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Sample records for 2-amino-3 hydroxy-4-phenyl thiazolium

  1. Synthesis, structure and solvatochromic properties of some novel 5-arylazo-6-hydroxy-4-phenyl-3-cyano-2-pyridone dyes

    OpenAIRE

    Alimmari Adel; Mijin Dušan; Vukićević Radovan; Božić Bojan; Valentić Nataša; Vitnik Vesna; Vitnik Željko; Ušćumlić Gordana

    2012-01-01

    Abstract Background A series of some novel arylazo pyridone dyes was synthesized from the corresponding diazonium salt and 6-hydroxy-4-phenyl-3-cyano-2-pyridone using a classical reaction for the synthesis of the azo compounds. Results The structure of the dyes was confirmed by UV-vis, FT-IR, 1H NMR and 13C NMR spectroscopic techniques and elemental analysis. The solvatochromic behavior of the dyes was evaluated with respect to their visible absorption properties in various solvents. Conclusi...

  2. Mono- and bis-thiazolium salts have potent antimalarial activity.

    Science.gov (United States)

    Hamzé, Abdallah; Rubi, Eric; Arnal, Pascal; Boisbrun, Michel; Carcel, Carole; Salom-Roig, Xavier; Maynadier, Marjorie; Wein, Sharon; Vial, Henri; Calas, Michèle

    2005-05-19

    Three new series comprising 24 novel cationic choline analogues and consisting of mono- or bis (N or C-5-duplicated) thiazolium salts have been synthesized. Bis-thiazolium salts showed potent antimalarial activity (much superior to monothiazoliums). Among them, bis-thiazolium salts 12 and 13 exhibited IC(50) values of 2.25 nM and 0.65 nM, respectively, against P. falciparum in vitro. These compounds also demonstrated good in vivo activity (ED(50)

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

    DEFF Research Database (Denmark)

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

    2002-01-01

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

  4. 1,3-thiazolium-5-thiolates mesoionic compounds: semiempirical evaluation of their first static hyperpolarizabilities and synthesis of new examples

    Energy Technology Data Exchange (ETDEWEB)

    Lyra, Bruno F.; Morais, Soraya A. de; Rocha, Gerd B.; Athayde-Filho, Petronio F. de, E-mail: gbr@quimica.ufpb.b [Universidade Federal da Paraiba (UFPB), Joao Pessoa, PB (Brazil). Dept. de Quimica; Miller, Joseph [Universidade Federal da Paraiba (UFPB), Joao Pessoa, PB (Brazil). Lab. de Tecnologia Farmaceutica; Moura, Gustavo L.C.; Simas, Alfredo M. [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil). Dept. de Quimica Fundamental; Peppe, Clovis [Universidade Federal de Santa Maria (UFSM), RS (Brazil). Dept. de Quimica

    2010-07-01

    Semiempirical AM1-TDHF calculations of the static first hyperpolarizabilities, beta(0), of 1,3-thiazolium-5-thiolate mesoionic derivatives were performed. Guided by these results, two new mesoionic compounds - 2-(4-nitrophenyl)-3-methyl-4-(methylphenyl)-1,3-thiazolium-5-thiolate and 2-(4-nitrophenyl)-3-methyl-4-(methoxyphenyl)-1,3-thiazolium-5-thiolate - were synthesized and characterized by analytical and spectroscopic means. (author)

  5. Microwave promoted one-pot synthesis of 3-(2'-amino-3'-cyano-4'-arylpyrid-6'-yl) coumarins

    Institute of Scientific and Technical Information of China (English)

    Jian Feng Zhou; Gui Xia Gong; Feng Xia Zhu; San Jun Zhi

    2009-01-01

    A facile procedure for the synthesis of 3-(2'-amino-3'-cyano-4'-arylpyrid-6'-yl) coumarins are being reported starting from 3-acetylcoumarin, aromatic aldehydes and malononitrile. The reactions were carded out on microwave irradiation in good yield with short time and easy work-up. The structures of all the compounds have been confirmed on the basis of their analytical, IR,1H NMR,and mass spectral data.

  6. Cardiac damage induced by 2-amino-3-methyl-imidazo[4,5-f]quinoline in nonhuman primates.

    OpenAIRE

    Thorgeirsson, U P; Farb, A; Virmani, R.; Adamson, R. H.

    1994-01-01

    The heterocyclic aromatic amine 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) is a potent hepatocarcinogen in cynomolgus and rhesus monkeys. The finding of high cardiac IQ-DNA adduct levels prompted a histopathological study of perfusion-fixed hearts from 10 tumor-bearing monkeys chronically dosed with IQ at 10 mg/kg or 20 mg/kg 5 days per week for 48-80 months. Two monkeys dosed only with the vehicle for IQ, hydroxypropylcellulose, served as controls. All the monkeys had normal heart weights,...

  7. 2'-Aminoethoxy-2-amino-3-methylpyridine in triplex-forming oligonucleotides: high affinity, selectivity and resistance to enzymatic degradation.

    Science.gov (United States)

    Lou, Chenguang; Shelbourne, Montserrat; Fox, Keith R; Brown, Tom

    2011-12-23

    The phosphoramidite monomer of the C-nucleoside 2'-aminoethoxy-2-amino-3-methylpyridine (AE-MAP) has been synthesized for the first time and incorporated into triplex-forming oligonucleotides (TFOs). Ultraviolet melting and DNase I footprinting studies show that AE-MAP is a potent triplex-stabilizing monomer that is selective for GC base pairs. TFOs containing AE-MAP bind with high affinity to duplexes but only weakly to single stranded DNA. In addition, AE-MAP confers high nuclease resistance on oligonucleotides. TFOs containing AE-MAP have potential for gene knock-out and gene expression studies. PMID:22127905

  8. DNA adduct formation by 2-amino-3-methylimidazo [4,5-f] quinoline (IQ) in rat colon

    OpenAIRE

    Lin, Chun-xing; Mondan, Yasumasa; Umemoto, Atsushi

    2001-01-01

    A food-born carcinogen, 2-amino-3-methylimidazo [4,5-f] quinoline (IQ) induces cancer in the rat colon. The mechanism for colonic DNA adduct formation leading to cancer by IQ was studied using a colostomized F344 rat model. In this model, the transverse colon of the rat was colostomized, which produced a fecal stream-positive proximal colon and a negative distal colon were produced. When IQ (50 mg/kg) was administered into the distal colon of the colostomized rats (n=5), the ratio of the DNA ...

  9. Crystal structure of 2-amino-3-ethyl-4,5-dihydro-1,3-thiazol-3-ium 3-chlorobenzoate

    Directory of Open Access Journals (Sweden)

    Sara Maira M. Hizam

    2015-06-01

    Full Text Available The title salt, C5H11N2S+·C7H4ClO2−, comprises a 2-amino-3-ethyl-4,5-dihydro-1,3-thiazol-3-ium cation in which the five-membered ring adopts an envelope conformation with the methylene C adjacent to the S atom being the flap, and a planar 3-chlorobenzoate anion (r.m.s. deviation for the 10 non-H atoms = 0.021 Å. The most prominent feature of the crystal packing are N—H...O hydrogen bonds whereby the two amine H atoms bridge two carboxylate O atoms resulting in the formation of a centrosymmetric 12-membered {...HNH...OCO}2 synthon involving two cations and two anions. These aggregates are linked by C—H...O interactions to form a supramolecular chain along the a-axis direction.

  10. Photosensitized 2-amino-3-hydroxypyridine-induced mitochondrial apoptosis via Smac/DIABLO in human skin cells.

    Science.gov (United States)

    Goyal, Shruti; Amar, Saroj Kumar; Dwivedi, Ashish; Mujtaba, Syed Faiz; Kushwaha, Hari Narayan; Chopra, Deepti; Pal, Manish Kumar; Singh, Dhirendra; Chaturvedi, Rajnish Kumar; Ray, Ratan Singh

    2016-04-15

    The popularity of hair dyes use has been increasing regularly throughout the world as per the demand of hair coloring fashion trends and other cosmetic products. 2-Amino-3-hydroxypyridine (A132) is widely used as a hair dye ingredient around the world. We are reporting first time the phototoxicity mechanism of A132 under ambient environmental UV-B radiation. It showed maximum absorption in UV-B region (317 nm) and forms a photoproduct within an hour exposure of UV-B irradiation. Photocytotoxicity of A132 in human keratinocytes (HaCaT) was measured by mitochondrial (MTT), lysosomal (NRU) and LDH assays which illustrated the significant reduction in cell viability. The role of reactive oxygen species (ROS) generation for A132 phototoxicity was established photo- chemically as well as intracellularly. Noteworthy, formation of tail DNA (comet assay), micronuclei and cyclobutane pyrimidine dimers (CPDs) (immunocytochemistry) formation confirmed the photogenotoxic potential of dye. Cell cycle study (sub-G1peak) and staining with EB/AO revealed the cell cycle arrest and apoptosis. Further, mitochondrial mediated apoptosis was corroborated by reduced MMP, release of cytochrome c and upregulation of caspase-3. Release of mitochondrial Smac/DIABLO in cytoplasm demonstrated the caspase dependent apoptotic cell death by photolabile A132 dye. In-addition increased Bax/Bcl2 ratio again proved the apoptosis. Thus, study suggests that A132 induces photogenotoxicity, phototoxicity and apoptotic cell death through the involvement of Smac/DIABLO in mitochondrial apoptosis via caspase dependent manner. Therefore, the long term use of A132 dye and sunlight exposure jointly increased the oxidative stress in skin which causes premature hair loss, damage to progenitor cells of hair follicles. PMID:26933830

  11. Phosphotungstic Acid Catalyzed One-Pot Synthesis of 2-amino-3,5-dicarbonitrile-6-thio-pyridines in Aqueous Media

    International Nuclear Information System (INIS)

    In this study, we report the one-pot synthesis of 2-amino-3,5-dicarbonitrile-6-thio-pyridines with benzaldehyde, malononitrile, and thiophenol by using phosphotungstic acid as an efficient catalyst to aqueous media. This method has the advantages of easy separation, high storage stability, and environmental friendliness. (author)

  12. Genotoxicity, carcinogenicity, and mode of action of the fried food mutagen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ).

    OpenAIRE

    Weisburger, J H; Barnes, W S; Lovelette, C A; Tong, C; Tanaka, T; Williams, G.M.

    1986-01-01

    Because mutagens typified by 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) observed in cooked foods are widely consumed, detailed studies of their biochemical and biological properties including carcinogenicity are most important. IQ induces unscheduled DNA synthesis in liver cells, which when taken together with its powerful mutagenicity in the Salmonella typhimurium test system, predicts carcinogenicity. In female Sprague-Dawley rats, IQ did exhibit potent carcinogenicity for the mammary gla...

  13. Derivados de 2-amino-3,5-dicianopiridina y 2-cloro-3,5-dicianopiridina como inhibidores de las enzinas colinesterasas y con capacidad neuroprotectora

    OpenAIRE

    Samadi, Abdelouahid; Álvarez-Pérez, Mónica; Soriano, Elena; Valderas, Carolina; García García, Antonio

    2010-01-01

    Compuestos heterocíclicos derivados de 2-amino-3,5-dicianopiridina y 2-cloro-3,5-dicianopiridina como inhibidores de las enzimas colinesterasas con capacidad neuroprotectora, y por lo tanto, con posible utilidad en el tratamiento de procesos neurodegenerativos, preferiblemente los compuestos de la presente invención se pueden utilizar para el tratamiento o la prevención de la enfermedad de Alzheimer, la enfermedad de Parkinson o la enfermedad de Huntington.

  14. Racemic synthesis and solid phase peptide synthesis application of the chimeric valine/leucine derivative 2-amino-3,3,4-trimethyl-pentanoic acid.

    Science.gov (United States)

    Pelà, M; Del Zoppo, L; Allegri, L; Marzola, E; Ruzza, C; Calo, G; Perissutti, E; Frecentese, F; Salvadori, S; Guerrini, R

    2014-07-01

    The synthesis of non natural amino acid 2-amino-3,3,4-trimethyl-pentanoic acid (Ipv) ready for solid phase peptide synthesis has been developed. Copper (I) chloride Michael addition, followed by a Curtius rearrangement are the key steps for the lpv synthesis. The racemic valine/leucine chimeric amino acid was then successfully inserted in position 5 of neuropeptide S (NPS) and the diastereomeric mixture separated by reverse phase HPLC. The two diastereomeric NPS derivatives were tested for intracellular calcium mobilization using HEK293 cells stably expressing the mouse NPS receptor where they behaved as partial agonist and pure antagonist.

  15. Analysis of X-ray structure, dielectric properties and AC conductivity of (4E-2-amino-3-cyanobenzo[b]oxocin-6-one

    Directory of Open Access Journals (Sweden)

    Ali H.A.M.

    2016-06-01

    Full Text Available The crystal structure of (4E-2-amino-3-cyanobenzo[b]oxocin-6-one, denoted as 4(E-ACBO, was analyzed using X-ray diffraction technique. The dielectric and AC electrical conductivity measurements of the bulk 4(E-ACBO in the form of pellet were studied in the range of frequency 42 Hz to 5 MHz and the temperature range of 303 K to 373 K. The temperature and frequency dependence of dielectric constant (∊1, dielectric loss (∊2 and AC electrical conductivity (σAC were investigated. The relaxation time (τ for electrons to hop over a barrier of height WH was calculated at different temperatures. The AC activation energy was determined from the temperature dependence of σAC at different frequencies.

  16. IQ (2-amino-3-methylimidazo[4,5-f]quinoline)- induced aberrant crypt foci and colorectal tumour development in rats fed two different carbohydrate diets

    DEFF Research Database (Denmark)

    Mølck, A.M.; Meyer, Otto A.; Kristiansen, E.;

    2001-01-01

    In most aberrant crypt foci (ACF) and colorectal tumour studies, chemical carcinogens not normally found in food have been used as initiators. In the present study the food-related compound, IQ (2-amino-3-methylimidazo[4,5-f]quinoline), has been used. A diet high in refined carbohydrates has been...... associated with enhanced development of ACF and colorectal cancer in humans. The present study was designed as an integrated part of our earlier published ACF study and follows the animals until tumour development. The aim of the study was to investigate (1) the effect of a refined carbohydrate-rich diet......, liver, skin and Zymbal gland. The data demonstrate that a sucrose-rich diet enhance ACF development. A correlation between the outcome of early and late ACF was seen. However, as the tumour incidence of this study was very low it was not possible to obtain a meaningful correlation between ACF...

  17. Disposition and metabolism of the food mutagen 2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline (MeIQx) in rats

    Energy Technology Data Exchange (ETDEWEB)

    Sjoedin, P.W.; Wallin, H.; Alexander, J.; Jaegerstad, M.

    1989-07-01

    The disposition and metabolism of a common food mutagen, 2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline (MeIQx), was studied in rats. Five rats of both sexes were given a single oral dose of /sup 14/C-labeled MeIQx (3-4 mg/kg body wt). The male rats excreted 36% of the radioactivity and 15% of the mutagenic activity of the dose given in the urine collected during the first 24 h. In the females the corresponding urine contained 41% of the radioactivity and 12% of the mutagenicity. During the next 48 h only 1-3% of the radioactive dose was excreted in urine. The remaining dose was excreted in the feces except of less than 1% that was retained by the tissues after 72 h. The liver and kidney retained more radioactivity than other organs. In a separate study the metabolites of bile, urine and feces of both sexes were investigated. After a single oral dose of 20 mg /sup 14/C-labeled MeIQx/kg body wt, three major non-mutagenic metabolites were identified. These were 2-amino-4(or 5)-(beta-D-glucuronopyranosyloxy)-3,8-dimethylimidazo(4,5-f) quinoxaline, 2-amino-3,8-dimethylimidazo(4,5-f)quinoxalin-4(or 5)-yl sulfate and N-(3,8-dimethylimidazo(4,5-f)quinoxalin-2-yl) sulfamate. Another two metabolites present in bile, urine and feces were 2-(beta-D-glucuronopyranosylamino)-3,8-dimethylimidazo(4,5-f ) quinoxaline and 2-amino-8-hydroxymethyl-3-methylimidazo(4,5-f)quinoxalin-4 (or 5)yl sulfate. All metabolites were essentially non-mutagenic. Most of the mutagenicity still present in bile, urine and feces could be explained by unchanged MeIQx. Unchanged MeIQx was the most abundant form excreted in urine.

  18. Disposition of the Dietary Mutagen 2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline in Healthy and Pancreatic Cancer Compromised Humans.

    Science.gov (United States)

    Malfatti, Michael A; Kuhn, Edward A; Turteltaub, Kenneth W; Vickers, Selwyn M; Jensen, Eric H; Strayer, Lori; Anderson, Kristin E

    2016-03-21

    Pancreatic cancer is the fourth leading cause of cancer death in the U.S. Once diagnosed, prognosis is poor with a 5-year survival rate of less than 5%. Exposure to carcinogenic heterocyclic amines (HCAs) derived from cooked meat has been shown to be positively associated with pancreatic cancer risk. To evaluate the processes that determine the carcinogenic potential of HCAs for human pancreas, 14-carbon labeled 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), a putative human carcinogenic HCA found in well-done cooked meat, was administered at a dietary relevant dose to human volunteers diagnosed with pancreatic cancer undergoing partial pancreatectomy and healthy control volunteers. After (14)C-MeIQx exposure, blood and urine were collected for pharmacokinetic and metabolite analysis. MeIQx-DNA adducts levels were quantified by accelerator mass spectrometry from pancreatic tissue excised during surgery from the cancer patient group. Pharmacokinetic analysis of plasma revealed a rapid distribution of MeIQx with a plasma elimination half-life of approximately 3.5 h in 50% of the cancer patients and all of the control volunteers. In 2 of the 4 cancer patients, very low levels of MeIQx were detected in plasma and urine suggesting low absorption from the gut into the plasma. Urinary metabolite analysis revealed five MeIQx metabolites with 2-amino-3-methylimidazo[4,5-f]quinoxaline-8-carboxylic acid being the most abundant accounting for 25%-50% of the recovered 14-carbon/mL urine. There was no discernible difference in metabolite levels between the cancer patient volunteers and the control group. MeIQx-DNA adduct analysis of pancreas and duodenum tissue revealed adduct levels indistinguishable from background levels. Although other meat-derived HCA mutagens have been shown to bind DNA in pancreatic tissue, indicating that exposure to HCAs from cooked meat cannot be discounted as a risk factor for pancreatic cancer, the results from this current study show that

  19. Synthetic routes to the food carcinogen 2 amino-3,8-dimethylimidazo[4,5-f]quinoxaline (8-MeIQx) and related compounds.

    Science.gov (United States)

    Grivas, S

    1995-01-01

    A review of five different routes to the synthesis of the grilled or fried food carcinogen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (8-MeIQx) and of closely related compounds developed in different laboratories is presented. Interest in the synthesis of these amines began in the late 1970s when the research group led by Professor T. Sugimura (National Cancer Center, Tokyo) detected extremely high mutagenicity in the charred parts of fish and meat that could not be explained only by the presence of polyaromatic hydrocarbons. A number of new mutagenic heterocyclic amines have been detected, isolated and identified since then (de Meester, 1989; Overvik and Gustafsson, 1990; Felton and Knize, 1991; Jägerstad et al., 1991). It is still not entirely clear how these compounds are formed during cooking. For the "IQ-group" of the amines (2-amino-3-methylimidazo-quinoline and -quinoxaline congeners), a formation pathway from Maillard reaction products and creatinine was conceived by Professor K. Olsson (this laboratory) and presented at the 183rd meeting of the American Chemical Society, Las Vegas in 1982 (Jägerstad et al., 1983). However, the amounts of the amines formed during cooking or in model reaction systems are very small. Therefore, efficient and unambiguous synthetic methods yielding the compounds in isomerically pure form are required for reference purposes in analytical work and structure-biological activity studies. For instance, compare the mutagenicity of 4,8- and 5,8-DiMeIQx, and PhIP and its 3-methyl isomer shown on the following page. The pure compounds are also required in large quantities for long-term animal feeding studies. The length of this article does not allow a presentation of the published synthetic methods for all the heterocyclic amines. Therefore, the syntheses of only one of the food mutagens, 8-MeIQx, and some related compounds are presented. This will hopefully demonstrate the sort of problems the organic chemist encounters and some

  20. Paramagnetic relaxation enhancement of membrane proteins by incorporation of the metal-chelating unnatural amino acid 2-amino-3-(8-hydroxyquinolin-3-yl)propanoic acid (HQA)

    Energy Technology Data Exchange (ETDEWEB)

    Park, Sang Ho; Wang, Vivian S.; Radoicic, Jasmina; Angelis, Anna A. De; Berkamp, Sabrina; Opella, Stanley J., E-mail: sopella@ucsd.edu [University of California, San Diego, Department of Chemistry and Biochemistry (United States)

    2015-04-15

    The use of paramagnetic constraints in protein NMR is an active area of research because of the benefits of long-range distance measurements (>10 Å). One of the main issues in successful execution is the incorporation of a paramagnetic metal ion into diamagnetic proteins. The most common metal ion tags are relatively long aliphatic chains attached to the side chain of a selected cysteine residue with a chelating group at the end where it can undergo substantial internal motions, decreasing the accuracy of the method. An attractive alternative approach is to incorporate an unnatural amino acid that binds metal ions at a specific site on the protein using the methods of molecular biology. Here we describe the successful incorporation of the unnatural amino acid 2-amino-3-(8-hydroxyquinolin-3-yl)propanoic acid (HQA) into two different membrane proteins by heterologous expression in E. coli. Fluorescence and NMR experiments demonstrate complete replacement of the natural amino acid with HQA and stable metal chelation by the mutated proteins. Evidence of site-specific intra- and inter-molecular PREs by NMR in micelle solutions sets the stage for the use of HQA incorporation in solid-state NMR structure determinations of membrane proteins in phospholipid bilayers.

  1. Paramagnetic relaxation enhancement of membrane proteins by incorporation of the metal-chelating unnatural amino acid 2-amino-3-(8-hydroxyquinolin-3-yl)propanoic acid (HQA)

    International Nuclear Information System (INIS)

    The use of paramagnetic constraints in protein NMR is an active area of research because of the benefits of long-range distance measurements (>10 Å). One of the main issues in successful execution is the incorporation of a paramagnetic metal ion into diamagnetic proteins. The most common metal ion tags are relatively long aliphatic chains attached to the side chain of a selected cysteine residue with a chelating group at the end where it can undergo substantial internal motions, decreasing the accuracy of the method. An attractive alternative approach is to incorporate an unnatural amino acid that binds metal ions at a specific site on the protein using the methods of molecular biology. Here we describe the successful incorporation of the unnatural amino acid 2-amino-3-(8-hydroxyquinolin-3-yl)propanoic acid (HQA) into two different membrane proteins by heterologous expression in E. coli. Fluorescence and NMR experiments demonstrate complete replacement of the natural amino acid with HQA and stable metal chelation by the mutated proteins. Evidence of site-specific intra- and inter-molecular PREs by NMR in micelle solutions sets the stage for the use of HQA incorporation in solid-state NMR structure determinations of membrane proteins in phospholipid bilayers

  2. Effects of sucrose and cornstarch on 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)-induced colon and liver carcinogenesis in F344 rats

    DEFF Research Database (Denmark)

    Lindecrona, R.H.; Dragsted, Lars Ove; Poulsen, Morten;

    2004-01-01

    The purpose of the present study was to compare the effect of sucrose and cornstarch on colon and liver carcinogenesis induced by 0.02% of the food-borne carcinogen 2-amino-3-methylimidazo [4,5-f]quinoline (IQ) in the feed. Male F344 rats were allocated to four groups. Two groups were fed diets...... high in either cornstarch (68%) or sucrose (34% sucrose/34% cornstarch) and were initiated with IQ. The remaining two groups received the same two diets but did not receive any IQ. In both liver and colon, administration of IQ resulted in a higher level of DNA adducts. In animals not dosed with IQ......, sucrose increased the adduct level in both organs but to a lower level than IQ. However, simultaneous administration of IQ and sucrose did not further increase the adduct level. Both IQ and sucrose increased the expression of the DNA-repair enzyme ERCC1 in the liver. In the colon, the number of large...

  3. Metabolism of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline in human hepatocytes: 2-amino-3-methylimidazo[4,5-f]quinoxaline-8-carboxylic acid is a major detoxification pathway catalyzed by cytochrome P450 1A2.

    Science.gov (United States)

    Langouët, S; Welti, D H; Kerriguy, N; Fay, L B; Huynh-Ba, T; Markovic, J; Guengerich, F P; Guillouzo, A; Turesky, R J

    2001-02-01

    Metabolic pathways of the mutagen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) remain incompletely characterized in humans. In this study, the metabolism of MeIQx was investigated in primary human hepatocytes. Six metabolites were characterized by UV and mass spectroscopy. Novel metabolites were additionally characterized by 1H NMR spectroscopy. The carcinogenic metabolite, 2-(hydroxyamino)-3,8-dimethylimidazo[4,5-f]quinoxaline, which is formed by cytochrome P450 1A2 (P450 1A2), was found to be transformed into the N(2)-glucuronide conjugate, N(2)-(beta-1-glucosiduronyl)-2-(hydroxyamino)-3,8-dimethylimidazo[4,5-f]quinoxaline. The phase II conjugates N(2)-(3,8-dimethylimidazo[4,5-f]quinoxalin-2-yl)sulfamic acid and N(2)-(beta-1-glucosiduronyl)-2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, as well as the 7-oxo derivatives of MeIQx and N-desmethyl-MeIQx, 2-amino-3,8-dimethyl-6-hydro-7H-imidazo[4,5-f]quinoxalin-7-one (7-oxo-MeIQx), and 2-amino-6-hydro-8-methyl-7H-imidazo[4,5-f]quinoxalin-7-one (N-desmethyl-7-oxo-MeIQx), thought to be formed exclusively by the intestinal flora, were also identified. A novel metabolite was characterized as 2-amino-3-methylimidazo[4,5-f]quinoxaline-8-carboxylic acid (IQx-8-COOH), and it was the predominant metabolite formed in hepatocytes exposed to MeIQx at levels approaching human exposure. IQx-8-COOH formation is catalyzed by P450 1A2. This metabolite is a detoxication product and does not induce umuC gene expression in Salmonella typhimurium strain NM2009. IQx-8-COOH is also the principal oxidation product of MeIQx excreted in human urine [Turesky, R., et al. (1998) Chem. Res. Toxicol. 11, 217-225]. Thus, P450 1A2 is involved in both the metabolic activation and detoxication of this procarcinogen in humans. Analogous metabolism experiments were conducted with hepatocytes of untreated rats and rats pretreated with the P450 inducer 3-methylcholanthrene. Unlike human hepatocytes, the rat cell preparations did not produce IQx-8

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

    DEFF Research Database (Denmark)

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

    1994-01-01

    preparation was shown to be progressively reduced with increasing molar ratios of (R)-APPA/(S)-APPA. These compounds and the competitive antagonists (RS)-2-amino-3-(3-carboxymethoxy-5-methyl-4-isoxazolyl)propionic acid [(RS)-AMOA], 6-cyano-7-nitroquinoxalin-2,3-dione (CNQX) and 6-nitro-7-sulfamoylbenzo(f)quinoxalin...

  5. Identification of metabolites in urine and feces from rats dosed with the heterocyclic amine, 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeA alpha C)

    DEFF Research Database (Denmark)

    Frederiksen, H; Frandsen, H

    2004-01-01

    2-Amino-3-methyl-9H-pyrido[2,3-b]indole (MeA alpha C) is a proximate mutagenic and carcinogenic heterocyclic amine formed during ordinary cooking. In model systems, MeA alpha C can be formed by pyrolyses of either tryptophan or proteins of animal or vegetable origin. In the present study, the in...

  6. Chemoprevention of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)-induced colonic and hepatic preneoplastic lesions in the F344 rat by cruciferous vegetables administered simultaneously with the carcinogen

    NARCIS (Netherlands)

    Kassie, F.; Uhl, M.; Grasl-Kraupp, B.; Verkerk, R.; Kundi, M.; Chabicovsky, M.; Schulte-Hermann, R.; Knasmüller, S.

    2003-01-01

    The aim of this study was to investigate the chemopreventive effects of widely consumed cruciferous vegetables, namely Brussels sprouts and red cabbage towards 2-amino3-methylimidazo[4,5-f]quinoline (IQ)-induced preneoplastic lesions [liver glutathione-S-transferase placental positive (GST-P+) foci

  7. Push-pull 1,3-thiazolium-5-thiolates. Formation via concerted and stepwise pathways, and theoretical evaluation of NLO properties.

    Science.gov (United States)

    Cantillo, David; Avalos, Martín; Babiano, Reyes; Cintas, Pedro; Jiménez, José L; Light, Mark E; Palacios, Juan C; Rodríguez, Valentín

    2010-12-01

    The transformation of münchnones (mesoionic rings featuring the 1,3-oxazolium-5-olate core) into their sulfur counterparts (1,3-thiazolium-5-thiolates) by reaction with CS(2), pioneered by Huisgen and his group in the early 1970s, has been re-investigated in detail by means of both experimental and theoretical methods. The synthetic strategy can be tuned to incorporate donor and acceptor groups in appropriate positions. Calculations of molecular hyperpolarizabilities together with orbital topologies evidence that these sulfur-containing heterocycles exhibit nonlinear optical responses, thereby pointing to potential applications of mesoionic structures in the NLO field. From a mechanistic viewpoint, modeling of the whole systems at the B3LYP/6-31G(d) level reveals that concerted and stepwise pathways are operative depending on the substitution pattern of the parent münchnone, which also account for the experimental results.

  8. Resolution, configurational assignment, and enantiopharmacology of 2-amino-3-[3-hydroxy-5-(2-methyl-2H- tetrazol-5-yl)isoxazol-4-yl]propionic acid, a potent GluR3- and GluR4-preferring AMPA receptor agonist

    DEFF Research Database (Denmark)

    Vogensen, S B; Jensen, H S; Stensbøl, T B;

    2000-01-01

    We have previously shown that (RS)-2-amino-3-[3-hydroxy-5-(2-methyl-2H-tetrazol-5-yl)isoxazol -4-yl] propionic acid (2-Me-Tet-AMPA) is a selective agonist at (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) receptors, markedly more potent than AMPA itself, whereas the isomeric...

  9. Regioselective differences in C(8)- and N-oxidation of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline by human and rat liver microsomes and cytochromes P450 1A2.

    Science.gov (United States)

    Turesky, R J; Parisod, V; Huynh-Ba, T; Langouët, S; Guengerich, F P

    2001-07-01

    The metabolism of the mutagen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) was investigated with human and rat liver microsomes, recombinant human cytochrome P450 1A2 (P450 1A2) expressed in Escherichia coli cells, and rat P450 1A2. Human liver microsomes and human P450 1A2 catalyzed the oxidation of the exocyclic amine group of MeIQx to form the genotoxic product 2-(hydroxyamino)-3,8-dimethylimidazo[4,5-f]quinoxaline (HONH-MeIQx). Human P450 1A2 also catalyzed the oxidation of C(8)-methyl group of MeIQx to form 2-amino-(8-hydroxymethyl)-3-methylimidazo[4,5-f]quinoxaline (8-CH(2)OH-IQx), 2-amino-3-methylimidazo[4,5-f]quinoxaline-8-carbaldehyde (IQx-8-CHO), and 2-amino-3-methylimidazo[4,5-f]quinoxaline-8-carboxylic acid (IQx-8-COOH). Thus, chemically stable C(8)-oxidation products of MeIQx may be useful biomarkers of P450 1A2 activity in humans. Rat liver microsomes were 10-15-fold less active than the human counterpart at both N-oxidation and C(8)-oxidation of MeIQx when expressed as nanomoles of product formed per minute per nanomoles of P450 1A2. Differences in regioselective oxidation of MeIQx were also observed with human and rat liver microsomes and the respective P450 1A2 orthologs. In contrast to human liver microsomes and P450 1A2, rat liver microsomes and purified rat P4501A2 were unable to catalyze the oxidation of MeIQx to the carboxylic derivative IQx-8-COOH, an important detoxication product formed in humans. However, rat liver microsomes and rat P4501A2, but not human liver microsomes or human P450 1A2, extensively catalyzed ring oxidation at the C-5 position of MeIQx to form the detoxication product 2-amino-3,8-dimethyl-5-hydroxyimidazo[4,5-f]quinoxaline (5-HO-MeIQx). There are important differences between human and rat P450 1A2, both in catalytic activities and oxidation pathways of MeIQx, that may affect the biological activity of this carcinogen and must be considered when assessing human health risk.

  10. Mutagenicity of 2-amino-3-methylimidazo[4,5-f]quinoline in colon and liver of Big Blue rats: role of DNA adducts, strand breaks, DNA repair and oxidative stress

    DEFF Research Database (Denmark)

    Moller, P.; Wallin, H.; Vogel, U.;

    2002-01-01

    The contribution of oxidative stress, different types of DNA damage and expression of DNA repair enzymes in colon and liver mutagenesis induced by 2-amino-3-methylimidazo [4,5-f]quinoline (IQ) was investigated in four groups of six Big Blue rats fed diets with 0, 20, 70, and 200 mg IQ/kg for 3....... Investigations of oxidative stress biomarkers produced inconclusive results. Oxidative DNA damage detected by the endonuclease III enzyme and 7-hydro-8-oxo-2'-deoxyguanosine in colon, liver and/or urine was unaltered by IQ. However, there was increased level of gamma-glutamyl semialdehyde in liver proteins......, indicating a higher rate of protein oxidation in the liver following IQ administration. In plasma and erythrocytes there were unaltered levels of oxidized protein, malondialdehyde, and antioxidant enzyme activities (superoxide dismutase, glutathione peroxidase, catalase, glutathione reductase) indicating...

  11. Mutagenicity of 2-amino-3-methylimidazo[4,5-f]quinoline in colon and liver of Big Blue Rats: role of DNA adducts, strand breaks, DNA repair and oxidative stress

    DEFF Research Database (Denmark)

    Møller, Peter; Wallin, Håkan; Vogel, Ulla;

    2002-01-01

    The contribution of oxidative stress, different types of DNA damage and expression of DNA repair enzymes in colon and liver mutagenesis induced by 2-amino-3-methylimidazo [4,5-f]quinoline (IQ) was investigated in four groups of six Big Blue rats fed diets with 0, 20, 70, and 200 mg IQ/kg for 3....... Investigations of oxidative stress biomarkers produced inconclusive results. Oxidative DNA damage detected by the endonuclease III enzyme and 7-hydro-8-oxo-2'-deoxyguanosine in colon, liver and/or urine was unaltered by IQ. However, there was increased level of gamma-glutamyl semialdehyde in liver proteins......, indicating a higher rate of protein oxidation in the liver following IQ administration. In plasma and erythrocytes there were unaltered levels of oxidized protein, malondialdehyde, and antioxidant enzyme activities (superoxide dismutase, glutathione peroxidase, catalase, glutathione reductase) indicating...

  12. Refined carbohydrate enhancement of aberrant crypt foci (ACF) in rat colon induced by the food-borne carcinogen 2-amino-3-methyl-imidazo[4,5-f]quinoline (IQ)

    DEFF Research Database (Denmark)

    Kristiansen, E.; Meyer, Otto A.; Thorup, I.

    1996-01-01

    . In the present study it is shown that a feeding regimen with continuous low IQ doses (0.03% in the diet) throughout a study period of 10 weeks has a significant effect on the induction of ACF in the colon of male F344 rats. In addition, the study illustrates that the incidence of the IQ-induced ACF can...... be modulated by the amount of refined carbohydrates in the diet. Rats given a high sucrose/dextrin diet showed a significantly higher number of ACF compared to rats given a diet high in starches. The effect on tumor outcome will await the termination of a ongoing parallel study.......,2-dimethylhydrazine dihydrochloride (DMH) and azoxymethane (AOM), the use of a diet-related colon cancer initiator, such as the heterocyclic amine 2-amino-3-methyl-imidazo[4,5-f]quinoline (IQ) formed during meat cooking, would probably give a more relevant insight into diet-related colon carcinogenesis...

  13. Twenty six-week exposure to 2 amino-3 methylimidazo [4,5-f]quinoline (IQ) does not significantly increase the incidence of tumours in HMGCR/mts1 tg579 transgenic mice

    DEFF Research Database (Denmark)

    Mortensen, Alicja; Lukanidin, E.; Ambartsumian, N.S.;

    2004-01-01

    HMGCR/mtsl t9579 transgenic mice were designed to direct the expression of metastasis-promoting mts 1 (S100A4) gene to all the tissues. In order to test the usefulness of this mouse model for carcinogenicity tests shorter than that recommended by OECD guideline mr. 451, HMGCR/mtsl tg579 transgenic...... and C57BL/6ByA (wild type) mice (15 males and 15 females of each genotype per group) received either a control diet for 53 weeks or a control diet plus 0.03% 2-amino-3 methylimidazo[4,5-f]quinoline (IQ) for 26 weeks and a control diet for the remaining 27 weeks. IQ is a food mutagen with a carcinogenic...

  14. Prebiotics and age, but not probiotics affect the transformation of 2-amino-3-methyl-3H-imidazo[4,5-f]quinoline (IQ) by fecal microbiota - An in vitro study.

    Science.gov (United States)

    Nowak, Adriana; Czyżowska, Agata; Huben, Krzysztof; Sójka, Michał; Kuberski, Sławomir; Otlewska, Anna; Śliżewska, Katarzyna

    2016-06-01

    Heterocyclic aromatic amines (HAAs) are carcinogens which are formed in meat cooked using high-temperature methods. The human gastrointestinal (GI) microbiota plays a crucial role in maintaining health in humans of different ages, and especially in the elderly. However, the GI microbiota, whose metabolism and composition changes with age, may also be responsible for the activation of mutagenic substances reaching the colon with diet. Probiotics and prebiotics are promising in terms of reducing the destructive effects of HAAs. The aim of the study was to determine if fecal microbiota derived from the feces of 27 volunteers: infants (up to 18 months), adults (aged 23-39 years), the sub-elderly (aged 64-65 years), and the elderly (aged 76-87 years), and the presence of probiotics or prebiotics, affected the transformation of IQ (2-amino-3-methylimidazo[4,5-f]quinoline) to 7-OH-IQ (2-amino-3,6-dihydro-3-methyl-7H-imidazo[4,5-f]quinoline-7-one). The compounds were identified using LC-MS(n), NMR, and FTIR. Their genotoxicity was compared in the comet assay. Individual strains capable of IQ transformation were also identified. 7-OH-IQ was detected in six persons (two children and four elderly individuals). The degree of IQ conversion ranged from 26% (4-month-old girl) to 94% (81-year-old woman) of the initial quantity. Four Enterococcus isolates: two Enterococcus faecium and two Enterococcus faecalis strains, as well as one Clostridium difficile strain (LOCK 1030, from the culture collection) converted IQ to 7-OH-IQ. The genotoxicity of samples containing 7-OH-IQ was even three times higher (P < 0.05) than those with IQ and was correlated with the degree of IQ conversion and 7-OH-IQ concentration. PMID:27034248

  15. Bioactivation of the heterocyclic aromatic amine 2-amino-3-methyl-9H-pyrido [2,3-b]indole (MeA alpha C) in recombinant test systems expressing human xenobiotic-metabolizing enzymes

    DEFF Research Database (Denmark)

    Glatt, H.; Pabel, U.; Meinl, W.;

    2004-01-01

    co-expressing cytochrome (CYP) 1A2 and sulphotransferase (SULT) 1A1 even at a concentration of 30 nM, but was inactive in cells co-expressing CYP1A2 and N-acetyltransferase (NAT) 1 or 2. MeAalphaC, tested in the presence of rat liver post-mitochondrial fraction, showed strongly enhanced mutagenicity......2-Amino-3-methyl-9H-pyrido[2,3-b]indole (MeAalphaC) and some metabolites were investigated for mutagenicity in mammalian cell lines and bacterial strains engineered for the expression of human enzymes. MeAalphaC induced gene mutations (studied at the hprt locus) in Chinese hamster V79-derived cells...... in a Salmonella typhimurium strain expressing human SULT1A1 compared with the control (recipient) strain TA1538/1,8-DNP (deficient in endogenous acetyltransferase). Mutagenicity was also enhanced, although to a lesser extent, when NAT2 was expressed in the latter strain. The metabolite, 2-hydroxylamino-3-methyl-9...

  16. Comparative effects in rats of intact wheat bran and two wheat bran fractions on the disposition of the mutagen 2-amino-3-methylimidazo[4,5-f]quinoline

    Energy Technology Data Exchange (ETDEWEB)

    Ferguson, Lynnette R., E-mail: l.ferguson@auckland.ac.nz [Discipline of Nutrition, Faculty of Medicine and Health Sciences, University of Auckland, Auckland (New Zealand); Auckland Cancer Society Research Centre, Faculty of Medicine and Health Sciences, University of Auckland, Auckland (New Zealand); Harris, Philip J. [School of Biological Sciences, University of Auckland, Auckland (New Zealand); Kestell, Philip [Auckland Cancer Society Research Centre, Faculty of Medicine and Health Sciences, University of Auckland, Auckland (New Zealand); Zhu, Shuotun [Discipline of Nutrition, Faculty of Medicine and Health Sciences, University of Auckland, Auckland (New Zealand); Auckland Cancer Society Research Centre, Faculty of Medicine and Health Sciences, University of Auckland, Auckland (New Zealand); Munday, Rex; Munday, Christine M. [Agresearch, Ruakura Agricultural Research Centre, Hamilton (New Zealand)

    2011-11-01

    Wheat bran protects against mutations and cancer, but contains different plant cell types that are likely to have different protective effects. We previously described the production and chemical characterisation of an aleurone-rich fraction (ARF) and a pericarp-rich fraction (PRF) from wheat grain. We compared these with whole bran (WB), fed to rats as 10% of a high fat AIN-76 diet. All bran-supplemented diets increased faecal bulk, in the order PRF > WB > ARF. PRF increased the activity of NAD(P)H:quinone acceptor oxidoreductase only in the forestomach, whereas ARF and WB enhanced levels of glutathione S-transferase in the duodenum. ARF but not PRF was digested and fermented, and also encouraged bacterial growth. Rats were gavaged with the radioactive mutagen {sup 14}C-labelled IQ (2-amino-3-methylimidazo[4,5-f]quinoline), and effects of the brans on plasma radioactivity measured. Compared with the control diet, all bran-supplemented diets reduced the concentration of radioactivity in plasma, in the order ARF > PRF > WB. All brans increased faecal elimination of radioactivity, but only ARF and PRF enhanced urinary radioactivity. These data suggest that wheat bran may reduce mutation and cancers through direct adsorption and enhanced elimination of a dietary mutagen and/or its metabolites, and that wheat bran enriched in pericarp or aleurone cell walls may exert protective effects through different mechanisms.

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

    DEFF Research Database (Denmark)

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

    1996-01-01

    ]pyridine (PhIP) for 7 months or with 0.03% 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) for 6 months, PhIP and IQ are heterocyclic amines formed during cooking of meat and fish and are mutagenic to bacteria and cultured mammalian cells, PhIP is a potent mouse lymphomagen, while IQ is a liver carcinogen...... and also causes lung tumors and tumors of the forestomach in mice. We found that transgenic E mu-pim-1 mice are highly susceptible to PhIP induced lymphomagenesis but do not respond to the IQ treatment, PhIP feeding of E mu-pim-1 mice not only increased the total number of T-cell lymphomas but also...... decreased the latency time compared to either transgenic or wild-type controls, The effect was most pronounced in the treated female E mu-pim-1 mice, which showed a higher incidence of PhIP induced T-cell lymphomas than transgenic males and a strongly reduced latency period after PhIP treatment compared...

  18. Synthesis and Crystal Structure of 7,7- Dimethyl-2-amino-3-cyano-4-(3,4-methylenedioxylphenyl)-5-oxo-5,6,7,8-tetrahydro-4H-benzo-[b]-pyran

    Institute of Scientific and Technical Information of China (English)

    王香善; 史达清; 屠树江; 姚昌盛; 王玉成

    2002-01-01

    The title compound 7,7-dimethyl-2-amino-3-cyano-4-(3,4-methylene- dioxylphenyl)-5-oxo-5,6,7,8-tetrahydro-4H-benzo-[b]-pyran(C19H18N2O4, Mr=338.35) is mono- clinic, space group C2/c with a=26.753(5), b=9.409(2), c=16.036(3)A,β=121.00(1)°, Z=8, V=3460(1)A3, Dc=1.299g/cm3, μ(MoKα=0.092mm-1, F(000)=1424, R=0.0410 and wR=0.0926 for 3138 observed reflections (I>2σ(I)). X-ray analysis reveals that atoms C(8), C(9), C(10), O(3), C(12) and C(13) form a six-membered ring in which the distances of C(9)-C(10) and C(12)-C(13) are 1.342(2) and 1.331(2)A, respectively, which show that they are C=C double bonds. In addition, there is hydrogen bond in the product molecule.

  19. Comparative effects in rats of intact wheat bran and two wheat bran fractions on the disposition of the mutagen 2-amino-3-methylimidazo[4,5-f]quinoline

    International Nuclear Information System (INIS)

    Wheat bran protects against mutations and cancer, but contains different plant cell types that are likely to have different protective effects. We previously described the production and chemical characterisation of an aleurone-rich fraction (ARF) and a pericarp-rich fraction (PRF) from wheat grain. We compared these with whole bran (WB), fed to rats as 10% of a high fat AIN-76 diet. All bran-supplemented diets increased faecal bulk, in the order PRF > WB > ARF. PRF increased the activity of NAD(P)H:quinone acceptor oxidoreductase only in the forestomach, whereas ARF and WB enhanced levels of glutathione S-transferase in the duodenum. ARF but not PRF was digested and fermented, and also encouraged bacterial growth. Rats were gavaged with the radioactive mutagen 14C-labelled IQ (2-amino-3-methylimidazo[4,5-f]quinoline), and effects of the brans on plasma radioactivity measured. Compared with the control diet, all bran-supplemented diets reduced the concentration of radioactivity in plasma, in the order ARF > PRF > WB. All brans increased faecal elimination of radioactivity, but only ARF and PRF enhanced urinary radioactivity. These data suggest that wheat bran may reduce mutation and cancers through direct adsorption and enhanced elimination of a dietary mutagen and/or its metabolites, and that wheat bran enriched in pericarp or aleurone cell walls may exert protective effects through different mechanisms.

  20. Use of the /sup 32/P-postlabeling method to detect DNA adducts of 2-amino-3-methylimidazolo(4,5-f)quinoline (IQ) in monkeys fed IQ: identification of the N-(deoxyguanosin-8-yl)-IQ adduct

    Energy Technology Data Exchange (ETDEWEB)

    Snyderwine, E.G.; Yamashita, K.; Adamson, R.H.; Sato, S.; Nagao, M.; Sugimura, T.; Thorgeirsson, S.S.

    1988-10-01

    Eight DNA adducts of 2-amino-3-methylimidazolo(4,5-f)-quinoline (IQ) were found by the standard /sup 32/P-postlabeling method in livers from male Cynomolgus monkeys fed IQ (5 days/week, 3 weeks, 20 mg/kg, nasal-gastric intubation). The IQ-DNA adduct fingerprints observed in monkeys were identical to those observed in rats that received IQ (0.03%) in the diet for 2 weeks. The C8-guanine-IQ adduct was identified by comigration with the synthetic 3',5'-bisphosphate derivative of N(-deoxyguanosin-8-yl)-IQ. DNA modified in vitro with N-hydroxy-IQ showed seven adducts, including the C8-guanine-IQ adduct, that were identical to those found in monkeys and rats. Thus it appears that N-hydroxy-IQ, the reactive metabolite of IQ, was responsible for all adducts found in vivo, except one. In order to detect adducts in other organs that were present at lower levels, the intensification (ATP-deficient) method for /sup 32/P-postlabeling was used. Five of the adducts detected under standard conditions, including the C8-guanine-IQ adduct, were also detected under intensification conditions. The total level of DNA-IQ adducts was highest in the liver, followed by the kidney, colon and stomach, and bladder. The adduct patterns were identical in all organs examined. The results indicate that IQ is potentially genotoxic in primates and therefore a likely human carcinogen.

  1. Dammar resin, a non-mutagen, induces [corrected] oxidative stress and metabolic enzymes in the liver of gpt delta transgenic mouse which is different from a mutagen, 2-amino-3-methylimidazo[4,5-f]quinoline.

    Science.gov (United States)

    Xie, Xiao-Li; Wei, Min; Kakehashi, Anna; Yamano, Shotaro; Okabe, Kyoko; Tajiri, Masaki; Wanibuchi, Hideki

    2012-10-01

    Dammar resin has long been used in foods as either a clouding or a glazing agent. In a recent study, 2% Dammar resin showed significant hepatocarcinogenicity in a rat 2-year bioassay. Therefore, for an accurate estimate of human risk, it is necessary to understand whether Dammar resin induces liver genotoxicity and the underlying mechanisms of its hepatocarcinogenicity. Modifying effects of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), a typical genotoxic carcinogen produced during cooking of protein-rich foods, was also studied in the present study. Exposure of gpt delta mice to Dammar resin at a dose of 2% for 12 weeks did not induce any obvious mutagenicity in the liver. However, the index of cell proliferation, the level of 8-OHdG, and bax, bcl-2, p53, cyp1a2, cyp2e1, gpx1 and gstm2 gene expression were all significantly increased when compared with the control group. In the IQ treatment group, at a dose of 300ppm, mutagenicity was readily detected, the index of cell proliferation increased, and p53, cyp2e1 and gpx1 gene expression was down-regulated in the liver. Down-regulation of p53, P450s, and gpx1 in the livers of IQ treated mice are consistent with its genotoxic mechanism of carcinogenicity observed in a 675-day study. In contrast, our results using gpt delta mice suggest that Dammar resin is not genotoxic. Instead, the Dammar resin-induced hepatocarcinogenicity seen in our previous 2-year study with rats may have been mediated by non-genotoxic mechanisms, including increased P450 enzyme activity, increased oxidative stress, altered gene expression, and promotion of cell proliferation.

  2. Functional characterization of Tet-AMPA [tetrazolyl-2-amino-3-(3-hydroxy-5-methyl- 4-isoxazolyl)propionic acid] analogues at ionotropic glutamate receptors GluR1-GluR4. The molecular basis for the functional selectivity profile of 2-Bn-Tet-AMPA

    DEFF Research Database (Denmark)

    Jensen, Anders A.; Christesen, Thomas; Bølcho, Ulrik;

    2007-01-01

    Four 2-substituted Tet-AMPA [Tet = tetrazolyl, AMPA = 2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid] analogues were characterized functionally at the homomeric AMPA receptors GluR1i, GluR2Qi, GluR3i, and GluR4i in a Fluo-4/Ca2+ assay. Whereas 2-Et-Tet-AMPA, 2-Pr-Tet-AMPA, and 2-iPr...

  3. 2-氨基-3-羟基吡啶-过氧化氢-辣根过氧化物酶伏安酶联免疫体系分析人血清癌胚抗原%2-Amino-3-hydroxylpyridinE-H2O2-Horseradish Peroxidase Voltammetric EnzymE-Linked Immunoassay for Detection of Carcionembryonic Antigen in Human Serum

    Institute of Scientific and Technical Information of China (English)

    于凤丽; 邹晋; 梅振华

    2009-01-01

    2-Amino-3-hydroxylpyridinE-H2O2-horseradish peroxidase (HRP) voltammetric enzymE-linked immunoassay based on N-heterocyclic substrate has been successfully applied for the detection of carcionembryonic antigen(CEA) in human serum. 2-Amino-3-hydroxylpyridine is oxidized with H2O2 catalyzed by HRP, and the resulting electroactive product produces a sensitive voltammetric peak at the potential of 0.36 V(vs. SCE) in Britton-Robinson (B-R) buffer solution. By this voltammetric peak, free HRP can be measured and immunoassay of HRP label can be developed. The enzymE-catalyzed reaction conditions and voltammetric detection conditions have been optimized, and the electrode procedure of the enzymatic product was investigated. The selected optimum reaction conditions were that the reaction medium was pH 6.0 B-R buffer solution for 10 mL reaction solution containing 1.0 mL of 0.2 mol/L B-R buffer solution, 3.0 mL of 8.0 mmol/L 2-amino-3-hydroxylpyridine solution and 1.5 mL of 0.5 mmol/L H2O2 solution, and the reaction time was 30 min at 37 ℃. The optimum detection conditions were that the supporting electrolyte was pH 7.0 B-R buffer solution for 10 mL of the overall detection solution containing 5 mL of reaction solution and 1.0 mL of 0.2 mol/L B-R buffer solution. The optimum instrumental conditions for the detection were chosen as follows: the initial potential, 0.00 V; the final potential, -0.80 V; the potential scanning rate, 400 mV/s; the mercury drop standing time, 7 s. Under the optimum conditions, the linear range for detection of free HRP was 4.0×10-4-1.0 μg/L with a detection limit of 0.12 μg/L. Based on the new immunoassay system, the linear range of the detection to CEA was 0.50-80 μg/L and the detection limit was 0.50 μg/L, which is 10 times lower than that of traditional spectrophotometric enzymE-linked immunosorbent assay method. The 2-Amino-3-hydroxylpyridinE-H2O2-HRP voltammetric enzymE-linked immunoassay new system exhibits excellent performance having

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

    Science.gov (United States)

    Sørensen, I K; Mortensen, A; Kristiansen, E; van Kreijl, C; Adamson, R H; Thorgeirsson, S S

    1996-10-01

    The usefulness of transgenic E(mu)-pim-1 mice over-expressing the pim-1 oncogene in lymphoid tissues, as sensitive test organisms was studied in a short-term carcinogenicity study. The mice were fed standard diet Altromin 1314 supplemented either with 0.03% 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) for 7 months or with 0.03% 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) for 6 months. PhIP and IQ are heterocyclic amines formed during cooking of meat and fish and are mutagenic to bacteria and cultured mammalian cells. PhIP is a potent mouse lymphomagen, while IQ is a liver carcinogen and also causes lung tumors and tumors of the forestomach in mice. We found that transgenic E(mu)-pim-1 mice are highly susceptible to PhIP induced lymphomagenesis but do not respond to the IQ treatment. PhIP feeding of E(mu)-pim-1 mice not only increased the total number of T-cell lymphomas but also decreased the latency time compared to either transgenic or wild-type controls. The effect was most pronounced in the treated female E(mu)-pim-1 mice, which showed a higher incidence of PhIP induced T-cell lymphomas than transgenic males and a strongly reduced latency period after PhIP treatment compared to non-transgenic mice. Our results suggest that the transgenic E(mu)-pim-1 mouse may be a useful model for short-term carcinogenicity screening of potential genotoxic carcinogens having the lymphoid system as target tissue. The carcinogen IQ which does not have the lymphoid system as a target was not recognized in this model. PMID:8895492

  5. 2-Amino-3,8-dimethylimidazo-[4,5-f]quinoxaline-induced DNA adduct formation and mutagenesis in DNA repair-deficient Chinese hamster ovary cells expressing human cytochrome P4501A1 and rapid or slow acetylator N-acetyltransferase 2.

    Science.gov (United States)

    Bendaly, Jean; Zhao, Shuang; Neale, Jason R; Metry, Kristin J; Doll, Mark A; States, J Christopher; Pierce, William M; Hein, David W

    2007-07-01

    2-Amino-3,8-dimethylimidazo-[4,5-f]quinoxaline (MeIQx) is one of the most potent and abundant mutagens in the western diet. Bioactivation includes N-hydroxylation catalyzed by cytochrome P450s followed by O-acetylation catalyzed by N-acetyltransferase 2 (NAT2). In humans, NAT2*4 allele is associated with rapid acetylator phenotype, whereas NAT2*5B allele is associated with slow acetylator phenotype. We hypothesized that rapid acetylator phenotype predisposes humans to DNA damage and mutagenesis from MeIQx. Nucleotide excision repair-deficient Chinese hamster ovary cells were constructed by stable transfection of human cytochrome P4501A1 (CYP1A1) and a single copy of either NAT2*4 (rapid acetylator) or NAT2*5B (slow acetylator) alleles. CYP1A1 and NAT2 catalytic activities were undetectable in untransfected Chinese hamster ovary cell lines. CYP1A1 activity did not differ significantly (P > 0.05) among the CYP1A1-transfected cell lines. Cells transfected with NAT2*4 had 20-fold significantly higher levels of sulfamethazine N-acetyltransferase (P = 0.0001) and 6-fold higher levels of N-hydroxy-MeIQx O-acetyltransferase (P = 0.0093) catalytic activity than cells transfected with NAT2*5B. Only cells transfected with both CYP1A1 and NAT2*4 showed concentration-dependent cytotoxicity and hypoxanthine phosphoribosyl transferase mutagenesis following MeIQx treatment. Deoxyguanosine-C8-MeIQx was the primary DNA adduct formed and levels were dose dependent in each cell line and in the following order: untransfected < transfected with CYP1A1 < transfected with CYP1A1 and NAT2*5B < transfected with CYP1A1 and NAT2*4. MeIQx DNA adduct levels were significantly higher (P < 0.001) in CYP1A1/NAT2*4 than CYP1A1/NAT2*5B cells at all concentrations of MeIQx tested. MeIQx-induced DNA adduct levels correlated very highly (r2 = 0.88) with MeIQx-induced mutants. These results strongly support extrahepatic activation of MeIQx by CYP1A1 and a robust effect of human NAT2 genetic polymorphism

  6. Protective activity of probiotic bacteria against 2-amino-3-methyl-3H-imidazo[4,5-f]quinoline (IQ) and 2-amino-1-methyl-6-phenyl-1H-imidazo[4,5-b]pyridine (PhIP) - an in vitro study.

    Science.gov (United States)

    Nowak, Adriana; Czyżowska, Agata; Stańczyk, Małgorzata

    2015-01-01

    Heterocyclic aromatic amines (HAAs) are carcinogenic compounds present in a typical Western diet rich in thermally processed meat. These nutritional factors can modulate the cytotoxicity of faecal water (FW) and induce tumours in the human gastrointestinal tract. Supplementation with probiotics is promising in terms of reducing the harmful effects of HAAs in the human body. The aim of the study was in vitro assessment of the protective activity of the probiotic strains Lb. rhamnosus 0900, Lb. rhamnosus 0908, Lb. casei 0919 and Lb. casei DN 114001 against IQ (2-amino-3-methyl-3H-imidazo[4,5-f]quinoline) and PhIP (2-amino-1-methyl-6-phenyl-1H-imidazo[4,5-b]pyridine) after incubation with faeces from 15 persons aged 4 months to 82 years (children, adults and the elderly). The highest mean cytotoxicity of FW was observed for the elderly (63.2% ± 3.7%) and the lowest for children (28.0% ± 9.5%), as estimated by a neutral red uptake assay. The probiotics lowered the average cytotoxicity of FW exposed to IQ or PhIP. The concentration of IQ and PhIP in FW was most effectively reduced by Lb. rhamnosus 0900 (47.5%) and Lb. casei 0919 (45.8%), respectively, as determined by high -performance liquid chromatography. All the tested strains bound PhIP to a higher extent than IQ. In an alkaline comet assay, Lb. casei 0919 and Lb. rhamnosus 0908 displayed the strongest protective effect against IQ and PhIP (up to 80% reduction of DNA damage). Also in a comet assay, Lb. rhamnosus 0908 exhibited antioxidative activity toward H2O2 and PhIP (up to 63% and 69.5% reduction of oxidative DNA damage, respectively). The protective activity of the probiotic strains was specific to a given person's FW, which implies the involvement of intestinal microbiota in the process. PMID:26295367

  7. Synthesis of novel 6-(substituted benzyl)imidazo[2,1-b][1,3]thiazole catalyzed by polystyrene-supported palladium(II) ethylenediamine complex

    International Nuclear Information System (INIS)

    The polymer-supported palladium(II) ethylenediamine complex, [PS-en-Pd(II)], is a highly active catalyst that could be used for the Sonogashira coupling reaction between an aryl iodide and 2-amino-3-(2-propynyl)-1,3-thiazolium bromide, 3. This heterogeneous palladium catalyst is efficient, stable, and recyclable. Reaction of compound 3 with various aryl iodides, 4a-f in the presence of the [PS-en-Pd(II)] complex leads to the production of the 6-(substituted benzyl)imidazo[2,1-b][1,3]thiazoles 5a-f. (author)

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

    DEFF Research Database (Denmark)

    Juknaite, Lina; Sugamata, Yutaro; Tokiwa, Kazuya;

    2013-01-01

    IKM-159 was developed and identified as a member of a new class of heterotricyclic glutamate analogs that act as AMPA receptor-selective antagonists. However, it was not known which enantiomer of IKM-159 was responsible for its pharmacological activities. Here, we report in vivo and in vitro...... neuronal activities of both enantiomers of IKM-159 prepared by enantioselective asymmetric synthesis. Employing (R)-2-amino-2-(4-methoxyphenyl)ethanol as a chiral auxiliary, (2R)-IKM-159 and the (2S)-counterpart were successfully synthesized in 0.70% and 1.5% yields, respectively, over total 18 steps. Both...

  9. Crystal structure of 2-amino-3-cyano-4-(4-methoxyphenyl-4H-1-benzothieno[3,2-b]pyran

    Directory of Open Access Journals (Sweden)

    Mohamed Bakhouch

    2015-12-01

    Full Text Available The three fused five- and six-membered rings in the title compound, C19H14N2O2S, are virtually coplanar, with the maximum deviation from the mean plane being 0.060 (1 Å. This benzothieno[3,2-b]pyran ring system is nearly perpendicular to the plane of the 4-methoxyphenyl ring, forming a dihedral angle of 83.65 (5°. In the crystal, molecules are linked by pairs of N—H...N hydrogen bonds into inversion dimers. The dimeric units are further connected by an N—H...O hydrogen bond into a tape running along the b axis. The tapes are linked together by C—H...N and π–π interactions [centroid–centroid distance = 3.7743 (8 Å], forming a three-dimensional network.

  10. System a amino acid transport-targeted brain and systemic tumor PET imaging agents 2-amino-3-[18 F]fluoro-2-methylpropanoic acid and 3-[18 F]fluoro-2-methyl-2-(methylamino)propanoic acid

    International Nuclear Information System (INIS)

    Introduction: Amino acid based radiotracers target tumor cells through increased uptake by membrane-associated amino acid transport (AAT) systems. In the present study, four structurally related non-natural 18 F-labeled amino acids, (R)- and (S)-[18 F]FAMP 1 and (R)- and (S)-[18 F]MeFAMP 2 have been prepared and evaluated in vitro and in vivo for their potential utility in brain and systemic tumor imaging based upon primarily system A transport with positron emission tomography (PET). Methods: The transport of enantiomers of [18 F]FAMP 1 and [18 F]MeFAMP 2 was measured through in vitro uptake assays in human derived cancer cells including A549 (lung), DU145 (prostate), SKOV3 (ovary), MDA MB468 (breast) and U87 (brain) in the presence and absence of amino acid transporter inhibitors. The in vivo biodistribution of these tracers was evaluated using tumor mice xenografts at 15, 30, 60 and 120 min post injection. Results: All four tracers showed moderate to high levels of uptake (1–9%ID/5 × 105 cells) by the cancer cell lines tested in vitro. AAT cell inhibition assays demonstrated that (R)-[18 F]1 and (S)-[18 F]1 entered these tumor cells via mixed AATs, likely but not limited to system A and system L. In contrast, (R)-[18 F]2 and (S)-[18 F]2 showed high selectivity for system A AAT. Similar to the results of in vitro cell studies, the tumor uptake of all four tracers was good to high and persisted over the 2 hours time course of in vivo studies. The accumulation of these tracers was higher in tumor than most normal tissues including blood, brain, muscle, bone, heart, and lung, and the tracers with the highest in vitro selectivity for system A AAT generally demonstrated the best tumor imaging properties. Higher uptake of these tracers was observed in the pancreas, kidney and spleen compared to tumors. Conclusions: These preclinical studies demonstrate good imaging properties in a wide range of tumors for all four amino acids evaluated with (R)-[18 F]2 having the highest selectivity for system A AAT

  11. Green chemistry synthesis: 2-amino-3-[(E)-(2-pyridyl)methylideneamino]but-2-enedinitrile monohydrate and 5-cyano-2-(2-pyridyl)-1-(2-pyridylmethyl)-1H-imidazole-4-carboxamide.

    Science.gov (United States)

    Altaf, Muhammad; Stoeckli-Evans, Helen

    2010-09-01

    The title compounds, C(10)H(9)N(5)O.H(2)O (L1.H(2)O) and C(16)H(12)N(6)O (L2), were synthesized by solvent-free aldol condensation at room temperature. L1, prepared by grinding picolinaldehyde with 2,3-diamino-3-isocyanoacrylonitrile in a 1:1 molar ratio, crystallized as a monohydrate. L2 was prepared by grinding picolinaldehyde with 2,3-diamino-3-isocyanoacrylonitrile in a 2:1 molar ratio. By varying the conditions of crystallization it was possible to obtain two polymorphs, viz. L2-I and L2-II; both crystallized in the monoclinic space group P2(1)/c. They differ in the orientation of one pyridine ring with respect to the plane of the imidazole ring. In L2-I, this ring is oriented towards and above the imidazole ring, while in L2-II it is rotated away from and below the imidazole ring. In all three molecules, there is a short intramolecular N-H...N contact inherent to the planarity of the systems. In L1.H(2)O, this involves an amino H atom and the C=N N atom, while in L2 it involves an amino H atom and an imidazole N atom. In the crystal structure of L1.H(2)O, there are N-H...O and O-H...O intermolecular hydrogen bonds which link the molecules to form two-dimensional networks which stack along [001]. These networks are further linked via intermolecular N-H...N(cyano) hydrogen bonds to form an extended three-dimensional network. In the crystal structure of L2-I, symmetry-related molecules are linked via N-H...N hydrogen bonds, leading to the formation of dimers centred about inversion centres. These dimers are further linked via N-H...O hydrogen bonds involving the amide group, also centred about inversion centres, to form a one-dimensional arrangement propagating in [100]. In the crystal structure of L2-II, the presence of intermolecular N-H...O hydrogen bonds involving the amide group results in the formation of dimers centred about inversion centres. These are linked via N-H...N hydrogen bonds involving the second amide H atom and the cyano N atom, to form two-dimensional networks in the bc plane. In L2-I and L2-II, C-H...pi and pi-pi interactions are also present. PMID:20814102

  12. Green chemistry synthesis: 2-amino-3-[(E)-(2-pyridyl)methylideneamino]but-2-enedinitrile monohydrate and 5-cyano-2-(2-pyridyl)-1-(2-pyridylmethyl)-1H-imidazole-4-carboxamide.

    Science.gov (United States)

    Altaf, Muhammad; Stoeckli-Evans, Helen

    2010-09-01

    The title compounds, C(10)H(9)N(5)O.H(2)O (L1.H(2)O) and C(16)H(12)N(6)O (L2), were synthesized by solvent-free aldol condensation at room temperature. L1, prepared by grinding picolinaldehyde with 2,3-diamino-3-isocyanoacrylonitrile in a 1:1 molar ratio, crystallized as a monohydrate. L2 was prepared by grinding picolinaldehyde with 2,3-diamino-3-isocyanoacrylonitrile in a 2:1 molar ratio. By varying the conditions of crystallization it was possible to obtain two polymorphs, viz. L2-I and L2-II; both crystallized in the monoclinic space group P2(1)/c. They differ in the orientation of one pyridine ring with respect to the plane of the imidazole ring. In L2-I, this ring is oriented towards and above the imidazole ring, while in L2-II it is rotated away from and below the imidazole ring. In all three molecules, there is a short intramolecular N-H...N contact inherent to the planarity of the systems. In L1.H(2)O, this involves an amino H atom and the C=N N atom, while in L2 it involves an amino H atom and an imidazole N atom. In the crystal structure of L1.H(2)O, there are N-H...O and O-H...O intermolecular hydrogen bonds which link the molecules to form two-dimensional networks which stack along [001]. These networks are further linked via intermolecular N-H...N(cyano) hydrogen bonds to form an extended three-dimensional network. In the crystal structure of L2-I, symmetry-related molecules are linked via N-H...N hydrogen bonds, leading to the formation of dimers centred about inversion centres. These dimers are further linked via N-H...O hydrogen bonds involving the amide group, also centred about inversion centres, to form a one-dimensional arrangement propagating in [100]. In the crystal structure of L2-II, the presence of intermolecular N-H...O hydrogen bonds involving the amide group results in the formation of dimers centred about inversion centres. These are linked via N-H...N hydrogen bonds involving the second amide H atom and the cyano N atom, to form two-dimensional networks in the bc plane. In L2-I and L2-II, C-H...pi and pi-pi interactions are also present.

  13. Effects of dietary antioxidants and 2-amino-3-methylimidazo[4,5-f]-quinoline (IQ) on preneoplastic lesions and on oxidative damage, hormonal status, and detoxification capacity in the rat

    DEFF Research Database (Denmark)

    Breinholt, Vibeke M.; Mølck, Anne-Marie; Svendsen, Gitte Winkel;

    2003-01-01

    The potential beneficial or adverse affect of prolonged dietary administration of moderate to high doses (1-100 mg/kg diet) of the antioxidants, lycopene, quercetin and resveratrol or a mixture of lycopene and quercetin was investigated in male F344 rats. Selected markers for toxicity and defense...

  14. Design, synthesis, and pharmacology of a highly subtype-selective GluR1/2 agonist, (RS)-2-amino-3-(4-chloro-3-hydroxy-5-isoxazolyl)propionic acid (Cl-HIBO)

    DEFF Research Database (Denmark)

    Bjerrum, Esben J; Kristensen, Anders S; Pickering, Darryl S;

    2003-01-01

    On the basis of structural studies, chloro-homoibotenic acid (Cl-HIBO) was designed and synthesized. Cl-HIBO was characterized in binding and electrophysiology experiments on native and cloned subtypes of GluRs. Electrophysiological selectivities ranged from 275 to 1600 for GluR1/2 over GluR3/4. ...

  15. In vitro metabolism of two heterocyclic andnes, 2-amino-9H-pyrido[2,3-b]indole (A alpha C) and 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeA alpha C) in human and rat hepatic microsomes

    DEFF Research Database (Denmark)

    Frederiksen, Hanne; Frandsen, Henrik Lauritz

    2002-01-01

    microsomes from human pools, rats induced with polychlorinated biphenyl (PCB) (Aroclor 1254) and control rats. The microsomes were incubated with AalphaC and MeAalphaC and the detoxified and activated metabolites of AalphaC and MeAalphaC were separated and characterised by HPLC-MS. AalphaC is metabolised to......-metabolites react partially in the incubation system with formation of protein adducts, dimers and the parent compound by reduction of the A(2)-OH-metabolites. The distribution between the detoxified and activated metabolites in the different types of hepatic microsomes showed same pattern for both AalphaC and Mc......AalphaC In PCB-induced rat microsomes, the major part of the metabolites are detoxified, only a little amount is activated. In control rat microsomes there is a fifty-ffty distribution between detoxification and activation, while the major part of the metabolites from the human microsomes are activated and...

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

    DEFF Research Database (Denmark)

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

    2003-01-01

    , activated cloned AMPA receptor subunits GluR1o, GluR3o, and GluR4o with EC(50) values in the range 4.5-15 microM and the coexpressed kainate-preferring subunits GluR6 + KA2 (EC(50) = 6.4 microM). Compound 6, but not 7, proved to be a very potent agonist (EC(50) = 0.13 microM) at the kainate-preferring GluR5...

  17. Positive Allosteric Modulators of 2-Amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic Acid Receptors Belonging to 4-Cyclopropyl-3,4-dihydro-2H-1,2,4-pyridothiadiazine Dioxides and Diversely Chloro-Substituted 4-Cyclopropyl-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-Dioxides

    DEFF Research Database (Denmark)

    Francotte, Pierre; Nørholm, Ann-Beth; Deva, Taru;

    2014-01-01

    Two 4-ethyl-substituted pyridothiadiazine dioxides belonging to α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor positive allosteric modulators were cocrystallized with the GluA2 ligand binding domain in order to decipher the impact of the position of the nitrogen atom on thei...

  18. Phase transitions and dielectric properties of a hexagonal ABX3 perovskite-type organic-inorganic hybrid compound: [C3H4NS][CdBr3].

    Science.gov (United States)

    Liao, Wei-Qiang; Ye, Heng-Yun; Zhang, Yi; Xiong, Ren-Gen

    2015-06-21

    A new organic-inorganic hexagonal perovskite-type compound with the formula ABX3, thiazolium tribromocadmate(ii) (1), in which thiazolium cations are situated in the space between the one-dimensional chains of face-sharing CdBr(6) octahedra, has been successfully synthesized. Systematic characterizations including differential scanning calorimetry measurements, variable-temperature structural analyses, and dielectric measurements reveal that it undergoes two structural phase transitions, at 180 and 146 K. These phase transitions are accompanied by remarkable dielectric relaxation and anisotropy. The thiazolium cations remain orientationally disordered during the two phase transition processes. The origins of the phase transitions at 180 and 146 K are ascribed to the slowing down and reorientation of the molecular motions of the cations, respectively. Moreover, the dielectric relaxation process well described by the Cole-Cole equation and the prominent dielectric anisotropy are also connected with the dynamics of the dipolar thiazolium cations.

  19. 金鸡纳-铂催化2-氧代-4-苯基丁酸乙酯的不对称加氢%Enantioselective Hydrogenation of Ethyl 2-Oxo-4-phenylbutyrate on Cinchona-Platinum Catalysts

    Institute of Scientific and Technical Information of China (English)

    夏涛; 任其龙; 吴平东

    2005-01-01

    Enantioselective hydrogenation of ethyl 2-oxo-4-phenylbutyrate to ethyl (R)-2-hydroxy-4-phenyl- bu-tyrate on Pt/γ-Al2O3 modified by 10,11-dihydrocinchonidine was studied by investigating the influences of the amount of modifier, initial concentration of reactant, pressure and temperature on conversion and enantiometric excess in a stirred autoclave and the effects of the liquid velocity, gas velocity, modifier concentration and various catalytic beds in a trickle-bed reactor. The maximum optical yields were about 50% and 60% in the two types of reactors, respectively. It was assumed that the total hydrogenation rate included the reaction rates over the unmodified and modified active sites on platinum surface and a kinetic model, which fitted the experimental data well in autoclave, was obtained. A simplified plug-flow model was proposed to describe the bed average efficiency of trickle-bed reactor.

  20. SYNTHESIS OF NOVEL BICYCLIC AND TRICYCLIC THIAZOLE AND IMIDAZOLE CONTAINING 2-AMINOPROPIONIC ACIDS Synthese von neuartigen bicyclischen und tricyclischen THIAZOLE und Imidazol MIT 2-Aminopropionsäuren

    Directory of Open Access Journals (Sweden)

    Tatjana Beresneva, Edgars Abele

    2011-04-01

    Full Text Available Synthesis of four novel bicyclic and tricyclic amino acids (2-amino-3-benzo[4,5]imidazo[2,1- b]thiazol-3-ylpropionic acid, 2-amino-3-benzo[d]imidazo[2,1-b]thiazol-2-ylpropionic acid, 2- amino-3-thiazolo[3,2-b][1,2,4]triazol-6-ylpropionic acid, 2-amino-3-(2- methylsulfanylimidazo[2,1-b][1,3,4]thiadiazol-6-ylpropionic acid were carried out.

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

    DEFF Research Database (Denmark)

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

    2000-01-01

    We have previously described the potent and selective (RS)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA) receptor agonist, (RS)-2-amino-3-(3-carboxy-5-methyl-4-isoxazolyl)propionic acid (ACPA), and the AMPA receptor antagonist (RS)-2-amino-3-[3-(carboxymethoxy)-5-methyl-4-isoxa...

  2. Organocatalytic upgrading of furfural and 5-hydroxymethyl furfural to C10 and C12 furoins with quantitative yield and atom-efficiency.

    Science.gov (United States)

    Zang, Hongjun; Chen, Eugene Y X

    2015-01-01

    There is increasing interest in the upgrading of C5 furfural (FF) and C6 5-hydroxymethyl furfural (HMF) into C10 and C12 furoins as higher energy-density intermediates for renewable chemicals, materials, and biofuels. This work utilizes the organocatalytic approach, using the in situ generated N,S-heterocyclic carbene catalyst derived from thiazolium ionic liquids (ILs), to achieve highly efficient self-coupling reactions of FF and HMF. Specifically, variations of the thiazolium IL structure have led to the most active and efficient catalyst system of the current series, which is derived from a new thiazolium IL carrying the electron-donating acetate group at the 5-ring position. For FF coupling by this IL (0.1 mol %, 60 °C, 1 h), when combined with Et3N, furoin was obtained in >99% yield. A 97% yield of the C12 furoin was also achieved from the HMF coupling by this catalyst system (10 mol % loading, 120 °C, 3 h). On the other hand, the thiazolium IL bearing the electron-withdrawing group at the 5-ring position is the least active and efficient catalyst. The mechanistic aspects of the coupling reaction by the thiazolium catalyst system have also been examined and a mechanism has been proposed.

  3. Comparison of excitotoxic profiles of ATPA, AMPA, KA and NMDA in organotypic hippocampal slice cultures

    DEFF Research Database (Denmark)

    Kristensen, Bjarne Winther; Noraberg, J; Zimmer, J

    2001-01-01

    The excitotoxic profiles of (RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl)propionic acid (ATPA), (RS)-2-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA), kainic acid (KA) and N-methyl-D-aspartate (NMDA) were evaluated using cellular uptake of propidium iodide (PI) as a measure for...

  4. Synthesis of Some Thienopyrimidine Derivatives

    Directory of Open Access Journals (Sweden)

    Hassan M. Al-Hazimi

    2006-07-01

    Full Text Available Thioxothienopyrimidinones, alkylthio- and arylalkylthiothienopyrimidinones, thienopyrimidinones, thienopyrimidines a thienopyrimidinedione and a thienotriazolo- pyrimidinone were prepared from 2-amino-3-carboethoxy-4,5-disubstituted thiophenes and 2-amino-3-cyano-4,5-disubstituted thiophenes via reactions with different reagents.

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

    DEFF Research Database (Denmark)

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

    2000-01-01

    We have studied the pharmacological effects of (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) and the enantiomers of (RS)-2-amino-3-(3-hydroxy-1,2, 5-thiadiazol-4-yl)propionic acid (TDPA) on cloned human excitatory amino acid transporter subtypes 1, 2 and 3 (EAAT1-3) expres...

  6. Influence of gelator structures on formation and stability of supramolecular hydrogels

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    A supramolecular hydrogel (defined as Gl) formed from 1,2,4,5-benzene tetracarboxylic acid (BTCA) and 2-amino-3-hydroxypyridine possessed higher Tgel than that of another hydrogel (defined as G2) formed from BTCA and 3-hydroxypyridine.Based on the analysis of their xerogels by 1H NMR, IR and XRD, the higher stability of G1 was attributed to the formation of stronger hydrogen binding enhanced by the ortho amino group of 2-amino-3-hydroxypyridine.

  7. Synthesis and tritium labeling of the food mutagens IQ and methyl-IQ

    Energy Technology Data Exchange (ETDEWEB)

    Waterhouse, A.L.; Rapoport, H. (California Univ., Berkeley (USA). Dept. of Chemistry)

    1985-03-01

    The mutagens found in cooked meat, 2-amino-3-methylimidazo(4,5-f)-quinoline (IQ) and 2-amino-3,4-dimethylimidazo(4,5-f)quinoline (Methyl-IQ), have been synthesized by unambiguous methods that allow for the preparation of sufficient quantities of material for biological studies. These methods avoid difficult separations of regioisomeric mixtures of products and incorporate specific high level tritium labeling, effected by hydrogenolysis of the appropriately substituted 5-bromo precursors.

  8. SYNTHESIS AND HALOCYCLIZATION OF ALLYL DERIVATIVES OF 4,5-DIHYDRO-1,3-THIAZOL-2-THIONE

    OpenAIRE

    Tarasova, N; Kim, D.

    2015-01-01

    2-Propenyl-(2-methyl-1-propenyl-, 2-butenylthioand (3-methylbutenyl-)thio4,5-dihydro-1,3-thiazoles are synthesized by alkylation of 4,5-dihydro-1,3-thiazol2-thione. These products were researched in halocyclization reactions with iodine and bromine.3-(halomethyl)-2,3,5,6-tetrahydrothiazolo[2,3-b]thiazolium and 6-halo-3,5,6,7-tetrahydro-2H-thiazolo[2,3-b]thiazinium halides were formed. The structure of all the synthesized compounds was confirmed by 1H NMR and gas chromatography-mass spectrometry.

  9. Binding of /sup 14/C-labeled food mutagens (IQ, MeIQ, MeIQx) by dietary fiber in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Sjoedin, P.B.; Nyman, M.E.; Nilsson, L.; Asp, N.L.; Jaegerstad, M.

    Binding of three mutagens, known to occur in fried or broiled foods, by thirteen different types of dietary fiber was investigated in vitro. Nonspecific binding by other food polymers was minimized by using protease and amylase treatment. Water-insoluble fiber components were responsible for most of the binding capacity. Generally, a slightly larger proportion of 2-amino-3,4-dimethylimidazo (4,5-f)quinoline (MeIQ) than of 2-amino-3-methylimidazo (4,5-f)quinoline (IQ) and 2-amino-3,8-dimethylimidazo) -4,5-f)quinoxaline (MeIQx) was bound. There was a significant correlation between Klason lignin content and binding of mutagens. Optimum pH for binding was between 4 and 6. Dietary fiber from sorghum had the highest binding capacity, which could be due to the presence of a large Klason lignin fraction.

  10. Binding of 14C-labeled food mutagens (IQ, MeIQ, MeIQx) by dietary fiber in vitro

    International Nuclear Information System (INIS)

    Binding of three mutagens, known to occur in fried or broiled foods, by thirteen different types of dietary fiber was investigated in vitro. Nonspecific binding by other food polymers was minimized by using protease and amylase treatment. Water-insoluble fiber components were responsible for most of the binding capacity. Generally, a slightly larger proportion of 2-amino-3,4-dimethylimidazo [4,5-f]quinoline (MeIQ) than of 2-amino-3-methylimidazo [4,5-f]quinoline (IQ) and 2-amino-3,8-dimethylimidazo] -4,5-f]quinoxaline (MeIQx) was bound. There was a significant correlation between Klason lignin content and binding of mutagens. Optimum pH for binding was between 4 and 6. Dietary fiber from sorghum had the highest binding capacity, which could be due to the presence of a large Klason lignin fraction

  11. Half-sandwich pentamethylcyclopentadienyl group 9 metal complexes of 2-aminopyridyl ligands: Synthesis, spectral and molecular study

    Indian Academy of Sciences (India)

    Mahesh Kalidasan; Scott Forbes; Yurij Mozharivskyj; Mohan Rao Kollipara

    2015-06-01

    Thereaction of [Cp*M(-Cl)Cl]2 (M = Rh, Ir) with 2-aminopyridyl based ligands lead to the formation of mononuclear neutral complexes of general formula [Cp*MCl2(L)] {where L1= 2-aminopyridine, L2= 2-amino-3-picoline, L3= 2-amino-3-nirtopyridine, and L4= 2-amino-3-pyridine carboxyaldehyde}. The complexes have been characterized by FT-IR, UV-Vis, 1H-13C NMR and mass spectroscopic methods. X-ray crystallographic studies of the complexes have shown typical piano-stool geometry around the metal centre in which 2-aminopyridyl ligand acts as an N-monodentate ligand and the amino functionality is not involved in metal coordination. The intra/intermolecular arrangement is due to hydrogen bonding.

  12. Heterocyclic amines content of meat and fish cooked by Brazilian methods

    OpenAIRE

    Iwasaki, Motoki; Kataoka, Hiroyuki; Ishihara, Junko; Takachi, Ribeka; Hamada, Gerson Shigeaki; Sharma, Sangita; Le Marchand, Loïc; Tsugane, Shoichiro

    2010-01-01

    Heterocyclic amine (HCA) concentrations were measured in meat and fish samples cooked by pan-frying, grilling and churrasco (Brazilian barbecue) to various levels of doneness in accordance with the cooking methods most commonly used in Brazil. HCAs were extracted by the Blue-rayon absorption method and measured by liquid chromatography–mass spectrometry. 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), and 2-amino-3,4,8-trimethylim...

  13. Studies on Aryl-Substituted Phenylalanines: Synthesis, Activity, and Different Binding Modes at AMPA Receptors

    DEFF Research Database (Denmark)

    Szymanska, Ewa; Frydenvang, Karla Andrea; Pickering, Darryl S;

    2016-01-01

    A series of racemic aryl-substituted phenylalanines was synthesized and evaluated in vitro at recombinant rat GluA1−3, at GluK1−3, and at native AMPA receptors. The individual enantiomers of two target compounds, (RS)-2-amino-3-(3,4-dichloro-5-(5-hydroxypyridin-3-yl)phenyl)- propanoic acid (37...

  14. Design, synthesis and in vitro pharmacology of GluK1 and GluK3 antagonists. Studies towards the design of subtype-selective antagonists through 2-carboxyethyl-phenylalanines with substituents interacting with non-conserved residues in the GluK binding sites

    DEFF Research Database (Denmark)

    Sköld, Niklas; Nielsen, Birgitte; Olsen, Jakob;

    2014-01-01

    In order to identify compounds selective for the GluK1 and GluK3 subtypes of kainate receptors we have designed and synthesized a series of (S)-2-amino-3-((2-carboxyethyl)phenyl)propanoic acid analogs with hydrogen bond donating and accepting substituents on the aromatic ring. Based on crystal st...

  15. 5-HTP

    Science.gov (United States)

    ... research shows that taking 5-HTP with D-phenylalanine and L-glutamine for 40 days can reduce ... 2-Amino-3-(5-Hydroxy-1H-Indol-3-yl)Propanoic Acid, 5 Hydroxy-Tryptophan, 5 Hydroxy-Tryptophane, 5-Hydroxytryptophan, 5-Hydroxytryptophane, 5-Hydroxy L-Tryptophan, 5-Hydroxy L- ...

  16. Hollow fibre-supported liquid membrane extraction and LC-MS/MS detection for the analysis of heterocyclic amines in urine samples

    DEFF Research Database (Denmark)

    Busquets, R.; Jonsson, J. A.; Frandsen, Henrik Lauritz;

    2009-01-01

    -1-methyl-6-phenylimidazo[4,5-b]pyridine being detected from 2 pg/g urine, levels comparable with a normal exposure. Good reproducibility and repeat-ability was obtained for 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, below 9% using isotopic...

  17. Competitive antagonism of AMPA receptors by ligands of different classes

    DEFF Research Database (Denmark)

    Hogner, Anders; Greenwood, Jeremy R; Liljefors, Tommy;

    2003-01-01

    Ionotropic glutamate receptors (iGluRs) constitute a family of ligand-gated ion channels that are essential for mediating fast synaptic transmission in the central nervous system. This study presents a high-resolution X-ray structure of the competitive antagonist (S)-2-amino-3-[5-tert-butyl-3-(ph...

  18. Pharmacological properties of homomeric and heteromeric GluR1o and GluR3o receptors

    DEFF Research Database (Denmark)

    Nielsen, B S; Banke, T G; Schousboe, A;

    1998-01-01

    .1+/-2.9. The pharmacological profiles of these receptors resembled that of native rat brain AMPA receptors: AMPA analogues > L-glutamate > quinoxaline-2,3-diones > kainate. In the Xenopus oocyte expression system we had previously shown that the agonist (R,S)-2-amino-3-(3-carboxy-5-methyl-4-isoxazolyl)propionate (ACPA...

  19. Long-term, repeated dose in vitro neurotoxicity of the glutamate receptor antagonist L-AP3, demonstrated in rat hippocampal slice cultures by using continuous propidium iodide incubation

    DEFF Research Database (Denmark)

    Kristensen, Bjarne W; Blaabjerg, Morten; Noraberg, Jens;

    2007-01-01

    Most in vitro models are only used to assess short-term effects of test compounds. However, as demonstrated here, hippocampal slice cultures can be used for long-term studies. The test compound used was the metabotropic glutamate receptor antagonist, L(+)-2-amino-3-phosphonopropionic acid (L-AP3)...

  20. Excitotoxic effects of non-NMDA receptor agonists in organotypic corticostriatal slice cultures

    DEFF Research Database (Denmark)

    Kristensen, B W; Noraberg, J; Jakobsen, B;

    1999-01-01

    The excitotoxic effects of the glutamate receptor agonists kainic acid (KA) and 2-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and the corresponding neuroprotective effects of the AMPA/KA receptor antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX) were examined...

  1. Molecular pharmacology of homologues of ibotenic acid at cloned metabotropic glutamic acid receptors

    DEFF Research Database (Denmark)

    Bräuner-Osborne, Hans; Nielsen, B; Krogsgaard-Larsen, P

    1998-01-01

    We have studied the effects of the enantiomers of 2-amino-3-(3-hydroxyisoxazol-5-yl)propionic acid (homoibotenic acid, HIBO) and analogues substituted with a methyl, bromo or butyl group in the four position of the ring at cloned metabotropic glutamate (mGlu) receptors expressed in Chinese hamste...

  2. A novel dualistic profile of an allosteric AMPA receptor modulator identified through studies on recombinant receptors, mouse hippocampal synapses and crystal structures

    DEFF Research Database (Denmark)

    Christiansen, G B; Harbak, Barbara; Hede, S E;

    2015-01-01

    Positive allosteric modulators (PAMs) of 2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA) receptors receive increasing interest as therapeutic drugs and have long served as important experimental tools in the study of the molecular mechanisms underlying glutamate-mediated neurotra...

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

    DEFF Research Database (Denmark)

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

    2002-01-01

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

  4. Synthesis and enantiopharmacology of new AMPA-kainate receptor agonists

    DEFF Research Database (Denmark)

    Conti, P; De Amici, M; De Sarro, G;

    1999-01-01

    , and the rat cortical wedge preparation. CIP-A showed a good affinity for both 2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) and kainic acid (KAIN) receptors. These results were confirmed in the cortical slice model where CIP-A displayed an EC(50) value very close to that of AMPA...

  5. The GABAA receptor agonist THIP is neuroprotective in organotypic hippocampal slice cultures

    DEFF Research Database (Denmark)

    Kristensen, Bjarne Winther; Noraberg, Jens; Zimmer, Jens

    2003-01-01

    The potential neuroprotective effects of the GABA(A) receptor agonists THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol) and muscimol, and the selective GluR5 kainate receptor agonist ATPA ((RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl)propanoic acid), which activates GABAergic interneu...

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

    DEFF Research Database (Denmark)

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

    1996-01-01

    -methylisoxazol-4-yl)hexanoic acid (10), were tested as ligands for metabotropic excitatory amino acid receptors (mGlu1 alpha, mGlu2, mGlu4a, and mGlu6). Whereas AMAA (6) and (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propinoic acid (AMPA, 7) are potent and highly selective agonists at N...

  7. Molecular co-crystals of 2-aminothiazole derivatives.

    Science.gov (United States)

    Lynch; Nicholls; Smith; Byriel; Kennard

    1999-10-01

    A series of molecular adducts of 2-aminothiazole derivatives - 2-aminothiazole, 2-amino-2-thiazoline and 2-aminobenzothiazole with the carboxylic-acid-substituted heterocyclics indole-2-carboxylic acid, N-methylpyrrole-2-carboxylic acid and thiophene-2-carboxylic acid - have been prepared and characterized using X-ray powder diffraction and in five cases by single-crystal X-ray diffraction methods. These five compounds are the adducts of 2-amino-2-thiazolium with indole-2-carboxylate [(C(3)H(7)N(2)S)(+)(C(9)H(6)NO(2))(-)], and N-methylpyrrole-2-carboxylate [(C(3)H(7)N(2)S)(+)-(C(6)H(6)NO(2))(-)], 2-aminobenzothiazolium with indole-2-carboxylate [(C(7)H(7)N(2)S)(+)(C(9)H(6)NO(2))(-)], N-methylpyrrole-2-carboxylate [(C(7)H(7)N(2)S)(+)(C(6)H(6)NO(2))(-)] and thiophene-2-carboxylate [(C(7)H(7)N(2)S)(+)(C(5)H(3)O(2)S)(-)]. All complexes involve proton transfer, as indicated by IR spectroscopy, while the five crystal structures display similar hydrogen-bonding patterns with the dominant interaction being an R(2)(2)(8) graph set dimer association between carboxylate groups and the amine/heterocyclic nitrogen sites. Futhermore, in each case a subsiduary interaction between an amino proton and a carboxylate oxygen completes a linear hydrogen-bonded chain. In addition to this, the indole-2-carboxylate molecules in the adduct structure with 2-amino-2-thiazolium form associated dimers which add to the hydrogen-bonding network.

  8. Michael-Addition Reaction of Malononitrile with α,β-Unsaturated Cycloketones Catalyzed by KF/Al2O3

    Institute of Scientific and Technical Information of China (English)

    WANG, Xiang-Shan(王香善); SHI, Da-Qing(史达清); TU, Shu-Jiang(屠树江)

    2004-01-01

    A series of KF/Al2O3 catalyzed Michael-addition reactions between malononitrile and α,β-unsaturated cycloketones in DMF solution were studied. At room temperature, 2-cyano-3-aryl-3-(1,2,3,4-tetrahydronaphthalen- 1-one-2-yl) propionitrile derivatives were synthesized by the reaction between 2-arylmethylidene-1,2,3,4-tetrahydronaphthalen-1-one and malononitrile. However, if the temperature was increased to 80 ℃, 2-amino-3-cyano-4- aryl-4H-benzo[h]chromene derivatives were obtained in high yields. When the α,β-unsaturated ketones were replaced by 2,6-biarylmethylidenecyclohexanone or 2,5-biarylmethylidenecyclopentanone, another series of 2-amino- 3-cyano-4H-pyran derivatives was isolated successfully. The structures of the products were confirmed by X-ray diffraction analysis.

  9. Tyr702 is an important determinant of agonist binding and domain closure of the ligand-binding core of GluR2

    DEFF Research Database (Denmark)

    Frandsen, Anne; Pickering, Darryl S.; Vestergaard, Bente;

    2005-01-01

    display selectivity among (S)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl) propionic acid (AMPA)-receptor subtypes. The present study provides X-ray structures of the glutamate receptor 2 (GluR2)-selective partial agonist (S)-2-amino-3-(1,3,5,6,7-pentahydro-2,4-dioxocyclopenta[e] pyrimidin-1-yl) propanoic...... acid [(S)-CPW399] in complex with the ligand-binding core of GluR2 (GluR2-S1S2J) and with a (Y702F)GluR2-S1S2J mutant. In addition, the structure of the nonselective partial agonist kainate in complex with (Y702F)GluR2-S1S2J was determined. The results show that the selectivity of (S)-CPW399 toward...

  10. A balance study of /sup 14/C-labelled /sup 3/H-imidazo(4,5-f)quinolin-2-amines (IQ and MeIQ) in rats

    Energy Technology Data Exchange (ETDEWEB)

    Sjoedin, P.; Jaegerstad, M.

    1984-03-01

    The absorption and excretion of /sup 14/C-labelled 2-amino-3-methylimidazo(4,5-f)quinoline (IQ) and 2-amino-3,4-dimethylimidazo(4,5-f)quinoline (MeIQ) were studied in rats of both sexes. The excretion was rapid and within 24 hr more than 90% of the radioactivity had left the rats. After 72 hr the faecal excretion of both compounds was approximately 45-65% and the corresponding excretion via the urine amounted to 37-49%. Only 1-2% was left in the carcasses and less than 0.2% was found in the expired air. About 70% of the IQ and 80% of the MeIQ was found in the bile fluid in a separate 24-hr study. The two compounds had different biliary excretion patterns and the mutagenicity of the bile correlated closely with the excretion of radioactivity.

  11. β-Pyrrolopyrazino Annulated Corroles via a Pictet-Spengler Approach.

    Science.gov (United States)

    Berionni Berna, Beatrice; Nardis, Sara; Galloni, Pierluca; Savoldelli, Andrea; Stefanelli, Manuela; Fronczek, Frank R; Smith, Kevin M; Paolesse, Roberto

    2016-07-15

    Reaction of 2-amino-3-(pyrrol-1-yl)-5,10,15-tris(4-tert-butylphenyl)corrolato copper(II) with arylaldehydes affords novel π-extended β,β'-pyrrolo(1,2-a)pyrazino-fused corroles via a Pictet-Spengler reaction. Corrole shows an unprecedented reaction pathway, leading to a mixture of phenyl-substituted and nonsubstituted pyrrolopyrazino annulated species as reaction products. PMID:27378478

  12. Resolution of 1- and 2-naphthylmethoxyacetic acids, NMR reagents for absolute configuration determination, by use of L-phenylalaninol.

    Science.gov (United States)

    Arita, Shoko; Yabuuchi, Tetsuya; Kusumi, Takenori

    2003-08-01

    Racemic 1- and 2-naphthylmethoxyacetic acids (1NMA and 2NMA), the chiral anisotropic reagents used for absolute configuration determination of chiral secondary alcohols and primary amines, were conveniently resolved to enantiomers (>99% ee) by condensation with L-phenylalaninol (2-amino-3-phenylpropanol), chromatographic separation of the diastereomers, and hydrolysis. This method enables large-scale preparation of enantiomeric 1NMA and 2NMA. PMID:12840826

  13. Dissimilation of cysteate via 3-sulfolactate sulfo-lyase and a sulfate exporter in Paracoccus pantotrophus NKNCYSA

    OpenAIRE

    Rein, Ulrike; Gueta, Ronnie; Denger, Karin; Ruff, Jürgen; Hollemeyer, Klaus; Cook, Alasdair M.

    2005-01-01

    Paracoccus pantotrophus NKNCYSA utilizes (R)-cysteate (2-amino-3-sulfopropionate) as a sole source of carbon and energy for growth, with either nitrate or molecular oxygen as terminal electron acceptor, and the specific utilization rate of cysteate is about 2 mkat (kg protein)(-1). The initial degradative reaction is catalysed by an (R)-cysteate : 2-oxoglutarate aminotransferase, which yields 3-sulfopyruvate. The latter was reduced to 3-sulfolactate by an NAD-linked sulfolactate dehydrogenase...

  14. Structural basis for AMPA receptor activation and ligand selectivity

    DEFF Research Database (Denmark)

    Hogner, A; Kastrup, Jette Sandholm Jensen; Jin, R;

    2002-01-01

    and binding experiments, has been used to increase our knowledge concerning the ionotropic glutamate receptor GluR2 at the molecular level. Five high-resolution X-ray structures of the ligand-binding domain of GluR2 (S1S2J) complexed with the three agonists (S)-2-amino-3-[3-hydroxy-5-(2-methyl-2H-tetrazol-5...

  15. 2-Ethoxy-6-[(3-methylpyridin-2-yliminomethyl]phenol

    Directory of Open Access Journals (Sweden)

    Xiao-Ling Yuan

    2011-05-01

    Full Text Available The title Schiff base compound, C15H16N2O2, was prepared by the condensation reaction of equimolar quantities of 3-ethoxysalicylaldehyde with 2-amino-3-methylpyridine in methanol. The dihedral angle between the benzene ring and the pyridine ring is 2.6 (2° and an intramolecular O—H...N hydrogen bond generates an S(6 ring.

  16. Characterization and toxicity of Amanita cokeri extract.

    Science.gov (United States)

    Drehmel, Dennis C; Chilton, William Scott

    2002-02-01

    The nonprotein amino acids 2-amino-3-cyclopropylbutanoic acid and 2-amino-5-chloro-4-pentenoic acid were isolated from the mushroom Amanita cokeri. The cyclopropyl amino acid is toxic to the fungus Cercospora kikuchii, the arthropod Oncopeltus fasciatus (milk weed bug), and the bacteria Agrobacterium tumefaciens, Erwinia amylovora, and Xanthomonas campestris. Toxicity to bacteria was reversible by addition of isoleucine to the medium. No toxicity was observed for 2-amino-5-chloro-4-pentenoic acid.

  17. Substances in human urine that strongly inhibit bacterial mutagenicity of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and related heterocyclic amines.

    Science.gov (United States)

    Malaveille, C; Hautefeuille, A; Brun, G; Vineis, P; Bartsch, H

    1992-12-01

    Extracts of human urine were shown to contain substances that strongly inhibited the liver S9-mediated mutagenicity of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in Salmonella typhimurium TA98 strain in a liquid incubation assay. The inhibitory effect was unrelated to cytotoxicity and was similar with urine extracts from smokers and non-smokers. Under similar assay conditions, the mutagenicity of the related amino-imidazoazaarenes, 2-amino-3-methyl-imidazo[4,5-f]quinoline, 2-amino-3,8-dimethylimidazo[4,5-f]-quinoline and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline was also found to be strongly inhibited by urine extracts. Decreased or enhanced mutagenicity was seen with 2-acetyl-aminofluorene and 2-aminoanthracene depending on the type of assay, and the time of incubation in liquid medium. A weak inhibition of the mutagenicity of 2-nitrofluorene, a direct-acting mutagen, was observed only after a short incubation time. Mutagenicity of 4-nitroquinoline N-oxide was not altered by the presence of urine extracts at concentrations shown to be inhibitory for the mutagenicity of heterocyclic aromatic amines. Our data suggest that the inhibitory substances in urine act through their capacity to non covalently bind the parent heterocyclic and aromatic amines, thus affecting their availability in aqueous medium for diffusion into liver microsomes where metabolic activation takes place. PMID:1473240

  18. Synthesis of methotrexate-1-15N and methotrexate-4-15NH2

    International Nuclear Information System (INIS)

    This paper describes an application of the pterin synthesis of methotrexate specifically labelled at the N1-ring nitrogen and at the 4-amino group with 99 atom percent 15N. Oximination of ethyl cyanoacetate-15N followed by reduction afforded ethyl 2-aminocyanoacetate-C15N. Condensation with 3-bromopyruvaldoxime and 4-methylamino-benzoic acid afforded 2-amino-3-carbethoxy-5-N-methyl-p-carboxy-anilinomethylpyrazine-1-oxide-2-15NH2. Treatment with ammonium hydroxide at room temperature gave the 3-carboxamide. Reduction of the N-oxide (Pl3), esterification, and dehydration of the amide (POCl3) afforded the 2-amino-3-cyano-pyrazine benzoate ester. Ring closure with guanidine followed by benzoate ester hydrolysis, glutamate coupling and hydrolysis of the glutamate diester yielded methotrexate-1-15N. Animation of the unlabeled 2-amino-3-carbethoxy pyrazine intermediate with 15N-labelled ammonium hydroxide gave the 15N-carboxamide which was carried through the process described above to afford methotrexate-4-15NH2. (author)

  19. Covalent binding of food carcinogens MeIQx, MeIQ and IQ to DNA and protein in microsomal incubations and isolated rat hepatocytes

    Energy Technology Data Exchange (ETDEWEB)

    Wallin, H.; Holme, J.A.; Alexander, J. (National Institute of Public Health, Department of Environmental Medicine, Oslo (Norway))

    1992-01-01

    The metabolic activation of {sup 14}C-labelled food carcinogens 2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline (MeIQx),2-amino-3,4-dimethylimidazo(4,5-f)quinoline(MeIQ) and 2-amino-3-methylimidazo(4,5-f)quinoline (IQ) to macromolecular bound species was studied in microsomal and hepatocellular incubations. Several data indicated that the covalent binding was dependent on P450 enzymes: It was dependent on NADPH, it was induced many times by the P450 IA1 and IA2 upregulators {beta}-naphthoflavone and polychlorinated biphenyls, and was inhibited by the P450 IA1 and IA2 inhibitor {alpha}-naphtoflavone. In both hepatocellular and microsomal incubations the three compounds bound with similar efficiency, with IQ being somewhat more potent compared to MeIQx and MeIQ. The binding appeared to follow saturation kinetics with K{sub m} values less than 20 {mu}M. In incubations with hepatocytes the compounds bound to both cellular DNA and to bovine serum albumin in the medium. The fact that 13-26% of total adducts were formed with bovine serum albumin, indicates that reactive metabolites of the compounds may be transported and react at distant sites from their formation without any further activation. (au).

  20. Covalent binding of food carcinogens MeIQx, MeIQ and IQ to DNA and protein in microsomal incubations and isolated rat hepatocytes

    International Nuclear Information System (INIS)

    The metabolic activation of 14C-labelled food carcinogens 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx),2-amino-3,4-dimethylimidazo[4,5-f]quinoline(MeIQ) and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) to macromolecular bound species was studied in microsomal and hepatocellular incubations. Several data indicated that the covalent binding was dependent on P450 enzymes: It was dependent on NADPH, it was induced many times by the P450 IA1 and IA2 upregulators β-naphthoflavone and polychlorinated biphenyls, and was inhibited by the P450 IA1 and IA2 inhibitor α-naphtoflavone. In both hepatocellular and microsomal incubations the three compounds bound with similar efficiency, with IQ being somewhat more potent compared to MeIQx and MeIQ. The binding appeared to follow saturation kinetics with Km values less than 20 μM. In incubations with hepatocytes the compounds bound to both cellular DNA and to bovine serum albumin in the medium. The fact that 13-26% of total adducts were formed with bovine serum albumin, indicates that reactive metabolites of the compounds may be transported and react at distant sites from their formation without any further activation. (au)

  1. Inhibitory Effect of Rosa rugosa Tea Extract on the Formation of Heterocyclic Amines in Meat Patties at Different Temperatures

    Directory of Open Access Journals (Sweden)

    Muneer Ahmed Jamali

    2016-01-01

    Full Text Available In previous studies, heterocyclic amines (HCAs have been identified as carcinogenic and a risk factor for human cancer. Therefore, the present study was designed to identify bioactive natural products capable of controlling the formation of HCAs during cooking. For this purpose we have evaluated the effect of Rosa rugosa tea extract (RTE on the formation of HCAs in ground beef patties fried at 160 °C or 220 °C. RTE is rich in phenolic compounds and capable of inhibiting the formation of free radicals. The pyrido[3,4-b]indole (norharman and 1-methyl-9H-pyrido[3,4-b]indole (harman contents were significantly (p < 0.05 decreased in RTE-treated patties at 220 °C. 9H-3-Amino-1-methyl-5H-pyrido[4,3-b]indole acetate (Trp-P-2 and 3-amino-1,4-dimethyl-5H-pyrido-[4,3-b]indole acetate (Trp-P-1 were not detected at 160 °C and were statistically (p < 0.01 reduced at 220 °C compared to the control. RTE remarkably inhibited the formation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP at 220 °C (p < 0.001 and at 160 °C (p < 0.05. 2-Amino-9H-pyrido[2,3-b]indole (AαC and 2-amino-3-methyl-9H-pyrido[2,3-b]-indole (MeAαC were only detected in the control group at 160 °C but were comparatively (p > 0.05 similar in the control and treated groups at 220 °C. 2-Amino-3-methylimidazo[4,5-f]quinoline (IQ, 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx, and 2-amino-3,4,8-trimethylimidazo[4,5-f]-quinoxaline (4,8-DiMeIQx were not detected in any sample. Total HCAs were positively correlated with cooking loss. In the RTE-treated groups, 75% of the total HCAs were decreased at 160 °C and 46% at 220 °C, suggesting that RTE is effective at both temperatures and can be used during cooking at high temperatures to lessen the amount of HCAs formed.

  2. The effect of 125I labeled anti-androgen receptor agent on the proliferation of prostate cancer cells

    International Nuclear Information System (INIS)

    Objective: Based on the previous experience of using anti-androgen receptor triple helix forming oligonucleotide (TFO) to inhibit proliferation of prostate cancer cells, a 125I labeled TFO was prepared and tested in this experiment as an androgen receptor targeted antigene radiotherapy. Methods: 125I-TFO was labeled through Iodogen and then transfected LNCaP prostate cancer cells via liposome. The unlabeled TFO, 125I, and naturally cultured cells served as controls. The cellular proliferation was detected by methyl thiazolium tetrazolium (MTT) method, the expression of androgen receptor gene was carried out by RT-PCR and immunohistochemical study. Results: The radiolabeling efficiency, radiochemical purity and specific activity of 125I-TFO were 63.7%, 95.6% and 80.1 kBq/μg, respectively. At the same TFO concentration, the androgen receptor expression level in 125I-TFO treated cells was markedly lower than that of TFO group (P125I-TFO on cellular proliferation was significantly higher (P< 0.01). Conclusion: The inhibitory effect on androgen receptor expression and cell proliferation of prostate cancer cells of antigene therapy with radio-labeled TFO were significantly more obvious than that of classical antigene therapy. (authors)

  3. Part I: RNA hydrolysis catalyzed by imidazole compounds. Part II. Hydrophobic acceleration of reactions and mimics of thiamin-dependent enzymes

    International Nuclear Information System (INIS)

    Catalysts modeled after the active site groups of the enzyme Ribonuclease A were synthesized and tested for catalysis of the hydrolysis of poly(rU), using a quantitative assay. The most effective of all the catalysts is N,N'-bis-imidazolylmethane, which gave a four-fold rate enhancement as compared to N-methyl-imidazole. The structure/activity relationships are discussed in light of the ribonuclease mechanism. Also examined were reactions catalyzed by the coenzyme thiamine. In an investigation of the effects of restricting conformational freedom, a thiazolium salt was attached in two positions to β-cyclodextrin. Since the catalyst gave about the same rate for tritium exchange from benzaldehyde as singly-attached catalysts, we surmise that any rate enhancement due to the restriction of bond rotations has been lost by forcing the structure into less productive conformations. The benzoin condensation catalyzed by cyanide was also investigated. The reaction was shown to be faster in water than in most organic solvents. Kinetic salt effects and the effects of added β- and γ-cyclodextrin were measured in water; salting-out ions and γ-cyclodextrin increase the rate, while salting-in ions and β-cyclodextrin decrease it. Negative salt effects were observed in formamide, ethylene glycol, and DMSO. All these media effects are discussed in relation to the compact, hydrophobic transition state for the reaction

  4. Crystal Structure of 1-Deoxy-D-xylulose 5-Phosphate Synthase, A Crucial Enzyme for Isoprenoids Biosynthesis

    Energy Technology Data Exchange (ETDEWEB)

    Xiang,S.; Usunow, G.; Busch, G.; Tong, L.

    2007-01-01

    Isopentenyl pyrophosphate (IPP) is a common precursor for the synthesis of all isoprenoids, which have important functions in living organisms. IPP is produced by the mevalonate pathway in archaea, fungi, and animals. In contrast, IPP is synthesized by a mevalonate-independent pathway in most bacteria, algae, and plant plastids. 1-Deoxy-D-xylulose 5-phosphate synthase (DXS) catalyzes the first and the rate-limiting step of the mevalonate-independent pathway and is an attractive target for the development of novel antibiotics, antimalarials, and herbicides. We report here the first structural information on DXS, from Escherichia coli and Deinococcus radiodurans, in complex with the coenzyme thiamine pyrophosphate (TPP). The structure contains three domains (I, II, and III), each of which bears homology to the equivalent domains in transketolase and the E1 subunit of pyruvate dehydrogenase. However, DXS has a novel arrangement of these domains as compared with the other enzymes, such that the active site of DXS is located at the interface of domains I and II in the same monomer, whereas that of transketolase is located at the interface of the dimer. The coenzyme TPP is mostly buried in the complex, but the C-2 atom of its thiazolium ring is exposed to a pocket that is the substrate-binding site. The structures identify residues that may have important roles in catalysis, which have been confirmed by our mutagenesis studies.

  5. Flexibility of thiamine diphosphate revealed by kinetic crystallographic studies of the reaction of pyruvate-ferredoxin oxidoreductase with pyruvate.

    Science.gov (United States)

    Cavazza, Christine; Contreras-Martel, Carlos; Pieulle, Laetitia; Chabrière, Eric; Hatchikian, E Claude; Fontecilla-Camps, Juan C

    2006-02-01

    Pyruvate-ferredoxin oxidoreductases (PFOR) are unique among thiamine pyrophosphate (ThDP)-containing enzymes in giving rise to a rather stable cofactor-based free-radical species upon the decarboxylation of their first substrate, pyruvate. We have obtained snapshots of unreacted and partially reacted (probably as a tetrahedral intermediate) pyruvate-PFOR complexes at different time intervals. We conclude that pyruvate decarboxylation involves very limited substrate-to-product movements but a significant displacement of the thiazolium moiety of ThDP. In this respect, PFOR seems to differ substantially from other ThDP-containing enzymes, such as transketolase and pyruvate decarboxylase. In addition, exposure of PFOR to oxygen in the presence of pyruvate results in significant inhibition of catalytic activity, both in solution and in the crystals. Examination of the crystal structure of inhibited PFOR suggests that the loss of activity results from oxime formation at the 4' amino substituent of the pyrimidine moiety of ThDP. PMID:16472741

  6. EPR spectroscopic and computational characterization of the hydroxyethylidene-thiamine pyrophosphate radical intermediate of pyruvate:ferredoxin oxidoreductase.

    Science.gov (United States)

    Mansoorabadi, Steven O; Seravalli, Javier; Furdui, Cristina; Krymov, Vladimir; Gerfen, Gary J; Begley, Tadhg P; Melnick, Jonathan; Ragsdale, Stephen W; Reed, George H

    2006-06-13

    The radical intermediate of pyruvate:ferredoxin oxidoreductase (PFOR) from Moorella thermoacetica was characterized using electron paramagnetic resonance (EPR) spectroscopy at X-band and D-band microwave frequencies. EPR spectra, obtained with various combinations of isotopically labeled substrate (pyruvate) and coenzyme (thiamine pyrophosphate (TPP)), were analyzed by spectral simulations. Parameters obtained from the simulations were compared with those predicted from electronic structure calculations on various radical structures. The g-values and 14N/15N-hyperfine splittings obtained from the spectra are consistent with a planar, hydroxyethylidene-thiamine pyrophosphate (HE-TPP) pi-radical, in which spin is delocalized onto the thiazolium sulfur and nitrogen atoms. The 1H-hyperfine splittings from the methyl group of pyruvate and the 13C-hyperfine splittings from C2 of both pyruvate and TPP are consistent with a model in which the pyruvate-derived oxygen atom of the HE-TPP radical forms a hydrogen bond. The hyperfine splitting constants and g-values are not compatible with those predicted for a nonplanar, sigma/n-type cation radical. PMID:16752902

  7. New bisphosphonate labeled with Iodine-131 for the palliative therapy for bone metastases pain

    International Nuclear Information System (INIS)

    The aim of this work was to obtain new bisphosphonate marked with 131I suitable for palliative treatment of bone metastases pain characteristics. Materials and Methods: It started with aromatic amino acids and the synthesis consisted of three stages: 1) Protection of amino groups by acetylation; 2) phosphonation protected amino acids with a mixture of phosphorous acid and phosphorus pentachloride; 3) Lack of protection of the amino groups by basic hydrolysis. The compounds obtained were characterized by IR, 1H NMR, RMN13-C mass. Los spectrometry bisphosphonic acids obtained were labeled with 131I using chloramine T and iodogen as oxidants. Stability of labeled compounds in aqueous solution was studied serum. 3 mg of 2-amino-3- (4-hydroxyphenyl) -1-hydroxypropyl-1,1-bisphosphonic acid labeled of 131I were administered to male wistar rats (170-190 g) through a lateral tail vein. The scintigraphic study was conducted at 2, 6 and 12 hours. Results: The yield of the reactions of the amino group protection four compounds ranged from 75 to 80%, while the phosphonation was between 50 and 60%. The radiochemical purity of 2-amino-3- (4-hydroxyphenyl) -1-hydroxypropyl-1,1- bisphosphonic acid labeled with 131I was (91.5 ± 1.4)% and its stability was satisfactory for 72h. Scintigraphic images suggest excretion by the kidneys of the compound and from 12 h post-administration begin to visualize bone structures of the animal, suggesting that the compound exhibits affinity for these tissues. Conclusions: A novel synthesis method with modifications that yielded the sodium salts of bisphosphonic acids starting from the respective aromatic amino acids was developed. 2-amino-3- (4-hydroxyphenyl) -1-hydroxypropyl-1,1-bisphosphonic acid 131I labeled was stable up to 72h and showed affinity for bone tissue. (author)

  8. Carcinogenicities in mice and rats of IQ, MeIQ, and MeIQx.

    Science.gov (United States)

    Ohgaki, H; Hasegawa, H; Kato, T; Suenaga, M; Sato, S; Takayama, S; Sugimura, T

    1985-01-01

    The mutagenic heterocyclic amines, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) are present in broiled fish, fried beef, and beef extract. Their carcinogenicities in CDF1 mice and F344 rats were tested by their oral administration in the diet. In mice given diet containing 0.03% IQ, tumors developed in the liver (hepatocellular carcinomas or hepatocellular adenomas), forestomach (squamous cell carcinomas or papillomas), and lung (adenocarcinomas or adenomas) at high incidences. In mice given diet containing 0.04% or 0.01% MeIQ, squamous cell carcinomas and papillomas of the forestomach developed at high incidences. About 40% of the squamous cell carcinomas induced in the forestomach by 0.04% MeIQ metastasized to the liver. Clear dose-response relations were seen in the incidences of tumors in the groups given 0.04% and 0.01% MeIQ. The squamous cell carcinoma-papilloma ratios were higher in 0.04% groups than in 0.01% groups. Female mice treated with 0.04% and 0.01% MeIQ showed significantly higher incidences of liver tumors than controls. The experiment on the carcinogenicity of MeIQx at a dose of 0.06% in mice is still in progress but by experimental week 74, 4 of 16 males and 7 of 18 females autopsied were found to have liver tumors. Rats given diet containing 0.03% IQ showed high incidences of hepatocellular carcinomas, adenocarcinomas of the small and large intestines, and squamous cell carcinomas of the Zymbal gand, clitoral gland, and skin. Except for the liver, the target organs of IQ in CDF1 mice and F344 rats were different. PMID:3842704

  9. Aminothiols: synthesis and effect on chicken brain aminopeptidases.

    Science.gov (United States)

    Weiss, B; Hui, K S; Hui, M; Lajtha, A

    1988-10-01

    An amino acid derivative, leucinethiol, was reported to be a strong inhibitor of aminopeptidase activity. In order to obtain selective inhibitors of various brain aminopeptidases, we tested the inhibition by amino acid analogs of brain aminopeptidase activity. In particular, we synthesized the trifluoroacetyl derivatives of phenylalaninol, tyrosinol, and leucinol; leucinethiol; and phenylalaninethiol and measured their effect on soluble puromycin-sensitive aminopeptidase S1 and SII purified in our laboratory. Two of the compounds, L-bis (1-thio-2-amino-4-methylpentane) dihydrochloride (TAMP) and L-bis (1-thio-2-amino-3-phenylpropane) dihydrochloride (TAPP), caused significant inhibition. PMID:3205972

  10. Determination of bromhexine in cough-cold syrups by absorption spectrophotometry and multivariate calibration using partial least-squares and hybrid linear analyses. Application of a novel method of wavelength selection.

    Science.gov (United States)

    Goicoechea, H C; Olivieri, A C

    1999-07-12

    The mucolitic bromhexine [N-(2-amino-3,5-dibromobenzyl)-N-methylcyclohexylamine] has been determined in cough suppressant syrups by multivariate spectrophotometric calibration, together with partial least-squares (PLS-1) and hybrid linear analysis (HLA). Notwithstanding the spectral overlapping between bromhexine and syrup excipients, as well as the intrinsic variability of the latter in unknown samples, the recoveries are excellent. A novel method of wavelength selection was also applied, based on the concept of net analyte signal regression, as adapted to the HLA methodology. This method allows one to improve the performance of both PLS-1 and HLA in samples containing nonmodeled interferences. PMID:18967655

  11. Three-dimensional structure of the ligand-binding core of GluR2 in complex with the agonist (S)-ATPA

    DEFF Research Database (Denmark)

    Lunn, Marie-Louise; Hogner, Anders; Stensbøl, Tine B;

    2003-01-01

    Two X-ray structures of the GluR2 ligand-binding core in complex with (S)-2-amino-3-(5-tert-butyl-3-hydroxy-4-isoxazolyl)propionic acid ((S)-ATPA) have been determined with and without Zn(2+) ions. (S)-ATPA induces a domain closure of ca. 21 degrees compared to the apo form. The tert-butyl moiety...... of (S)-ATPA is buried in a partially hydrophobic pocket and forces the ligand into the glutamate-like binding mode. The structures provide new insight into the molecular basis of agonist selectivity between AMPA and kainate receptors....

  12. Synthesis and receptor binding affinity of new selective GluR5 ligands

    DEFF Research Database (Denmark)

    Bunch, L; Johansen, T H; Bräuner-Osborne, Hans;

    2001-01-01

    Two hybrid analogues of the kainic acid receptor agonists, 2-amino-3-(5-tert-butyl-3-hydroxy-4-isoxazolyl)propionic acid (ATPA) and (2S,4R)-4-methylglutamic acid ((2S,4R)-4-Me-Glu), were designed, synthesized, and characterized in radioligand binding assays using cloned ionotropic and metabotropi.......0 and 2.0 microM. respectively. Their affinities in the [3H]AMPA binding assay on native cortical receptors were shown to correlate with their GluR2 affinity rather than their GluR5 affinity. No affinity for GluR6 was detected (IC50 > 100 microM)....

  13. One-Pot Synthesis of Tetrahydrobenzo-[b]-pyran Derivatives in Aqueous Media

    Institute of Scientific and Technical Information of China (English)

    JIN,Tong-Shou; WANG,Ai-Qing; ZHANG,Jian-She; LI,Tong-Shuang

    2004-01-01

    @@ In modem organic chemical research, 4H-benzo-[b]-pyran and their derivatives have attracted strong interest due to their useful biological and pharmacological properties. Herein, we report a clean one-pot synthesis of 2-amino-3-cyano-4-aryl-7,7-dimethyl-5-oxo-4H-5,6,7,8-tetrahydro-benzo-[b]-pyrans from aromatic aldehyde, malononitrile and 5,5-dimethyl-1,3-cyclohexadione using hexadecyl trimethyl ammonium bromide (HTMAB) as the catalyst. This method provides several advantages such as high yield, simple work-up procedure and environmental friendliness. All the products were characterized by 1H NMR and IR analyses.

  14. MeIQx-induced DNA adduct formation and mutagenesis in DNA repair deficient CHO cells expressing human CYP1A1 and rapid or slow acetylator NAT2

    OpenAIRE

    Bendaly, Jean; Zhao, Shuang; Neale, Jason R.; Metry, Kristin J.; Doll, Mark A; States, J. Christopher; Pierce, William M.; Hein, David W.

    2007-01-01

    2-Amino-3,8-dimethylimidazo-[4,5-f]quinoxaline (MeIQx) is one of the most potent and abundant mutagens in the western diet. Bioactivation includes N-hydroxylation catalyzed by cytochrome P450s followed by O-acetylation catalyzed by N-acetyltransferase 2 (NAT2). Nucleotide excision repair-deficient chinese hamster ovary (CHO) cells were constructed by stable transfection of human cytochrome P4501A1 (CYP1A1) and a single copy of either NAT2*4 (rapid acetylator) or NAT2*5B (slow acetylator) alle...

  15. Chemoprevention of aberrant crypt foci in the colon of rats by dietary onion.

    OpenAIRE

    Taché, Sylviane; Ladam, Aélis; Corpet, Denis E

    2007-01-01

    International audience Onion intake might reduce the risk of colorectal cancer, according to epidemiology. However, Femia showed in 2003 that diets with a 20% onion intake increase carcinogenesis in rats. We speculated this dose was too high. Prevention of initiation was thus tested in 60 rats given a 5% dried onion diet or AIN76 diet, and initiated 12 days later with azoxymethane (AOM, 1x20 mg/kg i.p.), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ, 2x200 mg/kg p.o.), or N-nitroso-N-methylu...

  16. SYNTHESIS AND ANTIMICROBIAL EVALUATION OF 3-AMINO-11-CYANO-4-IMINO- PYRAZOLO [4, 5-E]-4H-PYRIMIDO [2, 1-B] QUINOLINE AND THEIR SUBSTUITED DERIVATIVES SYNTHESIS und antimikrobielle EVALUATION von 3-Amino-11-Cyano-4-IMINO-pyrazol [4, 5-D]-4H-pyrimido [2, 1-b] chinolin UND IHR SUBSTUITED DERIVATE

    Directory of Open Access Journals (Sweden)

    Sambhaji P. Vartale, Nilesh K. Halikar and Yogesh D. Pawar

    2012-01-01

    Full Text Available 2-Amino-3-cyano quinoline (1 and bis (methylthio methylene malononitrile (2 were refluxed in N,N-dimethyl formamide (DMF in presence of catalytic amount of anhydrous potassium carbonate to afforded 3, 11-dicyano-4-imino-2-methylthio -4H-pyrimido [1, 2-a] quinoline (3. The latter were further reacted with different substituted hydrazino. Afforded to 3-amino-11- cyano-4-imino pyrazolo [4, 5-e]-4H-pyrimido [2, 1-b] quinoline and their 2-substuited derivatives (4a-j. All these newly synthesized compounds were characterized by elemental analysis and spectral data, and screened for their antimicrobial activities.

  17. Synthesis and biological activity of pyrimido [1, 2-a] quinoline moiety and its 2-substituted derivatives

    Science.gov (United States)

    Jadhav, A. G.; Halikar, N. K.

    2013-04-01

    2-Amino-3-cyano quinoline (1) and bis (methylthio) methylene malononitrile (2) were refluxed in N,N-dimethyl formamide (DMF) in presence of catalytic amount of anhydrous potassium carbonate to afforded 3, 11-dicyano-4-imino-2-methylthio -4H-pyrimido [1, 2-a] quinoline (3). The latter were further reacted with different substituted aniline, phenol, hetryl amine and compound containing active methyl group. Afforded to 3, 11-dicyano-4-imino -4H-pyrimido [1, 2-a] quinoline and their 2-substuited derivatives (4a-7c). All these newly synthesized compounds were characterized by elemental analysis and spectral data, and screened for their antimicrobial activities.

  18. Dicty_cDB: Contig-U16013-1 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available AU 105... 123 2e-26 CP000615_469( CP000615 |pid:none) Burkholderia vietnamiensis...1 1 ( CP000447 ) Shewanella frigidimarina NCIMB 400, complete genome. 48 1.1 1 ( AE016828 ) Coxiella burnetii RSA 493, co...olevulinate synthase, erythroid-spe... 215 3e-54 DQ029336_1( DQ029336 |pid:none) Toxoplasma gondii del...-23 CP000924_283( CP000924 |pid:none) Thermoanaerobacter pseudethanoli... 111 9e-23 (Q6GJB8) RecName: Full=2-amino-3-ketobutyrate coe...:none) Renibacterium salmoninarum ATCC... 127 1e-27 CP000036_3371( CP000036 |pid:none) Shigella boydii

  19. Thiophene based monoazo disperse dyes for polyester fabric

    Directory of Open Access Journals (Sweden)

    VITHAL SOMA PATEL

    2002-01-01

    Full Text Available A series of monoazo disperse dyes have been prepared by coupling 2-amino-3-carbethoxy-4,5-dimethylthiophene with various N-arylmaleimides. The monoazo disperse dyes were characterised by IR spectral studies and elemental analysis. These dyes were applied at 2 % depth on polyester fabrics and gave light yellow to brown colour hues with fair fastness to light and very good to excellent fastness to washing, rubbing, perspiration and sublimation. The percentage exhaustion of the dyebath and fixation on the fabric were found to be very good.

  20. Synthesis, spectroscopic characterization, solid state d.c. electrical conductivity and biological studies of some lanthanide(III) chloride complexes with a heterocyclic Schiff base ligand

    OpenAIRE

    K. Mohanan; N. Subhadrambika; R. Selwin Joseyphus; Swathy, S. S.; V.P. Nisha

    2016-01-01

    Condensation of 2-hydroxy-1-naphthaldehyde with 2-amino-3-carboxyethyl-4,5-dimethylthiophene in 1:1 molar ratio, yielded a potentially tridentate Schiff base viz. 2-[N-(2′-hydroxy-1-naphthylidene)amino]-3-carboxyethyl-4,5-dimethylthiophene (HNAT). This ligand formed complexes with lanthanum(III), cerium(III), praseodymium(III), neodymium(III), samarium(III), europium(III) and gadolinium(III) chloride under well defined conditions. These complexes were characterized through elemental analysis,...

  1. GC-MS study of Artabotrys odoratissimus fatty oil (leaves)

    OpenAIRE

    B. K.Mehta; Chaurey, Dilip; Desiraju, Srilakshami; Sharma, Megha

    2002-01-01

    GC-MS study of two fatty oil fractions from Artabotrys odoratissimus (leaves) indicated the presence of fifteen compounds namely, nonanoic acid; methyl phenyl propanoate; decanoic acid; diethyl phthalate; dibutyl phthalate; 2-amino-3-ethyl biphenyl; 5-methyl-9-phenylnonan-3-ol; hexadeca-2,7,11-triene; 2,6-dimethyl-1-phenylhepta-1-one; 2,5-dimethyltetradecahydrophenenthrene; 1-phenylundecane; 1-isopropyl-4,6-dimethyl naphthalene; 5-(2-butyl phenyl)pent-3-en-2-ol; 1-phenyldeca-1-one and 1-pheny...

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

    DEFF Research Database (Denmark)

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

    1994-01-01

    The 3-isoxazolol amino acids (S)-2-amino-3-(3-hydroxy-5-methyl-4- isoxazolyl)propionic acid [(S)-AMPA, 2] and (R,S)-2-amino-2-(3-hydroxy-5-methyl-4-isoxazolyl)acetic acid (AMAA, 5a) (Figure 1) are potent and specific agonists at the AMPA and N-methyl-D-aspartic acid (NMDA) subtypes, respectively......, of (S)-glutamic acid (1) receptors. A number of amino acids and diacids structurally related to AMAA were synthesized and tested electrophysiologically and in receptor-binding assays. The hydroxymethyl analogue 7c of AMAA was an NMDA agonist approximately equipotent with AMAA in the [3H...

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

    DEFF Research Database (Denmark)

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

    2002-01-01

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

  4. In vivo cytogenetic effects of the cooked-food-related mutagens Trp-P-2 and IQ in mouse bone marrow

    Energy Technology Data Exchange (ETDEWEB)

    Minkler, J.L.; Carrano, A.V.

    1984-01-01

    Sister-chromatid exchange and chromosomal aberrations were measured in vivo in mouse bone marrow following intraperitoneal injection of the cooked food mutagens, 3-amino-1-methyl-5H-pyrido(4,3-b)indole (Trp-P-2), and 2-amino-3-methylimidazo(4,5-f)quinoline (IQ). Trp-P-2 produced a significant positive dose response for both endpoints while IQ produced only a weak but significant sister-chromatid exchange response. The relative potency of these two chemicals is similar to that seen in mammalian cells in vitro but opposite to their potency in Salmonella.

  5. GC-MS study of Artabotrys odoratissimus fatty oil (leaves

    Directory of Open Access Journals (Sweden)

    Mehta, B. K.

    2002-06-01

    Full Text Available GC-MS study of two fatty oil fractions from Artabotrys odoratissimus (leaves indicated the presence of fifteen compounds namely, nonanoic acid; methyl phenyl propanoate; decanoic acid; diethyl phthalate; dibutyl phthalate; 2-amino-3-ethyl biphenyl; 5-methyl-9-phenylnonan-3-ol; hexadeca-2,7,11-triene; 2,6-dimethyl-1-phenylhepta-1-one; 2,5-dimethyltetradecahydrophenenthrene; 1-phenylundecane; 1-isopropyl-4,6-dimethyl naphthalene; 5-(2-butyl phenylpent-3-en-2-ol; 1-phenyldeca-1-one and 1-phenylundecan-1-one. Some of the compounds are rare occurring and biologically activeEl estudio por GC-MS de dos fracciones del aceite de la hoja de Artabotrys odoratissimus indicó la presencia de quince compuestos tales como: ácido nonanoico; fenil propanoato de metilo; ácido decanoico; ftalato de dietilo; ftalato de dibutilo; 2-amino-3-etil bifenilo; 5-metil-9-fenilnonan-3-ol; hexadeca-2,7,11-trieno; 2,6-dimetil-1-fenilheptan-1-ona; 2,5-dimetiltetradecahidrofenantreno; 1-fenilundecano; 1-isopropil-4,6-dimetil naftaleno; 5-(2-butilfenil-3-penten-2-ol; 1-fenildecan-1-ona y 1-fenilundecan-1-ona. Algunos de estos compuestos son poco frecuentes y activos biológicamente.

  6. 32P-postlabelling analysis of DNA adducted with urinary mutagens from smokers of black tobacco.

    Science.gov (United States)

    Peluso, M; Castegnaro, M; Malaveille, C; Talaska, G; Vineis, P; Kadlubar, F; Bartsch, H

    1990-08-01

    In order to characterize the tobacco-derived mutagens excreted in the urine of tobacco smokers, 32P-postlabelling techniques were used to examine DNA adducts formed from these mutagens with calf thymus DNA in the presence of a metabolic activation system (rat liver S9, Aroclor 1254-induced, with or without acetyl coenzyme A). Using either nuclease P1 or butanol extraction procedures, four-six and three spots, respectively, were reproducibly found on the autoradiograms in the case of the urine extract from two smokers of black tobacco. Using the urinary extract from a non-smoker, only three faint spots were detected after nuclease P1 enrichment. DNA adducts produced in smokers' urine were then compared with those formed by four N-hydroxyarylamines, N-hydroxy-2-amino-3,8-dimethyl-3H-imidazo[4,5-f]quinoxaline, N-hydroxy-2-amino-3-methyl-imidazo[4,5-f]quinoxaline, N-hydroxy-2-naphthylamine and N-hydroxy-4-aminobiphenyl. Visual inspection revealed that none of the reference aromatic amines contributed to the adduct pattern produced by the urinary mutagen(s). However, primary aromatic amines are mainly implicated as urinary mutagens because: (i) they produce frameshift mutations in Salmonella typhimurium strains, (ii) they are easily extractable with blue cotton and (iii) their mutagenicity is abolished by a nitrite treatment procedure for deamination. PMID:2387016

  7. Polyethyleneimine-modified superparamagnetic Fe{sub 3}O{sub 4} nanoparticles: An efficient, reusable and water tolerance nanocatalyst

    Energy Technology Data Exchange (ETDEWEB)

    Khoobi, Mehdi [Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 14176 (Iran, Islamic Republic of); Delshad, Tayebeh Modiri [Department of Chemistry, Islamic Azad University, Tehran-North Branch, Zafar St., Tehran (Iran, Islamic Republic of); Vosooghi, Mohsen; Alipour, Masoumeh [Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 14176 (Iran, Islamic Republic of); Hamadi, Hosein [Department of Chemistry, College of Science, Shahid Chamran University, Ahvaz (Iran, Islamic Republic of); Alipour, Eskandar [Department of Chemistry, Islamic Azad University, Tehran-North Branch, Zafar St., Tehran (Iran, Islamic Republic of); Hamedani, Majid Pirali [Iran Polymer and Petrochemical Institute, P.O. Box 14965/115, Tehran (Iran, Islamic Republic of); Sadat ebrahimi, Seyed Esmaeil [Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 14176 (Iran, Islamic Republic of); Safaei, Zahra [Department of Chemistry, Islamic Azad University, Tehran-North Branch, Zafar St., Tehran (Iran, Islamic Republic of); Foroumadi, Alireza [Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 14176 (Iran, Islamic Republic of); Shafiee, Abbas, E-mail: ashafiee@ams.ac.ir [Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 14176 (Iran, Islamic Republic of)

    2015-02-01

    A novel magnetically separable catalyst was prepared based on surface modification of Fe{sub 3}O{sub 4} magnetic nanoparticle (MNPs) with polyethyleneimine (PEI) via covalent bonding. [3-(2,3-Epoxypropoxy)propyl]trimethoxysilane (EPO) was used as cross linker to bond PEI on the surface of MNPs with permanent stability in contrast to PEI coating via electrostatic interactions. The synthesized catalyst was characterized by Fourier transform infrared (FT-IR), thermogravimetric analysis (TGA), X-ray powder diffraction (XRD), transmission electron microscopy (TEM) and vibrating sample magnetometry (VSM). The catalyst show high efficiency for one-pot synthesis of 2-amino-3-cyano-4H-pyran derivatives via multi-component reaction (MCR). This procedure offers the advantages of green reaction media, high yield, short reaction time, easy purification of the products and simple recovery and reuse of the catalyst by simple magnetic decantation without significant loss of catalytic activity. - Graphical abstract: Covalently grafted polyethyleneimine on Fe{sub 3}O{sub 4} magnetic nanoparticles as easily reusable catalyst for the synthesis of various 4H-pyrans. - Highlights: • Polyethyleneimine modified Fe{sub 3}O{sub 4} via covalent bonding as a novel water tolerance catalyst. • The catalyst showed high efficiency for one-pot synthesis of 2-amino-3-cyano-4H-pyrans in water. • Catalysts could be easily recovered and reused for several times without a significant loss in their catalytic activity.

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

    DEFF Research Database (Denmark)

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

    2002-01-01

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

  9. Nine-step synthesis of (/sup 14/C)flupirtine maleate labeled in the pyridine ring

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Y.M.; Kucharczyk, N.; Sofia, R.D.

    1987-01-01

    A nine-step procedure for microscale synthesis of ethyl 2-amino-6-brace((4-fluorophenyl)methyl)aminobrace-3-pyridinyl-2,6-/sup 14/C carbamate maleate, (/sup 14/C)flupirtine maleate, was developed. The synthesis started with potassium cyanide-/sup 14/C and 1,3-dibromopropane making the following intermediates: glutarontrile-/sup 14/C, glutarimide-/sup 14/C, 2,6-dichloropyridine-2,6-/sup 14/C, 2,6-dichloro-3-nitro-pyridine-2,6-/sup 14/C, 2-amino-3-nitro-6-chloropyridine-2,6-/sup 14/C, 2-amino-3-nitro-6-(p-fluorobenzylamino)pyridine-2,6-/sup 14/C, 2,3-diamino-6-(p-fluorobenzylamino)pyridine-2,6-/sup 14/C, and ethyl 2-amino-6-brace((4-fluorophenyl)-methyl)aminobrace-3-pyridinyl-2,6-/sup 14/C carbamic acid ester hydrochloride. The overall yield was 6.3% (5.4 mCi), and the radioactivity was 99.8% as determined by high performance liquid chromatography and liquid scintillation counting.

  10. A nine-step synthesis of [14C]flupirtine maleate labeled in the pyridine ring

    International Nuclear Information System (INIS)

    A nine-step procedure for microscale synthesis of ethyl 2-amino-6-brace[(4-fluorophenyl)methyl]aminobrace-3-pyridinyl-2,6-14C carbamate maleate, [14C]flupirtine maleate, was developed. The synthesis started with potassium cyanide-14C and 1,3-dibromopropane making the following intermediates: glutarontrile-14C, glutarimide-14C, 2,6-dichloropyridine-2,6-14C, 2,6-dichloro-3-nitro-pyridine-2,6-14C, 2-amino-3-nitro-6-chloropyridine-2,6-14C, 2-amino-3-nitro-6-(p-fluorobenzylamino)pyridine-2,6-14C, 2,3-diamino-6-(p-fluorobenzylamino)pyridine-2,6-14C, and ethyl 2-amino-6-brace[(4-fluorophenyl)-methyl)aminobrace-3-pyridinyl-2,6-14C carbamic acid ester hydrochloride. The overall yield was 6.3% (5.4 mCi), and the radioactivity was 99.8% as determined by high performance liquid chromatography and liquid scintillation counting. (author)

  11. Polyethyleneimine-modified superparamagnetic Fe3O4 nanoparticles: An efficient, reusable and water tolerance nanocatalyst

    International Nuclear Information System (INIS)

    A novel magnetically separable catalyst was prepared based on surface modification of Fe3O4 magnetic nanoparticle (MNPs) with polyethyleneimine (PEI) via covalent bonding. [3-(2,3-Epoxypropoxy)propyl]trimethoxysilane (EPO) was used as cross linker to bond PEI on the surface of MNPs with permanent stability in contrast to PEI coating via electrostatic interactions. The synthesized catalyst was characterized by Fourier transform infrared (FT-IR), thermogravimetric analysis (TGA), X-ray powder diffraction (XRD), transmission electron microscopy (TEM) and vibrating sample magnetometry (VSM). The catalyst show high efficiency for one-pot synthesis of 2-amino-3-cyano-4H-pyran derivatives via multi-component reaction (MCR). This procedure offers the advantages of green reaction media, high yield, short reaction time, easy purification of the products and simple recovery and reuse of the catalyst by simple magnetic decantation without significant loss of catalytic activity. - Graphical abstract: Covalently grafted polyethyleneimine on Fe3O4 magnetic nanoparticles as easily reusable catalyst for the synthesis of various 4H-pyrans. - Highlights: • Polyethyleneimine modified Fe3O4 via covalent bonding as a novel water tolerance catalyst. • The catalyst showed high efficiency for one-pot synthesis of 2-amino-3-cyano-4H-pyrans in water. • Catalysts could be easily recovered and reused for several times without a significant loss in their catalytic activity

  12. Ionic liquids as an electrolyte for the electro synthesis of organic compounds.

    Science.gov (United States)

    Kathiresan, Murugavel; Velayutham, David

    2015-12-25

    The use of ionic liquids (ILs) as a solvent and an electrolyte for electro organic synthesis has been reviewed. To date several ILs exist, however the ILs based on tetraalkylammonium, pyrrolidinium, piperidinium and imidazolium cations with BF4(-), PF6(-), and TFSI anions have been widely used and explored the most. Electro organic synthesis in ionic liquid media leading to the synthesis of a wide range of organic compounds has been discussed. Anodic oxidation or cathodic reduction will generate radical cation or anion intermediates, respectively. These radicals can undergo self coupling or coupling with other molecules yielding organic compounds of interest. The cation of the IL is known to stabilize the radical anion extensively. This stabilization effect has a specific impact on the electrochemical CO2 reduction and coupling to various organics. The relative stability of the intermediates in IL leads to the formation of specific products in higher yields. Electrochemical reduction of imidazolium or thiazolium based ILs generates N-heterocyclic carbenes that have been shown to catalyze a wide range of base or nucleophile catalyzed organic reactions in IL media, an aspect that falls into the category of organocatalysis. Electrochemical fluorination or selective electrochemical fluorination is another fascinating area that delivers selectively fluorinated organic products in Et3N·nHF or Et4NF·nHF adducts (IL) via anodic oxidation. Oxidative polymerization in ILs has been explored the most; although morphological changes were observed compared to the conventional methods, polymers were obtained in good yields and in some cases ILs were used as dopants to improve the desired properties.

  13. Structure-Derived Proton-Transfer Mechanism of Action Human Pyruvate Dehydrogenase

    Science.gov (United States)

    Ciszak, Ewa; Dominiak, Paulina

    2003-01-01

    The derivative of vitamin B1 thiamin pyrophosphate (TPP) is a cofactor of pyruvate dehydrogenase (E1p) that is involved in decarboxylation of pyruvate followed by reductive acetylation of lipoic acid covalently bound to a lysine residue of dihydrolipoamide acetyltransferase. The structure of E1p recently determined in our laboratory revealed patterns of association of foul subunits and specifics of two TPP binding sites. The mechanism of action in part includes a conserved hydrogen bond between the N1' atom of the aminopyrimidine ring of the cofactor and the carboxylate group of Glu59 from the beta subunits, and a V-conformation of the cofactor that brings the N4' atom of the aminopyrimidine ring to the distance of the intramolecular hydrogen bond formed with the C2-atom of the thiazolium moiety. The carboxylate group of Glu59 is the local proton acceptor that enables proton translocation within the aminopyrimidine ring and stabilization of the rare N4' - iminopyrimidine tautomer. Based on the analysis of E1p structure, we postulate that the protein environment drives N4' - amino/N4' - imino dynamics resulting in a concerted shuttle-like movement of the subunits. We also propose that this movement of the subunits is strictly coordinated with the two enzymatic reactions carried out in E1p by each of the two cofactor sites. It is proposed that these reactions are in alternating phases such that when one active site is involved in decarboxylation, the other is involved in acetylation of lipoyl noiety.

  14. Observation of an Acryloyl–Thiamin Diphosphate Adduct in the First Step of Clavulanic Acid Biosynthesis

    Science.gov (United States)

    Merski, Matthew

    2011-01-01

    The first committed biosynthetic step toward clavulanic acid, the clinically-important β-lactamase inhibitor, is catalyzed by the thiamin diphosphate (ThDP)-dependent enzyme N2-(2-carboxyethyl)arginine synthase (CEAS). This protein carries out a unique reaction among ThDP-dependent processes in which a C–N bond is formed, and an electrophilic acryloyl–thiazolium intermediate of ThDP is proposed to be involved, unlike the nucleophilic enamine species typically generated by this class of enzymes. Here we present evidence for the existence of the putative acryloyl adduct, and report the unexpected observation of a long-wavelength chromophore (λ = 433 nm), which we attribute to this enzyme bound species. Chemical models were synthesized that both confirm its expected absorption (λ = 310–320 nm), and exclude self-condensation and intramolecular imine formation with the cofactor as its cause. Circular dichroism experiments and others discount charge transfer as a likely explanation for the ~120 nm red shift of the chromophore (~25 kcal). Examples are well-known of charged molecules that exhibit significantly red-shifted UV-visible spectra compared to their neutral forms as, for example, polyene cations and dyes such as indigo and the cyanines. Rhodopsin is the classic biochemical example where the protein (opsin)-bound protonated Schiff base of retinal displays a remarkable range of red-shifted absorptions modulated by the protein environment. Similar tuning of the chromophoric behavior of the enzyme-bound CEAS acryloyl•ThDP species may be occurring. PMID:18052280

  15. Communication between thiamin cofactors in the Escherichia coli pyruvate dehydrogenase complex E1 component active centers: evidence for a "direct pathway" between the 4'-aminopyrimidine N1' atoms.

    Science.gov (United States)

    Nemeria, Natalia S; Arjunan, Palaniappa; Chandrasekhar, Krishnamoorthy; Mossad, Madouna; Tittmann, Kai; Furey, William; Jordan, Frank

    2010-04-01

    Kinetic, spectroscopic, and structural analysis tested the hypothesis that a chain of residues connecting the 4'-aminopyrimidine N1' atoms of thiamin diphosphates (ThDPs) in the two active centers of the Escherichia coli pyruvate dehydrogenase complex E1 component provides a signal transduction pathway. Substitution of the three acidic residues (Glu(571), Glu(235), and Glu(237)) and Arg(606) resulted in impaired binding of the second ThDP, once the first active center was filled, suggesting a pathway for communication between the two ThDPs. 1) Steady-state kinetic and fluorescence quenching studies revealed that upon E571A, E235A, E237A, and R606A substitutions, ThDP binding in the second active center was affected. 2) Analysis of the kinetics of thiazolium C2 hydrogen/deuterium exchange of enzyme-bound ThDP suggests half-of-the-sites reactivity for the E1 component, with fast (activated site) and slow exchanging sites (dormant site). The E235A and E571A variants gave no evidence for the slow exchanging site, indicating that only one of two active sites is filled with ThDP. 3) Titration of the E235A and E237A variants with methyl acetylphosphonate monitored by circular dichroism suggested that only half of the active sites were filled with a covalent predecarboxylation intermediate analog. 4) Crystal structures of E235A and E571A in complex with ThDP revealed the structural basis for the spectroscopic and kinetic observations and showed that either substitution affects cofactor binding, despite the fact that Glu(235) makes no direct contact with the cofactor. The role of the conserved Glu(571) residue in both catalysis and cofactor orientation is revealed by the combined results for the first time. PMID:20106967

  16. Communication between Thiamin Cofactors in the Escherichia coli Pyruvate Dehydrogenase Complex E1 Component Active Centers

    Science.gov (United States)

    Nemeria, Natalia S.; Arjunan, Palaniappa; Chandrasekhar, Krishnamoorthy; Mossad, Madouna; Tittmann, Kai; Furey, William; Jordan, Frank

    2010-01-01

    Kinetic, spectroscopic, and structural analysis tested the hypothesis that a chain of residues connecting the 4′-aminopyrimidine N1′ atoms of thiamin diphosphates (ThDPs) in the two active centers of the Escherichia coli pyruvate dehydrogenase complex E1 component provides a signal transduction pathway. Substitution of the three acidic residues (Glu571, Glu235, and Glu237) and Arg606 resulted in impaired binding of the second ThDP, once the first active center was filled, suggesting a pathway for communication between the two ThDPs. 1) Steady-state kinetic and fluorescence quenching studies revealed that upon E571A, E235A, E237A, and R606A substitutions, ThDP binding in the second active center was affected. 2) Analysis of the kinetics of thiazolium C2 hydrogen/deuterium exchange of enzyme-bound ThDP suggests half-of-the-sites reactivity for the E1 component, with fast (activated site) and slow exchanging sites (dormant site). The E235A and E571A variants gave no evidence for the slow exchanging site, indicating that only one of two active sites is filled with ThDP. 3) Titration of the E235A and E237A variants with methyl acetylphosphonate monitored by circular dichroism suggested that only half of the active sites were filled with a covalent predecarboxylation intermediate analog. 4) Crystal structures of E235A and E571A in complex with ThDP revealed the structural basis for the spectroscopic and kinetic observations and showed that either substitution affects cofactor binding, despite the fact that Glu235 makes no direct contact with the cofactor. The role of the conserved Glu571 residue in both catalysis and cofactor orientation is revealed by the combined results for the first time. PMID:20106967

  17. Communication between Thiamin Cofactors in the Escherichia coli Pyruvate Dehydrogenase Complex E1 Component Active Centers EVIDENCE FOR A DIRECT PATHWAY BETWEEN THE 4′-AMINOPYRIMIDINE N1′ ATOMS

    Energy Technology Data Exchange (ETDEWEB)

    Nemeria, Natalia S; Arjunan, Palaniappa; Chandrasekhar, Krishnamoorthy; Mossad, Madouna; Tittmann, Kai; Furey, William; Jordan, Frank [Pitt; (Goettingen); (VA); (Rutgers)

    2010-11-03

    Kinetic, spectroscopic, and structural analysis tested the hypothesis that a chain of residues connecting the 4{prime}-aminopyrimidine N1{prime} atoms of thiamin diphosphates (ThDPs) in the two active centers of the Escherichia coli pyruvate dehydrogenase complex E1 component provides a signal transduction pathway. Substitution of the three acidic residues (Glu{sup 571}, Glu{sup 235}, and Glu{sup 237}) and Arg{sup 606} resulted in impaired binding of the second ThDP, once the first active center was filled, suggesting a pathway for communication between the two ThDPs. (1) Steady-state kinetic and fluorescence quenching studies revealed that upon E571A, E235A, E237A, and R606A substitutions, ThDP binding in the second active center was affected. (2) Analysis of the kinetics of thiazolium C2 hydrogen/deuterium exchange of enzyme-bound ThDP suggests half-of-the-sites reactivity for the E1 component, with fast (activated site) and slow exchanging sites (dormant site). The E235A and E571A variants gave no evidence for the slow exchanging site, indicating that only one of two active sites is filled with ThDP. (3) Titration of the E235A and E237A variants with methyl acetylphosphonate monitored by circular dichroism suggested that only half of the active sites were filled with a covalent predecarboxylation intermediate analog. (4) Crystal structures of E235A and E571A in complex with ThDP revealed the structural basis for the spectroscopic and kinetic observations and showed that either substitution affects cofactor binding, despite the fact that Glu{sup 235} makes no direct contact with the cofactor. The role of the conserved Glu{sup 571} residue in both catalysis and cofactor orientation is revealed by the combined results for the first time.

  18. Croton lechleri Müll. Arg. (Euphorbiaceae) stem bark essential oil as possible mutagen-protective food ingredient against heterocyclic amines from cooked food.

    Science.gov (United States)

    Rossi, Damiano; Guerrini, Alessandra; Paganetto, Guglielmo; Bernacchia, Giovanni; Conforti, Filomena; Statti, Giancarlo; Maietti, Silvia; Poppi, Irene; Tacchini, Massimo; Sacchetti, Gianni

    2013-08-15

    The Amazonian Croton lechleri stem bark essential oil was tested for its anti-mutagenic potential by performing the Ames test against heterocyclic amines (HCAs), in continuing research on applicative functional profile of this phytocomplex as food ingredient (Rossi et al., 2011). Salmonella typhimurium strain TA98 was used with and without metabolic activation (S9 mix). The anti-mutagenic properties was assayed with the following HCAs: 2-amino-3-methylimidazo-[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo-[4,5-f]quinoline (MeIQ), 2-amino-3,8-dimethylimidazo-[4,5-f]quinoxaline (MeIQx), the imidazoles 2-amino-6-methyldipyrido-[1,2-a:3',2'-d]imidazole (Glu-P-1) and 2-aminodipirydo-[1,2-a:3',2'-d]imidazole (Glu-P-2). All HCAs with S9 induced mutagenicity at 10(-10) mol/plate. Without S9, IQ and MeIQ showed mutagenicity at 10(-8) mol/plate, MeIQx and Glu-P-1 at 10(-5) mol/plate, while Glu-P-2 was inactive. In presence of HACs (10(-9) mol/plate), C. lechleri essential oil was tested for mutagen-protective properties (concentration range: 0.01-0.10 mg/plate) taking the Highest Uneffective Dose (HUD) as threshold reference. With S9 mix, C. lechleri essential oil displayed a significant reduction of revertants at 0.05 mg/plate, from 21% to 34%. The essential oil showed mutagen-protective efficacy against IQ and MeIQ tested as direct mutagens (10(-7) mol/plate), with a revertants percentage reduction of 39% and 40%, respectively. No anti-mutagen capacity was noted for MeIQx and Glu-P-1 (10(-5) mol/plate). Since HACs are known as possible colon and liver cancer inducers, C. lechleri essential oil was tested for its cytotoxicity and anti-proliferative capacity against LoVo and HepG2 cancer cell lines showing IC50 of 74.95±0.05 μg/ml (LoVo) and 82.28±0.03 μg/ml (HepG2), displaying a promising role of this essential oil as a functional food ingredient with interesting mutagen preventing properties. PMID:23561129

  19. Acute effect of nitric oxide supplement on blood nitrate/nitrite and hemodynamic variables in resistance trained men.

    Science.gov (United States)

    Bloomer, Richard J; Williams, Sara A; Canale, Robert E; Farney, Tyler M; Kabir, Mohammad M

    2010-10-01

    Nitric oxide dietary supplements are extremely popular within the sport and bodybuilding community. Most products contain l-arginine, for which there is no direct evidence that oral L-arginine increases circulating nitric oxide or blood flow. A new molecule (2-[nitrooxy]thyl 2-amino-3-methylbutanoate) is being marketed as a sport supplement for purposes of delivering "real nitric oxide" to the circulation. In the present study, we measured the acute effects of this supplement on blood nitrate/nitrite and hemodynamic variables. Ten resistance trained men (26 ± 4 years old; 8 ± 6 years of resistance exercise training) reported to the laboratory in random order after a 10-hour overnight fast on 2 occasions separated by 1 week and were provided the supplement (2-[nitrooxy]ethyl 2-amino-3-methylbutanoate) or placebo. Heart rate and blood pressure were recorded, and venous blood samples were collected before and at 5, 15, 30, and 60 minutes after complete breakdown of the supplement (5 minutes post intake) or placebo. Blood samples were assayed for plasma nitrate/nitrite. No interaction (p = 0.99), condition (p = 0.18), or time (p = 0.98) effects were noted for plasma nitrate/nitrite, with values remaining nearly identical across time for placebo (∼27 μmol·L(-1)) and increasing a maximum of ∼6.7% (from 32.9 to 35.1 μmol·L(-1)) at the 15-minute collection period for the supplement. In regards to hemodynamic variables, no interaction, condition, or time effects were noted for heart rate, systolic, or diastolic blood pressure (p > 0.05), with values near identical between conditions and virtually unchanged across time. These findings indicate that 2-(nitrooxy)ethyl 2-amino-3-methylbutanoate has a small effect on increasing circulating nitrate/nitrite and does not cause any change in hemodynamic variables within the 1 hour postingestion period in a sample of resistance trained men.

  20. Prevention of heterocyclic amine-induced DNA damage in colon and liver of rats by different lactobacillus strains.

    Science.gov (United States)

    Zsivkovits, Markus; Fekadu, Kassie; Sontag, Gerhard; Nabinger, Ursula; Huber, Wolfgang W; Kundi, Michael; Chakraborty, Asima; Foissy, Helmuth; Knasmüller, Siegfried

    2003-12-01

    The aim of the present study was to investigate the impact of four different lactobacillus (LB) strains, namely Lactobacillus bulgaricus 291, Streptococcus thermophilus F4, S.thermophilus V3 and Bifidobacterium longum BB536, which are used for the production of yogurt, on the DNA-damaging effects of heterocyclic aromatic amines (HCAs). Male F344 rats were treated orally with HCA mixtures containing 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, 2-amino-3,4,8-trimethyl-3H-imidazo[4,5-f]quinoxaline, 2-amino-9H-pyrido[2,3-b]indole and 2-amino-3-methyl-3H- imidazo[4,5-f]quinoline, which were representative of the HCA contents found in fried beef ('beef mix') and chicken ('chicken mix'). Suspensions of LB were given by gavage to the animals simultaneously with and at different time periods before administration of the HCAs. Subsequently, the extent of DNA migration was measured in colon and liver cells in single cell gel electrophoresis (SCGE) assays. All four strains caused complete inhibition of DNA damage induced with beef mix after administration of 1 x 1010 LB cells/animal, whereas with chicken mix only marginal (non-significant) effects were seen. The inhibition of beef-induced DNA damage was dose dependent and was still significant when 1 x 107 cells/animal were administered. Kinetics studies showed that the protective effects were still significant when LB was given 12 h before the beef mix. A comparison of the present results with chemical analytical data from in vitro experiments suggests that the strong reduction in DNA migration seen in the animals can be only partly explained by direct binding effects. The results of the present study show that LB are highly protective against the genotoxic effects of HCAs under conditions which are relevant for humans and provide a possible explanation for the reduced colon cancer rates observed in some studies in individuals with either high LB counts in their feces or with

  1. Heterocyclic Aromatic Amines in Domestically Prepared Chicken and Fish from Singapore Chinese Households

    Energy Technology Data Exchange (ETDEWEB)

    Salmon, C P; Knize, M G; Felton, J S; Zhao, B; Seow, A

    2005-05-16

    Chicken and fish samples prepared by 42 Singapore Chinese in their homes were obtained. Researchers were present to collect data on raw meat weight, cooking time, maximum cooking surface temperature, and cooked meat weight. Each participant prepared one pan-fried fish sample and two pan-fried chicken samples, one marinated, one not marinated. The cooked samples were analyzed for five heterocyclic aromatic amine (HAA) mutagens, including MeIQx (2-amino 3,8-dimethylimidazo[4,5-f]quinoxaline); 4,8-DiMeIQx (2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline); 7,8-DiMeIQx (2-amino-3,7,8-trimethylimidazo[4,5-f]quinoxaline); PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine), and IFP (2-amino-(1,6-dimethylfuro[3,2-e]imidazo [4,5-b])pyridine). A paired Student's t-test showed that marinated chicken had lower concentrations of PhIP (p<0.05), but higher concentrations of MeIQx (p<0.05) and 4,8-DiMeIQx (p<0.001) than non-marinated chicken, and also that weight loss due to cooking was less in marinated chicken than in non-marinated chicken (p<0.001). Interestingly, the maximum cooking surface temperature was higher for fish than for either marinated or non-marinated chicken (P<0.001), yet fish was lower in 4,8-DiMeIQx per gram than marinated or non-marinated chicken (p<0.001), lower in PhIP than non-marinated chicken (P<0.05), and lost less weight due to cooking than either marinated or non-marinated chicken (P<0.001). Fish was also lower in MeIQx and 7,8-DiMeIQx than marinated chicken (P<0.05). This study provides new information on HAA content in the Singapore Chinese diet.

  2. Novel class of amino acid antagonists at non-N-methyl-D-aspartic acid excitatory amino acid receptors. Synthesis, in vitro and in vivo pharmacology, and neuroprotection

    Energy Technology Data Exchange (ETDEWEB)

    Krogsgaard-Larsen, P.; Ferkany, J.W.; Nielsen, E.O.; Madsen, U.; Ebert, B.; Johansen, J.S.; Diemer, N.H.; Bruhn, T.; Beattie, D.T.; Curtis, D.R. (Royal Danish School of Pharmacy, Copenhagen (Denmark))

    1991-01-01

    The isoxazole amino acid 2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl) propionic acid (AMPA) (1), which is a highly selective agonist at the AMPA subtype of excitatory amino acid (EAA) receptors, has been used as a lead for the development of two novel EAA receptor antagonists. One of the compounds, 2-amino-3-(3-(carboxymethoxy)-5-methylisoxazol-4-yl)propionic acid (AMOA, 7), was synthesized via O-alkylation by ethyl chloroacetate of the amino acid protected AMPA derivative 4. The other compound, 2-amino-3-(2-(3-hydroxy-5-methylisoxazol-4-yl)-methyl-5-methyl-3-+ ++oxoisoxazolin -4-yl)propionic acid (AMNH, 14) was synthesized with use of 4-(chloromethyl)-3-methoxy-5-methylisoxazole (8) as the starting material. The intermediate 4-(chloromethyl)-2-(3-methoxy-5-methylisoxazol-4-yl)methyl-5-me thylisoxazolin- 3-one (11) was converted into the acetamidomalonate (12), which was stepwise deprotected to give 14. Compounds 7 and 14 were stable in aqueous solution at pH values close to physiological pH. Neither 7 nor 14 showed detectable affinities for the receptor, ion channel, or modulatory sites of the N-methyl-D-aspartic acid (NMDA) receptor complex. Quantitative receptor autoradiographic and conventional binding techniques were used to study the affinities of 7 and 14 for non-NMDA receptor sites. Both compounds were inhibitors of the binding of (3H)AMPA (IC50 = 90 and 29 microM, respectively). Compounds 14 and 7 were both very weak inhibitors of the high-affinity binding of radioactive kainic acid ((3H)KAIN). Compound 14, but not 7, was, however, shown to be an inhibitor of low-affinity (3H)KAIN binding as determined in the presence of 100 mM calcium chloride. In the rat cortical slice preparation, 7 was shown to antagonize excitation induced by 1 with some selectivity, whereas 14 proved to be a rather selective antagonist of KAIN-induced excitation.

  3. Lanthanide metal complex-based membrane electrodes for sensing of biological amino alcohols

    International Nuclear Information System (INIS)

    Electrodes selective for amino alcohols were prepared by incorporating lanthanide tris(β-diketonates) in PVC membranes, which formed 1:1 highly coordinated complexes with amino alcohols. Several electrodes gave near-Nernstian slopes for 2-amino-3-methyl-1-butanol in the linear concentration range of 1.0 x 10-1 to 1.0 x 10-3 M, while the low detection limits of these electrodes were order of ∼10-4 M. Although the observed response profiles were significantly dependent on the natures of the targeted amino alcohols, the electrodes exhibited stable potentiometric signals in the pH range of 6-12 in short time period of 20 s. The related monoalcohol, diol, and zwitterionic amino acid substrates gave no response, indicating that the present type of lanthanide tris(β-diketonates) were applicable in potentiometric sensing of amino alcohols

  4. Anaerobic taurine oxidation: a novel reaction by a nitrate-reducing Alcaligenes sp.

    Science.gov (United States)

    Denger, K; Laue, H; Cook, A M

    1997-06-01

    Enrichment cultures were prepared under strictly anoxic conditions in medium representing fresh water and containing an organosulfonate as electron donor and carbon source, and nitrate as electron acceptor. The inoculum was from the anaerobic digestor of two communal sewage works. The natural organosulfonates 2-aminoethanesulfonate (taurine), DL-2-amino-3-sulfopropionate (cysteate) and 2-hydroxyethanesulfonate (isethionate) all gave positive enrichments, whereas unsubstituted alkanesulfonates, such as methanesulfonate and arenesulfonates, gave no enrichment. Two representative enrichments were used to obtain pure cultures, and strains NKNTAU (utilizing taurine) and NKNIS (utilizing isethionate) were isolated. Strain NKNTAU was examined in detail. Out of 18 tested organosulfonates, it utilized only one, taurine, and was identified as a novel Alcaligenes sp., a facultatively anaerobic bacterium. Carbon from taurine was converted to cell material and carbon dioxide. The amino group was released as ammonium ion and the sulfonate moiety was recovered as sulfate. Nitrate was reduced to nitrogen gas.

  5. Ambient temperature synthesis of β,β'-fused nickel(II) pyrrolo[1,2-a]pyrazinoporphyrins via a DBSA-catalyzed Pictet-Spengler approach.

    Science.gov (United States)

    Singh, Dileep Kumar; Nath, Mahendra

    2015-02-14

    A facile first synthetic strategy to construct novel π-extended β,β'-fused nickel(II) pyrrolo[1,2-a]pyrazinoporphyrins has been developed via a Pictet-Spengler reaction of newly prepared nickel(II) 2-amino-3-(pyrrol-1-yl)-5,10,15,20-tetraphenylporphyrin with various aromatic, aliphatic or heterocyclic aldehydes in the presence of 10 mol% p-dodecylbenzenesulfonic acid (DBSA) as an efficient Brønsted acid catalyst in 1,4-dioxane at 25 °C. A variety of these π-extended porphyrin analogues were obtained in moderate to good yields under mild conditions and characterized on the basis of spectral data and single crystal X-ray analysis. PMID:25504338

  6. Targeting the S1 and S3 subsite of trypsin with unnatural cationic amino acids generates antimicrobial peptides with potential for oral administration.

    Science.gov (United States)

    Karstad, Rasmus; Isaksen, Geir; Wynendaele, Evelien; Guttormsen, Yngve; De Spiegeleer, Bart; Brandsdal, Bjørn-Olav; Svendsen, John Sigurd; Svenson, Johan

    2012-07-26

    This study investigates how the S1 and S3 site of trypsin can be challenged with cationic amino acid analogues to yield active antimicrobial peptides with stability toward tryptic degradation. It is shown that unnatural analogues can be incorporated to generate stable peptides with maintained bioactivity to allow for a potential oral uptake. Selected peptides were studied using isothermal calorimetry and computational methods. Both stable and unstable peptides were found to bind stoichiometrically to trypsin with dissociation constants ranging 2-60 μM, suggesting several different binding modes. The stability of selected peptides was analyzed in whole organ extracts and the incorporation of homoarginine and 2-amino-(3-guanidino)propanoic acid resulted in a 14- and 50-fold increase in duodenal stability. In addition, a 40- and 70-fold increase in stomach stability is also reported. Overall, these results illustrate how the incorporation of cationic side chains can be employed to generate bioactive peptides with significant systemic stability.

  7. The metabotropic glutamate receptor agonist 1S,3R-ACPD stimulates and modulates NMDA receptor mediated excitotoxicity in organotypic hippocampal slice cultures

    DEFF Research Database (Denmark)

    Blaabjerg, M; Kristensen, Bjarne Winther; Bonde, C;

    2001-01-01

    The potential toxic effects of the metabotropic glutamate receptor agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD) and its interactions with the N-methyl-D-aspartate (NMDA) receptor were studied in hippocampal brain slice cultures, using densitometric measurements of the cellular....... The neurodegeneration induced by 2 mM ACPD was completely abolished by addition of 10 microM of the NMDA receptor antagonist (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801), while 20 microM of the 2-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)/kainic acid receptor antagonist...

  8. Pentafluorophenylammonium triflate (PFPAT catalyzed facile construction of substituted chromeno[2,3-d]pyrimidinone derivatives and their antimicrobial activity

    Directory of Open Access Journals (Sweden)

    Majid Ghashang

    2014-03-01

    Full Text Available A new, simple thermally efficient and solvent-free condensation of 2-amino-3-cyano-6-methyl-4-phenyl-4H-pyran-5-ethylcarboxylate derivatives with coumarin-3-carboxylic acid employing pentafluorophenylammonium triflate (PFPAT as an inexpensive organocatalyst for the synthesis of a series of ethyl 4,5-dihydro 7-methyl-2-(2-oxo-2H-chromen-3-yl-4-oxo-5-aryl-3H-chromeno[2,3-d]pyrimidine-6-carboxylate derivatives is described. This method has the advantages of high yields, a cleaner reaction, simple methodology, short reaction times, easy workup, and greener conditions. All the compounds were evaluated for their in vitro antimicrobial activity against different bacterial and fungal strains.

  9. Inhibition of MMP-13 with modified polymer particles

    Science.gov (United States)

    Tran, Hai; Bratlie, Kaitlin M.

    2016-06-01

    Matrix metalloproteinases (MMPs) are proteases that destroy the extracellular matrix and have important roles in the foreign body response, wound healing, and disease. Of particular importance is the chronic wound environment in which MMP activity is increased, resulting in destruction of the de novo extracellular matrix. One potential treatment of these wounds would be to use dressings that are capable of inhibiting MMP activity. In this study, we examined the effect of seven polymer modifiers (2-amino-3-guanidinopropionic acid, arginine, carnitine, citrulline, creatine, 3-guanidino propionic acid, and Nw-nitro-L-arginine) on MMP-13 activity. MMP-13 is a collagenase that is present in chronic wounds and is zinc dependent. Our results showed that these polymer modifiers were able to inhibit MMP-13 activity to varying degrees. The mechanism of inhibition appears to be binding zinc to the modifiers.

  10. Double Sonogashira reactions on dihalogenated aminopyridines for the assembly of an array of 7-azaindoles bearing triazole and quinoxaline substituents at C-5: Inhibitory bioactivity against Giardia duodenalis trophozoites.

    Science.gov (United States)

    Leboho, Tlabo C; Giri, Somnath; Popova, Inessa; Cock, Ian; Michael, Joseph P; de Koning, Charles B

    2015-08-01

    The synthesis of 2,3,5-trisubstituted 7-azaindoles as well as 2,5-disubstituted 7-azaindoles from 3,5-dihalogenated 2-aminopyridines is outlined. Using a double Sonogashira coupling reaction on 2-amino-3,5-diiodopyridine followed by the Cacchi reaction the synthesis of 2,3,5-trisubstituted 7-azaindoles was accomplished. In addition, using two sequential Sonogashira coupling reactions on 2-amino-5-bromo-3-iodopyridine and a potassium t-butoxide mediated ring closure reaction resulted in the assembly of 2,5-disubstituted 7-azaindoles. The 5-alkynyl substituent of the azaindole was easily converted into both quinoxaline and triazole substituents, the latter utilizing an alkyne-azide cycloaddition reaction. Some of these azaindole derivatives showed very promising biological activity against the gastrointestinal protozoal parasite Giardia duodenalis.

  11. Antimutagenic and anticancer activity of Al Madinah Alhasawy mint (Mentha longifolia) leaves extract.

    Science.gov (United States)

    Al-Ali, Khalil; Abdelrazik, Mohamad; Alghaithy, Abdulaziz; Diab, Atef; El-Beshbishy, Hesham; Baghdadi, Hussam

    2014-12-01

    Mentha is one of the genera of Lamiaceae family. The aim of the present study was to evaluate the antimutagenic and anticancer activity of the water and methanolic extract of Alhasawy mint (Mentha longifolia), that grown in Madina Province, western region, Saudi Arabia using three different bioassays namely; Brine shrimp bioassay, Ames mutagenicity bioassay using 3 Hist-Salmonella typhimurium strains of different mutations (TA98, TA97 and TA100) and 2 reference mutagenic drugs nitrosopiperidine (NP) and 2-amino-3-methylimidazo-quinolidine (IQ) and Mammalian cell lines bioassays using 2 different cell lines HepG2 and Vero cell lines. The plant extract showed an efficient antimutagenic activity against the studied bioassays in a directly proportional effect with concentration. PMID:26027170

  12. Antimutagenic and anticancer activity of Al Madinah Alhasawy mint (Mentha longifolia) leaves extract.

    Science.gov (United States)

    Al-Ali, Khalil; Abdelrazik, Mohamad; Alghaithy, Abdulaziz; Diab, Atef; El-Beshbishy, Hesham; Baghdadi, Hussam

    2014-12-01

    Mentha is one of the genera of Lamiaceae family. The aim of the present study was to evaluate the antimutagenic and anticancer activity of the water and methanolic extract of Alhasawy mint (Mentha longifolia), that grown in Madina Province, western region, Saudi Arabia using three different bioassays namely; Brine shrimp bioassay, Ames mutagenicity bioassay using 3 Hist-Salmonella typhimurium strains of different mutations (TA98, TA97 and TA100) and 2 reference mutagenic drugs nitrosopiperidine (NP) and 2-amino-3-methylimidazo-quinolidine (IQ) and Mammalian cell lines bioassays using 2 different cell lines HepG2 and Vero cell lines. The plant extract showed an efficient antimutagenic activity against the studied bioassays in a directly proportional effect with concentration.

  13. [Effect of excitant amino acid antagonists on glutamate receptors in the locust and on convulsions induced by glutamate, aspartate, kynurenine and quinolinic acid in mice].

    Science.gov (United States)

    Ryzhov, I V; Slepokurov, M V; Lapin, I P; Mandel'shtam, Iu E; Aleksandrov, V G

    1986-03-01

    All excitatory amino acid antagonists studied: diethyl esters of aspartic (DEEA) and glutamic (DEEG) acids, 2-amino-3-phosphono-propionic acid (APPA) and 2-amino-4-phosphono-butanoic acid (APBA), diminished the amplitude of excitatory postsynaptic potentials (EPP) of the locust (Locusta migratoria migratorioides) muscle fibers and arbitrary blocked glutamate (GLU) and aspartate (ASP) responses. Kynurenine (KYN) and quinolinic (QUI) acid had no effect on EPP even at a concentration of 2 X 10(-2) M. The antagonists were not strictly selective against intracerebroventricularly administered endogenous convulsants: GLU, ASP, KYN and QUI and in simulation of experimental seizures in mice. The antagonists structurally similar to ASP prevented ASP- and KYN-induced seizures in lower doses than GLU derivatives. Anti-KYN, but not anti-QUI DEEA, DEEG, APPA and APBA efficacy suggests that KYN and QUI act on different structures or binding sites. PMID:2869799

  14. Enantioselective and diastereoselective separation of synthetic pyrethroid insecticides on a novel chiral stationary phase by high-performance liquid chromatography.

    Science.gov (United States)

    Tan, Xulin; Hou, Shicong; Wang, Min

    2007-07-01

    A novel chiral packing material for high-performance liquid chromatography (HPLC) was prepared by connecting (R)-1-phenyl-2-(4-methylphenyl) ethylamine (PTE) amide derivative of (S)-isoleucine to aminopropyl silica gel through 2-amino-3,5-dinitro-1-carboxamido-benzene unit. This chiral stationary phase was applied to the enantioselective and diastereoselective separation of five pyrethroid insecticides by HPLC under normal phase condition. To achieve satisfactory baseline separation an optimization of the variables of mobile phase composition was required. The two enantiomers of fenpropathrin and four stereoisomers of fenvalerate were baseline separated using hexane-1,2-dichloroethane-2-propanol as mobile phase. The results show that the enantioselectivity of CSP is better than Pirkle type 1-A column for these compounds. Only partial separations for the cypermethrin and cyfluthrin stereoisomers were observed. Seven peaks and eight peaks were observed for cypermethrin and cyfluthrin, respectively. The elution orders were assigned by using different stereoisomer-enriched products.

  15. Preparation of a new chiral stationary phase for HPLC based on the (R)- 1-phenyl-2-(4-methylphenyl)ethylamine amide derivative of (S)-valine and 2-chloro-3,5-dinitrobenzoic acid: enantioseparation of amino acid derivatives and pyrethroid insecticides.

    Science.gov (United States)

    Tan, Xulin; Hou, Shicong; Jiang, Jingli; Wang, Min

    2007-08-01

    A novel chiral stationary phase (CSP) for HPLC was prepared by bonding (R)-1-phenyl-2-(4-methylphenyl)ethylamine amide derivative of (S)-valine to aminopropyl silica gel through a 2-amino-3,5-dinitro-1-carboxamido-benzene unit. The CSP was used for the separation of some amino acid derivatives and pyrethroid insecticides by chiral HPLC. Satisfactory baseline separation required optimization of the variables of mobile phase composition. Use of dichloromethane as modifier in the mobile phase gave baseline separations of amino acid derivatives. The two enantiomers of fenpropathrin and four stereoisomers of fenvalerate were baseline separated using hexane-dichloromethane-ethanol as mobile phase. The results show that the enantioselectivity of the new CSP is better than Pirkle type 1-A column for these compounds. Only partial separations were observed for the stereoisomers of cypermethrin and cyfluthrin, which gave even and eight peaks, respectively.

  16. Improved performance of carbon nanotubes—manganese doped cadmium sulfide quantum dot nanocomposite based solar cell

    Science.gov (United States)

    Kaur, Rajnish; Priya, Nidhi; Deep, Akash

    2016-01-01

    The nanocomposites of carbon nanotubes with quantum dots (MWCNT-QDS) display the capability of light induced charge dissociation and transport, which make them suitable for photovoltaic applications. The present work reports the coupling of multiwalled CNT (MWCNT) with L-cysteine (2-amino 3-mercaptopropionic acid) capped manganese doped cadmium sulfide QDs (CdS:Mn). The confirmation of the MWCNT-CdS:Mn nanocomposite formation is done with various instrumental techniques. Current-voltage studies of the MWCNT-CdS:Mn thin film indicate their semiconducting behavior. Further, cyclic voltammetry and frequency response analyses of the above MWCNT-CdS:Mn thin film have highlighted their potential application as a photoanode material in dye sanitized solar cells. It has been demonstrated that the use of MWCNT-CdS:Mn nanocomposite as a photoanode material offer better photocurrent characteristics as compared to QDS alone.

  17. An efficient synthesis and biological study of substituted 8-chloro-5-methoxy/8-chloro-4H-1,4-benzothiazines, their sulphones and ribofuranosides

    Indian Academy of Sciences (India)

    Nishidha Khandelwal; Abhilasha; Naveen Gautam; D C Gautam

    2013-01-01

    8-Chloro-5-methoxy/8-chloro-4H-1,4-benzothiazines were synthesized by condensation followed by oxidative cyclisation of 2-amino-6-chloro-3-methoxy/2-amino-3-chlorobenzenethiol with -diketones/-ketoesters in the presence of dimethyl sulphoxide. By treating 4H-1,4-benzothiazines with 30% hydrogen peroxide in glacial acetic acid, 4H-1,4-benzothiazine-1,1-dioxides (sulphones) were synthesized. The 4H-1,4-benzothiazines have also been used as a base to prepare ribofuranosides by the reaction with -D-ribofuranose-1-acetate-2,3,5-tribenzoate. All the synthesized compounds have been characterized by spectral and elemental analysis and have been examined for antimicrobial and anthelmintic activity.

  18. Direct Metal-Free Entry to Aminocyclobutenes or Aminocyclobutenols from Ynamides: Synthetic Applications.

    Science.gov (United States)

    Alcaide, Benito; Almendros, Pedro; Lázaro-Milla, Carlos

    2016-06-20

    The [2+2] cycloaddition of ynamides with the highly polarized reagent Tf2 C=CH2 has been developed to regioselectively afford bis(triflyl)aminocyclobutenes in the absence of catalyst under mild conditions. Incidentally, with the ynamides bearing electron-rich aromatic rings at the C-terminal, an interesting reactivity switch was observed; a cyclization/hydroxylation sequence yielded 2-amino-3-(triflyl)cyclobut-2-enols. Aminocyclobutene construction with addition of alcohols resulted in the formation of aminocyclobutenyl ethers through a cyclization/hydroalkoxylation process. Moreover, the utility of functionalized aminocyclobutenes as precursors for further elaboration was demonstrated with the preparation of α-amino-β,γ-unsaturated ketones and 3-(triflyl)buta-1,3-dien-2-amines through 4 π-electrocyclic ring opening. PMID:27230256

  19. Assessment of the non-protein amino acid BMAA in Mediterranean mussel Mytilus galloprovincialis after feeding with estuarine cyanobacteria.

    Science.gov (United States)

    Baptista, Mafalda S; Vasconcelos, Rita G W; Ferreira, Paula C; Almeida, C Marisa R; Vasconcelos, Vitor M

    2015-08-01

    To determine whether 2-amino-3-methylaminopropanoic acid (BMAA) could be taken up by marine organisms from seawater or their diet mussels Mytilus galloprovincialis, collected from the North Atlantic Portuguese shore, were exposed to seawater doped with BMAA standard (for up to 48 h) or fed with cyanobacteria (for up to 15 days). Mussels were able to uptake BMAA when exposed to seawater. Mussels fed with cyanobacteria Synechocystis salina showed a rise in BMAA concentration during feeding and a decline in concentration during the subsequent depuration period. Cells from the gills and hepatopancreas of mussels fed with S. salina showed lessened metabolic activity in mussels fed for longer periods of time. A hot acidic digestion (considered to account for total BMAA) was compared with a proteolytic digestion, using pepsin, trypsin and chymotrypsin. The latter was able to extract from mussels approximately 30% of total BMAA. Implications for BMAA trophic transfers in marine ecosystems are discussed.

  20. Spectroscopic studies on two mono nuclear iron (III) complexes derived from a schiff base and an azodye

    Energy Technology Data Exchange (ETDEWEB)

    Mini, S., E-mail: sadasivan.v@gmail.com; Sadasivan, V., E-mail: sadasivan.v@gmail.com [University College, M G Road, Palayam, Thiruvananthapuram 695 034 Kerala (India); Meena, S. S., E-mail: ssingh@barc.gov.in; Bhatt, Pramod, E-mail: ssingh@barc.gov.in [Solid State Physics Division, Bhabha Atomic Research Centre, Mumbai 400 085 (India)

    2014-10-15

    Two new mono nuclear Fe(III) complexes of an azodye (ANSN) and a Schiff base (FAHP) are reported. The azodye is prepared by coupling diazotized 1-amino-2-naphthol-4-sulphonicacid with 2-naphthol and the Schiff base is prepared by condensing 2-amino-3-hydroxy pyridine with furfural. The complexes were synthesized by the reaction of FeCl{sub 3}Ðœ‡2H{sub 2}O with respective ligands. They were characterized on the basis of elemental analysis and spectral studies like IR, NMR, Electronic and M.ssbauer. Magnetic susceptibility and Molar conductance of complexes at room temperature were studied. Based on the spectroscopic evidences and other analytical data the complexes are formulated as[Fe(ANSN)Cl(H{sub 2}O){sub 2}] and [Fe(FAHP)Cl{sub 2}(H{sub 2}O){sub 2}].

  1. Synthesis and biological evaluation of novel urea and thiourea derivatives of valacyclovir

    Directory of Open Access Journals (Sweden)

    Katla Ramana Venkata

    2014-01-01

    Full Text Available A series of novel urea and thiourea derivatives of valacyclovir were efficiently synthesized in high yields and evaluated their antiviral activity. 2-((6-Amino-4-oxo-4,5-dihydro-1H-imidazo[4,5-c]pyridin-1-ylmethoxyethyl-2-amino-3-ethylbutanoate (valacyclovir 1 is reacted with various aromatic isocyanates/thiocyanates 2 in the presence of N, N- dimethyl piperazine as a base in THF: pyridine (4:1 to obtain valacyclovir urea/thiourea derivatives 3(a-j. The structures of the title compounds 3(a-j were confirmed by IR, NMR (1H, 13C, mass spectral and elemental analysis. The newly synthesized compounds were screened for their antiviral activity against Tobacco mosaic virus (TMV and antioxidant activity was evaluated by DPPH, SOD and GST methods. The title compounds exhibited potent antiviral and good antioxidant activities.

  2. The human L-threonine 3-dehydrogenase gene is an expressed pseudogene

    Directory of Open Access Journals (Sweden)

    Edgar Alasdair J

    2002-10-01

    Full Text Available Abstract Background L-threonine is an indispensable amino acid. One of the major L-threonine degradation pathways is the conversion of L-threonine via 2-amino-3-ketobutyrate to glycine. L-threonine dehydrogenase (EC 1.1.1.103 is the first enzyme in the pathway and catalyses the reaction: L-threonine + NAD+ = 2-amino-3-ketobutyrate + NADH. The murine and porcine L-threonine dehydrogenase genes (TDH have been identified previously, but the human gene has not been identified. Results The human TDH gene is located at 8p23-22 and has 8 exons spanning 10 kb that would have been expected to encode a 369 residue ORF. However, 2 cDNA TDH transcripts encode truncated proteins of 157 and 230 residues. These truncated proteins are the result of 3 mutations within the gene. There is a SNP, A to G, present in the genomic DNA sequence of some individuals which results in the loss of the acceptor splice site preceding exon 4. The acceptor splice site preceding exon 6 was lost in all 23 individuals genotyped and there is an in-frame stop codon in exon 6 (CGA to TGA resulting in arginine-214 being replaced by a stop codon. These truncated proteins would be non-functional since they have lost part of the NAD+ binding motif and the COOH terminal domain that is thought to be involved in binding L-threonine. TDH mRNA was present in all tissues examined. Conclusions The human L-threonine 3-dehydrogenase gene is an expressed pseudogene having lost the splice acceptor site preceding exon 6 and codon arginine-214 (CGA is mutated to a stop codon (TGA.

  3. Metabolic activation of N-hydroxy arylamines, N-hydroxy heterocyclic amines and ring-hydroxymethyl polycyclic aromatic hydrocarbons by human sulfotransferases

    Energy Technology Data Exchange (ETDEWEB)

    Chou, H.C.

    1993-01-01

    Arylamines and polycyclic aromatic hydrocarbons (PAHs) are two major classes of chemical carcinogens. N-Hydroxylation of arylamines is regarded to be a necessary process for their mutagenicity and carcinogenicity, while alkyl-hydroxylation is the major metabolic pathway for alkyl-substituted PAHs. Evidence has been presented that sulfation of several N-hydroxy arylamines and hydroxymethyl PAHs is an important pathway leading to the formation of ultimate carcinogens in experiment animals. Sulfation of these chemicals forms putative sulfuric acid ester intermediates that can rearrange to electrophilic nitrenium or carbenium ions capable of forming covalent adducts with important cellular macromolecules. In order to study the metabolic activation by sulfotransferase(s) in various human tissue preparations an in vitro enzymatic assay was established. A metabolic phenotyping method was also developed for thermostable phenolsulfotransferase (TS-PST) in platelet homogenates (correlated with TS-PST activity in other tissues) based on a simple colorimetric assay using 2-naphthol as substrate. By using a PAPS-regenerating system to supply the activated sulfate and calf thymus DNA to trap the reactive metabolites, we found that N-hydroxy derivatives of the carcinogens, 4-aminobiphenyl (4-ABP), 4,4[prime]-methylene-bis(2-chloroaniline) (MOCA), 2-acetylaminofluorene (2-AAF), 2-aminofluorene (2-AF), 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP), and 2-amino-6-methyldipyrido [1,2-1:3[prime],2[prime]-d]imidazole (Glu-P-1) were metabolically activated by human TS-PST. On the other hand, three methyl-hydroxylated derivatives (7-OH, 12-OH, and 7,12-diOH) of 7, 12-dimethylbenz[a]anthracene (DMBA) were metabolically activated by human steroid sulfotransferase. Human sulfotransferase(s)-mediated activation of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) or 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) was not observed.

  4. Unsaturated amino acids derived from isoleucine trigger early membrane effects on plant cells.

    Science.gov (United States)

    Roblin, Gabriel; Laduranty, Joëlle; Bonmort, Janine; Aidene, Mohand; Chollet, Jean-François

    2016-10-01

    Unsaturated amino acids (UnsAA) have been shown to affect the activity of various biological processes. However, their mode of action has been investigated poorly thus far. We show in this work that 2-amino-3-methyl-4-pentenoic acid (C2) and 2-amino-3-methyl-4-pentynoic acid (C3) structurally derived from isoleucine (Ile) exhibited a multisite action on plant cells. For one, C2 and C3 induced early modifications at the plasma membrane level, as shown by the hyperpolarization monitored by microelectrode implantation in the pulvinar cells of Mimosa pudica, indicating that these compounds are able to modify ionic fluxes. In particular, proton (H(+)) fluxes were modified, as shown by the pH rise monitored in the bathing medium of pulvinar tissues. A component of this effect may be linked to the inhibitory effect observed on the proton pumping and the vanadate-sensitive activity of the plasma membrane H(+)-ATPase monitored in plasma membrane vesicles (PMVs) purified from pulvinar tissues of M. pudica and leaf tissues of Beta vulgaris. This effect may explain, in part, the inhibitory effect of the compounds on the uptake capacity of sucrose and valine by B. vulgaris leaf tissues. In contrast, an unexpected action was observed in cell reactions, implicating ion fluxes and water movement. Indeed, the osmocontractile reactions of pulvini induced either by a mechanical shock in M. pudica or by dark and light signals in Cassia fasciculata were increased, indicating that, compared to Ile, these compounds may modify in a specific way the plasma membrane permeability to water and ions. PMID:27254795

  5. Lactoperoxidase-catalyzed activation of carcinogenic aromatic and heterocyclic amines.

    Science.gov (United States)

    Gorlewska-Roberts, Katarzyna M; Teitel, Candee H; Lay, Jackson O; Roberts, Dean W; Kadlubar, Fred F

    2004-12-01

    Lactoperoxidase, an enzyme secreted from the human mammary gland, plays a host defensive role through antimicrobial activity. It has been implicated in mutagenic and carcinogenic activation in the human mammary gland. The potential role of heterocyclic and aromatic amines in the etiology of breast cancer led us to examination of the lactoperoxidase-catalyzed activation of the most commonly studied arylamine carcinogens: 2-amino-1-methyl-6-phenylimidazo[4,5-b]-pyridine (PhIP), benzidine, 4-aminobiphenyl (ABP), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx). In vitro activation was performed with lactoperoxidase (partially purified from bovine milk or human milk) in the presence of hydrogen peroxide and calf thymus DNA. Products formed during enzymatic activation were monitored by HPLC with ultraviolet and radiometric detection. Two of these products were characterized as hydrazo and azo derivatives by means of mass spectrometry. The DNA binding level of 3H- and 14C-radiolabeled amines after peroxidase-catalyzed activation was dependent on the hydrogen peroxide concentration, and the highest levels of carcinogen binding to DNA were observed at 100 microM H2O2. Carcinogen activation and the level of binding to DNA were in the order of benzidine > ABP > IQ > MeIQx > PhIP. One of the ABP adducts was identified, and the level at which it is formed was estimated to be six adducts/10(5) nucleotides. The susceptibility of aromatic and heterocyclic amines for lactoperoxidase-catalyzed activation and the binding levels of activated products to DNA suggest a potential role of lactoperoxidase-catalyzed activation of carcinogens in the etiology of breast cancer.

  6. Qualitative and quantitative approaches in the dose-response assessment of genotoxic carcinogens.

    Science.gov (United States)

    Fukushima, Shoji; Gi, Min; Kakehashi, Anna; Wanibuchi, Hideki; Matsumoto, Michiharu

    2016-05-01

    Qualitative and quantitative approaches are important issues in field of carcinogenic risk assessment of the genotoxic carcinogens. Herein, we provide quantitative data on low-dose hepatocarcinogenicity studies for three genotoxic hepatocarcinogens: 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and N-nitrosodiethylamine (DEN). Hepatocarcinogenicity was examined by quantitative analysis of glutathione S-transferase placental form (GST-P) positive foci, which are the preneoplastic lesions in rat hepatocarcinogenesis and the endpoint carcinogenic marker in the rat liver medium-term carcinogenicity bioassay. We also examined DNA damage and gene mutations which occurred through the initiation stage of carcinogenesis. For the establishment of points of departure (PoD) from which the cancer-related risk can be estimated, we analyzed the above events by quantitative no-observed-effect level and benchmark dose approaches. MeIQx at low doses induced formation of DNA-MeIQx adducts; somewhat higher doses caused elevation of 8-hydroxy-2'-deoxyquanosine levels; at still higher doses gene mutations occurred; and the highest dose induced formation of GST-P positive foci. These data indicate that early genotoxic events in the pathway to carcinogenesis showed the expected trend of lower PoDs for earlier events in the carcinogenic process. Similarly, only the highest dose of IQ caused an increase in the number of GST-P positive foci in the liver, while IQ-DNA adduct formation was observed with low doses. Moreover, treatment with DEN at low doses had no effect on development of GST-P positive foci in the liver. These data on PoDs for the markers contribute to understand whether genotoxic carcinogens have a threshold for their carcinogenicity. The most appropriate approach to use in low dose-response assessment must be approved on the basis of scientific judgment.

  7. Impact of Precursors Creatine, Creatinine, and Glucose on the Formation of Heterocyclic Aromatic Amines in Grilled Patties of Various Animal Species.

    Science.gov (United States)

    Gibis, Monika; Weiss, Jochen

    2015-11-01

    The impact of precursors such as creatine, creatinine, and glucose on the formation of mutagenic/carcinogenic heterocyclic amines (HAs) were studied in patties of 9 different animal species equally heat treated with a double-plate contact grill. All grilled patties of the various species (veal, beef, pork, lamb, horse, venison, turkey, chicken, ostrich) contained several HAs such as MeIQx (2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline; 0.5-1.4 ng/g), 4,8-DiMeIQx (2-amino-3,4,8-trimethylimidazo[4,5-f] quinoxaline, 0 to 1.3 ng/g), PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine, 1.2 to 10.5 ng/g), harman (1-methyl-9H-pyrido[3,4-b] indole; 0.5 to 3.2 ng/g), and/or norharman (9H-pyrido[3,4-b]indole 0.5 to 1.9 ng/g). Residual glycogen (glucose) content varied greatly from 0.07 to 1.46 wt% on a dry matter (DM) basis. Total creatin(in)e content in raw meat (1.36 to 2.0 wt% DM) hardly differed between species, except in turkey and ostrich (1.1 wt% DM). Chicken contained, compared to all other species, very low concentrations of glucose (0.07 wt% DM) and the highest levels of nonprotein nitrogen compounds. The free amino acids lysine (r = 0.77, P < 0.001), tyrosine, phenylalanine, proline, isoleucine, and aspartic acid (r = 0.47-0.56, P < 0.05) showed significant correlation to PhIP in chicken. Also a linear correlation was found to exist between PhIP (r = 0.87, P < 0.001) and MeIQx (r = 0.35, P < 0.01), and the molar ratio of creatin(in)e to glucose, respectively. Harman as co-mutagens was linearly correlated to the concentration of glucose (r = 0.65, P < 0.001). By contrast, norharman was not significant correlated to glucose levels. PMID:26445401

  8. Formation of heterocyclic amines in salami and ham pizza toppings during baking of frozen pizza.

    Science.gov (United States)

    Gibis, Monika; Weiss, Jochen

    2013-06-01

    Heterocyclic amines (HAs) are formed as Maillard reaction products in the crust of meat products during heating processes. Two typical pizza toppings--salami and cooked ham--were analyzed for the presence of HAs after baking frozen pizzas at top and bottom temperatures of 250 and 230 °C, respectively. After baking pizza slices for 12 min, MeIQx (2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline; 0.2 ng/g), 4,8-DiMeIQx (2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline; 0.5 ng/g), PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine; 0.2 ng/g), norharman (4.5 ng/g), and harman (2.5 ng/g) were found in the ham toppings, whereas only the comutagenic norharman (107.4 ng/g) and harman (11.4 ng/g) were found in the salami toppings. The content of MeIQx and 4,8-DiMeIQx in ham increased from 0.3 to 1.8 ng/g and 0.8 to 1.6 ng/g, respectively, when the recommended baking time was increased from 15 min (manufacturer's specification) to 18 min at 230 °C. MeIQx was formed in salami when the heating time was extended to 18 min. Moreover, higher concentrations of PhIP in salami or ham slices were found when baking temperatures were 250 °C rather than 230 °C (baking time of 12 min). However, sensory tests showed that panelists preferred longer-baked pizzas due to an increased crispiness. Thus, results show that a substantial formation of HAs may occur in pizza toppings such as ham and salami, with ham being particularly susceptible when compared to salami. Formation of HAs increases with increasing baking time and temperature. The occurrence of the cupping of ham or salami slices during baking may also increase the formation of HAs.

  9. The Amino Acid Specificity for Activation of Phenylalanine Hydroxylase Matches the Specificity for Stabilization of Regulatory Domain Dimers.

    Science.gov (United States)

    Zhang, Shengnan; Hinck, Andrew P; Fitzpatrick, Paul F

    2015-08-25

    Liver phenylalanine hydroxylase is allosterically activated by phenylalanine. The structural changes that accompany activation have not been identified, but recent studies of the effects of phenylalanine on the isolated regulatory domain of the enzyme support a model in which phenylalanine binding promotes regulatory domain dimerization. Such a model predicts that compounds that stabilize the regulatory domain dimer will also activate the enzyme. Nuclear magnetic resonance spectroscopy and analytical ultracentrifugation were used to determine the ability of different amino acids and phenylalanine analogues to stabilize the regulatory domain dimer. The abilities of these compounds to activate the enzyme were analyzed by measuring their effects on the fluorescence change that accompanies activation and on the activity directly. At concentrations of 10-50 mM, d-phenylalanine, l-methionine, l-norleucine, and (S)-2-amino-3-phenyl-1-propanol were able to activate the enzyme to the same extent as 1 mM l-phenylalanine. Lower levels of activation were seen with l-4-aminophenylalanine, l-leucine, l-isoleucine, and 3-phenylpropionate. The ability of these compounds to stabilize the regulatory domain dimer agreed with their ability to activate the enzyme. These results support a model in which allosteric activation of phenylalanine hydroxylase is linked to dimerization of regulatory domains.

  10. Synthesis, spectroscopic characterization, and thermal decomposition kinetics of some lanthanide(Ⅲ) nitrate complexes of 2-(N-o-hydroxyacetophenone) amino-3-carboxyethyl-4,5,6,7-tetrahydrobenzo[b]thiophene

    Institute of Scientific and Technical Information of China (English)

    K.Mohanan; M.Thankamony; B.Sindhu Kumari

    2008-01-01

    Complexes of La(Ⅲ), Ce(Ⅲ), Pr(Ⅲ), Nd(Ⅲ), Sm(Ⅲ), Eu(Ⅲ), Gd(Ⅲ), Dy(Ⅲ), Yb(Ⅲ), and Lu(Ⅲ) with 2-(N-o- hydroxyacetophenone)amino-3-carboxyethyl-4,5,6,7-tetrahydrobenzo[b]thiophene (HAAT) formed by the condensation of o-hydroxyacetophenone and 2-amino-3-carboxyethyl-4,5,6,7-tetrahydrobenzo[b]thiophene were synthesized and characterized on the basis of elemental analyses, molar conductance measurements, magnetic susceptibility data, UV-Visible, IR, and NMR spectral studies. The spectral data revealed that the ligand acted as a neutral tridentate coordinating to the metal ion through ONO donor sequence. A coordination number nine was proposed for the complexes. Thermal decomposition studies of the ligand and lanthanum(Ⅲ) complex were carried out and kinetic parameters were calculated using Coats-Redfern equation. The decomposition reactions followed random nucleation mechanism with one nucleus on each particle.

  11. Synthesis and characterization of a tetranuclear copper(Ⅱ) complex with a chiral Schiff base ligand

    Institute of Scientific and Technical Information of China (English)

    Hua Xiang; Long Jiang; Huan-Yong Li; Xiao-Dan Zheng; YU Li

    2013-01-01

    The title complex l-[CuⅡ4(Hvap)2(vap)2(MeOH)2](ClO4)2 1 has been synthesized and characterized by EA,IR,TGA,solid-state CD spectra and X-ray single-crystal analyses (I-H2vap:a Schiff base ligand derived from the condensation of o-vanillin and 1-2-amino-3-phenyl-1-propanol).Complex 1 crystallizes in monoclinic system,chiral space group P21 with a=10.4257(18),b=21.695(4),c=15.721(3) (A),β =94.443(3)°,V=3545.1 (11) (A)3,Z =2,Cu4C7oH78N4O22Cl2,Mr =1652.42,Dc =1.548 g/cm3,F(0 0 0) =1704 and μ(MoKα) =1.338 mm-1.The final R =0.0682 and wR =0.1420 for 6170 observed reflections with I > 2σ(Ⅰ) and R =0.1775 and wR =0.1830 for all data.The structure of complex 1 contains a boat-shaped {Cu4O4} motif.The solid-state CD spectra confirm the chiral nature of complex 1.

  12. Deficiency of Lipoprotein Lipase in Neurons Decreases AMPA Receptor Phosphorylation and Leads to Neurobehavioral Abnormalities in Mice.

    Directory of Open Access Journals (Sweden)

    Tian Yu

    Full Text Available Alterations in lipid metabolism have been found in several neurodegenerative disorders, including Alzheimer's disease. Lipoprotein lipase (LPL hydrolyzes triacylglycerides in lipoproteins and regulates lipid metabolism in multiple organs and tissues, including the central nervous system (CNS. Though many brain regions express LPL, the functions of this lipase in the CNS remain largely unknown. We developed mice with neuron-specific LPL deficiency that became obese on chow by 16 wks in homozygous mutant mice (NEXLPL-/- and 10 mo in heterozygous mice (NEXLPL+/-. In the present study, we show that 21 mo NEXLPL+/- mice display substantial cognitive function decline including poorer learning and memory, and increased anxiety with no difference in general motor activities and exploratory behavior. These neurobehavioral abnormalities are associated with a reduction in the 2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl propanoic acid (AMPA receptor subunit GluA1 and its phosphorylation, without any alterations in amyloid β accumulation. Importantly, a marked deficit in omega-3 and omega-6 polyunsaturated fatty acids (PUFA in the hippocampus precedes the development of the neurobehavioral phenotype of NEXLPL+/- mice. And, a diet supplemented with n-3 PUFA can improve the learning and memory of NEXLPL+/- mice at both 10 mo and 21 mo of age. We interpret these findings to indicate that LPL regulates the availability of PUFA in the CNS and, this in turn, impacts the strength of synaptic plasticity in the brain of aging mice through the modification of AMPA receptor and its phosphorylation.

  13. Exploring the GluR2 ligand-binding core in complex with the bicyclical AMPA analogue (S)-4-AHCP

    DEFF Research Database (Denmark)

    Nielsen, Bettina B; Pickering, Darryl S; Greenwood, Jeremy R;

    2005-01-01

    The X-ray structure of the ionotropic GluR2 ligand-binding core (GluR2-S1S2J) in complex with the bicyclical AMPA analogue (S)-2-amino-3-(3-hydroxy-7,8-dihydro-6H-cyclohepta[d]-4-isoxazolyl)propionic acid [(S)-4-AHCP] has been determined, as well as the binding pharmacology of this construct...... and of the full-length GluR2 receptor. (S)-4-AHCP binds with a glutamate-like binding mode and the ligand adopts two different conformations. The K(i) of (S)-4-AHCP at GluR2-S1S2J was determined to be 185 +/- 29 nM and at full-length GluR2(R)o it was 175 +/- 8 nM. (S)-4-AHCP appears to elicit partial agonism...... at GluR2 by inducing an intermediate degree of domain closure (17 degrees). Also, functionally (S)-4-AHCP has an efficacy of 0.38 at GluR2(Q)i, relative to (S)-glutamate. The proximity of bound (S)-4-AHCP to domain D2 prevents full D1-D2 domain closure, which is limited by steric repulsion, especially...

  14. Synthesis, spectroscopic characterization, solid state d.c. electrical conductivity and biological studies of some lanthanide(III chloride complexes with a heterocyclic Schiff base ligand

    Directory of Open Access Journals (Sweden)

    K. Mohanan

    2016-07-01

    Full Text Available Condensation of 2-hydroxy-1-naphthaldehyde with 2-amino-3-carboxyethyl-4,5-dimethylthiophene in 1:1 molar ratio, yielded a potentially tridentate Schiff base viz. 2-[N-(2′-hydroxy-1-naphthylideneamino]-3-carboxyethyl-4,5-dimethylthiophene (HNAT. This ligand formed complexes with lanthanum(III, cerium(III, praseodymium(III, neodymium(III, samarium(III, europium(III and gadolinium(III chloride under well defined conditions. These complexes were characterized through elemental analysis, molar conductance, magnetic moment measurements, IR, UV–Vis, FAB mass and 1H NMR spectral studies. Analytical data showed that all the metal complexes exhibited 1:1 metal–ligand ratio. Molar conductance values adequately confirmed the non-electrolytic nature of the metal complexes. The proton NMR spectral observations supplement the IR spectral assignments. The spectral data revealed that the ligand acted as neutral tridentate, coordinating to the metal ion through azomethine nitrogen, ester carbonyl and naphtholate oxygen without deprotonation. The ligand and its lanthanum(III chloride complex were subjected to XRD studies. The lanthanum(III chloride complex has undergone a facile transesterification reaction. The solid state d.c. electrical conductivity of some selected complexes were measured as a function of temperature, indicating the semiconducting nature of the metal complexes. The antimicrobial activities were examined by disk diffusion method against some pathogenic bacterial and fungal species.

  15. Excitatory amino acid receptor antagonists

    DEFF Research Database (Denmark)

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

    1997-01-01

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

  16. Alliin is a suicide substrate of Citrobacter freundii methionine γ-lyase: structural bases of inactivation of the enzyme.

    Science.gov (United States)

    Morozova, Elena A; Revtovich, Svetlana V; Anufrieva, Natalya V; Kulikova, Vitalia V; Nikulin, Alexey D; Demidkina, Tatyana V

    2014-11-01

    The interaction of Citrobacter freundii methionine γ-lyase (MGL) and the mutant form in which Cys115 is replaced by Ala (MGL C115A) with the nonprotein amino acid (2R)-2-amino-3-[(S)-prop-2-enylsulfinyl]propanoic acid (alliin) was investigated. It was found that MGL catalyzes the β-elimination reaction of alliin to form 2-propenethiosulfinate (allicin), pyruvate and ammonia. The β-elimination reaction of alliin is followed by the inactivation and modification of SH groups of the wild-type and mutant enzymes. Three-dimensional structures of inactivated wild-type MGL (iMGL wild type) and a C115A mutant form (iMGL C115A) were determined at 1.85 and 1.45 Å resolution and allowed the identification of the SH groups that were oxidized by allicin. On this basis, the mechanism of the inactivation of MGL by alliin, a new suicide substrate of MGL, is proposed.

  17. In Vitro Anti-Osteoporosis Properties of Diverse Korean Drynariae rhizoma Phenolic Extracts

    Directory of Open Access Journals (Sweden)

    Suk-Nam Kang

    2014-04-01

    Full Text Available Drynariae rhizoma has been used to prevent bone loss that occurs with increasing age. However, the chemical compounds in extracts that act on bone metabolism in herbal medicine are poorly understood. This study aimed to investigate and compare the extraction efficacy of polyphenolic compounds, antioxidant activity, and in vitro anti-osteoporosis properties of water extract (DR-DW and ethanol extract (DR-EtOH from D. rhizoma. Total phenolics and flavonoids were better extracted with 70% EtOH, and this extraction method also resulted in higher antioxidant activity and in vitro anti-osteoporosis properties in these extracts. In particular, the contents of phloroglucinol, protocatechuic acid ethyl ester, 2-amino-3,4-dimethyl-benzoic acid, 3-(3,5-dimethyl-pyrazol-1-yl-benzoic acid, chlorogenic acid, syringic acid, trans-ferulic acid, (−-epigallocatechin, epigallocatechin gallate, quercetin dehydrate, luteolin and emodin in DR-EtOH were higher than those in DR-DW. These results indicated that DR-EtOH could be a good source of natural herbs with anti-osteoporosis properties.

  18. In vitro anti-osteoporosis properties of diverse Korean Drynariae rhizoma phenolic extracts.

    Science.gov (United States)

    Kang, Suk-Nam; Lee, Jong Seok; Park, Joung-Hyun; Cho, Jae-Hyeon; Park, Jae-Hong; Cho, Kwang-Keun; Lee, Ok-Hwan; Kim, Il-Suk

    2014-04-01

    Drynariae rhizoma has been used to prevent bone loss that occurs with increasing age. However, the chemical compounds in extracts that act on bone metabolism in herbal medicine are poorly understood. This study aimed to investigate and compare the extraction efficacy of polyphenolic compounds, antioxidant activity, and in vitro anti-osteoporosis properties of water extract (DR-DW) and ethanol extract (DR-EtOH) from D. rhizoma. Total phenolics and flavonoids were better extracted with 70% EtOH, and this extraction method also resulted in higher antioxidant activity and in vitro anti-osteoporosis properties in these extracts. In particular, the contents of phloroglucinol, protocatechuic acid ethyl ester, 2-amino-3,4-dimethyl-benzoic acid, 3-(3,5-dimethyl-pyrazol-1-yl)-benzoic acid, chlorogenic acid, syringic acid, trans-ferulic acid, (-)-epigallocatechin, epigallocatechin gallate, quercetin dehydrate, luteolin and emodin in DR-EtOH were higher than those in DR-DW. These results indicated that DR-EtOH could be a good source of natural herbs with anti-osteoporosis properties. PMID:24763116

  19. Development of a Medium-term Animal Model Using gpt Delta Rats to Evaluate Chemical Carcinogenicity and Genotoxicity

    Science.gov (United States)

    Matsushita, Kohei; Kijima, Aki; Ishii, Yuji; Takasu, Shinji; Jin, Meilan; Kuroda, Ken; Kawaguchi, Hiroaki; Miyoshi, Noriaki; Nohmi, Takehiko; Ogawa, Kumiko; Umemura, Takashi

    2013-01-01

    In this study, the potential for development of an animal model (GPG46) capable of rapidly detecting chemical carcinogenicity and the underlying mechanisms of action were examined in gpt delta rats using a reporter gene assay to detect mutations and a medium-term rat liver bioassay to detect tumor promotion. The tentative protocol for the GPG46 model was developed based on the results of dose-response exposure to diethylnitrosamine (DEN) and treatment with phenobarbital over time following DEN administration. Briefly, gpt delta rats were exposed to various chemicals for 4 weeks, followed by a partial hepatectomy (PH) to collect samples for an in vivo mutation assay. The mutant frequencies (MFs) of the reporter genes were examined as an indication of tumor initiation. A single intraperitoneal (ip) injection of 10 mg/kg DEN was administered to rats 18 h after the PH to initiate hepatocytes. Tumor-promoting activity was evaluated based on the development of glutathione S-transferase placental form (GST-P)-positive foci at week 10. The genotoxic carcinogens 2-acetylaminofluorene (2-AAF), 2-amino-3-methylimidazo [4,5-f] quinolone (IQ) and safrole (SF), the non-genotoxic carcinogens piperonyl butoxide (PBO) and phenytoin (PHE), the non-carcinogen acetaminophen (APAP) and the genotoxic non-hepatocarcinogen aristolochic acid (AA) were tested to validate the GPG46 model. The validation results indicate that the GPG46 model could be a powerful tool in understanding chemical carcinogenesis and provide valuable information regarding human risk hazards. PMID:23723564

  20. Oxidative Stress in the Carcinogenicity of Chemical Carcinogens

    Directory of Open Access Journals (Sweden)

    Hideki Wanibuchi

    2013-10-01

    Full Text Available This review highlights several in vivo studies utilizing non-genotoxic and genotoxic chemical carcinogens, and the mechanisms of their high and low dose carcinogenicities with respect to formation of oxidative stress. Here, we survey the examples and discuss possible mechanisms of hormetic effects with cytochrome P450 inducers, such as phenobarbital, a-benzene hexachloride and 1,1-bis(p-chlorophenyl-2,2,2-trichloroethane. Epigenetic processes differentially can be affected by agents that impinge on oxidative DNA damage, repair, apoptosis, cell proliferation, intracellular communication and cell signaling. Non-genotoxic carcinogens may target nuclear receptors and induce post-translational modifications at the protein level, thereby impacting on the stability or activity of key regulatory proteins, including oncoproteins and tumor suppressor proteins. We further discuss role of oxidative stress focusing on the low dose carcinogenicities of several genotoxic carcinogens such as a hepatocarcinogen contained in seared fish and meat, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, arsenic and its metabolites, and the kidney carcinogen potassium bromate.

  1. Oxidative Stress in the Carcinogenicity of Chemical Carcinogens

    Energy Technology Data Exchange (ETDEWEB)

    Kakehashi, Anna; Wei, Min [Department of Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-Ku, Osaka 545-8585 (Japan); Fukushima, Shoji [Japan Bioassay Research Center, Japan Industrial Safety and Health Association, 2445 Hirasawa, Hadano, Kanagawa 257-0015 (Japan); Wanibuchi, Hideki, E-mail: wani@med.osaka-cu.ac.jp [Department of Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-Ku, Osaka 545-8585 (Japan)

    2013-10-28

    This review highlights several in vivo studies utilizing non-genotoxic and genotoxic chemical carcinogens, and the mechanisms of their high and low dose carcinogenicities with respect to formation of oxidative stress. Here, we survey the examples and discuss possible mechanisms of hormetic effects with cytochrome P{sub 450} inducers, such as phenobarbital, α-benzene hexachloride and 1,1-bis(p-chlorophenyl)-2,2,2-trichloroethane. Epigenetic processes differentially can be affected by agents that impinge on oxidative DNA damage, repair, apoptosis, cell proliferation, intracellular communication and cell signaling. Non-genotoxic carcinogens may target nuclear receptors and induce post-translational modifications at the protein level, thereby impacting on the stability or activity of key regulatory proteins, including oncoproteins and tumor suppressor proteins. We further discuss role of oxidative stress focusing on the low dose carcinogenicities of several genotoxic carcinogens such as a hepatocarcinogen contained in seared fish and meat, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, arsenic and its metabolites, and the kidney carcinogen potassium bromate.

  2. The metabolism of 4,8-DiMeIQx in conventional and germ-free rats

    Energy Technology Data Exchange (ETDEWEB)

    Knize, M.G.; Overik, E.; Midtvedt, T.; Turteltaub, K.W.; Happe, J.A.; Gustafsson, J.A.; Felton, J.S. (Lawrence Livermore National Lab., CA (USA))

    1989-08-01

    The aromatic amine mutagen, ({sup 14}C)2-amino-3,4-8-trimethyl-imidazo(4,5-f)quinoxaline (4,8-DiMeIQx), which is derived from cooked food, was administered to conventional and germ-free AGUS rats previously fed either a semi-synthetic diet containing the cytochrome P-450 inducer beta-naphthoflavone (BNF) or a control diet without BNF. The germ-free animals had longer fecal transit times and lower induction of 7-ethoxyresorufin-O-deethylase activity than conventional rats. Induction with BNF caused a greater percentage of the radioactivity to be excreted in the feces of both germ-free and conventional rats. Feeding BNF also caused a 4-fold induction in germ-free and a 24-fold induction in conventional rat intestinal enzyme levels. Analysis of the urinary and fecal metabolites showed no consistent differences between conventional and germ-free rats in the metabolite profile. Major metabolites were identified as 8-hydroxymethyl-DiMeIQx, N-acetyl-8-hydroxymethyl-DiMeIQx, and 3-N-dimethyl-4-hydroxy-methyl-DiMeIQx. The data from this study indicate that intestinal microflora do not play a major role in the metabolism of 4,8-DiMeIQx, but the induction of intestinal enzymes does not affect the route and rate of excretion.

  3. Crystal structure of Boc-(S-ABOC-(S-Ala-(S-ABOC-(S-Phe-OBn chloroform monosolvate

    Directory of Open Access Journals (Sweden)

    Emmanuel Wenger

    2015-10-01

    Full Text Available In the title compound, phenyl (S-2-[(S-(1-{2-[(S-(1-{[(tert-butoxycarbonyl]amino}bicyclo[2.2.2]octan-2-ylformamido]propanamido}bicyclo[2.2.2]octan-2-ylformamido]-3-phenylpropanoate chloroform monosolvate, C42H56N4O7·CHCl3, the α,β-hybrid peptide contains two non-proteinogenic amino acid residues of (S-1-aminobicyclo[2.2.2]octane-2-carboxylic acid [(S-ABOC], two amino acid residues of (S-2-aminopropanoic acid [(S-Ala] and (S-2-amino-3-phenylpropanoic acid [(S-Phe], and protecting groups of tert-butoxycarbonyl (Boc and benzyl ester (OBn. The tetramer folds into a right-handed mixed 11/9 helix stabilized by intramolecular i,i + 3 and i,i − 1 C=O...H—N hydrogen bonds. In the crystal, the oligomers are linked by N—H...O=C hydrogen bonds into chains along the a-axis direction. The chloroform solvent molecules are intercalated between the folded chains via C—H...O=C interactions.

  4. Proteomic analysis of kidney in rats chronically exposed to monosodium glutamate.

    Directory of Open Access Journals (Sweden)

    Amod Sharma

    Full Text Available Chronic monosodium glutamate (MSG intake causes kidney dysfunction and renal oxidative stress in the animal model. To gain insight into the renal changes induced by MSG, proteomic analysis of the kidneys was performed.Six week old male Wistar rats were given drinking water with or without MSG (2 mg/g body weight, n = 10 per group for 9 months. Kidneys were removed, frozen, and stored at -75°C. After protein extraction, 2-D gel electrophoresis was performed and renal proteome profiles were examined with Colloidal Coomassie Brilliant Blue staining. Statistically significant protein spots (ANOVA, p<0.05 with 1.2-fold difference were excised and analyzed by LC-MS. Proteomic data were confirmed by immunohistochemistry and Western blot analyses.The differential image analysis showed 157 changed spots, of which 71 spots were higher and 86 spots were lower in the MSG-treated group compared with those in the control group. Eight statistically significant and differentially expressed proteins were identified: glutathione S-transferase class-pi, heat shock cognate 71 kDa, phosphoserine phosphatase, phosphoglycerate kinase, cytosolic glycerol-3-phosphate dehydrogenase, 2-amino-3-carboxymuconate-6-semialdehyde decarboxylase, α-ketoglutarate dehydrogenase and succinyl-CoA ligase.The identified proteins are mainly related to oxidative stress and metabolism. They provide a valuable clue to explore the mechanism of renal handling and toxicity on chronic MSG intake.

  5. 一种改进的依替唑仑合成方法%An Improved Synthesis of Etizolam

    Institute of Scientific and Technical Information of China (English)

    开永茂; 李磊; 赵廷兴; 董战; 张丽娟; 梁德辉; 李鸿波

    2014-01-01

    依替唑仑是一种在临床上应用较为广泛的镇静、催眠、抗抑郁药。以2-氨基-3-(2-氯苯甲酰)-5-乙基噻吩(Ⅰ)为原料,经氯乙酰化,再在乙醇中与乌洛托品环合,制得关键中间体(Ⅲ)。中间体(Ⅲ)经硫化、环合反应制得依替唑仑(Ⅴ),4步反应总收率为56.4%。改进后的反应具有合成路线短、条件温和、操作简便、收率高等优点。%Etizolam is a sedative , hypnotic and antidepressant drug widely used in clinics .In this study , the key intermediate (Ⅲ) was synthesized through acetylation and then cyclization in ethanol with uro-tropin from 2-amino-3-( 2 -chlorobenzoyl ) -5 -ethylthiophene (Ⅰ) as raw material .The target product etizolam (Ⅴ) was successfully obtained from Ⅲvia sulfuration and cyclization .The total yield of the four steps was 56.4%.The improved synthetic process has such advantages as short synthetic route , mild reaction condition , simple operation , high yield and so on .

  6. Crystal structure of Boc-(S)-ABOC-(S)-Ala-(S)-ABOC-(S)-Phe-OBn chloro-form monosolvate.

    Science.gov (United States)

    Wenger, Emmanuel; Moulat, Laure; Legrand, Baptiste; Amblard, Muriel; Calmès, Monique; Didierjean, Claude

    2015-10-01

    In the title compound, phenyl (S)-2-[(S)-(1-{2-[(S)-(1-{[(tert-but-oxy)carbon-yl]amino}-bicyclo-[2.2.2]octan-2-yl)formamido]-propanamido}-bicyclo-[2.2.2]octan-2-yl)formamido]-3-phenyl-propano-ate chloro-form monosolvate, C42H56N4O7·CHCl3, the α,β-hybrid peptide contains two non-proteinogenic amino acid residues of (S)-1-amino-bicyclo-[2.2.2]octane-2-carb-oxy-lic acid [(S)-ABOC], two amino acid residues of (S)-2-amino-propanoic acid [(S)-Ala] and (S)-2-amino-3-phenyl-propanoic acid [(S)-Phe], and protecting groups of tert-but-oxy-carbonyl (Boc) and benzyl ester (OBn). The tetra-mer folds into a right-handed mixed 11/9 helix stabilized by intra-molecular i,i + 3 and i,i - 1 C=O⋯H-N hydrogen bonds. In the crystal, the oligomers are linked by N-H⋯O=C hydrogen bonds into chains along the a-axis direction. The chloro-form solvent mol-ecules are inter-calated between the folded chains via C-H⋯O=C inter-actions. PMID:26594404

  7. 32P Postlabelling analysis of urinary mutagens from smokers of black tobacco implicates 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) as a major DNA-damaging agent.

    Science.gov (United States)

    Peluso, M; Castegnaro, M; Malaveille, C; Friesen, M; Garren, L; Hautefeuille, A; Vineis, P; Kadlubar, F; Bartsch, H

    1991-04-01

    When mutagens extracted from the urine of two smokers of black tobacco were reacted with DNA in vitro in the presence of a metabolic activation system, several DNA adducts were detected by 32P-postlabelling analysis. Some of these adducts were also visible, but only faintly, on the autoradiogram for a non-smoker's urine. DNA adducts produced in vitro by 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline or 2-amino-1-methyl-6-phenylimidazo[3,5-b]pyridine could not account for the adduct pattern produced by the urinary mutagens. However, three or four 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-related DNA adducts were present among the five or six adducts observed for smokers in the autoradiograms of urinary mutagen-adducted nucleotides. Mutagenicity testing combined with HPLC fractionation of urinary extracts also supported the postlabelling data which implicates PhIP as a mutagen in the urine of smokers of black tobacco. PMID:2013135

  8. Allelopathic effects of essential oil from Eucalyptus grandis × E.urophylla on pathogenic fungi and pest insects

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    This study on the allelopathic effects and chemical components of the essential oil from Eucalyptus grandis × E.urophylla shows that the leaf oil emulsion of E.grandis × E.urophylla can inhibit the proliferation of pathogenic fungi Fusarium oxysporum,Pyriculerie grisea,Glorosprium musa rum and Phytophthora capsici.Pupation and feeding of the pest insects Spodopteralitura Fabricius and Helicoverpa armigera Hubner are shown to be affected with restraining effects which increase with the increasing levels of oil concentration.A GC/MS analysis of the leaf oil indicated that the main components,with a relative content of≥3%,were alloocimene (43.22%),α-pinene (13.63%),γ-terpinene (5.49%),(E)-3,7-dimethyl-2,6-octadien-1-ol (3.58%),β-fenchyl alcohol (4.58%),and 2-amino-3,5-dicyano-6-(4-methoxyphenoxy)-pyridine (3.67%).Terpenes played an important role in the inhibitory effects of E.grandis × E.urophylla essential oil on pathogenic fungi and pest insects.Poor biodiversity of eucalyptus plantations is a function of allelopathy.

  9. Organosilicon-Containing Thiazole Derivatives as Potential Lipoxygenase Inhibitors and Anti-Inflammatory Agents

    Directory of Open Access Journals (Sweden)

    Athina Geronikaki

    2007-07-01

    Full Text Available A number of trimethylsiloxyalkyl and trialkylsilylalkyl thiazole derivatives have been evaluated for their anti-inflammatory activity, lipoxygenase inhibiting properties, and cytotoxicity. The investigated compounds have been found to protect in vivo against carrageenin-induced edema, especially 3-(4-trimethylsiloxypiperidin-1-yl-N-(thiazol-2-yl-propionamide (21 and 2-amino-3-(γ-trimethylsilylpropylthiazolium iodide (22, which exhibited good anti-inflammatory activity: 57.2% CPE inhibition in dose of 0.2 mmol/kg for compound 21 and 55.0% in dose of 0.01 mmol/kg for compound 22. All the compounds tested inhibited soybean lipoxygenase activity. 2-(4-Trimethylsilyloxypiperidin-1-yl-N-[4-(p-methoxyphenyl-thiazol-2-yl]-acetamide (19 was the most potent displaying inhibition against lipoxygenase (ID50=0.01 mmol. It also possessed moderate cytotoxic effect (LC50=13 μg/mL, 3×10−8 mmol/mL concerning MG-22A cell lines.

  10. Highly Fluorescent Green Fluorescent Protein Chromophore Analogues Made by Decorating the Imidazolone Ring.

    Science.gov (United States)

    Gutiérrez, Sara; Martínez-López, David; Morón, María; Sucunza, David; Sampedro, Diego; Domingo, Alberto; Salgado, Antonio; Vaquero, Juan J

    2015-12-14

    The synthesis and photophysical behavior of an unexplored family of green fluorescent protein (GFP)-like chromophore analogues is reported. The compound (Z)-4-(4-hydroxybenzylidene)-1-propyl-2-(propylamino)-1H-imidazol-5(4 H)-one (p-HBDNI, 2 a) exhibits significantly enhanced fluorescence properties relative to the parent compound (Z)-5-(4-hydroxybenzylidene)-2,3-dimethyl-3,5-dihydro-4H-imidazol-4-one (p-HBDI, 1). p-HBDNI was considered as a model system and the photophysical properties of other novel 2-amino-3,5-dihydro-4H-imidazol-4-one derivatives were evaluated. Time-dependent DFT calculations were carried out to rationalize the results. The analogue AIDNI (2 c), in which the 4-hydroxybenzyl group of p-HBDNI was replaced by an azaindole group, showed improved photophysical properties and potential for cell staining. The uptake and intracellular distribution of 2 c in living cells was investigated by confocal microscopy imaging.

  11. Photosynthesis involvement in the mechanism of action of diphenyl ether herbicides.

    Science.gov (United States)

    Ensminger, M P; Hess, F D

    1985-05-01

    Photosynthesis is not required for the toxicity of diphenyl ether herbicides, nor are chloroplast thylakoids the primary site of diphenyl ether herbicide activity. Isolated spinach (Spinacia oleracea L.) chloroplast fragments produced malonyl dialdehyde, indicating lipid peroxidation, when paraquat (1,1'-dimethyl-4,4'-bipyridinium ion) or diuron [3-(3,4-dichlorophenyl)-1,1-dimethylurea] were added to the medium, but no malonyl dialdehyde was produced when chloroplast fragments were treated with the methyl ester of acifluorfen (methyl 5-[2-chloro-4-(trifluoromethyl)phenoxy]-2-nitrobenzoic acid), oxyfluorfen [2-chloro-1-(3-ethoxy-4-nitrophenoxy)-4-(trifluoromethyl)benzene], or MC15608 (methyl 5-[2-chloro-4-(trifluoromethyl)phenoxy]-2-chlorobenzoate). In most cases the toxicity of acifluorfen-methyl, oxyfluorfen, or MC15608 to the unicellular green alga Chlamydomonas eugametos (Moewus) did not decrease after simultaneous treatment with diuron. However, diuron significantly reduced cell death after paraquat treatment at all but the highest paraquat concentration tested (0.1 millimolar). These data indicate electron transport of photosynthesis is not serving the same function for diphenyl ether herbicides as for paraquat. Additional evidence for differential action of paraquat was obtained from the superoxide scavenger copper penicillamine (copper complex of 2-amino-3-mercapto-3-methylbutanoic acid). Copper penicillamine eliminated paraquat toxicity in cucumber (Cucumis sativus L.) cotyledons but did not reduce diphenyl ether herbicide toxicity. PMID:16664206

  12. Photosynthesis Involvement in the Mechanism of Action of Diphenyl Ether Herbicides 1

    Science.gov (United States)

    Ensminger, Michael P.; Hess, F. Dan

    1985-01-01

    Photosynthesis is not required for the toxicity of diphenyl ether herbicides, nor are chloroplast thylakoids the primary site of diphenyl ether herbicide activity. Isolated spinach (Spinacia oleracea L.) chloroplast fragments produced malonyl dialdehyde, indicating lipid peroxidation, when paraquat (1,1′-dimethyl-4,4′-bipyridinium ion) or diuron [3-(3,4-dichlorophenyl)-1,1-dimethylurea] were added to the medium, but no malonyl dialdehyde was produced when chloroplast fragments were treated with the methyl ester of acifluorfen (methyl 5-[2-chloro-4-(trifluoromethyl)phenoxy]-2-nitrobenzoic acid), oxyfluorfen [2-chloro-1-(3-ethoxy-4-nitrophenoxy)-4-(trifluoromethyl)benzene], or MC15608 (methyl 5-[2-chloro-4-(trifluoromethyl)phenoxy]-2-chlorobenzoate). In most cases the toxicity of acifluorfen-methyl, oxyfluorfen, or MC15608 to the unicellular green alga Chlamydomonas eugametos (Moewus) did not decrease after simultaneous treatment with diuron. However, diuron significantly reduced cell death after paraquat treatment at all but the highest paraquat concentration tested (0.1 millimolar). These data indicate electron transport of photosynthesis is not serving the same function for diphenyl ether herbicides as for paraquat. Additional evidence for differential action of paraquat was obtained from the superoxide scavenger copper penicillamine (copper complex of 2-amino-3-mercapto-3-methylbutanoic acid). Copper penicillamine eliminated paraquat toxicity in cucumber (Cucumis sativus L.) cotyledons but did not reduce diphenyl ether herbicide toxicity. PMID:16664206

  13. DPP IV inhibitor blocks mescaline-induced scratching and amphetamine-induced hyperactivity in mice.

    Science.gov (United States)

    Lautar, Susan L; Rojas, Camilo; Slusher, Barbara S; Wozniak, Krystyna M; Wu, Ying; Thomas, Ajit G; Waldon, Daniel; Li, William; Ferraris, Dana; Belyakov, Sergei

    2005-06-28

    Dipeptidyl peptidase IV (DPP IV) is a ubiquitous membrane-bound enzyme that cleaves the two N-terminal amino acids from peptides with a proline or alanine residue in the second position from the amino end. Potential substrates for DPP IV include several neuropeptides, suggesting a role for DPP IV in neurological processes. We have developed a potent DPP IV inhibitor (IC50 = 30 nM), 1-(2-amino-3-methyl-butyryl)-azetidine-2-carbonitrile (AMAC), which has shown efficacy in two established models of psychosis: mescaline-induced scratching and amphetamine-induced hyperactivity. In the mescaline-induced scratching model, AMAC treatment before mescaline administration reduced the number of scratching paroxysms by 68% (P < 0.01). The compound showed a dose-dependent effect, inhibiting significantly at 6, 20 and 60 mg/kg (37%, 39% and 68%, respectively). In the amphetamine-induced hyperactivity model, 50 and 60 mg/kg AMAC, given before injection of amphetamine, significantly reduced hyper-locomotion by 65% and 76%, respectively. Additionally, AMAC showed no significant activity in binding assays for 20 receptors thought to be involved in the pathology of schizophrenia, including dopamine, serotonin and glutamate. A structurally similar analog, 1-(2-dimethylamino-3-methyl-butyryl)-azetidine-2-carbonitrile (DAMAC), that does not inhibit DPP IV, was inactive in both models. Taken together, these data suggest that the antipsychotic effects of AMAC are the result of DPP IV inhibition.

  14. A fluorescent sensor based on methyldopa drug modified γ-Fe2O3 nanoparticles for ultrasensitive detection of calf thymus DNA

    Science.gov (United States)

    Shahabadi, Nahid; Maghsudi, Maryam; Kashanian, Soheila

    2016-03-01

    We reported the study of calf thymus DNA (ct-DNA) adsorption by the polymer of methyldopa (2-amino-3-(3,4-dihydroxyphenyl)-2-methyl acid, propanoic) (PMDP), magnetofluorescent PMDP-γ-Fe2O3 nanocrystal. The method is based on the extraordinarily high quenching efficiency of ct-DNA and the specific interaction between ct-DNA and PMDP-γ-Fe2O3 via guanine base and metal coordination, probably. It was found that the designed magnetic nanoparticles can adsorb ct-DNA in nM levels in the presence of NaCl and KCl. In acetate and phosphate buffers DNA were adsorbed completely. Also, we found that pH plays an important role in DNA adsorption onto PMDP-γ-Fe2O3 nanocrystal. PMDP-γ-Fe2O3 nanocrystal is highly hydrophilic and DNA desorption wasn't observed. We believe this study will further stimulate the application of PMDP-γ-Fe2O3 nanocrystal in bioanalytical chemistry and nanotechnology. PMDP-γ-Fe2O3 nanocrystal possesses the ability to interact with ct-DNA via a partial intercalative binding mechanism, as demonstrated by fluorescence displacement experiments and a significant red shift (ca, 10 nm) in UV-vis spectra.

  15. [Bromhexine residues in calves, pigs, and in the milk of cows].

    Science.gov (United States)

    Eichler, V D; Kreuzer, H

    1975-04-01

    After several oral applications of N-cyclohexyl-N-methyl-(2-amino-3,5-dibromobenzyl)-aminehydrochloride (bromhexine, Bisolvon-R) to various calves and pigs the residue behaviour was examined. In animals slaughtered immediately after the final application significant amounts of Bisolvon were found. The substance showed a greater affinity to liver and fat tissue whilst, in general, in the muscle tissue, the lungs and kidneys only very small amounts were traceable. In the liver and lungs 3 different metabolites appeared in small quantities. They were partly in conjugated and partly in free form. Within 2 days the amounts greatly decreased and after 7 days at the latest, no residues were traceable; only in the fat of both animal species and in the kidneys of the calves were small quantities of Bisolvon still to be found. Excretion by the milk following oral and parenteral application was also studied. Only traces of Bisolvon were found, which rapidly decreased. Results of the studies show that, neither at a later date of slaughtering nor immediately after the final application, the residues in the animal tissues and in the milk examined present a danger to the health of the human consumer.

  16. Simultaneous determination of nine heterocyclic aromatic amines in mutton products by solid phase extraction-high performance liquid chromatography%固相萃取-高效液相色谱法同时测定羊肉制品中9种杂环胺

    Institute of Scientific and Technical Information of China (English)

    郭海涛; 潘晗; 王振宇; 陈丽; 张德权

    2012-01-01

    建立了同时测定羊肉制品中9种杂环胺的固相萃取-高效液相色谱(SPE-HPLC)分析方法.样品经2 mol/LNaOH超声提取、80 mL二氯甲烷液-液萃取,利用阳离子交换柱(MCX柱)净化和富集后进行HPLC分析.采用反相C18色谱柱,以乙腈和0.01 mol/L磷酸溶液(用三乙胺调整pH3.6)为流动相对杂环胺进行梯度洗脱,使用二极管阵列检测器(DAD)分别在228 nm(2-氨基-9H-吡啶并[2,3-b]吲哚(AaC)、2-氨基-3-甲基-9H-吡啶并[2,3-b]吲哚( MeAaC))、253 nm(2-氨基-3-甲基咪唑并[4,5-f]喹啉(IQ)、1-甲基-9H-吡啶并[3,4-b]吲哚(Harman)、2-9H-吡啶并[3,4-b]吲哚(Norharman))、263 nm(2-氨基-3,8-二甲基咪唑并[4,5-f]喹喔啉(MeIQx)、2-氨基-3,4,8-三甲基咪唑并[4,5-f]喹喔啉(4,8-DiMeIQx)、3-氨基-1-甲基-5H-吡啶并[4,3-b]吲哚(Trp-p-2))、321 nm(2-氨基-1-甲基-6-苯基咪唑并[4,5-b]吡啶(PhIP))处进行检测.实验结果表明,9种杂环胺分离效果良好,回收率为50.27%~94.77%(n=6),相对标准偏差为0.08% ~4.42%;通过全波长扫描,确定检出限(以信噪比(S/N)=3计)为1.6~41.0 μg/L.该方法操作简单,结果准确,重现性好,可用于同时检测羊肉制品中9种杂环胺的含量.%A method was established for the simultaneous determination of nine heterocyclic aromatic amines (HAAs) in mutton products by solid phase extraction-high performance liquid chromatography (SPE-HPLC). As a result, the sample was prepared by ultrasound in 2 mol/L NaOH, and dichloromethane was selected as the extraction solvent. The extract was purified and concentrated with an MCX SPE column. The chromatographic separation was achieved on a reverse-phase C18 column by gradient elution using 0. 01 mol/L phosphoric acid (adjusted to pH 3. 6 by triethylamine) and acetonitrile, detected with a diode array detector (DAD) at 228 nm for 2-amino-9H-pyrido[2,3-6]indole (AaC) and 2-amino-3-methyl-9H-pyrido[2,3-6]indole (MeAaC); 253 nm for 2-amino-3-methylimidazo[4

  17. Lymphoma induction by heterocyclic amines in Eu-pim-1 transgenic mice

    DEFF Research Database (Denmark)

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

    1997-01-01

    were fed standard diet Altromin 1314 supplemented either with 0.03% 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) for 7 months or with 0.03% 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) for 6 months. PhIP and IQ are heterocyclic amines formed during cooking of meat and fish and are mutagenic...... to bacteria and cultured mammalian cells. PhIP is a potent mouse lymphomagen, while IQ is a liver, lung and forestomach carcinogen in mice. We found that transgenic E mu-pim-1 mice are highly susceptible to PhIP induced lymphomagenesis but do not respond to IQ treatment. PhIP feeding of E mu-pim-1 mice...... not only increased the total number of T-cell lymphomas but also decreased the latency time compared to either transgenic or wild-type controls. The effect was most pronounced in the treated female E mu-pim-1 mice, which showed a higher incidence of PhIP induced T-cell lymphomas than transgenic males...

  18. 固相萃取-高效液相色谱法同时测定传统禽肉制品中的9种杂环胺类化合物%Simultaneous determination of 9 heterocyclic aromatic amines in poultry products by solid-phase extraction-high performance liquid chromatography

    Institute of Scientific and Technical Information of China (English)

    邵斌; 彭增起; 杨洪生; 吴光红; 姚瑶; 万可慧

    2011-01-01

    A method was developed for the simultaneous determination of 9 heterocyclic aromatic amines (HAAs) including 2-amino-3-methylimidazo[4,5-f] quinoline (IQ), 2-amino-3,4-dimethylimidazo[ 4,5-f] quinoline ( MeIQ), 2-amino-3 , 8-dimethylimidazo [ 4, 5-f] quinoxaline (MelQx), 2-amino-3, 4, 8-trimethyl-imidazo [4,5-f] quinoxaline (4, 8-DiMeIQx) , 2-amino-l-methyl-6-phenylimidazo[4,5-b)]pyridine (PhIP), 3-amino-l-methyl-5ff-pyrido [4, 3-6 ] indole (Trp-p-2), 3-amino-l,4-dimethyl-5H-pyrido[4,3-6] indole (Trp-p-1), 9H-pyrido[ 3 ,4-6] indole (Norharman), 1-methyl-9H-pyrido[3,4-b] indole (Harman)) in poultry products using solid-phase extraction-high performance liquid chromatography (SPE-HPLC). The performance of 3 different organic extraction solutions, 2 solid phase extraction (SPE) procedures, three different reversed-phase columns and five different mobile phases were tested for optimizing separation conditions of the 9 HAAs from poultry products. In the end, ethyl acetate was selected as the extraction solution, and the extract was purified with propylsulfonic acid silica ( PRS) and C,, SPE columns. The analysis was performed on a TSK-gel ODS-80TM column using a gradientelution with the mobile phases of 0. 05 mol/L aqueous acetic acid-ammonium acetate buffer (pH 3.4) and acetonitrile. The results showed that the average recoveries (n =6) of the 9 HAAs spiked in meat samples at 3 levels ranged from 60. 47% to 90. 55% with the relative standard deviations ( RSDs) between 0.49% and 9. 74%, and the limits of detection ( LODs, S/N = 3) were in the range of 0. 1 -3.6 μg/kg. The method is simple, rapid, accurate and sensitive enough for the analysis of HAAs in poultry products.%建立了固相萃取-高效液相色谱同时测定传统禽肉制品中9种杂环胺类化合物(HAAs)(包括2-氨基-3-甲基咪唑并[4,5-f]喹啉、2-氨基-3,4-二甲基咪唑并[4,5-f]喹啉、2-氨基-3,8-二甲基咪唑并[4,5-f]喹喔啉、2-氨基-3,4,8-三甲基咪唑并[4,5-f]喹喔啉、2

  19. Sucrose and IQ induced mutations in rat colon by independent

    DEFF Research Database (Denmark)

    Hansen, Max; Hald, M. T.; Autrup, H.;

    2004-01-01

    Sucrose-rich diets have repeatedly been observed to have co-carcinogenic actions in colon and liver of rats and to increase the number of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) induced aberrant crypt foci in rat colon. To investigate a possible interaction between sucrose and IQ...... on the genotoxicity in rat liver and colon, we gave Big Blue rats(TM) a diet containing sucrose (0%, 3.45% or 13.4% w/w) and/or IQ (70 ppm) for a period of 3 weeks. Sucrose and IQ increased the mutation frequency in the colon. The effect of combined treatments with IQ and sucrose on the mutation frequencies...... was additive indicating that sucrose and IQ act independently. This was supported by the mutation spectra where sucrose expands the background mutations in the colon, whereas IQ, in other studies, more specifically has induced G:C --> T:A transversions. In the liver IQ increased the mutation frequency, whereas...

  20. Dietary low-dose sucrose modulation of IQ-induced genotoxicity in the colon and liver of Big Blue((TM)) rats

    DEFF Research Database (Denmark)

    Moller, P.; Hansen, Max; Autrup, H.;

    2003-01-01

    Earlier studies have indicated that sucrose increases 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)-induced aberrant crypt foci in the colon. In this study, we investigated the role of sucrose in IQ-induced genotoxicity of the colon mucosa and liver. Big Blue(TM) rats were fed with IQ (20 ppm...... in feed) and/or sucrose (3.45 or 6.85 wt.% in feed) for 3 weeks. IQ increased DNA strand breaks in the colon, whereas the mutation frequency was increased in the liver. The level of IQ-induced DNA adducts was elevated in both colon mucosa cells and liver. In the liver, high sucrose intake increased...... the level of DNA adducts above that of IQ and low sucrose intake. Oxidative DNA damage detected in terms of 7-hydro-8-oxo-2'-deoxyguanosine by HPLC-EC, or endonuclease HI or formamidopyrimidine DNA glycosylase sensitive sites were unaltered in the colon and liver. Expression of ERCC1 and OGG1 mRNA levels...

  1. Substrate-Tuned Catalysis of the Radical S-Adenosyl-L-Methionine Enzyme NosL Involved in Nosiheptide Biosynthesis.

    Science.gov (United States)

    Ji, Xinjian; Li, Yongzhen; Ding, Wei; Zhang, Qi

    2015-07-27

    NosL is a radical S-adenosyl-L-methionine (SAM) enzyme that converts L-Trp to 3-methyl-2-indolic acid, a key intermediate in the biosynthesis of a thiopeptide antibiotic nosiheptide. In this work we investigated NosL catalysis by using a series of Trp analogues as the molecular probes. Using a benzofuran substrate 2-amino-3-(benzofuran-3-yl)propanoic acid (ABPA), we clearly demonstrated that the 5'-deoxyadenosyl (dAdo) radical-mediated hydrogen abstraction in NosL catalysis is not from the indole nitrogen but likely from the amino group of L-Trp. Unexpectedly, the major product of ABPA is a decarboxylated compound, indicating that NosL was transformed to a novel decarboxylase by an unnatural substrate. Furthermore, we showed that, for the first time to our knowledge, the dAdo radical-mediated hydrogen abstraction can occur from an alcohol hydroxy group. Our study demonstrates the intriguing promiscuity of NosL catalysis and highlights the potential of engineering radical SAM enzymes for novel activities.

  2. Metabotropic glutamate receptors are required for the induction of long-term potentiation

    Science.gov (United States)

    Zheng, F.; Gallagher, J. P.

    1992-01-01

    Recent observations have led to the suggestion that the metabotropic glutamate receptor may play a role in the induction or maintenance of long-term potentiation (LTP). However, experimental evidence supporting a role for this receptor in the induction of LTP is still inconclusive and controversial. Here we report that, in rat dorsolateral septal nucleus (DLSN) neurons, which have the highest density of metabotropic receptors and show functional responses, the induction of LTP is not blocked by the NMDA receptor antagonist 2-amino-5-phosphonovalerate, but is blocked by two putative metabotropic glutamate receptor antagonists, L-2-amino-3-phosphonopropionic acid and L-2-amino-4-phosphonobutyrate. Furthermore, superfusion of (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid, a selective metabotropic glutamate agonist, resulted in a long-lasting potentiation of synaptic transmission similar to that induced by tetanic stimuli. Our results demonstrated that activation of postsynaptic metabotropic receptors is both necessary and sufficient for the induction of LTP in the DLSN, and we suggest that such a mechanism may be important at other CNS synapses.

  3. Indazole, Pyrazole, and Oxazole Derivatives Targeting Nitric Oxide Synthases and Carbonic Anhydrases.

    Science.gov (United States)

    Maccallini, Cristina; Di Matteo, Mauro; Vullo, Daniela; Ammazzalorso, Alessandra; Carradori, Simone; De Filippis, Barbara; Fantacuzzi, Marialuigia; Giampietro, Letizia; Pandolfi, Assunta; Supuran, Claudiu T; Amoroso, Rosa

    2016-08-19

    Nitric oxide (NO) is an essential endogenous mediator with a physiological role in the central nervous system as neurotransmitter and neuromodulator. A growing number of studies have demonstrated that abnormal nitrergic signaling is a crucial event in the development of neurodegeneration. In particular, the uncontrolled production of NO by neuronal nitric oxide synthase (nNOS) is observed in several neurodegenerative diseases. Moreover, it is well recognized that specific isoforms of human carbonic anhydrase (hCA) physiologically modulate crucial pathways of signal processing and that low expression of CA affects cognition, leading to mental retardation, Alzheimer's disease, and aging-related cognitive impairments. In light of this, dual agents that are able to target both NOS (inhibition) and CA (activation) could be useful drug candidates for the treatment of Alzheimer's disease, aging, and other neurodegenerative diseases. In the present work, we show the design, synthesis, and in vitro biological evaluation of new nitrogen-based heterocyclic compounds. Among the tested molecules, 2-amino-3-(4-hydroxyphenyl)-N-(1H-indazol-5-yl)propanamide hydrochloride (10 b) was revealed to be a potent dual agent, able to act as a selective nNOS inhibitor and activator of the hCA I isoform. PMID:27377568

  4. Concise Asymmetric Synthesis and Pharmacological Characterization of All Stereoisomers of Glutamate Transporter Inhibitor TFB-TBOA and Synthesis of EAAT Photoaffinity Probes.

    Science.gov (United States)

    Leuenberger, Michele; Ritler, Andreas; Simonin, Alexandre; Hediger, Matthias A; Lochner, Martin

    2016-05-18

    Glutamate is the major excitatory neurotransmitter in the mammalian brain. Its rapid clearance after the release into the synaptic cleft is vital in order to avoid toxic effects and is ensured by several transmembrane transport proteins, so-called excitatory amino acid transporters (EAATs). Impairment of glutamate removal has been linked to several neurodegenerative diseases and EAATs have therefore received increased attention as therapeutic targets. O-Benzylated l-threo-β-hydroxyaspartate derivatives have been developed previously as highly potent inhibitors of EAATs with TFB-TBOA ((2S,3S)-2-amino-3-((3-(4-(trifluoromethyl)benzamido)benzyl)oxy)succinic acid) standing out as low-nanomolar inhibitor. We report the stereoselective synthesis of all four stereoisomers of TFB-TBOA in less than a fifth of synthetic steps than the published route. For the first time, the inhibitory activity and isoform selectivity of these TFB-TBOA enantio- and diastereomers were assessed on human glutamate transporters EAAT1-3. Furthermore, we synthesized potent photoaffinity probes based on TFB-TBOA using our novel synthetic strategy. PMID:26918289

  5. Synthesis, Crystal Structure and Cytotoxicity Evaluation of 2-Phenoxy-4H-spiro{naphtho[2,3-e][1,4,2] oxazaphosphinane-5,10-dione,1 ′-cyclohexane} 2-Oxide

    Institute of Scientific and Technical Information of China (English)

    WANG Bin; WANG Jie; MIAO Zhi-Wei; CHEN Ru-Yu

    2006-01-01

    2-Phenoxy-4H-spiro { naphtho[2,3-e] [ 1 ,4,2]oxazaphosphinane-5,10-dione, 1 ′-cyclohexane}2-oxide (C22H20NO5P) was synthesized by the Mannich-type reaction of 2-amino-3-hydroxy-1,4-naphthoquinone with phenyl phosphorodichloridite and cyclohexanone, and structurally characterized by single-crystal X-ray diffraction analysis. It crystallizes in monoclinic, space group P21/n with a = 7.9133(11), b = 13.0269(18), c = 19.091(3) (A), β = 101.906(2)°, V = 1925.6(5)(A)3, Z = 4, Mr = 409.36, Dc = 1.412 g/cm3, F(000) = 856,μ = 0.178 mm-1, S = 1.015, the final R =0.0381 and wR = 0.0906 for 2718 observed reflections with I > 2σ(Ⅰ) and 262 variable parameters.This compound may be used as DNA-intercalator. Its cytotoxic activities were also tested in vitro on four human tumor cell lines.

  6. Synthesis, spectroscopic characterization, electrochemical behaviour, reactivity and antibacterial activity of some transition metal complexes with 2-( N-salicylideneamino)-3-carboxyethyl-4,5-dimethylthiophene

    Science.gov (United States)

    Daniel, Varughese P.; Murukan, B.; Kumari, B. Sindhu; Mohanan, K.

    2008-07-01

    Mn(II), Fe(II), Co(II), Ni(II), Cu(II) and Zn(II) complexes with a potentially tridentate Schiff base, formed by condensation of 2-amino-3-carboxyethyl-4,5-dimethylthiophene with salicylaldehyde were synthesized and characterized on the basis of elemental analyses, molar conductance values, magnetic susceptibility measurements, UV-vis, IR, EPR and NMR spectral data, wherever possible and applicable. Spectral studies reveal that the free ligand exists in a bifunctionally hydrogen bonded manner and coordinates to the metal ion in a tridentate fashion through the deprotonated phenolate oxygen, azomethine nitrogen and ester carbonyl group. On the basis of electronic spectral data and magnetic susceptibility measurements, suitable geometry has been proposed for each complex. The EPR spectral data of the Cu(II) complex showed that the metal-ligand bonds have considerable covalent character. The Ni(II) complex has undergone facile transesterification reaction when refluxed in methanol for a lengthy period. X-ray diffraction studies of Cu(II) complex showed that the complex has an orthorhombic crystal lattice. In view of the biological activity of thiophene derivatives, the ligand and the complexes were subjected to antibacterial screening. It has been observed that the antibacterial activity of the ligand increased on chelation with metal ion.

  7. Synthesis, spectroscopic characterization and crystallographic behavior of a biologically relevant novel indole-fused heterocyclic compound - Experimental and theoretical (DFT) studies

    Science.gov (United States)

    Sharma, Sakshi; Brahmachari, Goutam; Banerjee, Bubun; Nurjamal, Khondekar; Kumar, Abhishek; Srivastava, Ambrish Kumar; Misra, Neeraj; Pandey, Sarvesh Kumar; Rajnikant; Gupta, Vivek K.

    2016-08-01

    The present communication deals with the eco-friendly synthesis, spectral properties and X-ray crystal structure of an indole derivative - Ethyl 2'-amino-3'-cyano-6'-methyl-5-nitro-2-oxospiro [indoline-3,4'-pyran]-5'-carboxylate. The title compound was synthesized in 87% yield. The crystal structure of the molecule is stabilized by intermolecular Nsbnd H … N, Nsbnd H … O and Csbnd H … π interactions. The molecule is organized in the crystal lattice forming sheet like structure. To interpret the experimental data, ab initio computations of the vibrational frequencies were carried out using the Gaussian 09 program followed by the full optimizations done using Density Functional Theory (DFT) at B3LYP/6-31 + G(d,p) level. The combined use of experiments and computations allowed a firm assignment of the majority of observed bands for the compound. The calculated highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) with frontier orbital gap were presented. The electronic and charge transfer properties have been explained on the basis of highest occupied molecular orbitals (HOMOs), lowest unoccupied molecular orbitals (LUMOs) and density of states (DOS). From the optimized geometry of the molecule, molecular electrostatic potential (MEP) distribution, frontier molecular orbitals (FMOs) of the title compound have been calculated in the ground state theoretically. The theoretical results showed good agreement with the experimental values. First hyperpolarizability values have been calculated to describe the nonlinear optical (NLO) property of the synthesized compound.

  8. Modulating the Cyclic Guanosine Monophosphate Substrate Selectivity of the Phosphodiesterase 3 Inhibitors by Pyridine, Pyrido[2,3-d]pyrimidine Derivatives and Their Effects upon the Growth of HT-29 Cancer Cell Line

    Science.gov (United States)

    Abadi, Ashraf Hassan; Hany, Marwa Saeed; Elsharif, Shimaa Awadain; Eissa, Amal Abdel Haleem; Gary, Bernard DeWayne; Tinsley, Heather Nicole; Piazza, Gary Anthony

    2016-01-01

    Analogues with the scaffolds of 3-cyano-4-alkoxyphenyl-6-bromoaryl-2-pyridone and 2-amino-3-cyano-4-alkoxyphenyl-6-bromoarylpyridine were synthesized. Cyclization of the 2-amino derivatives with formic acid and formamide gave the corresponding pyrido[2,3-d]pyrimidin-4(3H)-one and the pyrido[2,3-d]pyrimidin-4-amine derivatives, respectively. Active phosphodiesterase 3 (PDE3) inhibitors were identified from each of the four aforementioned scaffolds. This is the first report that pyrido[2,3-d]pyrimidin-4(3H)-one and pyrido[2,3-d]pyrimidin-4-amine derivatives can inhibit PDE3. The analogues with the pyridone and pyrido[2,3-d]pyrimidin-4(3H)-one scaffolds inhibited both cAMP and cyclic guanosine monophosphate (cGMP) hydrolysis by PDE3, while the amine containing scaffolds were more selective for cGMP hydrolysis. This observation may set the base for substrate-selective pharmacological modulation of this important class of drug targets and with less side effects, particularly tachcardia. The dual inhibitors of PDE3 were more potent inhibitor towards the growth of HT-29 cancer cell lines. PMID:23546000

  9. Assessment of genotoxicity and antigenotoxicity of an aqueous extract of Cleistocalyx nervosum var. paniala in in vitro and in vivo models.

    Science.gov (United States)

    Charoensin, Suphachai; Taya, Sirinya; Wongpornchai, Sugunya; Wongpoomchai, Rawiwan

    2012-12-01

    Cleistocalyx nervosum var. paniala, an edible fruit found in Northern Thailand, contains high amounts of phenolic compounds with in vitro antioxidant activity. The aqueous extract of the ripe fruit was evaluated for its safety and beneficial effects using genotoxicity and toxicity tests. The C. nervosum extract was not only non-mutagenic in Salmonella typhimurium strains TA98 and TA100 in the presence and absence of metabolic activation, but exhibited also moderate antimutagenic effects against aflatoxin B1 and 2-amino-3,4-dimethylimidazo[4,5-f]quinoline-induced mutagenesis. Electrospray ionization-mass spectrometric analysis revealed the major anthocyanins, which included cyanidin-3,5-diglucoside, cyanidin-3-glucoside and cyanidin-5-glucoside. The administration of C. nervosum at concentration of 5,000 mg/kg bw did not induce acute toxicity in rats. A liver micronucleus test was performed to detect clastogenicity and anticlastogenicity. The extract in the dose of 1,000 mg/kg did not cause micronucleus formation in the liver of rats. Furthermore, in rats administered 100-1,000 mg/kg of the extract, no anticlastogenic effect against diethylnitrosamine-induced hepatic micronucleus formation was observed. These studies provide data concerning the safety and antimutagenic potency of an aqueous extract of C. nervosum fruit.

  10. Root exudate-induced alterations in Bacillus cereus cell wall contribute to root colonization and plant growth promotion.

    Directory of Open Access Journals (Sweden)

    Swarnalee Dutta

    Full Text Available The outcome of an interaction between plant growth promoting rhizobacteria and plants may depend on the chemical composition of root exudates (REs. We report the colonization of tobacco, and not groundnut, roots by a non-rhizospheric Bacillus cereus (MTCC 430. There was a differential alteration in the cell wall components of B. cereus in response to the REs from tobacco and groundnut. Attenuated total reflectance infrared spectroscopy revealed a split in amide I region of B. cereus cells exposed to tobacco-root exudates (TRE, compared to those exposed to groundnut-root exudates (GRE. In addition, changes in exopolysaccharides and lipid-packing were observed in B. cereus grown in TRE-amended minimal media that were not detectable in GRE-amended media. Cell-wall proteome analyses revealed upregulation of oxidative stress-related alkyl hydroperoxide reductase, and DNA-protecting protein chain (Dlp-2, in response to GRE and TRE, respectively. Metabolism-related enzymes like 2-amino-3-ketobutyrate coenzyme A ligase and 2-methylcitrate dehydratase and a 60 kDa chaperonin were up-regulated in response to TRE and GRE. In response to B. cereus, the plant roots altered their exudate-chemodiversity with respect to carbohydrates, organic acids, alkanes, and polyols. TRE-induced changes in surface components of B. cereus may contribute to successful root colonization and subsequent plant growth promotion.

  11. Titanium-catalyzed multicomponent couplings: efficient one-pot syntheses of nitrogen heterocycles.

    Science.gov (United States)

    Odom, Aaron L; McDaniel, Tanner J

    2015-11-17

    Nitrogen-based heterocycles are important frameworks for pharmaceuticals, natural products, organic dyes for solar cells, and many other applications. Catalysis for the formation of heterocyclic scaffolds, like many C-C and C-N bond-forming reactions, has focused on the use of rare, late transition metals like palladium and gold. Our group is interested in the use of Earth-abundant catalysts based on titanium to generate heterocycles using multicomponent coupling strategies, often in one-pot reactions. To be of maximal utility, the catalysts need to be easily prepared from inexpensive reagents, and that has been one guiding principle in the research. For this purpose, a series of easily prepared pyrrole-based ligands has been developed. Titanium imido complexes are known to catalyze the hydroamination of alkynes, and this reaction has been used to advantage in the production of α,β-unsaturated imines from 1,3-enynes and pyrroles from 1,4-diynes. Likewise, catalyst design can be used to find complexes applicable to hydrohydrazination, coupling of a hydrazine and alkyne, which is a method for the production of hydrazones. Many of the hydrazones synthesized are converted to indoles through Fischer cyclization by addition of a Lewis acid. However, more complex products are available in a single catalytic cycle through coupling of isonitriles, primary amines, and alkynes to give tautomers of 1,3-diimines, iminoamination (IA). The products of IA are useful intermediates for the one-pot synthesis of pyrazoles, pyrimidines, isoxazoles, quinolines, and 2-amino-3-cyanopyridines. The regioselectivity of the reactions is elucidated in some detail for some of these heterocycles. The 2-amino-3-cyanopyridines are synthesized through isolable intermediates, 1,2-dihydro-2-iminopyridines, which undergo Dimroth rearrangement driven by aromatization of the pyridine ring; the proposed mechanism of the reaction is discussed. The IA-based heterocyclic syntheses can be accomplished

  12. Cell-specific modulation of surfactant proteins by ambroxol treatment.

    Science.gov (United States)

    Seifart, Carola; Clostermann, Ursula; Seifart, Ulf; Müller, Bernd; Vogelmeier, Claus; von Wichert, Peter; Fehrenbach, Heinz

    2005-02-15

    Ambroxol [trans-4-(2-amino-3,5-dibromobenzylamino)-cyclohexanole hydrochloride], a mucolytic agent, was postulated to provide surfactant stimulatory properties and was previously used to prevent surfactant deficiency. Currently, the underlying mechanisms are not exactly clear. Because surfactant homeostasis is regulated by surfactant-specific proteins (SP), we analyzed protein amount and mRNA expression in whole lung tissue, isolated type II pneumocytes and bronchoalveolar lavage of Sprague-Dawley rats treated with ambroxol i.p. (75 mg/kg body weight, twice a day [every 12 h]). The methods used included competitive polymerase chain reaction (RT-PCR), Northern blotting, Western immunoblotting, and immunohistochemistry. In isolated type II pneumocytes of ambroxol-treated animals, SP-C protein and mRNA content were increased, whereas SP-A, -B and -D protein, mRNA, and immunoreactivity remained unaffected. However, ambroxol treatment resulted in a significant increase of SP-B and in a decrease of SP-D in whole lung tissue with enhanced immunostaining for SP-B in Clara Cells. SP-A and SP-D were significantly decreased in BAL fluid of ambroxol-treated animals. The data suggest that surfactant protein expression is modulated in a cell-specific manner by ambroxol, as type II pneumocytes exhibited an increase in SP-C, whereas Clara cells exhibited an increase in the immunoreactivity for SP-B accounting for the increased SP-B content of whole lung tissue. The results indicate that ambroxol may exert its positive effects, observed in the treatment of diseases related to surfactant deficiency, via modulation of surfactant protein expression.

  13. Identification of Kynoxazine, a Novel Fluorescent Product of the Reaction between 3-Hydroxykynurenine and Erythrulose in the Human Lens, and Its Role in Protein Modification.

    Science.gov (United States)

    Rakete, Stefan; Nagaraj, Ram H

    2016-04-29

    Kynurenine pathway metabolites and ascorbate degradation products are present in human lenses. In this study, we showed that erythrulose, a major ascorbate degradation product, reacts spontaneously with 3-hydroxykynurenine to form a fluorescent product. Structural characterization of the product revealed it to be 2-amino-4-(2-hydroxy-3-(2-hydroxyethyl)-2H-benzo[b][1,4]oxazin-5-yl)-4-oxobutanoic acid, which we named kynoxazine. Unlike 3-hydroxykynurenine, 3-hydroxykynurenine glucoside and kynurenine were unable to form a kynoxazine-like compound, which suggested that the aminophenol moiety in 3-hydroxykynurenine is essential for the formation of kynoxazine. This reasoning was confirmed using a model compound, 1-(2-amino-3-hydroxyphenyl)ethan-1-one, which is an aminophenol lacking the amino acid moiety of 3-hydroxykynurenine. Ultra-performance liquid chromatography-tandem mass spectrometry analyses showed that kynoxazine is present in the human lens at levels ranging from 0 to 64 pmol/mg lens. Kynoxazine as well as erythrulose degraded under physiological conditions to generate 3-deoxythreosone, which modified and cross-linked proteins through the formation of an arginine adduct, 3-deoxythreosone-derived hydroimidazolone, and a lysine-arginine cross-linking adduct, 3-deoxythreosone-derived hydroimidazolimine cross-link. Ultra-performance liquid chromatography-tandem mass spectrometry quantification showed that 32-169 pmol/mg protein of 3-deoxythreosone-derived hydroimidazolone and 1.1-11.2 pmol/mg protein of 3-deoxythreosone-derived hydroimidazolimine cross-link occurred in aging lenses. Taken together, these results demonstrate a novel biochemical mechanism by which ascorbate oxidation and the kynurenine pathway intertwine, which could promote protein modification and cross-linking in aging human lenses. PMID:26941078

  14. Pig kidney legumain: an asparaginyl endopeptidase with restricted specificity.

    Science.gov (United States)

    Dando, P M; Fortunato, M; Smith, L; Knight, C G; McKendrick, J E; Barrett, A J

    1999-01-01

    Legumain was recently discovered as a lysosomal endopeptidase in mammals [Chen, Dando, Rawlings, Brown, Young, Stevens, Hewitt, Watts and Barrett (1997) J. Biol. Chem. 272, 8090-8098], having been known previously only from plants and invertebrates. It has been shown to play a key role in processing of the C fragment of tetanus toxin for presentation by the MHC class-II system [Manoury, Hewitt, Morrice, Dando, Barrett and Watts (1998) Nature (London) 396, 695-699]. We examine here the specificity of the enzyme from pig kidney by use of protein, oligopeptide and synthetic arylamide substrates, all determinations being made at pH 5.8. In proteins, only about one in ten of the asparaginyl bonds were hydrolysed, and these were mostly predicted to be located at turns on the protein surface. Bonds that were not cleaved in tetanus toxin were cleaved when presented in oligopeptides, sometimes faster than an equivalent oligopeptide based on a bond that was cleaved in the protein. Legumain cleaved the bait region of rat alpha1-macroglobulin and was 'trapped' by the macroglobulin, as most other endopeptidases are, but did not interact with human alpha2-macroglobulin, which contains no asparagine residue in its bait region. Glycosylation of asparagine totally prevented hydrolysis by legumain. Specificity for arylamide substrates was evaluated with reference to benzyloxycarbonyl-Ala-Ala-Asn-aminomethylcoumarin, and the preference for the P3-position amino acid was Ala>Tyr(tertiary butyl)>Val>Pro>Phe=Tyr>Leu=Gly. There was no hydrolysis of substrate analogues containing mono- or di-N-methylasparagines, l-2-amino-3-ureidopropionic acid or citrulline in the P1 position. We conclude that mammalian legumain appears to be totally restricted to the hydrolysis of asparaginyl bonds in substrates of all kinds. There seem to be no strong preferences for particular amino acids in other subsites, and yet there are still unidentified factors that prevent hydrolysis of many asparaginyl bonds

  15. 1H-MAS-NMR Chemical Shifts in Hydrogen-Bonded Complexes of Chlorophenols (Pentachlorophenol, 2,4,6-Trichlorophenol, 2,6-Dichlorophenol, 3,5-Dichlorophenol, and p-Chlorophenol and Amine, and H/D Isotope Effects on 1H-MAS-NMR Spectra

    Directory of Open Access Journals (Sweden)

    Hisashi Honda

    2013-04-01

    Full Text Available Chemical shifts (CS of the 1H nucleus in N···H···O type hydrogen bonds (H-bond were observed in some complexes between chlorophenols [pentachlorophenol (PCP, 2,4,6-tricholorophenol (TCP, 2,6-dichlorophenol (26DCP, 3,5-dichlorophenol (35DCP, and p-chlorophenol (pCP] and nitrogen-base (N-Base by solid-state high-resolution 1H-NMR with the magic-angle-spinning (MAS method. Employing N-Bases with a wide range of pKa values (0.65–10.75, 1H-MAS-NMR CS values of bridging H atoms in H-bonds were obtained as a function of the N-Base’s pKa. The result showed that the CS values were increased with increasing pKa values in a range of DpKa 2: The maximum CS values was recorded in the PCP (pKa = 5.26–4-methylpyridine (6.03, TCP (6.59–imidazole (6.99, 26DCP (7.02–2-amino-4-methylpyridine (7.38, 35DCP (8.04–4-dimethylaminopyridine (9.61, and pCP (9.47–4-dimethylaminopyridine (9.61 complexes. The largest CS value of 18.6 ppm was recorded in TCP–imidazole crystals. In addition, H/D isotope effects on 1H-MAS-NMR spectra were observed in PCP–2-amino-3-methylpyridine. Based on the results of CS simulation using a B3LYP/6-311+G** function, it can be explained that a little changes of the N–H length in H-bond contribute to the H/D isotope shift of the 1H-MAS-NMR peaks.

  16. (90) Y/(177) Lu-labelled Cetuximab immunoconjugates: radiochemistry optimization to clinical dose formulation.

    Science.gov (United States)

    Chakravarty, Rubel; Chakraborty, Sudipta; Sarma, Haladhar Dev; Nair, K V Vimalnath; Rajeswari, Ardhi; Dash, Ashutosh

    2016-07-01

    Radiolabelled monoclonal antibodies (mAbs) are increasingly being utilized in cancer theranostics, which is a significant move toward tailored treatment for individual patients. Cetuximab is a recombinant, human-mouse chimeric IgG1 mAb that binds to the epidermal growth factor receptor with high affinity. We have optimized a protocol for formulation of clinically relevant doses (~2.22 GBq) of (90) Y-labelled Cetuximab and (177) Lu-labelled Cetuximab by conjugation of the mAb with a suitable bifunctional chelator, N-[(R)-2-amino-3-(paraisothiocyanato-phenyl)propyl]-trans-(S,S)-cyclohexane-1,2-diamine-N,N,N',N″,N″-pentaacetic acid (CHX-A″-DTPA). The radioimmunoconjugates demonstrated reasonably high specific activity (1.26 ± 0.27 GBq/mg for (90) Y-CHX-A″-DTPA-Cetuximab and 1.14 ± 0.15 GBq/mg for (177) Lu-CHX-A″-DTPA-Cetuximab), high radiochemical purity (>95%) and appreciable in vitro stability under physiological conditions. Preliminary biodistribution studies with both (90) Y-CHX-A″-DTPA-Cetuximab and (177) Lu-CHX-A″-DTPA-Cetuximab in Swiss mice bearing fibrosarcoma tumours demonstrated significant tumour uptake at 24-h post-injection (p.i.) (~16%ID/g) with good tumour-to-background contrast. The results of the biodistribution studies were further corroborated by ex vivo Cerenkov luminescence imaging after administration of (90) Y-CHX-A″-DTPA-Cetuximab in tumour-bearing mice. The tumour uptake at 24 h p.i. was significantly reduced with excess unlabelled Cetuximab, suggesting that the uptake was receptor mediated. The results of this study hold promise, and this strategy should be further explored for clinical translation. PMID:27264196

  17. Dissimilation of cysteate via 3-sulfolactate sulfo-lyase and a sulfate exporter in Paracoccus pantotrophus NKNCYSA.

    Science.gov (United States)

    Rein, Ulrike; Gueta, Ronnie; Denger, Karin; Ruff, Jürgen; Hollemeyer, Klaus; Cook, Alasdair M

    2005-03-01

    Paracoccus pantotrophus NKNCYSA utilizes (R)-cysteate (2-amino-3-sulfopropionate) as a sole source of carbon and energy for growth, with either nitrate or molecular oxygen as terminal electron acceptor, and the specific utilization rate of cysteate is about 2 mkat (kg protein)(-1). The initial degradative reaction is catalysed by an (R)-cysteate : 2-oxoglutarate aminotransferase, which yields 3-sulfopyruvate. The latter was reduced to 3-sulfolactate by an NAD-linked sulfolactate dehydrogenase [3.3 mkat (kg protein)(-1)]. The inducible desulfonation reaction was not detected initially in cell extracts. However, a strongly induced protein with subunits of 8 kDa (alpha) and 42 kDa (beta) was found and purified. The corresponding genes had similarities to those encoding altronate dehydratases, which often require iron for activity. The purified enzyme could then be shown to convert 3-sulfolactate to sulfite and pyruvate and it was termed sulfolactate sulfo-lyase (Suy). A high level of sulfite dehydrogenase was also induced during growth with cysteate, and the organism excreted sulfate. A putative regulator, OrfR, was encoded upstream of suyAB on the reverse strand. Downstream of suyAB was suyZ, which was cotranscribed with suyB. The gene, an allele of tauZ, encoded a putative membrane protein with transmembrane helices (COG2855), and is a candidate to encode the sulfate exporter needed to maintain homeostasis during desulfonation. suyAB-like genes are widespread in sequenced genomes and environmental samples where, in contrast to the current annotation, several presumably encode the desulfonation of 3-sulfolactate, a component of bacterial spores. PMID:15758220

  18. Antimicrobial activity of quinoxaline 1,4-dioxide with 2- and 3-substituted derivatives.

    Science.gov (United States)

    Vieira, Mónica; Pinheiro, Cátia; Fernandes, Rúben; Noronha, João Paulo; Prudêncio, Cristina

    2014-04-01

    Quinoxaline is a chemical compound that presents a structure that is similar to quinolone antibiotics. The present work reports the study of the antimicrobial activity of quinoxaline N,N-dioxide and some derivatives against bacterial and yeast strains. The compounds studied were quinoxaline-1,4-dioxide (QNX), 2-methylquinoxaline-1,4-dioxide (2MQNX), 2-methyl-3-benzoylquinoxaline-1,4-dioxide (2M3BenzoylQNX), 2-methyl-3-benzylquinoxaline-1,4-dioxide (2M3BQNX), 2-amino-3-cyanoquinoxaline-1,4-dioxide (2A3CQNX), 3-methyl-2-quinoxalinecarboxamide-1,4-dioxide (3M2QNXC), 2-hydroxyphenazine-N,N-dioxide (2HF) and 3-methyl-N-(2-methylphenyl)quinoxalinecarboxamide-1,4-dioxide (3MN(2MF)QNXC). The prokaryotic strains used were Staphylococcus aureus ATCC 6538, S. aureus ATCC 6538P, S. aureus ATCC 29213, Escherichia coli ATCC 25922, E. coli S3R9, E. coli S3R22, E. coli TEM-1 CTX-M9, E. coli TEM-1, E. coli AmpC Mox-2, E. coli CTX-M2 e E. coli CTX-M9. The Candida albicans ATCC 10231 and Saccharomyces cerevisiae PYCC 4072 were used as eukaryotic strains. For the compounds that presented activity using the disk diffusion method, the minimum inhibitory concentration (MIC) was determined. The alterations of cellular viability were evaluated in a time-course assay. Death curves for bacteria and growth curves for S. cerevisiae PYCC 4072 were also accessed. The results obtained suggest potential new drugs for antimicrobial activity chemotherapy since the MIC's determined present low values and cellular viability tests show the complete elimination of the bacterial strain. Also, the cellular viability tests for the eukaryotic model, S. cerevisiae, indicate low toxicity for the compounds tested.

  19. Embryonic turkey liver: activities of biotransformation enzymes and activation of DNA-reactive carcinogens

    Energy Technology Data Exchange (ETDEWEB)

    Perrone, Carmen E.; Duan, Jian Dong; Jeffrey, Alan M.; Williams, Gary M. [New York Medical College, Department of Pathology, Valhalla (United States); Ahr, Hans-Juergen; Schmidt, Ulrich [Bayer AG, Institute of Toxicology, Wuppertal (Germany); Enzmann, Harald H. [Federal Institute for Drugs and Medical Devices, Bonn (Germany)

    2004-10-01

    Avian embryos are a potential alternative model for chemical toxicity and carcinogenicity research. Because the toxic and carcinogenic effects of some chemicals depend on bioactivation, activities of biotransformation enzymes and formation of DNA adducts in embryonic turkey liver were examined. Biochemical analyses of 22-day in ovoturkey liver post-mitochondrial fractions revealed activities of the biotransformation enzymes 7-ethoxycoumarin de-ethylase (ECOD), 7-ethoxyresorufin de-ethylase (EROD), aldrin epoxidase (ALD), epoxide hydrolase (EH), glutathione S-transferase (GST), and UDP-glucuronyltransferase (GLUT). Following the administration of phenobarbital (24 mg/egg) on day 21, enzyme activities of ECOD, EROD, ALD, EH and GLUT, but not of GST, were increased by two-fold or higher levels by day 22. In contrast, acute administration of 3-methylcholanthrene (5 mg/egg) induced only ECOD and EROD activities. Bioactivation of structurally diverse pro-carcinogens was also examined using {sup 32}P-postlabeling for DNA adducts. In ovoexposure of turkey embryos on day 20 of gestation to 2-acetylaminofluorene (AAF), 4,4'-methylenebis(2-chloroaniline) (MOCA), benzo[a]pyrene (BaP), and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) resulted in the formation of DNA adducts in livers collected by day 21. Some of the DNA adducts had {sup 32}P-postlabeling chromatographic migration patterns similar to DNA adducts found in livers from Fischer F344 rats exposed to the same pro-carcinogens. We conclude that 21-day embryonic turkey liver is capable of chemical biotransformation and activation of genotoxic carcinogens to form DNA adducts. Thus, turkey embryos could be utilized to investigate potential chemical toxicity and carcinogenicity. (orig.)

  20. Raloxifene analogue LY117018 suppresses oxidative stress-induced endothelial cell apoptosis through activation of ERK1/2 signaling pathway.

    Science.gov (United States)

    Yu, Jing; Eto, Masato; Kozaki, Koichi; Akishita, Masahiro; Okabe, Tetsuro; Ouchi, Yasuyoshi

    2008-07-28

    A selective estrogen receptor modulator, raloxifene, has been shown to reduce cardiovascular events in relatively high-risk postmenopausal women with osteoporosis. However, the mechanisms by which raloxifene exerts a pharmacological effect on cardiovascular organs have not been fully elucidated. The present study was designed to examine whether the raloxifene analogue, 6-hydroxy-2-(p-hydroxyphenyl)-benzo(b) thien-3-yl-p-(2-(pyrrolidinyl)ethoxy phenyl ketone (LY117018), could inhibit apoptosis and to clarify the signaling pathway in vascular endothelial cells. LY117018 significantly inhibited hydrogen peroxide-induced apoptosis in bovine carotid artery endothelial cells. The anti-apoptotic effect of LY117018 was abolished by an estrogen receptor antagonist, 7alpha,7beta-(9[(4,4,5,5,5-Pentafluoropentyl)sulfinyl]nonyl) estra-1,3,5(10)-triene-3,17-diol (ICI 182,780). Mitogen-activated protein kinases (MAPK), including p38, c-Jun N-terminal kinase (JNK) and extracellular signal-regulated protein kinase1/2 (ERK1/2), and Akt, have been shown to act as apoptotic or anti-apoptotic signals. Phosphorylation of p38, JNK, ERK1/2 and Akt was examined. LY117018 increased ERK1/2 phosphorylation but did not enhance the phosphorylation of p38, JNK, or Akt. The anti-apoptotic effect of LY117018 was prevented by treatment with 2-[2'-amino-3'-methoxyphenyl]-oxanaphthalen-4-one (PD98059), an upstream inhibitor of ERK1/2. LY117018 stimulated an increase in ERK1/2 phosphorylation, which was diminished by ICI 182,780. The activation of ERK/1/2 by LY117018 was not inhibited by the transcription inhibitor, actinomycin D. These results suggest that estrogen receptors and the ERK1/2 signaling pathway are involved in the anti-apoptotic action of LY117018 in vascular endothelial cells. PMID:18541231

  1. Polymorphism in chloro derivatives of 1,4-naphthoquinone: Experiment and density functional theoretic investigations

    Science.gov (United States)

    Chaudhari, Dinkar; Gejji, Shridhar P.; Lande, Dipali N.; Chakravarty, Debamitra; Salunke-Gawali, Sunita

    2016-09-01

    Molecular interactions underlying polymorphs of chlorine containing 1,4-naphthoquinone derivatives have been investigated by employing single crystal X-ray, 1H NMR, FTIR and electronic spectra experiments combined with density functional theory. Two polymorphs of 2,3-dichloro-1,4-naphthoquinone possessing (i) triclinic space group P-1(A1 and A3), and (ii) orthorhombic with Pb21a (A2) space group were obtained. The polymorph A3 has two molecules in its asymmetric unit which facilitate Csbnd H⋯O interactions engendeing polymeric planar sheets. The two polymorphs of 2-amino-3-chloro-1,4-naphthoquinone reveal monoclinic forms with Pc (B1) and C2/C (B2) space groups. A tetramer of B2 molecule possess Nsbnd H⋯O interactions. The polymorphs of 2-chloro-3-hydroxy-1,4-naphthoquinone crystallizes in monoclinic space groups Pc (C1) and Pn (C2). Polymeric chain of C2 molecules results via Osbnd H⋯O interactions and the chains further are connected through Csbnd H⋯Cl and π-π stacking interactions those arise from benzenoid and quinonoid centroid. Moreover A3 facilitates the dimer via the halogen bonding interactions. Furthermore hydrogen bonding renders stability to the dimer C2. On the other hand compound B2 does not favor dimer formation. These inferences based on experimental observations are rationalized through the use of the dispersion corrected M06-2x functional based density functional theory. Further time dependent density functional theory has been used to assign the electronic transitions in UV-visible spectra of A3, B2 and C2.

  2. Crystal Structure, Cytotoxicity and Interaction with DNA of Zinc (II Complexes with o-Vanillin Schiff Base Ligands.

    Directory of Open Access Journals (Sweden)

    Mei-Ju Niu

    Full Text Available Two new zinc complexes, Zn(HL12 (1 and [Zn2(H2L2(OAc2]2 (2 [H2L1 = Schiff base derived from o-vanillin and (R-(+-2-amino-3-phenyl-1-propanol, H3L2 = Schiff base derived from o-vanillin and 2-amino-2-ethyl-1,3-propanediol], have been synthesized and characterized by single crystal X-ray diffraction, elemental analyses, TG analyses, solid fluorescence, IR, UV-Vis and circular dichroism spectra. The structural analysis shows that complex 1 has a right-handed double helical chain along the crystallographic b axis. A homochiral 3D supramolecular architecture has been further constructed by intermolecular C-H··· π, O-H···O and C-H···O interactions. Complex 2 includes two crystallographically independent binuclear zinc molecules. The two binuclear zinc molecules are isostructural. The 2-D sheet supramolecular structure was formed by intermolecular hydrogen bonding interaction. The fluorescence of ligands and complexes in DMF at room temperature are studied. The interactions of two complexes with calf thymus DNA (CT-DNA are investigated using UV-Vis, CD and fluorescence spectroscopy. The results show that complex 1 exhibits higher interaction with CT-DNA than complex 2. In addition, in vitro cytotoxicity of the complexes towards four kinds of cancerous cell lines (A549, HeLa, HL-60 and K562 were assayed by the MTT method. Investigations on the structures indicated that the chirality and nuclearity of zinc complexes play an important role on cytotoxic activity.

  3. Transformation of 2,4,6-trinitrotoluene in soil in the presence of the earthworm Eisenia andrei

    Energy Technology Data Exchange (ETDEWEB)

    Renoux, A.Y.; Sarrazin, M.; Hawari, J.; Sunahara, G.I.

    2000-06-01

    The ability of the earthworm Eisenia andrei to metabolize 2,4,6-trinitrotoluene (TNT) was studied in experiments with TNT-spiked soils, dermal contact tests, and with an in vitro assay. Lethality of TNT in a forest sandy soil was first determined. Then TNT at lethal and sublethal concentrations was applied to the same soil and was monitored along with its metabolites in extracts of soil and earthworm tissue for up to 14 d post application. High performance liquid chromatography-ultra violet analyses indicated that TNT was transformed in the presence of E. andrei by a reductive pathway to 2-amino-3,6-dinitrotoluene (2-ADNT), 4-amino-2,6-dinitrotoluene (4-ADNT), 2,4-diamino-6-nitrotoluene (2.4-DANT), and traces of 2,6-diamino-4-nitrotoluene (2,6-DANT) in earthworm tissues. This transformation could be explained by either a metabolic mechanism within the earthworm or by the enhancement of an earthworm-associated microbial activity or both. The TNT concentrations decreased from the spiked soils. However, the monoamino-dinitrotoluene (2-ADNT and 4-ADNT) concentrations increased with exposure duration and were dependent on the initial TNT soil concentrations. This was also observed to a lesser extent in the TNT-spiked soils with no earthworms present. The biotransformation of TNT into 2-ADNT, 4-ADNT, and 2,4-DANT and the presence of these metabolites in E. andrei after dermal contact on TNT-spiked filter paper showed that dermal uptake can be a significant exposure route for TNT. In vitro experiments showed that earthworm homogenate could metabolize TNT and form 2-ADNT and 4-ADNT at room temperature and at 37 C. This effect was inhibited by heat inactivation prior to incubation or by incubation at 4 C, suggesting that the biotransformation of TNT in the presence of E. andrei may be enzymatic in nature.

  4. Differential toxicity of heterocyclic aromatic amines and their mixture in metabolically competent HepaRG cells

    International Nuclear Information System (INIS)

    Human exposure to heterocyclic aromatic amines (HAA) usually occurs through mixtures rather than individual compounds. However, the toxic effects and related mechanisms of co-exposure to HAA in humans remain unknown. We compared the effects of two of the most common HAA, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), individually or in combination, in the metabolically competent human hepatoma HepaRG cells. Various endpoints were measured including cytotoxicity, apoptosis, oxidative stress and DNA damage by the comet assay. Moreover, the effects of PhIP and/or MeIQx on mRNA expression and activities of enzymes involved in their activation and detoxification pathways were evaluated. After a 24 h treatment, PhIP and MeIQx, individually and in combination, exerted differential effects on apoptosis, oxidative stress, DNA damage and cytochrome P450 (CYP) activities. Only PhIP induced DNA damage. It was also a stronger inducer of CYP1A1 and CYP1B1 expression and activity than MeIQx. In contrast, only MeIQx exposure resulted in a significant induction of CYP1A2 activity. The combination of PhIP with MeIQx induced an oxidative stress and showed synergistic effects on apoptosis. However, PhIP-induced genotoxicity was abolished by a co-exposure with MeIQx. Such an inhibitory effect could be explained by a significant decrease in CYP1A2 activity which is responsible for PhIP genotoxicity. Our findings highlight the need to investigate interactions between HAA when assessing risks for human health and provide new insights in the mechanisms of interaction between PhIP and MeIQx.

  5. Expression of specific ionotropic glutamate and GABA-A receptor subunits is decreased in central amygdala of alcoholics

    Directory of Open Access Journals (Sweden)

    Zhe eJin

    2014-09-01

    Full Text Available The central nucleus of amygdala (CeA has a role for mediating fear and anxiety responses. It is also involved in emotional imbalance caused by alcohol abuse and dependence and in regulating relapse to alcohol abuse. Growing evidences suggest that excitatory glutamatergic and inhibitory γ-aminobutyric acid-ergic (GABAergic transmissions in the CeA are affected by chronic alcohol exposure. Human post-mortem CeA samples from male alcoholics (n=9 and matched controls (n=9 were assayed for the expression level of ionotropic glutamate and GABA-A receptors subunit mRNAs using quantitative real-time reverse transcription-PCR (RT-qPCR. Our data revealed that out of the 16 ionotropic glutamate receptor subunits, mRNAs encoding two AMPA [2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-ylpropanoic acid] receptor subunits GluA1 and GluA4; one kainate receptor subunit GluK2; one NMDA (N-methyl-D-aspartate receptor subunit GluN2D and one delta receptor subunit GluD2 were significantly decreased in the CeA of alcoholics. In contrast, of the 19 GABA-A receptor subunits, only the mRNA encoding the α2 subunit was significantly down-regulated in the CeA of the alcoholics as compared with control subjects. Our findings imply that the down-regulation of specific ionotropic glutamate and GABA-A receptor subunits in the CeA of alcoholics may represent one of the molecular substrates underlying the new balance between excitatory and inhibitory neurotransmission in alcohol dependence.

  6. Glutamate Increases In Vitro Survival and Proliferation and Attenuates Oxidative Stress-Induced Cell Death in Adult Spinal Cord-Derived Neural Stem/Progenitor Cells via Non-NMDA Ionotropic Glutamate Receptors.

    Science.gov (United States)

    Hachem, Laureen D; Mothe, Andrea J; Tator, Charles H

    2016-08-15

    Traumatic spinal cord injury (SCI) leads to a cascade of secondary chemical insults, including oxidative stress and glutamate excitotoxicity, which damage host neurons and glia. Transplantation of exogenous neural stem/progenitor cells (NSPCs) has shown promise in enhancing regeneration after SCI, although survival of transplanted cells remains poor. Understanding the response of NSPCs to the chemical mediators of secondary injury is essential in finding therapies to enhance survival. We examined the in vitro effects of glutamate and glutamate receptor agonists on adult rat spinal cord-derived NSPCs. NSPCs isolated from the periventricular region of the adult rat spinal cord were exposed to various concentrations of glutamate for 96 h. We found that glutamate treatment (500 μM) for 96 h significantly increased live cell numbers, reduced cell death, and increased proliferation, but did not significantly alter cell phenotype. Concurrent glutamate treatment (500 μM) in the setting of H2O2 exposure (500 μM) for 10 h increased NSPC survival compared to H2O2 exposure alone. The effects of glutamate on NSPCs were blocked by the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptor antagonist GYKI-52466, but not by the N-methyl-D-aspartic acid receptor antagonist MK-801 or DL-AP5, or the mGluR3 antagonist LY-341495. Furthermore, treatment of NSPCs with AMPA, kainic acid, or the kainate receptor-specific agonist (RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl)propanoic acid mimicked the responses seen with glutamate both alone and in the setting of oxidative stress. These findings offer important insights into potential mechanisms to enhance NSPC survival and implicate a potential role for glutamate in promoting NSPC survival and proliferation after traumatic SCI. PMID:27316370

  7. Matching the decay half-life with the biological half-life: ImmunoPET imaging with (44)Sc-labeled cetuximab Fab fragment.

    Science.gov (United States)

    Chakravarty, Rubel; Goel, Shreya; Valdovinos, Hector F; Hernandez, Reinier; Hong, Hao; Nickles, Robert J; Cai, Weibo

    2014-12-17

    Scandium-44 (t1/2 = 3.9 h) is a relatively new radioisotope of potential interest for use in clinical positron emission tomography (PET). Herein, we report, for the first time, the room-temperature radiolabeling of proteins with (44)Sc for in vivo PET imaging. For this purpose, the Fab fragment of Cetuximab, a monoclonal antibody that binds with high affinity to epidermal growth factor receptor (EGFR), was generated and conjugated with N-[(R)-2-amino-3-(para-isothiocyanato-phenyl)propyl]-trans-(S,S)-cyclohexane-1,2-diamine-N,N,N',N″,N″-pentaacetic acid (CHX-A″-DTPA). The high purity of Cetuximab-Fab was confirmed by SDS-PAGE and mass spectrometry. The potential of the bioconjugate for PET imaging of EGFR expression in human glioblastoma (U87MG) tumor-bearing mice was investigated after (44)Sc labeling. PET imaging revealed rapid tumor uptake (maximum uptake of ∼12% ID/g at 4 h postinjection) of (44)Sc-CHX-A″-DTPA-Cetuximab-Fab with excellent tumor-to-background ratio, which might allow for same day PET imaging in future clinical studies. Immunofluorescence staining was conducted to correlate tracer uptake in the tumor and normal tissues with EGFR expression. This successful strategy for immunoPET imaging of EGFR expression using (44)Sc-CHX-A″-DTPA-Cetuximab-Fab can make clinically translatable advances to select the right population of patients for EGFR-targeted therapy and also to monitor the therapeutic efficacy of anti-EGFR treatments.

  8. A new derivatization approach with D-cysteine for the sensitive and simple analysis of acrylamide in foods by liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Lim, Hyun-Hee; Shin, Ho-Sang

    2014-09-26

    A liquid chromatography-tandem mass spectrometry method (LC-MS/MS) was developed in order to determine the amount of acrylamide in foods after derivatization with d-cysteine. The sulfhydryl group of d-cysteine was added at the β-site double bond of acrylamide to form 2-amino-3-(3-amino-3-oxo-propyl)sulfanyl-propanoic acid. Deuterated acrylamide (acrylamide-d3) was chosen as the internal standard (IS) for analyzing the food samples. Acrylamide was extracted from 2.0 g of food sample with 6 mL of methylene chloride, and the organic extract was diluted with 3 mL of hexane, and then the analyte was back-extracted with 0.5 mL of pure water. The derivatization of acrylamide was performed in the water extract. The best reaction conditions (3.0mg of d-cysteine, a pH 6.5, a reaction temperature of 90°C, and a heating time of 50 min) were established by the variation of parameters. The formed derivative was injected into the LC-MS/MS without further extraction or purification procedures. Separation and detection were improved with the use of an ion-pairing reagent of perfluorooctanoic acid. Under the established conditions, the limits of detection and the limits of quantification were 0.04 μg/kg and 0.14 μg/kg, respectively, and the inter-day relative standard deviation was less than 8% at concentrations of 20 and 100 μg/kg. The method was successfully applied to determine the amount of acrylamide in potato chips, French fries, and coffee.

  9. Antimutagenic activity of spearmint.

    Science.gov (United States)

    Yu, Tian-Wei; Xu, Meirong; Dashwood, Roderick H

    2004-01-01

    The antimutagenic activity of spearmint (Mentha spicata), a popular food flavoring agent, was studied in the Salmonella assay. Spearmint leaves were brewed in hot water for 5 min at concentrations up to 5% (w/v), and the water extracts were tested against the direct-acting mutagens 4-nitro-1,2-phenylenediamine (NPD) and 2-hydroxyamino-3-methyl-3H-imidazo[4,5-f]quinoline (N-OH-IQ) using Salmonella typhimurium strain TA98. Nontoxic concentrations of spearmint extract inhibited the mutagenic activity of N-OH-IQ in a concentration-dependent fashion, but had no effect against NPD. These experiments by design focused on the water extract consumed commonly as an herbal tea, but chloroform and methanol extracts of spearmint also possessed antimutagenic activity against N-OH-IQ. Water extract of spearmint inhibited the mutagenic activity of the parent compound, 2-amino-3-methyl-3H-imidazo[4,5-f]quinoline (IQ), in the presence of rat liver S9; however, the concentration for 50% inhibition (IC50) against IQ was approximately 10-fold higher than in assays with N-OH-IQ minus S9. At concentrations similar to those used in the Salmonella assays, spearmint extract inhibited two of the major enzymes that play a role in the metabolic activation of IQ, namely, cytochromes P4501A1 and 1A2, based on ethoxyresorufin O-deethylase and methoxyresorufin O-demethylase assays in vitro. In vivo, rats were given spearmint water extract (2%; w/v) as the sole source of drinking fluid before, during, and after 2-week treatment with IQ; colonic aberrant crypt foci were inhibited significantly at 8 weeks (P < 0.05, compared with rats given IQ alone). Collectively, these findings suggest that spearmint tea protects against IQ and possibly other heterocyclic amines through inhibition of carcinogen activation and via direct effects on the activated metabolite(s).

  10. Isoxanthohumol--Biologically active hop flavonoid.

    Science.gov (United States)

    Żołnierczyk, Anna Katarzyna; Mączka, Wanda Krystyna; Grabarczyk, Małgorzata; Wińska, Katarzyna; Woźniak, Edyta; Anioł, Mirosław

    2015-06-01

    Isoxanthohumol (IXN), apart from xanthohumol (XN) and 8-prenylnaringenin (8PN), is one of the most important prenylflavonoids found in hops. Another natural source of this compound is a shrub Sophora flavescens, used in traditional Chinese medicine. Main dietary source of IXN is beer, and the compound is produced from XN during wort boiling. In the human body, the compound is O-demethylated to 8PN, the strongest known phytoestrogen. This process takes place in the liver and in the intestine, where it is mediated by local microflora. It has been reported in some studies that even though beer contains small amounts of hops and its preparations, these compounds may affect the functioning of the human body. IXN exhibits an antiproliferative activity against human cell lines typical for breast cancer (MCF-7), ovarian cancer (A-2780), prostate cancer (DU145 and PC-3), and colon cancer (HT-29 and SW620) cells. It strongly inhibits the activation of the following carcinogens: 2-amino-3-methylimidazol-[4,5-f]quinoline and aflatoxin B1 (AFB1) via human cytochrome P450 (CYP1A2). It also inhibits the production of prostate specific antigen (PSA). IXN significantly reduces the expression of transforming growth factor-β (TGF-β) in the case of invasive breast cancer MDA-MB-231. It interferes with JAK/STAT signaling pathway and inhibits the expression of pro1inflammatory genes in the monoblastic leukemia cell line (MonoMac6). It activates apoptosis in human umbilical vein endothelial cells (HUVEC) and human aortic smooth muscle cells (HASMCs). In addition, IXN shows an antiviral activity towards herpes viruses (HSV1 and HSV2) and bovine viral diarrhea virus (BVDV). PMID:25771121

  11. Dextran sulfate sodium-induced colitis-associated neoplasia: a promising model for the development of chemopreventive interventions

    Institute of Scientific and Technical Information of China (English)

    Margie Lee CLAPPER; Harry Stanley COOPER; Wen-Chi Lee CHANG

    2007-01-01

    Individuals diagnosed with ulcerative colitis face a significantly increased risk of developing colorectal dysplasia and cancer during their lifetime. To date, little attention has been given to the development of a chemopreventive intervention for this high-risk population. The mouse model of dextran sulfate sodium (DSS) -induced colitis represents an excellent preclinical system in which to both charac-terize the molecular events required for tumor formation in the presence of inflam-marion and assess the ability of select agents to inhibit this process. Cyclic admin-istration of DSS in drinking water results in the establishment of chronic colitis and the development of colorectal dysplasias and cancers with pathological fea-tures that resemble those of human colitis-associated neoplasia. The incidence and multiplicity of lesions observed varies depending on the mouse strain used (ie, Swiss Webster, C57BL/6J, CBA, ICR) and the dose (0.7%-5.0%) and schedule (1-15 cycles with or without a subsequent recovery period) of DSS. The incidence of neoplasia can be increased and its progression to invasive cancer accelerated significantly by administering DSS in combination with a known colon carcinogen(azoxymethane (AOM), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)) or iron. More recent induction of colitis-associated neoplasia in genetically defined mouse strains has provided new insight into the role of specific genes (ie, adenomatous polyposis coli (Apc),p53, inducible nitric oxide synthase (iNOS), Msh2) in the development of colitis-associated neoplasias. Emerging data from chemopreventive intervention studies document the efficacy of several agents in inhibiting DSS-induced neoplasia and provide great promise that colitis-associated colorectal neoplasia is a pre-ventable disease.

  12. Synaptic transmission changes in fear memory circuits underlie key features of an animal model of schizophrenia.

    Science.gov (United States)

    Pollard, Marie; Varin, Christophe; Hrupka, Brian; Pemberton, Darrel J; Steckler, Thomas; Shaban, Hamdy

    2012-02-01

    Non-competitive antagonists of the N-methyl-d-aspartate receptor (NMDA) such as phencyclidine (PCP) elicit schizophrenia-like symptoms in healthy individuals. Similarly, PCP dosing in rats produces typical behavioral phenotypes that mimic human schizophrenia symptoms. Although schizophrenic behavioral phenotypes of the PCP model have been extensively studied, the underlying alterations of intrinsic neuronal properties and synaptic transmission in relevant limbic brain microcircuits remain elusive. Acute brain slice electrophysiology and immunostaining of inhibitory neurons were used to identify neuronal circuit alterations of the amygdala and hippocampus associated with changes in extinction of fear learning in rats following PCP treatment. Subchronic PCP application led to impaired long-term potentiation (LTP) and marked increases in the ratio of NMDA to 2-amino-3(5-methyl-3-oxo-1,2-oxazol-4-yl)propionic acid (AMPA) receptor-mediated currents at lateral amygdala (LA) principal neurons without alterations in parvalbumin (PV) as well as non-PV, glutamic acid decarboxylase 67 (GAD 67) immunopositive neurons. In addition, LTP was impaired at the Schaffer collateral to CA1 hippocampal pathway coincident with a reduction in colocalized PV and GAD67 immunopositive neurons in the CA3 hippocampal area. These effects occurred without changes in spontaneous events or intrinsic membrane properties of principal cells in the LA. The impairment of LTP at both amygdalar and hippocampal microcircuits, which play a key role in processing relevant survival information such as fear and extinction memory concurred with a disruption of extinction learning of fear conditioned responses. Our results show that subchronic PCP administration in rats impairs synaptic functioning in the amygdala and hippocampus as well as processing of fear-related memories. PMID:22085880

  13. Comparative genotoxic effects of the cooked-food-related mutagens Trp-P-2 and IQ in bacteria and cultured mammalian cells

    Energy Technology Data Exchange (ETDEWEB)

    Thompson, L.H.; Carrano, A.V.; Salazar, E.; Felton, J.S.; Hatch, F.T.

    1983-01-01

    As part of a major study to evaluate the mutagenicity of chemicals produced during the cooking of foods, we examined the responses of bacteria and cultured Chinese hamster cells to the compounds Trp-P-2 (3-amino-1-methyl-5H-pyrido(4,3-b)indole) and IQ (2-amino-3-methylimidazo(4,5-f)quinoline), constituents identified in cooked beef and fish. In the Ames/Salmonella tester strain TA1538, both compounds were confirmed to be extremely potent mutagens that were active at levels below 1 ng/plate in the presence of hamster-liver S9 microsomal fraction. 50-fold higher doses of both compounds were required for mutagenicity in the uvr/sup +/ tester strain TA1978. Trp-P-2 also behaved as a strong mutagen in CHO cells using the standard exogenous activation with hamster-liver S9 fraction. At concentrations below 1 ..mu..g/ml it produced dose-dependent increases in cell killing, mutations at the hprt and aprt loci, sister-chromatid exchanges, and chromosomal aberrations. An excision-repair-deficient strain was about 2-fold more sensitive than the normal CHO cells with respect to these genotoxic effects of Trp-P-2. IQ had unexpectedly weak activity for all genetic endpoints in the CHO cells, and it produced clear-cut responses only in the repair-deficient cells and only above a concentration of 10 ..mu..g/ml. The toxicity that was observed with IQ was not affected by the repair capacity of the cells and was not associated with chromosomal aberrations, indicating that damage to cellular structures other than nuclear DNA was likely the predominant pathway for cell killing. 38 references, 3 figures, 1 table.

  14. DNA polymerases κ and ζ cooperatively perform mutagenic translesion synthesis of the C8-2'-deoxyguanosine adduct of the dietary mutagen IQ in human cells.

    Science.gov (United States)

    Bose, Arindam; Pande, Paritosh; Jasti, Vijay P; Millsap, Amy D; Hawkins, Edward K; Rizzo, Carmelo J; Basu, Ashis K

    2015-09-30

    The roles of translesion synthesis (TLS) DNA polymerases in bypassing the C8-2'-deoxyguanosine adduct (dG-C8-IQ) formed by 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), a highly mutagenic and carcinogenic heterocyclic amine found in cooked meats, were investigated. Three plasmid vectors containing the dG-C8-IQ adduct at the G1-, G2- or G3-positions of the NarI site (5'-G1G2CG3CC-3') were replicated in HEK293T cells. Fifty percent of the progeny from the G3 construct were mutants, largely G→T, compared to 18% and 24% from the G1 and G2 constructs, respectively. Mutation frequency (MF) of dG-C8-IQ was reduced by 38-67% upon siRNA knockdown of pol κ, whereas it was increased by 10-24% in pol η knockdown cells. When pol κ and pol ζ were simultaneously knocked down, MF of the G1 and G3 constructs was reduced from 18% and 50%, respectively, to <3%, whereas it was reduced from 24% to <1% in the G2 construct. In vitro TLS using yeast pol ζ showed that it can extend G3*:A pair more efficiently than G3*:C pair, but it is inefficient at nucleotide incorporation opposite dG-C8-IQ. We conclude that pol κ and pol ζ cooperatively carry out the majority of the error-prone TLS of dG-C8-IQ, whereas pol η is involved primarily in its error-free bypass. PMID:26220181

  15. Cell-specific modulation of surfactant proteins by ambroxol treatment

    International Nuclear Information System (INIS)

    Ambroxol [trans-4-(2-amino-3,5-dibromobenzylamino)-cyclohexanole hydrochloride], a mucolytic agent, was postulated to provide surfactant stimulatory properties and was previously used to prevent surfactant deficiency. Currently, the underlying mechanisms are not exactly clear. Because surfactant homeostasis is regulated by surfactant-specific proteins (SP), we analyzed protein amount and mRNA expression in whole lung tissue, isolated type II pneumocytes and bronchoalveolar lavage of Sprague-Dawley rats treated with ambroxol i.p. (75 mg/kg body weight, twice a day [every 12 h]). The methods used included competitive polymerase chain reaction (RT-PCR), Northern blotting, Western immunoblotting, and immunohistochemistry. In isolated type II pneumocytes of ambroxol-treated animals, SP-C protein and mRNA content were increased, whereas SP-A, -B and -D protein, mRNA, and immunoreactivity remained unaffected. However, ambroxol treatment resulted in a significant increase of SP-B and in a decrease of SP-D in whole lung tissue with enhanced immunostaining for SP-B in Clara Cells. SP-A and SP-D were significantly decreased in BAL fluid of ambroxol-treated animals. The data suggest that surfactant protein expression is modulated in a cell-specific manner by ambroxol, as type II pneumocytes exhibited an increase in SP-C, whereas Clara cells exhibited an increase in the immunoreactivity for SP-B accounting for the increased SP-B content of whole lung tissue. The results indicate that ambroxol may exert its positive effects, observed in the treatment of diseases related to surfactant deficiency, via modulation of surfactant protein expression

  16. Estudio del comportamiento tribologico y de las interacciones de superficie de nuevos nanofluidos ionicos

    Science.gov (United States)

    Espinosa Rodriguez, Tulia

    Ionic liquids are molten salts which are liquid at room temperature or at low temperatures and present a unique combination of properties. In the present work, we focus on their use as lubricants in complex tribological problems such as the lubrication of metals that slide against themselves, the development of water based lubricants and new self-lubricated surfaces. When it is difficult to reduce friction and wear by lubrication, as in the case of magnesium alloys, ionic liquids are studied as protective coatings precursors. Surface interactions and corrosion processes with protic and aprotic ionic liquids on copper and steel have been determined in order to develop new lubricants and lubricant additives. In the copper/copper contact, all ionic liquids present better tribological performance than the polyalphaolefin synthetic oil, except for the oleate derivative. New protic ionic liquids are not only exceptional lubricants of the steel/sapphire contact as neat lubricants, but when they are used as additives in water, the formation of a boundary layer after water evaporation occurs, thus reducing friction and wear. The formation of this boundary layer on steel under static conditions is described in order to prevent the running-in period with respect to the solution of ionic liquid in water. The best lubricating behaviour for the copper/copper contact and also for the steel/sapphire contact is obtained for the diprotic ammonium dianionic adipate, that has two carboxylate groups in its anion. A higher polarity and a higher number of ammonium protons, carboxylate and hydroxyl groups would give rise to stronger surface interaction with the metal surfaces and more stable boundary films. The tribological performance of new aprotic thiazolium ionic liquids and commercial aprotic imidazolium ionic liquids has been compared as lubricants of the steel/sapphire contact, obtaining the best results for the bis(trifluoromethanesulfonyl)imide derivatives, and also preventing

  17. Anti-EGFRvIII monoclonal antibody armed with {sup 177}Lu: in vivo comparison of macrocyclic and acyclic ligands

    Energy Technology Data Exchange (ETDEWEB)

    Hens, Marc; Vaidyanathan, Ganesan; Zhao Xiaoguang [Department of Radiology, Duke University Medical Center, Durham, NC 27710 (United States); Bigner, Darell D. [Department of Pathology, Duke University Medical Center, Durham, NC 27710 (United States); Zalutsky, Michael R., E-mail: zalut001@mc.duke.ed [Department of Radiology, Duke University Medical Center, Durham, NC 27710 (United States)

    2010-10-15

    Introduction: Monoclonal antibody (mAb) L8A4 binds specifically to the epidermal growth factor receptor variant III (EGFRvIII) that is present on gliomas but not on normal tissues, and is internalized rapidly after receptor binding. Because of the short range of its {beta}-emissions, labeling this mAb with {sup 177}Lu would be an attractive approach for the treatment of residual tumor margins remaining after surgical debulking of brain tumors. Materials and Methods: L8A4 mAb was labeled with {sup 177}Lu using the acyclic ligands [(R)-2-amino-3-(4-isothiocyanatophenyl)propyl]-trans-(S,S)-cyclohexane-1, 2-diamine-pentaacetic acid (CHX-A''-DTPA) and 2-(4-isothiocyanatobenzyl)-6-methyldiethylene-triaminepentaacetic acid (1B4M-DTPA), and the macrocyclic ligands S-2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane-tetraacetic acid (C-DOTA) and {alpha}-(5-isothiocyanato-2-methoxyphenyl)-1,4,7,10-tetraazacyclododecane-1,4,7, 10-tetraacetic acid (MeO-DOTA). Paired-label tissue distribution experiments were performed in athymic mice bearing subcutaneous EGFRvIII-expressing U87.{Delta}EGFR glioma xenografts over a period of 1 to 8 days to directly compare {sup 177}Lu-labeled L8A4 to L8A4 labeled with {sup 125}I using N-succinimidyl 4-guanidinomethyl-3-[{sup 125}I]iodobenzoate ([{sup 125}I]SGMIB). Results: Except with C-DOTA, tumor uptake for the {sup 177}Lu-labeled mAb was significantly higher than the co-administered radioiodinated preparation; however, this was also the case for spleen, liver, bone and kidneys. Tumor/normal tissue ratios for {sup 177}Lu-1B4M-DTPA-L8A4 and, to an even greater extent, {sup 177}Lu-MeO-DOTA-L8A4 were higher than those for [{sup 125}I]SGMIB-L8A4 in most other tissues. Conclusions: Tumor and normal tissue distribution patterns for this anti-EGFRvIII mAb were dependent on the nature of the bifunctional chelate used for {sup 177}Lu labeling. Optimal results were obtained with 1B4M-DTPA and MeO-DOTA, suggesting no clear advantage

  18. Cytochrome P450 expression system for high-throughput real-time detection of genotoxicity: Application to the study of human CYP1A2 variants.

    Science.gov (United States)

    Palma, Bernardo Brito; Moutinho, Daniela; Urban, Philippe; Rueff, José; Kranendonk, Michel

    2016-08-01

    Individual variations in cytochrome P450-mediated metabolism are believed to contribute to individual susceptibility to chemical carcinogenesis. CYP1A2 is one of the major forms of cytochrome P450 involved in drug metabolism and bioactivation of carcinogens. We have applied a recently developed high-throughput Salmonella typhimurium TA1535 system for detection of DNA damaging agents to the study of CYP1A2 polymorphisms. Non-synonymous variants T83M [CYP1A2*9], S212C [CYP1A2*12], S298R [part of CYP1A2*21], G299S [CYP1A2*13], I314V [no allele designation], I386F [CYP1A2*4], C406Y [CYP1A2*5] and R456H [CYP1A2*8] were examined. The cDNAs for each of these variants and the wild-type were co-expressed with human NADPH cytochrome P450 oxidoreductase in the TA1535-based system. The bioactivation capacity of these CYP1A2 variants was investigated using three CYP1A2-dependent pro-mutagens, 1-aminopyrene (1AP), 2-aminoanthracene (2AA), and 2-amino-3-methylimidazo(4,5-f)quinoline (IQ). All CYP1A2 variants except R456H, T83M, and I386F gave positive responses with all three compounds. Variant R456H generated no detectable holoenzyme and no detectable response for any of the compounds; I386F did not bioactivate IQ; T83M did not bioactivate 1AP. Multivariate analysis indicated variant T83M to be substantially altered in catalytic properties when compared with wild-type CYP1A2; variants G299S and I386F are slightly but significantly different. These results corroborate our previous studies, indicating the effectiveness of this new high-throughput system, not only for examining the effect of CYP1A2 polymorphisms on pro-mutagen bioactivation, but also for obtaining insights on CYP1A2 function at the mechanistic level. PMID:27476332

  19. Evaluation of the cytotoxicity, mutagenicity and antimutagenicity of emerging edible plants.

    Science.gov (United States)

    Yen, G C; Chen, H Y; Peng, H H

    2001-11-01

    This study evaluates the toxic, mutagenic and antimutagenic effects of emerging edible plants that are consumed as new leafy vegetables in Taiwan. Among eight plant extracts, only the extracts of Sol (Solanum nigrum L.) showed cytotoxicity to Salmonella typhimurium TA100 in the absence of S9 mix. The toxicity of extracts from different parts of the Sol plant, such as leaf and stem, immature fruit and mature fruit, towards S. typhimurium TA100 and human lymphocytes was also assayed. The immature fruit extracts of Sol exhibited strong cytotoxicity with dose dependence and induced significant DNA damage in human lymphocytes based on the comet assay. However, no mutagenicity was found in eight plant extracts to TA98 or TA100 either with or without the S9 mixture. Sol and Sec [Sechium edule (Jacq.) Swartz] extracts showed the strongest inhibitory effect towards the mutagenicity of 2-amino-3-methyl-imidazo[4,5-f]quinoline (IQ) in S. typhimurium TA98 and TA100; the ID(50) was less then 1 mg/plate. Cra [Crassocephalum creidioides (Benth.) S. Moore] extracts also expressed moderate antimutagenic activities towards IQ and benzo[a]pyrene (B[a]P) either in TA98 or in TA100; the ID(50) was 1.63-2.41 mg/plate. The extracts from Bas (Basella alba L.), Bou (Boussingaultia gracilis Miers var. pseudobaselloides Bailey), Cen (Centella asiatica L. Urban), Cor (Corchorus olitorius L.) and Por (Portulaca oleracea L.) showed weak to moderate inhibition of mutagenicity of IQ. However, the potential antimutagenicity of these plant extracts towards B[a]P was weaker than that towards IQ. For a direct mutagen, 4-nitroquinoline-N-oxide (NQNO), only the Sol extracts showed strong inhibitory effects in the TA100 system. The antimutagenic activity of water extracts of Sec was partly reduced by heating at 100 degrees C for 20 min. The heat-stable antimutagens in Sec extracts could be produced in the plant extract preparation process. Fractions with molecular weights above 30,000 showed the

  20. MeIQx-induced DNA adduct formation and mutagenesis in DNA repair deficient CHO cells expressing human CYP1A1 and rapid or slow acetylator NAT2

    Science.gov (United States)

    Bendaly, Jean; Zhao, Shuang; Neale, Jason R.; Metry, Kristin J.; Doll, Mark A.; States, J. Christopher; Pierce, William M.; Hein, David W.

    2007-01-01

    2-Amino-3,8-dimethylimidazo-[4,5-f]quinoxaline (MeIQx) is one of the most potent and abundant mutagens in the western diet. Bioactivation includes N-hydroxylation catalyzed by cytochrome P450s followed by O-acetylation catalyzed by N-acetyltransferase 2 (NAT2). Nucleotide excision repair-deficient chinese hamster ovary (CHO) cells were constructed by stable transfection of human cytochrome P4501A1 (CYP1A1) and a single copy of either NAT2*4 (rapid acetylator) or NAT2*5B (slow acetylator) alleles. CYP1A1 and NAT2 catalytic activities were undetectable in untransfected CHO cell lines. CYP1A1 activity did not differ significantly (p > 0.05) among the CYP1A1-transfected cell lines. Cells transfected with NAT2*4 had significantly higher levels of sulfamethazine N-acetyltransferase (p = 0.0001) and N-hydroxy-MeIQx O-acetyltransferase (p = 0.0093) catalytic activity than cells transfected with NAT2*5B. Only cells transfected with both CYP1A1 and NAT2*4 showed concentration-dependent cytotoxicity and hypoxanthine phosphoribosyl transferase (hprt) mutagenesis following MeIQx treatment. dG-C8-MeIQx was the primary DNA adduct formed and levels were dose-dependent in each cell line and in the order: untransfected < transfected with CYP1A1 < transfected with CYP1A1 & NAT2*5B < transfected with CYP1A1 & NAT2*4. MeIQx DNA adduct levels were significantly higher (p < 0.001) in CYP1A1/NAT2*4 than CYP1A1/NAT2*5B cells at all concentrations of MeIQx tested. MeIQx-induced DNA adduct levels correlated very highly (r2 = 0.88) with MeIQx-induced mutants. These results strongly support extrahepatic activation of MeIQx by CYP1A1 and a robust effect of human NAT2 genetic polymorphism on MeIQx –induced DNA adducts and mutagenesis. The results provide laboratory-based support for epidemiological studies reporting higher frequency of heterocyclic amine-related cancers in rapid NAT2 acetylators. PMID:17627018

  1. Fruits and vegetables protect against the genotoxicity of heterocyclic aromatic amines activated by human xenobiotic-metabolizing enzymes expressed in immortal mammalian cells.

    Science.gov (United States)

    Platt, K L; Edenharder, R; Aderhold, S; Muckel, E; Glatt, H

    2010-12-21

    Heterocyclic aromatic amines (HAAs) can be formed during the cooking of meat and fish at elevated temperatures and are associated with an increased risk for cancer. On the other hand, epidemiological findings suggest that foods rich in fruits and vegetables can protect against cancer. In the present study three teas, two wines, and the juices of 15 fruits and 11 vegetables were investigated for their protective effect against the genotoxic effects of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). To closely mimic the enzymatic activation of these HAAs in humans, genetically engineered V79 Chinese hamster fibroblasts were employed that express human cytochrome P450-dependent monooxygenase (hCYP) 1A2 (responsible for the first step of enzymatic activation) and human N(O)-acetyltransferase (hNAT) 2*4 or human sulfotransferase (hSULT)1A1*1 (responsible for the second step of enzymatic activation): V79-hCYP1A2-hNAT2*4 for IQ activation and V79-hCYP1A2-hSULT1A1*1 for PhIP activation. HAA genotoxicity was determined by use of the comet assay. Black, green and rooibos tea moderately reduced the genotoxicity of IQ (IC(50)=0.8-0.9%), whereas red and white wine were less active. From the fruit juices, sweet cherry juice exhibited the highest inhibitory effect on IQ genotoxicity (IC(50)=0.17%), followed by juices from kiwi fruit, plum and blueberry (IC(50)=0.48-0.71%). The juices from watermelon, blackberry, strawberry, black currant, and Red delicious apple showed moderate suppression, whereas sour cherry, grapefruit, red currant, and pineapple juices were only weakly active. Granny Smith apple juice and orange juice proved inactive. Of the vegetable juices, strong inhibition of IQ genotoxicity was only seen with spinach and onion juices (IC(50)=0.42-0.54%). Broccoli, cauliflower, beetroot, sweet pepper, tomato, chard, and red-cabbage juices suppressed IQ genotoxicity only moderately, whereas cucumber juice was

  2. Osthole-mediated cell differentiation through bone morphogenetic protein-2/p38 and extracellular signal-regulated kinase 1/2 pathway in human osteoblast cells.

    Science.gov (United States)

    Kuo, Po-Lin; Hsu, Ya-Ling; Chang, Cheng-Hsiung; Chang, Jiunn-Kae

    2005-09-01

    The survival of osteoblast cells is one of the determinants of the development of osteoporosis in patients. Osthole (7-methoxy-8-isopentenoxycoumarin) is a coumarin derivative present in many medicinal plants. By means of alkaline phosphatase (ALP) activity, osteocalcin, osteopontin, and type I collagen, enzyme-linked immunosorbent assay, we have shown that osthole exhibits a significant induction of differentiation in two human osteoblast-like cell lines, MG-63 and hFOB. Induction of differentiation by osthole was associated with increased bone morphogenetic protein (BMP)-2 production and the activations of SMAD1/5/8 and p38 and extracellular signal-regulated kinase (ERK) 1/2 kinases. Addition of purified BMP-2 protein did not increase the up-regulation of ALP activity and osteocalcin by osthole, whereas the BMP-2 antagonist noggin blocked both osthole and BMP-2-mediated ALP activity enhancement, indicating that BMP-2 production is required in osthole-mediated osteoblast maturation. Pretreatment of osteoblast cells with noggin abrogated p38 activation but only partially decreased ERK1/2 activation, suggesting that BMP-2 signaling is required in p38 activation and is partially involved in ERK1/2 activation in osthole-treated osteoblast cells. Cotreatment of p38 inhibitor SB203580 [4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)-1H-imidazole] or p38 small interfering RNA (siRNA) expression inhibited osthole-mediated activation of ALP but only slightly affected osteocalcin production. In contrast, the production of osteocalcin induced by osthole was inhibited by the mitogen-activated protein kinase kinase inhibitor PD98059 (2'-amino-3'-methoxyflavone) or by expression of an ERK2 siRNA. These data suggest that BMP-2/p38 pathway links to the early phase, whereas ERK1/2 pathway is associated with the later phase in osthole-mediated differentiation of osteoblast cells. In this study, we demonstrate that osthole is a promising agent for treating osteoporosis

  3. Slow-binding and competitive inhibition of 8-amino-7-oxopelargonate synthase, a pyridoxal-5'-phosphate-dependent enzyme involved in biotin biosynthesis, by substrate and intermediate analogs. Kinetic and binding studies.

    Science.gov (United States)

    Ploux, O; Breyne, O; Carillon, S; Marquet, A

    1999-01-01

    ultraviolet/visible spectroscopy, and the data were consistent with the kinetic data (K = 4.2 microm). Among the other compounds tested, two potential transition state analogs, 4-carboxybutyl(1-amino-1-carboxyethyl)phosphonate (4) and 2-amino-3-hydroxy-2-methylnonadioic acid (5) were found to be competitive inhibitors with respect to l-alanine with Ki of 68 microm and 80 microm, respectively. PMID:9914476

  4. Detection of DNA damage by Escherichia coli UvrB-binding competition assay is limited by the stability of the UvrB-DNA complex.

    Science.gov (United States)

    Routledge, M N; Allan, J M; Garner, R C

    1997-07-01

    To investigate the use of UvrB-binding to detect DNA damage, mobility shift gel electrophoresis was used to detect binding of UvrB protein to a 136 bp DNA fragment that was randomly adducted with aflatoxin B1 8,9-epoxide and end-labelled with 32P. After polyacrylamide gel electrophoresis, the shifted band that contained DNA bound by UvrB was quantified as a percentage of total radioactive substrate DNA. This method was applied to analyse plasmid DNA that was adducted with various DNA modifying agents in vitro. These adducts competed for UvrB-binding to the labelled substrate. By competing for UvrB-binding with 10 ng of plasmid DNA that was adducted with known levels of aflatoxin B1, 2-amino-3-methylimidazo[4,5-f]quinoline, or benzo[a]pyrene diol epoxide, UvrB competition could be quantified for DNA adducted with between one adduct in 10(2) and one adduct in 10(5) normal nucleotides. However, plasmid DNA exposed to N-methyl-N-nitrosourea or methylene blue + visible light, did not compete for UvrB-binding, even though the presence of UvrABC sensitive sites were confirmed on this DNA by a UvrABC incision assay. Mono-adducted 96-bp DNA substrates, which contained an internal 32P-label and either a single apurinic site, aflatoxin B1-guanine adduct, O6-methylguanine, 8-oxo-deoxyguanosine or non-adducted guanine, were also used as substrates for UvrA- and UvrB-binding to examine the stability of UvrB-DNA complexes with specific adducts. Under similar conditions used for the competition assay, significant UvrB-binding was seen only for the aflatoxin adducted substrate. These results suggest that stability of UvrB-binding varies greatly between bulky and non-bulky adducts. It was also found that rat liver DNA from untreated rats inhibited UvrB-binding to the substrate DNA in the competition assay, to a degree that was equivalent to competition with plasmid adducted at one adduct in 10(3) normal nucleotides.

  5. Dietary phenolics as anti-mutagens and inhibitors of tobacco-related DNA adduction in the urothelium of smokers.

    Science.gov (United States)

    Malaveille, C; Hautefeuille, A; Pignatelli, B; Talaska, G; Vineis, P; Bartsch, H

    1996-10-01

    Human urine is known to contain substances that strongly inhibit bacterial mutagenicity of aromatic and heterocyclic amines in vitro. The biological relevance of these anti-mutagens was examined by comparing levels of tobacco-related DNA adducts in exfoliated urothelial cells from smokers with the anti-mutagenic activity in corresponding 24-h urine samples. An inverse relationship was found between the inhibition of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-mutagenicity by urine extracts in vitro and two DNA adduct measurements: the level of the putatively identified N-(deoxyguanosine-8-yl)-4-aminobiphenyl adduct and the total level of all tobacco-smoke-related carcinogen adducts including those probably derived from PhIP. Urinary anti-mutagenicity in vitro appears thus to be a good indicator of the anti-genotoxicity exerted by substances excreted in urine, that protect the bladder mucosal cells (and possibly other cells) against DNA damage. These substances appear to be dietary phenolics and/or their metabolites because (i) the anti-mutagenic activity of urine extracts (n = 18) was linearly related to their content in phenolics; (ii) the concentration ranges of these substances in urine extracts were similar to those of various plant phenols (quercetin, isorhamnetin and naringenin) for which an inhibitory effect on the liver S9-mediated mutagenicity of PhIP was obtained; (iii) treatment of urines with beta-glucuronidase and arylsulfatase enhanced both anti-mutagenicity and the levels of phenolics in urinary extracts; (iv) urinary extracts inhibited noncompetitively the liver S9-mediated mutagenicity of PhIP as did quercetin, used as a model phenolics. Several structural features of the flavonoids were identified as necessary for the inhibition of PhIP and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxiline mutagenicity. Fractionation by reverse-phase HPLC and subsequent analysis of two urinary extracts, showed the presence of several anti

  6. Study on Effect of Precursor Composition on the Formation of Heterocyclic Aromatic Amines%前体物含量对杂环胺形成的影响

    Institute of Scientific and Technical Information of China (English)

    廖国周; 王桂瑛; 徐幸莲; 周光宏

    2011-01-01

    将牛、猪、羊、鸡、鸭和鹅肉分别在200℃下煎烤10 min,分析其原料肉中前体物的含量与加工肉制品中杂环胺的形成量,以探讨不同动物原料肉中杂环胺的形成量及原料肉中前体物的含量对杂环胺形成的影响.结果表明,6种原料肉中前体物含量差异较大,肌酸与葡萄糖的摩尔浓度比在0.89~9.84之间.加工肉制品中共检测出10种杂环胺,其中9H-吡啶并[3,4-b]吲哚(Norharman)与1-甲基-9H-吡啶并[3,4-b]吲哚(Harman)在加工肉品中含量最高,分别在10.90~24.16 ng/g与4.64~14.04 ng/g之间.而2-氨基-3,8-二甲基咪唑并[4,5-f]喹喔啉(MeIQx)在牛肉中形成量较高,达3.55 ng/g,2-氨基-1-甲基-6-苯基-咪唑并[4,5-b]吡啶(PhIP)在禽肉中易于产生,其中鸡肉中含量最高,达15.26 ng/g.PhIP与肌酸和葡萄糖的摩尔浓度比存在相关性(P<0.05),随着葡萄糖浓度的增高,PhIP的形成量减少.%The meat pieces of following animals species, beef, pork, mutton, chicken, duck and goose were pan fried at 200 ℃ for 10 min to study the occurrence of HAAs in fried meat of various animal species and the effect of precursor composition in raw meat on the formation of HAAs in pan fried meat.The composition of precursor (free amino acids, creatine and glucose) was examined in raw meat and the HAAs were detected in pan fried meat.Results showed that great differences were found between the precursor content, both between the animal species and within any species.The molar ratio of total creatine/glucose was from 0.89 up to 9.84.Ten HAAs were detected in pan fried meat.9H-pyrido[4,3-b]indole(Norharman) and 1-methyl-9H-pyrido [4,3-b]indole (Harman) were detected at high levels in cooked meat, the concentrations of the two compounds ranged from 10.90 ng/gup to 24.16 ng/g and from4.64 ng/g to 14.04 ng/g respectively.2-amino-3, 8-dimethyl-imidazo[4,5-f]quinoxaline(MeIQx)was detected in amounts up to 3.55 ng/g in beef.2-amino-1-methyl-6

  7. 一些含杂环配体的过渡金属配合物的微波合成、光谱、热化学性质和生物活性%Microwave Synthesis, Spectral, Thermal and Biological Significance of Some Transition Metal Complexes Containing Heterocyclic Ligands

    Institute of Scientific and Technical Information of China (English)

    Jain Rajendra K; Mishra A P

    2012-01-01

    Some new Schiff base complexes of Cr(Ⅲ),Co(Ⅱ),Ni(Ⅱ) and Cu(Ⅱ) derived from 5-chlorosalicylaldehyde with 2-amino-5-nitrothiazole (L1H) and 4-chlorobenzaldehyde with 2-amino-3-hydroxypyridine (L2H) have been synthesized by conventional as well as microwave methods.These compounds have been characterized by elemental analysis,FTIR,FAB-mass,molar conductance,electronic spectra,1H-NMR,ESR,magnetic susceptibility,thermal,electrical conductivity and XRD analysis.The complexes are coloured and stable in air.Analytical data reveal that all the complexes exhibit 1∶2 (metal∶ligand) ratio with coordination number of 4 or 6.FAB-mass and thermal data show degradation pattern of the complexes.XRD patterns indicate crystalline nature for the complexes.The Schiff base and metal complexes show a good activity against the Gram-positive bacteria:Staphylococcus aureus and Gramnegative bacteria:Escherichia coli and fungi:Aspergillus niger and Candida albicans.%用5-氯邻羟苯甲醛与2-氨基-5-硝基噻唑(L1H)和4-氯苯甲醛与2-氨基-3-羟基吡啶(L2H)的反应,再用传统和微波方法将生成物与Cr(Ⅲ),Co(Ⅱ),Ni(Ⅱ)和Cu(Ⅱ)合成了一些席夫碱配合物.用元素分析,FTIR,快原子轰击质谱,摩尔电导率,电子光谱,1H-NMR,ESR,磁化率,热分析,电导率和XRD等对这些化合物进行了表征.这些配合物在空气中稳定并有颜色.分析数据表明所有配合物金属与配体的比均为1∶2,配位数为4或6.原子轰击质谱和热分析数据说明了这些配合物的降解方式.XRD图给出了这些配合物的结晶情况.席夫碱的上述金属配合物对革兰氏阳性菌:金黄色葡萄球菌和革兰氏阴性菌:大肠埃希菌(大肠杆菌)和真菌:黑曲霉和白色念珠菌显示出良好的抗菌活性.

  8. Investigation of magnetic exchange via non-bonding halides and aromatic polyamines (1,2,4-triazine, 1,2,4,5-tetrazine and the related derivatives as ligands)

    Science.gov (United States)

    Li, Lixin

    Low dimensional antiferromagnetic materials have received considerable attention from both chemists and physicists because of their potential application as functional materials, such as superconductors. Magnetic moments can propagate via multiple pathways such as via two-halide superexchange interactions in A2MX4 systems (where A is an organic cation and X is halides), or through bonding conjugated systems. One route for generating two-halide A2MX4 systems is via crystal packing of transition metal anions and organic cations. Following this method, we have prepared a series compounds in the (5-SAP)2CuX 4 family (where 5-SAP is a 5-substituted-2-aminopyridinium cation) and the A2CuX4 family. Eleven compounds have been prepared. They include bis(2-amino-5-fluoropyridinium) tetrachlorocuprate(II) (5-FAP) 2CuCl4 (1), bis(2-amino-5-fluoropyridinium) tetrabromocuprate(II) (5-FAP)2CuBr4 (2), bis(2-amino-5-iodopyridine) dibromocopper(II) (5-iap)2CuBr 2 dimer (3) and chain (4) forms, bis(2-amino-5-iodopyridine) dichlorocopper(II) hydrate (5-iap)2CuCl2·1.7H 2O (5), 2-amino-5-ammoniumpyridinium trichlorocuprate(II) chloride (DAP)(CuCl3)Cl (6), bis(2-amino-3-chloro-5-trifluoromethylpyridinium) tetrabromocuprate(II) (TMCAP)2CuBr4 (7) and its tetrachlorocuprate(II) analog (TMCAP)2CuCl4 (8), bis(4-aminopyridinium) tetrabromocuprate(II) monohydrate (4-AP) 2CuBr4-H2O (9), bis(3-methylpyridinium) tetrabromocuprate(II) (3-MP)2CuBr4 (10) and bis[methyl(2-phenylethyl)ammonium] tetrabromocuprate(II) (NMPH)2 CuBr4 (11). The structures and magnetic properties have been studied. Experimental data and theoretical calculations show that the strength of magnetic exchange is related to the geometric parameters of the non-bonding two-halide contacts, rather than direct contact between the copper(II) ions. The self-assembly technique can also be used to prepare magnetic networks. A variety of coordination polymers with magnetic properties have been synthesized based on different N