obtained results were found to be consistent with the experimental findings. The synthesized inhibitor was characterized by Fourier transform infrared (FTIR) and nuclear magnetic resonance (NMR) spectroscopic studies. PMID:25551187

  20. New Coumarin Derivative as an Eco-Friendly Inhibitor of Corrosion of Mild Steel in Acid Medium

    Ahmed A. Al-Amiery

    2014-12-01

    Full Text Available The anticorrosion ability of a synthesized coumarin, namely 2-(coumarin-4-yloxyacetohydrazide (EFCI, for mild steel (MS in 1 M hydrochloric acid solution has been studied using a weight loss method. The effect of temperature on the corrosion rate was investigated, and some thermodynamic parameters were calculated. The results indicated that inhibition efficiencies were enhanced with an increase in concentration of inhibitor and decreased with a rise in temperature. The IE value reaches 94.7% at the highest used concentration of the new eco-friendly inhibitor. The adsorption of inhibitor on MS surface was found to obey a Langmuir adsorption isotherm. Scanning electron microscopy (SEM was performed on inhibited and uninhibited mild steel samples to characterize the surface. The Density Function theory (DFT was employed for quantum-chemical calculations such as EHOMO (highest occupied molecular orbital energy, ELUMO (lowest unoccupied molecular orbital energy and μ (dipole moment, and the obtained results were found to be consistent with the experimental findings. The synthesized inhibitor was characterized by Fourier transform infrared (FTIR and nuclear magnetic resonance (NMR spectroscopic studies.

  1. The fatty acid synthase inhibitor triclosan: repurposing an anti-microbial agent for targeting prostate cancer

    Sadowski, Martin C.; Pouwer, Rebecca H.; Jennifer H. Gunter; Lubik, Amy A.; Quinn, Ronald J.; Nelson, Colleen C.

    2014-01-01

    Inhibition of FASN has emerged as a promising therapeutic target in cancer, and numerous inhibitors have been investigated. However, severe pharmacological limitations have challenged their clinical testing. The synthetic FASN inhibitor triclosan, which was initially developed as a topical antibacterial agent, is merely affected by these pharmacological limitations. Yet, little is known about its mechanism in inhibiting the growth of cancer cells. Here we compared the cellular and molecular e...

  2. Detection of Reduced GABA Synthesis Following Inhibition of GABA Transaminase Using in Vivo Magnetic Resonance Signal of [13C]GABA C1

    Yang, Jehoon; Johnson, Christopher; Shen, Jun

    2009-01-01

    Previous in vivo magnetic resonance spectroscopy (MRS) studies of gamma-aminobutyric acid (GABA) synthesis have relied on 13C label incorporation into GABA C2 from [1-13C] or [1,6-13C2]glucose. In this study, the [13C]GABA C1 signal at 182.3 ppm in the carboxylic/amide spectral region of localized in vivo 13C spectra was detected. GABA-transaminase of rat brain was inhibited by administration of gabaculine after pre-labeling of GABA C1 and its metabolic precursors with exogenous [2,5-13C2]glu...

  3. Outcomes in patients with nonerosive reflux disease treated with a proton pump inhibitor and alginic acid ± glycyrrhetinic acid and anthocyanosides

    Di Pierro F

    2013-03-01

    Full Text Available Francesco Di Pierro,1 Mario Gatti,2 Giuliana Rapacioli,3 Leandro Ivaldi4 1Velleja Research, Milan, 2Gastroenterology Department, Giussano Hospital, Monza-Brianza, 3AIOR, Piacenza, 4Digestive Endoscopic Department, Ceva Hospital, Ceva, Cuneo, Italy Background: The purpose of this study was to compare the efficacy of alginic acid alone versus alginic acid combined with low doses of pure glycyrrhetinic acid and bilberry anthocyanosides as an addon to conventional proton pump inhibitor therapy in relieving symptoms associated with nonerosive reflux disease. Methods: This prospective, randomized, 8-week, open-label trial was conducted at two centers. Sixty-three patients with persistent symptoms of gastroesophageal reflux disease and normal upper gastrointestinal endoscopy were eligible for the study. Patients in group A (n = 31 were treated with pantoprazole and a formula (Mirgeal® containing alginic acid and low doses of pure glycyrrhetinic acid + standardized Vaccinium myrtillus extract for 4 weeks, then crossed over to the multi-ingredient formula for a further 4 weeks. Patients in group B (n = 32 were treated pantoprazole and alginic acid alone twice daily, then crossed over to alginic acid twice daily for a further 4 weeks. Efficacy was assessed by medical evaluation of a symptom relief score, estimated using a visual analog scale (0–10. Side effects, tolerability, and compliance were also assessed. Results: Of the 63 patients enrolled in the study, 58 (29 in group A and 29 in group B completed the 8-week trial. The baseline characteristics were comparable between the two groups. During the study, significant differences were recorded in symptom scores for both groups. In group A, symptoms of chest pain, heartburn, and abdominal swelling were less serious than in group B. Treatment A was better tolerated, did not induce hypertension, and had fewer side effects than treatment B. No significant differences in compliance were found between the

  4. A Study of N,N-Diethylammonium O,O′-Di(p-methoxyphenyldithiophosphate as New Corrosion Inhibitor for Carbon Steel in Hydrochloric Acid Solution

    Chuan Lai

    2016-01-01

    Full Text Available N,N-Diethylammonium O,O′-di(p-methoxyphenyldithiophosphate (EAPP as a new corrosion inhibitor was synthesized in the present work. The corrosion inhibition of EAPP in hydrochloric acid for carbon steel was evaluated by potentiodynamic polarization measurements, electrochemical impedance spectroscopy, weight loss measurements, and scanning electron microscopy. The results indicate that the EAPP is mixed type inhibitor, and the adsorption of EAPP on carbon steel surface obeys Langmuir isotherm. In addition, the inhibition efficiency increases with increasing the concentration of inhibitor and decreases with increasing the hydrochloric acid concentration, temperature, and storage time.

  5. Anti-Tumor Effect in Human Lung Cancer by a Combination Treatment of Novel Histone Deacetylase Inhibitors: SL142 or SL325 and Retinoic Acids

    Shaoteng Han; Takuya Fukazawa; Tomoki Yamatsuji; Junji Matsuoka; Hiroyuki Miyachi; Yutaka Maeda; Mary Durbin; Yoshio Naomoto

    2010-01-01

    Histone deacetylase (HDAC) inhibitors arrest cancer cell growth and cause apoptosis with low toxicity thereby constituting a promising treatment for cancer. In this study, we investigated the anti-tumor activity in lung cancer cells of the novel cyclic amide-bearing hydroxamic acid based HDAC inhibitors SL142 and SL325. In A549 and H441 lung cancer cells both SL142 and SL325 induced more cell growth inhibition and cell death than the hydroxamic acid-based HDAC inhibitor suberoylanilide hydrox...

  6. Kinetics of Corrosion Inhibition of Aluminum in Acidic Media by Water-Soluble Natural Polymeric Pectates as Anionic Polyelectrolyte Inhibitors

    Refat M. Hassan

    2013-06-01

    Full Text Available Corrosion inhibition of aluminum (Al in hydrochloric acid by anionic polyeletrolyte pectates (PEC as a water-soluble natural polymer polysaccharide has been studied using both gasometric and weight loss techniques. The results drawn from these two techniques are comparable and exhibit negligible differences. The inhibition efficiency was found to increase with increasing inhibitor concentration and decrease with increasing temperature. The inhibition action of PEC on Al metal surface was found to obey the Freundlich isotherm. Factors such as the concentration and geometrical structure of the inhibitor, concentration of the corrosive medium, and temperature affecting the corrosion rates were examined. The kinetic parameters were evaluated and a suitable corrosion mechanism consistent with the kinetic results is discussed in the paper.

  7. Ellagic acid and polyhydroxylated urolithins are potent catalytic inhibitors of human topoisomerase II: an in vitro study.

    Furlanetto, Valentina; Zagotto, Giuseppe; Pasquale, Riccardo; Moro, Stefano; Gatto, Barbara

    2012-09-12

    Ellagic acid (EA), a natural polyphenol abundant in fruits and common in our diet, is under intense investigation for its chemopreventive activity resulting from multiple effects. EA inhibits topoisomerase II, but the effects on the human enzyme of urolithins, its monolactone metabolites, are not known. Therefore, the action of several synthetic urolithins toward topoisomerases II was evaluated, showing that polyhydroxylated urolithins, EA, and EA-related compounds are potent inhibitors of the α and β isoforms of human topoisomerase II at submicromolar concentrations. Competition tests demonstrate a dose-dependent relationship between ATP and the inhibition of the enzyme. Docking experiments show that the active compounds bind the ATP pocket of the human enzyme, thus supporting the hypothesis that EA and polyhydroxylated urolithins act as ATP-competitive inhibitors of human topoisomerase II. PMID:22924519

  8. Baphia nitida Leaves Extract as a Green Corrosion Inhibitor for the Corrosion of Mild Steel in Acidic Media

    V. O. Njoku

    2014-01-01

    Full Text Available The inhibiting effect of Baphia nitida (BN leaves extract on the corrosion of mild steel in 1 M H2SO4 and 2 M HCl was studied at different temperatures using gasometric and weight loss techniques. The results showed that the leaves extract is a good inhibitor for mild steel corrosion in both acid media and better performances were obtained in 2 M HCl solutions. Inhibition efficiency was found to increase with increasing inhibitor concentration and decreasing temperature. The addition of halides to the extract enhanced the inhibition efficiency due to synergistic effect which improved adsorption of cationic species present in the extract and was in the order KCl < KBr < KI suggesting possible role of radii of the halide ions. Thermodynamic parameters determined showed that the adsorption of BN on the metal surface is an exothermic and spontaneous process and that the adsorption was via a physisorption mechanism.

  9. Two phenylpyrimidine derivatives as new corrosion inhibitors for cold rolled steel in hydrochloric acid solution

    Highlights: • 4-PPM and 5-PPM are new good inhibitors for steel in HCl solution. • Inhibition efficiency follows the order: 4-PPM > 5-PPM. • The adsorption of phenylpyrimidine inhibitor obeys Langmuir adsorption isotherm. • There is a correlation between quantum chemical parameters and inhibition action. • 4-PPM and 5-PPM molecules adsorb on Fe (0 0 1) surface in the nearly flat manner. - Abstract: The inhibition effect of two phenylpyrimidine derivatives of 4-phenylpyrimidine (4-PPM) and 5-phenylpyrimidine (5-PPM) on the corrosion of cold rolled steel (CRS) in HCl solution was studied by weight loss, polarization curves, electrochemical impedance spectroscopy (EIS) and scanning electron microscope (SEM) methods. Quantum chemical calculation and molecular dynamics (MD) were applied to theoretically determine the relationship between molecular structure and inhibition efficiency. The results show that two phenylpyrimidine derivatives are good inhibitors, and inhibition efficiency follows the order: 4-PPM > 5-PPM. The adsorption of each inhibitor on steel surface obeys Langmuir adsorption isotherm. Two phenylpyrimidine derivatives act as mixed-type inhibitors

  10. Chemically modified natural polysaccharide as green corrosion inhibitor for mild steel in acidic medium

    Highlights: ► Polyacrylamide grafted with Okra mucilage is a biodegradable co-polymer. ► It is an effective green corrosion inhibitor for mild steel in 0.5 M H2SO4. ► The inhibition efficiency is both concentration and time dependent. ► It acts as a predominantly cathodic inhibitor. ► Physically adsorbed polymer film on the metal surface restricts the corrosion. - Abstract: A new green polymeric material, polyacrylamide grafted with Okra mucilage, a natural grade polysaccharide, was tested as corrosion inhibitor for mild steel in 0.5 M H2SO4 using gravimetric and electrochemical techniques. The inhibition efficiency was found to increase with increasing inhibitor concentration up to maximum 96.6% for 100 ppm at 25 °C. The effects of immersion time (3–72 h) and temperature (25–65 °C) on the inhibition of corrosion have also been discussed. The adsorption of this inhibitor on the mild steel surface obeys a Langmuir adsorption isotherm. The scanning electron micrographs of the inhibited specimens show smoothening of the surface.

  11. Rat brain slices produce and liberate kynurenic acid upon exposure to L-kynurenine

    Turski, W A; Gramsbergen, J B; Traitler, H; Schwarcz, R

    1989-01-01

    extracellular KYNA appears to occur at the level of L-KYN uptake and/or kynurenine transaminase, the biosynthetic enzyme of KYNA. KYNA production from L-KYN was linear up to 4 h and reached a plateau at a L-KYN concentration of 250 microM. The process was effectively inhibited by the transaminase inhibitor...

  12. An Investigation on the Tetrahydropyrimidine Derivatives as Acid Corrosion Inhibitors fro Mild Steel

    The corrosive behavior of mild steel in 0.05 M to 10 M H2SO4 solutions containing different concentrations of tetrahydropyrimidine derivatives (THPM) was investigated using weight loss method, gasometric technique, electrochemical studies which include AC- impedance and potentiodynamic polarization method, atomic absorption studies and synergistic effect. The results obtained reveal that THPM derivatives is an efficient mixed type inhibitor but slightly anodic and it is more effective in reducing corrosion of mild steel in H2SO4 media. The adsorption of the inhibitor on the mild steel surface obeys the Langmuir adsorption isotherm. The thermodynamic parameters of adsorption reveal a strong interaction and spontaneous adsorption of THPM on the mild steel surface. The influence of temperature and inhibitor concentration on the corrosion of mild steel has also been investigated

  13. Experimental and theoretical studies of thiazoles as corrosion inhibitors for mild steel in sulphuric acid solution

    Graphical abstract: The inhibition effect of 2-amino-5-mercapto-1,3,4-thiadiazole and 2-mercaptothiazoline on mild steel corrosion in 1.0 M H2SO4 was studied using electrochemical techniques. The effects of the presence of extra NH2 group and N atom in 2A5MT on the ability to act as corrosion inhibitors were investigated by theoretical calculations. Highlights: → The inhibition effects of thiazoles on mild steel corrosion in 1.0 M H2SO4 were studied. → It was shown that both thiazole compounds act as excellent corrosion inhibitors for mild steel. → The high inhibition efficiency was attributed to the adsorption of the inhibitor molecules on the metal surface. → Langmuir adsorption isotherm exhibited the best fit to the experimental data. → Quantum chemical calculations show there is a correlation between inhibitive property and molecular parameters. - Abstract: The inhibition effects of 2-amino-5-mercapto-1,3,4-thiadiazole (2A5MT) and 2-mercaptothiazoline (2MT) on mild steel corrosion in 1.0 M H2SO4 were studied with potentiodynamic polarization, linear polarization resistance and electrochemical impedance spectroscopy techniques. It was shown that both 2A5MT and 2MT act as good corrosion inhibitors for mild steel protection. The high inhibition efficiencies were attributed to the simple blocking effect by adsorption of inhibitor molecules on the steel surface. The effects of the presence of extra NH2 group and N atom in 2A5MT on the ability to act as corrosion inhibitors were investigated by theoretical calculations.

  14. Pomegranate (Punica granatum Peel Extract as a Green Corrosion Inhibitor for Mild Steel in Hydrochloric Acid Solution

    Habib Ashassi-Sorkhabi

    2015-01-01

    Full Text Available The inhibition effect of pomegranate peel extract (PPE on the corrosion of mild steel in hydrochloric acid (HCl solution was investigated. The polarization, mass loss, and electrochemical impendence techniques were used to evaluate the corrosion inhibition performance of the pomegranate peel extract. The results revealed that PPE acts as a corrosion inhibitor in HCl solution. The inhibition efficiency increased with the increase of extract concentration. The inhibition action was attributed to the adsorption of the chemical compounds present in the extract solution, on mild steel surface.

  15. Identification of Na+/K+-ATPase inhibitors in bovine plasma as fatty acids and hydrocarbons

    Tal, D M; Yanuck, M D; Van Hall, Gerrit;

    1989-01-01

    A preparative purification of endogenous inhibitors of the Na+/K+-ATPase has been carried out from bovine blood. Dried plasma was deproteinized, hexane-extracted and desalted, followed by further purification through a series of reverse-phase HPLC fractionations. Fractions active in inhibiting Na...

  16. Cyclopiazonic acid, an inhibitor of calcium-dependent ATPases with antiviral activity against human respiratory syncytial virus.

    Cui, Rui; Wang, Yizhuo; Wang, Liu; Li, Guiming; Lan, Ke; Altmeyer, Ralf; Zou, Gang

    2016-08-01

    Human respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infections in infants and young children worldwide, yet no vaccine or effective antiviral treatment is available. To search for new anti-RSV agents, we developed a cell-based assay that measures inhibition of RSV-induced cytopathic effect (CPE) and identified cyclopiazonic acid (CPA), an intracellular calcium ATPase inhibitor as a RSV inhibitor (EC50 values 4.13 μM) by screening of natural product library. CPA inhibited the replication of RSV strains belonging to both A and B subgroups and human parainfluenza virus type 3, but not Enterovirus 71. Mechanism of action study by time-of-addition assay and minigenome assay revealed that CPA acts at the step of virus genome replication and/or transcription. Moreover, two other calcium ATPase inhibitors (Thapsigargin and BHQ) and calcium ionophores (A23187 and ionomycin), but not calcium channel blockers (nifedipine, nimodipine, and tetrandrine), also had similar effect. These results indicate that an increase in intracellular calcium concentration is detrimental to RSV replication. Thus, our findings provide a new strategy for anti-RSV therapy via increasing intracellular calcium concentration. PMID:27210812

  17. Experimental and quantum chemical studies on two triazole derivatives as corrosion inhibitors for mild steel in acid media

    Li, W.; Tian, H.; Hou, B. [Key Laboratory of Corrosion Science, Shandong, Institute of Oceanology, Chinese Academy of Sciences, Qingdao (China); Hu, L.; Tao, Z. [College of Chemistry and Chemical Engineering, Chongqing University, Chongqing (China)

    2011-11-15

    Two triazole derivatives [1-phenyl-2-(5-(1,2,4) triazol-1-ylmethyl-(1,3,4) oxadizaol-2-ylsulphanyl)-ethanone (PTOE) and 2-(4-tert-butyl-benzylsulphanyl)-5-(1,2,4) triazol-1-ylmethyl-(1,3,4) oxadiazole (TBTO)] were synthesized as new corrosion inhibitors for the corrosion of mild steel in 1 M hydrochloric acid solutions. The inhibiting efficiency of the different inhibitors was evaluated by means of weight loss and electrochemical techniques such as electrochemical impedance spectroscopy (EIS) and polarization curves. The electrochemical investigation results indicate that these compounds act as mixed-type inhibitors retarding the anodic and cathodic corrosion reactions and do not change the mechanism of either hydrogen evolution reaction or mild steel dissolution. The studied compounds followed the Langmuir adsorption isotherm, and the thermodynamic parameters were determined and discussed. The effect of molecular structure on the inhibition efficiency has been investigated with ab initio calculations. The electronic properties such as highest occupied molecular orbital (HOMO) energy level, lowest unoccupied molecular orbital (LUMO) energy level, dipole moment ({mu}) and molecular orbital densities were calculated. (Copyright copyright 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  18. A Potent Systemically Active N-Acylethanolamine Acid Amidase Inhibitor that Suppresses Inflammation and Human Macrophage Activation.

    Ribeiro, Alison; Pontis, Silvia; Mengatto, Luisa; Armirotti, Andrea; Chiurchiù, Valerio; Capurro, Valeria; Fiasella, Annalisa; Nuzzi, Andrea; Romeo, Elisa; Moreno-Sanz, Guillermo; Maccarrone, Mauro; Reggiani, Angelo; Tarzia, Giorgio; Mor, Marco; Bertozzi, Fabio; Bandiera, Tiziano; Piomelli, Daniele

    2015-08-21

    Fatty acid ethanolamides such as palmitoylethanolamide (PEA) and oleoylethanolamide (OEA) are lipid-derived mediators that potently inhibit pain and inflammation by ligating type-α peroxisome proliferator-activated receptors (PPAR-α). These bioactive substances are preferentially degraded by the cysteine hydrolase, N-acylethanolamine acid amidase (NAAA), which is highly expressed in macrophages. Here, we describe a new class of β-lactam derivatives that are potent, selective, and systemically active inhibitors of intracellular NAAA activity. The prototype of this class deactivates NAAA by covalently binding the enzyme's catalytic cysteine and exerts profound anti-inflammatory effects in both mouse models and human macrophages. This agent may be used to probe the functions of NAAA in health and disease and as a starting point to discover better anti-inflammatory drugs. PMID:25874594

  19. Design, synthesis and evaluation of semi-synthetic triazole-containing caffeic acid analogues as 5-lipoxygenase inhibitors.

    De Lucia, Daniela; Lucio, Oscar Méndez; Musio, Biagia; Bender, Andreas; Listing, Monika; Dennhardt, Sophie; Koeberle, Andreas; Garscha, Ulrike; Rizzo, Roberta; Manfredini, Stefano; Werz, Oliver; Ley, Steven V

    2015-08-28

    In this work the synthesis, structure-activity relationship (SAR) and biological evaluation of a novel series of triazole-containing 5-lipoxygenase (5-LO) inhibitors are described. The use of structure-guided drug design techniques provided compounds that demonstrated excellent 5-LO inhibition with IC50 of 0.2 and 3.2 μm in cell-based and cell-free assays, respectively. Optimization of binding and functional potencies resulted in the identification of compound 13d, which showed an enhanced activity compared to the parent bioactive compound caffeic acid 5 and the clinically approved zileuton 3. Compounds 15 and 16 were identified as lead compounds in inhibiting 5-LO products formation in neutrophils. Their interference with other targets on the arachidonic acid pathway was also assessed. Cytotoxicity tests were performed to exclude a relationship between cytotoxicity and the increased activity observed after structure optimization. PMID:26197161

  20. Pengaruh Obat Anti-Tuberkulosis terhadap Perubahan Enzim Transaminase Hati dalam Dua Bulan Pengobatan Tahun 2015

    Jackson

    2016-01-01

    Since 1995, WHO recommends DOTS strategy to prevent TB in Indonesia. This strategy has high effectivity, but the cure rate is still low because of low compliance for regular treatment which one of the casues is drug side effect. Anti-TB Drug effects are various and one of them is hepatotoxicity which liver transaminase enzymes rise without clinical symptoms is a common episode after Anti-TB drug treatment so that BTS recommends liver function monitoring for two months. Therefore, the purpose ...

  1. Complexes of Imidazole with Poly(ethylene glycol) as a Corrosion Inhibitor for Carbon Steel in Sulphuric Acid

    Salimi, Saeed; Nasr-Esfahani, Mojtaba; Umoren, Saviour A.; Saebnoori, Ehsan

    2015-12-01

    The inhibiting action of polyethylene glycol and imidazole (PEG/IMZ)) complexes prepared by a simple deprotonation procedure on carbon steel corrosion in 0.5 mol/L sulphuric acid was evaluated using the weight loss, potentiodynamic polarization, and electrochemical impedance spectroscopy techniques complemented by surface analysis using scanning electron microscopy. The inhibiting effect of the PEG/IMZ complexes on carbon steel corrosion was compared with the non-complex forms. Results obtained show that PEG/IMZ complex is a very effective corrosion inhibitor of carbon steel in the acid environment. The inhibition efficiency increased with the increase in the temperature and also with increasing percentage of imidazole in the complex. Corrosion inhibition occurs by virtue of adsorption of PEG/IMZ complexes on the steel surface which was found to follow the Temkin adsorption isotherm model. The PEG/IMZ complexes function as a mixed-type inhibitor. Results from all the methods employed are in a reasonably good agreement.

  2. N-alkylated aminoacyl sulfamoyladenosines as potential inhibitors of aminoacylation reactions and microcin C analogues containing D-amino acids.

    Gaston H Vondenhoff

    Full Text Available Microcin C analogues were recently envisaged as important compounds for the development of novel antibiotics. Two issues that may pose problems to these potential antibiotics are possible acquisition of resistance through acetylation and in vivo instability of the peptide chain. N-methylated aminoacyl sulfamoyladenosines were synthesized to investigate their potential as aminoacyl tRNA synthetase inhibitors and to establish whether these N-alkylated analogues would escape the natural inactivation mechanism via acetylation of the alpha amine. It was shown however, that these compounds are not able to effectively inhibit their respective aminoacyl tRNA synthetase. In addition, we showed that (D-aspartyl-sulfamoyladenosine (i.e. with a (D-configuration for the aspartyl moiety, is a potent inhibitor of aspartyl tRNA synthetase. However, we also showed that the inhibitory effect of (D- aspartyl-sulfamoyladenosine is relatively short-lasting. Microcin C analogues with (D-amino acids throughout from positions two to six proved inactive. They were shown to be resistant against metabolism by the different peptidases and therefore not able to release the active moiety. This observation could not be reversed by incorporation of (L-amino acids at position six, showing that none of the available peptidases exhibit endopeptidase activity.

  3. Expression in Pichia pastoris and characterization of APETx2, a specific inhibitor of acid sensing ion channel 3.

    Anangi, Raveendra; Chen, Chih-Cheng; Lin, Yi-Wen; Cheng, Yuan-Ren; Cheng, Chun-Ho; Chen, Yi-Chun; Chu, Yuan-Ping; Chuang, Woei-Jer

    2010-12-01

    Acid sensing ion channels (ASICs) are family of proteins predominantly present in the central and peripheral nervous system. They are known to play important roles in the pathophysiology of pain and ischemic stroke. APETx2 is a potent and selective inhibitor of ASIC3-containing channels and was isolated from sea anemone Anthopleura elegantissima. To facilitate the study on the molecular determinants of ASIC3-ligand interactions, we expressed recombinant APETx2 in the Pichia pastoris (P. pastoris) expression system and purified it to homogeneity. Recombinant APETx2 produced in P. pastoris inhibited the acid-evoked ASIC3 current with the IC(50) value of 37.3 nM. The potency of recombinant toxin is similar to that of native APETx2. The sequential assignment and structure analysis of APETx2 were obtained by 2D and 3D (15)N-edited NMR spectra. Our NMR data suggests that APETx2 produced in P. pastoris retained its native fold. The results presented here provide the first direct evidence that highly disulfide bonded peptide inhibitor of ASIC3, APETx2, can be expressed in P. pastoris with correct fold and high yield. We also showed that the R17A mutant exhibited a decrease in activity, suggesting the feasibility of the use of this expression system to study the interactions between APETx2 and ASIC3. These evidences may serve as the basis for understanding the selectivity and activity of APETx2. PMID:20813121

  4. Development of Highly Potent GAT1 Inhibitors: Synthesis of Nipecotic Acid Derivatives by Suzuki-Miyaura Cross-Coupling Reactions.

    Petrera, Marilena; Wein, Thomas; Allmendinger, Lars; Sindelar, Miriam; Pabel, Jörg; Höfner, Georg; Wanner, Klaus T

    2016-03-01

    A new series of potent and selective mGAT1 inhibitors has been identified, featuring a nipecotic acid residue and an N-butenyl linker with a 2-biphenyl residue at the ω-position. Docking, combined with MD calculations, revealed a binding mode for the new compounds similar to that of tiagabine, the only mGAT1 inhibitor currently approved as antiepileptic drug. For the synthesis, a Suzuki-Miyaura cross-coupling reaction was used as a key step by which variously substituted biaryl subunits were assembled. Biological evaluation revealed several compounds that possess binding affinities and inhibitory potencies toward mGAT1, together with subtype selectivities against mGAT2-mGAT4 that were similar to or even higher than those for tiagabine. A derivative carrying the 2',4'-dichloro-2-biphenyl moiety attached to N-but-3-enylnipecotic acid at the terminal position of the linker chain was found to be the most potent binder, with the racemic form of the compound displaying a binding affinity of 8.05±0.13 (pKi ), while the R enantiomer exhibited an affinity value of 8.33±0.06 (pKi ). PMID:26683881

  5. Novel dispersed magnetite core-shell nanogel polymers as corrosion inhibitors for carbon steel in acidic medium

    Graphical abstract: Display Omitted Research highlights: → Through a one-step thermal reaction, magnetite nanoparticles were synthesized, and self-assembled mixed films of modified cross-linked ionic polymer magnetite nanoparticles were prepared on iron surface. → The size distribution and shape of magnetite nanoparticles were examined using transmission electron microscopy (TEM). → The corrosion inhibition efficiency of carbon steel in 1 M HCl by the synthesized Fe3O4 nanogel polymers has been studied using potentiodynamic polarization and EIS. → Scanning electron microscopy (SEM) measurements were applied to study the morphology of the carbon steel surface. - Abstract: Novel core-shell preparing poly(2-acrylamido-2-methylpropane sulfonic acid) (PAMPS) and copolymers with acrylic acid (AA) or acrylamide (AM) magnetic nanogels with controllable particle size produced via free aqueous polymerization at room temperature have been developed for the first time. The crosslinking polymerization was carried out in the presence of N,N'-methylenebisacrylamide (MBA) as a crosslinker, N,N,N',N'-tetramethylethylenediamine (TEMED) and potassium peroxydisulfate (KPS) as redox initiator system. The structure and morphology of the magnetic nanogels were characterized by Fourier transform infrared spectroscopy (FTIR), transmission and scanning electron microscopy (TEM and SEM). The effectiveness of the synthesized compounds as corrosion inhibitors for carbon steel in 1 M HCl was investigated by various electrochemical techniques such as potentiodynamic polarization and electrochemical impedance spectroscopy (EIS). The results showed enhancement in inhibition efficiencies with increasing the inhibitor concentrations and temperatures. The results showed the nanogel particles act as mixed inhibitors. Adsorption of nanogel particles was found to fit the Langmuir isotherm and was chemisorption.

  6. Organic compounds as corrosion inhibitors for mild steel in acidic media: correlation between inhibition efficiency and chemical structure

    Elias, Elizandra C.S.; Chrisman, Erika C.A.N. [Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ (Brazil). Escola de Quimica

    2009-12-19

    The use of inhibitors for mild steels corrosion control which are in contact with aggressive environment is an accepted practice in acid treatment of oil-wells. Organic compounds have been studied to evaluate their corrosion inhibition potential. Film-forming corrosion inhibitors, commonly used to protect oil-field equipment, can be absorbed on the steel surface to give structurally ordered layers. Therefore, the electrons should act as an important role for this adsorption. Studies reveal that organic compounds show significant inhibition efficiency. For this purpose, their molecules should contain N, O and S heteroatoms in various functional groups, long hydrocarbon linear or branched radical and anion and cation active components. However, most of these compounds are not only expensive but also toxic to living beings. According to the 'Green Chemistry' rules, corrosion inhibitors based on organic compounds should be cheap, with low toxicity and have high inhibition efficiency. In this study, the effects of some organic compounds with different groups such as amide, ether, phenyldiamine, anime and aminophenol on the corrosion behavior of mild steel in acidic media have been investigated. The experimental data were obtained by gravimetric measurements. The results show that these compounds reveal a promising corrosion inhibition where phenyldiamine is the most efficient. The effect of molecular structure on the corrosion inhibition efficiency was investigated by semi-empirical quantum chemical calculations. The electronic properties such as highest occupied molecular orbital (HOMO), lowest unoccupied molecular orbital (LUMO) energy levels, and LUMO-HOMO energy gap orbital density were calculated. The relations between the inhibition efficiency and some quantum parameters are discussed and correlations are proposed. The highest values for the HOMO densities were found in the vicinity nitrogen atom, indicating that it is the most probable adsorption center

  7. Towards a standardized way of reporting physicochemical data and process metrics for transaminase reactions

    Tufvesson, Pär

    Transaminase catalyzed transformations have the potential of becoming a standard tool for the synthesis of optically pure chiral amines [1]. Many studies show the wide span of substrate acceptance and the excellent enantioselectivity that can be achieved [2]. However, many times critical informat......Transaminase catalyzed transformations have the potential of becoming a standard tool for the synthesis of optically pure chiral amines [1]. Many studies show the wide span of substrate acceptance and the excellent enantioselectivity that can be achieved [2]. However, many times critical...... information about the system and the reaction performance is lacking in the otherwise very useful scientific reports at laboratory scale. For instance, although K equilibrium is one of the key determining factors for the design and scale-up any transaminase process, it is very rarely reported [3]. In order...... to build a broader understanding of the correlation between the underlying physicochemical properties of the system (e.g. substrate volatility) and the process performance (e.g. gram of product per gram of biocatalyst), it would be highly beneficial if these data were reported, and ideally in a consistent...

  8. Marked elevation of transaminases and pancreatic enzymes in severe malnourished male with eating disorder.

    Urso, C; Brucculeri, S; Caimi, G

    2013-01-01

    We report a case of a 45 year old Caucasian malnourished male with an history of eating disorder who developed severe liver and pancreatic damage and multiorgan disfunction. At admission to our department, his body mass index (BMI) was 11.1. Biochemical evaluation showed elevated serum levels of transaminases (AST= 2291 U/L, ALT= 1792 U/L), amylase (3620 U/L), lipase (4102 U/L), CPK= 1370 U/L, LDH= 2082 U/L. No other cause of acute liver and pancreatic damage was evidenced. Haematological disorders (anemia, thrombocytopenia, leukopenia) found on admission seem related to bone marrow hypoplasia and to gelatinous marrow transformation described in severe state of malnutrition. Although a moderate increase in liver and pancreatic enzymes are a common finding in malnourished patients, only a small number of reports describes severe liver injury and multiorgan dysfunction. After a few days of treatment (hydration and nutritional support) a marked decrease of serum transaminases, lipase, amylase, CPK, LDH occurred, despite a transient increase in these levels secondary to refeeding syndrome. The association of chronic malnutrition and a decrease in systemic perfusion may be responsible for multiorgan dysfunction. In our patient the high levels of transaminases and pancreatic enzymes were the most important biochemical abnormalities normalized after refeeding. PMID:24217841

  9. Advances in the discovery of N-acylethanolamine acid amidase inhibitors

    Bandiera, Tiziano; Ponzano, Stefano; Piomelli, Daniele

    2014-01-01

    N-acylethanolamine acid amidase (NAAA) is a cysteine amidase that hydrolyzes saturated or monounsaturated fatty acid ethanolamides, such as palmitoylethanolamide (PEA) and oleoylethanolamide (OEA). PEA has been shown to exert analgesic and anti-inflammatory effects by engaging peroxisome proliferator-activated receptor-α. Like other fatty acid ethanolamides, PEA is not stored in cells, but produced on demand from cell membrane precursors, and its actions are terminated by intracellular hydrol...

  10. Nucleoside phosphonic acids as selective inhibitors of human pyrimidine- specific 5'-nucleotidases

    Šimák, Ondřej (ed.); Buděšínský, Miloš; Petrová, Magdalena; Zborníková, Eva; Pachl, Petr; Brynda, Jiří; Rosenberg, Ivan

    Montreal : International Society of Nucleosides, Nucleotides and Nucleic Acids, 2012. s. 49-49. [International Round Table on Nucleosides Nucleotides and Nucleic Acids /20./. 05.08.2012-09.08.2012, Montreal] R&D Projects: GA AV ČR KAN200520801; GA ČR GA203/09/0820 Institutional support: RVO:61388963 ; RVO:68378050 Keywords : nucleoside phosphonic acids Subject RIV: CC - Organic Chemistry