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Sample records for acetamide

  1. Compound list: acetamide [Open TG-GATEs

    Lifescience Database Archive (English)

    Full Text Available acetamide AAA 00169 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/acetamide....Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/acetamide.Rat.in_vivo.Liver.Repeat.zip ...

  2. 2-Chloro-N-methyl-N-[2-(methylaminophenyl]acetamide

    Directory of Open Access Journals (Sweden)

    Yu-Bin Bai

    2013-02-01

    Full Text Available The title compound, C10H13ClN2O, was obtained as a by-product in the reaction of 2-chloromethyl-1H-benzimidazole, dimethyl sulfate and toluene to synthesise 2-chloromethyl-1-methylbenzimidazole. The dihedral angle between the benzene ring and the acetamide group is 89.72  (6° while that between the aromatic ring and the chloracetyl group is 84.40 (4°. In the crystal, adjacent molecules are linked by pairs of N—H...O hydrogen bonds into inversion dimers.

  3. Nanomorphology in thin films of acetamide end-functionalised quaterthiophene

    Energy Technology Data Exchange (ETDEWEB)

    Zeilmann, Nina; Rösner, Benedikt; Späth, Andreas [Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) Department Chemie und Pharmazie, Physikalische Chemie 2 and ICMM, Egerlandstraße 3, 91058 Erlangen (Germany); Schmidt, Ute [WITec GmbH, Lise-Meitner-Straße 6, 89081 Ulm (Germany); Fink, Rainer H., E-mail: rainer.fink@fau.de [Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) Department Chemie und Pharmazie, Physikalische Chemie 2 and ICMM, Egerlandstraße 3, 91058 Erlangen (Germany)

    2015-05-29

    α,ω-Functionalised oligothiophenes are promising materials for organic field effect transistors due to their high degree of molecular ordering, crystallinity and π-π stacking. We employ several complementary microspectroscopic probes to investigate the formation of thermally evaporated films of 5,5‴-bis(N-acetamido-2-ethyl)-2,2′:5′,2″:5″,2‴quaterthiophene on inert substrates. These films were found to grow in a mixed fashion, featuring layer-by-layer domains with thicknesses of several monolayers and needle-shaped three-dimensional crystals. Detailed analysis of atomic force microscopy (AFM) and photoluminescence microscopy reveals the micro- and nanomorphology of the films. Linear dichroism in the near edge x-ray absorption fine structure and polarisation-dependent laser excitation corroborate the findings of AFM, i.e., upright standing molecules in the multilayer regime. The shape of the 3-dimensional crystallites and multilayer domains indicates strongly anisotropic growth favoured by the herringbone-arrangement of the thiophene moieties and additional stabilisation by hydrogen bonding of the acetamide end groups. - Highlights: • Growth study of end-functionalised quaterthiophene on inert substrates is presented. • Complementary nanoprobes were employed to investigate the growth behaviour. • The molecular orientation was revealed by the use of linearly polarised light.

  4. Inhibitory effect of acetamide-45 on airway inflammation and phosphodiesterase 4 in allergic rats

    Institute of Scientific and Technical Information of China (English)

    Kai WANG; Hua-hao SHEN; Jun-chun CHEN; Zhong CHEN

    2005-01-01

    Aim: To determine the effects of acetamide-45 on respiratory function, airway inflammation, and the activity of phosphodiesterase 4 (PDE4) in allergic rats.Methods: Rats were sensitized by a single intramuscular injection with ovalbumin (OVA) and were challenged with ovalbumin applied by using an aerosol repeatedly for 7 d after 2 weeks. Acetamide-45 at concentrations of 5, 10, or 30 mg/kg was then administered by intraperitoneal injection. Changes in dynamic lung compliance and lung resistance, the accumulation of inflammatory cells in bronchoalveolar lavage, PDE4 activity, and the concentration of interleukin-4 in rat lung tissue were determined. Results: Seven days of treatment with acetamide-45 prevented eosinophil accumulation in allergic rats. At doses of 5, 10, and 30 mg/kg, acetamide-45 decreased lung resistance to 0.20±0.04, 0.25±0.07, and 0.22±0.05compliance to 0.41±0.07, 0.39±0.06, and 0.42±0.09 mL/cmH2O (P<0.05 vs OVA).After being treated with different doses of acetamide-45, the PDE4 activities in the concentrations of interleukin-4 in lung tissue were 6.22± 1.13, 5.95± 1.20,and 5.68±2.20 μg/g protein (P<0.05 vs OVA). Conclusions: Acetamide-45 was found to improve respiratory function and inhibit airway inflammation in this animal model, and the PDE4 activity of lung tissue was obviously inhibited.Acetamide-45 was an effective anti-inflammatory agent in respiratory inflammation,and the mechanism of its action might depend on inhibition of PDE4.

  5. Influence of Nanoparticles and Graphite Foam on the Supercooling of Acetamide

    Directory of Open Access Journals (Sweden)

    Jia Yu

    2014-01-01

    Full Text Available Acetamide is a promising phase change materials (PCMs for thermal storage,but the large supercooling during the freezing process has limited its application. In this study, we prepared acetamide-SiO2 composites by adding nano-SiO2 into acetamide. This modified PCM was then impregnated into the porous graphite foam forming acetamide-SiO2-graphite foam form-stable composites. These composites were subjected to melting-solidification cycles 50 times; the time-temperature curves were tracked and recorded during these cycles. The time-temperature curves showed that, for the acetamide containing 2 wt. % SiO2, the supercooling phenomenon was eliminated and the material’s performance was stable for 50 cycles. The solidification temperature of the acetamide-SiO2-graphite foam samples was 65°C and the melting temperature was lowered to 65°C. The samples exhibited almost no supercooling and the presence of SiO2 had no significant effect on the melting-solidification temperature. The microscopic supercooling of the acetamide-SiO2 composite was measured using differential scanning calorimetry (DSC. The results indicated that when the content of SiO2 was 1 wt. to 2 wt. %, the supercooling could be reduced to less than 10°C and heat was sufficiently released during solidification. Finally, a set of algorithms was derived using MATLAB software for simulating the crystallization of samples based on the classical nucleation theory. The results of the simulation agreed with the experiment results.

  6. Synthesis and characterization of 2-hydroxy-N-methyl-N-phenyl-acetamide

    Institute of Scientific and Technical Information of China (English)

    周忠诚; 舒万艮

    2002-01-01

    2-hydroxy-N-methyl-N-phenyl-acetamide was synthesized by using N-methylaniline, chloracetyl chloride, anhydrous sodium acetate and methanol through the acetylation, esterfication and ester interchange steps. The acetylation of N-methylaniline with chloracetyl chloride, catalyzed by triethylamide with mole ratio n(C6H5NHCH3)∶n(ClCH2C(O)Cl)∶n(N(C2H5)3)=1∶1.05∶1, the yield of 2-chloro-N-methyl-N-phenyl- acetamide(Ⅰ) was 93.8%; Then the esterification of Ⅰ with anhydrous sodium acetate in the presence of phase transfer catalyst tetrabutyl ammonia bromide gave 97.3% yield of 2-acetoxyl-N-methyl-N-phenyl-acetamide (Ⅱ); The ester interchange of with methanol catalyzed by potassium hydroxide gave 2-hydroxy-N-methyl-N-phenyl-acetamide (Ⅲ) in 96.4% yield. And the total yield was 88.0%. IR and MS spectroscopy of products were analyzed and their characteristic peaks were assigned. Combining the results of elemental analysis, the molecular structure of Ⅰ, Ⅱ and Ⅲ was identified.

  7. Synthesis and pharmacological evaluation of benzofuran-acetamides as "antineophobic" mitochondrial DBI receptor complex ligands

    NARCIS (Netherlands)

    Liao, Y; Kozikowski, AP; Guidotti, A; Costa, E

    1998-01-01

    A series of novel benzofuran analogues of N,N-di-n-hexyl-2-phenylindole-3-acetamide (5, FGIN-1-27), a potent and highly specific mitochondrial DBI receptor complex ligand, were synthesized by a modified Fischer method and found in vitro and in vivo to be equally potent and selective as FGIN-1-27. (C

  8. Gas chromatographic-mass spectrometric analysis of acrylamide and acetamide in cigarette mainstream smoke after on-column injection.

    Science.gov (United States)

    Diekmann, Joerg; Wittig, Arno; Stabbert, Regina

    2008-08-01

    A method is described for the simultaneous determination of two short-chained amides, acrylamide and acetamide (classified by the International Agency for Research on Cancer as probable and possible human carcinogens, respectively), in total particulate matter using gas chromatography-on-column injection and mass spectrometric detection. Sample preparation is kept to a minimum, and the proposed analytical procedure proves to be fast, sensitive, and precise. Validation studies show good linearity with a regression coefficient of r2=.000 for both compounds. Quantitation limits are 32 ng/mL for acrylamide and 70 ng/mL for acetamide. In the particulate phase of mainstream smoke from the University of Kentucky Reference Cigarette 2R4F, 2.3 microg/cig acrylamide and 4.7 microg/cig acetamide are found; no acetamide and only .0074 microg/cig acrylamide is found in the gas phase. Possible mechanisms of formation in cigarette smoke are discussed.

  9. Synthesis of N-acetamide C60 nitride and its performance of optical limiting

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    N-acetamide C60 nitride (N-acetamide-1,2-dihydro-1,2-aza-fullerene[60]) has been synthesized by the reaction of C60 and azidoacetamide and initially characterized. Its mechanism was that the objective product is formed through intermediate triazoline. The computational study shows that N-nitride structure is thermodynamically more stable by using the semi-empirical AM1 SCF-MO method. The properties of optical limiting were tested by using double frequency Nd∶YAG pulse laser system and showed that the optical limiting mechanism is reverse saturation absorption. A wavelength of 532 nm, compared with optical limiting for ns pulse, this new material has good optical limiting character for ps pulse. At wavelength of 707 nm, the capacity of optical limiting of the derivative is prior to C60.

  10. Simple preparation of new N-aryl-N-(3-indolmethyl acetamides and their spectroscopic analysis

    Directory of Open Access Journals (Sweden)

    José A. Henao

    2009-12-01

    Full Text Available To prepare new indolic molecules and characterize them by spectroscopic methods. Materials and methods: All reagentswere purchased from Aldrich, commercial grade. The purity of the products and the composition of the reaction mixtures were monitoredby thin layer chromatography over Silufol UV254 0.25 mm-thick chromatoplates. Product isolation and purification were performed bycolumn chromatography (SiO2, using ethyl acetate-petroleum ether mixtures as eluents. Results. The synthesis of new N-aryl-N-(3-indolmethyl acetamides based on first step iminization reaction of indol-3-carbaldehyde is accomplished. The structures of the C-3substituted indoles were confirmed by 1H-NMR and 13C-NMR studies supported by inverse-detected 2D NMR experiments and alsothrough monocrystal X-ray diffraction. Conclusions. An efficient, economic, and fast synthetic route was designed to the construction ofthe N-aryl-N-(3-indolmethyl acetamides, structural analogues of some alkaloids.

  11. Design, synthesis and evaluation of benzofuran-acetamide scaffold as potential anticonvulsant agent

    Directory of Open Access Journals (Sweden)

    Shakya Ashok K.

    2016-09-01

    Full Text Available A series of N-(2-(benzoyl/4-chlorobenzoyl-benzofuran- 3-yl-2-(substituted-acetamide derivatives (4a-l, 5a-l was synthesized in good yield. All synthesized compounds were in agreement with elemental and spectral data. The anticonvulsant activity of all synthesized compounds was assessed against the maximal electroshock induced seizures (MES model in mice. Neurotoxicity was evaluated using the rotarod method. The majority of compounds exhibited anticonvulsant activity at a dose of 30 mg kg-1 body mass during 0.5-4 h, indicating their ability to prevent seizure spread at low doses. Relative to phenytoin, [N-(2-(4-chlorobenzoylbenzofuran-3-yl-2-(cyclohexyl( methyl amino-acetamide] (5i and [N-(2-(4-chlorobenzoylbenzofuran-3-yl-2-(4-methylpiperidin-1- yl-acetamide] (5c demonstrated comparable relative anticonvulsant potency of 0.74 and 0.72, respectively, whereas [(N-(2-(4-chlorobenzoylbenzofuran-3-yl-2-(4-(furan-2-carbonyl-piperazin-1-yl-acetamide] (5f exhibited the lowest relative potency of 0.16. The ALD50 of tested compounds ranged from 1.604 to 1.675 mmol kg-1 body mass. The ED50 of synthesized compounds ranged from 0.055 to 0.259 mmol kg-1 (~23.4 to 127.6 mg kg-1 body mass. The pharmacophore mapping of the examined compounds on standard drugs (phenobarbital, phenytoin, ralitolin and carbamazepine strongly suggests that these compounds may exert their anticonvulsant activity via the same established mechanism as that of known drugs.

  12. Acetamide-45抑制组胺和乙酰甲胆碱引起的豚鼠离体气管收怂%Acetamide-45 inhibits histamine- and methacholine-induced contraction of isolated guinea pig trachea

    Institute of Scientific and Technical Information of China (English)

    卢韵碧; 陈忠; 吴明

    2002-01-01

    AIM:To investigate the effects of the new antiallergic agent N-( pyridin-4-yl )-( indol-3-yl ) acetamide-45(acetamide-45) on histamine- and methacholine-induced contraction of the isolated guinea pig trachea.METHODS:Cumulative histamine or methacholine concentration-contraction studies were carried out in the absence or presence of acetamide-45.Changes in isometric force were measured by force transducers and recorded on a multi-channel polygraph recorder.RESULTS:Acetamide-45 (1- 30 μmol/L) concentration-dependently inhibited histamine- or methacholineinduced contractile response of isolated guinea pig trachea.At concentrations of 3,10,30 μmol/L,acetamide-45 significantly decreased maximum contractile response to histamine by 21% -51%,and EC50 values (95 % confidence limits) were 31.1 (24.4- 39.8),34.7(26.8 - 45.0),and 134.4 (82.2 - 220.0) μmol/ L,respectively.Similarly,acetamide-45 also inhibited the contraction induced by methacholine in isolated guinea pig trachea.CONCLUSION:Acetamide-45 inhibited histamine- or methacholine-induced contraction of isolated guinea pig trachea,and these effects might be nonspecific for either histamine receptor or cholinoceptor.%目的:探讨新型抗变态反应药N-对氟苄基-3-[(N-4-吡啶)-乙酰胺]-吲哚-45(acetamide-45)对组胺和乙酰甲胆碱引起的豚鼠离体气管收缩的影响.方法:以acetamide-45预处理气管标本后,以累积剂量法给予组胺和乙酰甲胆碱,观察acetamide-45对组胺和乙酰甲胆碱量效曲线的影响.气管张力的变化通过换能器转变为电信号并由记录仪记录.结果:Acetamide-45(1-30μmol/L)浓度依赖地抑制组胺和乙酰甲胆碱引起的豚鼠离体气管收缩.Acetamide-45(3,10,30 μmol/L)使组胺的量效曲线的最大效应下降了21%-51%,使组胺的EC50值(95%可信限)分别增加到31.1(24.4-39.8),34.7(26.8-45.0)和134.4(82.2-220.0)μmol/L.另一方面,acetamide-45更有效地抑制乙酰甲胆碱引起的豚鼠离体气管收缩.结论:Acetamide

  13. An insight into the photophysical properties of amide hydrogen bonded N-(benzo[d]thiazol-2-yl) acetamide crystals

    Science.gov (United States)

    Balijapalli, Umamahesh; Udayadasan, Sathiskumar; Panyam Muralidharan, Vivek; Sukumarapillai, Dileep Kumar; Shanmugam, Easwaramoorthi; Paduthapillai Gopal, Aravindan; S. Rathore, Ravindranath; Kulathu Iyer, Sathiyanarayanan

    2017-02-01

    Three distinct, hydrogen bond associated N-(benzo[d]thiazol-2-yl) acetamides were synthesized by refluxing benzothiazoles with acetic acid. The nature of the assemblies was characteristic to the substituent in the benzothiazole moiety. In N-(benzo[d]thiazol-2-yl)acetamide, water acts as a bridge for forming three hydrogen bonds, as an acceptor to amide Nsbnd H, and donors to carbonyl of amide and thiazole nitrogen assembles of three different N-(benzo[d]thiazol-2-yl)acetamide molecules. The N-(6-methylbenzo[d]thiazol-2-yl)acetamide formed a (amide) N-H…N (thiazole) bonded R22(8) molecular dimers by two homo-intermolecular hydrogen bonding interactions. N-(6-methoxybenzo[d]thiazol-2-yl)acetamide formed (amide)N-H…O (acid) & (acid)O-H…N (thiazole) interactions with the acetic acid, forming a R22(8) hydrogen-bonded ring by two hetero-intermolecular hydrogen bonding interactions.

  14. Peptide bond formation through gas-phase reactions in the interstellar medium: formamide and acetamide as prototypes

    Energy Technology Data Exchange (ETDEWEB)

    Redondo, Pilar; Barrientos, Carmen; Largo, Antonio, E-mail: predondo@qf.uva.es [Computational Chemistry Group, Departamento de Química Física, Facultad de Ciencias, Universidad de Valladolid, E-47011 Valladolid (Spain)

    2014-09-20

    A theoretical study of the reactions of NH{sub 4}{sup +} with formaldehyde and CH{sub 5}{sup +} with formamide is carried out. The viability of these gas-phase ion-molecule reactions as possible sources of formamide and acetamide under the conditions of interstellar medium is evaluated. We report a theoretical estimation of the reaction enthalpies and an analysis of their potential energy surfaces. Formation of protonated formamide from the reaction between ammonium cation and formaldehyde is an exothermic process, but all the channels located on the potential energy surface leading to this product present net activation energies. For the reaction between methanium and formamide, different products are possible from a thermodynamic point of view. An analysis of its potential energy surface showed that formation of protonated acetamide and amino acetaldehyde takes place through barrier-free paths. Therefore, this reaction could be a feasible source of acetamide and amino acetaldehyde in space.

  15. Electrochemical studies on La-Co alloy film in acetamide-urea-NaBr melt system

    Institute of Scientific and Technical Information of China (English)

    GUO Cheng-yu; WANG Jian-chao; CHEN Bi-qing; WANG Jing-gui

    2005-01-01

    The kinetics of La-Co alloy film in acetamide-urea-NaBr molten salt electrolyte at 353 K was investigated. It is shown that the reduction of Co( Ⅱ ) to Co is irreversible reaction with the transfer coefficient of 0.28 and the diffusion coefficient of 7.46 × 10-5cm2/s. While La( Ⅲ ) cannot be reduced to La directly; but can be codeposited with cobalt. The content of La in the uncrystallized La-Co alloy film increases with increasing cathodic overpotential, molar ratio of La3+ to Co2+ and electrolysis time as well, and reaches the maximum of 66.32%.

  16. Oxidation Reactivity Channels for 2-(Pyridin-2-yl)-N,N-diphenyl-acetamides

    Energy Technology Data Exchange (ETDEWEB)

    Pailloux, Sylvie [University of New Mexico, Albuquerque; Binyamin, Iris [University of New Mexico, Albuquerque; Kim, Sung-jun [University of New Mexico, Albuquerque; Deck, Lorraine M. [University of New Mexico, Albuquerque; Rapko, Brian M. [Pacific Northwest National Laboratory (PNNL); Hay, Benjamin [ORNL; Duesler, Eileen N. [University of New Mexico, Albuquerque; Paine, Robert T. [University of New Mexico, Albuquerque

    2007-11-01

    Synthetic routes to 2-(pyridin-2-yl)-N,N-diphenylacetamide and 2-(6-methylpyridin-2-yl)-N,N-diphenyl-acetamide are described along with results from the chemical oxidation of these compounds with peracetic acid, m-chloroperbenzoic acid, and OXONE. In each case, oxidations generate four products in varying amounts depending on the oxidant and reaction conditions. Each product has been characterized by spectroscopic methods and the molecular structures of several of the new compounds have been confirmed by X-ray crystallography.

  17. Preparation of Y-Co alloy film in acetamide-urea-NaBr melt

    Institute of Scientific and Technical Information of China (English)

    王建朝; 徐常威; 刘鹏; 童叶翔; 刘冠昆

    2002-01-01

    Electroreduction of Co(Ⅱ) to Co in acetamide-urea-NaBr melt at 353K is irreversible in one step. α and D are determined as 0.23 and 2.24×10-7cm2*s-1. Y(Ⅲ) is not reduced to Y alone, but can be inductively codeposited with Co(Ⅱ). The amorphous Y-Co alloy film was obtained by potentiostatic electrolysis. The content of yttrium in the yettrium-cobalt deposits changes with the cathode potential, molar ratio of Y(Ⅲ)/Co(Ⅱ) and the electrolysis time, and can reach 83.93%.

  18. Preparation of Gd-Co alloy film in acetamide-urea-NaBr melt

    Institute of Scientific and Technical Information of China (English)

    徐常威; 潘文杰; 袁定胜; 童叶翔; 刘冠昆

    2002-01-01

    Electroreduction of Co(Ⅱ) to metallic Co in acetamide-urea-NaBr melt at 353K is irreversible in one step. Gd(Ⅲ) is not reduced to Gd alone, but can be inductively codeposited with Co(Ⅱ). The amorphous Gd-Co alloy films were obtained by potentiostatic electrolysis. With the cathode potential shifting to negative direction, the content of gadolinium in the alloy increases and can get to 65.89% (mass fraction). The additive of Na2EDTA can make the diameter of the particles of crystalline alloy smaller and change the shape of particles.

  19. SYNTHESIS OF BIOLOGICALLY ACTIVE 2-CHLORO-N-ALKYL/ARYL ACETAMIDE DERIVATIVES

    Directory of Open Access Journals (Sweden)

    S.A.Katke

    2011-07-01

    Full Text Available Medicinal chemistry plays an important role in development of drug for cure; maintain and improved health of human being. It is also equally important to design chemical entities for prevent the growth of micro-organism, which come in contact with human being in day-to-day life. We have synthesized 2-chloro-N-alkyl/aryl Acetamide derivatives with an aim as new bioactive agent, which can be used as anti microbial agents such as herbicides, antifungal, disinfectant. The present study involves the synthesis, purification and characterization of various N-substituted chloroacetamide derivatives. The chloroacetyl chloride treated with various aliphatic and aromatic amines at room temperature with stirring for few hours with monitoring reaction by thin layer chromatography gave 2-chloro-N-alkyl/aryl Acetamide as solid compounds. We checked the melting point of synthesized compounds with an open ended capillary tube method. The spectral techniques like Infra red and GC-MS have been used for characterization and establishment of structure of synthesized compounds. The antimicrobial screening of the synthesized chloroacetamides have shown excellent antibacterial and antifungalactivity.

  20. Microstructures and their lifetimes in acetamide/electrolyte deep eutectics: anion dependence

    Indian Academy of Sciences (India)

    SUMAN DAS; BISWAROOP MUKHERJEE; RANJIT BISWAS

    2017-07-01

    Extensive computer simulations with deep eutectics made of acetamide (CH₃CONH₂) and lithium salts (LiX) have been performed at 303 K and 350 K to identify the solution-phase microstructures in these media and investigate the anion dependence of the size and lifetime distributions of these microstructures. In addition, we explore how the added electrolyte interferes with the natural hydrogen bonded (H-bonded) network structure of liquid acetamide. For this purpose several radial distribution functions have been analysedand visualised. The results reveal that amide–amide H-bond interaction decreases significantly upon the addition of electrolyte, and the interactions of Li⁺ and X⁻ (X⁻ being NO⁻3 , Br⁻ and ClO⁻4 ) with CH₃CONH₂ lead to heterogeneous solution structures. Furthermore, we have obtained the cluster size and lifetime distributions in order to estimate the size of local microstructures and their stability. Both these distributions are analysed by separating the contributions arising from (a)CH₃CONH₂−CH₃CONH₂, (b)Li⁺−CH₃CONH₂ and (c) Li⁺−X⁻ interactions. The size distribution of Li⁺−X⁻ clusters is found to be different from those for the other two. Also, the lifetime distributions show a pronounced anion dependence and suggest cluster stability time up to a fewnanoseconds.

  1. Elucidation of Structural Elements for Selectivity across Monoamine Transporters: Novel 2-[(Diphenylmethyl)sulfinyl]acetamide (Modafinil) Analogues

    DEFF Research Database (Denmark)

    Okunola-Bakara, Oluyomi; Cao, Jianjing; Kopajtic, Theresa;

    2014-01-01

    2-[(Diphenylmethyl)sulfinyl]acetamide (modafinil, (±)-1) is a unique dopamine uptake inhibitor that binds the dopamine transporter (DAT) differently than cocaine and may have potential for the treatment of psychostimulant abuse. To further investigate structural requirements for this divergent bi...

  2. Synthesis of N-(3-acetylphenyl) acetamide%3-乙酰氨基苯乙酮的合成

    Institute of Scientific and Technical Information of China (English)

    刘艳丽; 张书桥; 吴达俊

    2001-01-01

    N-(3-acetylphenyl)acetamide was synthesized with the purpose of developing new pharmaceuticals to be used as anxiolytic, antiepiletic and sedative-hypotic agents as well as skeletal muscle relaxants.%苯乙酮经硝化、还原及酰化反应得到新型镇静催眠药佐匹隆(Zaleplon)的重要中间体3-乙酰氨基苯乙酮.

  3. Synthesis of N-(6-Arylbenzo[d]thiazole-2-acetamide Derivatives and Their Biological Activities: An Experimental and Computational Approach.

    Science.gov (United States)

    Gull, Yasmeen; Rasool, Nasir; Noreen, Mnaza; Altaf, Ataf Ali; Musharraf, Syed Ghulam; Zubair, Muhammad; Nasim, Faiz-Ul-Hassan; Yaqoob, Asma; DeFeo, Vincenzo; Zia-Ul-Haq, Muhammad

    2016-02-25

    A new series of N-(6-arylbenzo[d]thiazol-2-yl)acetamides were synthesized by C-C coupling methodology in the presence of Pd(0) using various aryl boronic pinacol ester/acids. The newly synthesized compounds were evaluated for various biological activities like antioxidant, haemolytic, antibacterial and urease inhibition. In bioassays these compounds were found to have moderate to good activities. Among the tested biological activities screened these compounds displayed the most significant activity for urease inhibition. In urease inhibition, all compounds were found more active than the standard used. The compound N-(6-(p-tolyl)benzo[d]thiazol-2-yl)acetamide was found to be the most active. To understand this urease inhibition, molecular docking studies were performed. The in silico studies showed that these acetamide derivatives bind to the non-metallic active site of the urease enzyme. Structure-activity studies revealed that H-bonding of compounds with the enzyme is important for its inhibition.

  4. Blending Behavior of Polysulfone, Polyvinyl Acetate and Amines in Dimethyl Acetamide Solvent

    Directory of Open Access Journals (Sweden)

    Asim Mushtaq

    2014-02-01

    Full Text Available In this study, research will be carried out to classify the blending behavior of glassy and rubbery polymer in solvent with amines. Commercially preface of a polymer prepared from a new monomer is uncertain and enormously expensive. A strategy to introduce new products into the market without a large investment is to take dissimilar polymers, amines and blend them together to make a new product with unique properties. The blending of polyvinyl acetate, polysulfone and diethanol amine, methyl diethanol amine, mono ethanol amine are examined with dimethyl acetamide solvent, which gives the results of appearance, pH and viscosity values by using measuring device viscometer and general pH testing technique. Through getting these results, the intrinsic miscibility of the mixture was finally established which shows that the homogenous or heterogeneous blends are depending on the blend preparation method and percentage of polymers and amines. The achievement of this advance has been restricted, because the mechanical properties of the blend with amines are classically worse than a simple mixing law would predict.

  5. Adamantyl carboxamides and acetamides as potent human 11β-hydroxysteroid dehydrogenase type 1 inhibitors.

    Science.gov (United States)

    Su, Xiangdong; Halem, Heather A; Thomas, Mark P; Moutrille, Cecile; Culler, Michael D; Vicker, Nigel; Potter, Barry V L

    2012-11-01

    The modulation of 11β-HSD1 activity with selective inhibitors has beneficial effects on various metabolic disorders including insulin resistance, dyslipidemia and obesity. Here we report the discovery of a series of novel adamantyl carboxamide and acetamide derivatives as selective inhibitors of human 11β-HSD1 in HEK-293 cells transfected with the HSD11B1 gene. Optimization based on an initially identified 11β-HSD1 inhibitor (3) led to the discovery of potent inhibitors with IC(50) values in the 100 nM range. These compounds are also highly selective 11β-HSD1 inhibitors with no activity against 11β-HSD2 and 17β-HSD1. Compound 15 (IC(50)=114 nM) with weak inhibitory activity against the key human cytochrome P450 enzymes and moderate stability in incubation with human liver microsomes is worthy of further development. Importantly, compound 41 (IC(50)=280 nM) provides a new lead that incorporates an adamantyl group surrogate and should enable further series diversification.

  6. Synthesis and characterization of new N-heterocyclic carbene ligands: 1,3-Bis(acetamide)imidazol-3-ium bromide and 3-(acetamide)-1-(3-aminopropyl)-1H-imidazol-3-ium bromide

    Science.gov (United States)

    Turkyilmaz, Murat; Uluçam, Gühergül; Aktaş, Şaban; Okan, S. Erol

    2017-05-01

    Two new pincer type N-heterocyclic carbene ligands were synthesized. The compounds were characterized by FTIR, NMR (1H, 13C) GC-MS and elemental analyses. They were also both modelled by DFT calculations as the crystal structure of 1,3-bis(acetamide)imidazol-3-ium bromide was determined by XRD which is an orthorhombic system with space group P21212. The structural analyses in gas phase were realized by comparing the experimental NMR and IR spectra with those of the theoretical calculations. In vitro biological activities of the molecules were determined and found that one of them exhibits significant cytotoxic activity.

  7. FORMATION OF PEPTIDE BONDS IN SPACE: A COMPREHENSIVE STUDY OF FORMAMIDE AND ACETAMIDE IN Sgr B2(N)

    Energy Technology Data Exchange (ETDEWEB)

    Halfen, D. T.; Ziurys, L. M. [Departments of Chemistry and Astronomy, University of Arizona, Tucson, AZ 85721 (United States); Ilyushin, V., E-mail: halfendt@as.arizona.edu, E-mail: lziurys@as.arizona.edu [Institute of Radio Astronomy of the National Academy of Sciences Ukraine, Chervonopraporna 4, 61002 Kharkov (Ukraine)

    2011-12-10

    Extensive observations of acetamide (CH{sub 3}CONH{sub 2}) and formamide (NH{sub 2}CHO) have been conducted toward Sgr B2(N) at 1, 2, and 3 mm using the Submillimeter Telescope (SMT) and the 12 m antenna of the Arizona Radio Observatory. Over the frequency range 65-280 GHz, 132 transitions of acetamide have been observed as individual, distinguishable features, although in some cases they are partially blended. The unblended transitions in acetamide indicate V{sub LSR} = 63.2 {+-} 2.8 km s{sup -1} and {Delta}V{sub 1/2} = 12.5 {+-} 2.9 km s{sup -1}, line parameters that are very similar to that of formamide (NH{sub 2}CHO) and other organic species in Sgr B2(N). For formamide, 79 individual transitions were identified over the same frequency region. Rotational diagram analyses indicate the presence of two components for both species in Sgr B2(N). For acetamide, the colder component (E{sub u} < 40 K) exhibits a rotational temperature of T{sub rot} = 17 {+-} 4 K and a column density of N{sub tot} = 5.2 {+-} 3.5 Multiplication-Sign 10{sup 13} cm{sup -2}; the higher energy component has T{sub rot} = 171 {+-} 4 K and N{sub tot} = 6.4 {+-} 4.7 Multiplication-Sign 10{sup 14} cm{sup -2}. In the case of formamide, T{sub rot} = 26 {+-} 4 K and N{sub tot} = 1.6 {+-} 0.7 Multiplication-Sign 10{sup 14} cm{sup -2} for the colder component with T{sub rot} = 134 {+-} 17 K and N{sub tot} = 4.0 {+-} 1.2 Multiplication-Sign 10{sup 14} cm{sup -2} for the warmer region. The fractional abundances of acetamide are f (H{sub 2}) = 1.7 Multiplication-Sign 10{sup -11} and 2.1 Multiplication-Sign 10{sup -10} for the cold and warm components, and in formamide, f (H{sub 2}) = 5.3 Multiplication-Sign 10{sup -11} and 1.3 Multiplication-Sign 10{sup -10}. The similarity between the abundances and distributions of CH{sub 3}CONH{sub 2} and NH{sub 2}CHO suggests a synthetic connection. The abundance of acetamide, moreover, is only a factor of three lower than that of formaldehyde, and very similar to

  8. Extraction kinetics of phenol with N, N-di (1-methyl-heptyl)acetamide-kerosene using hollow fiber membrane extractor

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Extraction kinetics of phenol with N, N-di(l-methyl-heptyl) acetamide-kerosene using hollow fiber membrane extractor has been studied. The rate regularities and kinetic types of forward and backward extraction were obtained respectively by determining the forward and backward extraction rate under various experimental conditions. The mass transfer mechanism was discussed. Both the forward and backward extraction of phenol might be controlled by diffusion processes, and the diffusion resistance for both forward and backward extraction mainly exists in aqueous phase. In addition, ways to optimize the extraction process of phenol were discussed as well.

  9. Novel nanofiltration membrane with low concentration of polyvinylchloride: Investigation of solvents’ mixing ratio effect (Dimethyl acetamide/Tetrahydrofuran

    Directory of Open Access Journals (Sweden)

    E. Bagheripour

    2017-05-01

    Full Text Available In the current research polyvinylchloride (PVC nanofiltration membrane was prepared using Dimethyl acetamide (DMAC/Tetrahydrofuran (THF as solvents via the phase inversion method. The effect of solvents’ mixing ratio (DMAC to THF in the casting solution and also phase separation time in coagulation bath on membrane flux and selectivity were studied. The membrane tensile strength measurement and scanning electron microscope (SEM analysis were also carried out in membrane characterization. The highest membrane selectivity and flux were found at (85:15 solvents’ mixing ratio (DMAC to THF.

  10. Comparative study of N-[(4-methoxyphenyl (morpholin-4-ylmethyl]acetamide (MMPA and N-[morpholin-4-yl(phenylmethyl]acetamide (MPA as corrosion inhibitors for mild steel in sulfuric acid solution

    Directory of Open Access Journals (Sweden)

    A. Jamal Abdul Nasser

    2017-02-01

    Full Text Available Two Mannich bases namely, N-[(4-methoxyphenyl(morpholin-4-ylmethyl]acetamide (MMPA and N-[morpholin-4-yl(phenylmethyl]acetamide (MPA were synthesized and their influence on the inhibition of corrosion of mild steel in 1.0 M H2SO4 was investigated by weight loss, potentiodynamic polarization, electrochemical impedance spectroscopy (EIS, scanning electron microscopy (SEM and FT-IR spectroscopy. The weight loss measurements showed that these inhibitors have excellent inhibiting effect at a concentration of 0.01 M. The inhibitor efficiency was found to depend on both concentration and molecular structure of the inhibitor. Both the compounds have been found to be relatively good inhibitors. Potentiodynamic polarization curves revealed that the studied inhibitors represent a mixed-type, predominantly cathodic control. An equivalent circuit is suggested based on an analysis of EIS data. The negative value of standard free energy of adsorption in the presence of inhibitor suggests spontaneous adsorption of inhibitors on the mild steel surface. The activation energy of corrosion and other thermodynamic parameters were calculated to elaborate the mechanism of corrosion inhibition. The Temkin isotherm was found to provide an accurate description of the adsorption behavior of the inhibitors. Surface analysis using scanning electron microscope (SEM shows a significant morphological improvement on the mild steel surface with the addition of inhibitors. FT-IR spectra revealed the interaction between inhibitor molecules and mild steel surface.

  11. Complementary pharmacological and toxicological characterization data on the pharmacological profile of N-(2,6-dichlorophenyl)-2-(4-methyl-1-piperidinyl) acetamide

    OpenAIRE

    Myrna Déciga-Campos; Gabriel Navarrete-Vázquez; Francisco Javier López-Muñoz; Tadeusz Librowski; Amanda Sánchez-Recillas; Victor Yañez-Pérez; Rolffy Ortiz-Andrade

    2016-01-01

    This text presents complementary data corresponding to pharmacological and toxicological characterization of N-(2,6-dichlorophenyl)-2-(4-methyl-1-piperidinyl)acetamide (LIA) compound. These data support our research article entitled “Pharmacological profile of N-(2,6-dichlorophenyl)-2-(4-methyl-1-piperidinyl)acetamide, a novel analog of lidocaine” Déciga-Campos M., Navarrete-Vázquez G., López-Muñoz F.J., Librowski T., Sánchez-Recillas A., Yañez-Pérez V., Ortiz-Andrade R. (2016) [1]. Toxicity ...

  12. Monitoring 2-phenylethanamine and 2-(3-hydroxyphenyl)acetamide sulfate in doping controls.

    Science.gov (United States)

    Sigmund, Gerd; Dib, Josef; Tretzel, Laura; Piper, Thomas; Bosse, Christina; Schänzer, Wilhelm; Thevis, Mario

    2015-01-01

    2-Phenylethanamine (phenethylamine, PEA) represents the core structure of numerous drugs with stimulant-like properties and is explicitly featured as so-called specified substance on the World Anti-Doping Agency (WADA) Prohibited List. Due to its natural occurrence in humans as well as its presence in dietary products, studies concerning the ability of test methods to differentiate between an illicit intake and the renal elimination of endogenously produced PEA were indicated. Following the addition of PEA to the Prohibited List in January 2015, retrospective evaluation of routine doping control data of 10 190 urine samples generated by combined gas chromatography-mass spectrometry and nitrogen phosphorus-specific detection (GC-MS/NPD) was performed. Signals for PEA at approximate concentrations > 500 ng/mL were observed in 31 cases (0.3%), which were subjected to a validated isotope-dilution liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS) test method for accurate quantification of the target analyte. Further, using elimination study urine samples collected after a single oral administration of 250 mg of PEA hydrochloride to two healthy male volunteers, two tentatively identified metabolites of PEA were observed and evaluated concerning their utility as discriminative markers for PEA intake. The ID-LC-MS/MS approach was extended to allow for the simultaneous detection of PEA and 2-(3-hydroxyphenyl)acetamide sulfate (M1), and concentration ratios of M1 and PEA were calculated for elimination study urine samples and a total of 205 doping control urine samples that returned findings for PEA at estimated concentrations of 50-2500 ng/mL. Urine samples of the elimination study with PEA yielded concentration ratios of M1/PEA up to values of 9.4. Notably, the urinary concentration of PEA did increase with the intake of PEA only to a modest extent, suggesting a comprehensive metabolism of the orally administered substance. Conversely, doping control

  13. Copper(II) bromide, nitrate and perchlorate complexes with sterically demanding N-(6-methylpyridin-2-yl)acetamide ligands.

    Science.gov (United States)

    Smolentsev, Anton I

    2017-08-01

    Functionalized acid amides are widely used in biology, medicine, environmental chemistry and many other areas. Among them, pyridine-substituted amides, in particular N-(pyridin-2-yl)acetamide and its derivatives, play an important role due to their excellent chelating properties. The donor properties of these ligands can be effectively modified by introducing electron-donating substituents (e.g. alkyl groups) into the heterocycle. On the other hand, substituents in the α-position of the pyridine ring can create steric hindrance, which significantly influences the coordination number and geometry. To achieve a better understanding of these effects, copper(II) complexes with sterically demanding N-(6-methylpyridin-2-yl)acetamide ligands (L) and monoanions of different size, shape and coordination ability have been chosen as model compounds. The crystal structures of three new compounds, bromidobis[N-(6-methylpyridin-2-yl-κN)acetamide-κO]copper(II) bromide, [CuBr(C8H10N2O)]Br, (I), aquabis[N-(6-methylpyridin-2-yl-κN)acetamide-κO]copper(II) dinitrate, [Cu(C8H10N2O)(H2O)](NO3)2, (II), and aquabis[N-(6-methylpyridin-2-yl-κN)acetamide-κO]copper(II) bis(perchlorate), [Cu(C8H10N2O)(H2O)](ClO4)2, (III), have been determined by single-crystal X-ray diffraction analysis. It has been shown that the presence of the 6-methyl group results in either a distorted square-pyramidal or a distorted trigonal-bipyramidal coordination geometry around the Cu(II) centres instead of the typical octahedral geometry observed when the methyl substituent is absent or occupies any other position on the pyridine ring. Moreover, due to the steric hindrance provided by the L ligands, only the bromide ligand, the smallest of the series, enters into the first coordination sphere of the Cu(II) ion in (I). In (II) and (III), the vacant coordination site of the Cu(II) ion is occupied by a water molecule, while the nitrate and perchlorate anions are not involved in coordination to the metal centre

  14. VUV photoionization of acetamide studied by electron/ion coincidence spectroscopy in the 8-24 eV photon energy range

    Energy Technology Data Exchange (ETDEWEB)

    Schwell, Martin, E-mail: Martin.Schwell@lisa.u-pec.fr [LISA UMR CNRS 7583, Universite Paris Est Creteil and Universite Paris Diderot, Institut Pierre Simon Laplace, 61 Avenue du General de Gaulle, 94010 Creteil (France); Benilan, Yves; Fray, Nicolas; Gazeau, Marie-Claire; Es-Sebbar, Et. [LISA UMR CNRS 7583, Universite Paris Est Creteil and Universite Paris Diderot, Institut Pierre Simon Laplace, 61 Avenue du General de Gaulle, 94010 Creteil (France); Garcia, Gustavo A.; Nahon, Laurent [Synchrotron SOLEIL, L' Orme des Merisiers, St. Aubin, B.P. 48, 91192 Gif-sur-Yvette Cedex (France); Champion, Norbert [LERMA UMR CNRS 8112, Observatoire de Paris-Meudon, 5 place Jules-Jansen, 92195 Meudon (France); Leach, Sydney, E-mail: Sydney.Leach@obspm.fr [LERMA UMR CNRS 8112, Observatoire de Paris-Meudon, 5 place Jules-Jansen, 92195 Meudon (France)

    2012-01-17

    Highlights: Black-Right-Pointing-Pointer We study the VUV photoionization of acetamide in the 8-24 eV photon energy range. Black-Right-Pointing-Pointer Electron/ion coincidence measurements are performed using synchrotron radiation. Black-Right-Pointing-Pointer The adiabatic ionization energy of acetamide is determined by TPEPICO measurements. Black-Right-Pointing-Pointer VUV induced fragmentation pathways of acetamide are assigned and discussed. - Abstract: A VUV photoionization study of acetamide was carried out over the 8-24 eV photon energy range using synchrotron radiation and photoelectron/photoion coincidence (PEPICO) spectroscopy. Threshold photoelectron photoion coincidence (TPEPICO) measurements were also made. Photoion yield curves and branching ratios were measured for the parent ion and six fragment ions. The adiabatic ionization energy of acetamide was determined as I.E. (1{sup 2}A Prime ) = (9.71 {+-} 0.02) eV, in agreement with an earlier reported photoionization mass spectrometry (PIMS) value. The adiabatic energy of the first excited state of the ion, 1{sup 2}A Double-Prime , was determined to be Almost-Equal-To 10.1 eV. Assignments of the fragment ions and the pathways of their formation by dissociative photoionization were made. The neutral species lost in the principal dissociative photoionization processes are CH{sub 3}, NH{sub 2}, NH{sub 3}, CO, HCCO and NH{sub 2}CO. Heats of formation are derived for all ions detected and are compared with literature values. Some astrophysical implications of these results are discussed.

  15. Conformational analysis of some N,N-diethyl-2-[(4'-substituted) phenylthio] acetamides.

    Science.gov (United States)

    Vinhato, Elisângela; Olivato, Paulo R; Zukerman-Schpector, Julio; Dal Colle, Maurizio

    2013-11-01

    The conformational analysis of some N,N-diethyl-2[(4'-substituted)phenylthio]acetamides bearing the substituents OMe 1, Me 2, H 3, Cl 4, Br 5 and NO26, was performed by νCO IR analysis, along with B3LYP/6-311++G(d,p) and Polarisable Continuum Model (PCM) calculations, as well as NBO analysis for 1, 3, and 6 and X-ray diffraction for 4. The results of the calculations indicated the existence of two stable conformation pairs, i.e. gauche (anti; syn) (most stable) and cis (anti; syn) in the gas phase. The gauche conformers were less polar with respect to the cis ones for 1 and 3, but more polar for 6. The most intense IR carbonyl doublet component observed at the lower frequency can be ascribed to the gauche conformers g(anti; syn) for 3-6 in n-C6H14, which is in agreement with the gauche and cis relative stabilities and frequencies resulting from the PCM calculations. Similarly, the single IR band for 1 and 2 in n-hexane may be attributed to the gauche conformers. The PCM calculations compared well with the IR data for the compounds in solution, showing that there is a progressive increase of the cis/gauche population ratio as the solvent polarity increases. The NBO analysis indicated that the gauche(anti; syn) conformation in the gas phase was stabilized by the relevant LPS4→πC2O1(∗),πC2O1→σC3S4(∗),σC3S4→πC2O1(∗),πC2O1(∗)→σC3S4(∗), and LPO1→σ(∗)C11H28 orbital interactions, which were absent in the cis(anti; syn) conformer. On the contrary, the cis conformer for derivatives 1, 3, and 6 were stabilized by the σC3-S4(∗)→σ(∗)C2N5 orbital interaction (through bond coupling), along with the additional LPO1→σ(∗)S4C10 interaction for 6. Moreover, the electrostatic repulsion between the C(δ+)S(δ-) and C(δ+)O(δ-) dipoles (Repulsive Field Effect) contributed to both the larger destabilization and increase of the νCO frequency of the cis conformer with respect to the gauche conformer. X-ray single crystal analysis indicates that

  16. Larvicidal activity and click synthesis of 2-alkoxyl-2-(1,2,3-triazole-1- yl)acetamide library.

    Science.gov (United States)

    Su, Na-Na; Xiong, Li-Xia; Yu, Shu-Jing; Zhang, Xiao; Cui, Can; Li, Zheng-Ming; Zhao, Wei-Guang

    2013-07-01

    Heterogeneous copper-in-charcoal-catalyzed click synthesis in 96-well polypropylene filter plates is an efficient method for the rapid generation of sufficient pure 2-alkoxyl-2-(1,2,3-triazole-1-yl) acetamide derivatives library by simple filtration, which directly assay the products for larvicidal activity against mosquitoes. In this procedure, copper nanoparticles on charcoal were arrayed into each well on a 96-well plate, reagents were delivered using a pipette gun, and a constant temperature shaker bath was used to complete the click reaction in 24-72 hours under temperature-controlled conditions. The results of bioassays indicated that the target compounds possessed excellent larvacidal activities against mosquitoes. In particular, the larvacidal activities against mosquitoes of compounds 8[2,3] and 8[7,1] at 2 µg.mL⁻¹ were 100% and 73% respectively.

  17. Backing of 2-(diethylamino-N-(2, 6-dimethylphenyl-acetamide with molecular, electronic and docking studies

    Directory of Open Access Journals (Sweden)

    J. Deva Anban

    2017-09-01

    Full Text Available In this study, the anaesthetic compound 2-(diethylamino-N-(2, 6-dimethylphenyl-acetamide (DEAL was optimized with the B3LYP-6-311+G (d, p density functional theory method. Hyper conjugative interactions revealed the bioactivity of the molecule by natural bond orbital analysis. The current–potential curves were noted at well-defined scan rates by cyclic voltammetry. The solvation free energy was calculated by applying the solvation model on density. Molecular docking simulations were carried out to understand the pharmacokinetic behaviour of the drug. Besides, total energy levels of HOMO-LUMO orbitals, Mulliken atomic charges, natural population analysis and polarizability properties of the molecule were calculated. We found that the secondary amide increases the stability of this molecule. The π → π∗ interactions increase the biological activity of the compound, leading to a very high stabilization.

  18. Novel energy saving strategy for separating acetic acid – water in extractive distillation with N-methyl acetamide as entrainer

    Science.gov (United States)

    You, Xinqiang; Peng, Changjun; Liu, Honglai

    2017-09-01

    The design of homogeneous extractive distillation for acetic acid (AA) dehydration with N-methyl acetamide (NMA) as entrainer was investigated. It belongs to the classification of 0.0-1. The main challenge is that NMA and AA will lead to another pinch point, probably leading to energy cost and total annual cost (TAC) increase. Through analyzing thermodynamic insight, we have proposed a new strategy: low recycling entrainer purity for the extractive distillation of class 0.0-1 with no univolatility line existing. The strategy could save energy cost by avoiding the approach of the pinch point between AA and NMA. We have run sequence iterative optimization method for the process optimization. The total eleven variables are optimized. Results show that energy consumption and TAC are reduced by 50.6% and 52.1%, respectively. The results also reveal that a suitable shift of the feed tray locations improves the efficiency of the separation, even when less entrainer is used.

  19. Synthesis of N-(6-Arylbenzo[d]thiazole-2-acetamide Derivatives and Their Biological Activities: An Experimental and Computational Approach

    Directory of Open Access Journals (Sweden)

    Yasmeen Gull

    2016-02-01

    Full Text Available A new series of N-(6-arylbenzo[d]thiazol-2-ylacetamides were synthesized by C-C coupling methodology in the presence of Pd(0 using various aryl boronic pinacol ester/acids. The newly synthesized compounds were evaluated for various biological activities like antioxidant, haemolytic, antibacterial and urease inhibition. In bioassays these compounds were found to have moderate to good activities. Among the tested biological activities screened these compounds displayed the most significant activity for urease inhibition. In urease inhibition, all compounds were found more active than the standard used. The compound N-(6-(p-tolylbenzo[d]thiazol-2-ylacetamide was found to be the most active. To understand this urease inhibition, molecular docking studies were performed. The in silico studies showed that these acetamide derivatives bind to the non-metallic active site of the urease enzyme. Structure-activity studies revealed that H-bonding of compounds with the enzyme is important for its inhibition.

  20. Vibrational, spectroscopic, molecular docking and density functional theory studies on N-(5-aminopyridin-2-yl)acetamide

    Science.gov (United States)

    Asath, R. Mohamed; Rekha, T. N.; Premkumar, S.; Mathavan, T.; Benial, A. Milton Franklin

    2016-12-01

    Conformational analysis was carried out for N-(5-aminopyridin-2-yl)acetamide (APA) molecule. The most stable, optimized structure was predicted by the density functional theory calculations using the B3LYP functional with cc-pVQZ basis set. The optimized structural parameters and vibrational frequencies were calculated. The experimental and theoretical vibrational frequencies were assigned and compared. Ultraviolet-visible spectrum was simulated and validated experimentally. The molecular electrostatic potential surface was simulated. Frontier molecular orbitals and related molecular properties were computed, which reveals that the higher molecular reactivity and stability of the APA molecule and further density of states spectrum was simulated. The natural bond orbital analysis was also performed to confirm the bioactivity of the APA molecule. Antidiabetic activity was studied based on the molecular docking analysis and the APA molecule was identified that it can act as a good inhibitor against diabetic nephropathy.

  1. Distinct molecular structures and hydrogen bond patterns of α,α-diethyl-substituted cyclic imide, lactam, and acetamide derivatives in the crystalline phase

    Science.gov (United States)

    Krivoshein, Arcadius V.; Ordonez, Carlos; Khrustalev, Victor N.; Timofeeva, Tatiana V.

    2016-10-01

    α,α-Dialkyl- and α-alkyl-α-aryl-substituted cyclic imides, lactams, and acetamides show promising anticonvulsant, anxiolytic, and anesthetic activities. While a number of crystal structures of various α-substituted cyclic imides, lactams, and acetamides were reported, no in-depth comparison of crystal structures and solid-state properties of structurally matched compounds have been carried out so far. In this paper, we report molecular structure and intermolecular interactions of three α,α-diethyl-substituted compounds - 3,3-diethylpyrrolidine-2,5-dione, 3,3-diethylpyrrolidin-2-one, and 2,2-diethylacetamide - in the crystalline phase, as studied using single-crystal X-ray diffraction and IR spectroscopy. We found considerable differences in the patterns of H-bonding and packing of the molecules in crystals. These differences correlate with the compounds' melting points and are of significance to physical pharmacy and formulation development of neuroactive drugs.

  2. Mechanistic Insights into the Palladium(II)-catalyzed Intramolecular Cyclization of o-Alkynylphenylphosphonamide and N-(o-Alkynylphenyl)acetamide by Electrospray Ionization Mass Spectrometry

    Institute of Scientific and Technical Information of China (English)

    ZHOU Jing; TANG Wei; GUO Yinlong; DING Yixiang

    2009-01-01

    The intramolecular cyclization of o-alkynylphenylphosphonamide and N-(o-alkynylphenyl)acetamide was monitored by electrospray ionization mass spectrometry(ESI-MS)and its tandem version(ESI-MS/MS).The proposed intermediates were successfully intercepted and characterized.In addition,the intermediates composed of the substrate coordinated to the palladium(Ⅱ)center in the reaction of o-alkynylphenylphosphonamide were unexpected before,and this interesting phenomenon of the substrate coordination seems associated with the unique structure of substrates.

  3. Dielectric relaxation of ethanol and -methyl acetamide polar mixture in C6H6 at 9.90 GHz

    Indian Academy of Sciences (India)

    S Sahoo; T R Middya; S K Sit

    2014-10-01

    Debye relaxation times $(_{jk})$ and dipole moments $(_{jk})$ of binary ($jk$) polar mixtures of ethanol (EtOH) and -methyl acetamide (NMA) dissolved in benzene(i) are studied by studying conductivity of solution at 9.90 GHz for different temperatures, different mole fractions ($x_j$) of ethanol and different weight fractions $(w_{jk})$ of the mixtures, respectively. The variation of $_{jk}−x_j$ from linear slope of imaginary ($''_{ijk}$) against real ($'_{ijk}$) part of total conductivity ($^{*}_{ijk}$) curve reveals solute–solute (dimer) or solute–solvent (monomer) molecular associations up to $x_j$ = 0.0−0.3 and thereafter, solute–solvent molecular associations. $_{jk}$s from the ratio of slopes of $''_{ijk}$−w_{jk}$ and $'_{ijk}$−w_{jk}$ curves exhibit solute–solvent molecular association for all $x_j$s which are consistent with the $_{jk}−x_j$ curves at all temperatures except at 35°C. This signifies the validity of both the proposed methods in estimating and . The molecular dynamics of the polar mixture are ascertained from Eyring rate theory. Theoretical dipole moments from bond angles and bond moments ($_{\\text{theo}}$) are also calculated to predict associational aspects.

  4. Synthesis, Structural Elucidation, and Antibacterial Evaluation of Some New Molecules Derived from Coumarin, 1,3,4-Oxadiazole, and Acetamide

    Directory of Open Access Journals (Sweden)

    Shahid Rasool

    2016-01-01

    Full Text Available Because of the reported biological activities of coumarin, 1,3,4-oxadiazole, and acetamides, some new compounds incorporating these moieties were synthesized and evaluated for their biological potential against Gram-positive and Gram-negative bacteria. In the present work, 4-chlororesorcinol (1 and ethyl acetoacetate (2 were mixed in a strong acidic medium to synthesize 6-chloro-7-hydroxy-4-methyl-2-oxo-2H-chromene (3 which was subjected to the intermolecular cyclization after consecutive three steps to synthesize 5-[(6-chloro-4-methyl-2-oxo-2H-chromen-7-yloxy]methyl-1,3,4-oxadiazol-2-thiol (6. A series of acetamoyl electrophiles, 8a–o, were synthesized from aralkyl/alkyl/aryl amines, 7a–o, in an aqueous basic medium. The final compounds, 9a–o, were synthesized by the reaction of compounds 6 and 8a–o in DMF/NaH. The synthesized compounds were structurally elucidated by spectral data analysis of IR, 1H-NMR, and EIMS. The most of the synthesized compounds remained moderate to excellent antibacterial agents. The molecules, 9e, 9j, and 9k, were the most efficient ones against all the five bacterial strains taken into account.

  5. Synthesis of nitro(benzo)thiazole acetamides and in vitro antiprotozoal effect against amitochondriate parasites Giardia intestinalis and Trichomonas vaginalis.

    Science.gov (United States)

    Navarrete-Vázquez, Gabriel; Chávez-Silva, Fabiola; Colín-Lozano, Blanca; Estrada-Soto, Samuel; Hidalgo-Figueroa, Sergio; Guerrero-Álvarez, Jorge; Méndez, Sara T; Reyes-Vivas, Horacio; Oria-Hernández, Jesús; Canul-Canché, Jaqueline; Ortiz-Andrade, Rolffy; Moo-Puc, Rosa

    2015-05-01

    We synthesized four 5-nitrothiazole (1-4) and four 6-nitrobenzothiazole acetamides (5-8) using an easy two step synthetic route. All compounds were tested in vitro against amitochondriate parasites Giardia intestinalis and Trichomonas vaginalis, showing excellent antiprotozoal effects. IC₅₀'s of the most potent compounds range from nanomolar to low micromolar order, being more active than their drugs of choice. Compound 1 (IC₅₀=122 nM), was 44-times more active than Metronidazole, and 10-fold more effective than Nitazoxanide against G. intestinalis and showed good trichomonicidal activity (IC₅₀=2.24 μM). This compound did not display in vitro cytotoxicity against VERO cells. The in vitro inhibitory effect of compounds 1-8 and Nitazoxanide against G. intestinalis fructose-1,6-biphosphate aldolase (GiFBPA) was evaluated as potential drug target, showing a clear inhibitory effect over the enzyme activity. Molecular docking of compounds 1, 4 and Nitazoxanide into the ligand binding pocket of GiFBPA, revealed contacts with the active site residues of the enzyme. Ligand efficiency metrics of 1 revealed optimal combinations of physicochemical and antiprotozoal properties, better than Nitazoxanide.

  6. Enantioselective synthesis and teratogenicity of propylisopropyl acetamide, a CNS-active chiral amide analogue of valproic acid.

    Science.gov (United States)

    Spiegelstein, O; Bialer, M; Radatz, M; Nau, H; Yagen, B

    1999-01-01

    Propylisopropyl acetamide (PID), an amide analogue of the major antiepileptic drug valproic acid (VPA), possesses favorable anticonvulsant and CNS properties. PID contains one chiral carbon atom and therefore exists in two enantiomeric forms. The purpose of this work was to synthesize the two PID enantiomers and evaluate their enantiospecific teratogenicity. Enantioselective synthesis of PID enantiomers was achieved by coupling valeroyl chloride with optically pure (4S)- and (4R)-benzyl-2-oxazolidinone chiral auxiliaries. The two oxazolidinone enolates were alkylated with isopropyl triflate, hydrolyzed, and amidated to yield (2R)- and (2S)-PID. These two PID enantiomers were obtained with excellent enantiomeric purity, exceeding 99.4%. Unlike VPA, both (2R)- and (2S)-PID failed to exert teratogenic effects in NMRI mice following a single 3 mmol/kg subcutaneous injection. From this study we can conclude that individual PID enantiomers do not demonstrate stereoselective teratogenicity in NMRI mice. Due to its better anticonvulsant activity than VPA and lack of teratogenicity, PID (in a stereospecific or racemic form) has the potential to become a new antiepileptic and CNS drug.

  7. Synthesis and Antibacterial Activity Study of N-Substituted Acetamide Derivatives of 4-Hydroxy-2-oxo-2H-Chromene

    Directory of Open Access Journals (Sweden)

    *Aziz-ur-Rehman

    2015-06-01

    Full Text Available The heterocyclic coumarin derivatives are well known for their biological potential. The presented work demonstrates the evaluation of some N-substituted acetamoyl derivatives of 4-hydroxy-2-oxo-2H-chromene (4 against certain strains of gram bacteria. First, N¬-substituted-2-bromoacetamide, 3a-r, were synthesized by the reaction of aralkyl/aryl amines, 1a-r, with 2-bromoacetyl bromide (2 in an aqueous medium under definite pH control. In the second step, the resulted electrophiles, 3a-r, were made to react 4 in a polar aprotic solvent using a weak base as an activator to synthesize the final N-substituted-2-[(2-oxo-2H-chromen-4-yloxy]acetamide, 5a-r. The synthesis of compounds, 5a-r, was corroborated by TLC initially and spectral data of IR, 1H-NMR and EIMS finally. The MIC results of antibacterial activity rendered these molecules valuable inhibitors of all the bacterial strains taken into account.

  8. Density relaxation and particle motion characteristics in a non-ionic deep eutectic solvent (acetamide + urea): Time-resolved fluorescence measurements and all-atom molecular dynamics simulations

    Energy Technology Data Exchange (ETDEWEB)

    Das, Anuradha; Das, Suman; Biswas, Ranjit, E-mail: ranjit@bose.res.in [Chemical, Biological and Macromolecular Sciences, S. N. Bose National Centre for Basic Sciences, Block-JD, Sector-III, Salt Lake, Kolkata, West Bengal 700098 (India)

    2015-01-21

    Temperature dependent relaxation dynamics, particle motion characteristics, and heterogeneity aspects of deep eutectic solvents (DESs) made of acetamide (CH{sub 3}CONH{sub 2}) and urea (NH{sub 2}CONH{sub 2}) have been investigated by employing time-resolved fluorescence measurements and all-atom molecular dynamics simulations. Three different compositions (f) for the mixture [fCH{sub 3}CONH{sub 2} + (1 − f)NH{sub 2}CONH{sub 2}] have been studied in a temperature range of 328-353 K which is ∼120-145 K above the measured glass transition temperatures (∼207 K) of these DESs but much lower than the individual melting temperature of either of the constituents. Steady state fluorescence emission measurements using probe solutes with sharply different lifetimes do not indicate any dependence on excitation wavelength in these metastable molten systems. Time-resolved fluorescence anisotropy measurements reveal near-hydrodynamic coupling between medium viscosity and rotation of a dissolved dipolar solute. Stokes shift dynamics have been found to be too fast to be detected by the time-resolution (∼70 ps) employed, suggesting extremely rapid medium polarization relaxation. All-atom simulations reveal Gaussian distribution for particle displacements and van Hove correlations, and significant overlap between non-Gaussian (α{sub 2}) and new non-Gaussian (γ) heterogeneity parameters. In addition, no stretched exponential relaxations have been detected in the simulated wavenumber dependent acetamide dynamic structure factors. All these results are in sharp contrast to earlier observations for ionic deep eutectics with acetamide [Guchhait et al., J. Chem. Phys. 140, 104514 (2014)] and suggest a fundamental difference in interaction and dynamics between ionic and non-ionic deep eutectic solvent systems.

  9. Synthesis and evaluation of 2-(5-(aryl)-1,3,4-oxadiazol-2-ylthio)-N-(3-(trifluoromethyl)phenyl)acetamides and N-(4-chloro-3-fluorophenyl)-2-(5-(aryl)-1,3,4-oxadiazol-2-ylthio)acetamides as antimicrobial agents

    Indian Academy of Sciences (India)

    Kalpesh Parikh; Deepkumar Joshi

    2014-05-01

    A series of 2-mercapto-5-phenyl-1,3,4-oxadiazole derivatives have been condensed with different phenyl acetamide derivatives possessing fluorine atom at meta position; resulting in the formation of 2-(5-aryl- 1,3,4-oxadiazol-2-ylthio)-N-(3-(trifluoromethyl)phenyl)acetamide (5a-j) and N-(4-chloro-3-fluorophenyl)-2-(5-aryl-1,3,4-oxadiazol-2-ylthio)acetamide (5k-t) derivatives. The antimicrobial properties of the synthesized entities (5a-t) measured as their MIC (Minimum Inhibitory Concentration) values were evaluated by using the broth dilution method against Gram-positive bacteria (S. aureus and E. faecalis), Gram-negative bacteria (E. coli and P. aeruginosa) and fungi (C. albicans and A. niger). The results of antimicrobial activities (in g/ml) revealed the fact that the compounds 5a and g bearing a maximum number of fluorine atoms showed the highest potency among the synthesized compounds against the broad panel of bacterial and fungal strains. The presence of fluorine atom at the meta position in the phenyl ring of final derivatives (5a-t) brought about an enhancement of their antimicrobial properties to a notable extent.

  10. Extraction kinetics of phenol with N, N-di (1-methyl-heptyl) acetamide-kerosene using hollow fiber membrane extractor.

    Science.gov (United States)

    Yang, Z X; Du, H F; Sun, X B; Xia, Y; Zhou, Z M

    2001-07-01

    Extraction kinetics of phenol with N,N-di(1-methyl-heptyl) acetamide-kerosene using hollow fiber membrane extractor has been studied. The rate regularities and kinetic types of forward and backward extraction were obtained respectively by determining the forward and backward extraction rate under various experimental conditions. The mass transfer mechanism was discussed. Both the forward and backward extraction of phenol might be controlled by diffusion processes, and the diffusion resistance for both forward and backward extraction mainly exists in aqueous phase. In addition, ways to optimize the extraction process of phenol were discussed as well.

  11. Electrochemical preparation of few layer-graphene nanosheets via reduction of oriented exfoliated graphene oxide thin films in acetamide-urea-ammonium nitrate melt under ambient conditions

    Energy Technology Data Exchange (ETDEWEB)

    Dilimon, V.S.; Sampath, S., E-mail: sampath2562@gmail.co

    2011-01-31

    Electrochemical reduction of exfoliated graphene oxide, prepared from pre-exfoliated graphite, in acetamide-urea-ammonium nitrate ternary eutectic melt results in few layer-graphene thin films. Negatively charged exfoliated graphene oxide is attached to positively charged cystamine monolyer self-assembled on a gold surface. Electrochemical reduction of the oriented graphene oxide film is carried out in a room temperature, ternary molten electrolyte. The reduced film is characterized by atomic force microscopy (AFM), conductive AFM, Fourier-transform infrared spectroscopy and Raman spectroscopy. Ternary eutectic melt is found to be a suitable medium for the regulated reduction of graphene oxide to reduced graphene oxide-based sheets on conducting surfaces.

  12. Inhibition of β-N-acetylglucosaminidase by acetamide affects sperm motility and fertilization success of rainbow trout (Oncorhynchus mykiss) and Siberian sturgeon (Acipenser baerii).

    Science.gov (United States)

    Sarosiek, B; Glogowski, J; Cejko, B I; Kujawa, R; Szczepkowski, M; Kuźmiński, H; Dobosz, S; Kowalski, R K

    2014-03-15

    β-N-Acetylglucosaminidase (β-NAGase) is an enzyme found in the sperm acrosome of numerous animal species including fish. Fish spermatozoa differ in their morphology including acrosome or acrosomeless aquasperm in chondrostean (e.g., sturgeon) and teleostean (e.g., rainbow trout). It has been shown that β-NAGase exists with high activity in both eggs and sperm of these species. The present study shows the potency of β-NAGase in fertilization. In rainbow trout, increase in sperm motility parameters (VAP and MOT) were observed in the presence of acetamide, an inhibitor for β-NAGase. In contrast, sperm motility parameters (VCL, VSL, VAP, MOT, and PRG) were reduced on the Siberian sturgeon in the presence of acetamide. The inhibition of the activity of β-NAGase in rainbow trout spermatozoa was led to a reduction in the number of fertilized eggs from 79% to 40%, whereas in sturgeon no change was observed in fertilization. Moreover, inhibition of β-NAGase in both spermatozoa and eggs of trout and sturgeon resulted in significant decrease in fertilization rate from 79% to 1% in rainbow trout and from 84% to 12% in Siberian sturgeon. Our research proves that β-NAGase can play a significant role in the fertilization process in teleosteans.

  13. VUV photoionization of acetamide studied by electron/ion coincidence spectroscopy in the 8-24 eV photon energy range

    KAUST Repository

    Schwell, Martin

    2012-01-01

    A VUV photoionization study of acetamide was carried out over the 8-24 eV photon energy range using synchrotron radiation and photoelectron/photoion coincidence (PEPICO) spectroscopy. Threshold photoelectron photoion coincidence (TPEPICO) measurements were also made. Photoion yield curves and branching ratios were measured for the parent ion and six fragment ions. The adiabatic ionization energy of acetamide was determined as I.E. (1 2A′) = (9.71 ± 0.02) eV, in agreement with an earlier reported photoionization mass spectrometry (PIMS) value. The adiabatic energy of the first excited state of the ion, 1 2A″, was determined to be ≈10.1 eV. Assignments of the fragment ions and the pathways of their formation by dissociative photoionization were made. The neutral species lost in the principal dissociative photoionization processes are CH 3, NH 2, NH 3, CO, HCCO and NH 2CO. Heats of formation are derived for all ions detected and are compared with literature values. Some astrophysical implications of these results are discussed. © 2011 Elsevier B.V. All rights reserved.

  14. Synthesis and pharmacological evaluation of 2-(1-alkylpiperidin-4-yl)-n-[(1r)-1-(4-fluorophenyl)-2-methylpropyl]acetamide Derivatives as Novel Antihypertensive Agents.

    Science.gov (United States)

    Watanuki, Susumu; Matsuura, Keisuke; Tomura, Yuichi; Okada, Minoru; Okazaki, Toshio; Ohta, Mitsuaki; Tsukamoto, Shin-ichi

    2012-01-01

    We synthesized and evaluated the inhibitory activity of a series of 2-(1-alkylpiperidin-4-yl)-N-[(1R)-1-(4-fluorophenyl)-2-methylpropyl]acetamide derivatives against T-type Ca(2+) channels. Structure-activity relationship studies revealed that the position of the amide structure was important for the potent inhibitory activity toward T-type Ca(2+) channels. In addition, the introduction of an appropriate substituent on the pendant benzene ring played a crucial role for the selectivity towards T-type Ca(2+) channels over L-type Ca(2+) channels and the potent bradycardic activity of these derivatives. Oral administration of N-[(1R)-1-(4-fluorophenyl)-2-methylpropyl]-2-(1-{2-[2-(2-methoxyethoxy)phenyl]ethyl}piperidin-4-yl)acetamide (4f), which had superior selectivity for T-type Ca(2+) channels over L-type Ca(2+) channels, lowered blood pressure in spontaneously hypertensive rats without inducing reflex tachycardia, which is often caused by traditional L-type Ca(2+) channel blockers.

  15. In Vivo Quantification of Cerebral Translocator Protein Binding in Humans Using 6-Chloro-2-(4′-123I-Iodophenyl)-3-(N,N-Diethyl)-Imidazo[1,2-a]Pyridine-3-Acetamide SPECT

    DEFF Research Database (Denmark)

    Feng, Ling; Svarer, Claus; Thomsen, Gerda;

    2014-01-01

    UNLABELLED: This study provides the first comprehensive quantification of translocator protein (TSPO) binding using SPECT and 6-chloro-2-(4'-(123)I-iodophenyl)-3-(N,N-diethyl)-imidazo[1,2-a]pyridine-3-acetamide ((123)I-CLINDE) in neurologic patients. (123)I-CLINDE is structurally related to well...

  16. Some Unusual Rheological Responses of Poly(Vinylidene Fluoride-Co-Hexafluoropropylene) Solutions in Dimethyl Acetamide and Their Effects on the Electrospinning Process

    Science.gov (United States)

    Seo, Jae Sik; Lee, Ki Hyun; Kim, Byoung Chul

    2008-07-01

    The rheological properties of poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) in dimethyl acetamide (DMAc) were investigated to obtain preliminary data for electrospinning. Intrinsic viscosity data suggested that solubility of PVDF-HFP was reduced with increasing temperature. Over the temperature range of 30 to 70 °C, the dynamic viscosity of the concentrated solutions was increased with increasing temperature and Bingham behavior became more noticed. In addition, increase of temperature and concentration of the solutions increased yield stress and relaxation time. Although the dynamic viscosity was increased with increasing temperature, electrospinning temperature had little effects on the resultant fiber morphology on the condition that other spinning conditions were identical.

  17. A Distributed Computing Method for Crystal Structure Prediction of Flexible Molecules:  An Application to N-(2-Dimethyl-4,5-dinitrophenyl) Acetamide.

    Science.gov (United States)

    Bazterra, Victor E; Thorley, Matthew; Ferraro, Marta B; Facelli, Julio C

    2007-01-01

    In this paper, we describe a new distributed computing framework for crystal structure prediction that is capable of performing crystal structure searches for flexible molecules within any space group and with an arbitrary number of molecules in the asymmetric unit. The distributed computing framework includes a series of tightly integrated computer programs for generating the molecule's force field, sampling possible crystal structures using a distributed parallel genetic algorithm, locally minimizing these structures and classifying, sorting, and archiving the most relevant ones. As an example, we report the results of its application to the prediction of the crystal structure of the elusive N-(2-dimethyl-4,5-dinitrophenyl) acetamide, a molecule for which its crystal structure proved to be one of the most difficult cases in the last CSP2004 blind test for crystal structure prediction.

  18. Selective and potent adenosine A3 receptor antagonists by methoxyaryl substitution on the N-(2,6-diarylpyrimidin-4-yl)acetamide scaffold.

    Science.gov (United States)

    Yaziji, Vicente; Rodríguez, David; Coelho, Alberto; García-Mera, Xerardo; El Maatougui, Abdelaziz; Brea, José; Loza, María Isabel; Cadavid, María Isabel; Gutiérrez-de-Terán, Hugo; Sotelo, Eddy

    2013-01-01

    The influence of diverse methoxyphenyl substitution patterns on the N-(2,6-diarylpyrimidin-4-yl)acetamide scaffold is herein explored in order to modulate the A(3) adenosine receptor antagonistic profile. As a result, novel ligands exhibiting excellent potency (K(i) on A(3) AR < 20 nM) and selectivity profiles (above 100-fold within the adenosine receptors family) are reported. Moreover, our joint theoretical and experimental approach allows the identification of novel pharmacophoric elements conferring A(3)AR selectivity, first established by a robust computational model and thereafter characterizing the most salient features of the structure-activity and structure-selectivity relationships in this series.

  19. Study on Deactivation by Sulfur and Regeneration of Pd/C Catalyst in Hydrogenation of N-(3-nitro-4-methoxyphenyl) Acetamide

    Institute of Scientific and Technical Information of China (English)

    ZHANG Qunfeng; L(U) Jinghui; MA Lei; LU Chunshan; LIU Wei; LI Xiaonian

    2013-01-01

    Deactivation of Pd/C catalyst often occurs in liquid hydrogenation using industrial materials.For instance,the Pd/C catalyst is deactivated severely in the hydrogenation of N-(3-nitro-4-methoxyphenyl) acetamide.In this study,the chemisorption of sulfur on the surface of deactivated Pd/C was detected by energy dispersive spectrometer and X-ray photoelectron spectroscopy.Sulfur compounds poison the Pd/C catalyst and increase the formation of azo deposit,reducing the activity of catalyst.We report a mild method to regenerate the Pd/C catalyst:wash the deposit by N,N-dimethylformamide and oxidize the chemisorbed sulfur by hot air.The regenerated Pd/C catalyst can be reused at least ten runs with stable activity.

  20. Synthesis of 2-(3-methyl-2-oxoquinoxalin-1(2)-yl)acetamide-based azetidinone derivatives as potent antibacterial and antifungal agents

    Indian Academy of Sciences (India)

    Shiv Kumar; Nitin Kumar; Sushma Drabu; Md Akram Minhaj

    2013-01-01

    Twelve compounds belonging to series N-[3-chloro-2-oxo-4-(substituted)phenylazetidin-1-yl]-2-(3-methyl-2-oxoquinoxalin-1(2)-yl)acetamide (5a-l) were synthesized. These compounds were evaluated for their in vitro antibacterial against E. coli, S. aureus, K. pneumoniae, P. aeruginosa and antifungal activity against C. albicans, A. niger and A. flavus by cup-plate method. Structures of all the newly synthesized compounds were confirmed by their spectral data interpretation. Compound 5g having -dimethylaminophenyl group on 4-position of azetidinone ring attached to N-atom of acetamido group on 1-position of 3-methyl-1-quinoxaline-2-one, was found to be active against all the bacterial and fungal strains under investigation.

  1. Density functional studies of molecular structures of N-methyl formamide, N,N-dimethyl formamide, and N,N-dimethyl acetamide

    Indian Academy of Sciences (India)

    V Renugopalakrishnan; G Madrid; G Cuevas; A T Hagler

    2000-02-01

    Density functional theory was applied to the calculation of molecular structures of N-methyl formamide (NMF), N,N-dimethyl formamide (DMF), and N,Ndimethyl acetamide (DMA). DFT calculations on NMF, DMF, and DMA were performed using a combination of the local functional of Vosko, Wilk, and Nusair (VWN) with the nonlocal exchange functional of Becke and the nonlocal correlational functional of Lee, Yang, and Parr (BLYP). The adiabatic connection method (ACM) of Becke has also been used, for the first time, for the calculation of molecular structures of NMF, DMF, and DMA. The calculated molecular structures are in excellent agreement with the experimental geometries of NMF and DMA derived from gas-phase electron-diffraction studies. Sparse experimental data on the gas-phase geometry of DMF reported in the literature compares well with the DFT results on DMF. DFT emerges as a powerful method to calculate molecular structures.

  2. A novel 2-(2-Formyl-4-methyl-phenoxy)-N-phenyl-acetamide-based fluorescence turn-on chemosensor for selenium determination with high selectivity and sensitivity

    Science.gov (United States)

    Song, Cairui; Fei, Qiang; Shan, Hongyan; Feng, Guodong; Cui, Minghui; Liu, Yameng; Huan, Yanfu

    2013-12-01

    A novel turn-on fluorescent chemosensor, 2-(2-Formyl-4-methyl-phenoxy)-N-phenyl-acetamide (FMPPA) was designed and synthesized, and its photophysical properties were characterized. Upon coordination with Se (IV), the chemosensor showed incredible fluorescence enhancement (turn-on), other alkali, alkaline earth, transitional metal ions, and common anions including Li+, Na+, K+, Rb+, Cs+, Be2+, Mg2+, Ca2+, Sr2+, Ba2+, Ni2+, Cu2+, Cd2+, Zn2+, Mn2+, As3+, Pt4+, V5+, Fe3+, Mo6+, Al3+, CO32-, Cl-, SCN-, AC-, NO3-, F-, SO42- had no significant interference on Se (IV) determination. The chemosensor exhibits a dynamic response range for Se (IV) from 3.32 × 10-7 to 2.63 × 10-6 M, with a detection limit of 9.38 × 10-9 M (3σ).

  3. N-[4-Acetyl-5-(2-methylprop-1-enyl-5-(2-p-tolylpropyl-4,5-dihydro-1,3,4-thiadiazol-2-yl]acetamide

    Directory of Open Access Journals (Sweden)

    Noureddine Mazoir

    2009-06-01

    Full Text Available The title heterocyclic compound, C20H27N3O2S, was synthesized from 2-(4-methylcyclohex-3-enyl-6-methylhepta-2,5-dien-4-one, which was isolated from the essential oil Cedrus atlantica. The thiadiazole ring is essentially planar [maximum deviation 0.006 (2 Å] and it forms a dihedral angle of 18.08 (9° with the benzene ring. The dihedral angle between the thiadiazole ring and the acetamide plane is 7.62 (10°. In the crystal, molecules are linked into chains running along the c axis by intermolecular N—H...O hydrogen bonds.

  4. SYNTHESIS OF N-(ALKYL OR ARYL-2-(1H-BENZOTRIAZOL-1-YL-ACETAMIDES AS SELECTIVE COX-2 INHIBITOR

    Directory of Open Access Journals (Sweden)

    Amruta Patil* and Gita Chaurasia

    2013-11-01

    Full Text Available Microwave assisted organic synthesis (MAOS has emerged as frontier in pharmaceutical research for synthesis of newer drugs and implementing GREEN chemistry. Arylacetamides are pharmaceutically interesting as they show various biological activities such as analgesic, local anesthetic, antiarthritic, antiarrhythmic activities, etc. In arylacetamides the nature of aromatic ring and its substituent is primary determinant for its activity. To serve this purpose, we have decided to substitute arylacetamide with benzotriazole which may exploit the analgesic potential of newly synthesized derivatives i.e N-(Alkyl or Aryl-2-(1H-benzotriazol-1-yl-acetamides and thus it may be helpful in reducing the pain without having side effect of ulcerogenicity.

  5. Rare earth complexes with a novel ligand N-(naphthalen-2-yl)- N-phenyl-2-(quinolin-8-yloxy)acetamide: Preparation and spectroscopic studies

    Science.gov (United States)

    Wu, Wei-Na; Tang, Ning; Yan, Lan

    2008-12-01

    Six complexes of rare earth nitrates (Ln = La, Sm, Eu, Gd, Tb, Dy) with a new amide type ligand, N-(naphthalen-2-yl)- N-phenyl-2-(quinolin-8-yloxy)acetamide (L) have been prepared and characterized by elemental analysis, conductivity measurements, IR and and 1H NMR spectra. Under excitation, Eu(III) and Sm(III) complexes exhibited strong red emissions. And the luminescence intensity of Sm(III) complex is higher than that of Eu(III) complex. Thus the Eu(III) and Sm(III) complexes are the potential light conversion agent. However, the Tb(III) and Dy(III) complexes cannot exhibit characteristic emissions of terbium and dysprosium ions, respectively. The results of phosphorescence spectrum show that the triplet-state energy level of the ligand matches better to the resonance level of Eu(III) than Tb(III) ion. In addition, the luminescence of the Eu(III) complex is also relatively strong in highly diluted tetrahydrofuran solution (2 × 10 -4 mol/L) compared with the powder. This is not only due to the solvate effects but also to the changes of the structure of the Eu(III) complex after being dissolved into the solvents. Furthermore, owing to the co-luminescence effect, the proper La(III) or Gd(III) doped Eu(III) complexes show stronger luminescence than the pure Eu(III) complex.

  6. Glass transition dynamics and conductivity scaling in ionic deep eutectic solvents: The case of (acetamide + lithium nitrate/sodium thiocyanate) melts

    Energy Technology Data Exchange (ETDEWEB)

    Tripathy, Satya N., E-mail: satyanarayantripathy@gmail.com; Wojnarowska, Zaneta; Knapik, Justyna; Paluch, Marian [Institute of Physics, University of Silesia, Uniwersytecka 4, 40-007 Katowice (Poland); Silesian Center for Education and Interdisciplinary Research, 75 Pulku Piechoty 1A, 41-500 Chorzow (Poland); Shirota, Hideaki [Department of Nanomaterial Science and Department of Chemistry, Chiba University, 1-33 Yayoi, Inage-ku, Chiba 263-8522 (Japan); Biswas, Ranjit [Department of Chemical, Biological and Macromolecular Sciences, S. N. Bose National Centre for Basic Sciences, JD Block, Sector III, Salt Lake, Kolkata 700098 (India)

    2015-05-14

    A detailed investigation on the molecular dynamics of ionic deep eutectic solvents (acetamide + lithium nitrate/sodium thiocyanate) is reported. The study was carried out employing dielectric relaxation spectroscopy covering seven decades in frequency (10{sup −1}-10{sup 6} Hz) and in a wide temperature range from 373 K down to 173 K, accessing the dynamic observables both in liquid and glassy state. The dielectric response of the ionic system has been presented in the dynamic window of modulus formalism to understand the conductivity relaxation and its possible connection to the origin of localized motion. Two secondary relaxation processes appear below glass transition temperature. Our findings provide suitable interpretation on the nature of secondary Johari-Goldstein process describing the ion translation and orientation of dipoles in a combined approach using Ngai’s coupling model. A nearly constant loss feature is witnessed at shorter times/lower temperatures. We also discuss the ac conductivity scaling behavior using Summerfield approach and random free energy barrier model which establish the time-temperature superposition principle. These experimental observations have fundamental importance on theoretical elucidation of the conductivity relaxation and glass transition phenomena in molten ionic conductors.

  7. Renal reduced nicotinamide adenine dinucleotide phosphate:cytochrome c reductase-mediated metabolism of the carcinogen N-(4-(5-nitro-2-furyl)-2-thiazolyl)acetamide

    Energy Technology Data Exchange (ETDEWEB)

    Mattammal, M.B.; Zenser, T.V.; Palmier, M.O.; Davis, B.B.

    1985-01-01

    N-(4-(5-Nitro-2-furyl)-2-thiazolyl)acetamide (NFTA) metabolism was examined in vitro using microsomes prepared from rat liver and renal cortex and from rabbit liver and renal cortex and outer and inner medulla. NFTA nitroreduction was observed with each tissue. Three mol of NADPH were used per mol of NFTA reduced. Substrate and inhibitor specificity suggested that the microsomal nitroreduction was due to NADPH:cytochrome c reductase. Metabolite(s) formed bound to protein, RNA, DNA, and synthetic polyribonucleotides. Maximum covalent binding was seen with polyguanylic acid. A guanosine-NFTA adduct was isolated. Binding was inhibited by sulfhydryl compounds and vitamin E. The (/sup 14/C)NFTA:glutathione or (/sup 3/H)glutathione:NFTA conjugates obtained from microsomal incubations showed identical chromatographic properties as the product obtained by the reaction of synthetic N-hydroxy-NFTA with (/sup 3/H)glutathione. Structures of synthetic N-hydroxy-NFTA and the microsomal reduction product 1-(4-(2-acetylaminothiazolyl))-3-cyano-1-propanone were established by mass spectrometry. The latter reduction product did not bind macromolecules. These results suggest that renal NADPH:cytochrome c reductase reduces NFTA to an N-hydroxy-NFTA intermediate that binds nucleophilic sites on macromolecules.

  8. Evaluation of Stability of Complexes of Inner Transition Metal Ions with 2-Oxo-1-pyrrolidine Acetamide and Role of Systematic Errors

    Directory of Open Access Journals (Sweden)

    Sangita Sharma

    2011-01-01

    Full Text Available BEST FIT models were used to study the complexation of inner transition metal ions like Y(III, La(III, Ce(III, Pr(III, Nd(III, Sm(III, Gd(III, Dy(III and Th(IV with 2-oxo-1-pyrrolidine acetamide at 30 °C in 10%, 20, 30, 40, 50% and 60% v/v dioxane-water mixture at 0.2 M ionic strength. Irving Rossotti titration method was used to get titration data. Calculations were carried out with PKAS and BEST Fortran IV computer programs. The expected species like L, LH+, ML, ML2 and ML(OH3, were obtained with SPEPLOT. Stability of complexes has increased with increasing the dioxane content. The observed change in stability can be explained on the basis of electrostatic effects, non electrostatic effects, solvating power of solvent mixture, interaction between ions and interaction of ions with solvents. Effect of systematic errors like effect of dissolved carbon dioxide, concentration of alkali, concentration of acid, concentration of ligand and concentration of metal have also been explained here.

  9. Self-organization ability of chiral Nα-substituted, Nβ-Boc protected α-hydrazino acetamides in the crystal and solution states.

    Science.gov (United States)

    Moussodia, Ralph-Olivier; Romero, Eugenie; Wenger, Emmanuel; Jamart-Grégoire, Brigitte; Acherar, Samir

    2017-08-29

    The limitations of peptides have severely hampered their use in pharmacology, thus prompting the design of new peptidomimetic foldamers. This requires precise knowledge of the secondary structure of new compounds and the ability to predict their self-organization. Conformational studies of the basic units of these foldamers can be of invaluable assistance in designing new bioactive compounds. To this end, we investigated the conformation of three chiral Nα-substituted, Nβ-Boc protected α-hydrazino acetamide model compounds containing various side chains both on the Nα- and Cα- atoms in both the crystal and solution states. On the basis of IR spectroscopy, NMR and X-ray diffraction experiments, we demonstrated that these three models adopt conformational preferences, relying on eight-, six- or five-membered H-bonded pseudocycles (C8, C6 or C5), depending on the steric bulk of both Nα- or Cα- side chains. This study sheds light onto the versatile self-organization ability of the specific class of α-Nα-hydrazinopeptides and emphasizes the key role of the Cα- side chain on the conformational preference of the self-structuration.

  10. Pharmacological profile of N-(2,6-dichlorophenyl)-2-(4-methyl-1-piperidinyl)acetamide, a novel analogue of lidocaine.

    Science.gov (United States)

    Déciga-Campos, Myrna; Navarrete-Vázquez, Gabriel; López-Muñoz, Francisco Javier; Librowski, Tadeusz; Sánchez-Recillas, Amanda; Yañez-Pérez, Victor; Ortiz-Andrade, Rolffy

    2016-06-15

    N-(2,6-Dichlorophenyl)-2-(4-methyl-1-piperidinyl)acetamide (LIA), a lidocaine analogue, has potential applications in treating neuropathic pain. The aim of this work was to characterize the pharmacological activity of LIA related with central nervous system and cardiovascular activity. Anesthetic effect was tested in guinea pigs and mice. Ambulatory activity, anti-anxiety effect, sodium pentobarbital (PB)-induced hypnosis and pentylenetetrazol (PTZ)-induced seizures test were evaluated in mice to determine the possible central nervous system activity. The cardiovascular activities in vivo and ex vivo were analyzed in rats. LIA (2%) presents, similar to lidocaine (2%), anesthetic activity on the corneal reflex, infiltration anesthesia and tail immersion test. LIA (1-100mg/kg, i.p.), similar to lidocaine (1-100mg/kg, i.p.), presents a dose-dependent sedative-hypnotic effect in mice. Both compounds did not produce anti-anxiety activity in mice. LIA did not prevent PTZ-induced seizures. However, LIA itself did not produce seizures at high doses in mice, as lidocaine does. LIA is a vasorelaxant compound for smooth muscle cells and presents hypotensive effect in vivo without increments to the heart rate significantly. High doses of lidocaine produce seizures and vasoconstriction. In this study, we found that LIA shares a similar pharmacological profile as lidocaine's but without the primary adverse effects of seizures and vasoconstriction. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. In vivo protection studies of bis-quaternary 2-(hydroxyimino)- N-(pyridin-3-yl) acetamide derivatives (HNK oximes) against tabun and soman poisoning in Swiss albino mice.

    Science.gov (United States)

    Kumar, P; Swami, D; Nagar, D P; Singh, K P; Acharya, J; Karade, H N; Yadav, R

    2017-01-01

    The study reports antidotal efficacy of three HNK [ bis quaternary 2-(hydroxyimino)-N-(pyridin-3yl) acetamide derivatives] and pralidoxime (2-PAM), against soman and tabun poisoning in Swiss albino mice. Protection index (PI) was determined (treatment doses: HNK oximes, ×0.20 of their median lethal dose (LD50) and 2-PAM, 30 mg/kg, intramuscularly (im)) together with atropine (10 mg/kg, intraperitoneally). Probit log doses with difference of 0.301 log of LD50 of the nerve agents administered and inhibition of acetylcholinesterase (AChE) activity by 50% (IC50) was calculated at optimized time in brain and serum. Using various doses of tabun and soman (subcutaneously (sc)), in multiples of their IC50, AChE reactivation ability of the oximes was studied. Besides, acute toxicity (0.8× LD50, im, 24 h postexposure) of HNK-102 and 2-PAM was also compared by determining biochemical, hematological variables and making histopathological observations. Protection offered by HNK-102 against tabun poisoning was found to be four times higher compared to 2-PAM. However, nearly equal protection was noted with all the four oximes against soman poisoning. HNK-102 reactivated brain AChE activity by 1.5 times more than 2-PAM at IC50 dose of soman and tabun. Acute toxicity studies of HNK-102 and 2-PAM showed sporadic changes in urea, uric acid, aspartate aminotransferase, and so on compared to control group, however, not supported by histopathological investigations. The present investigation showed superiority of newly synthesized HNK-102 oxime over standard 2-PAM, as a better antidote, against acute poisoning of tabun (4.00 times) and soman (1.04 times), in Swiss albino mice.

  12. Synthesis and anti-Parkinson′s screening of some novel 2-(naphthalen-1-yl-N-[2-substituted (4-oxothiazolidin-3-yl]acetamide derivatives

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    S Gomathy

    2012-01-01

    Full Text Available Context: The objective of this study is to synthesize some novel 2-(naphthalen-1-yl-N-[2-substituted (4-oxothiazolidin-3-yl] acetamide derivatives and to study their anti-Parkinson′s activity. Materials and Methods: Ethyl (naphthalen-1-yl acetate (1 was prepared from naphthalene-1-yl acetic acid in ethanol. Condensation of ethyl (naphthalen-1-yl acetate (1 with an equimolar quantity of hydrazine hydrate in methanol afforded 2-(naphthalen-1-yl acetohydrazide (2. Compound 2 which on condensation with different aromatic aldehydes yielded respective Schiff bases (3a-e. The Schiff bases are then cyclised with mercaptoacetic acid in dioxane to yield the corresponding naphthalene bearing 4-thiazolidinone derivatives (4a-e. The structures of the synthesized compounds have been established based on their analytical and spectral data such as FT-IR, Mass and NMR spectroscopy. Results: The synthesized compounds were evaluated for their anti-Parkinson′s screening using in vitro free radical scavenging assay. Compounds 4c, 4d, and 4e showed potent free radical scavenging activity giving 82%, 74% and 76% respectively. Three compounds 4c, 4d and 4e were taken for in vivo anti-Parkinson′s screening by 6-Hydroxydopamine lesioned rat′s model (6-OHDA. Among these, one of the 4-thiazolidinone derivatives having a 3-nitro phenyl group at 2 nd position 4c exhibited maximum anti-Parkinson′s activity. Conclusion: Thiazolidinone derivatives showed significant anti-Parkinson′s activity in the 6-OHDA lesioned rat model. The estimated parameters were closely relevant to clinical parkinsonism, and the drug treatment protected the diseased brain of a rat. We appreciate further detailed studies with these drugs in anti-Parkinson′s pharmacology and toxicology.

  13. A acetamida de pirrolidona como medicação auxiliar no tratamento da paralisia cerebral Pyrrolidone acetamide as an auxiliary drug in the treatment of cerebral palsy

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    Francisca Salete Pinheiro Chagas Ribeiro

    1976-06-01

    Full Text Available Vinte crianças, com diagnóstico de paralisia cerebral (PC e sob tratamento clássico, fisioterápico e pedagógico, receberam piracetam (acetamida de pirrolidona como medicação auxiliar. O objetivo foi melhorar os problemas de espasticidade, apredizagem, neurolabilidade, visando a um rendimento melhor do tratamento global da PC. O grupo medicado foi comparado com um grupo controle de 20 crianças que só eram objeto do tratamento habitual. A comparação mostrou resultados favoráveis no grupo medicado. A droga foi administrada na dose de 80 mg/kg/dia durante 10 semanas. Os critérios de avaliação dos resultados foram psicológicos, clínico, fisioterápico e pedagógico. A droga foi administrada em nova forma de apresentação: solução, para uso oral, a 6%.Twenty children, with the diagnosis of cerebral palsy (CP and under classical, physiotherapeutical and pedagogical, treatment, received piracetam (pyrrolidine acetamide as an auxiliary drug. The goal was to better spasticity, learning and nervous instability problems aiming at better results of over-all treatment of CP. The group that received the drug has been compared to a control group of 20 children treated by the customary treatment only. The comparison showed favourable results for the medicated group. The drug was administered in the dose of 80 mg/kg/day during 10 weeks. The criteria for evaluation have been psychological, clinical, physiotherapeutical and pedagogical. The drug has been given in a new form of presentation: 6% solution for oral use.

  14. Methods of Analysis by the U.S. Geological Survey Organic Geochemistry Research Group?Determination of acetamide herbicides and their degradation products in water using online solid-phase extraction and liquid chromatography/mass spectrometry

    Science.gov (United States)

    Lee, E.A.; Strahan, A.P.

    2003-01-01

    An analytical method for the determination of 6 acetamide herbicides (acetochlor, alachlor, dimethenamid, flufenacet, metolachlor, and propachlor) and 16 of their degradation products in natural water samples using solid-phase extraction and liquid chromatography/mass spectrometry is described in this report. Special consideration was given during the development of the method to prevent the formation of degradation products during the analysis. Filtered water samples were analyzed using octadecylsilane as the solid-phase extraction media on online automated equipment followed by liquid chromatography/mass spectrometry. The method uses only 10 milliliters of sample per injection. Three different water-sample matrices, a reagent-water, a ground-water, and a surface-water sample spiked at 0.10 and 1.0 microgram per liter, were analyzed to determine method performance. Method detection limits ranged from 0.004 to 0.051 microgram per liter for the parent acetamide herbicides and their degradation products. Mean recoveries for the acetamide compounds in the ground- and surface-water samples ranged from 62.3 to 117.4 percent. The secondary amide of acetochlor/metolachlor ethanesulfonic acid (ESA) was recovered at an average rate of 43.5 percent. The mean recoveries for propachlor and propachlor oxanilic acid (OXA) were next lowest, ranging from 62.3 to 95.5 percent. Mean recoveries from reagent-water samples ranged from 90.3 to 118.3 percent for all compounds. Overall the mean of the mean recoveries of all compounds in the three matrices spiked at 0.10 and 1.0 microgram per liter ranged from 89.9 to 100.7 percent, including the secondary amide of acetochlor/metolachlor ESA and the propachlor compounds. The acetamide herbicides and their degradation products are reported in concentrations ranging from 0.05 to 2.0 micrograms per liter. The upper concentration limit is 2.0 micrograms per liter for all compounds without dilution. With the exception of the secondary amide of

  15. Characterization of an Indole-3-Acetamide Hydrolase from Alcaligenes faecalis subsp. parafaecalis and Its Application in Efficient Preparation of Both Enantiomers of Chiral Building Block 2,3-Dihydro-1,4-Benzodioxin-2-Carboxylic Acid.

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    Pradeep Mishra

    Full Text Available Both the enantiomers of 2,3-dihydro-1,4-benzodioxin-2-carboxylic acid are valuable chiral synthons for enantiospecific synthesis of therapeutic agents such as (S-doxazosin mesylate, WB 4101, MKC 242, 2,3-dihydro-2-hydroxymethyl-1,4-benzodioxin, and N-[2,4-oxo-1,3-thiazolidin-3-yl]-2,3-dihydro-1,4-benzodioxin-2-carboxamide. Pharmaceutical applications require these enantiomers in optically pure form. However, currently available methods suffer from one drawback or other, such as low efficiency, uncommon and not so easily accessible chiral resolving agent and less than optimal enantiomeric purity. Our interest in finding a biocatalyst for efficient production of enantiomerically pure 2,3-dihydro-1,4-benzodioxin-2-carboxylic acid lead us to discover an amidase activity from Alcaligenes faecalis subsp. parafaecalis, which was able to kinetically resolve 2,3-dihydro-1,4-benzodioxin-2-carboxyamide with E value of >200. Thus, at about 50% conversion, (R-2,3-dihydro-1,4-benzodioxin-2-carboxylic acid was produced in >99% e.e. The remaining amide had (S-configuration and 99% e.e. The amide and acid were easily separated by aqueous (alkaline-organic two phase extraction method. The same amidase was able to catalyse, albeit at much lower rate the hydrolysis of (S-amide to (S-acid without loss of e.e. The amidase activity was identified as indole-3-acetamide hydrolase (IaaH. IaaH is known to catalyse conversion of indole-3-acetamide (IAM to indole-3-acetic acid (IAA, which is phytohormone of auxin class and is widespread among plants and bacteria that inhabit plant rhizosphere. IaaH exhibited high activity for 2,3-dihydro-1,4-benzodioxin-2-carboxamide, which was about 65% compared to its natural substrate, indole-3-acetamide. The natural substrate for IaaH indole-3-acetamide shared, at least in part a similar bicyclic structure with 2,3-dihydro-1,4-benzodioxin-2-carboxamide, which may account for high activity of enzyme towards this un-natural substrate. To

  16. Crystal structures of 2-[(4,6-di­amino­pyrimidin-2-yl)sulfan­yl]-N-(3-nitro­phen­yl)acetamide monohydrate and N-(2-chloro­phen­yl)-2-[(4,6-di­amino­pyrimidin-2-yl)sulfan­yl]acetamide

    Science.gov (United States)

    Subasri, S.; Timiri, Ajay Kumar; Barji, Nayan Sinha; Jayaprakash, Venkatesan; Vijayan, Viswanathan; Velmurugan, Devadasan

    2016-01-01

    The title compounds, C12H12N6O3S·H2O, (I), and C12H12ClN5OS, (II), are 2-[(4,6-di­amino­pyrimidin-2-yl)sulfan­yl]acetamides. Compound (I) crystallized as a monohydrate. In both compounds, the mol­ecules have a folded conformation, with the pyrimidine ring being inclined to the benzene ring by 56.18 (6)° in (I) and by 67.84 (6)° in (II). In both mol­ecules, there is an intra­molecular N—H⋯N hydrogen bond stabilizing the folded conformation. In (I), there is also a C—H⋯O intra­molecular short contact, and in (II) an intra­molecular N—H⋯Cl hydrogen bond is present. In the crystal of (I), mol­ecules are linked by a series of N—H⋯O, O—H⋯O and O—H⋯N hydrogen bonds, forming undulating sheets parallel to the (100). The sheets are linked via an N—H⋯Owater hydrogen bond, forming a three-dimensional network. In the crystal of (II), mol­ecules are linked by a series of N—H⋯O, N—H⋯N and C—H⋯O hydrogen bonds, forming slabs parallel to (001). PMID:27536406

  17. Crystal structures of 2-[(4,6-di-amino-pyrimidin-2-yl)sulfan-yl]-N-(3-nitro-phen-yl)acetamide monohydrate and N-(2-chloro-phen-yl)-2-[(4,6-di-amino-pyrimidin-2-yl)sulfan-yl]acetamide.

    Science.gov (United States)

    Subasri, S; Timiri, Ajay Kumar; Barji, Nayan Sinha; Jayaprakash, Venkatesan; Vijayan, Viswanathan; Velmurugan, Devadasan

    2016-08-01

    The title compounds, C12H12N6O3S·H2O, (I), and C12H12ClN5OS, (II), are 2-[(4,6-di-amino-pyrimidin-2-yl)sulfan-yl]acetamides. Compound (I) crystallized as a monohydrate. In both compounds, the mol-ecules have a folded conformation, with the pyrimidine ring being inclined to the benzene ring by 56.18 (6)° in (I) and by 67.84 (6)° in (II). In both mol-ecules, there is an intra-molecular N-H⋯N hydrogen bond stabilizing the folded conformation. In (I), there is also a C-H⋯O intra-molecular short contact, and in (II) an intra-molecular N-H⋯Cl hydrogen bond is present. In the crystal of (I), mol-ecules are linked by a series of N-H⋯O, O-H⋯O and O-H⋯N hydrogen bonds, forming undulating sheets parallel to the (100). The sheets are linked via an N-H⋯Owater hydrogen bond, forming a three-dimensional network. In the crystal of (II), mol-ecules are linked by a series of N-H⋯O, N-H⋯N and C-H⋯O hydrogen bonds, forming slabs parallel to (001).

  18. Crystal structures of 2-[(4,6-di­amino­pyrimidin-2-yl)sulfan­yl]-N-(naphthalen-1-yl)acetamide and 2-[(4,6-di­amino­pyrimidin-2-yl)sulfan­yl]-N-(4-fluoro­phen­yl)acetamide

    Science.gov (United States)

    Subasri, S.; Kumar, Timiri Ajay; Sinha, Barij Nayan; Jayaprakash, Venkatesan; Viswanathan, Vijayan; Velmurugan, Devadasan

    2017-01-01

    The title compounds, C16H15N5OS, (I), and C12H12FN5OS, (II), are [(di­amino­pyrimidine)­sulfan­yl]acetamide derivatives. In (I), the pyrimidine ring is inclined to the naphthalene ring system by 55.5 (1)°, while in (II), the pyrimidine ring is inclined to the benzene ring by 58.93 (8)°. In (II), there is an intra­molecular N—H⋯N hydrogen bond and a short C—H⋯O contact. In the crystals of (I) and (II), mol­ecules are linked by pairs of N—H⋯N hydrogen bonds, forming inversion dimers with R 2 2(8) ring motifs. In the crystal of (I), the dimers are linked by bifurcated N—H⋯(O,O) and C—H⋯O hydrogen bonds, forming layers parallel to (100). In the crystal of (II), the dimers are linked by N—H⋯O hydrogen bonds, also forming layers parallel to (100). The layers are linked by C—H⋯F hydrogen bonds, forming a three-dimensional architecture.

  19. Synthesis and in vitro reactivation study of isonicotinamide derivatives of 2-(hydroxyimino)-N-(pyridin-3-yl)acetamide as reactivators of Sarin and VX inhibited human acetylcholinesterase (hAChE).

    Science.gov (United States)

    Karade, Hitendra N; Raviraju, G; Acharya, B N; Valiveti, Aditya Kapil; Bhalerao, Uma; Acharya, Jyotiranjan

    2016-09-15

    Previously (Karade et al., 2014), we have reported the synthesis and in vitro evaluation of bis-pyridinium derivatives of pyridine-3-yl-(2-hydroxyimino acetamide), as reactivators of sarin and VX inhibited hAChE. Few of the molecules showed superior in vivo protection efficacy (mice model) (Kumar et al., 2014; Swami et al., 2016) in comparison to 2-PAM against DFP and sarin poisoning. Encouraged by these results, herein we report the synthesis and in vitro evaluation of isonicotinamide derivatives of pyridine-3-yl-(2-hydroxyimino acetamide) (4a-4d) against sarin and VX inhibited erythrocyte ghost hAChE. Reactivation kinetics of these compounds was studied and the determined kinetic parameters were compared with that of commercial reactivators viz. 2-PAM and obidoxime. In comparison to 2-PAM and obidoxime, oxime 4a and 4b exhibited enhanced reactivation efficacy toward sarin inhibited hAChE while oxime 4c showed far greater reactivation efficacy toward VX inhibited hAChE. The acid dissociation constant and IC50 values of these oximes were determined and correlated with the observed reactivation potential.

  20. Pharmacological evaluation of [{sup 123}I]-CLINDE: a radioiodinated imidazopyridine-3-acetamide for the study of peripheral benzodiazepine binding sites (PBBS)

    Energy Technology Data Exchange (ETDEWEB)

    Mattner, Filomena; Katsifis, Andrew [Australian Nuclear Science and Technology Organisation, Radiopharmaceuticals Research Institute, PMB 1 Menai, N.S.W., Sydney (Australia); Mardon, Karine [The University of Queensland, Centre for Studies in Drug Disposition, Brisbane (Australia)

    2008-04-15

    The study aims to evaluate the iodinated imidazopyridine, N',N'-diethyl-6-Chloro-(4'-[{sup 123}I]iodophenyl)imidazo[1,2-a]pyridine-3-acetamide ([{sup 123}I]-CLINDE) as a tracer for the study of peripheral benzodiazepine binding sites (PBBS). In vitro studies were performed using membrane homogenates and sections from kidney, adrenals, and brain cortex of Sprague-Dawley (SD) rats and incubated with [{sup 123}I]-CLINDE. For in vivo studies, the rats were injected with [{sup 123}I]-CLINDE. In competition studies, PBBS-specific drugs PK11195 and Ro 5-4864 and the CBR specific drug Flumazenil were injected before the radiotracer. In vitro binding studies in adrenal, kidney, and cortex mitochondrial membranes indicated that [{sup 123}I]-CLINDE binds with high affinity to PBBS, K{sub d} = 12.6, 0.20, and 3.84 nM, respectively. The density of binding sites was 163, 5.3, and 0.34 pmol/mg protein, respectively. In vivo biodistribution indicated high uptake in adrenals (5.4), heart (1.5), lungs (1.5), kidney (1.5) %ID/g at 6 h p.i. In the central nervous system (CNS), the olfactory bulbs displayed the highest uptake; up to six times the activity in blood. Pre-administration of unlabeled CLINDE, PK11195 and Ro 5-4864 (1 mg/kg) reduced the uptake of [{sup 123}I]-CLINDE by 70-55% in olfactory bulbs. In the kidney and heart, a reduction of 60-80% ID/g was observed, while an increase was observed in the adrenals requiring 10 mg/kg for significant displacement. Flumazenil had no effect on uptake in peripheral organs and brain. Metabolite analysis indicated >90% of the radioactivity in the above tissues was intact [{sup 123}I]-CLINDE. [{sup 123}I]-CLINDE displays high and selective uptake for the PBBS and warrants further development as a probe for imaging PBBS using single photon emission computed tomography (SPECT). (orig.)

  1. Inclusion of 1-naphthylacetic acid and 2-(1-naphthyl)acetamide into three typical multiresidue methods for LC/MS/MS analysis of tomatoes and zucchini.

    Science.gov (United States)

    Lozano, Ana; Pérez-Parada, Andrés; Heinzen, Horacio; Fernández-Alba, Amadeo R

    2012-01-01

    In spite of high plant growth regulator application rates, little has been reported in the literature on determination of their residues in fruits and vegetables. This would be useful in monitoring good manufacturing practices and overall safety through the enforcement of maximum residue levels (MRLs). The present work describes method validation for the determination of 1-naphthylacetic acid (NAA) and 2(1-naphthyl)acetamide (NAAm) in tomato and zucchini using the mini-Luke, ethyl acetate (EtOAc) and acetate-buffered quick, easy, cheap, effective, rugged, and safe (QuEChERS) methods. Samples were spiked at two different levels: 50 and 100 pg/kg for NAA and 20 and 100 pg/kg for NAAm. These compounds were analyzed within the same chromatographic run with LC coupled to triple quadrupole MS (LC/(QqQ)MS/MS) in positive and negative electrospray ionization [ESI(+) and ESI(-)] modes for NAAm and NAA, respectively. For analyte confirmation, LC/ESI(-)QTOF-MS was also investigated given that NAA has only one multiple reaction monitoring transition (185.1-*140.9 m/z). These three common methods were used to determine linearity, recoveries, precision (RSD), matrix effects, repeatability, and reproducibility (n = 5) for the selected matrixes. In terms of the Directorate-General for Health and Consumers (DG-SANCO) guidelines, only insignificant differences were found for the multiresidue methods tested, regardless of the commodity. Matrix-matched calibration was used, and LODs were below 10.1 pg/kg for NAA and 6.0 pg/kg for NAAm, which were lower than the MRLs established in current European Union legislation for these compounds. Obtained recoveries for NAA ranged from 87 to 107% with RSD values below 10% for mini-Luke, 83 to 107% with RSD 0.996) for all methods used. Good repeatability and reproducibility in terms of RSD were obtained (11.3-17.8%) for these analytical methods. The results were acceptable within the studied ranges for both analytes in all methods. As these

  2. Radiosynthesis and Preclinical Evaluation of [(18)F]F-DPA, A Novel Pyrazolo[1,5a]pyrimidine Acetamide TSPO Radioligand, in Healthy Sprague Dawley Rats.

    Science.gov (United States)

    Keller, Thomas; Krzyczmonik, Anna; Forsback, Sarita; Picón, Francisco R López; Kirjavainen, Anna K; Takkinen, Jatta; Rajander, Johan; Cacheux, Fanny; Damont, Annelaure; Dollé, Frédéric; Rinne, Juha O; Haaparanta-Solin, Merja; Solin, Olof

    2017-01-12

    Many neurological conditions result in the overexpression of the translocator protein 18 kDa (TSPO), today recognized as a biomarker for microglial activation and neuroinflammation imaging. The pyrazolo[1,5-a]pyrimidine acetamides are a particularly attractive class of TSPO-specific ligands, prompting the development of several positron emission tomography (PET) radiotracers. This includes F-DPA, a recently reported fluorinated ligand (K i = 1.7 nM), wherein the fluorine atom is directly linked to the phenyl moiety without the presence of an alkyl or alkoxy spacer chain. Reported here is the preparation of [(18)F]F-DPA using [(18)F]Selectfluor bis(triflate) and the preliminary evaluation of [(18)F]F-DPA in healthy rats. Its metabolic profile and biodistribution in rats are compared with that of [(18)F]DPA-714, a closely related structure. [(18)F]F-DPA was synthesized by electrophilic fluorination using [(18)F]Selectfluor bis(triflate), [(18)F]DPA-714 was synthesized by conventional nucleophilic fluorination. The biodistribution of both radiotracers was compared in Sprague Dawley rats. Radiometabolites of both radiotracers in plasma and brain homogenates were analyzed by radioTLC. The radiochemical yield of [(18)F]F-DPA was 15 ± 3 % and the specific activity was 7.8 ± 0.4 GBq/μmol. The radiochemical purity exceeded 99 %. The in vivo time activity curves of [(18)F]F-DPA demonstrate rapid entry into the brain and a concentration equilibrium at 20-30 min after injection. The metabolic profiles at 90 min after radiotracer injection in the plasma show that unchanged [(18)F]F-DPA and [(18)F]DPA-714 account for 28.3 ± 6.4 and 11.1 ± 2.6 % of the remaining radioactivity, respectively. In the brain, unchanged [(18)F]F-DPA accounts for 93.5 ± 2.8 % of the radioactivity; whereas for [(18)F]DPA-714, this value is 53.6 ± 1.6 %. [(18)F]Selectfluor bis(triflate) was successfully used to label F-DPA with fluorine-18. The labeling

  3. N-[4-(Ethylsulfamoylphenyl]acetamide

    Directory of Open Access Journals (Sweden)

    Jeveria Rehman

    2011-09-01

    Full Text Available The title compound, C10H14N2O3S, crystallized with two molecules (A and B in the asymmetric unit. The terminal methyl group of the ethylsulfonamide moiety in molecule B is disordered over two sets of sites with an occupancy ratio of 0.61 (1:0.39 (1. Both molecules have L-shaped conformations. In molecule A, the dihedral angles between the benzene ring and its ethylsulfonamide and methylamide substituents are 83.5 (3 and 13.34 (18°, respectively. Equivalent values for molecule B are 87.9 (3 and 6.32 (16°, respectively. The C—S—N—C torsion angles are 66.5 (3° for A and −64.4 (3° for B, indicating similar twists about the S—N bonds, but in opposite senses. In the crystal, the A molecules are linked by pairs of Ns—H...O (s = sulfonamide hydrogen bonds, generating inversion dimers containing R22(8 rings, while the B molecules are linked by Ns—H...O hydrogen bonds into C(10 [100] chains. Finally, Na—H...O (a = amide hydrogen bonds link the A-molecule dimers and B-molecule chains into a three-dimensional network.

  4. [{sup 18}F]D.P.A.-714: a novel fluorine-18-labelled pyrazolo[1,5-a]pyrimidine acetamide for imaging the peripheral benzodiazepine receptors with PET - radiosynthesis on a zymate-xp robotic system

    Energy Technology Data Exchange (ETDEWEB)

    Dolle, F.; Damont, A.; Hinnen, F.; Kuhnast, B.; Chauveau, F.; Van camp, N.; Hantraye, P.; Tavitian, B. [Servvice Hospitalier Frederic Joliot, I2BM/DSV, 91 - Orsay (France); James, M.; Creelman, A.; Fulton, R.; Kassiou, M. [Sydney Univ., Brain and Mind Research Institute, NSW (Australia); Vercouillie, J.; Guilloteau, D. [Universite Francois Rabelais de Tours, 37 (France); Vercouillie, J.; Guilloteau, D. [Centre Hospitalier Regional Universitaire, 37 - Tours (France); Selleri, S.; Kassiou, M. [Sydney Univ., Discipline of Medical Radiations, Sciences and School of Chemistry, NSW (Australia)

    2008-02-15

    {sup 11}C D.P.A.-713 (N,N-diethyl-2-[2-(4-[{sup 11}C]methoxy-phenyl)-5,7-dimethyl-pyrazolo [1,5-a]pyrimidin-3-yl]acetamide) is a recently developed carbon-11-labelled (half life: 20.4 min)pyrazolo[1,5-a]pyrimidine acetamide for the in vivo imaging of the peripheral benzodiazepine receptors (P.B.R. or translocator protein (18 kDa, T.S.P.O.)). Preliminary results obtained in a rodent-model demonstrates that {sup 11}C D.P.A.-713 showed a high potential to in vivo image neuro-inflammation and additionally, this radioligand allowed a higher contrast between the lesioned area and the corresponding area in the intact contralateral hemisphere when compared to the radioligand of reference. D.P.A-714 (N,N-diethyl-2-[2-[4-(2-fluoro-ethoxy)phenyl] -5,7-dimethyl-pyrazolo[1,5-a]pyrimidin-3-yl]acetamide), a chemically closely related derivative of D.P.A.-713, had been designed with a fluorine atom in its structure, allowing ultimate labelling with fluorine-18, a longer-lived positron-emitter (half life:109.8 min) and today one of the most attractive PET isotopes for radiopharmaceutical chemistry. D.P.A.-714 as well as its corresponding tosylated derivative have been re-synthesized in 2 chemicals steps from D.P.A.-713. D.P.A.-714 has then been labelled at its aromatic fluoro-ethoxy group from the corresponding tosyl-derivative using the K{sup 18}FF-kryptofix{sub 222} (in CH{sub 3}CN (3 mL) at 85 degrees C for 5 min or D.M.S.O. (600 {mu}L) at 130 degrees C for 5 min). {sup 18}FD.P.A.-714 was then purified using semi preparative X terra reverse phase H.P.L.C., adequately formulated for i.v. injection and was found to be > 95% chemically and radiochemically pure. The total synthesis time was less than 90 min and the specific radioactivities at the end of the radiosynthesis ranged from 1 to 3 Ci/micro-mole. (N.C.)

  5. 2-Substituted-thio-N-(4-substituted-thiazol/1H-imidazol-2-yl)acetamides as BACE1 inhibitors: Synthesis, biological evaluation and docking studies.

    Science.gov (United States)

    Yan, Gang; Hao, Lina; Niu, Yan; Huang, Wenjie; Wang, Wei; Xu, Fengrong; Liang, Lei; Wang, Chao; Jin, Hongwei; Xu, Ping

    2017-09-08

    In this work, a series of 2-substituted-thio-N-(4-substituted-thiazol/1H-imidazol-2-yl)acetamide derivatives were developed as β-secretase (BACE-1) inhibitors. Supported by docking study, a small library of derivatives were designed, synthesized and biologically evaluated in vitro. In addition, the selected compounds were tested with affinity (KD) towards BACE-1, blood brain barrier (BBB) permeability and cytotoxicity. The studies revealed that the most potent analog 41 (IC50 = 4.6 μM) with high predicted BBB permeability and low cellular cytotoxicity, could serve as a good lead structure for further optimization. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  6. N-[4-Acetyl-5-(2-methylprop-1-enyl)-5-(2-p-tolyl-prop-yl)-4,5-dihydro-1,3,4-thia-diazol-2-yl]acetamide.

    Science.gov (United States)

    Mazoir, Noureddine; El Ammari, Lahcen; Bouhmaida, Nouzha; Dahaoui, Slimane; Benharref, Ahmed; Berraho, Moha

    2009-05-14

    The title heterocyclic compound, C(20)H(27)N(3)O(2)S, was synthesized from 2-(4-methyl-cyclo-hex-3-en-yl)-6-methyl-hepta-2,5-dien-4-one, which was isolated from the essential oil Cedrus atlantica. The thia-diazole ring is essentially planar [maximum deviation 0.006 (2) Å] and it forms a dihedral angle of 18.08 (9)° with the benzene ring. The dihedral angle between the thia-diazole ring and the acetamide plane is 7.62 (10)°. In the crystal, mol-ecules are linked into chains running along the c axis by inter-molecular N-H⋯O hydrogen bonds.

  7. Synthesis and evaluation of N-(5-fluoro-2-phenoxyphenyl)-N-(2-[(18)F]fluoromethoxy-d(2)-5-methoxybenzyl)acetamide: a deuterium-substituted radioligand for peripheral benzodiazepine receptor.

    Science.gov (United States)

    Zhang, Ming-Rong; Maeda, Jun; Ito, Takehito; Okauchi, Takashi; Ogawa, Masanao; Noguchi, Junko; Suhara, Tetsuya; Halldin, Christer; Suzuki, Kazutoshi

    2005-03-01

    N-(5-Fluoro-2-phenoxyphenyl)-N-(2-[(18)F]fluoromethoxy-d(2)-5-methoxybenzyl)acetamide ([(18)F]2) is a potent ligand (IC(50): 1.71 nM) for peripheral benzodiazepine receptor (PBR). However, in vivo evaluation on rodents and primates showed that this ligand was unstable and rapidly metabolized to [(18)F]F(-) by defluorination of the [(18)F]fluoromethyl moiety. In this study, we designed a deuterium-substituted analogue, N-(5-fluoro-2-phenoxyphenyl)-N-(2-[(18)F]fluoromethoxy-d(2)-5-methoxybenzyl)acetamide ([(18)F]5) as a radioligand for PBR to reduce the in vivo metabolic rate of the non-deuterated [(18)F]2. The design principle was based on the hypothesis that the deuterium substitution may reduce the rate of defluorination initiated by cleavage of the C-H bond without altering the binding affinity for PBR. The non-radioactive 5 was prepared by reacting diiodomethane-d(2) (CD(2)I(2), 6) with a phenol precursor 7, followed by treatment with tetrabutylammonium fluoride. The ligand [(18)F]5 was synthesized by the alkylation of 7 with [(18)F]fluoromethyl iodide-d(2) ([(18)F]FCD(2)I, [(18)F]9). Compound 5 displayed a similar in vitro affinity to PBR (IC(50): 1.90 nM) with 2. In vivo evaluation demonstrated that [(18)F]5 was metabolized by defluorination to [(18)F]F(-) as a main radioactive component, but its metabolic rate was slower than that of [(18)F]2 in the brain of mice. The deuterium substitution decreased the radioactivity level of [(18)F]5 in the bone of mouse, augmented by the percentage of specific binding to PBR in the rat brain determined by ex vivo autoradiography. However, the PET image of [(18)F]5 for monkey brain showed high radioactivity in the brain and skull, suggesting a possible species difference between rodents and primates.

  8. Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases.

    Science.gov (United States)

    Ruggeri, Roger B; Buckbinder, Leonard; Bagley, Scott W; Carpino, Philip A; Conn, Edward L; Dowling, Matthew S; Fernando, Dilinie P; Jiao, Wenhua; Kung, Daniel W; Orr, Suvi T M; Qi, Yingmei; Rocke, Benjamin N; Smith, Aaron; Warmus, Joseph S; Zhang, Yan; Bowles, Daniel; Widlicka, Daniel W; Eng, Heather; Ryder, Tim; Sharma, Raman; Wolford, Angela; Okerberg, Carlin; Walters, Karen; Maurer, Tristan S; Zhang, Yanwei; Bonin, Paul D; Spath, Samantha N; Xing, Gang; Hepworth, David; Ahn, Kay; Kalgutkar, Amit S

    2015-11-12

    Myeloperoxidase (MPO) is a heme peroxidase that catalyzes the production of hypochlorous acid. Clinical evidence suggests a causal role for MPO in various autoimmune and inflammatory disorders including vasculitis and cardiovascular and Parkinson's diseases, implying that MPO inhibitors may represent a therapeutic treatment option. Herein, we present the design, synthesis, and preclinical evaluation of N1-substituted-6-arylthiouracils as potent and selective inhibitors of MPO. Inhibition proceeded in a time-dependent manner by a covalent, irreversible mechanism, which was dependent upon MPO catalysis, consistent with mechanism-based inactivation. N1-Substituted-6-arylthiouracils exhibited low partition ratios and high selectivity for MPO over thyroid peroxidase and cytochrome P450 isoforms. N1-Substituted-6-arylthiouracils also demonstrated inhibition of MPO activity in lipopolysaccharide-stimulated human whole blood. Robust inhibition of plasma MPO activity was demonstrated with the lead compound 2-(6-(5-chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999, 8) upon oral administration to lipopolysaccharide-treated cynomolgus monkeys. On the basis of its pharmacological and pharmacokinetic profile, PF-06282999 has been advanced to first-in-human pharmacokinetic and safety studies.

  9. A facile synthesis of new 5-aryl-thiophenes bearing sulfonamide moiety via Pd(0-catalyzed Suzuki–Miyaura cross coupling reactions and 5-bromothiophene-2-acetamide: As potent urease inhibitor, antibacterial agent and hemolytically active compounds

    Directory of Open Access Journals (Sweden)

    Mnaza Noreen

    2017-01-01

    Full Text Available The present study reports a convenient approach for the synthesis of thiophene sulfonamide derivatives (3a–3k via Suzuki cross coupling reaction. This method of synthesis involved the reactions of various aryl boronic acids and esters with 5-bromthiophene-2-sulfonamide (2 under mild and suitable temperature conditions. The compounds synthesized in the present study were subjected to urease inhibition and hemolytic activities. The substitution pattern and the electronic effects of different functional groups (i.e., Cl, CH3, OCH3, F etc. available on the aromatic ring are found to have significant effect on the overall results. The compound 5-Phenylthiophene-2-sulfonamide 3a showed the highest urease inhibition activity with IC50 value ∼ 30.8 μg/mL compared with the thiourea (used as standard having IC50 value ∼ 43 μg/mL. Moreover, almost all of the compounds were examined for the hemolytic activity against triton X-100 with positive results obtained in most of the cases. In addition, the antibacterial activities of the derivatives of 5-arylthiophene-2-sulfonamide and 5-bromothiophene-2-acetamide were also investigated during the course of the study.

  10. Efecto bactericida de la acetamida furánica bromada frente a cepas salvajes de Pasteurella multocida in vitro (Evaluation of bactericide effect of bromade furanic acetamid against to wilds strains of multocide Pasterella in vitr

    Directory of Open Access Journals (Sweden)

    Estrada, C., Osmaida

    2007-11-01

    Full Text Available Resumen Se realizó una evaluación del efecto la Acetamida furánica bromada frente a cepas salvajes de Pasteurella multocida in vitro, en el Laboratorio Provincial de Diagnóstico Veterinario de Granma. Se determinó la Concentración Mínima Inhibitoria (CMI y Concentración Máxima Bactericida (CMB, empleando el método de diluciones seriadas en tubos. La CMI y la CMB fueron iguales a 8 (µg en una dilución de 1:4. Se realizó una prueba de hipótesis entre proporciones, con un nivel de significación de ( p<0.05. Se concluye que la acetamida furánica bromada posee acción bactericida sobre la Pasteurella multocida in vitro, lo que puede constituir una opción en el tratamiento del Cólera en las aves, previo estudio. Abstract The effect of the Bromade Furanic Acetamide in the group of multocida Pasteurella in vitro, was evaluated. Determined the minimun Concentration Inhibets (MCI and Maximun Concentration Germicide (MCG, using the dilution seriade in tubes method. It was determined that the MCI and MCG were some (8. 2 µg/ml in a dilution of 1:4. An Hypothesis test for proportions was done with the singnificance level (p<0.05. It is concluded that the product possesses germicide positive action on the Pasteurella multocida in vitro, so it may constitute an option the treatment of aviar cholera, previous study.

  11. Different molecular conformations co-exist in each of three 2-aryl-N-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)acetamides: hydrogen bonding in zero, one and two dimensions.

    Science.gov (United States)

    Narayana, Badiadka; Yathirajan, Hemmige S; Rathore, Ravindranath S; Glidewell, Christopher

    2016-09-01

    4-Antipyrine [4-amino-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one] and its derivatives exhibit a range of biological activities, including analgesic, antibacterial and anti-inflammatory, and new examples are always of potential interest and value. 2-(4-Chlorophenyl)-N-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)acetamide, C19H18ClN3O2, (I), crystallizes with Z' = 2 in the space group P\\overline{1}, whereas its positional isomer 2-(2-chlorophenyl)-N-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)acetamide, (II), crystallizes with Z' = 1 in the space group C2/c; the molecules of (II) are disordered over two sets of atomic sites having occupancies of 0.6020 (18) and 0.3980 (18). The two independent molecules of (I) adopt different molecular conformations, as do the two disorder components in (II), where the 2-chlorophenyl substituents adopt different orientations. The molecules of (I) are linked by a combination of N-H...O and C-H...O hydrogen bonds to form centrosymmetric four-molecule aggregates, while those of (II) are linked by the same types of hydrogen bonds forming sheets. The related compound N-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-2-(3-methoxyphenyl)acetamide, C20H21N3O3, (III), is isomorphous with (I) but not strictly isostructural; again the two independent molecules adopt different molecular conformations, and the molecules are linked by N-H...O and C-H...O hydrogen bonds to form ribbons. Comparisons are made with some related structures, indicating that a hydrogen-bonded R2(2)(10) ring is the common structural motif.

  12. Infrared spectra, Raman laser, XRD, DSC/TGA and SEM investigations on the preparations of selenium metal, (Sb2O3, Ga2O3, SnO and HgO) oxides and lead carbonate with pure grade using acetamide precursors

    Indian Academy of Sciences (India)

    Moamen S Refat; Khaled M Elsabawy

    2011-07-01

    Ga2O3, Se metal, SnO, Sb2O3, HgO and PbCO3 are formed upon the reaction of acetamide aqueous solutions with Ga(NO3)3, SeO2, SnCl2, SbCl3, HgCl2 and Pb(NO3)2, respectively, at 90°C. Different amorphous or crystalline phases can be obtained depending upon the experimental conditions (molar ratios, metal salts and temperature). The chemical mechanisms for the formations of this metal, oxides or carbonate are discussed and the X-ray diffraction, scanning electron microscopy (SEM) and atomic force microscope (AFM) are described. The type of metal ions plays an important role in the decomposition of acetamide, leading to the formation of solid stable (metal, oxides or carbonate), soluble and gases species. These new precursors are more stable preventing the rapid precipitation of metal, oxides or carbonate. Furthermore, this route allows the formation of pure compounds in solutions.

  13. 乙酰胺-尿素- NaBr熔体中电沉积Gd-Mg-Ni合金的研究%Study on Electrodeposition of Gd-Mg-Ni Alloy Film in Acetamide - urea - NaBr Melt

    Institute of Scientific and Technical Information of China (English)

    陈必清; 王建朝; 郭承育

    2011-01-01

    RE - Mg - Ni ternary alloy is a new AB3 type hydrogen storage material.The electrodeposition preparation of the alloys in acetamide - urea - NaBr melt at 353 K was studied. The cyclic voltammetry experiment proved that Gd ( III ) and Mg( II ) cannot be reduced to Gd and Mg directly on Pt or Cu electrodes but can be inductively codeposited with Ni (II). The amorphous Gd - Mg - Ni alloy films was obtained on Cu electrodes by potentiostatic electrolysis. The content of Gd and Mg in the Gd - Mg - Ni alloy film changes with the cathode potential , molar ratio of Gd( III )/ Mg( II )/ Ni( II ) and the electrolysis time.The electrochemistry behavior of Ni ( II ) on Pt or Cu electrodes was studied. The results showed that the reduction is irreversible in one step. Diffusion coefficient a and electron transfer coefficient D0 were measured.%RE-Mg-Ni系三元合金是AB3型新型储氢材料.研究了在乙酰胺-尿素- NaBr熔体中(353K)电沉积制备该合金的可行性.循环伏安法研究证实,该熔体中,Gd(Ⅲ)、Mg(Ⅱ)在Pt、Cu电极上不能单独沉积,但可以被铁族Ni(Ⅱ)诱导共沉积.在Cu基体上由恒电位电解法成功的沉积出Gd-Mg-Ni合金膜,合金膜中Gd和Mg的含量随电解电位、时间及Gd(Ⅲ)/Mg(Ⅱ)/Ni(Ⅱ)摩尔比的变化而变化.实验同时研究了Ni(Ⅱ)在Pt、Cu电极上的电化学行为,表明其还原为一步完全不可逆反应,并测得其传递系数α和扩散系数Do.

  14. Development of a new radioligand, N-(5-fluoro-2-phenoxyphenyl)-N-(2-[18F]fluoroethyl-5-methoxybenzyl)acetamide, for pet imaging of peripheral benzodiazepine receptor in primate brain.

    Science.gov (United States)

    Zhang, Ming-Rong; Maeda, Jun; Ogawa, Masanao; Noguchi, Junko; Ito, Takehito; Yoshida, Yuichiro; Okauchi, Takashi; Obayashi, Shigeru; Suhara, Tetsuya; Suzuki, Kazutoshi

    2004-04-22

    To develop a positron emission tomography (PET) ligand for imaging the 'peripheral benzodiazepine receptor' (PBR) in brain and elucidating the relationship between PBR and brain diseases, four analogues (4-7) of N-(2,5-dimethoxybenzyl)-N-(5-fluoro-2-phenoxyphenyl)acetamide (2) were synthesized and evaluated as ligands for PBR. Of these compounds, fluoromethyl (4) and fluoroethyl (5) analogues had similar or higher affinities for PBR than the parent compound 2 (K(i) = 0.16 nM for PBR in rat brain sections). Iodomethyl analogue 6 displayed a moderate affinity, whereas tosyloxyethyl analogue 7 had weak affinity. Radiolabeling was performed for the fluoroalkyl analogues 4 and 5 using fluorine-18 ((18)F, beta(+); 96.7%, T(1/2) = 109.8 min). Ligands [(18)F]4 and [(18)F]5 were respectively synthesized by the alkylation of desmethyl precursor 3 with [(18)F]fluoromethyl iodide ([(18)F]8) and 2-[(18)F]fluoroethyl bromide ([(18)F]9). The distribution patterns of [(18)F]4 and [(18)F]5 in mice were consistent with the known distribution of PBR. However, compared with [(18)F]5, [(18)F]4 displayed a high uptake in the bone of mice. The PET image of [(18)F]4 for monkey brain also showed significant radioactivity in the bone, suggesting that this ligand was unstable for in vivo defluorination and was not a useful PET ligand. Ligand [(18)F]5 displayed a high uptake in monkey brain especially in the occipital cortex, a region with richer PBR than the other regions in the brain. The radioactivity level of [(18)F]5 in monkey brain was 1.5 times higher than that of [(11)C]2, and 6 times higher than that of (R)-(1-(2-chlorophenyl)-N-[(11)C]methyl,N-(1-methylpropyl)isoquinoline ([(11)C]1). Moreover, the in vivo binding of [(18)F]5 was significantly inhibited by PBR-selective 2 or 1, indicating that the binding of [(18)F]5 in the monkey brain was mainly due to PBR. Metabolite analysis revealed that [(18)F]4 was rapidly metabolized by defluorination to [(18)F]F(-) in the plasma and brain of

  15. N-[4-(4-Chlorobenzenesulfonamidophenylsulfonyl]acetamide

    Directory of Open Access Journals (Sweden)

    Islam Ullah Khan

    2012-06-01

    Full Text Available In the title compound, C14H13ClN2O5S2, the dihedral angles between the central benzene ring and the pendant chlorobenzene ring and the N-acetyl group are 82.35 (5 and 79.71 (6°, respectively, and the overall conformation of the molecule approximates to a U shape. Both the C—S—N—C conformations are gauche, but with opposite senses [torsion angles = −59.29 (15 and 63.68 (16°]. An intramolecular C—H...O interaction generates an S(6 ring. In the crystal, inversion dimers linked by pairs of N—H...O hydrogen bonds generate R22(20 loops. A second N—H...O hydrogen bond links the dimers into (101 layers.

  16. 1H and 13C NMR Spectral Studies on N-(Aryl)-Substituted Acetamides, C6H5NHCOCH3-iXi and 2/4-XC6H4NHCOCH3-iXi (where X = Cl or CH3 and i = 0, 1, 2 or 3)

    Science.gov (United States)

    Gowda, B. Thimme; Usha, K. M.; Jayalakshmi, K. L.

    2003-12-01

    35 N-(Phenyl)-, N-(2/4-chlorophenyl)- and N-(2/4-methylphenyl)-substituted acetamides are prepared, characterised and their NMR spectra studied in solution state. The variation of the chemical shifts of the aromatic protons in these compounds follow more or less the same trend with changes in the side chain. The chemical shifts remain almost the same on introduction of Cl substituent to the benzene ring, while that of methyl group lowers the chemical shifts of the aromatic protons. But only 13C-1 and 13C-4 chemical shifts in these compounds are sensitive to variations of the side chain. The incremental shifts in the chemical shifts of the aromatic protons and carbons due to -COCH3-iXi or NHCOCH3-iXi groups in all the N-(phenyl)-substituted acetamides, C6H5NHCOCH3-iXi (where X = Cl or CH3 and i = 0, 1, 2 or 3) are calculated. These incremental chemical shifts are used to calculate the chemical shifts of the aromatic protons and carbons in all the N-(2/4-chlorophenyl)- and N-(2/4-methylphenyl)-substituted acetamides, in two ways. In the first way, the chemical shifts of aromatic protons or carbons are computed by adding the incremental shifts due to -COCH3-iXi groups and the substituents at the 2nd or 4th position in the benzene ring to the chemical shifts of the corresponding aromatic protons or carbons of the parent aniline. In the second way, the chemical shifts are calculated by adding the incremental shifts due to -NHCOCH3-iXi groups and the substituents at the 2nd or 4th position in the benzene ring to the chemical shift of a benzene proton or carbon, respectively. Comparison of the two sets of calculated chemical shifts of the aromatic protons or carbons of all the compounds revealed that the two procedures of calculation lead to almost the same values in most cases and agree well with the experimental chemical shifts.

  17. Factors Affecting Formation of THMs During Dissolved Organic Nitrogen Acetamide Chlorination in Drinking Water%溶解性有机氮乙酰胺氯化生成饮用水THMs的影响因素研究

    Institute of Scientific and Technical Information of China (English)

    楚文海; 高乃云; 赵世嘏; 李青松

    2009-01-01

    Chlorination disinfection greatly reduced bacteria and virus in drinking water. However,there is an unintended consequence of disinfection,the generation of chemical disinfection by-products (DBPs). Dissolved organic nitrogen (DON) as the important precursor of DBPs is of current concern. As acetamide (AcAm) occur in important bimolecular,we studied formation pathways for THMs during chlorination of model AcAm. The experiments are designed by Plackett-Burman and Box-Behnken methods. Factors affecting formation of THMs such as AcAm initial concentration,chlorine dosage,pH,temperature,Br- concentration and contact time were investigated. The results indicate that AcAm initial concentration,pH and temperature have little effects on formation of THMs. On the contrary,three other factors have important effects on formation of THMs,especially Br- concentration. The capacity of THMs generation varies very little when Br- has a constant concentration. Generation amount of THMs attach maximum under the condition that dosage of active chlorine,Br- concentration and contact time is 8.77 mg/L,0.77 mg/L and 6.20 h respectively. Bromine ion plays a catalysis role on THMs formation. Controlling the concentration of bromine ion can reduce total generation amount of THMs via AcAm. Bromine partition coefficient tends to increasing along with contact time lapse. Controlling chlorination reaction time can lower the cancer risk. At last,the pathway is proposed for THMs formation via AcAm,and the catalysis mechanism of Br- was addressed.%氯化消毒可以有效杀灭细菌,但同时会产生危害人体健康的消毒副产物(DBPs).溶解性有机氮(DON)是DBPs的重要前体物,为考察DON对THMs的影响,首次选取乙酰胺(AcAm)作为前体物DON的代表物质,采用Plackett-Burman和Box-Behnken方法设计试验,考察了AcAm初始浓度、加氯量、pH、温度、溴离子浓度和反应时间等因素对三卤甲烷(THMs)生成的影响.结果表明,在AcAm生成THMs的

  18. Imaging of peripheral-type benzodiazepine receptor in tumor: in vitro binding and in vivo biodistribution of N-benzyl-N-[{sup 11}C]methyl-2- (7-methyl-8-oxo-2-phenyl-7,8-dihydro-9H-purin-9-yl) acetamide

    Energy Technology Data Exchange (ETDEWEB)

    Yamasaki, Tomoteru; Kumata, Katsushi; Yanamoto, Kazuhiko; Hatori, Akiko [Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Takei, Makoto; Nakamura, Yukio [Tokyo Nuclear Service Co. Ltd., Tokyo 141-8686 (Japan); Koike, Sachiko; Ando, Koichi [Heavy-ion Radiobiology Research Group, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Suzuki, Kazutoshi [Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Zhang, Ming-Rong [Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan)], E-mail: zhang@nirs.go.jp

    2009-10-15

    Introduction: The aim of this study was to evaluate N-benzyl-N-[{sup 11}C]methyl-2- (7-methyl-8-oxo-2-phenyl-7,8-dihydro-9H-purin-9-yl) acetamide ([{sup 11}C]DAC) as a novel peripheral-type benzodiazepine receptor (PBR) ligand for tumor imaging. Methods: [{sup 11}C]DAC was synthesized by the reaction of a desmethyl precursor with [{sup 11}C]CH{sub 3}I. In vitro uptake of [{sup 11}C]DAC was examined in PBR-expressing C6 glioma and intact murine fibrosarcoma (NFSa) cells. In vivo distribution of [{sup 11}C]DAC was determined using NFSa-bearing mice and small-animal positron emission tomography (PET). Results: [{sup 11}C]DAC showed specific binding to PBR in C6 glioma cells, a standard cell line with high PBR expression. Specific binding of [{sup 11}C]DAC was also confirmed in NFSa cells, a target tumor cell line in this study. Results of PET experiments using NFSa-bearing mice, showed that [{sup 11}C]DAC was taken up specifically into the tumor, and pretreatment with PK11195 abolished the uptake. Conclusions: [{sup 11}C]DAC was taken up into PBR-expressing NFSa. [{sup 11}C]DAC is a promising PET ligand that can be used for imaging PBR in tumor-bearing mice.

  19. A comparison of vasodilation mode among selexipag (NS-304; [2-{4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy}-N-(methylsulfonyl)acetamide]), its active metabolite MRE-269 and various prostacyclin receptor agonists in rat, porcine and human pulmonary arteries.

    Science.gov (United States)

    Fuchikami, Chiaki; Murakami, Kohji; Tajima, Koyuki; Homan, Junko; Kosugi, Keiji; Kuramoto, Kazuya; Oka, Michiko; Kuwano, Keiichi

    2017-01-15

    Selexipag (NS-304; [2-{4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy}-N- (methylsulfonyl)acetamide]) is a novel, orally available non-prostanoid prostacyclin receptor (IP receptor) agonist that has recently been approved for the treatment of pulmonary arterial hypertension (PAH). We examined the effect of the active metabolite of selexipag, MRE-269, and IP receptor agonists that are currently available as PAH therapeutic drugs on the relaxation of rat, porcine and human pulmonary artery. cAMP formation in human pulmonary artery smooth muscle cells was induced by all test compounds (MRE-269, epoprostenol, iloprost, treprostinil and beraprost sodium) and suppressed by IP receptor antagonists (CAY10441 and 2-[4-(1H-indol-4-yloxymethyl)-benzyloxycarbonylamino]-3-phenyl-propionic acid). MRE-269 induced endothelium-independent vasodilation of rat extralobar pulmonary artery (EPA). In contrast, endothelial denudation or the addition of a nitric oxide synthase inhibitor markedly attenuated the vasodilation of EPA induced by epoprostenol, treprostinil and beraprost sodium but not iloprost. The vasorelaxant effects of MRE-269 on rat small intralobar pulmonary artery (SIPA) and EPA were the same, while the other IP receptor agonists induced less vasodilation in SIPA than in EPA. Furthermore, a prostaglandin E receptor 3 antagonist enhanced the vasodilation induced by all IP receptor agonists tested except MRE-269. We also investigated the relaxation induced by IP receptor agonists in pulmonary arteries from non-rodent species and found similar vasodilation modes in porcine and human as in rat preparations. These results suggest that MRE-269, in contrast to other IP receptor agonists, works as a selective IP receptor agonist, thus leading to pronounced vasorelaxation of rat, porcine and human pulmonary artery.

  20. Evaluation of N-benzyl-N-[11C]methyl-2- (7-methyl-8-oxo-2-phenyl-7,8-dihydro-9H-purin-9-yl)acetamide ([11C]DAC) as a novel translocator protein (18 kDa) radioligand in kainic acid-lesioned rat.

    Science.gov (United States)

    Yanamoto, Kazuhiko; Yamasaki, Tomoteru; Kumata, Katsushi; Yui, Joji; Odawara, Chika; Kawamura, Kazunori; Hatori, Akiko; Inoue, Osamu; Yamaguchi, Masatoshi; Suzuki, Kazutoshi; Zhang, Ming-Rong

    2009-11-01

    The aim of this study was to evaluate N-benzyl-N-[11C]methyl-2-(7-methyl-8-oxo-2-phenyl-7,8-dihydro-9H-purin-9-yl)acetamide ([11C]DAC) as a new translocator protein (18 kDa) [TSPO, formerly known as the peripheral-type benzodiazepine receptor (PBR)] positron emission tomography (PET) ligand in normal mice and unilateral kainic acid (KA)-lesioned rats. DAC is a derivative of AC-5216, which is a potent and selective PET ligand for the clinical investigation of TSPO. The binding affinity and selectivity of DAC for TSPO were similar to those of AC-5216, and DAC was less lipophilic than AC-5216. The distribution pattern of [11C]DAC was in agreement with TSPO distribution in rodents. No radioactive metabolite of [11C]DAC was found in the mouse brain, although it was metabolized rapidly in mouse plasma. Using small-animal PET, we examined the in vivo binding of [11C]DAC for TSPO in KA-lesioned rats. [11C]DAC and [11C]AC-5216 exhibited similar brain uptake in the lesioned and nonlesioned striatum, respectively. The binding of [11C]DAC to TSPO was increased significantly in the lesioned striatum, and [(11)C]DAC showed good contrast between the lesioned and nonlesioned striatum (the maximum ratio was about threefold). In displacement experiments, the uptake of [11C]DAC in the lesioned striatum was eventually blocked using an excess of either unlabeled DAC or PK11195 injected. [11C]DAC had high in vivo specific binding to TSPO in the injured rat brain. Therefore, [11C]DAC is a useful PET ligand for TSPO imaging, and its specific binding to TSPO is suitable as a new biomarker for brain injury.

  1. Hydrothermal oxidation of an epoxy resin through the study of two model molecules: N-methyl-acetamide and N,N-di[1(phenoxy)2-hydroxy propyl-3] propyl-amine; Oxydation hydrothermale d'une resine epoxyde au travers de l'etude de deux molecules modeles: le N-methylacetamide et la N,N-di[1-(phenoxy) 2-hydroxy propyl-3] propylamine

    Energy Technology Data Exchange (ETDEWEB)

    Moutonnet-Fromonteil, C. [CEA/Cadarache, Dept. d' Etudes des Combustibles (DEC), 13 - Saint-Paul-lez-Durance (France)]|[Bordeaux-1 Univ., 33 (France)

    2000-07-01

    The study consists in choosing and developing a technology to realize damage experiments of an epoxy resin which is used as coating of embedded nuclear samples. Hydrothermal oxidation is the chosen method. We first identified the chemical composition of the epoxy resin. Then we studied hydrolysis and oxidation of a molecule which contains a function of the epoxy network: N-methyl-acetamide. The comparison between our results and those already existing allowed to validate this degradation method. In a second part, we studied a model molecule of the polymer network: N, N-di[1(phenoxy)2-hydroxy propyl-3] propyl-amine. The hydrolysis temperatures are relatively high: the compound is totally destroyed at 300 deg C. Its oxidation leads to the formation of acetic acid from 220 deg C. In the third study, we determined the best experimental conditions to destroy the epoxy resin. Experiments were performed at different temperatures between 200 deg C and 410 deg C. The degradation rates are classically defined by amounts of constituents in liquid and gaseous phases. (author)

  2. N-[(2-Hydroxy-1-naphthyl(3-nitrophenylmethyl]acetamide

    Directory of Open Access Journals (Sweden)

    M. NizamMohideen

    2009-04-01

    Full Text Available The title compound, C19H16N2O4, is of interest as a precursor to biologically active substituted quinolines and related compounds. The dihedral angle between the naphthalene ring system and the benzene ring is 81.9 (1°. The crystal structure is stabilized by N—H...O intermolecular hydrogen bonds, linking the molecules into pairs around a center of symmetry. The crystal structure is further stabilized by intermolecular O—H...O hydrogen bonds, which link the molecules into chains running along a axis. An intramolecular C—H...O short contact is also present.

  3. Synthesis of 2- [ (4-Hydroxylcarbomylphenyl) -methylamino ] - N- ( 2- aminophenyl ) acetamide

    Institute of Scientific and Technical Information of China (English)

    YUE Guo-Ren; DU Zhen-Ting; MA Jun-Ying; QUAN Wei-Guo; PAN Xin-Fu

    2003-01-01

    @@ Early studies revealed that the hybrid polar/apolar compound N, N′-hexamethylene bisacetaamide (HMBA) was a very effective inducer of differentiation in a transformed cell lines. [1] The use of this polar/apolar compound to induce murine erythroleukemia cells (MELC) to undergo erythoid differentiation with suppression of oncogenicity has proved a useful model to study inducer-mediated differentiation of transformed cell. [2] To search more effective inducers, we utilized the computer to design a new target compound. Herein, we reported the synthesis of title compound.

  4. N-[3-(tert-Butyldimethylsiloxymethyl-5-nitrophenyl]acetamide

    Directory of Open Access Journals (Sweden)

    David Barker

    2008-10-01

    Full Text Available The title compound, C15H24N2O4Si, was prepared by the reaction of (3-acetamido-5-nitrobenzylmethanol with tert-butyldimethylsilyl chloride and is a key intermediate in the synthesis of novel nonsymmetrical DNA minor groove-binding agents. There are two independent molecules in the structure, which differ primarily in the rotation about the C—O bond next to the Si atom. Two strong N—H...O hydrogen bonds align the molecules into a wide ribbon extending approximately parallel to the b axis.

  5. S33138 (N-[4-[2-[(3aS,9bR)-8-cyano-1,3a,4,9b-tetrahydro[1] benzopyrano[3,4-c]pyrrol-2(3H)-yl)-ethyl]phenyl-acetamide), a preferential dopamine D3 versus D2 receptor antagonist and potential antipsychotic agent: III. Actions in models of therapeutic activity and induction of side effects.

    Science.gov (United States)

    Millan, Mark J; Loiseau, Florence; Dekeyne, Anne; Gobert, Alain; Flik, Gunnar; Cremers, Thomas I; Rivet, Jean-Michel; Sicard, Dorothée; Billiras, Rodolphe; Brocco, Mauricette

    2008-03-01

    In contrast to clinically available antipsychotics, the novel benzopyranopyrrolidine derivative, S33138 (N-[4-[2-[(3aS,9bR)-8-cyano-1,3a,4,9b-tetrahydro[1]benzopyrano[3,4-c]pyrrol-2(3H)-yl)-ethyl]phenyl-acetamide), behaves as a preferential antagonist of D(3) versus D(2) receptors and does not interact with histamine H(1) and muscarinic receptors. In contrast to haloperidol, clozapine, olanzapine, and risperidone, S33138 (0.16-2.5 mg/kg s.c.) did not disrupt performance in passive-avoidance and five-choice serial reaction time procedures. Furthermore, upon either systemic administration (0.04-2.5 mg/kg s.c.) or introduction into the frontal cortex (0.04-0.63 mug/side), S33138 potently attenuated the perturbation of social recognition by scopolamine or a prolonged intersession delay. Over a comparable and low-dose range, S33138 (0.04-0.63 mg/kg s.c.) elevated dialysis levels of acetylcholine in the frontal cortex of freely moving rats. At higher doses (2.5-10.0 mg/kg s.c.), S33138 also increased frontocortical levels of histamine, whereas monoamines, glutamate, glycine, and GABA were unaffected. By analogy to the other antipsychotics, S33138 (0.63-10.0 mg/kg s.c.) inhibited conditioned avoidance responses in rats, apomorphine-induced climbing in mice, and hyperlocomotion elicited by amphetamine, cocaine, dizocilpine, ketamine, and phencyclidine in rats. S33138 (0.16-2.5 mg/kg s.c.) also blocked the reduction of prepulse inhibition elicited by apomorphine. In comparison with the above actions, only "high" doses of S33138 (10.0-40.0 mg/kg s.c.) elicited catalepsy. To summarize, reflecting preferential blockade of D(3) versus D(2) receptors, S33138 preserves and/or enhances cognitive function, increases frontocortical cholinergic transmission, and is active in models of antipsychotic properties at doses well below those inducing catalepsy. In comparison with clinically available agents, S33138 displays, thus, a distinctive and promising profile of potential

  6. Novel and High Affinity 2-[(Diphenylmethyl)sulfinyl]acetamide (Modafinil) Analogues as Atypical Dopamine Transporter Inhibitors

    DEFF Research Database (Denmark)

    Cao, Jianjing; Slack, Rachel D.; Bakare, Oluyomi M.

    2016-01-01

    pharmacological profiles in animal models of cocaine and methamphetamine abuse. Herein, we report a series of modafinil analogues that have an atypical DAT inhibitor profile. We extended SAR by chemically manipulating the oxidation states of the sulfoxide and the amide functional groups, halogenating the phenyl...

  7. N-(4-((E)-3-arylacryloyl)phenyl)acetamide derivatives and their antileishmanial activity

    Energy Technology Data Exchange (ETDEWEB)

    Pacheco, Dency J.; Trilleras, Jorge; Prent, Luis; Coaves, Tobinson, E-mail: jorgetrilleras@mail.uniatlantico.edu.co [Universidad del Atlantico, Barranquilla-Atlantico (Colombia). Facultad de Ciencias Basicas. Grupo de Investigacion en Compuestos Heterociclicos; Quiroga, Jairo [Universidad del Valle, Cali (Colombia). Dept. de Quimica. Grupo de Investigacion de Compuestos Heterociclicos; Gutierrez, Jennifer; Delgado, Gabriela [Universidad Nacional de Colombia, Bogota, D.C. (Colombia). Facultad de Ciencias. Departamento de Farmacia. Grupo de Investigacion en Inmunotoxicologia; Marin, Juan C. [Universidad Nacional de Colombia, Bogota, D.C. (Colombia). Facultad de Ciencias. Departamento de Farmacia. Grupo de Investigacion Farmacognosia y Fitoquimica

    2013-10-15

    The antileishmanial activity of a series of enonic derivatives (chalcones) synthesized via Claisen-Schmidt condensation reactions assisted by ultrasonic radiation was characterized by analyzing their cytotoxicity against Leishmania (Viannia) panamensis promastigotes, a species responsible for over 90% of Leishmania cases in Colombia. Two compounds were active against Leishmania with selectivity indexes of LC{sub 50} EC{sub 50} {sup -1} (lethal concentration 50 and effective concentration 50) higher than 27 and 3, respectively. These results suggest that a substitution on one of the two chalcone rings (aromatic ring A) with oxygen is convenient. Compound 3g should be further investigated for its antileishmanial activity, especially for being easy to obtain in high yields, making it possible to produce drugs for the treatment of cutaneous leishmaniasis. (author)

  8. Design and synthesis of novel diphenyl oxalamide and diphenyl acetamide derivatives as anticonvulsants.

    Science.gov (United States)

    Nikalje, Anna Pratima G; Ghodke, Mangesh; Girbane, Amol

    2012-01-01

    A series of novel N(1) -substituted-N(2) ,N(2) -diphenyl oxalamides 3a-l were synthesized in good yield by stirring diphenylcarbamoyl formyl chloride (2) and various substituted aliphatic, alicyclic, aromatic, heterocyclic amines in DMF and K(2) CO(3) . Also 2-substituted amino-N,N-diphenylacetamides 5a-m were designed by pharmacophore generation and synthesized by stirring 2-chloro-N,N-diphenylacetamide (4) and various substituted amines in acetone using triethyl amine as a catalyst. All the synthesized compounds were screened for anticonvulsant activity in Swiss albino mice by MES and ScPTZ induced seizure tests. Neurotoxicity screening and behavioral testing was also carried out. Some of the synthesized test compounds were found to be more potent than the standard drug.

  9. Low energy electron induced reactions in fluorinated acetamide - probing negative ions and neutral stable counterparts*

    Science.gov (United States)

    Kopyra, Janina; König-Lehmann, Constanze; Illenberger, Eugen; Warneke, Jonas; Swiderek, Petra

    2016-06-01

    Electron impact to trifluoroacetamide (CF3CONH2, TFAA) in the energy range 0-12 eV leads to a variety of negative fragment ions which are formed via dissociative electron attachment (DEA). The underlying reactions range from single bond cleavages to remarkably complex reactions that lead to loss of the neutral units HF, H2O and HNCO as deduced from their directly observed ionic counterparts (M - H2O)-, (M - HF)- and (M - HNCO)-. Also formed are the pseudo-halogen ions CN- and OCN-. All these reactions proceed dominantly via a resonance located near 1 eV, i.e., electrons at subexcitation energies trigger reactions involving multiple bond cleavages. The electron induced generation of the neutral molecules HF, H2O and HNCO in condensed TFAA films is probed by temperature controlled thermal desorption spectrometry (TDS) which can be viewed as a complementary techniques to gas-phase experiments in DEA to directly probe the neutral counterparts. Contribution to the Topical Issue "Advances in Positron and Electron Scattering", edited by Paulo Limao-Vieira, Gustavo Garcia, E. Krishnakumar, James Sullivan, Hajime Tanuma and Zoran Petrovic.

  10. Synthesis and characterization of novel substituted N-benzothiazole-2-yl-acetamides

    Directory of Open Access Journals (Sweden)

    H.C. Sakarya

    2016-11-01

    Full Text Available Schiff base derivatives of benzothiazole 2a–e have been synthesized by reacting with substituted 2-aminobenzothiazole 1a–e and different substituted benzaldehydes 5a–e. The obtained Schiff bases reaction with NaBH4 has afforded the corresponding some novel amines 3a–e. The condensation of amines with chloroacetylchloride leads to novel amide derivatives 4a–e. The structures of the synthesized compounds are characterized by elemental analysis, IR, MS, 1H NMR and 13C NMR.

  11. 2,2-Dichloro-N-(phenyl­sulfon­yl)­acetamide

    Science.gov (United States)

    Gowda, B. Thimme; Foro, Sabine; Nirmala, P. G.; Sowmya, B. P.; Fuess, Hartmut

    2008-01-01

    The conformation of the N—H and C=O bonds in the title compound, C8H7Cl2NO3S, is trans. The benzene ring and the SO2—NH—CO—C group form a dihedral angle of 79.75 (8)°. Mol­ecules are connected via N—H⋯O hydrogen bonds to form linear supra­molecular chains. PMID:21203230

  12. 2-Chloro-N-(2,5-dichloro­phen­yl)acetamide

    Science.gov (United States)

    Gowda, B. Thimme; Foro, Sabine; Terao, Hiromitsu; Fuess, Hartmut

    2009-01-01

    The conformation of the N—H bond in the structure of the title compound, C8H6Cl3NO, is anti to the C=O bond. The N—H H atom shows close intra­molecular N—H⋯Cl hydrogen bonds with both the ring Cl atom in the ortho position and the side-chain Cl atom. The mol­ecules crystallize in planes parallel to (221). PMID:21583283

  13. Clinical survey on treatment of fluorine acetamide poisoning with both acetamide and ethyl alcohol%乙酰胺联合乙醇抢救氟乙酰胺中毒临床观察

    Institute of Scientific and Technical Information of China (English)

    段华玲; 车娟婷

    2006-01-01

    目的探讨乙酰胺联合无水乙醇抢救急性氟乙酰胺中毒效果.方法在常规治疗氟乙酰胺中毒基础上,加用无水乙醇,比较107例治疗组患者及99例对照组患者疗效.结果治疗组在抽搐改善方面优于对照组(P<0.05).结论乙酰胺联合无水乙醇抢救急性重度氟乙酰胺中毒是一种有效而安全的方法.

  14. Crystal structure of N-[3-(2-chlorobenzoyl-5-ethylthiophen-2-yl]-2-[(E-(2-hydroxybenzylideneamino]acetamide

    Directory of Open Access Journals (Sweden)

    Manpreet Kaur

    2014-09-01

    Full Text Available In the title compound, C22H19ClN2O3S, the dihedral angle between the mean planes of the thiophene ring and the chlorophenyl and hydroxyphenyl rings are 70.1 (1 and 40.2 (4°, respectively. The benzene rings are twisted with respect to each other by 88.9 (3°. The imine bond lies in an E conformation. Intramolecular O—H...N and N—H...O hydrogen bonds each generate S(6 ring motifs. In the crystal, weak C—H...O interactions link the molecules, forming chains along the c axis and zigzag chains along the b axis, generating sheets lying parallel to (100.

  15. N-[3-Methyl-1-phenyl-1-(1H-tetrazol-1-ylbutan-2-yl]acetamide

    Directory of Open Access Journals (Sweden)

    Selvaraj Geetha

    2016-11-01

    Full Text Available In the molecule of the title compound, C14H19N5O, the dihedral angle formed between the tetrazole and phenyl rings is 68.39 (4°. In the crystal, molecules are linked by N—H...N, C—H...N and C—H...O hydrogen bonds to form two-dimensional networks extending parallel to the bc plane.

  16. Heterocyclic acetamide and benzamide derivatives as potent and selective beta3-adrenergic receptor agonists with improved rodent pharmacokinetic profiles.

    Science.gov (United States)

    Goble, Stephen D; Wang, Liping; Howell, K Lulu; Bansal, Alka; Berger, Richard; Brockunier, Linda; DiSalvo, Jerry; Feighner, Scott; Harper, Bart; He, Jiafang; Hurley, Amanda; Hreniuk, Donna; Parmee, Emma; Robbins, Michael; Salituro, Gino; Sanfiz, Anthony; Streckfuss, Eric; Watkins, Eloisa; Weber, Ann E; Struthers, Mary; Edmondson, Scott D

    2010-03-15

    A series of amide derived beta(3)-adrenergic receptor (AR) agonists is described. The discovery and optimization of several series of compounds derived from 1, is used to lay the SAR foundation for second generation beta(3)-AR agonists for the treatment of overactive bladder.

  17. 2,2,2-Trichloro-N-(2,5-dimethyl­phen­yl)acetamide

    Science.gov (United States)

    Gowda, B. Thimme; Foro, Sabine; Fuess, Hartmut

    2008-01-01

    The N—H bond in the title compound, C10H10Cl3NO, is syn to the 2-methyl and anti to the 5-methyl substituent of the aromatic ring. Adjacent mol­ecules are linked into chains through N—H⋯O hydrogen bonding. Two Cl atoms are each disordered equally over two sites. PMID:21202317

  18. Complementary pharmacological and toxicological characterization data on the pharmacological profile of N-(2,6-dichlorophenyl-2-(4-methyl-1-piperidinyl acetamide

    Directory of Open Access Journals (Sweden)

    Myrna Déciga-Campos

    2016-09-01

    Full Text Available This text presents complementary data corresponding to pharmacological and toxicological characterization of N-(2,6-dichlorophenyl-2-(4-methyl-1-piperidinylacetamide (LIA compound. These data support our research article entitled “Pharmacological profile of N-(2,6-dichlorophenyl-2-(4-methyl-1-piperidinylacetamide, a novel analog of lidocaine” Déciga-Campos M., Navarrete-Vázquez G., López-Muñoz F.J., Librowski T., Sánchez-Recillas A., Yañez-Pérez V., Ortiz-Andrade R. (2016 [1]. Toxicity was predicted through the ACD/ToxSuite software and evaluated in vivo using brine shrimp larvae (Artemia salina L. and mice. Also, we used the micronucleus assay to determine genotoxicity. We used the platform admetSAR to predict absorption properties of LIA and lidocaine.

  19. Synthesis of novel pyrazolo[3,4-b]quinolinyl acetamide analogs, their evaluation for antimicrobial and anticancer activities, validation by molecular modeling and CoMFA analysis.

    Science.gov (United States)

    G, Jitender Dev; Y, Poornachandra; K, Ratnakar Reddy; R, Naresh Kumar; N, Ravikumar; D, Krishna Swaroop; P, Ranjithreddy; G, Shravan Kumar; Nanubolu, Jagadeesh B; C, Ganesh Kumar; B, Narsaiah

    2017-02-22

    A series of novel alkyl amide functionalized 2,3-pyrazole fused quinoline derivatives 5, 6 and 7 have been prepared starting from quinoline-2(1H)one 1 in a series of steps. All the final products were screened for antibacterial activity, the promising lead compound 5r was identified with MIC values ranging between 3.9 and 7.8 μg/mL against different bacterial strains. Compound 5r also showed good antifungal and anti-biofilm activities against the tested panel of various fungal and bacterial strains. Compound 5r when treated on mature biofilms of S. aureus strain MLS16, showed increased levels of intracellular ROS accumulation suggesting its contribution to the bactericidal activity. All the compounds were also screened for anticancer activity against a panel of four human cancer cell lines. Based on these studies, compounds 5c, 5d, 5r and 7f were considered as promising and exhibited significant cytotoxicity with IC50 values of <15 μM. The biological activity data was further validated by molecular modeling and CoMFA studies.

  20. Antinociceptive effects of a new sigma-1 receptor antagonist (N-(2-morpholin-4-yl-ethyl)-2-(1-naphthyloxy)acetamide) in two types of nociception.

    Science.gov (United States)

    García-Martínez, Betzabeth Anali; Jaramillo-Morales, Osmar Antonio; Espinosa-Juárez, Josué Vidal; Navarrete-Vázquez, Gabriel; Melo-Hernández, Luis Alberto; Medina-López, José Raúl; Domínguez-Ramírez, Adriana Miriam; Schepmann, Dirk; Wünsch, Bernhard; López-Muñoz, Francisco Javier

    2016-01-15

    Pain has become an active clinical challenge due its etiological heterogeneity, symptoms and mechanisms of action. In the search for new pharmacological therapeutic alternatives, sigma receptors have been proposed as drug targets. This family consists of sigma-1 and sigma-2 receptors. The sigma-1 system is involved in nociception through its chaperone activity. Additionally, it has been shown that agonist to these receptors promote related sensitisation and pain hypersensitisation, suggesting the possible use of antagonists for sigma-1 receptors as an alternative therapy. The aim of this study was to evaluate the antinociceptive effect of a new sigma-1 receptor antagonist N-(2-morpholin-4-yl-ethyl)-2-(1-naphthyloxy)acetamida (NMIN) in two types of pain (arthritic and neuropathic) and to compare its efficacy and potency with reference drugs. The antinociceptive effects of NMIN were quantitatively evaluated using the pain-induced functional impairment model in the rat and the acetone test in a rat model of neuropathic pain. NMIN (sigma-1 receptor affinity of 324nM) did not show any antinociceptive activity in the arthritic pain model but showed a dose-dependent anti-allodynic effect in neuropathic pain. NMIN showed a similar efficacy compared to the effects obtained with morphine and the sigma-1 antagonist BD-1063. However, these reference drugs showed increased potency compared with NMIN. Our results suggest that sigma-1 receptors may play an important direct role in neuropathic pain but not in arthritic pain, supporting the hypothesis that NMIN may be useful for the treatment of neuropathic pain.

  1. Synthesis and Anticonvulsant Properties of New 3,3-Diphenyl-2,5-dioxo-pyrrolidin-1-yl-acetamides and 3,3-Diphenyl-propionamides.

    Science.gov (United States)

    Obniska, Jolanta; Rapacz, Anna; Rybka, Sabina; Góra, Małgorzata; Żmudzki, Paweł; Kamiński, Krzysztof

    2017-04-01

    The focused library of new amides derived from 3,3-diphenyl-2,5-dioxo-pyrrolidin-1-yl-acetic acid (2a-t) and 3,3-diphenyl-propionic acid (3a-t) as potential anticonvulsant agents was synthesized. The final products were obtained in the amidation reaction of the given carboxylic acid (2, 3) with appropriate secondary amines in the presence of carbonyldiimidazole (CDI) as a coupling reagent. The initial anticonvulsant screening was performed in mice intraperitoneally (i.p.) using the "classical" maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) seizure models, whereas the acute neurological toxicity was determined applying the rotarod test. Additionally, several compounds were studied also in the 6-Hz seizures recognized as the animal model of human pharmacoresistant epilepsy. In this series, compound 3q displayed a broad spectrum of activity across the preclinical seizure models (ED50 MES = 31.64 mg/kg; ED50 scPTZ = 75.41 mg/kg, ED50 6-Hz (32 mA) = 38.15 mg/kg). Consequently, compound 3q revealed a wider spectrum of protection, higher activity or/and a better safety profile than the commonly used antiepileptic drugs such as phenytoin, ethosuximide, valproic acid, or/and levetiracetam. Notably, the in vitro studies showed that the most possible mechanism of action of 3q may be connected to the interaction with neuronal voltage-sensitive sodium channels (site 2). Other substances were active predominantly in the chemically induced seizures. The results of the current studies indicate that the presence of the pyrrolidine-2,5-dione ring is important but not indispensable for anticonvulsant activity. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. N-[4-Acetyl-5-methyl-5-(2-p-tolyl-prop-yl)-4,5-dihydro-1,3,4-thia-diazol-2-yl]acetamide.

    Science.gov (United States)

    Tebaa, Mohamed; Mazoir, Noureddine; Maya, Celia M; Nouzha, Bouhmaida; Benharref, Ahmed; Berraho, Moha

    2009-01-10

    The title heterocyclic compound, C(17)H(23)N(3)O(2)S, was synthesized from 4-(4-methyl-cyclo-hex-3-en-yl)pent-3-en-2-one, which was isolated from Cedrus atlantica essential oil. The thia-diazole ring adopts a flattened envelope conformation, with the flap sp(3)-hybridized C atom lying 0.259 (1) Å out of the plane of the other four atoms. The screw-related mol-ecules are linked into chains along the b axis by inter-molecular N-H⋯O hydrogen bonds.

  3. N-[4-Acetyl-5-methyl-5-(2-p-tolylpropyl-4,5-dihydro-1,3,4-thiadiazol-2-yl]acetamide

    Directory of Open Access Journals (Sweden)

    Moha Berraho

    2009-02-01

    Full Text Available The title heterocyclic compound, C17H23N3O2S, was synthesized from 4-(4-methylcyclohex-3-enylpent-3-en-2-one, which was isolated from Cedrus atlantica essential oil. The thiadiazole ring adopts a flattened envelope conformation, with the flap sp3-hybridized C atom lying 0.259 (1 Å out of the plane of the other four atoms. The screw-related molecules are linked into chains along the b axis by intermolecular N—H...O hydrogen bonds.

  4. (±-N-[4-Acetyl-5-methyl-5-(4-methylcyclohex-3-enyl-4,5-dihydro-1,3,4-thiadiazol-2-yl]acetamide

    Directory of Open Access Journals (Sweden)

    Ahmed Benharref

    2008-03-01

    Full Text Available The new title thiadiazole compound, C14H21N3O2S, was semi-synthesized starting from 1-(4-methylcyclohex-3-enylethanone, a natural product isolated from Cedrus atlantica essential oil. The stereochemistry has been confirmed by single-crystal X-ray diffraction. The thiadiazoline ring is roughly planar, although it may be regarded as having a half-chair conformation. The cyclohexenyl ring has a half-chair conformation. The most interesting feature is the formation of a pseudo-ring formed by four molecules associated through N—H...O hydrogen bonds around a fourfold inversion axis, forming an R44(28 motif.

  5. N-[4-Acetyl-5-isobutyl-5-(2-p-tolylpropyl-4,5-dihydro-1,3,4-thiadiazol-2-yl]acetamide ethyl acetate hemisolvate

    Directory of Open Access Journals (Sweden)

    Noureddine Mazoir

    2009-01-01

    Full Text Available The racemic title compound, a new terpenoid, C20H29N3O2S·0.5C4H8O2, was synthesized from Cedrus Atlantica essential oil. The compound crystallizes with a disordered ethyl acetate solvent molecule. The thiadiazole ring is almost planar, with a maximum deviation from the mean plane of 0.015 (2 Å for the C atom connected to the isobutyl group and has a puckering amplitude of 0.026 (2 Å. The dihedral angle between the benzene and thiadiazole rings is 18.32 (8°. The crystal packing involves intermolecular N—H...O hydrogen bonds.

  6. Formation of iodo-trihalomethanes, iodo-acetic acids, and iodo-acetamides during chloramination of iodide-containing waters: Factors influencing formation and reaction pathways

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Shaogang [Key Laboratory of Drinking Water Science and Technology, Research Center for Eco-Environmental Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 18 Shuang-qing Road, Beijing, 100085 (China); Guangxi Colleges and Universities Key Laboratory of Food Safety and Pharmaceutical Analytical Chemistry, Guangxi Key Laboratory of Chemistry and Engineering of Forest Products, School of Chemistry and Chemical Engineering, Guangxi University for Nationalities, Nanning, 530006, Guangxi (China); Li, Zhenlin [Guangxi Colleges and Universities Key Laboratory of Food Safety and Pharmaceutical Analytical Chemistry, Guangxi Key Laboratory of Chemistry and Engineering of Forest Products, School of Chemistry and Chemical Engineering, Guangxi University for Nationalities, Nanning, 530006, Guangxi (China); Dong, Huiyu [Key Laboratory of Drinking Water Science and Technology, Research Center for Eco-Environmental Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 18 Shuang-qing Road, Beijing, 100085 (China); Goodman, Bernard A. [College of Physical Science and Engineering, State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi University, Nanning, 520004, Guangxi (China); Qiang, Zhimin, E-mail: qiangz@rcees.ac.cn [Key Laboratory of Drinking Water Science and Technology, Research Center for Eco-Environmental Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 18 Shuang-qing Road, Beijing, 100085 (China)

    2017-01-05

    This study investigated systematically the factors influencing the formation of iodinated disinfection by-products (I-DBPs) during chloramination of I{sup −}-containing waters, including reaction time, NH{sub 2}Cl dose, I{sup −} concentration, pH, natural organic matter (NOM) concentration, Br{sup −}/I{sup −} molar ratio, and water matrix. Among the I-DBPs detected, iodoform (CHI{sub 3}), iodoacetic acid (IAA), diiodoacetic acid (DIAA), triiodoacetic acid (TIAA), and diiodoacetamide (DIAcAm) were the major species produced from reactions between reactive iodine species (HOI/I{sub 2}) and NOM. A kinetic model involving the reactions of NH{sub 2}Cl auto-decomposition, iodine species transformation and NOM consumption was developed, which could well describe NH{sub 2}Cl decay and HOI/I{sub 2} evolution. Higher concentrations of CHI{sub 3}, IAA, DIAA, TIAA, and DIAcAm were observed in chloramination than in chlorination, whereas IO{sub 3}{sup −} was only formed significantly in chlorination. Maximum formation of I-DBPs occurred at pH 8.0, but acidic conditions favored the formation of iodinated haloacetic acids and DIAcAm. Increasing Br{sup −}/I{sup −} molar ratio from 1 to 10 did not increase the total amount of I-DBPs, but produced more bromine-substituting species. In addition, chloramination of 18 model compounds indicated that low-SUVA{sub 254} (specific ultraviolet absorbance at 254 nm) NOM generally favored the formation of I-DBPs compared to high-SUVA{sub 254} NOM. Finally, potential pathways for I-DBPs formation from chloramination of NOM were proposed.

  7. N-[4-(9-Chloro-quino[3,2-b]benzo[1,4]thia-zin-6-yl)but-yl]acetamide.

    Science.gov (United States)

    Jeleń, Małgorzata; Suwińska, Kinga; Pluta, Krystian; Morak-Młodawska, Beata

    2012-12-01

    In the title mol-ecule, C21H20ClN3OS, the tetra-cyclic system is close to planar [r.m.s. deviation = 0.110 (4) Å]. The dihedral angle between the quinoline ring system and the benzene ring is 178.3 (1)° and the angle between two (S-C=C-N) halves of the thia-zine ring is 173.4 (1)°. In the crystal, mol-ecules are arranged via π-π inter-actions [centroid-centroid distances = 3.603 (2)-3.739 (2) Å] into slipped stacks extending along [010]. Inter-molecular N-H⋯O hydrogen bonds link the amide groups of neighbouring mol-ecules along the stack, generating a C(4) motif. The title compound shows promising anti-proliferative and anti-cancer activity.

  8. Crystal structure of N-(4-oxo-2-sulfanyl-idene-1,3-thia-zolidin-3-yl)-2-(thio-phen-3-yl)acetamide.

    Science.gov (United States)

    Vu Quoc, Trung; Nguyen Ngoc, Linh; Nguyen Tien, Cong; Thang Pham, Chien; Van Meervelt, Luc

    2017-06-01

    The title compound, C9H8N2O2S3, crystallizes with two mol-ecules (A and B) in the asymmetric unit. Both have similar conformations (overlay r.m.s. deviation = 0.209 Å) and are linked by an N-H⋯O hydrogen bond. In both mol-ecules, the thio-phene rings show orientational disorder, with occupancy factors of 0.6727 (17) and 0.3273 (17) for mol-ecule A, and 0.7916 (19) and 0.2084 (19) for mol-ecule B. The five-membered rings make an angle of 79.7 (2)° in mol-ecule A and an angle of 66.8 (2)° in mol-ecule B. In the crystal, chains of mol-ecules running along the a-axis direction are linked by N-H⋯O hydrogen bonds. The inter-action of adjacent chains through N-H⋯O hydrogen bonds leads to two types of ring structures containing four mol-ecules and described by the graph-set motifs R4(4)(18) and R4(2)(14).

  9. 2-[(1RS,3RS,3aRS,6aSR-5-Benzyl-4,6-dioxo-3-phenyloctahydropyrrolo[3,4-c]pyrrol-1-yl]acetamide

    Directory of Open Access Journals (Sweden)

    Konstantin V. Kudryavtsev

    2011-12-01

    Full Text Available In the title compound, C21H21N3O3, the relative stereochemistry of the four stereogenic C atoms has been determined. The dihedral angle between the phenyl rings is 77.63 (7°. In the crystal, ribbons spread along the a axis are formed by N—H...O hydrogen bonds. C—H...π interactions also occur.

  10. Efecto bactericida de la acetamida furánica bromada frente a cepas salvajes de Pasteurella multocida in vitro (Evaluation of bactericide effect of bromade furanic acetamid against to wilds strains of multocide Pasterella in vitr)

    OpenAIRE

    Estrada, C.; Cadrelo, T. Surelis; Salazar, A. Ana Ivis; Almeida, S; Montero, V. R; Peillón, V. O; Cos, D., Yusel; Bárzaga, R; Campuzano, Y

    2007-01-01

    Resumen Se realizó una evaluación del efecto la Acetamida furánica bromada frente a cepas salvajes de Pasteurella multocida in vitro, en el Laboratorio Provincial de Diagnóstico Veterinario de Granma. Se determinó la Concentración Mínima Inhibitoria (CMI) y Concentración Máxima Bactericida (CMB), empleando el método de diluciones seriadas en tubos. La CMI y la CMB fueron iguales a 8 (µg) en una dilución de 1:4. Se realizó una prueba de hipótesis entre proporciones, con un nivel de sign...

  11. Efecto bactericida de la acetamida furánica bromada frente a cepas salvajes de Pasteurella multocida in vitro (Evaluation of bactericide effect of bromade furanic acetamid against to wilds strains of multocide Pasterella in vitr)

    OpenAIRE

    Estrada, C.; Cadrelo, T. Surelis; Salazar, A. Ana Ivis; Almeida, S; Montero, V. R; Cos, D., Yusel; Bárzaga, R; Campuzano, Y

    2007-01-01

    Se realizó una evaluación del efecto la Acetamida furánica bromada frente a cepas salvajes de Pasteurella multocida in vitro, en el Laboratorio Provincial de Diagnóstico Veterinario de Granma. Se determinó la Concentración Mínima Inhibitoria (CMI) y Concentración Máxima Bactericida (CMB), empleando el método de diluciones seriadas en tubos. La CMI y la CMB fueron iguales a 8 (µg) en una dilución de 1:4. Se realizó una prueba de hipótesis entre proporciones, con un nivel de significació...

  12. Synthesis, characterization, crystal structure, and thermal analysis of 2-chloro-N-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl) acetamide

    Energy Technology Data Exchange (ETDEWEB)

    Sharma, R. [University of Jammu, X-ray Crystallography Laboratory, Post-Graduate Department of Physics & Electronics (India); Nayak, P. S.; Narayana, B. [Mangalore University, Mangalagangotri, Department of Studies in Chemistry (India); Kant, R., E-mail: rkvk.paper11@gmail.com [University of Jammu, X-ray Crystallography Laboratory, Post-Graduate Department of Physics & Electronics (India)

    2015-12-15

    The title compound, C{sub 13}H{sub 14}O{sub 2}N{sub 3}Cl, has been synthesized by the reaction of chloroacetyl chloride with 4-aminoantipyrine in basic media and characterized by FT-IR, CHN elemental analysis, UV-Vis, TGA, DTA, DSC and single crystal X-ray diffraction. crystals are monoclinic, sp. gr. P2{sub 1}/c, a = 6.9994(6), b = 12.4035(13), c = 15.836(2) Å, β = 100.367(9)°, Z = 4. The crystal structure is stabilized by N–H···O and C–H···O interactions, the former interactions result in the formation of dimers corresponding to R{sub 2}{sup 2} (10) graphset motif and the dimers are further connected by C–H···O hydrogen bonding forming chains. In addition, the thermal stability of the compound was determined by TGA, DTA, DSC analysis, and absorption at λ{sub max} = 298 nm was determined by UV-Vis spectrophotometer.

  13. N-[4-Acetyl-5-isobutyl-5-(2-p-tolyl-prop-yl)-4,5-dihydro-1,3,4-thia-diazol-2-yl]acetamide ethyl acetate hemisolvate.

    Science.gov (United States)

    Loughzail, Mohamed; Mazoir, Noureddine; Maya, Celia M; Berraho, Moha; Benharref, Ahmed; Bouhmaida, Nouzha

    2008-12-03

    The racemic title compound, a new terpenoid, C(20)H(29)N(3)O(2)S·0.5C(4)H(8)O(2), was synthesized from Cedrus Atlantica essential oil. The compound crystallizes with a disordered ethyl acetate solvent mol-ecule. The thia-diazole ring is almost planar, with a maximum deviation from the mean plane of 0.015 (2) Å for the C atom connected to the isobutyl group and has a puckering amplitude of 0.026 (2) Å. The dihedral angle between the benzene and thia-diazole rings is 18.32 (8)°. The crystal packing involves inter-molecular N-H⋯O hydrogen bonds.

  14. (±)-N-[4-Acetyl-5-methyl-5-(4-methyl-cyclo-hex-3-en-yl)-4,5-dihydro-1,3,4-thia-diazol-2-yl]acetamide.

    Science.gov (United States)

    Mohammed, Tebbaa; Mazoir, Noureddine; Daran, Jean-Claude; Berraho, Moha; Benharref, Ahmed

    2008-02-20

    The new title thiadiazole compound, C(14)H(21)N(3)O(2)S, was semi-synthesized starting from 1-(4-methyl-cyclo-hex-3-en-yl)ethanone, a natural product isolated from Cedrus atlantica essential oil. The stereochemistry has been confirmed by single-crystal X-ray diffraction. The thia-diazo-line ring is roughly planar, although it may be regarded as having a half-chair conformation. The cyclo-hexenyl ring has a half-chair conformation. The most inter-esting feature is the formation of a pseudo-ring formed by four mol-ecules associated through N-H⋯O hydrogen bonds around a fourfold inversion axis, forming an R(4) (4)(28) motif.

  15. N-[4-(9-Chloro­quino[3,2-b]benzo[1,4]thia­zin-6-yl)but­yl]acetamide1

    Science.gov (United States)

    Jeleń, Małgorzata; Suwińska, Kinga; Pluta, Krystian; Morak-Młodawska, Beata

    2012-01-01

    In the title mol­ecule, C21H20ClN3OS, the tetra­cyclic system is close to planar [r.m.s. deviation = 0.110 (4) Å]. The dihedral angle between the quinoline ring system and the benzene ring is 178.3 (1)° and the angle between two (S—C=C—N) halves of the thia­zine ring is 173.4 (1)°. In the crystal, mol­ecules are arranged via π–π inter­actions [centroid–centroid distances = 3.603 (2)–3.739 (2) Å] into slipped stacks extending along [010]. Inter­molecular N—H⋯O hydrogen bonds link the amide groups of neighbouring mol­ecules along the stack, generating a C(4) motif. The title compound shows promising anti­proliferative and anti­cancer activity. PMID:23476166

  16. Studies of linear correlation factor of dielectric polarization and excess dipolar free energies of amides in apolar solvents

    Indian Academy of Sciences (India)

    M Malathi; R Sabesan; S Krishnan

    2005-09-01

    The Kirkwood–Frohlich correlation factor (), Eyring's parameters and * and the dipolar excess free energies of dilute solutions of formamide, acetamide, -methyl acetamide, , -dimethyl formamide and , -dimethyl acetamide in 1,4-dioxan/benzene were obtained from a measurement of their static dielectric permittivities at 308 K. The fluid structure of these amides is discussed. Both in formamide and acetamide a dimeric linear chain with the individual dipoles more or less parallely oriented is preferred. In -methyl acetamide, the antiparallel orientation of dipoles at lower concentrations turns into a parallel orientation with increase of concentration. In tertiary amides, with increase of concentration, parallel orientation of dipoles with global value of tending to unity is observed. The dipolar excess free energy of mixing in a given solvent is of the order primary amide > secondary amide > tertiary amide.

  17. Discovery of N-{4-[5-(4-Fluorophenyl)-3-methyl-2-methylsulfanyl-3H-imidazol-4-yl]-pyridin-2-yl}-acetamide (CBS-3595), a Dual p38α MAPK/PDE-4 Inhibitor with Activity against TNFα-Related Diseases.

    Science.gov (United States)

    Albrecht, Wolfgang; Unger, Anke; Bauer, Silke M; Laufer, Stefan A

    2017-07-13

    The anti-inflammatory potential of p38 mitogen-activated protein kinase (MAPK) inhibitors was coincidentally expanded to a dual inhibition of p38α MAPK and phosphodiesterase 4 (PDE4), and the potential benefits arising from the blockage of both inflammation-related enzymes were thoroughly investigated. The most promising compound, CBS-3595 (1), was successively evaluated in in vitro experiments as well as in ex vivo and in vivo preclinical studies after administration of 1 to rodents, dogs, and monkeys. The resulting data clearly indicated a potent suppression of tumor necrosis factor alpha release. For reconfirming the findings of the animal studies when administering 1 to healthy human volunteers, a phase I clinical trial was conducted. Apart from further information regarding the pharmacokinetic and pharmacodynamic characteristics of 1, it was demonstrated that dual inhibition of p38α MAPK and PDE4 is able to synergistically attenuate the excessive anti-inflammatory response.

  18. Synthesis, SAR, and series evolution of novel oxadiazole-containing 5-lipoxygenase activating protein inhibitors: discovery of 2-[4-(3-{(r)-1-[4-(2-amino-pyrimidin-5-yl)-phenyl]-1-cyclopropyl-ethyl}-[1,2,4]oxadiazol-5-yl)-pyrazol-1-yl]-N,N-dimethyl-acetamide (BI 665915).

    Science.gov (United States)

    Takahashi, Hidenori; Riether, Doris; Bartolozzi, Alessandra; Bosanac, Todd; Berger, Valentina; Binetti, Ralph; Broadwater, John; Chen, Zhidong; Crux, Rebecca; De Lombaert, Stéphane; Dave, Rajvee; Dines, Jonathon A; Fadra-Khan, Tazmeen; Flegg, Adam; Garrigou, Michael; Hao, Ming-Hong; Huber, John; Hutzler, J Matthew; Kerr, Steven; Kotey, Adrian; Liu, Weimin; Lo, Ho Yin; Loke, Pui Leng; Mahaney, Paige E; Morwick, Tina M; Napier, Spencer; Olague, Alan; Pack, Edward; Padyana, Anil K; Thomson, David S; Tye, Heather; Wu, Lifen; Zindell, Renee M; Abeywardane, Asitha; Simpson, Thomas

    2015-02-26

    The synthesis, structure-activity relationship (SAR), and evolution of a novel series of oxadiazole-containing 5-lipoxygenase-activating protein (FLAP) inhibitors are described. The use of structure-guided drug design techniques provided compounds that demonstrated excellent FLAP binding potency (IC50 < 10 nM) and potent inhibition of LTB4 synthesis in human whole blood (IC50 < 100 nM). Optimization of binding and functional potencies, as well as physicochemical properties resulted in the identification of compound 69 (BI 665915) that demonstrated an excellent cross-species drug metabolism and pharmacokinetics (DMPK) profile and was predicted to have low human clearance. In addition, 69 was predicted to have a low risk for potential drug-drug interactions due to its cytochrome P450 3A4 profile. In a murine ex vivo whole blood study, 69 demonstrated a linear dose-exposure relationship and a dose-dependent inhibition of LTB4 production.

  19. Discovery, Synthesis, And Structure-Based Optimization of a Series of N-(tert-Butyl)-2-(N-arylamido)-2-(pyridin-3-yl) Acetamides (ML188) as Potent Noncovalent Small Molecule Inhibitors of the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) 3CL Protease

    Energy Technology Data Exchange (ETDEWEB)

    Jacobs, Jon [Vanderbilt Univ., Nashville, TN (United States); Vanderbilt Specialized Chemistry Center for Probe Development (MLPCN), Nashville, TN (United States); Grum-Tokars, Valerie [Northwestern Univ., Chicago, IL (United States); Zhou, Ya [Vanderbilt Univ., Nashville, TN (United States); Vanderbilt Specialized Chemistry Center for Probe Development (MLPCN), Nashville, TN (United States); Turlington, Mark [Vanderbilt Univ., Nashville, TN (United States); Vanderbilt Specialized Chemistry Center for Probe Development (MLPCN), Nashville, TN (United States); Saldanha, S. Adrian [Sripps Research Inst. Molecular Screening Center, Jupiter, FL (United States); Chase, Peter [Sripps Research Inst. Molecular Screening Center, Jupiter, FL (United States); Eggler, Aimee [Purdue Univ., West Lafayette, IN (United States); Dawson, Eric S. [Vanderbilt Univ., Nashville, TN (United States); Vanderbilt Specialized Chemistry Center for Probe Development (MLPCN), Nashville, TN (United States); Baez-Santos, Yahira M. [Purdue Univ., West Lafayette, IN (United States); Tomar, Sakshi [Purdue Univ., West Lafayette, IN (United States); Mielech, Anna M. [Loyola Univ. Medical Center, Maywood, IL (United States); Baker, Susan C. [Loyola Univ. Medical Center, Maywood, IL (United States); Lindsley, Craig W. [Vanderbilt Univ., Nashville, TN (United States); Vanderbilt Specialized Chemistry Center for Probe Development (MLPCN), Nashville, TN (United States); Hodder, Peter [Sripps Research Inst. Molecular Screening Center, Jupiter, FL (United States); Mesecar, Andrew [Purdue Univ., West Lafayette, IN (United States); Stauffer, Shaun R. [Vanderbilt Univ., Nashville, TN (United States); Vanderbilt Specialized Chemistry Center for Probe Development (MLPCN), Nashville, TN (United States)

    2012-12-11

    A high-throughput screen of the NIH molecular libraries sample collection and subsequent optimization of a lead dipeptide-like series of severe acute respiratory syndrome (SARS) main protease (3CLpro) inhibitors led to the identification of probe compound ML188 (16-(R), (R)-N-(4-(tert-butyl)phenyl)-N-(2-(tert-butylamino)-2-oxo-1-(pyridin-3-yl)ethyl)furan-2-carboxamide, Pubchem CID: 46897844). But, unlike the majority of reported coronavirus 3CLpro inhibitors that act via covalent modification of the enzyme, 16-(R) is a noncovalent SARS-CoV 3CLpro inhibitor with moderate MW and good enzyme and antiviral inhibitory activity. A multicomponent Ugi reaction was utilized to rapidly explore structure–activity relationships within S1', S1, and S2enzyme binding pockets. Moreover, the X-ray structure of SARS-CoV 3CLpro bound with 16-(R) was instrumental in guiding subsequent rounds of chemistry optimization. 16-(R) provides an excellent starting point for the further design and refinement of 3CLpro inhibitors that act by a noncovalent mechanism of action.

  20. Biotransformation of Indole to 3-Methylindole by Lysinibacillus xylanilyticus Strain MA

    Directory of Open Access Journals (Sweden)

    Pankaj Kumar Arora

    2015-01-01

    Full Text Available An indole-biotransforming strain MA was identified as Lysinibacillus xylanilyticus on the basis of the 16S rRNA gene sequencing. It transforms indole completely from the broth culture in the presence of an additional carbon source (i.e., sodium succinate. Gas-chromatography-mass spectrometry identified indole-3-acetamide, indole-3-acetic acid, and 3-methylindole as transformation products. Tryptophan-2-monooxygenase activity was detected in the crude extracts of indole-induced cells of strain MA, which confirms the formation of indole-3-acetamide from tryptophan in the degradation pathway of indole. On the basis of identified metabolites and enzyme assay, we have proposed a new transformation pathway for indole degradation. Indole was first transformed to indole-3-acetamide via tryptophan. Indole-3-acetamide was then transformed to indole-3-acetic acid that was decarboxylated to 3-methylindole. This is the first report of a 3-methylindole synthesis via the degradation pathway of indole.

  1. Delocalized mixed-valence bi- and trinuclear complexes with short Cu-Cu bonds.

    Science.gov (United States)

    Yang, Lei; Powell, Douglas R; Klein, Eric L; Grohmann, Andreas; Houser, Robert P

    2007-08-20

    Two mixed-valence copper complexes were synthesized with ligands N-(2-pyridylmethyl)acetamide (Hpmac) and N,N'-(2-methyl-2-pyridylpropan-1,3-diyl)bis(acetamide) (H2pp(ac)2). Dimer [Cu2(pmac)2]OTf and trimer [Cu3(pp(ac)2)2].NaOTf both contain fully delocalized, mixed-valence Cu(1.5)Cu(1.5) moieties.

  2. Photoinduced intramolecular substitution reaction of aryl halide with carbonyl oxygen of amide group

    CERN Document Server

    Park, Y T; Kim, M S; Kwon, J H

    2002-01-01

    Photoreaction of N-(o-halophenyl)acetamide in basic acetonitrile produces an intramolecular substituted product, 2-methylbenzoxazole in addition to reduced product, acetanilide, whereas photoreaction of N-(o-halobenzyl)acetamide affords a reduced product, N-benzylacetamide only. On the basis of preparative reaction, kinetics, and UV/vis absorption behavior, an electrophilic aromatic substitution of aryl halide with oxygen of its amide bond are proposed.

  3. Isolasi Nanokristal Selulosa Dari Tongkol Jagug (Zea mays L) Dengan Metode hidrolisa Menggunakan Pelarut Dimetil Asetamida/Litium Klorida (DMAc/LiCl)

    OpenAIRE

    Kasrawati

    2014-01-01

    Isolation of cellulose nanocrystal from corncorb (Zea Mays, L) by hydrolyzed method using solvent dimethyl acetamide/lithium chloride (DMAc/LiCl) have been done. Corncorb was delignificated with 3.5% nitric acid and sodium nitrite, then the residue was treated with 17.5% sodium hydroxide, and bleached with 10% hydrogen peroxide. Cellulose nanocrystal was done by hydrolysis method using solvent dimethyl acetamide / lithium klodida (DMAc/LiCl). From the image of transmission electron microscopy...

  4. Terminal group effects on the fluorescence spectra of europium(III) nitrate complexes with a family of amide-based 2,3-dihydroxynaphthalene derivatives

    Science.gov (United States)

    Lei, Ke-Wei; Liu, Wei-Sheng

    2006-09-01

    Three ligands 2,2'-[2,3-naphthylenebis(oxy)]-bis( N, N-diethyl(acetamide)) (L a), 2,2'-[2,3-naphthylenebis(oxy)]-bis( N, N-diisopropyl(acetamide)) (L b) and 2,2'-[2,3-naphthylenebis(oxy)]-bis( N, N-dibutyl(acetamide)) (L c) and their europium(III) nitrate complexes were synthesized. The complexes were characterized by elemental analysis, IR, fluorescence spectroscopy and conductivity. The europium atoms are coordinated by O-atoms from C dbnd O, Ar-O-C. With the difference of the ligands, the solid fluorescent intensities of the Eu complexes vary regularly. Some factors that influencing the fluorescent intensity were discussed.

  5. Compound list: thioacetamide [Open TG-GATEs

    Lifescience Database Archive (English)

    Full Text Available thioacetamide TAA 00017 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/thio...acetamide.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/thio...acetamide.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Single/thio...edbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/thioacetamide.Rat.in_vivo.Liver.Repeat.zip ftp:...//ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Kidney/Single/thioacetamide.Rat.in_vivo.Kidne

  6. (3-Methylbenzonitrile-κNtetrakis(μ-N-phenylacetamidato-κ4N:O;κ4O:N-dirhodium(II(Rh—Rh

    Directory of Open Access Journals (Sweden)

    Jennie Tan

    2013-12-01

    Full Text Available In the title compound, [Rh2(C8H8NO4(C8H7N], the four acetamidate ligands bridging the dirhodium core are arranged in a 2,2-trans manner. One RhII atom is five-coordinate, in a distorted pyramidal geometry, while the other is six-coordinate, with a disorted octahedral geometry. For the six-coordinate RhII atom, the axial nitrile ligand shows a non-linear Rh–nitrile coordination with an Rh—N—C bond angle of 166.4 (4° and a nitrile N—C bond length of 1.138 (6 Å. Each unique RhII atom is coordinated by a trans pair of N atoms and a trans pair of O atoms from the four acetamide ligands. The Neq—Rh—Rh—Oeq torsion angles on the acetamide bridge varies between 12.55 (11 and 14.04 (8°. In the crystal, the 3-methylbenzonitrile ring shows a π–π interaction with an inversion-related equivalent [interplanar spacing = 3.360 (6 Å]. A phenyl ring on one of the acetamide ligands also has a face-to-face π–π interaction with an inversion-related equivalent [interplanar spacing = 3.416 (5 Å].

  7. 40 CFR Appendix Vi to Part 265 - Compounds With Henry's Law Constant Less Than 0.1 Y/X

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 25 2010-07-01 2010-07-01 false Compounds With Henry's Law Constant Less Than 0.1 Y/X VI Appendix VI to Part 265 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Law Constant Less Than 0.1 Y/X Compound name CAS No. Acetaldol 107-89-1 Acetamide 60-35-5...

  8. The Aspergillus nidulans amdS gene as a marker for the identification of multicopy T-DNA integration events in Agrobacterium-mediated transformation of Aspergillus awamori

    NARCIS (Netherlands)

    Michielse, C.B.; Ram, A.F.J.; Hondel, C.A.M.J.J. van den

    2004-01-01

    The Aspergillus nidulans amdS selection marker was used for the identification of multicopy T-DNA insertions in Agrobacterium-mediated transformation of Asp. awamori. The selection of transformants on agar plates containing acetamide as sole nitrogen source and hygromycin resulted in a six-fold decr

  9. Enzymatic synthesis of 5-/sup 3/H-indole-3-acetic acid and 5-/sup 3/H-indole-3-acetyl-myo-inositol from 5-/sup 3/H-L-trytophan

    Energy Technology Data Exchange (ETDEWEB)

    Michalczuk, L.; Chisnell, J.R. (Michigan State Univ., East Lansing (USA). Dept. of Botany and Plant Pathology)

    1982-01-01

    Labeled 1-tryptophan is converted to indole-3-acetamide and then to indole-3-acetic acid by enzymes from Pseudomonas savastanoi. Labeled indole-3-acetic acid can be converted to indole-3-acetyl-1-O-..beta..-D-glucose and to indole-3-acetyl-myo-inositol by enzymes from kernels of Zea mays sweet corn.

  10. 2,2,2-Trichloro-N-(3-nitrophenylacetamide

    Directory of Open Access Journals (Sweden)

    A. N. Prabhu

    2012-10-01

    Full Text Available In the title compound, C8H5Cl3N2O3, the dihedral angle between the nitrophenyl ring and the acetamide group is 5.47 (6°. In the crystal, N—H...O and C—H...O hydrogen bonds link the molecules into chains running parallel to the b axis.

  11. A New Alkaloid from Sinomenium acutum

    Institute of Scientific and Technical Information of China (English)

    Wei Ming CHENG; Feng QIU; Li Jun WU; Xin Sheng YAO

    2005-01-01

    Sinomenium acutum is widely used in East and South Asia for the treatment of many diseases, especially rheumatoid arthritis (RA). The chemical research on Sinomenium acutum led to the isolation of a new alkaloid compound (1). On the basis of chemical evidences and spectral analysis, 1 was identified as N-(1, 7-dimethoxylphenanthren-2-yl)acetamide.

  12. ANTI INFLAMMATORY ACTIVITY OF SOME NEW THIO-ETHER DERIVATIVES OF QUINOXALINE

    Directory of Open Access Journals (Sweden)

    Singh, Dharmchand Prasad

    2010-12-01

    Full Text Available A series of thioether derivatives of 2-Chloro-3-methylquinoxaline have been synthesized by reacting 3- methylquinoxalin-2-thiosodium with 2-chloro-N-(substituted aryl/alkyl-acetamides. The synthesis was initiated with the reaction of o-phenylenediamine (1 with ethyl pyruvate in n-butanol to yield 2-hydroxy-3-methyl quinoxaline (2, which on treatment with POCl3 ,yielded 2-chloro-3-methylquinoxaline(3.A mixture of the compound(3 and sodium sulphide in DMF was refluxed to yield 3-methylquinoxalin-2-thiosodium(4,which on treatment with different Nsubstituted chloroacetamides afforded the one pot synthesis of 2-(2-methylquinoxalin-3-ylthio-N-substitutedaryl/ alkyl-acetamides(5a-k. 2-chloro-N-substituted acetamides were prepared by treating substituted anilines in glacial acetic acid with chloroacetylchloride, warming on the water bath for half an hour and then precipitating, 2- chloro-N-substituted acetamides by addition of saturated aqueous solution of anhydrous sodium acetate. A compound 2-(benzylthio-3-methylquinoxaline 5l was also prepared. The newly synthesized compounds have been characterized by IR, and 1HNMR spectra, analysis. All compounds (5a-l were screened for their in vivo anti inflammatory activity by carrageenan induced rat paw edema method. Compounds 5a, 5b, 5d, 5e, 5g and 5k have been found to possess good anti inflammatory activity.

  13. A general approach to aza-heterocycles by means of domino sequences driven by hydroformylation.

    Science.gov (United States)

    Airiau, Etienne; Spangenberg, Thomas; Girard, Nicolas; Schoenfelder, Angèle; Salvadori, Jessica; Taddei, Maurizio; Mann, André

    2008-01-01

    The development of hydroformylative domino reactions of easily accessible vinyl acetamides is described. Extremely regioselective hydroformylation of terminal double bounds provides a transient N-acyliminium that can be trapped by various nucleophiles to give several aza-heterocylic scaffolds in a diastereoselective manner.

  14. Deuteration of acetanilides

    Energy Technology Data Exchange (ETDEWEB)

    Chin, S.K.; Collier, R.; Hutchinson, D.W. (Warwick Univ., Coventry (UK). Dept. of Chemistry and Molecular Sciences)

    1982-09-01

    The base-catalysed exchange of a proton of the methyl groups in acetanilides can be used to incorporate deuterium into these amides. 4'-Hydroxyl-2(/sup 2/H)acetanilide (acetaminophen, paracetamol) can be prepared by the demethylation with boron tribromide of 4'-methoxy-2(/sup 2/H) acetamide obtained by this base-catalysed exchange.

  15. Ambient temperature deposition of gallium nitride/gallium oxynitride from a deep eutectic electrolyte, under potential control.

    Science.gov (United States)

    Sarkar, Sujoy; Sampath, S

    2016-05-11

    A ternary, ionically conducting, deep eutectic solvent based on acetamide, urea and gallium nitrate is reported for the electrodeposition of gallium nitride/gallium indium nitride under ambient conditions; blue and white light emitting photoluminescent deposits are obtained under potential control.

  16. Cardiac effects of r-79595 and its isomers (r-80122 and r-80123) in an acute heart-failure model - a new class of cardiotonic agents with highly selective phosphodiesterase-iii inhibitory properties

    NARCIS (Netherlands)

    SCHNEIDER, J; BECK, E; HEERS, C; CONRAD, C; DECOURCELLES, DD; WILFFERT, B; Peters, Thies

    1992-01-01

    R 79595 (N-cyclohexyl-N-methyl-2-[[[phenyl (1,2,3,5-tetrahydro-2 oxoimidazo [2,1-b]-quinazolin-7-yl) methylene] amin] oxy] acetamide) and its isomers represent a novel class of compounds with phosphodiesterase (PDE) inhibitory and cardiotonic (positive inotropic) actions. The cardiac effects of this

  17. Solid supported reagents for effecting selective transformation in natural products

    Directory of Open Access Journals (Sweden)

    V.P. Santhanakrishnan

    2016-11-01

    Full Text Available Polymer supported N-bromoacetamide resin can be easily prepared by the bromination of the acetamide resin and can be used for the transformation of furan ring in tetranortriterpenoids to butryolactone with excellent selectivity and in good yield in shorter time under microwave irradiation condition.

  18. (3-Methyl-benzo-nitrile-κN)tetra-kis(μ-N-phenyl-acetamidato)-κ(4) N:O;κ(4) O:N-di-rhodium(II)(Rh-Rh).

    Science.gov (United States)

    Eagle, Cassandra T; Atem-Tambe, Nkongho; Kpogo, Kenneth K; Tan, Jennie; Quarshie, Fredricka

    2013-11-06

    In the title compound, [Rh2(C8H8NO)4(C8H7N)], the four acetamidate ligands bridging the dirhodium core are arranged in a 2,2-trans manner. One Rh(II) atom is five-coordinate, in a distorted pyramidal geometry, while the other is six-coord-in-ate, with a disorted octa-hedral geometry. For the six-coord-inate Rh(II) atom, the axial nitrile ligand shows a non-linear Rh-nitrile coordination with an Rh-N-C bond angle of 166.4 (4)° and a nitrile N-C bond length of 1.138 (6) Å. Each unique Rh(II) atom is coordinated by a trans pair of N atoms and a trans pair of O atoms from the four acetamide ligands. The Neq-Rh-Rh-Oeq torsion angles on the acetamide bridge varies between 12.55 (11) and 14.04 (8)°. In the crystal, the 3-methyl-benzo-nitrile ring shows a π-π inter-action with an inversion-related equivalent [inter-planar spacing = 3.360 (6) Å]. A phenyl ring on one of the acetamide ligands also has a face-to-face π-π inter-action with an inversion-related equivalent [inter-planar spacing = 3.416 (5) Å].

  19. METHOD 535: MEASUREMENT OF CHLOROACETANILIDE AND CHLOROACETAMIDE HERBICIDE DEGRADATES IN DRINKING WATER BY SOLID PHASE EXTRACTION AND LIQUID CHROMATOGRAPHY/TANDEM MASS SPECTROMETRY (LC/MS/MS)

    Science.gov (United States)

    Over the past several years, ethanesulfonic acid (ESA) and oxanilic acid (OA) degradation products of acetanilide/acetamide herbicides have been found in U.S. ground waters and surface waters. The substitution of the sulfonic acid or the carbonic acid for the chlorine atom great...

  20. Millimeter-Wave Spectroscopy for Analytical Chemistry: Thermal Evolution of Low Volatility Impurities and Detection with a Fourier Transform Molecular Rotational Resonance Spectrometer (tev Ft-Mrr

    Science.gov (United States)

    Harris, Brent; Fields, Shelby S.; Neill, Justin L.; Pulliam, Robin; Muckle, Matt; Pate, Brooks

    2016-06-01

    Recent advances in Fourier transform millimeter-wave spectroscopy techniques have renewed the application reach of molecular rotational spectroscopy for analytical chemistry. We present a sampling method for sub ppm analysis of low volatility impurities by thermal evolution from solid powders using a millimeter-wave Fourier transform molecular rotational resonance (FT-MRR) spectrometer for detection. This application of FT-MRR is relevant to the manufacturing of safe oral pharmaceuticals. Low volatility impurities can be challenging to detect at 1 ppm levels with chromatographic techniques. One such example of a potentially mutagenic impurity is acetamide (v.p. 1 Torr at 40 C, m.p. 80 C). We measured the pure reference spectrum of acetamide by flowing the sublimated vapor pressure of acetamide crystals through the FT-MRR spectrometer. The spectrometer lower detection level (LDL) for a broadband (> 20 GHz, 10 min.) spectrum is 300 nTorr, 30 pmol, or 2 ng. For a 50 mg powder, perfect sample transfer efficiency can yield a w/w % detection limit of 35 ppb. We extended the sampling method for the acetamide reference measurement to an acetaminophen sample spiked with 5000 ppm acetamide in order to test the sample transfer efficiency when liberated from an pharmaceutical powder. A spectral reference matching algorithm detected the presence of several impurities including acetaldehyde, acetic acid, and acetonitrile that evolved at the melting point of acetaminophen, demonstrating the capability of FT-MRR for identification without a routine chemical standard. The method detection limit (MDL) without further development is less than 10 ppm w/w %. Resolved FT-MRR mixture spectra will be presented with a description of sampling methods.

  1. Comparative metabolism of chloroacetamide herbicides and selected metabolites in human and rat liver microsomes.

    Science.gov (United States)

    Coleman, S; Linderman, R; Hodgson, E; Rose, R L

    2000-01-01

    Acetochlor [2-chloro-N-(ethoxymethyl)-N-(2-ethyl-6-methyl-phenyl)-acetamide], alachlor [N-(methoxymethyl)-2-chloro-N-(2, 6-diethyl-phenyl)acetamide], butachlor [N-(butoxymethyl)-2-chloro-N-(2,6-diethyl-phenyl)acetamide], and metolachlor [2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-1-methylethyl) acetamide] are pre-emergent herbicides used in the production of agricultural crops. These herbicides are carcinogenic in rats: acetochlor and alachlor cause tumors in the nasal turbinates, butachlor causes stomach tumors, and metolachlor causes liver tumors. It has been suggested that the carcinogenicity of these compounds involves a complex metabolic activation pathway leading to a DNA-reactive dialkylbenzoquinone imine. Important intermediates in this pathway are 2-chloro-N-(2,6-diethylphenyl)acetamide (CDEPA) produced from alachlor and butachlor and 2-chloro-N-(2-methyl-6-ethylphenyl)acetamide (CMEPA) produced from acetochlor and metolachlor. Subsequent metabolism of CDEPA and CMEPA produces 2,6-diethylaniline (DEA) and 2-methyl-6-ethylaniline (MEA), which are bioactivated through para-hydroxylation and subsequent oxidation to the proposed carcinogenic product dialkylbenzoquinone imine. The current study extends our earlier studies with alachlor and demonstrates that rat liver microsomes metabolize acetochlor and metolachlor to CMEPA (0.065 nmol/min/mg and 0.0133 nmol/min/mg, respectively), whereas human liver microsomes can metabolize only acetochlor to CMEPA (0.023 nmol/min/mg). Butachlor is metabolized to CDEPA to a much greater extent by rat liver microsomes (0.045 nmol/min/mg) than by human liver microsomes (< 0.001 nmol/min/mg). We have determined that both rat and human livers metabolize both CMEPA to MEA (0.308 nmol/min/mg and 0.541 nmol/min/mg, respectively) and CDEPA to DEA (0.350 nmol/min/mg and 0.841 nmol/min/mg, respectively). We have shown that both rat and human liver microsomes metabolize MEA (0.035 nmol/min/mg and 0.069 nmol/min/mg, respectively

  2. (3-Methyl­benzo­nitrile-1κN)-cis-tetra­kis(μ-N-phenyl­acetamidato)-1:2κ4 N:O;1:2κ4 O:N-dirhodium(II)(Rh—Rh)

    Science.gov (United States)

    Eagle, Cassandra T.; Quarshie, Fredricka; Cook, Kevin M.

    2014-01-01

    The complex molecule of the title compound, [Rh2{N(C6H5)COCH3}4(NCC7H7)], has crystallographically-imposed mirror symmetry. The four acetamide ligands bridging the dirhodium core are arranged in a 2,2-cis manner with two N atoms and two O atoms coordinating to the unique RhII atom cis to one another. The Neq—Rh—Rh—Oeq torsion angles on the acetamide bridge are 0.75 (7) and 1.99 (9)°. The axial nitrile ligand completes the distorted octa­hedral coordination sphere of one RhII atom and shows a nonlinear coordination, with an Rh—N—C bond angle of 162.8 (5)°; the N—C bond length is 1.154 (7) Å. PMID:25249885

  3. Crystal structure of tetra­kis­(μ-N-phenyl­acetamidato)-κ4 N:O;κ4 O:N-bis­[(2-methyl­benzo­nitrile-κN)rhodium(II)](Rh—Rh)

    Science.gov (United States)

    Eagle, Cassandra T.; Atem-Tambe, Nkongho; Kpogo, Kenneth K.; Tan, Jennie; Cook, Kevin M.

    2014-01-01

    The complex molecule of the title compound, [Rh2{N(C6H5)COCH3}4(C8H7N)2], exhibits inversion symmetry. The four acetamidate ligands bridging the dirhodium core are arranged in a 2,2-trans manner with two N atoms and two O atoms coordinating to each RhII atom trans to one another. The Neq—Rh—Rh—Oeq torsion angles on the acetamidate bridge vary between −4.07 (5) and −6.78 (7)°. The axial nitrile ligands complete the distorted octa­hedral coordination sphere of each RhII atom and show a nonlinear coordination with Rh—N—C bond angles of 151.6 (3) and 152.5 (3)°. The bond lengths of the two nitrile triple bonds are 1.133 (5) and 1.137 (5) Å. PMID:25309187

  4. (3-Methylbenzonitrile-1κN-cis-tetrakis(μ-N-phenylacetamidato-1:2κ4N:O;1:2κ4O:N-dirhodium(II(Rh—Rh

    Directory of Open Access Journals (Sweden)

    Cassandra T. Eagle

    2014-08-01

    Full Text Available The complex molecule of the title compound, [Rh2{N(C6H5COCH3}4(NCC7H7], has crystallographically-imposed mirror symmetry. The four acetamide ligands bridging the dirhodium core are arranged in a 2,2-cis manner with two N atoms and two O atoms coordinating to the unique RhII atom cis to one another. The Neq—Rh—Rh—Oeq torsion angles on the acetamide bridge are 0.75 (7 and 1.99 (9°. The axial nitrile ligand completes the distorted octahedral coordination sphere of one RhII atom and shows a nonlinear coordination, with an Rh—N—C bond angle of 162.8 (5°; the N—C bond length is 1.154 (7 Å.

  5. N-(1,5-Dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-ylacetamide–naphthalene-2,3-diol (1/1

    Directory of Open Access Journals (Sweden)

    Abdullah M. Asiri

    2010-07-01

    Full Text Available In the reaction of naphthalene-2,3-diol and 4-aminoantipyrine in the presence of acetic acid, the amine function is acetylated and the resulting acetamide co-crystallizes with the diol in the title compound, C13H15N3O2·C10H8O2, with 1:1 molar stoichiometry. The two components are linked by two O–H...O=C hydrogen bonds. One of the hydroxy groups interacts with the pyrazolone carbonyl O atom and the other hydroxy group interacts with the amide O atom of another component, generating a chain motif. Adjacent chains are linked into a layer motif via N—H...O interactions involving only the heterocyclic acetamide component.

  6. Effect of primary degradation-reaction products from Ammonia Fiber Expansion (AFEX)-treated corn stover on the growth and fermentation of Escherichia coli KO11.

    Science.gov (United States)

    Lau, Ming W; Dale, Bruce E

    2010-10-01

    The primary degradation-reaction products (DRP) identified in Ammonia Fiber Expansion (AFEX)-pretreated corn stover are acetate, lactate, 4-hydroxybenzaldehyde (4HBD) and acetamide. The effects of these products at a broad concentration range were tested on Escherichia coli KO11, a strain engineered for cellulosic ethanol production. Fermentations using glucose or xylose as the sole carbohydrate source and a sugar mixture of glucose and xylose were conducted to determine how these products and sugar selection affected fermentation performance. Co-fermentation of the sugar mixture exhibited the lowest overall ethanol productivity compared to single-sugar fermentations and was more susceptible to inhibition. Metabolic ethanol yield increased with the increasing initial concentration of acetate. Although these degradation-reaction products (with exception of acetamide) are generally perceived to be inhibitory, organic acids and 4-hydroxybenzaldehyde at low levels stimulated fermentation. Adaptation of cells to these products prior to fermentation increased overall fermentation rate.

  7. Radiolysis of paracetamol in dilute aqueous solution

    Science.gov (United States)

    Szabó, László; Tóth, Tünde; Homlok, Renáta; Takács, Erzsébet; Wojnárovits, László

    2012-09-01

    Using radiolytic experiments hydroxyl radical (main reactant in advanced oxidation processes) was shown to effectively destroy paracetamol molecules. The basic reaction is attachment to the ring. The hydroxy-cyclohexadienyl radical produced in the further reactions may transform to hydroxylated paracetamol derivatives or to quinone type molecules and acetamide. The initial efficiency of aromatic ring destruction in the absence of dissolved O2 is c.a. 10%. The efficiency is 2-3 times higher in the presence of O2 due to its reaction with intermediate hydroxy-cyclohexadienyl radical and the subsequent ring destruction reactions through peroxi radical. Upon irradiation the toxicity of solutions at low doses increases with the dose and then at higher doses it decreases. This is due to formation of compounds with higher toxicity than paracetamol (e.g. acetamide, hidroquinone). These products, however, are highly sensitive to irradiation and degrade easily.

  8. Synthesis and pharmacological investigation of 2-(4-dimethylaminophenyl)-3,5-disubstituted thiazolidin-4-ones as anticonvulsants.

    Science.gov (United States)

    Senthilraja, Manavalan; Alagarsamy, Veerachamy

    2012-10-01

    A new series of 2-(4-dimethylaminophenyl)-3-substituted thiazolidin-4-one-5-yl-acetyl acetamides/benzamides were synthesized by the nucleophilic substitution of 3-substituted-2-(4-dimethylaminophenyl)-thiazolidin-4-one-5-yl-acetylchloride with acetamide and benzamide. The starting material 3-substituted-2-(4-dimethylaminophenyl)-thiazolidin-4-one-5-yl-acetylchloride was synthesized from 3-substituted-2-(4-dimethylaminophenyl)-thiazolidin-4-one-5-yl-acetic acid, which in turn was prepared by one-pot reaction of amino component, p-dimethylamino benzaldehyde and mercapto succinic acid. The title compounds were investigated for their anticonvulsant activities; among the test compounds, compound 2-(4-dimethylaminophenyl)-3-phenylamino-thiazolidine-4-one-5-yl-acetylbenzamide (14) emerged as the most active compound of the series and as moderately more potent than the reference standard diazepam.

  9. Synthesis, characterization, fluorescence and DNA-binding studies of europium(Ⅲ) pirates complexes with amide-based 2,3-dihydroxynaphthalene derivatives

    Institute of Scientific and Technical Information of China (English)

    LI Hanyu; YANG Tianlin; DING Ling; WANG Wenhua

    2012-01-01

    Two ligands 2,2'-[2,3-naphthylenebis(oxy)]-bis(N-benzyl(acetamide)(L1) and 22'-[23-naphthylenebis (oxy)]-bis(N,N-diphenyl (acetamide)(L2) and their europium(Ⅲ) picrate complexes were synthesized.The complexes were characterized by elemental analysis,infrared (IR),thermogravimetry and differential thermal analysis (TG-DTA) and molar conductivity.Fluorescent experiments showed that the resonance level of the Eu(Ⅲ) matched better to the triplet state energy level of the ligand L2 than that of the ligand L1 and the fluorescence intensifies of the complexes were reduced with the raising coordination ability of solvent.In addition,the interactions between the complexes and DNA were studied by means of spectrometry and cyclic voltammetry.The results suggested that the complexes could bind to DNA through intercalation and the complex 1 binded to DNA more strongly than the complex 2.

  10. Catalytic atom-transfer radical cyclization by copper/bipyridine species encapsulated in polysiloxane gel.

    Science.gov (United States)

    Motoyama, Yukihiro; Kamo, Kazuyuki; Yuasa, Akihiro; Nagashima, Hideo

    2010-04-07

    Novel polysiloxane gel, in which CuCl/bipyridine species are immobilized, is prepared by treatment of polymethylhydrosiloxane with 4,4'-bis[(2-propenyl)oxy]-2,2'-bipyridine and 1,5-hexadine in the presence of Karstedt's catalyst followed by addition of CuCl. This polysiloxane gel acts as a reusable catalyst in the atom-transfer radical cyclization of alpha-halogenated acetamide derivatives in high turnover numbers without allowing leakage of the metal species.

  11. N-(Diphenyl-vinyl-idene)-2,6-diisopropyl-aniline.

    Science.gov (United States)

    Imhof, Wolfgang

    2008-12-06

    The title compound, C(26)H(27)N, was prepared by the elimination of water from N-(2,6-diisopropyl-phen-yl)-2,2-diphenyl-acetamide. The angle at the central C atom of the cumulene measures 172.5 (4)°. Mol-ecules are connected into infinite chains by inter-molecular C-H⋯N inter-actions.

  12. SYNTHESIS AND EVALUATION OF OXAZOLIDINONES HAVING BENZO THIAZINEN MOIETIES AS ANTIMICROBIAL AND ANTI-INFLAMMATORY AGENTS

    OpenAIRE

    Jennifer Fernandes; Pankaj Kumar; Abhishek Kumar

    2013-01-01

    Phenyl oxazolidinones were prepared from R-glycidyl butarate and Para bromo aniline, further (3-(4-bromophenyl) methylene oxazolidine-5yl) and substituted benzothiazinen was refluxed resulted in oxazolidinones benzothiazinen moieties. Treatment of these oxazolidinones benzo thiazinen moieties with methane sulfonyl gives its sulphonates on further treatment with sodium azide and tri phenyl phosphine in acetic anhydride gives acetamide derivatives. Further synthesized compounds were characteriz...

  13. Validation of the U.S. Army’s Current Hazardous Waste Data

    Science.gov (United States)

    1990-04-01

    100 RATIO OF TOTAL SCORE TO POSSIBLE SCORE. I Z I 44 APPENDIX E: CARCINOGEN LIST Acetamide Acetophenetidin Acrylamide Acrylonitrile Actinomycin D... Carcinogen List 45 APPENDIX F: Priority Pollutants 48 APPENDIX G: Prioritization Example 52 DISTRIBUTION Acoession For NTIS GRA&I DTIC TAB Q Unannounced...Restoration Program (IRP) sites and the resulting exposure to humans and the environment rather than the materials themselves RCRA 3002 (b) requires that

  14. Effect of DNA damage caused by cryopreservation of spermatozoa using a modified Single cell gell electrophoresis in the freshwater catfish Pangasianodon hypophthalmus (Fowler, 1936)

    OpenAIRE

    Kuppusamy Umaa Rani; Natesan Munuswamy

    2014-01-01

    Objective: To detect the integrity of sperm DNA in the catfish Pangasianodon hypophthalmus cryopreserved with Hanks balanced salt solution, 5%-30% dimethyl acetamide (DMA) using the single-cell gel electrophoresis in order to test how sperm cryopreservation affected nuclear DNA stability. Methods: Electrophoresis was conducted for 60 min at 130 mA and 15 V. The comet images were analyzed using software CometScore 1.5, and parameters such as comet length, tail length an...

  15. Synthesis and Antimicrobial Activity of Some Novel Substituted Piperazinyl-quinazolin-3(4H-ones

    Directory of Open Access Journals (Sweden)

    N. M. Raghavendra

    2008-01-01

    Full Text Available Several substituted-quinazolin-3(4H-ones were synthesized by condensation of 2-chloro-N-(4-oxo-substituted-quinazolin-3(4H-yl-acetamides with various substituted piperazines through single step reaction. Elemental analysis, IR, 1HNMR and mass spectral data confirmed the structure of the newly synthesized compounds. Synthesized quinazolin-4-one derivatives were investigated for their antibacterial and antifungal activities.

  16. One-pot synthesis of 1-amidoalkyl-2-naphthols catalyzed by melamine-Br3 under solvent-free conditions

    Institute of Scientific and Technical Information of China (English)

    Arash Ghorbani-Choghamarani; Shima Rashidimoghadam

    2014-01-01

    A facile and efficient method has been developed for the synthesis of 1-amidoalkyl-2-naphthols via the one-pot multi-component condensation of 2-naphthol with aromatic aldehydes and acetamide or thioacetamide in the presence of melamine-Br3 under solvent-free conditions. There are several advantages to this reaction, including high yields, short reaction time, and high catalytic efficiency.

  17. N-Bromosuccinimide Catalyzed One-pot and Rapid Synthesis of Acetamidobenzyl Naphthols under Mild and Solvent-free Conditions

    Institute of Scientific and Technical Information of China (English)

    SHATERIAN Hamid Reza; YARAHMADI Hossein; GHASHANG Majid; SAFARI MEHMANDOSTI Moharram

    2008-01-01

    An efficient,facile and expeditious direct protocol for the preparation of acetamidobenzyl naphthols employing a multi-component and one-pot condensation reaction of 2-naphthoi,benzaldehydes,and acetamide in the presence of N-bromosuccinimide(NBS)under thermal and microwave irradiation conditions has been described.The present protocol with NBS catalyst is convincingly superior to the recently reported catalytic methods.

  18. Preparation and Application of Perchloric Acid Supported on Alumina (Al2O3-HCIO4) to the Synthesis of α-(α-Amidobenzyl)-β-naphthols

    Institute of Scientific and Technical Information of China (English)

    SHATERIAN,Hamid Reza; KHORAMI,Fahimeh; AMIRZADEH,Azita; GHASHANG,Majid

    2009-01-01

    Preparation of perchloric acid supported on alumina and its primary application as a solid supported heterogeneous catalyst to the synthesis of α-(α-amidobenzyl)-β-naphthols by a one-pot,three-component condensation of benzaldehydes,β-naphthol and acetamide or benzamide under thermal solvent-free conditions were described.The present methodology offers several advantages such as simple procedure,shorter reaction time,and excellent yields.

  19. Design and synthesis of a novel, orally active, brain penetrant, tri-substituted thiophene based JNK inhibitor

    Energy Technology Data Exchange (ETDEWEB)

    Bowers, Simeon; Truong, Anh P.; Neitz, R. Jeffrey; Neitzel, Martin; Probst, Gary D.; Hom, Roy K.; Peterson, Brian; Galemmo, Jr., Robert A.; Konradi, Andrei W.; Sham, Hing L.; Tóth, Gergley; Pan, Hu; Yao, Nanhua; Artis, Dean R.; Brigham, Elizabeth F.; Quinn, Kevin P.; Sauer, John-Michael; Powell, Kyle; Ruslim, Lany; Ren, Zhao; Bard, Frédérique; Yednock, Ted A.; Griswold-Prenner, Irene (Elan)

    2012-02-28

    The SAR of a series of tri-substituted thiophene JNK3 inhibitors is described. By optimizing both the N-aryl acetamide region of the inhibitor and the 4-position of the thiophene we obtained single digit nanomolar compounds, such as 47, which demonstrated an in vivo effect on JNK activity when dosed orally in our kainic acid mouse model as measured by phospho-c-jun reduction.

  20. 40 CFR Appendix Viii to Part 261 - Hazardous Constituents

    Science.gov (United States)

    2010-07-01

    ... U003 Acetophenone Ethanone, 1-phenyl- 98-86-2 U004 2-Acetylaminefluarone Acetamide, N-9H-fluoren-2-yl... Mercury compounds, N.O.S. 1 Mercury fulminate Fulminic acid, mercury(2+) salt 628-86-4 P065 Metam Sodium...-hydroxy-2-methyl- 75-86-5 P069 Methyl methacrylate 2-Propenoic acid, 2-methyl-, methyl ester 80-62-6...

  1. Structural requirements for roxatidine in the stimulant effect of rat gastric mucin synthesis and the participation of nitric oxide in this mechanism

    OpenAIRE

    1997-01-01

    The structural requirements of the histamine H2-receptor antagonist, roxatidine (2-acetoxy-N-(3-[m-(1-piperidinylmethyl)phenoxy]-propyl)acetamide hydrochloride), for the stimulant effect on mucin biosynthesis and their relation to histamine H2-receptor antagonism were identified by considering the structural analogues of this drug using an organ culture system of the rat stomach and competition studies with [125I]iodoaminopotentidine ([125I]-APT) binding to membranes of the guinea pig striatu...

  2. Optimization of a novel class of benzimidazole-based farnesoid X receptor (FXR) agonists to improve physicochemical and ADME properties.

    Science.gov (United States)

    Richter, Hans G F; Benson, G M; Bleicher, K H; Blum, D; Chaput, E; Clemann, N; Feng, S; Gardes, C; Grether, U; Hartman, P; Kuhn, B; Martin, R E; Plancher, J-M; Rudolph, M G; Schuler, F; Taylor, S

    2011-02-15

    Structure-guided lead optimization of recently described benzimidazolyl acetamides addressed the key liabilities of the previous lead compound 1. These efforts culminated in the discovery of 4-{(S)-2-[2-(4-chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclohexyl-acetylamino}-3-fluoro-benzoic acid 7g, a highly potent and selective FXR agonist with excellent physicochemical and ADME properties and potent lipid lowering activity after oral administration to LDL receptor deficient mice.

  3. Piracetam and TRH analogues antagonise inhibition by barbiturates, diazepam, melatonin and galanin of human erythrocyte D-glucose transport

    OpenAIRE

    2004-01-01

    Nootropic drugs increase glucose uptake into anaesthetised brain and into Alzheimer's diseased brain. Thyrotropin-releasing hormone, TRH, which has a chemical structure similar to nootropics increases cerebellar uptake of glucose in murine rolling ataxia. This paper shows that nootropic drugs like piracetam (2-oxo 1 pyrrolidine acetamide) and levetiracetam and neuropeptides like TRH antagonise the inhibition of glucose transport by barbiturates, diazepam, melatonin and endogenous neuropeptide...

  4. Synthesis and Antimicrobial Activity of SomeNovel Benzimidazolyl Chalcones

    OpenAIRE

    2009-01-01

    Some novel benzimidazolyl chalcones were synthesized by condensation of N-(4-(1H-benzo[d]imidazol-2-yl)phenyl)acetamide with aromatic aldehydes in presence of aqueous potassium hydroxide solution at room temperature. All the synthesized compounds were characterized on the basis of their IR, 1H NMR spectroscopic data and elemental analysis. All the compounds have been screened for antimicrobial activity by the cup-plate method.

  5. Synthesis of substituted [{sup 123}I]imidazo[1,2-a]pyridines as potential probes for the study of the peripheral benzodiazepine receptors using SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Katsifis, A.; Mattner, F.; Dikic, B.; Papazian, V. [Radiopharmaceuticals Div. R and D, ANSTO, Menai, NSW (Australia)

    2000-07-01

    The imidazo[1,2-a]pyridines N,N'-dimethyl-6-chloro-(4'-iodophenyl)imidazo[1,2-a]pyridine-3-acetamide 1. N,N'-diethyl-6-chloro-(4'-iodophenyl)imidazo[1,2-a]pyridine-3-acetamide 2, and N-methyl-6-chloro-(4'-iodophenyl)imidazo[1,2-a]pyridine-3-acetamide 3, are high affinity and selective ligands for the peripheral benzodiazepineodiazepine receptors (PBR). The [{sup 123}I]1-3 labelled analogues of these compounds were subsequently synthesised for the potential study of the PBR in vivo using SPECT. Radioiodination was achieved by iododestannylation reactions of the corresponding tributyl tin precursors with Na[{sup 123}I] in the presence of peracetic acid, chloramine-T or Iodogen. Purification of the crude product was achieved by semipreparative C-18 RP HPLC to give the products in radiochemical yields of 40-85%. The products were obtained in >97% chemical and radiochemical purity and with specific activities >80 GBq/{mu}mol. (orig.)

  6. Dielectric relaxation of amides and tetrahydrofuran polar mixture in C6H6 from conductivity measurement under 9.90 GHz electric field

    Science.gov (United States)

    Sahoo, S.; Sit, S. K.

    2017-01-01

    Dielectric relaxation studies of binary ( jk) polar mixtures of tetrahydrofuran with N-methyl acetamide, N, N-dimethyl acetamide, N-methyl formamide and N, N-dimethyl formamide dissolved in benzene(i) for different weight fractions ( w j k 's) of the polar solutes and mole fractions ( x j 's) of tetrahydrofuran at 25 ∘C are attempted by measuring the conductivity of the solution under 9.90 GHz electric field using Debye theory. The estimated relaxation time ( τ j k 's) and dipole moment ( μ j k 's) agree well with the reported values signifying the validity of the proposed methods. Structural and associational aspects are predicted from the plot of τ j k and μ j k against x j of tetrahydrofuran to arrive at solute-solute (dimer) molecular association upto x j =0.3 of tetrahydrofuran and thereafter solute-solvent (monomer) molecular association upto x j =1.0 for all systems except tetrahydrofuran + N, N-dimethyl acetamide.

  7. Numerical heat transfer studies of PCMs used in a box-type solar cooker

    Energy Technology Data Exchange (ETDEWEB)

    Chen, C.R.; Sharma, Atul [Department of Mechanical Engineering, Kun Shan University, 949 Da-Wan Road, Yung-Kung City, Tainan Hsien 710 (China); Tyagi, S.K. [Department of Building Services Engineering, The Hong Kong Polytechnic University, Hung Hom, Kowloon (China); Buddhi, D. [Thermal Energy Storage Laboratory, School of Energy and Environmental Studies, Khandwa Road Campus, Devi Ahilya University, Indore 452017 (India)

    2008-05-15

    Theoretical investigations on the phase change materials (PCMs) used as the heat storage media for box-type solar cookers have been conducted in this study. The selected PCMs are magnesium nitrate hexahydrate, stearic acid, acetamide, acetanilide and erythritol. For a two-dimensional simulation model based on the enthalpy approach, calculations have been made for the melt fraction with conduction only. Different materials such as glass, stainless steel, tin, aluminum mixed, aluminum and copper are used as the heat exchanger container materials in the numerical calculations. The large value of thermal conductivity of heat exchanger container material did not make a significant contribution on the melt fraction except for at very low thermal conductivities. Based on the theoretical results, stearic acid and acetamide are found to be good compatibility with latent heat storage system. It is also found that the initial temperature of PCM does not have very important effects on the melting time, while the boundary wall temperature plays an important role during the melting and has a strong effect on the melt fraction. The results also show that the effect of thickness of container material on the melt fraction is insignificant. The results obtained in this paper show that in a box-type solar cooker, acetamide and stearic acid should be used as a latent heat storage materials. (author)

  8. Synthesis and antitumor activity evaluation of new 2-(4-aminophenyl)benzothiazole derivatives bearing different heterocyclic rings.

    Science.gov (United States)

    Yurttaş, Leyla; Tay, Funda; Demirayak, Şeref

    2015-06-01

    Twenty-five new N-[4-(benzothiazole-2-yl)phenyl]acetamide derivatives bearing different heterocyclic ring systems were synthesized using 2-(4-aminophenyl)benzothiazole structure as a pharmacophoric group. Final compounds were screened for their potential antitumor activity in vitro against approximately 60 human tumor cell lines derived from nine neoplastic diseases at National Cancer Institute, USA. 2-(4-Aminophenyl)benzothiazole structure was prepared by the reaction of 4-aminobenzoic acid and 2-aminothiophenol in polyphosphoric acid using microwave irradiation. After acetylation reaction, amide compounds 2a and 2b were obtained, which were then reacted with 2-mercapto(benz)imidazole/benzothiazole/benzoxazole derivatives in acetone with the presence of potassium carbonate to gain final compounds (3-27). Among all tested compounds, compound 10, namely N-[4-(benzothiazole-2-yl)-3-chlorophenyl]-2-[(benzimidazole-2-yl)thio]acetamide, and compound 16, namely N-[4-(benzothiazole-2-yl)phenyl]-2-[(1,5-diphenyl-1H-imidazole-2-yl)thio]acetamide, were found to be of considerable anticancer activity against some cancer cell lines.

  9. Design and synthesis of novel antimicrobial acyclic and heterocyclic dyes and their precursors for dyeing and/or textile finishing based on 2-N-acylamino-4,5,6,7-tetrahydro-benzo[b]thiophene systems.

    Science.gov (United States)

    Shams, Hoda Zaki; Mohareb, Rafat Milad; Helal, Maher Helmy; Mahmoud, Amira El-Sayed

    2011-07-26

    A series of novel polyfunctionalized acyclic and heterocyclic dye precursors and their respective azo (hydrazone) counterpart dyes and dye precursors based on conjugate enaminones and/or enaminonitrile moieties were synthesized. The dyes and their precursors are based on 2-cyano-N-(3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)-acetamide, 2-ethoxycarbonyl-N-(3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)-acetamide or 2-phenylcarbamoyl-N-(3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)-acetamide systems as precursors. The latter compounds were used to synthesize polyfunctional thiophene-, thiazole-, pyrazole, pyridine-, pyrimidine-, oxazine-, as well as acyclic moieties. The dyes and dye precursors were characterized by elemental analysis and spectral methods. All dyes and their precursors were screened in vitro and evaluated for both their antibacterial and antifungal activities. MIC data of the novel dye systems and their respective precursors showed significant antimicrobial activity against most tested organisms. Some compounds exhibited comparable or even higher efficiency than selected standards. Dyes were applied at 5% depth for disperse dyeing of nylon, acetate and polyester fabrics. Their spectral characteristics and fastness properties were measured and evaluated.

  10. Dielectric behaviour of some amides and formamides dissolved in nonpolar solvents under static electric field

    Indian Academy of Sciences (India)

    S Sahoo; S K Sit

    2011-08-01

    Structural and associational aspects of polar amides () like formamide, acetamide, Nmethyl acetamide (NMA), N,N-dimethyl formamide (DMF), N,N-dimethyl acetamide (DMA) and acetanilide dissolved in the nonpolar solvent () benzene or 1,4-dioxan have been estimated from the measured static relative permittivity 0 and high-frequency permittivity ∞ at different weight fractions s of polar solute at 35°C under static electric field using Debye model of polar liquid molecule. The static dipole moments s are compared with s reported from conductivity method and theoretical theos to get exact cal $\\cdot$ theos of the molecules are predicted from the available bond angles and bond moments where difference in electron affinity exists between two adjacent atoms of a polar group due to inductive, mesomeric and electromeric effects in them. Solute–solute molecular association for NMA in benzene and solute–solvent association for other amides are ascertained to arrive at their conformational structures.

  11. Dielectric relaxation of amides and tetrahydrofuran polar mixture in C$_{6}$H$_{6}$ from conductivity measurement under 9.90 GHz electric field

    Indian Academy of Sciences (India)

    S SAHOO; S K SIT

    2017-01-01

    Dielectric relaxation studies of binary ($jk$) polar mixtures of tetrahydrofuran with $N$-methyl acetamide, $N,N$-dimethyl acetamide, $N$-methyl formamide and $N,N$-dimethyl formamide dissolved in benzene(i) for different weight fractions ($w_{jk}$’s) of the polar solutes and mole fractions ($x_{j}$ ’s) of tetrahydrofuran at 25◦C are attempted by measuring the conductivity of the solution under 9.90 GHz electric field using Debye theory. The estimated relaxation time ($\\tau_{jk}$’s) and dipole moment ($\\mu_{jk}$’s) agree well with the reported values signifying the validity of the proposed methods. Structural and associational aspects are predicted from the plot of $\\tau_{jk}$ and $\\mu_{jk}$ against $x_{j}$ of tetrahydrofuran to arrive at solute–solute (dimer) molecular association upto $x_{j} = 0.3$ of tetrahydrofuran and thereafter solute–solvent (monomer) molecular association upto $x_{j} = 1.0$ for all systems except tetrahydrofuran + $N,N$-dimethyl acetamide.

  12. Design and Synthesis of Novel Antimicrobial Acyclic and Heterocyclic Dyes and Their Precursors for Dyeing and/or Textile Finishing Based on 2-N-Acylamino-4,5,6,7-tetrahydro-benzo[b]thiophene Systems

    Directory of Open Access Journals (Sweden)

    Rafat Milad Mohareb

    2011-07-01

    Full Text Available A series of novel polyfunctionalized acyclic and heterocyclic dye precursors and their respective azo (hydrazone counterpart dyes and dye precursors based on conjugate enaminones and/or enaminonitrile moieties were synthesized. The dyes and their precursors are based on 2-cyano-N-(3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl-acetamide, 2-ethoxycarbonyl-N-(3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl-acetamide or 2-phenylcarbamoyl-N-(3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl-acetamide systems as precursors. The latter compounds were used to synthesize polyfunctional thiophene-, thiazole-, pyrazole, pyridine-, pyrimidine-, oxazine-, as well as acyclic moieties. The dyes and dye precursors were characterized by elemental analysis and spectral methods. All dyes and their precursors were screened in vitro and evaluated for both their antibacterial and antifungal activities. MIC data of the novel dye systems and their respective precursors showed significant antimicrobial activity against most tested organisms. Some compounds exhibited comparable or even higher efficiency than selected standards. Dyes were applied at 5% depth for disperse dyeing of nylon, acetate and polyester fabrics. Their spectral characteristics and fastness properties were measured and evaluated.

  13. Radiosynthesis of [{sup 11}C]D.P.A.-713, [{sup 11}C]D.P.A.-715 and [{sup 11}C]clinme, selected carbon-11-labelled novel potential radioligands for imaging the peripheral benzodiazepine receptors with PET

    Energy Technology Data Exchange (ETDEWEB)

    Dolle, F.; Thominiaux, C.; Hinnen, F.; Demphel, S.; Le helleix, S.; Chauveau, F.; Boutin, H.; Herard, A.S.; Hantraye, P.; Tavitian, B. [Service Hospitalier Frederic Joliot, I2BM/DSV, 91 - Orsay (France); Kassiou, M.; James, M.; Creelman, A.; Fulton, R. [Sydney Univ., Brain and Mind Research Institute, NSW (Australia); Kassiou, M. [Sydney Univ., Discipline of Medical Radiations, Sciences and School of Chemistry, NSW (Australia); Katsifis, A.; Greguric, I.; Mattner, F.; Loch, C. [Radiopharmaceuticals Research Institute, ANSTO, NSW (Australia); Selleri, S. [Degli Studi di Firenze Univ., Dipt. di Scienze Farmaceutiche (Italy)

    2008-02-15

    {sup 11}C P.K.11195 is not only the oldest, but also the most widely used PET radiotracer for in vivo imaging of the peripheral benzodiazepine receptors (P.B.R. or translocator protein (18 kDa, T.S.P.O.). With the aim of developing a new PET imaging probe for the in vivo study of the P.B.R., two pyrazol [1,5-a]pyrimidineacetamides (D.P.A.-713 and D.P.A.-715) and one imidazol[1,2-a]pyridine-acetamide (C.L.I.N.M.E.) were radiolabelled with the positron emitters carbon{sup 11} (half life: 20.38 min) [1-5]. Briefly, C.L.I.N.M.E. (2-[6-chloro-2(4-iodophenyl)-imidazol[1,2-a]pyridin-3-yl] -N-ethyl-N-methyl-acetamide) was labelled at its methyl-acetamide moity chain from the corresponding nor-analogue using[{sup 11}C]methyl iodide (in D.M.S.O./D.M.F (100/200 {mu}L) containing powdered K.O.H. (3-5 mg) at 110 degrees C for 3 min. D.P.A.-713 (N,N-diethyl-2-[2-(4-methoxy-phenyl)-5,7-dimethyl-pyrazolo[1,5-a]pyrimidin -3-yl]acetamide) and D.P.A.-715 (N,N-diethyl-2-[2-(4-methoxy-phenyl)-5,7-bis-tri-fluoro-methyl-pyrazolo [1,5-a]pyrimidin-3-yl]acetamide) were labelled at their aromatic methoxy groups from the corresponding nor-derivatives using [{sup 11}C]methyl triflate (in acetone (300{mu}L) containing aq. 3 M NaOH (4{mu}L) at 110 degrees C for 1 min). All radioligands were purified using semi preparative Zorbax reverse phase H.P.L.C., were adequately formulated for in vivo injection within 30 min and were found to be > 95% chemically and radiochemically pure. (N.C.)

  14. Centrally acting oximes in reactivation of tabun-phosphoramidated AChE.

    Science.gov (United States)

    Kovarik, Zrinka; Maček, Nikolina; Sit, Rakesh K; Radić, Zoran; Fokin, Valery V; Barry Sharpless, K; Taylor, Palmer

    2013-03-25

    Organophosphates (OP) inhibit acetylcholinesterase (AChE, EC 3.1.1.7), both in peripheral tissues and central nervous system (CNS), causing adverse and sometimes fatal effects due to the accumulation of neurotransmitter acetylcholine (ACh). The currently used therapy, focusing on the reactivation of inhibited AChE, is limited to peripheral tissues because commonly used quaternary pyridinium oxime reactivators do not cross the blood brain barrier (BBB) at therapeutically relevant levels. A directed library of thirty uncharged oximes that contain tertiary amine or imidazole protonable functional groups that should cross the BBB as unionized species was tested as tabun-hAChE conjugate reactivators along with three reference oximes: DAM (diacetylmonoxime), MINA (monoisonitrosoacetone), and 2-PAM. The oxime RS150D [N-((1-(3-(2-((hydroxyimino)methyl)-1H-imidazol-1-yl)propyl)-1H-1,2,3-triazol-4-yl)methyl)benzamide] was highlighted as the most promising reactivator of the tabun-hAChE conjugate. We also observed that oximes RS194B [N-(2-(azepan-1-yl)ethyl)-2-(hydroxyimino)acetamide] and RS41A [2-(hydroxyimino)-N-(2-(pyrrolidin-1-yl)ethyl)acetamide], which emerged as lead uncharged reactivators of phosphylated hAChE with other OPs (sarin, cyclosarin and VX), exhibited only moderate reactivation potency for tabun inhibited hAChE. This implies that geometry of oxime access to the phosphorus atom conjugated to the active serine is an important criterion for efficient reactivation, along with the chemical nature of the conjugated moiety: phosphorate, phosphonate, or phosphoramidate. Moreover, modification of the active center through mutagenesis enhances the rates of reactivation. The phosphoramidated-hAChE choline-binding site mutant Y337A showed three-times enhanced reactivation capacity with non-triazole imidazole containing aldoximes (RS113B, RS113A and RS115A) and acetamide derivative (RS194B) than with 2PAM.

  15. Assessment of radioactive residues arising from radiolabel instability in a multiple dose tissue distribution study in rats

    Energy Technology Data Exchange (ETDEWEB)

    Slatter, J.G. [Pharmacia Corp., Peapack, NJ (United States); Sams, J.P.; Easter, J.A. [Pharmacia Corp., Kalamazoo, MI (United States)] [and others

    2003-05-01

    Our study objectives were to quantitatively determine the effect of radiolabel instability on terminal phase radioactive tissue residues in a multiple dose tissue distribution study, to quantitatively compare tissue residue artifacts (non drug-related radioactivity) from two chemically-distinct radiolabel locations, and to conduct a definitive multiple dose tissue distribution study using the better of the two radiolabeled compounds. We compared the excretion and tissue distribution in rats of [{sup 14}C]linezolid, radiolabeled in two different locations, after 7 consecutive once daily [{sup 14}C] oral doses. The radiolabels were in the acetamide (two carbon) and oxazolidinone (isolated carbon) functional groups. Terminal phase tissue residue and excretion data were compared to data from rats dosed orally with [{sup 14}C]sodium acetate. Drug-related radioactivity was excreted rapidly over 24 h. After a single dose, the acetamide and oxazolidinone radiolabel sites both gave 3% of dose as exhaled {sup 14}CO{sub 2}. After 7 daily [{sup 14}C] oral doses, terminal phase radioactive tissue residues were higher from the acetamide radiolabel, relative to the oxazolidinone radiolabel, and were primarily not drug-related. In the definitive tissue distribution study, low concentrations of drug-related radioactivity in skin and thyroid were observed. We conclude that although small amounts of radiolabel instability do not significantly affect single dose tissue radioactivity C{sub max} and area under the curve (AUC), artifacts arising from radiolabel instability can prolong the apparent terminal phase half life and complicate study data interpretation. When possible, it is always preferable to use a completely stable radiolabel site. (author)

  16. 淀粉/PVA生物降解材料的热塑性研究%Study on Thermoplasticity of Starch/PVA Blends

    Institute of Scientific and Technical Information of China (English)

    周向阳; 贾德民; 崔跃飞; 严志云

    2011-01-01

    将聚乙烯醇(PVA)、淀粉、增塑剂在Hakke流变仪中共混制备了热塑性淀粉/PvA材料,研究了2种PVA-PVA1799、PVA1788,2种淀粉-玉米淀粉、木薯淀粉的热塑性情况;比较了甘油、乙二醇、乙酰胺3种增塑剂的增塑效果.结果表明:采用合适的增塑剂与适当的PVA、淀粉组合可以使PVA/淀粉共混体系在高温下热塑成型;乙酰胺能跟PVA和淀粉形成很强的氢键,具有明显的增塑作用,使淀粉/PVA充分塑化,并保持较好的力学性能.%PVA, starch and plasticizers were blended in Hake Rheometer to prepare the thermoplastic starch/ PVA blends. Two kinds of PVA (PVA1799 and PVA1788) and two kinds of starch( com starch and cassava starch) were used to plastify the blends. The plasticizing effects of 3 kinds of plasticizers( glycol, glycerol and acetamide) were studied. Results showed that PVA and starch could be thermoplasticly processed with appropriate plasticizer,PVA and starch. Acetamide could form strong hydrogenolysis with PVA and starch, resulting in better plastification on the blends. The PVA/starch blends were well plastified by acetamide and maintained favorable mechanical properties.

  17. Synthesis of [{sup 3}]DIPPA: a potent irreversible antagonist selective for the {kappa} opioid receptor

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Anchih; Portoghese, P.S. [Minnesota Univ., Minneapolis, MN (United States). College of Pharmacy; Trometer, J.D. [E.I. Du Pont de Nemours and Co., Inc., Boston, MA (United States)

    1995-06-01

    2-(3,4-Dichlorophenyl)-N-methyl-N-[(1S)-1-(3-isothiocyanatophe nyl)-2-(1-pyrrolidinyl)ethyl]acetamide (1,DIPPA) has been previously reported to be an opioid receptor affinity label that produces selective and long-lasting {kappa} opioid receptor antagonism in mice. High specific activity [{sup 3}H]DIPPA (39.7 Ci/mmol) was prepared by bromination and catalytic tritiation of the amino precursor of DIPPA followed by conversion to the isothiocyanate with thiophosgene. (Author).

  18. Electrodeposition of indium

    Energy Technology Data Exchange (ETDEWEB)

    Fouda, A.S.; Ahmed, A.I.; Madkour, L.H.

    Metallic indium was deposited from aqueous solutions of indium trichloride containing also, acetate, thiocyanate, chloride, iodide, sulphate, oxalate, ethanol, acetamide and citrate of sodium or potassium. The optimum conditions are: pH 2-5, current density 2-25 mA cm/sup -2/, temperature 30/sup O/C and metal ion concentration O.2 mol l/sup -1/. Deposits have been obtained on a platinum sheet cathode. Chemical analysis reveals that the purity of the indium is better than 99%. The rate of deposition is also determined. 15 refs.

  19. Structural study on few co-crystals and a salt of quinoline derivatives having amide bond

    Science.gov (United States)

    Karmakar, Anirban; Kalita, Dipjyoti; Baruah, Jubaraj B.

    2009-10-01

    The N-[2-(4-Methoxy-phenyl)-ethyl]-2-(quinolin-8-yloxy)-acetamide forms 1:1 co-crystals with aromatic diols namely 1,4-dihydroxybenzene, 1,5-dihydroxynaphthalene. In the later case co-crystal is formed in hydrated form. The hydrated form of co-crystal with 1,5-naphthalenediol has two symmetry independent host molecules in its unit cell, whereas such phenomenon in the co-crystal 1,4-dihydroxybenzene is not observed. The crystal structure of perchloric acid salt of (Quinolin-8-ylamino)-acetic acid is determined and this salt also shows two symmetry independent parent molecules in unit cell.

  20. Electrochemical reduction of nitrate in the presence of an amide

    Science.gov (United States)

    Dziewinski, Jacek J.; Marczak, Stanislaw

    2002-01-01

    The electrochemical reduction of nitrates in aqueous solutions thereof in the presence of amides to gaseous nitrogen (N.sub.2) is described. Generally, electrochemical reduction of NO.sub.3 proceeds stepwise, from NO.sub.3 to N.sub.2, and subsequently in several consecutive steps to ammonia (NH.sub.3) as a final product. Addition of at least one amide to the solution being electrolyzed suppresses ammonia generation, since suitable amides react with NO.sub.2 to generate N.sub.2. This permits nitrate reduction to gaseous nitrogen to proceed by electrolysis. Suitable amides include urea, sulfamic acid, formamide, and acetamide.

  1. N-(4-Sulfamoylphenylacetamide

    Directory of Open Access Journals (Sweden)

    Abdullah M. Asiri

    2012-04-01

    Full Text Available In the title compound, C8H10N2O3S, the dihedral angle between the acetamide group and the benzene ring is 15.59 (12° and the amino group is close to being perpendicular to the benzene ring [N—S—Car—Car (ar = aromatic torsion angle = 109.4 (2°]. In the crystal, molecules are linked into supramolecular tubes parallel to [001] by amine–amide N—H...O interactions and these are connected into the three-dimensional architecture by amide–sulfonamide N—H...O hydrogen bonds. The crystal studied was a racemic twin.

  2. A facile, green, one-pot synthesis of amidoalkyl naphthols under solvent-free conditions catalyzed by a carbon-based solid acid

    Institute of Scientific and Technical Information of China (English)

    Abolghasem Davoodnia; Rahil Mahjoobin; Niloofar Tavakoli-Hoseini

    2014-01-01

    An efficient, environmentally friendly procedure for the synthesis of amidoalkyl naphthols through the one-pot, three-component reaction of β-naphthol, aryl aldehydes, and acetamide in the presence of a carbon-based solid acid under thermal solvent-free conditions is described. The beneficial fea-tures of this new synthetic approach include short reaction time, high yields, clean reaction profiles, and a simple work-up procedure. Furthermore, the catalyst can be readily recycled and reused four times without obvious significant loss of activity. The structure of the catalyst was confirmed by Fourier transform infrared spectroscopy, N2 adsorption/desorption analysis, and X-ray diffraction.

  3. Enantiospecific Synthesis of All Four Stereoisomers of Novel Bicyclic Arylacetamides as κ-Opioid Agonists

    Institute of Scientific and Technical Information of China (English)

    LONG,Ya-Qiu(龙亚秋); MOU,Qi-Yong(牟奇勇); QIU,Da-Ping(仇达萍); WU,Rui-Qin(吴瑞琴)

    2002-01-01

    Conformationally constrained bicyclic derivatives of the potent and selective κ-opioid receptor agonist 2-(3,4-dichlorophenyl)-N-methyl- N- [ (1S ) - 1-phenyl-2- (1-pyrrolidinyl)-ethyl] acetamide (3, ICI-199,441) were designed to explore the effect of the conformational restriction and stereochemistry of the pharmacophoric ethylenediamine incorporated into the pyrrolidine on the affinity and κ-selectivity. A facile enantiospecific synthetic route was established to afford all four stereoisomers starting from readily available amino acids through mild cyclization and amide formation.

  4. Enantiospecific Synthesis of All Four Stereoisomers of Novel Bicyclic Arylacetamides as κ—Opioid Agonists

    Institute of Scientific and Technical Information of China (English)

    龙亚秋; 牟奇勇; 仇达萍; 吴瑞琴

    2002-01-01

    Conformationally constrained bicyclic derivatives of the potent and selective κ-opioid receptor agonist 2-(3,4-dichlorophenyl)-N-methyl-N-[(1S)-1-Phenyl-2-(1-Pyrrolidinyl)-ethyl]acetamide(3,ICI-199,441)were designed to explore the effect of the conformational restriction and stereochemistry of the pharmacophoric ethylenediamine incorporated into the pyrrolidine on the affinity and κ-selectivity.A facile enantiosipecitfic synthetic route was extablished to afford all four stereoisomers starting from readily available amino acids through mild cyclization and amide formation.

  5. 2-Heteroaryl Benzimidazole Derivatives as Melanin Concentrating Hormone Receptor 1 (MCH-R1) Antagonists

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Chae Jo; Kim, Jeong Young; Lee, Byung Ho; Oh, Kwangseok; Yi, Kyu Yang [Korea Research Institute of Chemical Technology, Daejeon (Korea, Republic of)

    2013-08-15

    A novel series of 2-heteroaryl substituted benzimidazole derivatives, containing the piperidinylphenyl acetamide group at the 1-position, were synthesized and evaluated as MCH-R1 antagonists. Extensive SAR investigation probing the effects of C-2 heteroaryl group led to the identification of 2-[2-(pyridin-3-yl)ethyl] analog 3o, which exhibits highly potent MCH-R1 binding activity with an IC{sub 50} value of 1 nM. This substance 3o also has low hERG binding activity, good metabolic stability, and favorable pharmacokinetic properties.

  6. The two conformers of acetanilide unraveled using LA-MB-FTMW spectroscopy

    Science.gov (United States)

    Cabezas, C.; Varela, M.; Caminati, W.; Mata, S.; López, J. C.; Alonso, J. L.

    2011-07-01

    Acetanilide has been investigated by laser ablation molecular beam Fourier transform microwave LA-MB-FTMW spectroscopy. The rotational spectrum of both trans and cis conformers have been analyzed to determine the rotational and 14N quadrupole coupling the constants. The spectrum of the less abundant cis conformer has been assigned for the first time. The doublets observed for this conformer have been interpreted in terms of the tunneling motion between two equivalent non-planar conformations through a small barrier in which the acetamide group and phenyl ring plane are perpendicular. The results are compared with those of the related formanilide.

  7. Two half-sandwiched ruthenium (II compounds containing 5-fluorouracil derivatives: synthesis and study of DNA intercalation.

    Directory of Open Access Journals (Sweden)

    Zhao-Jun Li

    Full Text Available Two novel coordination compounds of half-sandwiched ruthenium(II containing 2-(5-fluorouracil-yl-N-(pyridyl-acetamide were synthesized, and their intercalation binding modes with calf thymus DNA were revealed by hyperchromism of ultraviolet-visible spectroscopy; the binding constants were determined according to a Langmuir adsorption equation that was deduced on the base of careful cyclic voltammetry measurements. The two compounds exhibited DNA intercalation binding activities with the binding constants of 1.13×106 M-1 and 5.35 ×105 M-1, respectively.

  8. Two half-sandwiched ruthenium (II) compounds containing 5-fluorouracil derivatives: synthesis and study of DNA intercalation.

    Science.gov (United States)

    Li, Zhao-Jun; Hou, Yong; Qin, Da-An; Jin, Zhi-Min; Hu, Mao-Lin

    2015-01-01

    Two novel coordination compounds of half-sandwiched ruthenium(II) containing 2-(5-fluorouracil)-yl-N-(pyridyl)-acetamide were synthesized, and their intercalation binding modes with calf thymus DNA were revealed by hyperchromism of ultraviolet-visible spectroscopy; the binding constants were determined according to a Langmuir adsorption equation that was deduced on the base of careful cyclic voltammetry measurements. The two compounds exhibited DNA intercalation binding activities with the binding constants of 1.13×106 M-1 and 5.35 ×105 M-1, respectively.

  9. Synthesis and antispasmodic activity of lidocaine derivatives endowed with reduced local anesthetic action.

    Science.gov (United States)

    Costa, Jorge C S; Neves, Josiane S; de Souza, Marcus V N; Siqueira, Rodrigo A; Romeiro, Nelilma C; Boechat, Nubia; e Silva, Patrícia M R; Martins, Marco A

    2008-02-01

    The present structure-activity relationship (SAR) study focused on chemical modifications of the structure of the local anesthetic lidocaine, and indicated analogues having reduced anesthetic potency, but with superior potency relative to the prototype in preventing anaphylactic or histamine-evoked ileum contraction. From the SAR analysis, 2-(diethylamino)-N-(trifluoromethyl-phenyl) and 2-(diethylamino)-N-(dimethyl-phenyl) acetamides were selected as the most promising compounds. New insights into the applicability of non-anesthetic lidocaine derivatives as templates in drug discovery for allergic syndromes are provided.

  10. The occurrence of abscisic acid in inhibitors B1 and C from immature fruit of Ceratonia siliqua L. (carob) and in commercial carob syrup.

    Science.gov (United States)

    Most, B H; Gaskin, P; Macmillan, J

    1970-03-01

    The presence of abscisic acid in the inhibitors B1 and C from immature carob fruit, whole and minus seed, has been established by thin-layer and gas chromatography and by combined gas chromatography-mass spectrometry. Abscisic acid has been identified in commercial carob syrup by the same means. Most, if not all, of the growth inhibitory activity in these fractions is accounted for as abscisic acid by quantitative gas chromatography as the methyl ester. Trimethylsilylation of abscisic acid with bis (trimethylsilyl) acetamide in pyridine gives two isomeric tris(trimethylsilyl) derivatives.

  11. Synthesis and characterization of new polyesters based on 2,5-bis[(4-chloro carboxyanilino)carbonyl]pyridine and aromatic diols

    Institute of Scientific and Technical Information of China (English)

    Khalil; Faghihi

    2010-01-01

    Six new polyesters 7a-f were synthesized through the solution polycondensation reaction of diacid chloride 5 with six aromatic diols 6a-f in N,N-dimethyl acetamide(DMAc) as solvent in the presence of pyridine as base.The polycondensation reaction produced a series of novel polyester containing pyridyl moiety in the main chain in high yields with inherent viscosities between 0.35 and 0.54 dL/g.The resulted polymers were fully characterized by means of FT-IR spectroscopy,elemental analyses,inherent viscosi...

  12. Subtractive cDNA cloning using oligo(dT)30-latex and PCR: isolation of cDNA clones specific to undifferentiated human embryonal carcinoma cells.

    OpenAIRE

    1991-01-01

    The human embryonal carcinoma cell line NEC14 can be induced to differentiate by the addition of 10(-2)M N,N'-hexamethylene-bis-acetamide (HMBA). A subtractive cDNA library specific to undifferentiated NEC14 cells was constructed using oligo(dT)30-Latex and polymerase chain reaction (PCR). The method was designed to improve the efficiency of subtraction and the enrichment of cDNA clones corresponding to low abundance mRNAs. The single strand of cDNA was made from mRNA prepared from the HMBA-t...

  13. National legislation, international conventions and exposure to harmful chemicals

    CSIR Research Space (South Africa)

    Hietkamp, S

    2006-06-01

    Full Text Available contaminant in chlorinated phenols. Slide 15 © CSIR 2006 www.csir.co.za Dioxin exposure (in TEQ units) • Centre of Decease Control 0.1 pg (10Exp-12)TEQ/kg/day Intake in food <1 ppb. • Pathway From emission point to atmosphere... • Chlorobenzilate • DDT • Dieldrin • DNOC and its salts • Dinoseb Slide 25 © CSIR 2006 www.csir.co.za ANNEX III list • 1,2 dibromoethane (EDB) • Ethylene dichloride • Ethylene oxide • Fluoro acetamide • HCH (mixed isomers...

  14. Chemoenzymatic preparation of optically active trans-cyclohexane-1,2-diamine derivatives: an efficient synthesis of the analgesic U-(-)-50,488.

    Science.gov (United States)

    González-Sabín, Javier; Gotor, Vicente; Rebolledo, Francisca

    2004-11-05

    Stereoespecific syntheses of (+/-)-trans-N,N-cyclohexane-1,2-diamines ((+/-)-4 a-g) were carried out from the corresponding (+/-)-trans-N,N-dialkylaminocyclohexanols by successive treatment with mesyl chloride and aqueous ammonia. The stereochemical outcome indicates the formation of a meso-aziridinium ion intermediate. Kinetic resolutions of diamines (+/-)-4 were efficiently accomplished in aminolysis reactions catalyzed by lipase B from Candida antarctica with ethyl acetate as the solvent and acyl donor. Acetamides and the remaining diamines, isolated as the benzyloxycarbonyl derivatives, were obtained with very high ee values (92-99%). One of the carbamates was used as a precursor of the analgesic U-(-)-50,488.

  15. Oxygen transfer from an intramolecularly coordinated diaryltellurium oxide to acetonitrile. Formation and combined AIM and ELI-D analysis of a novel diaryltellurium acetimidate.

    Science.gov (United States)

    Mallow, Ole; Bolsinger, Jens; Finke, Pamela; Hesse, Malte; Chen, Yu-Sheng; Duthie, Andrew; Grabowsky, Simon; Luger, Peter; Mebs, Stefan; Beckmann, Jens

    2014-08-01

    The reaction of the intramolecularly coordinated diaryltellurium(IV) oxide (8-Me2NC10H6)2TeO with acetonitrile proceeds with oxygen transfer and gives rise to the formation of the novel zwitterionic diaryltelluronium(IV) acetimidate (8-Me2NC10H6)2TeNC(O)CH3 (1) in 57% yield. Hydrolysis of 1 with hydrochloric acid affords acetamide and the previously known diarylhydroxytelluronium(IV) chloride [(8-Me2NC10H6)2Te(OH)]Cl.

  16. Organic synthesis using (diacetoxyiodobenzene (DIB: Unexpected and novel oxidation of 3-oxo-butanamides to 2,2-dihalo-N-phenylacetamides

    Directory of Open Access Journals (Sweden)

    Wei-Bing Liu

    2012-03-01

    Full Text Available A novel and reliable method for the direct preparation of 2,2-dihalo-N-phenylacetamides is reported. The key transformation involves the cleavage of a carbon–carbon bond in the presence of DIB and a Lewis acid as the halogen source, and thus this method significantly expands the value of DIB as a unique and powerful tool in chemical synthesis. This protocol not only adds a new aspect to reactions that use other hypervalent iodine reagents but also provides a wide space for the synthesis of disubstituted acetamides.

  17. Organic synthesis using (diacetoxyiodo)benzene (DIB): Unexpected and novel oxidation of 3-oxo-butanamides to 2,2-dihalo-N-phenylacetamides

    Science.gov (United States)

    Chen, Cui; Zhang, Qing

    2012-01-01

    Summary A novel and reliable method for the direct preparation of 2,2-dihalo-N-phenylacetamides is reported. The key transformation involves the cleavage of a carbon–carbon bond in the presence of DIB and a Lewis acid as the halogen source, and thus this method significantly expands the value of DIB as a unique and powerful tool in chemical synthesis. This protocol not only adds a new aspect to reactions that use other hypervalent iodine reagents but also provides a wide space for the synthesis of disubstituted acetamides. PMID:22509203

  18. Structural requirements for roxatidine in the stimulant effect of rat gastric mucin synthesis and the participation of nitric oxide in this mechanism.

    Science.gov (United States)

    Ichikawa, T; Ishihara, K; Saigenji, K; Hotta, K

    1997-11-01

    1. The structural requirements of the histamine H2-receptor antagonist, roxatidine (2-acetoxy-N-(3-[m-(1-piperidinylmethyl)phenoxy]-propyl)acetamide hydrochloride), for the stimulant effect on mucin biosynthesis and their relation to histamine H2-receptor antagonism were identified by considering the structural analogues of this drug using an organ culture system of the rat stomach and competition studies with [125I]iodoaminopotentidine ([125I]-APT) binding to membranes of the guinea pig striatum. 2. [3H]Glucosamine incorporation into mucin during 5 h incubation period was stimulated by roxatidine and its structural analogues A (2-hydroxy-N-(3-[m-(1-piperidinylmethyl)phenoxy]-propyl)acetamide) and B (N-(3-[m-(1-piperidinylmethyl)phenoxy]-propyl)acetamide). This effect was seen in mucosal cultures of the corpus, but not antrum, region. 3. Structural analogues, in which the length of the flexible chain between the benzene ring and the amide structure differs from that of roxatidine, failed to activate mucin synthesis. No significant change in mucus synthesis occurred with the addition of analogues in which the piperidine ring attached to the benzene ring via a methylene bridge was changed. 4. Specific [125I]-APT binding to the histamine H2 receptor of guinea pig brain membranes was inhibited by roxatidine and all structural analogues used in this study, except F (N-(3-[m-(N, N-dimethyl-aminomethyl)phenoxy]-propyl)acetamide). 5. Ranitidine at 10(-4) M did not suppress the roxatidine-induced increase in [3H]glucosamine incorporation into mucin. 6. Roxatidine-induced stimulation of [3H]glucosamine incorporation into mucin was completely blocked by the addition of either NG-nitro-L-arginine (10(-5) M) or 2-(4-carboxyphenyl)-4,4,5,5,-tetramethylimidazoline-1-oxyl-3-oxide sodium salt (10(-5) M). The inhibitory action of NG-nitro-L-arginine was totally reversed by L-arginine (5 x 10(-3) M). 7. These results suggest that the cardinal chemical features of roxatidine for the

  19. 14N NQR study of nicotinamide and related compounds.

    Science.gov (United States)

    Seliger, J; Zagar, V

    2008-01-01

    14N nuclear quadrupole resonance (NQR) frequencies have been measured in picolinamide, nicotinamide, isonicotinamide, 2,6-pyridine dicarboxamide, and acetamide by double resonance. The 14N NQR spectra in picolinamide, nicotinamide, isonicotinamide, and 2,6-pyridine dicarboxamide show the presence of two distinct nitrogen positions: the ring position with the quadrupole coupling constant about 4,5 MHz and the amide position with the quadrupole coupling constant about 2.6 MHz. The NQR data are related to the structure of the investigated compounds and to the N--H...O hydrogen bonds.

  20. Single-dose safety and pharmacokinetic evaluation of fluorocoxib A: pilot study of novel cyclooxygenase-2-targeted optical imaging agent in a canine model

    OpenAIRE

    Cekanova, Maria; Uddin, Md. Jashim; Legendre, Alfred M.; Galyon, Gina; Bartges, Joseph W.; Callens, Amanda; Martin-Jimenez, Tomas; Marnett, Lawrence J.

    2012-01-01

    We evaluated preclinical single-dose safety, pharmacokinetic properties, and specific uptake of the new optical imaging agent fluorocoxib A in dogs. Fluorocoxib A, N-[(5-carboxy-X-rhodaminyl)but-4-yl]-2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetamide, selectively binds and inhibits the cyclooxygenase-2 (COX-2) enzyme, which is overexpressed in many cancers. Safety pilot studies were performed in research dogs following intravenous (i.v.) administration of 0.1 and 1  mg/kg fluo...

  1. Kinetic Study of the Reaction of the Phthalimide-N-oxyl Radical with Amides: Structural and Medium Effects on the Hydrogen Atom Transfer Reactivity and Selectivity.

    Science.gov (United States)

    Bietti, Massimo; Forcina, Veronica; Lanzalunga, Osvaldo; Lapi, Andrea; Martin, Teo; Mazzonna, Marco; Salamone, Michela

    2016-12-02

    A kinetic study of the hydrogen atom transfer (HAT) reactions from a series of secondary N-(4-X-benzyl)acetamides and tertiary amides to the phthalimide-N-oxyl radical (PINO) has been carried out. The results indicate that HAT is strongly influenced by structural and medium effects; in particular, the addition of Brønsted and Lewis acids determines a significant deactivation of C-H bonds α to the amide nitrogen of these substrates. Thus, by changing the reaction medium, it is possible to carefully control the regioselectivity of the aerobic oxidation of amides catalyzed by N-hydroxyphthalimide, widening the synthetic versatility of this process.

  2. New thermally stable polyesters based on 2,5-pyridinedicarbonyl dichloride and aromatic diols: Synthesis and characterization

    Institute of Scientific and Technical Information of China (English)

    Hossein Nasr Isfahani; Khalil Faghihi

    2009-01-01

    Six new thermally stable polyesters (4a-f) were synthesized through the solution polycondensation reaction of 2,5-pyridine dicarbonyldichloride (2) with six aromatic diols in N,N'-dimethyl acetamide (DMAc) solution and in the presence of pyridine as a base. The polycondensation reactions produce a series of new polyesters (4a-f) in high yields, and inherent viscosity between 0.30 and 0.55 dL/g. The resulting polyesters were characterized by elemental analysis, viscosity measurements, thermal gravimetric analysis (TGA and DTG), solubility test, Fourier transform infrared (FT-IR) spectroscopy and gel permeation chromatography (GPC).

  3. Synthesis of novel tricyclic oxazolidinones by a tandem SN2 and SNAr reaction: SAR studies on conformationally constrained analogues of Linezolid.

    Science.gov (United States)

    Selvakumar, N; Yadi Reddy, B; Sunil Kumar, G; Khera, Manoj Kumar; Srinivas, D; Sitaram Kumar, M; Das, Jagattaran; Iqbal, Javed; Trehan, Sanjay

    2006-08-15

    A series of conformationally constrained analogues of Linezolid were synthesised by employing a tandem SN(2) and SNAr reaction as the key step and tested for antibacterial activity. While the hexahydroazolo-quinoxaline compounds were inactive, the tetrahydroazolo-benzothiazine compounds exhibited interesting antibacterial activity. The introduction of fluorine in the aromatic ring further made the compounds more potent in acetamide compounds resulting in an interesting analogue 32. However, the introduction of fluorine (analogue 34) on the already potent non-fluorine thiocarbamate 21 did not have any influence on the activity.

  4. Radiosynthesis of F-18 DPA-714, a selective radioligand for imaging the translocator protein (18 kDa) with PET

    Energy Technology Data Exchange (ETDEWEB)

    Damont, A.; Hinnen, F.; Kuhnast, B.; Schollhorn-Peyronneau, M.A.; Tavitian, B.; Dolle, F. [CEA, I2BM, Service Hospitalier Frederic Joliot, Laboratoired' Imagerie Moleculaire Experimentale, F-91401 Orsay (France); James, M.; Luus, C. [University of Sydney, Department of Pharmacology, NSW 2006 (Australia); James, M.; Luus, C.; Kassiou, M. [University of Sydney, Brain and Mind Research Institute, NSW 2050 (Australia); Tavitian, B. [INSERM, U803, Service Hospitalier Frederic Joliot, F-91401 Orsay (France); Kassiou, M. [University of Sydney, Discipline of Medical Radiation Sciences, NSW 2006 (Australia); Kassiou, M. [University of Sydney, School of Chemistry, NSW 2006 (Australia)

    2008-07-01

    Recently, a novel series of 2-phenyl-pyrazolo[1,5-a]pyrimidine-acetamides has been reported as selective ligands of the translocator protein (18 kDa). Within this series, DPA-714 (NN-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo[1,5-a] pyrimidin-3-yl)acetamide, K-i=7.0 nM) is a compound, which had been designed with a fluorine atom in its structure, allowing labelling with fluorine-18 (half-life: 109.8 min) and in vivo imaging using positron emission tomography. DPA-714 and its tosyl-oxy derivative (NN-diethyl-2- (2- (4- (2-toluene-sulfonyl-oxy-ethoxy)phenyl) -5,7-dimethyl-pyrazolo [1,5-a]pyrimidin-3-yl) acetamide) as precursor for the labelling with fluorine-18 were synthesized in two steps from DPA-713 (N,N-diethyl-2-(2-(4-methoxy-phenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin -3-yl)acetamide) and obtained in 32 and 42% yields, respectively. [(18)FIDPA-714 was synthesized using a simple one-step process (a tosyl-oxy-for-fluorine nucleophilic aliphatic substitution), which has been fully automated on our Zymate-XP robotic system. It involves: (A) reaction of K[F-18]F-Kryptofix 222 with the tosyl-oxy precursor (4.5-5.0 mg, 8.2-9.1 {mu}mol) at 165 degrees C for 5 min in dimethyl sulfoxide (0.6 ml) followed by (B) C18 PrepSep cartridge pre-purification and finally (C) semi-preparative high-performance liquid chromatography (HPLC) purification on a Waters X-Terra(TM) RP18. Typically, 5.6-7.4 GBq of [F-18]DPA-714 ({>=} 95% chemically and radiochemically pure) could be obtained with specific radioactivities ranging from 37 to 111 GBq/{mu}mol within 85-90 min (HPLC purification and SepPak (R)-based formulation included), starting from a 37 GBq[F-18]fluoride batch (overall non-decay-corrected and isolated radiochemical yield: 15-20%). (authors)

  5. Novel polymorphs of the anti-Trypanosoma cruzi drug benznidazole

    Science.gov (United States)

    Honorato, Sara Braga; Mendonça, Jorge Souza; Boechat, Nubia; Oliveira, Alcemira Conceição; Mendes Filho, Josué; Ellena, Javier; Ayala, Alejandro Pedro

    2014-01-01

    Benznidazole (N-benzyl-2-(2-nitro-1H-imidazol-1-yl)acetamide), is a nitro-heterocyclic drug used in the treatment of Chagas disease. Despite the fact that this drug was released more than 30 years ago, little information about its solid state properties is available in the literature. In this study, it was verified that this drug exhibits three polymorphs, which were characterized in situ by X-ray powder diffraction, thermal analysis, hot stage microscopy and infrared spectroscopy. The thermodynamic relationships among these polymorphs were also discussed.

  6. Piracetam--an old drug with novel properties?

    Science.gov (United States)

    Winnicka, Katarzyna; Tomasiak, Marian; Bielawska, Anna

    2005-01-01

    Piracetam (2-oxo-1-pyrrolidine-acetamide), the most common of the nootropic drugs, is a cyclic derivative of gamma-aminobutyric acid. The treatment with piracetam improves learning, memory, brain metabolism, and capacity. Piracetam has been shown to alter the physical properties of the plasma membrane by increasing its fluidity and by protecting the cell against hypoxia. It increases red cell deformability and normalizes aggregation of hyperactive platelets. Piracetam is an agent with antithrombotic, neuroprotective and rheological properties. The interaction of this molecule with the membrane phospholipids restores membrane fluidity and could explain the efficacy of piracetam in various disorders ranging from dementia and vertigo to myoclonus and stroke.

  7. Synthesis and biological evaluation of imidazole thioacetanilides as novel non-nucleoside HIV-1 reverse transcriptase inhibitors.

    Science.gov (United States)

    Zhan, Peng; Liu, Xinyong; Zhu, Junjie; Fang, Zengjun; Li, Zhenyu; Pannecouque, Christophe; Clercq, Erik De

    2009-08-15

    A series of 2-(1-aryl-1H-imidazol-2-ylthio)acetamide [imidazole thioacetanilide (ITA)] derivatives were synthesized and evaluated as potent inhibitors of human immunodeficiency virus type-1 (HIV-1). Among them, the most potent HIV-1 inhibitors were 4a5 (EC(50)=0.18microM), and 4a2 (EC(50)=0.20microM), which were more effective than the lead compound L1 (EC(50)=2.053microM) and the reference drugs nevirapine and delavirdine. The preliminary structure-activity relationship (SAR) of the newly synthesized congeners is discussed.

  8. Synthesis and Evaluation of 8-[131I]Iodo-substituted Imidazopyridine Derivative as Single Photon Emission Computed Tomography Tracer for Peripheral Benzodiazepine Receptors

    Institute of Scientific and Technical Information of China (English)

    Bin LI; Jian Feng LI; Xiao Guang SUN; Gang HUANG

    2006-01-01

    A novel N-methyl, N-phenyl-[6-chloro-2-(4-chlorophenyl)-8-iodoimidazo[1, 2-a]-pyridine-3-yl]acetamide (compound Ⅴ) was synthesized, radiolabelled with 131I and evaluated in vitro. In vitro cell uptake studies showed that MDA-MB-231 cells yield four-fold higher specific uptake of [131I]-compound Ⅵ than MCF-7 cells, corresponding to the increased expression of PBR in MDA-MB-231 cells. Blocking studies significantly reduced the MDA-MB-231 cells uptake of[131I]-compound Ⅵ. It indicated that [131I]-compound Ⅵ might be a potential SPECTradioligand for imaging of PBR.

  9. One-Step Preparation of N-Doped Nanowhisker TiO2 by Micro Arc Oxidation

    Institute of Scientific and Technical Information of China (English)

    SU Yu-Cheng; ZHANG Gu-Ling; WANG Wen-Zhong; ZOU Bin; AO Le

    2011-01-01

    @@ Flowers, trees and coral like TiO2 Rlms are first produced by the micro-arc-oxidation method in electrolyte of phosphate.Nanowhiskers with high surface area grow at the tail ends of the coralloid film when the positive current density is set to be 17.14 A/dm2.With acetamide in electrolyte, N element is doped.The analysis results indicate that the ratio of anatase phase to rutile phases is about 2 : 1 in the micro-arc-oxidation produced N-TiO2 film.The optical absorption edge red shifts in the presence of N doping.%Flowers, trees and coral like TiO2 films are first produced by the micro-arc-oxidation method in electrolyte of phosphate. Nanowhiskers with high surface area grow at the tail ends of the coralloid film when the positive current density is set to be 17.14 A/dm2. With acetamide in electrolyte, N element is doped. The analysis results indicate that the ratio of anatase phase to rutile phases is about 2: 1 in the micro-arc-oxidation produced N-TiO2 film. The optical absorption edge red shifts in the presence of N doping.

  10. Synthesis and Antiproliferative Activities of Benzimidazole-Based Sulfide and Sulfoxide Derivatives.

    Science.gov (United States)

    Gaballah, Samir T; El-Nezhawy, Ahmed O H; Amer, Hassan; Ali, Mamdouh Moawad; Mahmoud, Abeer Essam El-Din; Hofinger-Horvath, Andreas

    2016-01-01

    The design, synthesis, and in vitro antiproliferative activity of a novel series of sulfide (4a-i) and sulfoxide (5a-h) derivatives of benzimidazole, in which different aromatic and heteroaromatic acetamides are linked to benzimidazole via sulfide (4a-i) and sulfoxide (5a-h) linker, are reported and the structure-activity relationship is discussed. The new derivatives were prepared by coupling 2-(mercaptomethyl)benzimidazole with 2-bromo-N-(substituted) acetamides in dry acetone in the presence of anhydrous potassium carbonate. With very few exceptions, all of the synthesized compounds showed varying antiprolific activities against HepG2, MCF-7, and A549 cell lines. Compound 5a was very similar in potency to doxorubicin as an anticancer drug, with IC50 values 4.1 ± 0.5, 4.1 ± 0.5, and 5.0 ± 0.6 µg/mL versus 4.2 ± 0.5, 4.9 ± 0.6, and 6.1 ± 0.6 µg/mL against HepG2, MCF-7, and A549 cell lines, respectively. In contrast, none of the compounds showed activity against human prostate PC3 cancer cells. Additionally, the sulfoxide derivatives were more potent than the corresponding sulfides.

  11. Expression control of nitrile hydratase and amidase genes in Rhodococcus erythropolis and substrate specificities of the enzymes.

    Science.gov (United States)

    Rucká, Lenka; Volkova, Olga; Pavlík, Adam; Kaplan, Ondřej; Kracík, Martin; Nešvera, Jan; Martínková, Ludmila; Pátek, Miroslav

    2014-06-01

    Bacterial amidases and nitrile hydratases can be used for the synthesis of various intermediates and products in the chemical and pharmaceutical industries and for the bioremediation of toxic pollutants. The aim of this study was to analyze the expression of the amidase and nitrile hydratase genes of Rhodococcus erythropolis and test the stereospecific nitrile hydratase and amidase activities on chiral cyanohydrins. The nucleotide sequences of the gene clusters containing the oxd (aldoxime dehydratase), ami (amidase), nha1, nha2 (subunits of the nitrile hydratase), nhr1, nhr2, nhr3 and nhr4 (putative regulatory proteins) genes of two R. erythropolis strains, A4 and CCM2595, were determined. All genes of both of the clusters are transcribed in the same direction. RT-PCR analysis, primer extension and promoter fusions with the gfp reporter gene showed that the ami, nha1 and nha2 genes of R. erythropolis A4 form an operon transcribed from the Pami promoter and an internal Pnha promoter. The activity of Pami was found to be weakly induced when the cells grew in the presence of acetonitrile, whereas the Pnha promoter was moderately induced by both the acetonitrile or acetamide used instead of the inorganic nitrogen source. However, R. erythropolis A4 cells showed no increase in amidase and nitrile hydratase activities in the presence of acetamide or acetonitrile in the medium. R. erythropolis A4 nitrile hydratase and amidase were found to be effective at hydrolysing cyanohydrins and 2-hydroxyamides, respectively.

  12. ADSORPTION OF TANNIN FROM AQUEOUS SOLUTION ONTO MACROPOROUS CROSSLINKED POLY(N—VINYL—ACETAMIDE)VIA HYDROGEN BONDING

    Institute of Scientific and Technical Information of China (English)

    XUMancai; XUMingcheng; 等

    2000-01-01

    A Strongly hydrophilic hydrogen-bonding adsorbent-macroporous crosslinked Poly(Nvinyl-acetamide),which contain both hydrogen bond acceptor and donator,was synthesized.Adsorption mechanism and dynamic adsorption of tannin from aqueous solution onto the adsorbent were investigated.Most of the differntial adsorption heats for various adsorption capacities calculated from the adsorption isotherms according to Clapeyron-Clausius equation lay in the range of hydrogen bond energy(8-50J/mol).Adsorption properties of the adsorbent were studied in detail.These results revealed a hydrogen bonding mechanism of the adsorption of tannin from aqueous solution onto the adsorbent.The result of the dynamic adsorption of tanning with the initial concentration under 600mg/L showed that the adsorption rate of tannin exceeded 90% when the flow rate was 3BV/h and the effluent volume reached 100BV.Therefore,the developed hydrogen-bonding adsorbent-macroporous crosslinked poly(N-vinyl-acetamide)-is an excellent adsorbent to remove tannin from extract of natural products,and has great value in application.

  13. Urinary Metabolomic Approach Provides New Insights into Distinct Metabolic Profiles of Glutamine and N-Carbamylglutamate Supplementation in Rats.

    Science.gov (United States)

    Liu, Guangmang; Cao, Wei; Fang, Tingting; Jia, Gang; Zhao, Hua; Chen, Xiaoling; Wu, Caimei; Wang, Jing

    2016-08-04

    Glutamine and N-carbamylglutamate can enhance growth performance and health in animals, but the underlying mechanisms are not yet elucidated. This study aimed to investigate the effect of glutamine and N-carbamylglutamate supplementation in rat metabolism. Thirty rats were fed a control, glutamine, or N-carbamylglutamate diet for four weeks. Urine samples were analyzed by nuclear magnetic resonance (NMR)-based metabolomics, specifically high-resolution ¹H NMR metabolic profiling combined with multivariate data analysis. Glutamine significantly increased the urine levels of acetamide, acetate, citrulline, creatinine, and methymalonate, and decreased the urine levels of ethanol and formate (p carbamylglutamate significantly increased the urine levels of creatinine, ethanol, indoxyl sulfate, lactate, methymalonate, acetoacetate, m-hydroxyphenylacetate, and sarcosine, and decreased the urine levels of acetamide, acetate, citrulline, creatine, glycine, hippurate, homogentisate, N-acetylglutamate, phenylacetyglycine, acetone, and p-hydroxyphenylacetate (p carbamylglutamate could modify urinary metabolome related to nitrogen metabolism and gut microbiota metabolism. Moreover, N-carbamylglutamate could alter energy and lipid metabolism. These findings indicate that different arginine precursors may lead to differences in the biofluid profile in rats.

  14. Primary amino acid derivatives: substitution of the 4'-N'-benzylamide site in (R)-N'-benzyl 2-amino-3-methylbutanamide, (R)-N'-benzyl 2-amino-3,3-dimethylbutanamide, and (R)-N'-benzyl 2-amino-3-methoxypropionamide provides potent anticonvulsants with pain-attenuating properties.

    Science.gov (United States)

    King, Amber M; Salomé, Christophe; Salomé-Grosjean, Elise; De Ryck, Marc; Kaminski, Rafal; Valade, Anne; Stables, James P; Kohn, Harold

    2011-10-13

    Recently, we reported that select N'-benzyl 2-substituted 2-amino acetamides (primary amino acid derivatives (PAADs)) exhibited pronounced activities in established whole animal anticonvulsant (i.e., maximal electroshock seizure (MES)) and neuropathic pain (i.e., formalin) models. The anticonvulsant activities of C(2)-hydrocarbon N'-benzyl 2-amino acetamides (MES ED(50) = 13-21 mg/kg) exceeded those of phenobarbital (ED(50) = 22 mg/kg). Two additional studies defining the structure-activity relationship of PAADs are presented in this issue of the journal. In this study, we demonstrated that the anticonvulsant activities of (R)-N'-benzyl 2-amino-3-methylbutanamide and (R)-N'-benzyl 2-amino-3,3-dimethylbutanamide were sensitive to substituents at the 4'-N'-benzylamide site; electron-withdrawing groups retained activity, electron-donating groups led to a loss of activity, and incorporating either a 3-fluorobenzyloxy or 3-fluorophenoxymethyl group using a rationally designed multiple ligand approach improved activity. Additionally, we showed that substituents at the 4'-N'-benzylamide site of (R)-N'-benzyl 2-amino-3-methoxypropionamide also improved anticonvulsant activity, with the 3-fluorophenoxymethyl group providing the largest (∼4-fold) increase in activity (ED(50) = 8.9 mg/kg), a value that surpassed phenytoin (ED(50) = 9.5 mg/kg). Collectively, the pharmacological findings provided new information that C(2)-hydrocarbon PAADs represent a novel class of anticonvulsants.

  15. Anticonvulsants Based on the α-Substituted Amide Group Pharmacophore Bind to and Inhibit Function of Neuronal Nicotinic Acetylcholine Receptors.

    Science.gov (United States)

    Krivoshein, Arcadius V

    2016-03-16

    Although the antiepileptic properties of α-substituted lactams, acetamides, and cyclic imides have been known for over 60 years, the mechanism by which they act remains unclear. I report here that these compounds bind to the nicotinic acetylcholine receptor (nAChR) and inhibit its function. Using transient kinetic measurements with functionally active, nondesensitized receptors, I have discovered that (i) α-substituted lactams and cyclic imides are noncompetitive inhibitors of heteromeric subtypes (such as α4β2 and α3β4) of neuronal nAChRs and (ii) the binding affinity of these compounds toward the nAChR correlates with their potency in preventing maximal electroshock (MES)-induced convulsions in mice. Based on the hypothesis that α-substituted amide group is the essential pharmacophore of these drugs, I found and tested a simple compound, 2-phenylbutyramide. This compound indeed inhibits nAChR and shows good anticonvulsant activity in mice. Molecular docking simulations suggest that α-substituted lactams, acetamides, and cyclic imides bind to the same sites on the extracellular domain of the receptor. These new findings indicate that inhibition of brain nAChRs may play an important role in the action of these antiepileptic drugs, a role that has not been previously recognized.

  16. Structure-activity relationships of diverse oxazolidinones for linezolid-resistant Staphylococcus aureus strains possessing the cfr methyltransferase gene or ribosomal mutations.

    Science.gov (United States)

    Locke, Jeffrey B; Finn, John; Hilgers, Mark; Morales, Gracia; Rahawi, Shahad; G C, Kedar; Picazo, Juan José; Im, Weonbin; Shaw, Karen Joy; Stein, Jeffrey L

    2010-12-01

    Staphylococcal resistance to linezolid (LZD) is mediated through ribosomal mutations (23S rRNA or ribosomal proteins L3 and L4) or through methylation of 23S rRNA by the horizontally transferred Cfr methyltransferase. To investigate the structural basis for oxazolidinone activity against LZD-resistant (LZD(r)) strains, we compared structurally diverse, clinically relevant oxazolidinones, including LZD, radezolid (RX-1741), TR-700 (torezolid), and a set of TR-700 analogs (including novel CD-rings and various A-ring C-5 substituents), against a panel of laboratory-derived and clinical LZD(r) Staphylococcus aureus strains possessing a variety of resistance mechanisms. Potency against all strains was correlated with optimization of C- and D-rings, which interact with more highly conserved regions of the peptidyl transferase center binding site. Activity against cfr strains was retained with either hydroxymethyl or 1,2,3-triazole C-5 groups but was reduced by 2- to 8-fold in compounds with acetamide substituents. LZD, which possesses a C-5 acetamide group and lacks a D-ring substituent, demonstrated the lowest potency against all strains tested, particularly against cfr strains. These data reveal key features contributing to oxazolidinone activity and highlight structural tradeoffs between potency against susceptible strains and potency against strains with various resistance mechanisms.

  17. Biodegradation of butachlor by Rhodococcus sp. strain B1 and purification of its hydrolase (ChlH) responsible for N-dealkylation of chloroacetamide herbicides.

    Science.gov (United States)

    Liu, Hong-Ming; Cao, Li; Lu, Peng; Ni, Haiyan; Li, Yun-Xiang; Yan, Xin; Hong, Qing; Li, Shun-Peng

    2012-12-19

    Rhodococcus sp. strain B1 could degrade 100 mg/L butachlor within 5 days. Butachlor was first hydrolyzed by strain B1 through N-dealkylation, which resulted in the production of butoxymethanol and 2-chloro-N-(2,6-dimethylphenyl)acetamide. Butoxymethanol could be further degraded and utilized as the carbon source for the growth of strain B1, whereas 2-chloro-N-(2,6-dimethylphenyl)acetamide could not be degraded further. The hydrolase designated ChlH, responsible for the N-dealkylation of the side chain of butachlor, was purified 185.1-fold to homogeneity with 16.1% recovery. The optimal pH and temperature of ChlH were observed to be 7.0-7.5 and 30 °C, respectively. This enzyme was also able to catalyze the N-dealkylation of other chloroacetamide herbicides; the catalytic efficiency followed the order alachlor > acetochlor >butachlor > pretilachlor, which indicated that the alkyl chain length influenced the N-dealkylation of the chloroacetamide herbicides. This is the first report on the biodegradation of chloroacetamide herbicides at the enzyme level.

  18. Structure-Activity Relationships of Diverse Oxazolidinones for Linezolid-Resistant Staphylococcus aureus Strains Possessing the cfr Methyltransferase Gene or Ribosomal Mutations▿

    Science.gov (United States)

    Locke, Jeffrey B.; Finn, John; Hilgers, Mark; Morales, Gracia; Rahawi, Shahad; G. C., Kedar; Picazo, Juan José; Im, Weonbin; Shaw, Karen Joy; Stein, Jeffrey L.

    2010-01-01

    Staphylococcal resistance to linezolid (LZD) is mediated through ribosomal mutations (23S rRNA or ribosomal proteins L3 and L4) or through methylation of 23S rRNA by the horizontally transferred Cfr methyltransferase. To investigate the structural basis for oxazolidinone activity against LZD-resistant (LZDr) strains, we compared structurally diverse, clinically relevant oxazolidinones, including LZD, radezolid (RX-1741), TR-700 (torezolid), and a set of TR-700 analogs (including novel CD-rings and various A-ring C-5 substituents), against a panel of laboratory-derived and clinical LZDr Staphylococcus aureus strains possessing a variety of resistance mechanisms. Potency against all strains was correlated with optimization of C- and D-rings, which interact with more highly conserved regions of the peptidyl transferase center binding site. Activity against cfr strains was retained with either hydroxymethyl or 1,2,3-triazole C-5 groups but was reduced by 2- to 8-fold in compounds with acetamide substituents. LZD, which possesses a C-5 acetamide group and lacks a D-ring substituent, demonstrated the lowest potency against all strains tested, particularly against cfr strains. These data reveal key features contributing to oxazolidinone activity and highlight structural tradeoffs between potency against susceptible strains and potency against strains with various resistance mechanisms. PMID:20837751

  19. The postprandial plasma rye fingerprint includes benzoxazinoid-derived phenylacetamide sulfates.

    Science.gov (United States)

    Hanhineva, Kati; Keski-Rahkonen, Pekka; Lappi, Jenni; Katina, Kati; Pekkinen, Jenna; Savolainen, Otto; Timonen, Oskari; Paananen, Jussi; Mykkänen, Hannu; Poutanen, Kaisa

    2014-07-01

    The bioavailability of whole-grain rye-derived phytochemicals has not yet been comprehensively characterized, and different baking and manufacturing processes can modulate the phytochemical composition of breads and other rye products. The aim of our study was to find key differences in the phytochemical profile of plasma after the consumption of 3 breads containing rye bran when compared with a plain white wheat bread control. Plasma metabolite profiles of 12 healthy middle-aged men and women were analyzed using LC quadrupole time-of-flight mass spectrometry metabolomics analysis while fasting and at 60 min, 120 min, 240 min, and 24 h after consuming a meal that contained either 100% whole-grain sourdough rye bread or white wheat bread enriched with native unprocessed rye bran or bioprocessed rye bran. White wheat bread was used as the control. The meals were served in random order after a 12-h overnight fast, with at least 3 d between each occasion. Two sulfonated phenylacetamides, hydroxy-N-(2-hydroxyphenyl) acetamide and N-(2-hydroxyphenyl) acetamide, potentially derived from the benzoxazinoid metabolites, were among the most discriminant postprandial plasma biomarkers distinguishing intake of breads containing whole-meal rye or rye bran from the control white wheat bread. Furthermore, subsequent metabolite profiling analysis of the consumed breads indicated that different bioprocessing/baking techniques involving exposure to microbial metabolism (e.g., sourdough fermentation) have a central role in modulating the phytochemical content of the whole-grain and bran-rich breads.

  20. GC-MS Metabolite Profiling of Extreme Southern Pinot noir Wines: Effects of Vintage, Barrel Maturation, and Fermentation Dominate over Vineyard Site and Clone Selection.

    Science.gov (United States)

    Schueuermann, Claudia; Khakimov, Bekzod; Engelsen, Søren Balling; Bremer, Phil; Silcock, Patrick

    2016-03-23

    Wine is an extremely complex beverage that contains a multitude of volatile and nonvolatile compounds. This study investiged the effect of vineyard site and grapevine clone on the volatile profiles of commercially produced Pinot noir wines from central Otago, New Zealand. Volatile metabolites in Pinot noir wines produced from five grapevine clones grown on six vineyard sites in close proximity, over two consecutive vintages, were surveyed using gas chromatography-mass spectrometry (GC-MS). The raw GC-MS data were processed using parallel factor analysis (PARAFAC2), and final metabolite data were analyzed by principal component analysis (PCA). Winemaking conditions, vintage, and barrel maturation were found to be the most dominant factors. The effects of vineyard site and clone were mostly vintage dependent. Although four compounds including β-citronellol, homovanillyl alcohol, N-(3-methylbutyl)acetamide, and N-(2-phenylethyl)acetamide discriminated the vineyard sites independent of vintage, Pinot noir wines from different clones were only partially discriminated by PCA, and marker compound selection remained challenging.

  1. A Green Ultrasound Synthesis, Characterization and Antibacterial Evaluation of 1,4-Disubstituted 1,2,3-Triazoles Tethering Bioactive Benzothiazole Nucleus.

    Science.gov (United States)

    Rezki, Nadjet

    2016-04-18

    The synthesis of N-(benzo[d]thiazol-2-yl)-2-(4-substituted-1H-1,2,3-triazol-1-yl)acetamides 5a-r via the 1,3-dipolar cycloaddition reaction between 2-azido-N-(benzo[d]thiazol-2-yl)acetamide derivatives 3a-c and different alkynes were performed in the presence and absence of ultrasound irradiation. The synthesis was carried out using t-BuOH/H₂O (1:1, v/v) as reaction solvents and CuSO₄·5H₂O/sodium ascorbate as the catalyst. The copper catalyst was implemented to provide the regioselective 1,4-disubstituted 1,2,3-triazoles 5a-r. Significant reductions in reaction times with comparably higher yields were observed when the reactions were carried out under ultrasound irradiation. The structures of the newly synthesized 1,2,3-triazoles were elucidated by IR, NMR, MS, and elemental analyses. They were also screened for their antimicrobial activity against three gram-positive (Streptococcus pneumonia, Bacillus subtilis, and Staphylococcus aureus), three gram-negative (Pseudomonas aeuroginosa, Escherichia coli, and Klebsiella pneumonia), and two fungal strains (Aspergillus fumigates and Candida albicans). Most of the tested compounds displayed promising antimicrobial activities at a Minimum Inhibition Concentration (MIC) of 4-16 μg/mL.

  2. Synthesis and evaluation of novel fluorinated pyrazolo-1,2,3-triazole hybrids as antimycobacterial agents.

    Science.gov (United States)

    Emmadi, Narender Reddy; Bingi, Chiranjeevi; Kotapalli, Sudha Sravanti; Ummanni, Ramesh; Nanubolu, Jagadeesh Babu; Atmakur, Krishnaiah

    2015-08-01

    A library of novel 3-trifluoromethyl pyrazolo-1,2,3-triazole hybrids (5-7) were accomplished starting from 5-phenyl-3-(trifluoromethyl)-1H-pyrazol-4-amine (1) via key intermediate 2-azido-N-(5-phenyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)acetamide (3) through click chemistry approach. Thus obtained compounds in 5-7 series were evaluated for in vitro antimycobacterial activity against Mycobacterium smegmatis (MC(2) 155) and also verified the cytotoxicity. These studies engendered promising lead compounds 5q, 7b and 7c with MIC (μg/mL) values 15.34, 16.18 and 16.60, respectively. Amongst these three compounds, 2-(4-(4-methoxybenzoyl)-1H-1,2,3-triazol-1-yl)-N-(5-phenyl-3-(trifluoromethyl)-1H-pyrazol-4-yl) acetamide (5q) emerged as the most promising antitubercular agent with lowest cytotoxicity against the A549 cancer cell line. This is the first report to demonstrate the pyrazolo triazole hybrids as potential antimycobacterial agents.

  3. Sulfuric acid nucleation: An experimental study of the effect of seven bases

    Science.gov (United States)

    Glasoe, W. A.; Volz, K.; Panta, B.; Freshour, N.; Bachman, R.; Hanson, D. R.; McMurry, P. H.; Jen, C.

    2015-03-01

    Nucleation of particles with sulfuric acid, water, and nitrogeneous bases was studied in a flow reactor. Sulfuric acid and water levels were set by flows over sulfuric acid and water reservoirs, respectively, and the base concentrations were determined from measured permeation rates and flow dilution ratios. Particle number distributions were measured with a nano-differential-mobility-analyzer system. Results indicate that the nucleation capability of NH3, methylamine, dimethylamine, and trimethylamine with sulfuric acid increases from NH3 as the weakest, methylamine next, and dimethylamine and trimethylamine the strongest. Three other bases were studied, and experiments with triethylamine showed that it is less effective than methylamine, and experiments with urea and acetamide showed that their capabilities are much lower than the amines with acetamide having basically no effect. When both NH3 and an amine were present, nucleation was more strongly enhanced than with just the amine present. Comparisons of nucleation rates to predictions and previous experimental work are discussed, and the sulfuric acid-base nucleation rates measured here are extrapolated to atmospheric conditions. The measurements suggest that atmospheric nucleation rates are significantly affected by synergistic interactions between ammonia and amines.

  4. Nitro radical anions from megazol and related nitroimidazoles in aprotic media. A father-son type reaction triggered by an acidic proton

    Energy Technology Data Exchange (ETDEWEB)

    Bonta, M.; Chauviere, G.; Perie, J.; Nunez-Vergara, L.J.; Squella, J.A

    2002-09-25

    We have studied the electrochemical reduction of some nitroimidazoles such as megazol(2-amino-5-(1-methyl-5-nitro-2-imidazolyl)-1,3,4-thiadiazol, CAS 19622-55-0) and two related derivatives in aprotic media (100% DMF, 0.1 M TBAP). All the studied compounds were easily reducible in aprotic media generating the corresponding nitro radical anions as products of the one electron reduction of the parent compound. The nitro radical anions decay by a dimerization reaction and the dimerization rate constants were obtained according to the Olmstead's approach by obtaining values of 150{+-}24, 1690{+-}42 and 640{+-}32 M{sup -1} s{sup -1} for megazol, GC-361 and GC-284, respectively. The existence of an acidic proton on the acetamide group in the GC-361 molecule triggered the appearance of father-son type reactions between the nitro radical anion from GC-361 (son compound) and GC-361 (father compound) generating the neutral radical and the conjugate base of GC-361. Thus the nitro radical anion from GC-361 acts as a Broensted base abstracting the proton of the acetamide group in the GC-361 derivative of megazol.

  5. Enhanced production of amidase from Rhodococcus erythropolis MTCC 1526 by medium optimisation using a statistical experimental design.

    Science.gov (United States)

    Vaidya, Bhalchandra K; Mutalik, Snehal R; Joshi, Renuka M; Nene, Sanjay N; Kulkarni, Bhaskar D

    2009-05-01

    In the present work, statistical experimental methodology was used to enhance the production of amidase from Rhodococcus erythropolis MTCC 1526. R. erythropolis MTCC 1526 was selected through screening of seven strains of Rhodococcus species. The Placket-Burman screening experiments suggested that sorbitol as carbon source, yeast extract and meat peptone as nitrogen sources, and acetamide as amidase inducer are the most influential media components. The concentrations of these four media components were optimised using a face-centred design of response surface methodology (RSM). The optimum medium composition for amidase production was found to contain sorbitol (5 g/L), yeast extract (4 g/L), meat peptone (2.5 g/L), and acetamide (12.25 mM). Amidase activities before and after optimisation were 157.85 units/g dry cells and 1,086.57 units/g dry cells, respectively. Thus, use of RSM increased production of amidase from R. erythropolis MTCC 1526 by 6.88-fold.

  6. Synthesis of a New Scaffold: the 7H,8H-Pyrimido[1,6-b]pyridazin-6,8-dione Nucleus

    Directory of Open Access Journals (Sweden)

    Jadwiga Turło

    2007-12-01

    Full Text Available This paper describes a modified method of preparation of a number of α-aryl-α-(pyridazin-3-yl-acetonitriles via the C-arylation reaction of the corresponding carbanionsof phenylacetonitriles using 3-chloropyridazine derivatives. KOH and DMSO were used inthe deprotonation process, which made the reaction very simple and safe to perform.Nitriles were obtained in the hydrolysis reaction to the corresponding α-aryl-α-(pyridazin-3-yl-acetamide derivatives, which were next subjected to cyclization to afford the finalproducts. A number of new derivatives of 7H,8H-pyrimido[1,6-b]pyridazin-6,8-dione weresynthesized in the cyclocondensation reaction of respective α-aryl-α-(pyridazin-3-yl-acetamides with diethyl carbonate in the presence of EtONa. The structure andcomposition of the new compounds were confirmed by IR, 1H- and 13C- NMR analysesand by elemental C, H and N analysis.

  7. Comparative transport efficiencies of urea analogues through urea transporter UT-B.

    Science.gov (United States)

    Zhao, Dan; Sonawane, N D; Levin, Marc H; Yang, Baoxue

    2007-07-01

    Expression of urea transporter UT-B confers high urea permeability to mammalian erythrocytes. Erythrocyte membranes also permeate various urea analogues, suggesting common transport pathways for urea and structurally similar solutes. In this study, we examined UT-B-facilitated passage of urea analogues and other neutral small solutes by comparing transport properties of wildtype to UT-B-deficient mouse erythrocytes. Stopped-flow light-scattering measurements indicated high UT-B permeability to urea and chemical analogues formamide, acetamide, methylurea, methylformamide, ammonium carbamate, and acrylamide, each with P(s)>5.0 x 10(-6) cm/s at 10 degrees C. UT-B genetic knockout and phloretin treatment of wildtype erythrocytes similarly reduced urea analogue permeabilities. Strong temperature dependencies of formamide, acetamide, acrylamide and butyramide transport across UT-B-null membranes (E(a)>10 kcal/mol) suggested efficient diffusion of these amides across lipid bilayers. Urea analogues dimethylurea, acryalmide, methylurea, thiourea and methylformamide inhibited UT-B-mediated urea transport by >60% in the absence of transmembrane analogue gradients, supporting a pore-blocking mechanism of UT-B inhibition. Differential transport efficiencies of urea and its analogues through UT-B provide insight into chemical interactions between neutral solutes and the UT-B pore.

  8. A Novel Multifunctional β-N-Acetylhexosaminidase Revealed through Metagenomics of an Oil-Spilled Mangrove

    Directory of Open Access Journals (Sweden)

    Fábio Lino Soares

    2017-07-01

    Full Text Available The use of culture-independent approaches, such as metagenomics, provides complementary access to environmental microbial diversity. Mangrove environments represent a highly complex system with plenty of opportunities for finding singular functions. In this study we performed a functional screening of fosmid libraries obtained from an oil contaminated mangrove site, with the purpose of identifying clones expressing hydrolytic activities. A novel gene coding for a β-N-acetylhexosaminidase with 355 amino acids and 43KDa was retrieved and characterized. The translated sequence showed only 38% similarity to a β-N-acetylhexosaminidase gene in the genome of Veillonella sp. CAG:933, suggesting that it might constitute a novel enzyme. The enzyme was expressed, purified, and characterized for its enzymatic activity on carboxymethyl cellulose, p-Nitrophenyl-2acetamide-2deoxy-β-d-glucopyranoside, p-Nitrophenyl-2acetamide-2deoxy-β-d-galactopyranoside, and 4-Nitrophenyl β-d-glucopyranoside, presenting β-N-acetylglucosaminidase, β-glucosidase, and β-1,4-endoglucanase activities. The enzyme showed optimum activity at 30 °C and pH 5.5. The characterization of the putative novel β-N-acetylglucosaminidase enzyme reflects similarities to characteristics of the environment explored, which differs from milder conditions environments. This work exemplifies the application of cultivation-independent molecular techniques to the mangrove microbiome for obtaining a novel biotechnological product.

  9. Detection and Quantification of Nitrogen Compounds in the First Drilled Martian Solid Samples by the Sample Analysis at Mars (SAM) Instrument Suite on the Mars Science Laboratory (MSL)

    Science.gov (United States)

    Stern, Jennifer C.; Navarro-Gonzalez, Rafael; Freissinet, Caroline; McKay, Christopher P.; Archer, P. Douglas, Jr.; Buch, Arnaud; Coll, Patrice; Eigenbrode, Jennifer L.; Franz, Heather B.; Glavin, Daniel P.; Ming, Douglas W.; Steele, Andrew; Szopa, Cyril; Wray, James J.; Conrad, Pamela G.; Mahaffy, Paul R.

    2014-01-01

    The Sampl;e Analysis at Mars (sam) instrument suite on the Mars Science Laboratory (MSL) Curiosity Rover detected both reduced and oxidized nitrogen bearing compounds during the pyrolysis of surface materials from the three sites at Gale Crater. Preliminary detections of nitrogen species include No, HCN, ClCN, and TFMA ((trifluoro-N-methyl-acetamide), Confirmation of indigenous Martian nitrogen-bearing compounds requires quantifying N contribution from the terrestrial derivatization reagents carried for SAM's wet chemistry experiment that contribute to the SAM background. Nitrogen species detected in the SAM solid sample analyses can also be produced during laboratory pyrolysis experiments where these reagents are heated in the presence of perchlorate a compound that has also been identified by SAM in Mars solid samples.

  10. A highly sensitive method for quantification of iohexol

    DEFF Research Database (Denmark)

    Schulz, A.; Boeringer, F.; Swifka, J.

    2014-01-01

    lohexol (1-N,3-N-bis(2,3-dihydroxypropyl)-5-IN-(2,3-dihydroxypropyl) acetamide-2,4,6-triiodobenzene1,3-dicarboxamide) is used for accurate determination of the glomerular filtration rate (GFR) in chronic kidney disease (CKD) patients. However, high iohexol amounts might lead to adverse effects in...... in organisms. In order to minimize the iohexol dosage required for the GFR determination in humans, the development of a sensitive quantification method is essential. Therefore, the objective of our preclinical study was to establish and validate a simple and robust liquid...... with a cut-off of 3 kDa. The chromatographic separation was achieved on an analytical Zorbax SB C18 column. The detection and quantification were performed on a high capacity trap mass spectrometer using positive ion ESI in the multiple reaction monitoring (MRM) mode. Furthermore, using real-time polymerase...

  11. Nano magnetite (Fe3O4, an efficient and robust catalyst for the one-pot synthesis of 1-(aryl(piperidin-1-ylmethylnaphthalene-2-ol and 1-(α-amido alkyl-2-naphthol under ultrasound irradiation

    Directory of Open Access Journals (Sweden)

    Masoud Mokhtary

    2017-01-01

    Full Text Available The direct three component reaction via condensation of aldehydes, 2-naphthol and piperidine or acetamide to generate 1-(aryl(piperidin-1-ylmethylnaphthalene-2-ol and N-((2-hydroxy naphthalene-1-yl(arylmethylacetamide derivatives has been carried out over Fe3O4 magnetic nanoparticle with high efficiency under ultrasound irradiation. These reactions were studied under different conditions. In terms of reaction time and yield, it was found that optimum results were obtained for the synthesis of 1-(aryl(piperidin-1-ylmethylnaphthalene-2-ol under solvent free condition and for preparation of N-((2-hydroxynaphthalene-1-yl(arylmethylacetamide in acetic acid under ultrasound irradiation at 80 °C. Clean methodologies, easy workup procedure, and high yields are some advantages of this work.

  12. Crystal structure of catena-poly[[potassium-tri-μ-dimethylacetamide-κ6O:O] iodide

    Directory of Open Access Journals (Sweden)

    Cezar-Catalin Comanescu

    2014-10-01

    Full Text Available The structure of catena-poly[[potassium-tri-μ-dimethylacetamide-κ6O:O] iodide], {[K(C4H9NO3]I}n, at 120 K has trigonal (P-3 symmetry. The structure adopts a linear chain motif parallel to the crystallographic c axis. Two crystallographically independent K+ cations are present in the asymmetric unit located on threefold rotoinversion axes at [0, 0, 0] and [0, 0, 1/2] and are bridged by the O atoms of the acetamide moiety. This is an example of a rare μ2-bridging mode for dimethylacetamide O atoms. The iodide counter-ion resides on a threefold rotation axis in the channel formed by the [K(C4H9NO]+ chains.

  13. Synthesis and evaluation of 4-substituted coumarins as novel acetylcholinesterase inhibitors.

    Science.gov (United States)

    Razavi, Seyyede Faeze; Khoobi, Mehdi; Nadri, Hamid; Sakhteman, Amirhossein; Moradi, Alireza; Emami, Saeed; Foroumadi, Alireza; Shafiee, Abbas

    2013-06-01

    A series of 4-hydroxycoumarin derivatives were designed and synthesized as new acetylcholinesterase (AChE) inhibitors which could be considered for Alzheimer's disease therapeutics. Among the 19 coumarin-derived compounds tested toward Electrophorus electricus acetylcholinesterase (eelAChE) and horse serum butyrylcholinesterase (eqBChE), N-(1-benzylpiperidin-4-yl)acetamide derivative 4m displayed highest AChE inhibitory activity (IC50 = 1.2 μM) and good selectivity (37 times). The docking study of the most potent compound 4m, indicated that Phe330 is responsible for ligand recognition and trafficking by forming π-cation interaction with benzylpiperidine moiety. Furthermore, the formation of an additional π-π interaction between coumarin moiety and Trp279 of peripheral anionic site could stabilize the ligand in the active site resulting in more potent inhibition of the enzyme. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  14. On large amplitude motions of simplest amides in the ground and excited electronic states

    Science.gov (United States)

    Tukachev, N. V.; Bataev, V. A.; Godunov, I. A.

    2016-12-01

    For the formamide, acetamide, N-methylformamide and N-methylacetamide molecules in the ground (S0) and lowest excited singlet (S1) and triplet (T1) electronic states equilibrium geometry parameters, harmonic vibrational frequencies, barriers to conformational transitions and conformer energy differences were estimated by means of MP2, CCSD(T), CASSCF, CASPT2 and MRCI ab initio methods. One-, two- and three-dimensional potential energy surface (PES) sections corresponding to different large amplitude motions (LAM) were calculated by means of MP2/aug-cc-pVTZ (S0) and CASPT2/cc-pVTZ (S1,T1). For these molecules, in each excited electronic state six minima were found on 2D PES sections. Using PES sections, different anharmonic vibrational problems were solved and the frequencies of large amplitude vibrations were determined.

  15. Effects of solution properties on the morphology and diameters of nanofibers fabricated by electrospinning

    Science.gov (United States)

    Jing, Hongjun; Jiang, Yadong; Du, Xiaosong

    2010-10-01

    In this paper, four different series of polymer solutions were presented to study the effects of solution properties on the morphology and diameters of nanofibers, including the polyethersulfone (PES) dissolving in N, N-dimethylformamide, polyvinylpyrrolidone (PVP) in ethanol, poly(acrylic acid) (PAA) in water and poly(vinylidene fluoride) (PVDF) in N, Ndimethyl acetamide. These solutions revealed different conditions of the formation of beads, the spatial structures and the diameter of fibers. The PVDF nanofibers had plenty of small beads on the fibers, while the other three were uniform fibers without beads. The nanofibers of PES, PVP and PVDF showed good three dimensional structures except the PAA fibrous membranes. The change of fiber diameters of PVDF was much larger than that of PVP.

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

    Science.gov (United States)

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

    2014-07-15

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

  17. Auto-Tandem Catalysis in Ionic Liquids: Synthesis of 2-Oxazolidinones by Palladium-Catalyzed Oxidative Carbonylation of Propargylic Amines in EmimEtSO4

    Directory of Open Access Journals (Sweden)

    Raffaella Mancuso

    2016-07-01

    Full Text Available A convenient carbonylative approach to 2-oxazolidinone derivatives carried out using an ionic liquid (1-ethyl-3-methylimidazolium ethyl sulfate, EmimEtSO4 as the solvent is presented. It is based on the sequential concatenation of two catalytic cycles, both catalyzed by the same metal species (auto-tandem catalysis: the first cycle corresponds to the oxidative monoaminocarbonylation of the triple bond of propargylic amines to give the corresponding 2-ynamide intermediates, while the second one involves the cyclocarbonylation of the latter to yield 2-(2-oxooxazolidin-5-ylidene-acetamides. Reactions are carried out using a simple catalytic system consisting of PdI2 in conjunction with an excess of KI, and the catalyst/solvent system could be recycled several times without appreciable loss of activity after extraction of the organic product with Et2O.

  18. SYNTHESIS AND EVALUATION OF OXAZOLIDINONES HAVING BENZO THIAZINEN MOIETIES AS ANTIMICROBIAL AND ANTI-INFLAMMATORY AGENTS

    Directory of Open Access Journals (Sweden)

    Jennifer Fernandes

    2013-08-01

    Full Text Available Phenyl oxazolidinones were prepared from R-glycidyl butarate and Para bromo aniline, further (3-(4-bromophenyl methylene oxazolidine-5yl and substituted benzothiazinen was refluxed resulted in oxazolidinones benzothiazinen moieties. Treatment of these oxazolidinones benzo thiazinen moieties with methane sulfonyl gives its sulphonates on further treatment with sodium azide and tri phenyl phosphine in acetic anhydride gives acetamide derivatives. Further synthesized compounds were characterized by IR, H NMR1 and Mass spectral studies. The synthesized compounds were evaluated for antibacterial activity against Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and antifungal activity against, Candida albicans and Aspergillus niger. The synthesized compound was screened for their anti-inflammatory activity by carrageenan induced paw-edema method.

  19. A carbon-13 NMR spin-lattice relaxation study of the molecular conformation of the nootropic drug 2-oxopyrrolidin-1-ylacetamide

    Science.gov (United States)

    Baldo, M.; Grassi, A.; Guidoni, L.; Nicolini, M.; Pappalardo, G. C.; Viti, V.

    The spin-lattice relaxation times ( T1) of carbon-13 resonances of the drug 2-oxopyrrolidin- 1-ylacetamide ( 2OPYAC) were determined in CDCl 3 + DMSO and H 2O solutions to investigate the internal conformational flexibility. The measured T1s for the hydrogen-bearing carbon atoms of the 2-pyrrolidone ring fragment were diagnostic of a rigid conformation with respect to the acetamide linked moiety. The model of anisotropic reorientation of a rigid body was used to analyse the measured relaxation data in terms of a single conformation. Owing to the small number of T1 data available the fitting procedure for each of the possible conformations failed. The structure corresponding to the rigid conformation was therefore considered to be the one that is strongly stabilized by internal hydrogen bonding as predicted on the basis of theoretical MO ab initio quantum chemical calculations.

  20. 4-Acetamidoanilinium nitrate monohydrate

    Directory of Open Access Journals (Sweden)

    Sana Riahi

    2012-06-01

    Full Text Available In the title hydrated salt, C8H11N2O+·NO3−·H2O, the N—C bond distances [1.349 (2 and 1.413 (2 Å] along with the sum of the angles (359.88° around the acetamide N atom clearly indicate that the heteroatom has an sp2 character. The ammonium group is involved in a total of three N—H...O hydrogen bonds, two of these are with a water molecule, which forms two O—H...O hydrogen bonds. All these hydrogen bonds link the ionic units and the water molecule into infinite planar layers parallel to (100. The remaining two N—H...O interactions in which the ammoniun group is involved link these layers into an infinite three-dimensional network.

  1. Acylguanidine inhibitors of beta-secretase: optimization of the pyrrole ring substituents extending into the S1' substrate binding pocket.

    Science.gov (United States)

    Jennings, Lee D; Cole, Derek C; Stock, Joseph R; Sukhdeo, Mohani N; Ellingboe, John W; Cowling, Rebecca; Jin, Guixian; Manas, Eric S; Fan, Kristi Y; Malamas, Michael S; Harrison, Boyd L; Jacobsen, Steve; Chopra, Rajiv; Lohse, Peter A; Moore, William J; O'Donnell, Mary-Margaret; Hu, Yun; Robichaud, Albert J; Turner, M James; Wagner, Erik; Bard, Jonathan

    2008-01-15

    The proteolytic enzyme beta-secretase (BACE-1) produces amyloid beta (Abeta) peptide, the primary constituent of neurofibrillary plaques, implicated in Alzheimer's disease, by cleavage of the amyloid precursor protein. A small molecule inhibitor of BACE-1, (diaminomethylene)-2,5-diphenyl-1H-pyrrole-1-acetamide (1, BACE-1 IC(50)=3.7 microM), was recently described, representing a new small molecule lead. Initial SAR investigation demonstrated the potential of accessing the nearby S(3) and S(1)(') substrate binding pockets of the BACE-1 enzyme by building substituents off one of the phenyl substituents and guanidinyl functional group. We report here the optimization of guanidinyl functional group substituents on 1, leading to potent submicromolar BACE-1 inhibitors.

  2. Electrodeposition Behavior of Nickel from a Low Temperature Urea-molten Salt

    Institute of Scientific and Technical Information of China (English)

    张启波; 华一新

    2013-01-01

    The electrodeposition behavior of nickel at glassy carbon (GC) and stainless steel (SS) electrodes in low temperature urea-acetamide-NaBr-KBr melt was investigated using cyclic voltammetry, chrono-amperometric current-time transients and scanning electron microscopy. Cyclic voltammograms and dimensionless chronoamperometric current-time transients analysis show that the elec-trodeposition of nickel is an irreversible process and proceeds via three-dimensional progressive nucleation with diffusion-controlled growth on both GC and SS substrates. Scanning electron microscopic analysis indicates the nickel deposits obtained on SS electrode are generally uniform, dense, and adherent to the substrate with rounded crystallites in the nanometer size regime. It is also found that the crystal structure of the electrodeposited nickel is independent on the deposition potential. The nickel deposits produced from the melt at higher cathodic potential exhibit larger grain size.

  3. Synthesis and structure-activity relationship studies of novel [6,6,5] tricyclic oxazolidinone derivatives as potential antibacterial agents.

    Science.gov (United States)

    Xue, Tao; Ding, Shi; Guo, Bin; Chu, Wenjing; Wang, Hui; Yang, Yushe

    2015-01-01

    In our previous Letter, we reported the discovery of a novel benzoxazinyl-oxazolidinone antibacterial candidate 2. In order to identify a potential backup compound, extensive modifications on the B/C ring and C3 side chain were undertaken. A series of novel [6,6,5] tricyclic analogues were synthesized and their in vitro antibacterial activities were tested against a panel of susceptible and resistant Gram-positive pathogens. Among of them, benzothiazinyl-oxazolidinones with acetamide or thioamide as C3 side chains exhibited moderate to good antibacterial activity, such as compounds 54, 58, 59 and 63. In vitro liver microsomal stability was further evaluated and the results manifested that compounds 54 and 58 were both metabolically stable in rat and human liver microsomes. Additionally, insights gained from this investigation should provide directions for the further research of new oxazolidinone antibiotics.

  4. Synthesis, Characterization and Antimicrobial Activities of Some New Heterocyclic Schiff Bases Derived from Thiocarbohydrazide.

    Science.gov (United States)

    El-Mahdy, Kamelia; El-Kazak, Azza; Abdel-Megid, Mohamed; Seada, Magdyand; Farouk, Osama

    2016-01-01

    The reaction of prazolobenzothienopyrimidine-3-carbaldehyde 1 with thiocarbohydrazide afforded the Schiff's base 3. The latter compound reacted with some electrophilic reagents to give 1,2,4-triazoles 4-6 and 1,2,4-triazines 7-9. Treatment of compound 3 with 2-cyano-3,3-bis(methylthio)acrylonitrile gave the corresponding 5-amino-4-cyano-3-methylthiopyrazole derivative 11. The reaction of pyrazole 11 with carbon disulfide afforded dithioxopyrazolopyrimidine 12. Acylation of compound 11 by using acetic anhydride yielded acetamide 13. On the other hand, the cyclocondensation of pyrazole 11 with acetic anhydride in pyridine yielded pyrazolopyrimidine derivative 14. The reactivity of compound 11 towards formamide and phenylisothiocyanate to give the pyrazolopyrimidines 15 and 16 was studied. The newly synthesized compounds were screened for their antimicrobial activity.

  5. A fluorescent probe for zinc detection based on organically functionalized SBA-15

    Science.gov (United States)

    Dong, Zhengping; Dong, Zihao; Wang, Pan; Tian, Xin; Geng, Huamei; Li, Rong; Ma, Jiantai

    2010-11-01

    In this study, highly ordered mesoporous silica material (SBA-15) functionalized with N-(quinoline-8-yl)-2-(3-triethoxysilyl-propylamino)-acetamide (QTPA) as zinc probe has been reported. The anchoring to the surface of the SBA-15 was carried out by the reaction between the precursor and the hydroxyl groups available on the inner surface of the support. The primary ordered mesoporous structure of SBA-15 was well preserved after the grafting procedure. Fluorescence characterization showed that the obtained organic-inorganic hybrid composite displayed highly selective and sensitive to Zn 2+ ion over other cations such as Cd 2+, Pb 2+, Ni 2+ and Co 2+. And the hybrid material has ideal chemical and spectroscopic properties for further biological and environmental applications.

  6. Hybrid chemistry. Part 4: Discovery of etravirine-VRX-480773 hybrids as potent HIV-1 non-nucleoside reverse transcriptase inhibitors.

    Science.gov (United States)

    Wan, Zheng-Yong; Tao, Yuan; Wang, Ya-Feng; Mao, Tian-Qi; Yin, Hong; Chen, Fen-Er; Piao, Hu-Ri; De Clercq, Erik; Daelemans, Dirk; Pannecouque, Christophe

    2015-08-01

    A novel series of etravirine-VRX-480773 hybrids were designed using structure-guided molecular hybridization strategy and fusing the pharmacophore templates of etravirine and VRX-480773. The anti-HIV-1 activity and cytotoxicity was evaluated in MT-4 cell cultures. The most active hybrid compound in this series, N-(2-chlorophenyl)-2-((4-(4-cyano-2,6-dimethylphenoxy)pyrimidin-2-yl)thio)acetamide 3d (EC50=0.24 , SI>1225), was more potent than delavirdine (EC50=0.66 μM, SI>67) in the anti-HIV-1 in vitro cellular assay. Studies of structure-activity relationships established a correlation between anti-HIV activity and the substitution pattern of the acetanilide group.

  7. Kinetics of Oxidation of 3-Benzoylpropionic Acid by N-Bromoacetamide in Aqueous Acetic Acid Medium

    Directory of Open Access Journals (Sweden)

    N. A. Mohamed Farook

    2011-01-01

    Full Text Available The kinetics of oxidation of 3-benzoylpropionic acid (KA with N-bromoacetamide (NBA have been studied potentiometrically in 50:50 (v/v aqueous acetic acid medium at 298 K The reaction was first order each with respect to [KA], [NBA] and [H+]. The main product of the oxidation is the corresponding carboxylic acid. The rate decreases with the addition of acetamide, one of the products of the reaction. Variation in ionic strength of the reaction medium has no significant effect on the rate of oxidation. But the rate of the reaction is enhanced by lowering the dielectric constant of the reaction medium. A mechanism consistent with observed results have been proposed and the related rate law was deduced.

  8. Cation Tuning toward the Inference of the Gelation Behavior of Supramolecular Gels

    Science.gov (United States)

    Xue, Peng; Wu, Huiqiong; Wang, Xiaojuan; He, Ting; Shen, Rujuan; Yue, Fan; Wang, Jide; Zhang, Yi

    2016-01-01

    We serendipitously discovered that the tripeptide Asp–Phe–Phe trifluoroacetic acid salt (hereafter abbreviated as β-AspFF) formed a reversible thermotropic gel in chloroform solution (at temperatures higher than the boiling point of chloroform), and a stable gel in toluene solution (at equal to or lower than the room temperature). Experimental results indicate that doping metal ions into β-AspFF toluene gels can trigger morphological variations in the gel skeleton, thereby increasing gel volume and inducing the collapse of organogels. Investigation on the cation-tuned gelation behavior of β-AspFF can be used to elucidate heating-induced gel collapse (of normal gel) or reverse thermotropic gelation as well as select carbamide and acetamide as activators of β-AspFF gels in chloroform solution at room temperature. PMID:27138527

  9. Cation Tuning toward the Inference of the Gelation Behavior of Supramolecular Gels

    Science.gov (United States)

    Xue, Peng; Wu, Huiqiong; Wang, Xiaojuan; He, Ting; Shen, Rujuan; Yue, Fan; Wang, Jide; Zhang, Yi

    2016-05-01

    We serendipitously discovered that the tripeptide Asp–Phe–Phe trifluoroacetic acid salt (hereafter abbreviated as β-AspFF) formed a reversible thermotropic gel in chloroform solution (at temperatures higher than the boiling point of chloroform), and a stable gel in toluene solution (at equal to or lower than the room temperature). Experimental results indicate that doping metal ions into β-AspFF toluene gels can trigger morphological variations in the gel skeleton, thereby increasing gel volume and inducing the collapse of organogels. Investigation on the cation-tuned gelation behavior of β-AspFF can be used to elucidate heating-induced gel collapse (of normal gel) or reverse thermotropic gelation as well as select carbamide and acetamide as activators of β-AspFF gels in chloroform solution at room temperature.

  10. Modafinil increases histamine release in the anterior hypothalamus of rats.

    Science.gov (United States)

    Ishizuka, Tomoko; Sakamoto, Yasuhiko; Sakurai, Toshimi; Yamatodani, Atsushi

    2003-03-20

    Modafinil, (RS)-2-(Diphenylmethylsulfinyl)acetamide, is a well known wake promoting drug used for the treatment of narcolepsy. We investigated the effect of modafinil on the hypothalamic histamine release in the anesthetized rat using in vivo microdialysis. Modafinil (150 mg/kg, i.p.) increased histamine release by 150% of the basal release. The intracerebroventricular (i.c.v.) injection of modafinil (1 nmol) also increased histamine release, however, when modafinil (1 nmol) was injected directly into the tuberomammillary nucleus, a limited region where cell bodies of the histaminergic neurons are located, histamine release was not altered. These observations suggest that modafinil may promote waking via the activation of the histaminergic system, although it does not appear to be a direct pharmacological target of modafinil.

  11. MODIFICATION OF X-5 RESIN AND ADSORPTION PROPERTY OF THE MODIFIED RESINS

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Three polymeric adsorbents with hydrogen bonding acceptors, methylamine,N-methyl-acetamide and aminotri(hydroxymethyl)methane modified resins are synthesized fromchloromethylated X-5 resin. Adsorption isotherms of phenol and theophylline onto the three modifiedresins and the original X-5 resin from aqueous solution are measured. The results show thatadsorption of compounds with hydrogen bonding donor onto methylamine and N-methylacetamidemodified resins is enhanced as compared with that onto X-5 resin, and adsorption mechanismbetween the adsorbents and the adsorbates is mainly based on hydrogen bonding and hydrophobicinteraction. While adsorption of compounds with hydrogen bonding donor ontoaminotri(hydroxymethyl)methane modified resin is lowered as compared with that onto X-5 resin, andadsorption mechanism between the adsorbent and the adsorbates is mainly based on hydrophobicinteraction.

  12. Visualization of micro glial activation in the L.A.S. by PET molecular imaging: use of a tracer specific of T.S.P.O, the [{sup 18}F]-D.P.A.-714; Visualisation de l'activation microgliale dans la SLA par l'imagerie moleculaire TEP: utilisation d'un traceur specifique des TSPO, le [{sup 18}F]-DPA-714

    Energy Technology Data Exchange (ETDEWEB)

    Tauber, C.; Vercouillie, J.; Le Borgne, A.; Guilloteau, D.; Venel, Y.; Le Pogam, A.; Aesch-Prunier, C.; Corcia, P.; Baulieu, J.L. [CHU de Tours, Inserm U930, medecine nucleaire, 37 (France); Kassiou, M. [Brain and Mind Research Institute, Sydney (Australia)

    2010-07-01

    The [{sup 18}F]-D.P.A.-714 (N, N-diethyl-2-[2-(4-(2-fluoro-ethoxy)phenyl)-5,7-dimethyl-pyrazolo1,5-a] pyrimidine-3-yl]-acetamide) is a new ligand of high affinity of T.S.P.O. (trans-locator proteins [18kDa], current name of Peripheral-type benzodiazepine receptor) expressed during micro glial activation. The aim of this work was to explore the feasibility of the cerebral PET with [{sup 18}F]-D.P.A.-714 and to evaluate the micro glial activation in the lateral amyotrophic scleroses (L.A.S.). PET with this new ligand is feasible in man. The preliminary results do not provide ant argument for a specific micro glial activation in the brain of patients suffering of L.A.S.. (N.C.)

  13. Synthesis and electrochemical performances of LiCoO2 recycled from the incisors bound of Li-ion batteries

    Institute of Scientific and Technical Information of China (English)

    LI Jinhui; ZHONG Shengwen; XIONG Daoling; CHEN Hao

    2009-01-01

    A new LiCoO2 recovery technology for Li-ion batteries was studied in this paper. LiCoO2 was peeled from the Al foil with dimethyl acetamide (DMAC), and then polyvinylidene fluoride (PVDF) and carbon powders in the active material were eliminated by high tempera-1.00. The new LiCoO2 was obtained by calcining the mixture at 850℃ for 12 h in air. The structure and morphology of the recycled powders and resulting samples were studied by XRD and SEM techniques, respectively. The layered structure of LiCoO2 synthesized by adding Li2CO3 is the best, and it is found to have the best characteristics as a cathode material in terms of charge-discharge capacity and cycling mAh.g-1.

  14. Germination Requirements of Bacillus macerans Spores

    Science.gov (United States)

    Sacks, L. E.; Thompson, P. A.

    1971-01-01

    2-Phenylacetamide is an effective germinant for spores of five strains of Bacillus macerans, particularly in the presence of fructose. Benzyl penicillin, the phenyl acetamide derivative of penicillin, and phenylacetic acid are also good germinants. l-Asparagine is an excellent germinant for four strains. α-Amino-butyric acid is moderately effective. Pyridoxine, pyridoxal, adenine, and 2,6-diaminopurine are potent germinants for NCA strain 7X1 only. d-Glucose is a powerful germinant for strain B-70 only. d-Fructose and d-ribose strongly potentiate germination induced by other germinants (except l-asparagine) but have only weak activity by themselves. Niacinamide and nicotinamide-adenine dinucleotide, inactive by themselves, are active in the presence of fructose or ribose. Effects of pH, ion concentration, and temperature are described. PMID:4251279

  15. Discovery of efficient stimulators for adult hippocampal neurogenesis based on scaffolds in dragon's blood.

    Science.gov (United States)

    Liang, Jian-Hua; Yang, Liang; Wu, Si; Liu, Si-Si; Cushman, Mark; Tian, Jing; Li, Nuo-Min; Yang, Qing-Hu; Zhang, He-Ao; Qiu, Yun-Jie; Xiang, Lin; Ma, Cong-Xuan; Li, Xue-Meng; Qing, Hong

    2017-08-18

    Reduction of hippocampal neurogenesis caused by aging and neurological disorders would impair neural circuits and result in memory loss. A new lead compound (N-trans-3',4'-methylenedioxystilben-4-yl acetamide 27) has been discovered to efficiently stimulate adult rats' neurogenesis. In-depth structure-activity relationship studies proved the necessity of a stilbene scaffold that is absent in highly cytotoxic analogs such as chalcones and heteroaryl rings and inactive analogs such as diphenyl acetylene and diphenyl ethane, and validated the importance of an NH in the carboxamide and a methylenedioxy substituent on the benzene ring. Immunohistochemical staining and biochemical analysis indicate, in contrast to previously reported neuroprotective chemicals, N-stilbenyl carboxamides have extra capacity for neuroproliferation-type neurogenesis, thereby providing a foundation for improving the plasticity of the adult mammalian brain. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  16. [Cloning of new acylamidase gene from Rhodococcus erythropolis and its expression in Escherichia coli].

    Science.gov (United States)

    Lavrov, K V; Ianenko, A S

    2013-10-01

    The gene for new Rhodococcus erythropolis TA37 acylamidase, which possesses unique substrate specificity, has been cloned and expressed in E. coli. Substrates for this enzyme are not only simple amides, such as acetamide and propionamide, but also N-substituted amides, such as 4'-nitroacetanilide. The 1431-bp gene was expressed in E. coli BL21 (DE3) cells on pET16b plasmid under the control of a promoter of the φ 10 gene from the T7 phage. The molecular mass of recombinant acylamidase in E. coli was 55 kDa, which corresponded to that of native acylamidase from Rhodococcus erythropolis TA37. Recombinant acylamidase was able to hydrolize N-substituted amides. A search of a nucleotide database and multiple alignment revealed that acylamidase belonged to the Amidase protein family PF01425, but its nucleotide and amino acid sequences differed significantly from those of the described amidases.

  17. Synthesis and in vitro anticancer activity of 2,4-azolidinedione-acetic acids derivatives.

    Science.gov (United States)

    Kaminskyy, Danylo; Zimenkovsky, Borys; Lesyk, Roman

    2009-09-01

    The synthesis and evaluation of anticancer activity of 2,4-thia(imida)zolidinedione-3- and 5-acetic acids amides were described. The structures of compounds were determined by IR, (1)H NMR, and MS analysis. In vitro anticancer activity of these compounds has been tested in National Cancer Institute (NCI) and the relationships between structure and anticancer activity are discussed. Among 2,4-azolidinedione-acetic acids derivatives 2-[5-(4-chlorobenzylidene)-2,4-dioxo-imidazolidin-3-yl]-N-(2-trifluoromethyl-phenyl)-acetamide (Ic) was superior to other related compounds in terms of high selectivity for the leukemia CCRF-CEM (logGI(50)=-6.06), HL-60(TB) (logGI(50)=-6.53), MOLT-4 (logGI(50)=-6.52) and SR (logGI(50)=-6.51) cell lines.

  18. amiA is a negative regulator of acetamidase expression in Mycobacterium smegmatis

    Directory of Open Access Journals (Sweden)

    Turner Jane

    2001-08-01

    Full Text Available Abstract Background The acetamidase of Mycobacterium smegmatis is a highly inducible enzyme. Expression of this enzyme is increased 100-fold when the substrate acetamide is present. The acetamidase gene is found immediately downstream of three open reading frames. Two of these are proposed to be involved in regulation. Results We constructed a deletion mutant in one of the upstream ORFs (amiA. This mutant (Mad1 showed a constitutively high level of acetamidase expression. We identified four promoters in the upstream region using a β-galactosidase reporter gene. One of these (P2 was inducible in the wild-type, but was constitutively active in Mad1. Conclusions These results demonstrate that amiA encodes a negative regulatory protein which interacts with P2. Since amiA has homology to DNA-binding proteins, it is likely that it exerts the regulatory effect by binding to the promoter to prevent transcription.

  19. Cytotoxic diterpenoid pseudodimers from the Korean sponge Phorbas gukhulensis.

    Science.gov (United States)

    Jeon, Ju-eun; Liao, Lijuan; Kim, Heegyu; Sim, Chung J; Oh, Dong-Chan; Oh, Ki-Bong; Shin, Jongheon

    2013-09-27

    Four new cytotoxic diterpenoid pseudodimers (2-5), along with a previously reported one, gukulenin A (1), were isolated from the marine sponge Phorbas gukhulensis collected off the coast of Gagu-do, Korea. These novel compounds, designated gukulenins C-F (2-5), were determined by extensive spectroscopic analyses to be pseudodimers of the gagunins, like gukulenin A. The termini of the tropolone-containing side chains in gukulenins C-E (2-4) were found to have diverse modifications involving acetamides or taurine, whereas gukulenin F (5) was formed from 1 by the ring-opening of a cyclic hemiketal. The relative and absolute configurations were assigned by Murata's and modified Snatzke's methods using a HETLOC experiment and a CD measurement of a dimolybdenum complex, respectively. All of these compounds exhibited significant cytotoxicity against the K562 and A549 cell lines.

  20. Analysis of Pyrolysates for Polysulphoneamide Fiber by Py-GC/MS

    Institute of Scientific and Technical Information of China (English)

    QIAN He-sheng; LIN Dan-li

    2006-01-01

    Pyrolysis of polysulphoneamide fiber has been investigated using pyrolysis gas chromatography-mass spectroscopy at the different temperatures from 420℃ to 750℃. Its compositions of pyrolysates have been analyzed. At 420 ℃,pyrolysis of molecular chain could not completely take place, 12 compounds of pyrolysis have only been identified.When the temperature increases, the compositions of pyrolysate increase sharply. Several compounds, especially sulfur dioxide, benzene, aniline, benzoic acid, 1,4-benzene dicaronitrile, N-phenyl-acetamide, diphenylamine, benzo[g]isoquinoline, N-phenyl-benzamide, N-( 4-cyanophenyl )benzamide, could be formed. The degradation mechanisms which are determined by structure and amount of the thermal decomposition products are described. During pyrolysis, for polysulphoneamide, polymeric chain scissions take place as a successive removal of the monomer units from the polymeric chain. The chain scissions are followed by secondary reactions, which lead to a variety of compounds.Additional reactions can also take place during pyrolysis.

  1. PREPARATION OF POLYSULFONAMIDE AND MODIFIED TITANIUM OXIDE NANOCOMPOSITES BY IN-SITU POLYMERIZATION

    Institute of Scientific and Technical Information of China (English)

    WANG Weitao; LIU Li; DENG Jie; WANG Xiaopeng; TANG Zhiyong

    2006-01-01

    A kind of new nano composite with ultraviolet (UV) ray resistance and high temperature stability was prepared by in-situ polymerization in low temperature. Polysulfonamide (PSA) was synthesized with 4, 4'-diaminodiphenyl sulfone (DDS) and terephthaloyl chloride (TPC) in the common solvent N, N-Dimethyl- -acetamide (DMAc). Nano filler is a certain nano titanium oxide modified by silicon oxide (TMS), which plays the role of UV resistance additives. Properties of the novel composite materials were characterized by Atomic Force microscopy (AFM), thermal gravimetric Analysis (TGA) and Ultraviolet Spectroscopy. AFM had showed the sizes and distributions of TMS particles in the nanocomposite. Ultraviolet Spectroscopy for the nanocomposites showed a large absorption in UV band. TGA showed the decomposition temperature was increased over ten degrees with 0.5% wt TMS for this nanocomposite compared with pure PSA.

  2. Optimization of thienopyrrole-based finger-loop inhibitors of the hepatitis C virus NS5B polymerase.

    Science.gov (United States)

    Martin Hernando, Jose Ignacio; Ontoria, Jesus Maria; Malancona, Savina; Attenni, Barbara; Fiore, Fabrizio; Bonelli, Fabio; Koch, Uwe; Di Marco, Stefania; Colarusso, Stefania; Ponzi, Simona; Gennari, Nadia; Vignetti, Sue Ellen; Del Rosario Rico Ferreira, Maria; Habermann, Jörg; Rowley, Michael; Narjes, Frank

    2009-10-01

    Infections caused by the hepatitis C virus (HCV) are a significant world health problem for which novel therapies are in urgent demand. The NS5B polymerase of HCV is responsible for the replication of viral RNA and has been a prime target in the search for novel treatment options. We had discovered allosteric finger-loop inhibitors based on a thieno[3,2-b]pyrrole scaffold as an alternative to the related indole inhibitors. Optimization of the thienopyrrole series led to several N-acetamides with submicromolar potency in the cell-based replicon assay, but they lacked oral bioavailability in rats. By linking the N4-position to the ortho-position of the C5-aryl group, we were able to identify the tetracyclic thienopyrrole 40, which displayed a favorable pharmacokinetic profile in rats and dogs and is equipotent with recently disclosed finger-loop inhibitors based on an indole scaffold.

  3. Design of benzothiazole-1,3,4-thiadiazole conjugates: synthesis and anticonvulsant evaluation.

    Science.gov (United States)

    Siddiqui, Nadeem; Ahuja, Priya; Malik, Sachin; Arya, Satish K

    2013-11-01

    Various 2-[(6-substituted-1,3-benzothiazol-2-yl)amino]-N-[5-substituted-phenyl-1,3,4-thiadiazol-2-yl]acetamides were synthesized with a prospective exploration of "lead hopping", using pharmacophoric elements for in vivo anticonvulsant activity. This yielded three potent candidates (5i, 5t, and 5u) in the preliminary screening employing the maximal electroshock seizure (MES) and the subcutaneous pentylenetetrazole (scPTZ) test, showing minimal neurotoxicity. Their quantitative study indicated an increase of nearly 2-10 times for the MES test and 7- to 67-fold for the scPTZ test in the protective index, the keystone in drug discovery for anticonvulsant activity.

  4. Synthesis and in vitro Evaluation of New Benzothiazole Derivatives as Schistosomicidal Agents

    Directory of Open Access Journals (Sweden)

    Mona A Mahran

    2007-03-01

    Full Text Available A series of benzothiazol-2-yl-dithiocarbamates 3a-d along with their copper complexes 4a-c were synthesized via the reaction of suitable alkyl, aralkyl or heteroaryl halides with the sodium salt of benzothiazol-2-yl-dithiocarbamic acid, followed by complexation with copper sulphate. N-(4-Acetyl-5-aryl-4,5-dihydro-1,3,4-thiadiazol-2-yl-N-benzothiazol-2-yl-acetamides 7a-c were synthesized by cyclization of the appropriate thiosemicarbazones 6a-c in acetic anhydride. Selected compounds were screened for in vitro schistosomicidal activity against Schistosoma mansoni at three different dosage levels (10, 50 and 100 μg/ mL. Three of these products, 4a-c, showed schistosomicidal activity similar to praziquantel, with 100% worm mortality at 10 μg/mL. These compounds would constitute a new class of potent schistosomicidal agents.

  5. Volatiles, a glutarimide alkaloid and antimicrobial effects of Croton pullei (Euphorbiaceae).

    Science.gov (United States)

    Peixoto, Rosana N S; Guilhon, Giselle M S P; das Graças B Zoghbi, Maria; Araújo, Isabella S; Uetanabaro, Ana Paula T; Santos, Lourivaldo S; do S B Brasil, Davi

    2013-03-12

    Chemical investigation of Croton pullei (Euphorbiaceae) collected in the Brazilian Amazon region was revisited. The chemical composition of the essential oils of leaves and stems was analyzed by GC/MS. It was found that both the oils comprise mainly terpenes, among which linalool was the major one (24.90 and 39.72%, respectively). Phytochemical investigation of the stem methanol extract led to the isolation of a new natural product from the glutarimide alkaloid group named N-[2,6-dioxo-1-(2-phenylethyl)-3-piperidinyl]-acetamide, confirming that C. pullei is a rich source of this class of alkaloids. The hexane and methanol extracts of the stems of C. pullei showed moderate antibacterial and antifungal activity and the highest inhibition was observed when the methanol extract was tested against Staphylococcus aureus CCMB 262 and CCMB 263.

  6. PREPARATION OF POLYSULFONAMIDE/TiO2 NANOCOMPOSITES BY SOL-GEL

    Institute of Scientific and Technical Information of China (English)

    WANG Xiaopeng; WANG Weitao; MA Ji; DENG Jie; LIU Li

    2006-01-01

    Polysulfonamide (PSA) was synthesized at room temperature, the polymerization based on terephthaloyl chloride and 3,3 '-diaminodiphenylsulfone in the common solvent N,N -Dimethyl-acetamide (DMAc). Polysulfonamide/titanium oxide nanocomposites were prepared by sol-gel method. Tetrabutyl titanate(TBT) was added into the polysulfonamide solution, at the same time ,some water was mixed to make the TBT hydrolyze. In the process, hydrochloric acid was used to catalyze the reaction. The polysulfonamide chemistry structure was characterized by FT-IR spectrum. Atomic force microscopy (AFM) was employed to observe the microstructure of the composite film. The thermal property was investigated by TGA.The results show that we have succeeded to synthesize the polysulfonamide, TiO2particles were well distributed in the composite film and average size was about 20 nm on average, the heat-resistance of nanocomposite was batter than the pure polysulfonamide.

  7. Enantioselective Degradation of Rac-Metolachlor and S-Metolachlor in Soil

    Institute of Scientific and Technical Information of China (English)

    MA Yun; LIU Wei-Ping; WEN Yue-Zhong

    2006-01-01

    Separation of chiral enantiomers and the dissipation of rac-metolachlor and S-metolachlor in soil were evaluated using achiral high-performance liquid chromatography (HPLC) and chiral gas chromatography (GC) methods. Under the experimental conditions the possible metabolite was considered to be N-(2-ethyl-6-methyl-phenyl)-2-hydroxy-acetamide.Because of the presence of two chiral elements (asymmetrically substituted carbon and chiral axis), the baseline separation of metolachlor enantiomers was not achieved. S-metolachlor degraded faster in soil than rac-metolachlor. After a 42-day incubation, 73.4% of rac-metolachlor and 90.0% of S-metolachlor were degraded. However, due to the absence of biological processes the degradation process in sterilized soil showed no enantioselectivity. The results indicated that enantioselective degradations could greatly affect the environmental fate of metolachlor and should be considered when the environmental behavior of these compounds was assessed.

  8. FTIR Study of Enhanced Polymeric Blend Membrane with Amines

    Directory of Open Access Journals (Sweden)

    Asim Mushtaq

    2014-03-01

    Full Text Available In this study, research will be carried out to identify the functional group behavior of glassy and rubbery polymeric blend membrane with amines. Polymeric blend membranes with different blending ratios were prepared and the developed membranes were characterized by FTIR to see the effect of blend ratio on different functional groups. The developed membranes are flat dense sheet membrane of 20% wt/wt. The pure and blend membrane polysulfone, polyethersulfone, polyvinyl acetate with different composition, with 10% methyl diethanol amine, mono ethanol amine, diethanol amine are developed with dimethyl acetamide solvent. Fourier Transform Infrared (FTIR spectroscopy was utilized to study the interaction between two polymers and to analyze the type of bonding present. To observed frequencies were assigned to various mode of vibration in terms of fundamentals and combination. These spectral changes indicated the existence of molecular interaction among the enhanced polymeric blends; highlight the compatible nature among each other.

  9. Multifaceted characterization of cell wall decomposition products formed during ammonia fiber expansion (AFEX) and dilute acid based pretreatments.

    Science.gov (United States)

    Chundawat, Shishir P S; Vismeh, Ramin; Sharma, Lekh N; Humpula, James F; da Costa Sousa, Leonardo; Chambliss, C Kevin; Jones, A Daniel; Balan, Venkatesh; Dale, Bruce E

    2010-11-01

    Decomposition products formed/released during ammonia fiber expansion (AFEX) and dilute acid (DA) pretreatment of corn stover (CS) were quantified using robust mass spectrometry based analytical platforms. Ammonolytic cleavage of cell wall ester linkages during AFEX resulted in the formation of acetamide (25mg/g AFEX CS) and various phenolic amides (15mg/g AFEX CS) that are effective nutrients for downstream fermentation. After ammonolysis, Maillard reactions with carbonyl-containing intermediates represent the second largest sink for ammonia during AFEX. On the other hand, several carboxylic acids were formed (e.g. 35mg acetic acid/g DA CS) during DA pretreatment. Formation of furans was 36-fold lower for AFEX compared to DA treatment; while carboxylic acids (e.g. lactic and succinic acids) yield was 100-1000-fold lower during AFEX compared to previous reports using sodium hydroxide as pretreatment reagent. Copyright 2010 Elsevier Ltd. All rights reserved.

  10. Millimeter and Submillimeter Wave Spectra of N-Methylformamide and Propionamide

    Science.gov (United States)

    Mescheryakov, A. A.; Alekseev, E. A.; Ilyushin, V.; Motiyenko, R. A.; Margulès, L.

    2014-06-01

    We present the rotational spectra studies of two acetamide conjugated molecules, namely, N-methylformamide (CH_3NHCHO) and propionamide (CH_3CH_2CONH_2). New measurements have been performed in the frequency range 50 - 150 GHz using the spectrometer in Kharkov, and in the frequency range 150 - 630 GHz using the spectrometer in Lille. The analysis of the rotational spectra of both molecules is complicated by the methyl top internal rotation and nuclear quadrupole hyperfine structure. In case of N-methylformamide the barrier to internal rotation is relatively small, V_3 = 51.7 wn, whereas for propionamide the barrier is high, V_3 = 751.9 wn. For propionamide the presence of the low-lying excited vibrational state (60 wn) makes difficult the analysis within the classical rho-axis method Hamiltonian. In this case only the rotational transitions with K_aFrench CNRS-PICS 6051 project.

  11. Measurement and Correlation for Solubility of Dimethyl-2,6-naphthalene Dicarboxylate in Organic Solvents%2,6-萘二甲酸二甲酯在有机溶剂中溶解度的测定与关联

    Institute of Scientific and Technical Information of China (English)

    夏清; 马沛生

    2007-01-01

    Solubility of dimethyl-2,6-naphthalene dicarboxylate in acetic acid,N,N-dimethyl acetamide,dimethyl sulphoxide,and N-methyl-2-ketopyrrolidine were determined using a dynamic method.The measured systems were correlated by UNIFAC group contribution method.A new main group (atomatic ester, ACCOO) was defined to express the activity coefficients of the aromatic ester.New interaction parameters of the ACCOO group were expressed as the first-order function of temperature and were determined from the experimental data.The calculated results for the new interaction parameters were satisfactory.The measured systems were also correlated with the Wilson and λ-h models,and the results were compared with those of the UNIFAC model.

  12. Rapid screening of phytosterols in orange juice by solid-phase microextraction on polyacrylate fibre derivatisation and gas chromatographic-mass spectrometric.

    Science.gov (United States)

    Balme, Sébastien; Gülaçar, Fazil O

    2012-05-01

    The potential of solid-phase microextraction on polyacrylate coated fibre, with sequential or simultaneous trimethylsilyl derivatisation followed by gas chromatographic-mass spectrometric analysis, was evaluated for a rapid determination of the distribution of the phytosterols in aqueous food matrixes. Influences of different parameters (bis(trimethylsilyl)trifluoro-acetamide and sterol exposure time, sterol concentration and experimental protocol) on the recovery of sterols were investigated to determine optimum conditions which were tested for sterol extraction and analysis from orange juice. Best selectivity, sterol recovery and derivatisation yields were obtained by extraction and simultaneous derivatisation through immersion of the SPME-PA fibre in the orange juice (10min, 65°C) after headspace absorption of BSTFA (30min, 65°C) on the fibre. Nevertheless the method developed cannot be used for quantitative analysis. But the possibility to effect rapid screen of phytosterol containing in complex media have been shown.

  13. 4'-Acetamidochalcone Derivatives as Potential Antinociceptive Agents

    Directory of Open Access Journals (Sweden)

    Valdir Cechinel-Filho

    2007-04-01

    Full Text Available Nine acetamidochalcones were synthesized and evaluated as antinociceptive agents using the mice writhing test. Given intraperitoneally all the compounds were more effective than the two reference analgesic drugs (acetylsalicylic acid and acetaminophen used for comparison. N-{4-[(2E-3-(4-nitrophenylprop-2-enoyl]phenyl}acetamide (6 was the most effective compound and was therefore selected for more detailed studies. It caused dose-related inhibition in the writhing test, being about 32 to 34-fold more potent than the standard drugs. It was also effective in the second phase of the formalin test and the capsaicin test. These acetamidochalcones, especially compound 6, might be further used as models to obtain new and more potent analgesic drugs.

  14. Volatiles, A Glutarimide Alkaloid and Antimicrobial Effects of Croton pullei (Euphorbiaceae

    Directory of Open Access Journals (Sweden)

    Lourivaldo S. Santos

    2013-03-01

    Full Text Available Chemical investigation of Croton pullei (Euphorbiaceae collected in the Brazilian Amazon region was revisited. The chemical composition of the essential oils of leaves and stems was analyzed by GC/MS. It was found that both the oils comprise mainly terpenes, among which linalool was the major one (24.90 and 39.72%, respectively. Phytochemical investigation of the stem methanol extract led to the isolation of a new natural product from the glutarimide alkaloid group named N-[2,6-dioxo-1-(2-phenylethyl-3-piperidinyl]-acetamide, confirming that C. pullei is a rich source of this class of alkaloids. The hexane and methanol extracts of the stems of C. pullei showed moderate antibacterial and antifungal activity and the highest inhibition was observed when the methanol extract was tested against Staphylococcus aureus CCMB 262 and CCMB 263.

  15. Detection and Quantification of Nitrogen Compounds in the First Drilled Martian Solid Samples by the Sample Analysis at Mars (SAM) Instrument Suite on the Mars Science Laboratory (MSL)

    Science.gov (United States)

    Stern, J. C.; Navarro-Gonzales, R.; Freissinet, C.; McKay, C. P.; Archer, P. D., Jr.; Buch, A.; Brunner, A. E.; Coll, P.; Eigenbrode, J. L.; Franz, H. B.; Glavin, D. P.; McAdam, A. C.; Ming, D.; Steele, A.; Sutter, B.; Szopa, C.; Wray, J. J.; Conrad, P.; Mahaffy, P. R.

    2014-01-01

    The Sample Analysis at Mars (SAM) instrument suite on the Mars Science Laboratory (MSL) Curiosity Rover detected both reduced and oxidized nitrogen-bearing compounds during the pyrolysis of surface materials at Yellowknife Bay in Gale Crater. Preliminary detections of nitrogen species include NO, HCN, ClCN, CH3CN, and TFMA (trifluoro-N-methyl-acetamide). Confirmation of indigenous Martian N-bearing compounds requires quantifying N contribution from the terrestrial derivatization reagents (e.g. N-methyl-N-tertbutyldimethylsilyltrifluoroacetamide, MTBSTFA and dimethylformamide, DMF) carried for SAM's wet chemistry experiment that contribute to the SAM background. Nitrogen species detected in the SAM solid sample analyses can also be produced during laboratory pyrolysis experiments where these reagents are heated in the presence of perchlorate, a compound that has also been identified by SAM in Mars solid samples.

  16. SYNTHESIS, COMPUTATIONAL STUDY AND PRELIMINARY PHARMACOLOGICAL EVALUATION OF 2-[4-(2-CHLOROBENZYL/BENZOYL SUBSTITUTED PIPERAZIN-1-YL]-N-PHENYLACETAMIDE: POTENTIAL ANTIPSYCHOTICS

    Directory of Open Access Journals (Sweden)

    Tomar Amita

    2011-06-01

    Full Text Available Benzyl and benzoyl substituted acetamides have been synthesized and evaluated as potential antipsychotic agents. The target compounds (4a-b were prepared by reaction of substituted anilines with chloroacetylchloride which further treated with 2-chlorobenzyl or 2-chlorobenzoyl piperazine in presence of potassium carbonate and potassium iodide as catalyst in acetonitrile. The structures of the target compounds (4a-b were characterized on the basis of their M.P., TLC, IR and 1H-NMR data. Computational studies of target compounds (4a-b were carried out by using software programs. The target compounds showed good similarity with respect to standard drugs. The target compounds (4a-b showed inhibition of 5-HTP induced head twitches behavior and low induction of catalepsy in mice.

  17. Effects of the organic matter from swine wastewater on the adsorption and desorption of alachlor in soil.

    Science.gov (United States)

    Dal Bosco, Tatiane C; Sampaio, Silvio C; Coelho, Silvia R M; Cosmann, Natássia J; Smanhotto, Adriana

    2012-01-01

    The application of swine wastewater to the soil for agricultural purposes results in the addition of total and dissolved organic matter to the soil, which may interfere with the dynamics of pesticides in the soil. The objective of this study was to evaluate the effects of the application of total and dissolved organic matter from a biodigester and a treatment lagoon of swine wastewater in the adsorption and desorption of alachlor [2-chloro-2,6-diethyl-N(methoxymethyl acetamide)]. The assay was performed by the batch equilibrium method, and the results were fitted to the Freundlich model. The curve comparison test revealed a greater adsorption of alachlor in the soil treated with swine wastewater from the biodigester. The adsorption and desorption of alachlor increased in the soils where swine wastewater was added, and hysteresis was observed in all of the treatments.

  18. A novel analytical procedure for assaying lysozyme activity using an end-blocked chitotetraose derivative as substrate.

    Science.gov (United States)

    Ogata, Makoto; Matsui, Megumi; Kono, Haruka; Matsuzaki, Yuka; Kato, Yuna; Usui, Taichi

    2017-09-23

    An end-modified β-d-galactosyl chitotetraose derivative [4(4)-O-β-d-galactosyl-β-tri-N-acetylchitotriosyl 2-acetamide-2,3-dideoxy-glucopyranose; Gal(GlcN)3D] was designed and synthesized from chitin tetrasaccharide. The derivative was chemically modified by dehydration of the reducing end GlcN and enzymatic addition of a Gal group to the non-reducing end GlcN. Hydrolysis of Gal(GlcN)3D and related compounds using hen egg-white lysozyme was then examined. Gal(GlcN)3D was specifically cleaved to Gal(GlcN)2 and GlcND. Kinetic studies and docking simulations were further conducted to elucidate its mode of binding to lysozyme. These analyses revealed the binding of Gal(GlcN)3D to lysozyme is more favorable than that of (GlcN)4D. We conclude the 4-O-substituted Gal group at the non-reducing end of Gal(GlcN)3D does not prohibit the action of lysozyme, but gives some affinity to the subsite (i.e. equivalent to GlcN). From these results, a new assay method for quantifying lysozyme was established by utilizing the Morgan-Elson reaction based on the generation of product D (2-acetamide-2,3-dideoxy-glucopyranose), which serves as a chromophore, formed from Gal(GlcN)3D by lysozyme through a conjugated reaction involving β-N-acetylhexosaminidase. The assay system gave a linear dose-response curve in the range of 2-31 μg of lysozyme during a 15 min incubation. This novel assay method for the quantification of lysozyme is highly specific, sensitive, accurate and reproducible. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. A comparison of chemical shift sensitivity of trifluoromethyl tags: optimizing resolution in {sup 19}F NMR studies of proteins

    Energy Technology Data Exchange (ETDEWEB)

    Ye, Libin; Larda, Sacha Thierry; Frank Li, Yi Feng [University of Toronto, UTM, Department of Chemistry (Canada); Manglik, Aashish [Stanford University School of Medicine, Department of Molecular and Cellular Physiology (United States); Prosser, R. Scott, E-mail: scott.prosser@utoronto.ca [University of Toronto, UTM, Department of Chemistry (Canada)

    2015-05-15

    The elucidation of distinct protein conformers or states by fluorine ({sup 19}F) NMR requires fluorinated moieties whose chemical shifts are most sensitive to subtle changes in the local dielectric and magnetic shielding environment. In this study we evaluate the effective chemical shift dispersion of a number of thiol-reactive trifluoromethyl probes [i.e. 2-bromo-N-(4-(trifluoromethyl)phenyl)acetamide (BTFMA), N-(4-bromo-3-(trifluoromethyl)phenyl)acetamide (3-BTFMA), 3-bromo-1,1,1-trifluoropropan-2-ol (BTFP), 1-bromo-3,3,4,4,4-pentafluorobutan-2-one (BPFB), 3-bromo-1,1,1-trifluoropropan-2-one (BTFA), and 2,2,2-trifluoroethyl-1-thiol (TFET)] under conditions of varying polarity. In considering the sensitivity of the {sup 19}F NMR chemical shift to the local environment, a series of methanol/water mixtures were prepared, ranging from relatively non-polar (MeOH:H{sub 2}O = 4) to polar (MeOH:H{sub 2}O = 0.25). {sup 19}F NMR spectra of the tripeptide, glutathione ((2S)-2-amino-4-{[(1R)-1-[(carboxymethyl)carbamoyl] -2-sulfanylethyl]carbamoyl}butanoic acid), conjugated to each of the above trifluoromethyl probes, revealed that the BTFMA tag exhibited a significantly greater range of chemical shift as a function of solvent polarity than did either BTFA or TFET. DFT calculations using the B3LYP hybrid functional and the 6-31G(d,p) basis set, confirmed the observed trend in chemical shift dispersion with solvent polarity.

  20. Synthesis and biological evaluation of Schiff bases and azetidinones of 1-naphthol

    Directory of Open Access Journals (Sweden)

    Sushil Kumar

    2012-01-01

    Full Text Available Introduction: Schiff bases and azetidinones form an important structural class possessing wide spectrum of biological activities that include antibacterial and antifungal activity. A series of Schiff′s bases N′-(substituted benzylidene-2-(naphthalen-1-yloxy acetohydrazides (3a-f and azetidinones N-[3-chloro-2-oxo-4-(substituted phenyl-azetidin-1-yl]-2-(naphthalen-1-yloxy acetamides (4a-b were synthesized and tested for antimicrobial activity. Materials and Methods: The chemical structures of synthesized compounds were elucidated on the basis of IR and 1H NMR spectroscopy. The synthesized compounds were screened for antibacterial activity against E. coli (ESS 2231 and B. subtilis (MTCC 441. The compounds were also tested for antifungal activity against A. niger (NCIM 618 and C. albicans (NCIM 3557 by the cup diffusion method. Results and Discussion: The in vitro antimicrobial activity results showed that the N-[3-chloro-2-oxo-4-(4-substitutedphenyl-azetidin-1-yl]-2-(naphthalen-1-yloxy acetamides (4a-b exhibited better antibacterial activity than the synthesized N′-(substituted benzylidene-2-(naphthalen-1-yloxy-acetohydrazides (3a-f. Compound (4b displayed potent antibacterial activity against the B. subtilis and E. coli (MIC values of 16-64 μg/mL. The antifungal activity of the synthesized compounds (3a-f and 4a-b against the A. niger and C. albicans was relatively weak, most of the compounds showed poor activities (MIC >128μg/mL. Conclusion: The antibacterial activity of the synthesized compounds was moderate to low and antifungal activity was relatively weak. Therefore, a further study with this class of compounds is necessary to elucidate the mechanism and structure activity relationship.

  1. Changes in the metabolome of rats after exposure to arginine and N-carbamylglutamate in combination with diquat, a compound that causes oxidative stress, assessed by 1H NMR spectroscopy.

    Science.gov (United States)

    Liu, Guangmang; Xiao, Liang; Cao, Wei; Fang, Tingting; Jia, Gang; Chen, Xiaoling; Zhao, Hua; Wu, Caimei; Wang, Jing

    2016-02-01

    Numerous factors can induce oxidative stress in animal production and lead to growth retardation, disease, and even death. Arginine and N-carbamylglutamate can alleviate the effects of oxidative stress. However, the systematic changes in metabolic biochemistry linked to oxidative stress and arginine and N-carbamylglutamate treatment remain largely unknown. This study aims to examine the effects of arginine and N-carbamylglutamate on rat metabolism under oxidative stress. Thirty rats were randomly divided into three dietary groups (n = 10 each). The rats were fed a basal diet supplemented with 0 (control), 1% arginine, or 0.1% N-carbamylglutamate for 30 days. On day 28, the rats in each treatment were intraperitoneally injected with diquat at 12 mg per kg body weight or sterile solution. Urine and plasma samples were analyzed by metabolomics. Compared with the diquat group, the arginine + diquat group had significantly lower levels of acetamide, alanine, lysine, pyruvate, tyrosine, α-glucose, and β-glucose in plasma; N-carbamylglutamate + diquat had higher levels of 3-hydroxybutyrate, 3-methylhistidine, acetone, allantoin, asparagine, citrate, phenylalanine, trimethylamine-N-oxide, and tyrosine, and lower levels of low density lipoprotein, lipid, lysine, threonine, unsaturated lipid, urea, and very low density lipoprotein (P carbamylglutamate + diquat group had significantly higher levels of allantoin, citrate, homogentisate, phenylacetylglycine, α-ketoglutarate, and β-glucose while lower levels of acetamide, acetate, acetone, benzoate, citrulline, ethanol, hippurate, lactate, N-acetylglutamate, nicotinamide, ornithine, and trigonelline (P carbamylglutamate can alter the metabolome associated with energy metabolism, amino acid metabolism, and gut microbiota metabolism under oxidative stress.

  2. Interactions of melatonin and its metabolites with the ABTS cation radical: extension of the radical scavenger cascade and formation of a novel class of oxidation products, C2-substituted 3-indolinones.

    Science.gov (United States)

    Rosen, Joachim; Than, Ni Ni; Koch, Dorothea; Poeggeler, Burkhard; Laatsch, Hartmut; Hardeland, Rüdiger

    2006-11-01

    Melatonin had previously been shown to reduce up to four 2,2'-azino-bis-(3-ethylbenzthiazoline-6-sulfonic acid) cation radicals (ABTS*+) via a scavenger cascade ending with N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK). However, when melatonin is added to the reaction system in much lower quantities than ABTS*+, the number of radicals scavenged per melatonin molecule is considerably higher and can attain a value of ten. Under conditions allowing for such a stoichiometry, novel products have been detected which derive from AFMK (1). These were separated by repeated chromatography and the major compounds were characterized by spectroscopic methods, such as mass spectrometry (HPLC-MS, EI-MS and ESI-HRMS), 1H nuclear magnetic resonance (NMR) and 13C NMR, heteronuclear multiple bond connectivity (HMBC) correlations. The identified substances are formed by re-cyclization and represent 3-indolinones carrying the side chain at C2; the N-formyl group can be maintained, but deformylated analogs seem to be also generated, according to MS. The primary product from AFMK (1) is N-(1-formyl-5-methoxy-3-oxo-2,3-dihydro-1H-indol-2-ylidenemethyl)-acetamide (2), which is obtained after purification as E- and Z-isomers (2a, 2b); a secondary product has been identified as N-(1-formyl-2-hydroxy-5-methoxy-3-oxo-2,3-dihydro-1H-indol-2-ylmethyl)-acetamide (3). When H2O2 is added to the ABTS*+ reaction mixture in quantities not already leading to substantial reduction of this radical, compound 3 is isolated as the major product, whereas 2a and 2b are virtually absent. The substances formed differ from all previously known oxidation products which derive from melatonin and are, among these, the first 3-indolinones. Moreover, the aliphatic side chain at C2 is reminiscent of other substances which have been synthesized in the search for melatonin receptor ligands.

  3. Novel cycloheximide derivatives targeting the moonlighting protein Mip exhibit specific antimicrobial activity against Legionella pneumophila

    Directory of Open Access Journals (Sweden)

    Janine eRasch

    2015-03-01

    Full Text Available Mip (macrophage infectivity potentiator and Mip-like proteins are virulence factors in a wide range of pathogens including Legionella pneumophila. These proteins belong to the FK506 binding protein (FKBP family of peptidyl-prolyl-cis/trans-isomerases (PPIases. In L. pneumophila the PPIase activity of Mip is required for invasion of macrophages, transmigration through an in vitro lung-epithelial barrier, and full virulence in the guinea pig infection model. Additionally, Mip is a moonlighting protein that binds to collagen IV in the extracellular matrix. Here, we describe the development, and synthesis of cycloheximide derivatives with adamantyl moieties as novel FKBP ligands, and analyze their effect on the viability of L. pneumophila and other bacteria. All compounds efficiently inhibited PPIase activity of the prototypic human FKBP12 as well as Mip with IC50-values as low as 180 nM and 1.7 µM, respectively. Five of these derivatives inhibited the growth of L. pneumophila at concentrations of 30 to 40 µM, but exhibited no effect on other tested bacterial species indicating a specific spectrum of antibacterial activity. The derivatives carrying a 3,5‐dimethyladamantan‐1‐[yl]acetamide substitution (MT_30.32, and a 3‐ethyladamantan‐1‐[yl]acetamide substitution (MT_30.51 had the strongest effects in PPIase- and liquid growth assays. MT_30.32 and MT_30.51 were also inhibitory in macrophage infection studies without being cytotoxic. Accordingly, by applying a combinatorial approach we were able to generate novel, hybrid inhibitors consisting of cycloheximide and adamantane, two known FKBP inhibitors that interact with different parts of the PPIase domain, respectively. Interestingly, despite the proven Mip-inhibitory activity, the viability of a Mip-deficient strain was affected to the same degree as its wild type. Hence, we also propose that cycloheximide derivatives with adamantyl moieties are potent PPIase inhibitors with multiple

  4. Cytochrome P450 enzymes involved in the metabolic pathway of the histamine 2 (H2)-receptor antagonist roxatidine acetate by human liver microsomes.

    Science.gov (United States)

    Sasaki, M; Nakayama, M; Numazawa, S; Oguro, T; Honma, S; Iwamura, S; Tsukamoto, K; Yoshida, T

    2001-01-01

    Roxatidine acetate hydrochloride (ROX, 2-acetoxy-N-[3-[m-(1-piperidinylmethyl)phenoxy]propyl]acetamide hydrochloride, CAS 78273-80-0), a histamine 2 (H2)-receptor antagonist, has been clinically applied for the treatment of gastritis, gastric and duodenal ulcers. There is no report on the identification of the metabolic enzyme of M-1 (2-hydroxy-N-[3-[m-(1-piperidinylmethyl)phenoxy]propyl]acetamide), the pharmacologically active metabolite, in humans. In this study, the Cytochrome P450 (CYP or P450) enzymes which participate in the metabolism of ROX were identified using human liver microsomes and S9 fractions. M-1 was converted to M-4 (3-[m-(1-piperidinyl-methyl)phenoxy]propylamine) by the enzyme reaction with the S9 but not with microsomes. M-4 was further metabolized to M-5 (3-[m-(1-piperidinylmethyl)phenoxy]propanol) by microsomes. The metabolism was inhibited by coumarin and anti-CYP2A1 serum. (3-[m-(1-piperidinylmethyl)-phenoxy]propionic acid) and M-3 (m-(1-piperidinylmethyl) phenol) formation from M-5 were inhibited by quinidine and anti-CYP2D6 serum. Moreover, M-5 was converted to M-2 and M-3 by cDNA-expressed CYP2D6. In conclusion, this study shows that microsomal enzymes do not participate in the clearance of the active metabolite M-1, CYP2A6 primarily catalyzes M-5 formation from M-4, and CYP2D6 primarily catalyzes M-2 and M-3 formation from M-5 in humans.

  5. Reasonable Selection for Streptomyces Spiramyceticus%螺旋链霉菌的推理选育

    Institute of Scientific and Technical Information of China (English)

    邹娟; 叶蕊芳; 郑黎; 吴阳; 张立; 戴维

    2011-01-01

    以螺旋链霉菌25-1为出发菌株,分别采用紫外线(UV)、Co60射线、甲基磺酸乙酯(EMS)、氯化锂(LiCl)、UV+LiCl、亚硝基胍(NTG)+UV进行诱变筛选,比较各方法的致死率、正变率、最大提高幅度及对传代稳定性的影响,结果发现UV、Co60射线、UV+LiCl 3种方法对螺旋链霉茵的诱变效果较好,化学诱变剂对螺旋链霉菌的稳定性影响较大;同时采用丙二酸钠和乙酰胺进行高通量筛选,丙二酸钠不但筛选效果好,且对效价有一定的促进作用,乙酰胺对菌株稳定性有一定的影响.%With Streptomyces spiramyceticus 25-1 as primitive strain, ultraviolet (UV), Co60-ray, ethyl methane sulphonate (EMS), lithium chloride (LiCl), UV+LiCl, nitrosoguanidine (NTG)+UV were used for mutation screening. By comparing the death rate, positive rate, maximum improve percentage and the stability, UV, Co60-ray and UV+LiCl exhibited better mutation effect on Streptomyces spiramyceticus, and chemical mutagenesis was not good for the stability. In addition, malonate sodium and acetamide were used for highthroughput screening. The result showed that, malonate sodium could not only screen the strains well, but also promote the titer to a certain degree, while acetamide exerted some influence on the stability of the strains.

  6. A comparative autoradiography study in post mortem whole hemisphere human brain slices taken from Alzheimer patients and age-matched controls using two radiolabelled DAA1106 analogues with high affinity to the peripheral benzodiazepine receptor (PBR) system.

    Science.gov (United States)

    Gulyás, Balázs; Makkai, Boglárka; Kása, Péter; Gulya, Károly; Bakota, Lidia; Várszegi, Szilvia; Beliczai, Zsuzsa; Andersson, Jan; Csiba, László; Thiele, Andrea; Dyrks, Thomas; Suhara, Tetsua; Suzuki, Kazutoshi; Higuchi, Makato; Halldin, Christer

    2009-01-01

    The binding of two radiolabelled analogues (N-(5-[125I]Iodo-2-phenoxyphenyl)-N-(2,5-dimethoxybenzyl)acetamide ([125I]desfluoro-DAA1106) and N-(5-[125I]Fluoro-2-phenoxyphenyl)-N-(2-[125I]Iodo-5-methoxybenzyl)acetamide ([125I]desmethoxy-DAA1106) of the peripheral benzodiazepine receptor (PBR) (or TSPO, 18kDa translocator protein) ligand DAA1106 was examined by in vitro autoradiography on human post mortem whole hemisphere brain slices obtained from Alzheimer's disease (AD) patients and age-matched controls. Both [(125)I]desfluoro-IDAA1106 and [(125)I]desmethoxy-IDAA1106 were effectively binding to various brain structures. The binding could be blocked by the unlabelled ligand as well as by other PBR specific ligands. With both radiolabelled compounds, the binding showed regional inhomogeneity and the specific binding values proved to be the highest in the hippocampus, temporal and parietal cortex, the basal ganglia and thalamus in the AD brains. Compared with age-matched control brains, specific binding in several brain structures (temporal and parietal lobes, thalamus and white matter) in Alzheimer brains was significantly higher, indicating that the radioligands can effectively label-activated microglia and the up-regulated PBR/TSPO system in AD. Complementary immunohistochemical studies demonstrated reactive microglia activation in the AD brain tissue and indicated that increased ligand binding coincides with increased regional microglia activation due to neuroinflammation. These investigations yield further support to the PBR/TSPO binding capacity of DAA1106 in human brain tissue, demonstrate the effective usefulness of its radio-iodinated analogues as imaging biomarkers in post mortem human studies, and indicate that its radiolabelled analogues, labelled with short half-time bioisotopes, can serve as prospective in vivo imaging biomarkers of activated microglia and the up-regulated PBR/TSPO system in the human brain.

  7. Synthesis, antifungal activity, and QSAR studies of 1,6-dihydropyrimidine derivatives

    Directory of Open Access Journals (Sweden)

    Chirag Rami

    2013-01-01

    Full Text Available Introduction: A practical synthesis of pyrimidinone would be very helpful for chemists because pyrimidinone is found in many bioactive natural products and exhibits a wide range of biological properties. The biological significance of pyrimidine derivatives has led us to the synthesis of substituted pyrimidine. Materials and Methods: With the aim of developing potential antimicrobials, new series of 5-cyano-6-oxo-1,6-dihydro-pyrimidine derivatives namely 2-(5-cyano-6-oxo-4-substituted (aryl-1,6-dihydropyrimidin-2-ylthio-N-substituted (phenyl acetamide (C1-C41 were synthesized and characterized by Fourier transform infrared spectroscopy (FTIR, mass analysis, and proton nuclear magnetic resonance ( 1 H NMR. All the compounds were screened for their antifungal activity against Candida albicans (MTCC, 227. Results and Discussion: Quantitative structure activity relationship (QSAR studies of a series of 1,6-dihydro-pyrimidine were carried out to study various structural requirements for fungal inhibition. Various lipophilic, electronic, geometric, and spatial descriptors were correlated with antifungal activity using genetic function approximation. Developed models were found predictive as indicated by their square of predictive regression values (r 2pred and their internal and external cross-validation. Study reveals that CHI_3_C, Molecular_SurfaceArea, and Jurs_DPSA_1 contributed significantly to the activity along with some electronic, geometric, and quantum mechanical descriptors. Conclusion: A careful analysis of the antifungal activity data of synthesized compounds revealed that electron withdrawing substitution on N-phenyl acetamide ring of 1,6-dihydropyrimidine moiety possess good activity.

  8. CHARACTERIZATION OF THE IN VITRO METABOLISM OF SELECTIVE ANDROGEN RECEPTOR MODULATOR USING HUMAN, RAT, AND DOG LIVER ENZYME PREPARATIONS

    Science.gov (United States)

    Gao, Wenqing; Wu, Zengru; Bohl, Casey E.; Yang, Jun; Miller, Duane D.; Dalton, James T.

    2007-01-01

    Compound S4 [S-3-(4-acetylamino-phenoxy)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethyl-phenyl)-propionamide] is a novel nonsteroidal selective androgen receptor modulator that demonstrates tissue-selective androgenic and anabolic effects. The purpose of this in vitro study was to identify the phase I metabolites, potential species differences in metabolism, and the cytochromes P450 (P450s) involved in the phase I metabolism of S4 using 14C-S4, recombinant P450s, and other liver enzyme preparations from human, rat, and dog. The major phase I metabolism pathways of S4 in humans were identified as deacetylation of the B-ring acetamide group, hydrolysis of the amide bond, reduction of the A-ring nitro group, and oxidation of the aromatic rings, with deacetylation being the predominant pathway observed with most of the enzyme preparations tested. Among the major human P450 enzymes tested, CYP3A4 appeared to be one of the major phase I enzymes that could be responsible for the phase I metabolism of S4 [Km = 16.1 μM, Vmax = 1.6 pmol/(pmol · min)] in humans and mainly catalyzed the deacetylation, hydrolysis, and oxidation of S4. In humans, the cytosolic enzymes mainly catalyzed the hydrolysis reaction, whereas the microsomal enzymes primarily catalyzed the deacetylation reactions. Similar phase I metabolic profiles were observed in rats and dogs as well, except that the amide bond hydrolysis seemed to occur more rapidly in rats. In summary, these results showed that the major phase I reaction of S4 in human, rat, and dog is acetamide group deacetylation. PMID:16272404

  9. PARP inhibition delays progression of mitochondrial encephalopathy in mice.

    Science.gov (United States)

    Felici, Roberta; Cavone, Leonardo; Lapucci, Andrea; Guasti, Daniele; Bani, Daniele; Chiarugi, Alberto

    2014-07-01

    Mitochondrial disorders are deadly childhood diseases for which therapeutic remedies are an unmet need. Given that genetic suppression of the nuclear enzyme poly (adenine diphosphate-ribose) polymerase(PARP)-1 improves mitochondrial functioning, we investigated whether pharmacological inhibition of the enzyme affords protection in a mouse model of a mitochondrial disorder. We used mice lacking the Ndufs4 subunit of the respiratory complex I (Ndufs4 knockout [ KO] mice); these mice undergo progressive encephalopathy and die around postnatal day 50. Mice were treated daily with the potent PARP inhibitor N-(6-oxo-5,6-dihydrophenanthridin-2-yl)-(N,N-dimethylamino)acetamide hydrochloride (PJ34); neurological parameters, PARP activity, and mitochondrial homeostasis were evaluated. We found that mice receiving N-(6-oxo-5,6-dihydrophenanthridin-2-yl)-(N,N-dimethylamino)acetamide hydrochloride from postnatal day 30 to postnatal day 50 show reduced neurological impairment, and increased exploratory activity and motor skills compared with vehicle-treated animals. However, drug treatment did not delay or reduce death. We found no evidence of increased PARP activity within the brain of KO mice compared with heterozygous, healthy controls. Conversely, a 10-day treatment with the PARP inhibitor significantly reduced basal poly(ADP-ribosyl)ation in different organs of the KO mice, including brain, skeletal muscle, liver, pancreas, and spleen. In keeping with the epigenetic role of PARP-1, its inhibition correlated with increased expression of mitochondrial respiratory complex subunits and organelle number. Remarkably, pharmacological targeting of PARP reduced astrogliosis in olfactory bulb and motor cortex, but did not affect neuronal loss of KO mice. In light of the advanced clinical development of PARP inhibitors, these data emphasize their relevance to treatment of mitochondrial respiratory defects.

  10. Theme-Based Bidisciplinary Chemistry Laboratory Modules

    Science.gov (United States)

    Leber, Phyllis A.; Szczerbicki, Sandra K.

    1996-12-01

    methanol to effect transesterification (3) and examining the effect of variations in leaf type and season on lipid composition. A second "Plant Assay" study involves preparing and characterizing analogs of naphthalene-1-acetamide, which is the active growth-promoting ingredient in commercial preparations such as Transplantone® and Rootone®. There are two direct methods for synthesizing the amide from the native plant growth regulator ("auxin") or carboxylic acid: acid-catalyzed hydrolysis of the nitrile or ammonolysis of the acid chloride derivative, prepared in situ from the acid by treatment with thionyl chloride (4). In the spring of 1996, organic chemistry students synthesized the amide derivatives of a number of auxins via the acid chloride intermediate, which is more efficiently prepared using oxalyl chloride (40-60% overall yield) instead of thionyl chloride (20-40% overall yield), or via nitrile hydrolysis (72-99% yield). Plant bioassays, based on measurement of pea stem segment elongation (5) have only been performed on the acetamide derivatives of three auxins, indole-3-acetic acid (IAA), naphthalene-1-acetic acid (1-NAA), and naphthalene-2-acetic acid (2-NAA). In comparison with the control, indole-3-acetamide and naphthalene-1-acetamide promoted growth by 50% and 90%, respectively. The acetamide of 2-NAA impeded growth by 30% relative to the control, an observation consistent with the known antiauxin activity of 2-NAA (6). Acquisition of the necessary imaging system for the teaching laboratory will enable students to extend these quantitative studies to other auxin conjugates. Acknowledgment We are grateful to the NSF for financial support through the Division of Undergraduate Education (DUE-9455693 and DUE-9550890). Literature Cited 1. Mayo, D. W.; Pike, R. M.; Trumper, P. K. Microscale Organic Laboratory, 3rd ed; John Wiley & Sons: New York, 1994; pp 202-203. 2. Browse, J.; McCourt, P. J.; Somerville, C. R. Anal. Biochem. 1986, 152, 141. 3. Rodig, O. R

  11. Lanthanide(III) complexation with an amide derived pyridinophane.

    Science.gov (United States)

    Castro, Goretti; Bastida, Rufina; Macías, Alejandro; Pérez-Lourido, Paulo; Platas-Iglesias, Carlos; Valencia, Laura

    2015-02-16

    Herein we report a detailed investigation of the solid state and solution structures of lanthanide(III) complexes with the 18-membered pyridinophane ligand containing acetamide pendant arms TPPTAM (TPPTAM = 2,2',2″-(3,7,11-triaza-1,5,9(2,6)-tripyridinacyclododecaphane-3,7,11-triyl)triacetamide). The ligand crystallizes in the form of a clathrated hydrate, where the clathrated water molecule establishes hydrogen-bonding interactions with the amide NH groups and two N atoms of the macrocycle. The X-ray structures of 13 different Ln(3+) complexes obtained as the nitrate salts (Ln(3+) = La(3+)-Yb(3+), except Pm(3+)) have been determined. Additionally, the X-ray structure of the La(3+) complex obtained as the triflate salt was also obtained. In all cases the ligand provides 9-fold coordination to the Ln(3+) ion, ten coordination being completed by an oxygen atom of a coordinated water molecule or a nitrate or triflate anion. The bond distances of the metal coordination environment show a quadratic change along the lanthanide series, as expected for isostructural series of Ln(3+) complexes. Luminescence lifetime measurements obtained from solutions of the Eu(3+) and Tb(3+) complexes in H2O and D2O point to the presence of a water molecule coordinated to the metal ion in aqueous solutions. The analysis of the Ln(3+)-induced paramagnetic shifts indicates that the complexes are ten-coordinated throughout the lanthanide series from Ce(3+) to Yb(3+), and that the solution structure is very similar to the structures observed in the solid state. The complexes of the light Ln(3+) ions are fluxional due to a fast Δ(λλλλλλ) ↔ Λ(δδδδδδ) interconversion that involves the inversion of the macrocyclic ligand and the rotation of the acetamide pendant arms. The complexes of the small Ln(3+) ions are considerably more rigid, the activation free energy determined from VT (1)H NMR for the Lu(3+) complex being ΔG(⧧)298 = 72.4 ± 5.1 kJ mol(-1).

  12. Anticonvulsant effects of structurally diverse GABA(B) positive allosteric modulators in the DBA/2J audiogenic seizure test: Comparison to baclofen and utility as a pharmacodynamic screening model.

    Science.gov (United States)

    Brown, Jordan W; Moeller, Achim; Schmidt, Martin; Turner, Sean C; Nimmrich, Volker; Ma, Junli; Rueter, Lynne E; van der Kam, Elizabeth; Zhang, Min

    2016-02-01

    The GABA(B) receptor has been indicated as a promising target for multiple CNS-related disorders. Baclofen, a prototypical orthosteric agonist, is used clinically for the treatment of spastic movement disorders, but is associated with unwanted side-effects, such as sedation and motor impairment. Positive allosteric modulators (PAM), which bind to a topographically-distinct site apart from the orthosteric binding pocket, may provide an improved side-effect profile while maintaining baclofen-like efficacy. GABA, the major inhibitory neurotransmitter in the CNS, plays an important role in the etiology and treatment of seizure disorders. Baclofen is known to produce anticonvulsant effects in the DBA/2J mouse audiogenic seizure test (AGS), suggesting it may be a suitable assay for assessing pharmacodynamic effects. Little is known about the effects of GABA(B) PAMs, however. The studies presented here sought to investigate the AGS test as a pharmacodynamic (PD) screening model for GABA(B) PAMs by comparing the profile of structurally diverse PAMs to baclofen. GS39783, rac-BHFF, CMPPE, A-1295120 (N-(3-(4-(4-chloro-3-fluorobenzyl)-6-methoxy-3,5-dioxo-4,5-dihydro-1,2,4-triazin-2(3H)-yl)phenyl)acetamide), and A-1474713 (N-(3-(4-(4-chlorobenzyl)-3,5-dioxo-4,5-dihydro-1,2,4-triazin-2(3H)-yl)phenyl)acetamide) all produced robust, dose-dependent anticonvulsant effects; a similar profile was observed with baclofen. Pre-treatment with the GABA(B) antagonist SCH50911 completely blocked the anticonvulsant effects of baclofen and CMPPE in the AGS test, indicating such effects are likely mediated by the GABA(B) receptor. In addition to the standard anticonvulsant endpoint of the AGS test, video tracking software was employed to assess potential drug-induced motor side-effects during the acclimation period of the test. This analysis was sensitive to detecting drug-induced changes in total distance traveled, which was used to establish a therapeutic index (TI = hypoactivity

  13. Nitrogen metabolism and growth enhancement in tomato plants challenged with Trichoderma harzianum expressing the Aspergillus nidulans acetamidase amdS gene

    Directory of Open Access Journals (Sweden)

    Sara Domínguez

    2016-08-01

    Full Text Available Trichoderma is a fungal genus that includes species that are currently being used as biological control agents and/or as biofertilizers. In addition to the direct application of Trichoderma spp. as biocontrol agents in plant protection, recent studies have focused on the beneficial responses exerted on plants, stimulating the growth, activating the defenses, and/or improving nutrient uptake. The amdS gene, encoding an acetamidase of Aspergillus, has been used as a selectable marker for the transformation of filamentous fungi, including Trichoderma spp., but the physiological effects of the introduction of this gene into the genome of these microorganisms still remains unexplored. No evidence of amdS orthologous genes has been detected within the Trichoderma spp. genomes and the amdS heterologous expression in T. harzianum T34 did not affect the growth of this fungus in media lacking acetamide. However, it did confer the ability for the fungus to use this amide as a nitrogen source. Although a similar antagonistic behavior was observed for T34 and amdS transformants in dual cultures against Rhizoctonia solani, Botrytis cinerea and Fusarium oxysporum, a significantly higher antifungal activity was detected in amdS transformants against F. oxysporum, compared to that of T34, in membrane assays on media lacking acetamide. In Trichoderma-tomato interaction assays, amdS transformants were able to promote plant growth to a greater extent than the wild-type T34, although compared with this strain the transformants showed similar capability to colonize tomato roots. Gene expression patterns from aerial parts of 3-week-old tomato plants treated with T34 and the amdS transformants have also been investigated using GeneChip Tomato Genome Arrays. The downregulation of defense genes and the upregulation of carbon and nitrogen metabolism genes observed in the microarrays were accompanied by i enhanced growth, ii increased carbon and nitrogen levels and iii a

  14. Detection of Five Kinds of Amide Compounds in Leather by GC-MS%气相色谱质谱法检测皮革中五种酰胺化合物

    Institute of Scientific and Technical Information of China (English)

    王华; 李支薇; 任祥祥

    2014-01-01

    采用甲醇作为溶剂,对待测样品进行超声萃取,选择Rxi-624sil MS气相色谱柱,用气相色谱-质谱联用仪对丙烯酰胺、N-甲基乙酰胺、N,N-二甲基甲酰胺、甲酰胺、N,N-二甲基乙酰胺五种酰胺类化合物进行检测。在优化的分析条件下,五种酰胺类化合物在15 min内能达到很好的分离效果。所有目标化合物在0.01~10 mg/L的质量浓度范围内线性关系良好,线性相关系数均大于0.9995,检出限达到0.01 mg/L,相对标准偏差约2.5%,加标回收率为80%~105%。本方法简便快捷、准确可靠,满足REACH法规对酰胺类有害物质检测的要求。%Five kinds of amide compounds, such as acrylamide, N-methyl acetamide, N,N-dimethyl for-mamide, formamide, N,N-dimethyl acetamide in leather were detected by gas chromatography-mass spec-trometry (GC-MS) using methanol as an extracting solvent with ultrasonic assistance and selecting chro-matographic column of Sil Rxi-624 MS. Under optimized conditions, very good chromatographic peaks and separation effect were reached within 15 minutes. All the target compounds are in accordance with a suit-able linear relation to their concentration range of 0.01-10 mg/L, and each correlation coefficient of them is greater than 0.9995. The detection limit is 0.01 mg/L, the relative standard deviations is below 2.5%, and the recovery of spiked sample is 80%-105%. The results show that this method is accurate and reli-able, and it is satisfying for detection requirements of the REACH regulation.

  15. Mechanical Performances of Carbonitriding Films on Cast Iron by Plasma Electrolytic Carbonitriding

    Institute of Scientific and Technical Information of China (English)

    PANG Hua; ZHANG Gu-Ling; WANG Xing-Quan; LV Guo-Hua; CHEN Huan; YANG Si-Ze

    2011-01-01

    The plasma electrolytic carbonitriding (PEC/N) process is applied to cast iron using an aqueous solution of acetamide and glycerin as the electrolyte. Mechanical properties of the carbonitriding layers on cast iron are investigated. After the PEC/N treatment, the microhardness and wear resistance of cast iron are improved significantly compared to the untreated substrate. When the substrate is processed at 350 V for 60s, the coating presents the highest microhardness and it is about 554.14HK0.02, and the coating with the highest hardness has the best wear resistance.%The plasma electrolytic carbonitriding (PEC/N) process is applied to cast iron using an aqueous solution of acetamide and glycerin as the electrolyte.Mechanical properties of the carbonitriding layers on cast iron are investigated.After the PEC/N treatment,the microhardness and wear resistance of cast iron are improved significantly compared to the untreated substrate.When the substrate is processed at 350 V for 60s,the coating presents the highest microhardness and it is about 554.14HK0.02,and the coating with the highest hardness has the best wear resistance.Plasma electrolytic saturation (PES) is a relatively novel surface engineering technique,which operates at room temperature and atmospheric pressure.[1-3]It includes plasma electrolytic carburizing (PEC),[4,5]plasma electrolytic nitriding (PEN)[6] and plasma electrolytic carbonitriding (PEC/N).[7-10] The relatively unrestrained size and shape,and shorter treatment time compared to vacuum-plasma processes make the PES a desirable and flexible technique for industrial use.The PES treatments on low carbon steel,[11] stainless steel[3,12] and pure iron[13] have been investigated.Researchers studied the microstructure,phase composition,corrosion resistance,microhardness and wear performance of the PES-treated samples.It was found that the diffusion of N into stainless steels can improve the corrosion resistance of stainless steels,[14] while the

  16. 聚乙烯醇的共混改性%Blending modification of polyvinyl alcohol

    Institute of Scientific and Technical Information of China (English)

    张纪成; 吴清兰; 李雅迪; 周冬; 唐龙祥; 方治齐

    2013-01-01

    将两种牌号聚乙烯醇(PVA)(PVA1799和PVA0599)混合,然后分别加入甘油/三甘醇、甘油/乙酰胺复合增塑剂对其进行改性.加入复合增塑剂使PVA1799/PVA0599的熔点、结晶度和热分解温度降低;与PVA1799/PVA0599体系相比,改性PVA1799/PVA0599的拉伸强度下降、拉伸断裂应变明显提高;随着PVA0599含量增加,改性PVA1799/PVA0599的熔体流动速率增大;m(PVA1799)/m(PVA0599)为3∶2时,随复合增塑剂用量增加,改性PVA1799/PVA0599的流动性变好;甘油/乙酰胺增塑效果优于甘油/三甘醇;改性PVA1799/PVA0599体系在复合增塑剂为30 phr时可望实现熔融加工.%The authors blended two grades of polyvinyl alcohol (PVA), PVA1799 and PVA0599, and then added glycerin/triethylene glycol or glycerin/acetamide composite plasticizer with the aim of modifying PVA. The melting point, crystallinity and thermal decomposition temperature of the modified PVA1799/PVA0599 reduced with the addition of the composite plasticizers. The modified PVA1799/PVA0599 had decreased tensile strength but significantly increased tensile strain at break in comparison with the PVA1799/PVA0599 blend. The melt flow rate of the modified PVA1799/PVA0599 blend rose with increasing the content of PVA0599. The flowability of the modified PVA1799/PVA0599 became better with the increase in the composite plasticizer content when the mass ratio of PVA 1799 to PVA0599 was 3 : 2. Moreover, the plasticizing effect in glycerin/acetamide composite plasticizer was superior to that of glycerin/triethylene glycol composite plasticizer. When the content of the composite plasticizer is 30 phr, the modified PVA1799/PVA0599 blend seems to realize melt processing.

  17. Synthesis and application of dual core Schiff base metal manganese like enzyme complex%双核希夫碱金属锰仿酶配合物的合成及其应用

    Institute of Scientific and Technical Information of China (English)

    张海希; 周向东

    2016-01-01

    以水杨醛、浓硫酸、碳酸钠与1,3-二氨基-2-丙醇为原料,采用2步法合成工艺制得双水杨醛磺酸钠缩二氨基-2-丙醇配体,再将配体与金属盐乙酸锰进行配位得到双核希夫碱金属锰配合物,红外光谱和能量色散X-射线能谱表征了配合物。将配合物应用于棉织物的低温漂白,探讨了配合物浓度、pH和乙酰胺用量对漂白效果的影响。结果表明,在配合物浓度为8μmol/L、pH为10.5~11.0、乙酰胺用量为8~9 g/L的条件下,处理后的棉织物白度达77.7%,毛细管效应达8.7 cm/30 min。%Dual core Schiff base metal manganese complex was synthesized by two step process. Firstly, double salicylic aldehyde condensation diamino-2-hydroxypropane ligand was synthesized by salicylaldehyde, concentrated sulfuric acid, sodium carbonate and 1,3-diamino-2-hydroxypropane. Then, Schiff base metal manganese complex was obtained through the coordination of ligand and manganese acetate. The complex was characterization by infrared and EDS. The complex was applied in low temperature bleaching of cotton fabric and the effects of complex concentration, pH, acetamide dosage on the bleaching were discussed. The results showed that when the cotton fabric treated with 8 μmol/L Schiff base complex, 8~9 g/L acetamide, pH=10.5~11.0, the whiteness of treated cotton fabric reached 77.7%, capil ary effect reached 8.7 cm/30 min.

  18. Evaluation of a radiolabelled peripheral benzodiazepine receptor ligand in the central nervous system inflammation of experimental autoimmune encephalomyelitis: a possible probe for imaging multiple sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Mattner, F.; Katsifis, A.; Ballantyne, P. [ANSTO, Radiopharmaceuticals Division, Lucas Heights (Australia); Staykova, M.; Willenborg, D.O. [Australian National University Medical School, The Canberra Hospital, Neurosciences Research Unit, Woden, Canberra (Australia)

    2005-04-01

    Peripheral benzodiazepine receptors (PBRs) are upregulated on macrophages and activated microglia, and radioligands for the PBRs can be used to detect in vivo neuroinflammatory changes in a variety of neurological insults, including multiple sclerosis. Substituted 2-phenyl imidazopyridine-3-acetamides with high affinity and selectivity for PBRs have been prepared that are suitable for radiolabelling with a number of positron emission tomography and single-photon emission computed tomography (SPECT) isotopes. In this investigation, the newly developed high-affinity PBR ligand 6-chloro-2-(4'-iodophenyl)-3-(N,N-diethyl)imidazo[1,2-a]pyridine-3-acetamide, or CLINDE, was radiolabelled with{sup 123}I and its biodistribution in the central nervous system (CNS) of rats with experimental autoimmune encephalomyelitis (EAE) evaluated. EAE was induced in male Lewis rats by injection of an emulsion of myelin basic protein and incomplete Freund's adjuvant containing Mycobacterium butyricum. Biodistribution studies with{sup 123}I-CLINDE were undertaken on EAE rats exhibiting different clinical disease severity and compared with results in controls. Disease severity was confirmed by histopathology in the spinal cord of rats. The relationship between inflammatory lesions and PBR ligand binding was investigated using ex vivo autoradiography and immunohistochemistry on rats with various clinical scores. {sup 123}I-CLINDE uptake was enhanced in the CNS of all rats exhibiting EAE when compared to controls. Binding reflected the ascending nature of EAE inflammation, with lumbar/sacral cord > thoracic cord > cervical cord > medulla. The amount of ligand binding also reflected the clinical severity of disease. Ex vivo autoradiography and immunohistochemistry revealed a good spatial correspondence between radioligand signal and foci of inflammation and in particular ED-1{sup +} cells representing macrophages and microglia. These results demonstrate the ability of {sup 123}I

  19. Comparative Evaluation of the Translocator Protein Radioligands {sup 11}C-DPA-713, {sup 18}F-DPA- 714, and {sup 11}C-PK11195 in a Rat Model of Acute Neuro-inflammation

    Energy Technology Data Exchange (ETDEWEB)

    Chauveau, F.; Van Camp, N.; Dolle, F.; Kuhnast, B.; Hinnen, F.; Damont, A.; Boutin, H.; Tavitian, B. [CEA, DSV, I2BM, LIME, Orsay (France); Chauveau, F.; Van Camp, N.; Boutin, H; Tavitian, B. [INSERM, U803, Orsay (France); Chauveau, F. [CREATIS-LRMN, CNRS, UMR 5220, and INSERM, U630, Bron (France); Boutin, H. [Faculty of Life Sciences, AV Hill Building, University of Manchester, Manchester (GB); James, M. [Brain and Mind Research Institute, University of Sydney, Sydney, New South Wales (Australia); Kassiou, M. [Discipline of Medical Radiation Sciences, University of Sydney, Sydney, New SouthWales (Australia); Kassiou, M. [School of Chemistry, University of Sydney, Sydney, New SouthWales (Australia)

    2009-07-01

    Overexpression of the translocator protein, TSPO (18 kDa), formerly known as the peripheral benzodiazepine receptor, is a hallmark of activation of cells of monocytic lineage (micro-glia and macrophages) during neuro-inflammation. Radiolabeling of TSPO ligands enables the detection of neuro-inflammatory lesions by PET. Two new radioligands, {sup 11}C-labeled N, N-diethyl-2-[2-(4- methoxy-phenyl)-5, 7-dimethylpyrazolo[1, 5-a]pyrimidin-3-yl] acetamide (DPA-713) and {sup 18}F-labeled N, N-diethyl-2-(2-(4-(2- fluoroethoxy)phenyl)-5, 7-dimethylpyrazolo[1, 5-a]pyrimidin-3-yl) acetamide (DPA-714), both belonging to the pyrazolopyrimidine class, were compared in vivo and in vitro using a rodent model of neuro-inflammation. Methods: {sup 11}C-DPA-713 and {sup 18}F-DPA-714, as well as the classic radioligand {sup 11}C-labeled (R)-N-methyl- N-(1-methylpropyl)-1-(2-chlorophenyl)isoquinoline-3-carboxamide (PK11195), were used in the same rat model, in which intra-striatal injection of (R, S)-a-amino-3-hydroxy-5-methyl-4-isoxazolopropionique gave rise to a strong neuro-inflammatory response. Comparative endpoints included in vitro autoradiography and in vivo imaging on a dedicated small-animal PET scanner under identical conditions. Results: {sup 11}C-DPA-713 and {sup 18}F-DPA-714 could specifically localize the neuro-inflammatory site with a similar signal-to-noise ratio in vitro. In vivo, {sup 18}F-DPA-714 performed better than {sup 11}C-DPA-713 and {sup 11}C-PK11195, with the highest ratio of ipsilateral to contralateral uptake and the highest binding potential. Conclusion: {sup 18}F-DPA-714 appears to be an attractive alternative to {sup 11}C-PK11195 because of its increased bioavailability in brain tissue and its reduced nonspecific binding. Moreover, its labeling with {sup 18}F, the preferred PET isotope for radiopharmaceutical chemistry, favors its dissemination and wide clinical use. {sup 18}F-DPA-714 will be further evaluated in longitudinal studies of neuro

  20. Inhibiting heat-shock protein 90 reverses sensory hypoalgesia in diabetic mice

    Directory of Open Access Journals (Sweden)

    Brian S J Blagg

    2010-08-01

    Full Text Available Increasing the expression of Hsp70 (heat-shock protein 70 can inhibit sensory neuron degeneration after axotomy. Since the onset of DPN (diabetic peripheral neuropathy is associated with the gradual decline of sensory neuron function, we evaluated whether increasing Hsp70 was sufficient to improve several indices of neuronal function. Hsp90 is the master regulator of the heat-shock response and its inhibition can up-regulate Hsp70. KU-32 (N-{7-[(2R,3R,4S,5R-3,4-dihydroxy-5-methoxy-6,6-dimethyl-tetrahydro-2H-pyran-2-yloxy]-8-methyl-2-oxo-2H-chromen-3-yl}acetamide was developed as a novel, novobiocin-based, C-terminal inhibitor of Hsp90 whose ability to increase Hsp70 expression is linked to the presence of an acetamide substitution of the prenylated benzamide moiety of novobiocin. KU-32 protected against glucose-induced death of embryonic DRG (dorsal root ganglia neurons cultured for 3 days in vitro. Similarly, KU-32 significantly decreased neuregulin 1-induced degeneration of myelinated Schwann cell DRG neuron co-cultures prepared from WT (wild-type mice. This protection was lost if the co-cultures were prepared from Hsp70.1 and Hsp70.3 KO (knockout mice. KU-32 is readily bioavailable and was administered once a week for 6 weeks at a dose of 20 mg/kg to WT and Hsp70 KO mice that had been rendered diabetic with streptozotocin for 12 weeks. After 12 weeks of diabetes, both WT and Hsp70 KO mice developed deficits in NCV (nerve conduction velocity and a sensory hypoalgesia. Although KU-32 did not improve glucose levels, HbA1c (glycated haemoglobin or insulin levels, it reversed the NCV and sensory deficits in WT but not Hsp70 KO mice. These studies provide the first evidence that targeting molecular chaperones reverses the sensory hypoalgesia associated with DPN.

  1. Inhibiting heat-shock protein 90 reverses sensory hypoalgesia in diabetic mice.

    Science.gov (United States)

    Urban, Michael J; Li, Chengyuan; Yu, Cuijuan; Lu, Yuanming; Krise, Joanna M; McIntosh, Michelle P; Rajewski, Roger A; Blagg, Brian S J; Dobrowsky, Rick T

    2010-08-11

    Increasing the expression of Hsp70 (heat-shock protein 70) can inhibit sensory neuron degeneration after axotomy. Since the onset of DPN (diabetic peripheral neuropathy) is associated with the gradual decline of sensory neuron function, we evaluated whether increasing Hsp70 was sufficient to improve several indices of neuronal function. Hsp90 is the master regulator of the heat-shock response and its inhibition can up-regulate Hsp70. KU-32 (N-{7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-methoxy-6,6-dimethyl-tetrahydro-2H-pyran-2-yloxy]-8-methyl-2-oxo-2H-chromen-3-yl}acetamide) was developed as a novel, novobiocin-based, C-terminal inhibitor of Hsp90 whose ability to increase Hsp70 expression is linked to the presence of an acetamide substitution of the prenylated benzamide moiety of novobiocin. KU-32 protected against glucose-induced death of embryonic DRG (dorsal root ganglia) neurons cultured for 3 days in vitro. Similarly, KU-32 significantly decreased neuregulin 1-induced degeneration of myelinated Schwann cell DRG neuron co-cultures prepared from WT (wild-type) mice. This protection was lost if the co-cultures were prepared from Hsp70.1 and Hsp70.3 KO (knockout) mice. KU-32 is readily bioavailable and was administered once a week for 6 weeks at a dose of 20 mg/kg to WT and Hsp70 KO mice that had been rendered diabetic with streptozotocin for 12 weeks. After 12 weeks of diabetes, both WT and Hsp70 KO mice developed deficits in NCV (nerve conduction velocity) and a sensory hypoalgesia. Although KU-32 did not improve glucose levels, HbA1c (glycated haemoglobin) or insulin levels, it reversed the NCV and sensory deficits in WT but not Hsp70 KO mice. These studies provide the first evidence that targeting molecular chaperones reverses the sensory hypoalgesia associated with DPN.

  2. Investigation of the Mechanism of Electron Capture and Electron Transfer Dissociation of Peptides with a Covalently Attached Free Radical Hydrogen Atom Scavenger.

    Science.gov (United States)

    Sohn, Chang Ho; Yin, Sheng; Peng, Ivory; Loo, Joseph A; Beauchamp, J L

    2015-11-15

    The mechanisms of electron capture and electron transfer dissociation (ECD and ETD) are investigated by covalently attaching a free-radical hydrogen atom scavenger to a peptide. The 2,2,6,6-tetramethylpiperidin-l-oxyl (TEMPO) radical was chosen as the scavenger due to its high hydrogen atom affinity (ca. 280 kJ/mol) and low electron affinity (ca. 0.45 ev), and was derivatized to the model peptide, FQX(TEMPO)EEQQQTEDELQDK. The X(TEMPO) residue represents a cysteinyl residue derivatized with an acetamido-TEMPO group. The acetamide group without TEMPO was also examined as a control. The gas phase proton affinity (882 kJ/mol) of TEMPO is similar to backbone amide carbonyls (889 kJ/mol), minimizing perturbation to internal solvation and sites of protonation of the derivatized peptides. Collision induced dissociation (CID) of the TEMPO tagged peptide dication generated stable odd-electron b and y type ions without indication of any TEMPO radical induced fragmentation initiated by hydrogen abstraction. The type and abundance of fragment ions observed in the CID spectra of the TEMPO and acetamide tagged peptides are very similar. However, ECD of the TEMPO labeled peptide dication yielded no backbone cleavage. We propose that a labile hydrogen atom in the charge reduced radical ions is scavenged by the TEMPO radical moiety, resulting in inhibition of N-Cα backbone cleavage processes. Supplemental activation after electron attachment (ETcaD) and CID of the charge-reduced precursor ion generated by electron transfer of the TEMPO tagged peptide dication produced a series of b + H (b(H)) and y + H (y(H)) ions along with some c ions having suppressed intensities, consistent with stable O-H bond formation at the TEMPO group. In summary, the results indicate that ECD and ETD backbone cleavage processes are inhibited by scavenging of a labile hydrogen atom by the localized TEMPO radical moiety. This observation supports the conjecture that ECD and ETD processes involve long

  3. Inhibition of HIF-1{alpha} activity by BP-1 ameliorates adjuvant induced arthritis in rats

    Energy Technology Data Exchange (ETDEWEB)

    Shankar, J. [Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago (United States); Thippegowda, P.B., E-mail: btprabha@uic.edu [Department of Pharmacology, (M/C 868), College of Medicine, University of Illinois at Chicago, 835 S. Wolcott Ave., Chicago, IL 60612 (United States); Kanum, S.A. [Department of Chemistry, Yuvaraj' s College, University of Mysore, Mysore (India)

    2009-09-18

    Rheumatoid arthritis (RA) is a chronic inflammatory, angiogenic disease. Inflamed synovitis is a hallmark of RA which is hypoxic in nature. Vascular endothelial growth factor (VEGF), one of the key regulators of angiogenesis, is overexpressed in the pathogenesis of RA. VEGF expression is regulated by hypoxia-inducible factor-1{alpha} (HIF-1{alpha}), a master regulator of homeostasis which plays a pivotal role in hypoxia-induced angiogenesis. In this study we show that synthetic benzophenone analogue, 2-benzoyl-phenoxy acetamide (BP-1) can act as a novel anti-arthritic agent in an experimental adjuvant induced arthritis (AIA) rat model by targeting VEGF and HIF-1{alpha}. BP-1 administered hypoxic endothelial cells and arthritic animals clearly showed down regulation of VEGF expression. Further, BP-1 inhibits nuclear translocation of HIF-1{alpha}, which in turn suppresses transcription of the VEGF gene. These results suggest a further possible clinical application of the BP-1 derivative as an anti-arthritic agent in association with conventional chemotherapeutic agents.

  4. On the temperature dependence of amide I frequencies of peptides in solution.

    Science.gov (United States)

    Amunson, Krista E; Kubelka, Jan

    2007-08-23

    The temperature dependence of the amide I vibrational frequencies of peptides in solution was investigated. In D2O, the amide I' bands of both an alpha-helical oligopeptide, the random-coil poly(L-lysine), and the simplest amide, N-methyl acetamide (NMA), exhibit linear frequency shifts of approximately 0.07 cm(-1)/degrees C with increasing temperature. Similar amide I frequency shifts are also observed for NMA in both polar (acetonitrile and DMSO) and nonpolar (1,4-dioxane) organic solvents, thus ruling out hydrogen-bonding strength as the cause of these effects. The experimental NMA amide I frequencies in the organic solvents can be accurately described by a simple theory based on the Onsager reaction field with temperature-dependent solvent dielectric properties and a solute molecular cavity. DFT-level calculations (BPW91/cc-pVDZ) for NMA with an Onsager reaction field confirm the significant contribution of the molecular cavity to the predicted amide I frequencies. Comparison of the computations to experimental data shows that the frequency-dependent response of the reaction field, taken into account by the index of refraction, is crucial for describing the amide I frequencies in polar solvents. The poor predictions of the model for the NMA amide I band in D2O might be due, in part, to the unknown temperature dependence of the refractive index of D2O in the mid-IR range, which was approximated by the available values in the visible region.

  5. Screening of chemokine receptor CCR4 antagonists by capillary zone electrophoresis

    Institute of Scientific and Technical Information of China (English)

    Zhe Sun; Lin-Jie Tian; Qian Lin; Xiao-Mei Ling; Jun-Hai Xiao; Ying Wang

    2011-01-01

    Abstract CC chemokine receptor 4 (CCR4) is a kind of G-protein-coupled receptor, which plays a pivotal role in allergic inflammation. The interaction between 2-(2-(4-chloro-phenyl)-5-{[(naphthalen-1- ylmethyl)-carbamlyl]-methyl-4-oxo-thiazolidin-3-yl)-N-(3-morpholin-4-yl-propyi)-acetamide (S009) and the N-terminal extracellular tail (ML40) of CCR4 has been validated to be high affinity by capillary zone electrophoresis (CZE).The S009 is a known CCR4 antagonist. Now, a series of new thiourea derivatives have been synthesized. Compared with positive control S009, they were screened using ML40 as target by CZE to find some new drugs for allergic inflammation diseases. The synthesized compounds XJH-5, XJH-4, XJH-17 and XJH-1 displayed the interaction with ML40, but XJH-9, XJH-10, XJH-I 1, XJH-12, XJH-13, XJH-14, XJH-3, XJH-8, XJH-6, XJH-7, XJH-15, XJH-16 and XJH-2 did not bind to ML40. Both qualification and quantification characterizations of the binding were determined. The affinity of the four compounds was valued by the binding constant, which was similar with the results of chemotactic experiments. The established CEZ method is capable of sensitive and fast screening for a series of lactam analogs in the drug discovery for allergic inflammation diseases.

  6. Differentiation between decomposed remains of human origin and bigger mammals.

    Science.gov (United States)

    Rosier, E; Loix, S; Develter, W; Van de Voorde, W; Cuypers, E; Tytgat, J

    2017-08-01

    This study is a follow-up study in the search for a human specific marker in the decomposition where the VOC-profile of decomposing human, pig, lamb and roe remains were analyzed using a thermal desorber combined with a gas chromatograph coupled to a mass spectrometer in a laboratory environment during 6 months. The combination of 8 previously identified human and pig specific compounds (ethyl propionate, propyl propionate, propyl butyrate, ethyl pentanoate, 3-methylthio-1-propanol, methyl(methylthio)ethyl disulfide, diethyl disulfide and pyridine) was also seen in these analyzed mammals. However, combined with 5 additional compounds (hexane, heptane, octane, N-(3-methylbutyl)- and N-(2-methylpropyl)acetamide) human remains could be separated from pig, lamb and roe remains. Based on a higher number of remains analyzed, as compared with the pilot study, it was no longer possible to rely on the 5 previously proposed esters to separate pig from human remains. From this follow-up study reported, it was found that pyridine is an interesting compound specific to human remains. Such a human specific marker can help in the training of cadaver dogs or in the development of devices to search for human remains. However, further investigations have to verify these results. Copyright © 2017 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  7. Key role of intramolecular metal chelation and hydrogen bonding in the cobalt-mediated radical polymerization of N-vinyl amides.

    Science.gov (United States)

    Debuigne, Antoine; Morin, Aurélie N; Kermagoret, Anthony; Piette, Yasmine; Detrembleur, Christophe; Jérôme, Christine; Poli, Rinaldo

    2012-10-01

    This work reveals the preponderance of an intramolecular metal chelation phenomenon in a controlled radical polymerization system involving the reversible trapping of the radical chains by a cobalt complex bis(acetylacetonato)cobalt(II). The cobalt-mediated radical polymerization (CMRP) of a series of N-vinyl amides was considered with the aim of studying the effect of the cobalt chelation by the amide moiety of the last monomer unit of the chain. The latter reinforces the cobalt-polymer bond in the order N-vinylpyrrolidonepolymerizations observed for the last two monomers. Such a double linkage between the controlling agent and the polymer, through a covalent bond and a dative bond, is unique in the field of controlled radical polymerization and represents a powerful opportunity to fine tune the equilibrium between latent and free radicals. Possible hydrogen bond formation is also taken into account in the case of N-vinyl acetamide and N-vinyl formamide. These results are essential for understanding the factors influencing Co-C bond strength in general, and the CMRP mechanism in particular, but also for developing a powerful platform for the synthesis of new precision poly(N-vinyl amide) materials, which are an important class of polymers that sustain numerous applications today.

  8. Silicon nanowires-based fluorescence sensor for Cu(II).

    Science.gov (United States)

    Mu, Lixuan; Shi, Wensheng; Chang, Jack C; Lee, Shuit-Tong

    2008-01-01

    Si nanowires (SiNWs) were covalently modified by fluorescence ligand, N-(quinoline-8-yl)-2-(3-triethoxysilyl-propylamino)-acetamide (QlOEt) and finally formed an optical sensor to realize a highly sensitive and selective detection for Cu(II). The QlOEt-modified SiNWs sensor has sensitivity for Cu(II) down to 10(-8) M, which is more sensitive than QlOEt alone. Metal ions interferences have no observable effect on the sensitivity and selectivity of QlOEt-modified SiNWs sensor. The SiNWs-based fluorescence sensor is reversible by addition of acid to replace Cu(II). The sensing mechanisms of QlOEt-modified SiNWs to Cu(II) and the rationale for the increase in sensitivity and selectivity of QlOEt-modified SiNWs over QlOEt on Cu(II) are discussed. The current sensor structure may be extendable to other chemo- and biosensors, and even to nanosensors for direct detection of specific materials in intracellular environment.

  9. Indole signalling and (micro)algal auxins decrease the virulence of Vibrio campbellii, a major pathogen of aquatic organisms.

    Science.gov (United States)

    Yang, Qian; Pande, Gde Sasmita Julyantoro; Wang, Zheng; Lin, Baochuan; Rubin, Robert A; Vora, Gary J; Defoirdt, Tom

    2017-05-01

    Vibrios belonging to the Harveyi clade are major pathogens of marine vertebrates and invertebrates, causing major losses in wild and cultured organisms. Despite their significant impact, the pathogenicity mechanisms of these bacteria are not yet completely understood. In this study, the impact of indole signalling on the virulence of Vibrio campbellii was investigated. Elevated indole levels significantly decreased motility, biofilm formation, exopolysaccharide production and virulence to crustacean hosts. Indole furthermore inhibited the three-channel quorum sensing system of V. campbellii, a regulatory mechanism that is required for full virulence of the pathogen. Further, indole signalling was found to interact with the stress sigma factor RpoS. Together with the observations that energy-consuming processes (motility and bioluminescence) are downregulated, and microarray-based transcriptomics demonstrating that indole decreases the expression of genes involved in energy and amino acid metabolism, the data suggest that indole is a starvation signal in V. campbellii. Finally, it was found that the auxins indole-3-acetic acid and indole-3-acetamide, which were produced by various (micro)algae sharing the aquatic environment with V. campbellii, have a similar effect as observed for indole. Auxins might, therefore, have a significant impact on the interactions between vibrios, (micro)algae and higher organisms, with major ecological and practical implications. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

  10. Design and Synthesis of Some Thiazolidin-4-ones Based on (7-Hydroxy-2-oxo-2H-chromen-4-yl Acetic Acid

    Directory of Open Access Journals (Sweden)

    Valentina Rajkovic

    2009-07-01

    Full Text Available (7-Hydroxy-2-oxo-2H-chromen-4-yl-acetic acid methyl ester(1 upon reaction with ethyl bromoacetate furnishes (7-ethoxycarbonylmethoxy-2-oxo-2H-chromen-4-yl-acetic acid methylester (2, which on treatment with 100% hydrazine hydrate yields (7-hydrazinocarbonylmethoxy-2-oxo-2H-chromen-4-yl-acetic acid hydrazide (3. The condensation of compound 3 with different aromatic aldehydes afforded a series of [7-(arylidenehydrazinocarbonylmethoxy-2-oxo-2H-chromen-4-yl]-acetic acid arylidene-hydrazide Schiff’s bases 4a-k. Cyclo-condensation of compounds 4a-k with 2-mercapto-acetic acid in N,N-dimethylformamide in the presence of anhydrous ZnCl2 affordsN-(2-aryl-4-oxothiazolidin-3-yl-2-(4-(2-aryl-4-oxothiazolidin-3-ylcarbamoyl-methyl-2-oxo-2H-chromen-7-yloxy-acetamides 5a-k. Structure elucidation of the products has been accomplished on the basis of elemental analysis, IR, 1H-NMR and 13C-NMR data. Compounds 4a-k and 5a-k will be screened for their antibacterial activity against both Gram-positive and Gram-negative bacteria and the results reported elsewhere in due course.

  11. Influence of herbicides on growth of one-year-old trees of sour cherry cv. Łutówka

    Directory of Open Access Journals (Sweden)

    Stanisław Wociór

    2013-12-01

    Full Text Available The studies performed in 1997 - 1999 have shown that herbicides such as Azotop 50 (simazine, 6-chloro-N, N-diethyl-1,3,5-triazine-2,4-diamine in the dose lkg ha-1 or Afalon 50 WP (linuron, N'-(3,4-dichlorophenylN-methoxy-N-methylurea in dose 1,5 kg ha-1 or its mixture with Dual 960 EC (metolachlor, 2-chloro-N(2-ethyl-6-methylphenyl-N-(2-methoxy-1-methylethyl acetamide in dose 1,5 l ha-1 applied in early spring significantly decreased number of weeds in nursery of sourcherry trees cv. Lut6wka budded on Prunus mahaleb L rootstocks as compared with mechanical weed control. Both, Azotop 50 and Azotop 50 in mixture with Dual 960 EC eliminated weeds for the longer period than Afalon 50 WP and Afalon 50 WP with Dual 960 EC. Herbicides did not affect tree trunk diameter (at 30 cm. from the ground level, the number and total length of shoots of one-year-old sour cherry trees in comparison with mechanical control of weeds.

  12. Toxicological evaluation of a novel cooling compound: 2-(4-methylphenoxy-N-(1H-pyrazol-3-yl-N-(2-thienylmethylacetamide

    Directory of Open Access Journals (Sweden)

    Donald S. Karanewsky

    2015-01-01

    Full Text Available A toxicological evaluation of a novel cooling agent, 2-(4-methylphenoxy-N-(1H-pyrazol-3-yl-N-(2-thienylmethyl acetamide (S2227; CAS 1374760-95-8, was completed for the purpose of assessing its safety for use in food and beverage applications. S2227 undergoes rapid oxidative metabolism in vitro, and in rat and dog pharmacokinetic studies is rapidly converted to its component carboxylic acid and secondary amine. S2227 was not found to be mutagenic or clastogenic in vitro, and did not induce micronuclei in polychromatic erythrocytes in vivo. The secondary amine hydrolysis product, N-(2-thienylmethyl-1H-pyrazol-3-amine (M179, was also evaluated for genotoxicity. In subchronic oral toxicity studies in rats, the no-observed-adverse-effect-level (NOAEL for S2227 was 100 mg/kg/day (highest dose tested when administered by oral gavage for 90 consecutive days. Furthermore, S2227 demonstrated a lack of maternal toxicity, as well as adverse effects on fetal morphology at the highest dose tested, providing a NOAEL of 1000 mg/kg/day for both maternal toxicity and embryo/fetal development when administered orally during gestation to pregnant rats.

  13. Humidity-enhanced sub-ppm sensitivity to ammonia of covalently functionalized single-wall carbon nanotube bundle layers

    Science.gov (United States)

    Rigoni, F.; Freddi, S.; Pagliara, S.; Drera, G.; Sangaletti, L.; Suisse, J.-M.; Bouvet, M.; Malovichko, A. M.; Emelianov, A. V.; Bobrinetskiy, I. I.

    2017-06-01

    A low-cost method for carbon nanotubes (CNTs) network production from solutions on flexible polyethylene naphthalate substrates has been adopted to prepare high quality and well characterized SWCNT bundle layers to be used as the active layer in chemiresistor gas sensors. Two types of SWCNTs have been tested: pristine SWCNTs, deposited from a surfactant solution, and covalently functionalized SWCNTs, deposited from a dimethyl-acetamide solution. The humidity effects on the sensitivity of the SWCNTs network to NH3 have been investigated. The results show that relative humidity favors the response to NH3, confirming recent theoretical predictions. The COOH-functionalized sample displays the largest response owing to both its hydrophilic nature, favoring the interaction with H2O molecules, and its largest surface area. Compared to data available in the literature, the present sensors display a remarkable sensitivity well below the ppm range, which makes them quite promising for environmental and medical applications, where NH3 concentrations (mostly of the order of tens of ppb) have to be detected.

  14. The response of Chlamydomonas reinhardtii to nitrogen deprivation: a systems biology analysis.

    Science.gov (United States)

    Park, Jeong-Jin; Wang, Hongxia; Gargouri, Mahmoud; Deshpande, Rahul R; Skepper, Jeremy N; Holguin, F Omar; Juergens, Matthew T; Shachar-Hill, Yair; Hicks, Leslie M; Gang, David R

    2015-02-01

    Drastic alteration in macronutrients causes large changes in gene expression in the photosynthetic unicellular alga Chlamydomonas reinhardtii. Preliminary data suggested that cells follow a biphasic response to this change hinging on the initiation of lipid accumulation, and we hypothesized that drastic repatterning of metabolism also followed this biphasic modality. To test this hypothesis, transcriptomic, proteomic, and metabolite changes that occur under nitrogen (N) deprivation were analyzed. Eight sampling times were selected covering the progressive slowing of growth and induction of oil synthesis between 4 and 6 h after N deprivation. Results of the combined, systems-level investigation indicated that C. reinhardtii cells sense and respond on a large scale within 30 min to a switch to N-deprived conditions turning on a largely gluconeogenic metabolic state, which then transitions to a glycolytic stage between 4 and 6 h after N depletion. This nitrogen-sensing system is transduced to carbon- and nitrogen-responsive pathways, leading to down-regulation of carbon assimilation and chlorophyll biosynthesis, and an increase in nitrogen metabolism and lipid biosynthesis. For example, the expression of nearly all the enzymes for assimilating nitrogen from ammonium, nitrate, nitrite, urea, formamide/acetamide, purines, pyrimidines, polyamines, amino acids and proteins increased significantly. Although arginine biosynthesis enzymes were also rapidly up-regulated, arginine pool size changes and isotopic labeling results indicated no increased flux through this pathway.

  15. Molecules with a peptide link in protostellar shocks: a comprehensive study of L1157

    CERN Document Server

    Mendoza, E; López-Sepulcre, A; Ceccarelli, C; Codella, C; Boechat-Roberty, H M; Bachiller, R

    2014-01-01

    Interstellar molecules with a peptide link -NH-C(=O)-, like formamide (NH$_2$CHO), acetamide (NH$_2$COCH$_3$) and isocyanic acid (HNCO) are particularly interesting for their potential role in pre-biotic chemistry. We have studied their emission in the protostellar shock regions L1157-B1 and L1157-B2, with the IRAM 30m telescope, as part of the ASAI Large Program. Analysis of the line profiles shows that the emission arises from the outflow cavities associated with B1 and B2. Molecular abundance of $\\approx~(0.4-1.1)\\times 10^{-8}$ and $(3.3-8.8)\\times 10^{-8}$ are derived for formamide and isocyanic acid, respectively, from a simple rotational diagram analysis. Conversely, NH$_2$COCH$_3$ was not detected down to a relative abundance of a few $\\leq 10^{-10}$. B1 and B2 appear to be among the richest Galactic sources of HNCO and NH$_2$CHO molecules. A tight linear correlation between their abundances is observed, suggesting that the two species are chemically related. Comparison with astrochemical models favou...

  16. Polysulfone nanofibers prepared by electrospinning and gas/jet-electrospinning

    Institute of Scientific and Technical Information of China (English)

    Yao Yongyi; Zhu Puxin; Ye Hai; Niu Anjian; Gao Xushan; Wu Dacheng

    2006-01-01

    Polysulfone nanofibers were prepared by electrospinning.The electrospinning equipment was designed in a new way,wherein the spinneret was combined with a gas jet device.The intrinsic viscosity of the used polysulfone was 0.197 dL/g in dimethyl acetamide,which was also the solvent in electrospinning.The gas used in this gas jet/electrostatic spinning was nitrogen.The relationship between the process parameters and the average diameter of polysulfone nanofibers was investigated.The main process parameters studied in this work were the voltage,the flow rate of the spinning fluid,the distance between the spinneret and the nanofiber collector and the temperature in the spinning chamber.The other important factors determining the nanometer diameter were the spinning fluid properties including its viscosity,surface tension and electrical conductivity.The average diameter and the diameter distribution of electrospinning nanofibers were measured experimentally by using scanning electron microscopy.The diameter of polysnlfone nanofibers prepared by the gas jet/electrostatic spinning was in the range 50-500 nm.It was found that the diameter of nanofibers mainly depended on high voltage,the gap between the spinneret and the collector and the concentration of polymer solutions.It is concluded that the gas-jet/electrospinning is a better method than the conventional electrospinning,in that it makes the nanofibers finer and more uniform and exhibits higher efficiency in the process of electrospinning.

  17. Production of Induced Secondary Metabolites by a Co-Culture of Sponge-Associated Actinomycetes, Actinokineospora sp. EG49 and Nocardiopsis sp. RV163

    Directory of Open Access Journals (Sweden)

    Yousef Dashti

    2014-05-01

    Full Text Available Two sponge-derived actinomycetes, Actinokineospora sp. EG49 and Nocardiopsis sp. RV163, were grown in co-culture and the presence of induced metabolites monitored by 1H NMR. Ten known compounds, including angucycline, diketopiperazine and β-carboline derivatives 1–10, were isolated from the EtOAc extracts of Actinokineospora sp. EG49 and Nocardiopsis sp. RV163. Co-cultivation of Actinokineospora sp. EG49 and Nocardiopsis sp. RV163 induced the biosynthesis of three natural products that were not detected in the single culture of either microorganism, namely N-(2-hydroxyphenyl-acetamide (11, 1,6-dihydroxyphenazine (12 and 5a,6,11a,12-tetrahydro-5a,11a-dimethyl[1,4]benzoxazino[3,2-b][1,4]benzoxazine (13a. When tested for biological activity against a range of bacteria and parasites, only the phenazine 12 was active against Bacillus sp. P25, Trypanosoma brucei and interestingly, against Actinokineospora sp. EG49. These findings highlight the co-cultivation approach as an effective strategy to access the bioactive secondary metabolites hidden in the genomes of marine actinomycetes.

  18. A comparison of the alpha and gamma radiolysis of CMPO

    Energy Technology Data Exchange (ETDEWEB)

    Bruce J. Mincher; Stephen P. Mezyk; Gary Groenewold; Gracy Elias

    2011-06-01

    The radiation chemistry of CMPO has been investigated using a combination of irradiation and analytical techniques. The {alpha}-, and {gamma}-irradiation of CMPO resulted in identical degradation rates (G-value, in {mu}mol Gy{sup -1}) for both radiation types, despite the difference in their linear energy transfer (LET). Similarly, variations in {gamma}-ray dose rates did not affect the degradation rate of CMPO. The solvent extraction behavior was different for the two radiation types, however. Gamma-irradiation resulted in steadily increasing distribution ratios for both forward and stripping extractions, with respect to increasing absorbed radiation dose. This was true for samples irradiated as a neat organic solution, or irradiated in contact with the acidic aqueous phase. In contrast, {alpha}-irradiated samples showed a rapid drop in distribution ratios for forward and stripping extractions, followed by essentially constant distribution ratios at higher absorbed doses. These differences in extraction behavior are reconciled by mass spectrometric examination of CMPO decomposition products under the different irradiation sources. Irradiation by {gamma}-rays resulted in the rupture of phosphoryl-methylene bonds with the production of phosphinic acid products. These species are expected to be complexing agents for americium that would result in higher distribution ratios. Irradiation by {alpha}-sources appeared to favor rupture of carbamoyl-methylene bonds with the production of less deleterious acetamide products.

  19. Single-dose safety and pharmacokinetic evaluation of fluorocoxib A: pilot study of novel cyclooxygenase-2-targeted optical imaging agent in a canine model

    Science.gov (United States)

    Cekanova, Maria; Uddin, Md. Jashim; Legendre, Alfred M.; Galyon, Gina; Bartges, Joseph W.; Callens, Amanda; Martin-Jimenez, Tomas; Marnett, Lawrence J.

    2012-11-01

    We evaluated preclinical single-dose safety, pharmacokinetic properties, and specific uptake of the new optical imaging agent fluorocoxib A in dogs. Fluorocoxib A, N-[(5-carboxy-X-rhodaminyl)but-4-yl]-2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetamide, selectively binds and inhibits the cyclooxygenase-2 (COX-2) enzyme, which is overexpressed in many cancers. Safety pilot studies were performed in research dogs following intravenous (i.v.) administration of 0.1 and 1 mg/kg fluorocoxib A. Blood and urine samples collected three days after administration of each dose of fluorocoxib A revealed no evidence of toxicity, and no clinically relevant adverse events were noted on physical examination of exposed dogs over that time period. Pharmacokinetic parameters were assessed in additional research dogs from plasma collected at several time points after i.v. administration of fluorocoxib A using high-performance liquid chromatography analysis. The pharmacokinetic studies using 1 mg/kg showed a peak of fluorocoxib A (92±28 ng/ml) in plasma collected at 0.5 h. Tumor specific uptake of fluorocoxib A was demonstrated using a dog diagnosed with colorectal cancer expressing COX-2. Our data support the safe single-dose administration and in vivo efficacy of fluorocoxib A, suggesting a high potential for successful translation to clinical use as an imaging agent for improved tumor detection in humans.

  20. Rebalancing Redox to Improve Biobutanol Production by Clostridium tyrobutyricum

    Directory of Open Access Journals (Sweden)

    Chao Ma

    2015-12-01

    Full Text Available Biobutanol is a sustainable green biofuel that can substitute for gasoline. Carbon flux has been redistributed in Clostridium tyrobutyricum via metabolic cell engineering to produce biobutanol. However, the lack of reducing power hampered the further improvement of butanol production. The objective of this study was to improve butanol production by rebalancing redox. Firstly, a metabolically-engineered mutant CTC-fdh-adhE2 was constructed by introducing heterologous formate dehydrogenase (fdh and bifunctional aldehyde/alcohol dehydrogenase (adhE2 simultaneously into wild-type C. tyrobutyricum. The mutant evaluation indicated that the fdh-catalyzed NADH-producing pathway improved butanol titer by 2.15-fold in the serum bottle and 2.72-fold in the bioreactor. Secondly, the medium supplements that could shift metabolic flux to improve the production of butyrate or butanol were identified, including vanadate, acetamide, sodium formate, vitamin B12 and methyl viologen hydrate. Finally, the free-cell fermentation produced 12.34 g/L of butanol from glucose using the mutant CTC-fdh-adhE2, which was 3.88-fold higher than that produced by the control mutant CTC-adhE2. This study demonstrated that the redox engineering in C. tyrobutyricum could greatly increase butanol production.

  1. Significant changes in the photo-reactivity of TiO2 in the presence of a capped natural dissolved organic matter layer.

    Science.gov (United States)

    Peng, Hong; Chen, Yuan; Mao, Lu; Zhang, Xu

    2017-03-01

    Natural dissolved organic matter (NDOM) in surface waters has a high sorption affinity for TiO2 during long contact. An attached NDOM layer can act as a conduction band electron and/or valance band hole acceptor, and NDOM can also decrease the concentration of hydroxyl radicals (OH) in the bulk phase. Therefore, the degradation kinetics and mechanism for degradation of acetaminophen on NDOM capped TiO2 (NDOM-TiO2) are significantly different from those on raw TiO2. Quantum calculation results suggest that hydroxylation to the ortho position in relation to the acetamide group is more favorable. Although OH induced hydroxylation is the predominant pathway for degradation of acetaminophen on TiO2, one-electron oxidation of acetaminophen by a valance band hole, excited triplet NDOM or NDOM radical cation is the major degradation pathway on NDOM-TiO2. This study is the first to detect and confirm APAP oligomers as intermediates during the degradation of acetaminophen by TiO2 photocatalysis, especially when using NDOM-TiO2 as a catalyst. The results suggest the reactivity of TiO2 could change significantly after long exposure to natural water, which need to be concerned about for removal of micropollutants in surface water by TiO2 photocatalysis.

  2. GC-MS analysis of bioactive compounds in the methanol extract of Clerodendrum viscosum leaves

    Directory of Open Access Journals (Sweden)

    Pritipadma Panda

    2015-01-01

    Full Text Available Background: Clerodendrum viscosum is commonly found in India and Bangladesh. Previously, various parts of this plant were reported for treatment of different types of diseases and there was no report on GC-Ms analysis. Objective: To analyze and characterize the phytochemical compounds of methanol extract of Clerodendrum viscosum using GC-MS. Materials and Methods: The preliminary phytochemical screening of methanol extract was carried out according to standard procedures described in WHO guidelines. Various bioactive compounds of the extract were determined by GC-MS technique. Results: The presence of steroids, triterpenoids, alkaloids, saponins, flavonoids, tannins and carbohydrate was found on phytochemical screening of methanol extract of the leaves. The GC-MS analysis showed 16 peaks of different phytoconstituents namely acetamide,N,N-carbonylbis-, 4-Pyranone,2,3-dihydro-, alpha-D-Galactofuranoside, methyl 2,3,5,6-tetra-O-methyl-, Glycerin, Xylitol, N,N-Dimethylglycine, 4H-Pyran-4-one,2,3-dihydro-3, 5-dihydroxy-6-methyl-, Benzofuran,2,3-dihydro-, 5-Hydroxymethylfurfural, 2(1HPyrimidinone,1-methyl-, 2,4-Dihydroxy-5,6-dimethylpyrimidine, 3-Deoxy-d-mannoic lactone, 1,3-Methylene-d-arabitol, Orcinol, n-Hexadecanoic acid and Phenol,4,4′-(1-methyl ethylidene bis etc. Conclusion: The bioactive compounds present in the methanol extract of Clerodendrum viscosum suggest the application of this extract for the treatment of various diseases by the aborigine tribes.

  3. Synthesis and antimicrobial evaluation of some novel thiazole, pyridone, pyrazole, chromene, hydrazone derivatives bearing a biologically active sulfonamide moiety.

    Science.gov (United States)

    Darwish, Elham S; Fattah, Azza M Abdel; Attaby, Fawzy A; Al-Shayea, Oqba N

    2014-01-17

    This study aimed for the synthesis of new heterocyclic compounds incorporating sulfamoyl moiety suitable for use as antimicrobial agents via a versatile, readily accessible N-[4-(aminosulfonyl)phenyl]-2-cyanoacetamide (3). The 2-pyridone derivatives were obtained via reaction of cyanoacetamide with acetylacetone or arylidenes malononitrile. Cycloaddition reaction of cyanoacetamide with salicyaldehyde furnished chromene derivatives. Diazotization of 3 with the desired diazonium chloride gave the hydrazone derivatives 13a-e. Also, the reactivity of the hydrazone towards hydrazine hydrate to give Pyrazole derivatives was studied. In addition, treatment of 3 with elemental sulfur and phenyl isothiocyanate or malononitrile furnished thiazole and thiophene derivatives respectively. Reaction of 3 with phenyl isothiocyanate and KOH in DMF afforded the intermediate salt 17 which reacted in situ with 3-(2-bromoacetyl)-2H-chromen-2-one and methyl iodide afforded the thiazole and ketene N,S-acetal derivatives respectively. Finally, reaction of 3 with carbon disulfide and 1,3-dibromopropane afforded the N-[4-(aminosulfonyl) phenyl]-2-cyano-2-(1,3-dithian-2-ylidene)acetamide product 22. All newly synthesized compounds were elucidated by considering the data of both elemental and spectral analysis. The compounds were evaluated for both their in vitro antibacterial and antifungal activities and showed promising results.

  4. Preparation of polyvinylidene fluoride/cellulose acetate blend membrane with polyethylene glycol additive for apple juice clarification

    Science.gov (United States)

    Fitri, Shatila Jihadiyah; Widiastuti, Nurul

    2017-03-01

    Polyvinylidene Fluoride (PVDF)/Cellulose Acetate (CA) blend membrane with polyethylene (PEG) addition of casting solution were synthesised to determine its morphology. This purpose of this research is to investigate the effect of PEG addition to membrane performance and its application to the clarification of apple juice. The membranes were prepared from polymer blends of CA and PVDF, dimethyl acetamide (DMAc) as solvent, and PEG as additive. Phase inversion was used to prepare membranes by mixing the polymer blends, solvent and additive to be reacted at temperature 60 °C for 24 hours. The variation of PEG weight percentage were 0, 1 wt%, 3 wt%, and 5 wt%. The addition of PEG increased porosity and fluxes, but decreased membrane rejection. Scanning Electron Microscope (SEM), Atomic Force Microscope (AFM), and Fourier Transform Infrared (FTIR) were applied to evaluate the morphology of membranes, which investigated increasing of pore size, pore distribution, and surface roughness. Apple juice clarification by membrane with 1% PEG was obtained 95,1% clearer than the pure sample.

  5. In vivo imaging of neuroinflammation in the rodent brain with [{sup 11}C]SSR180575, a novel indoleacetamide radioligand of the translocator protein (18 kDa)

    Energy Technology Data Exchange (ETDEWEB)

    Chauveau, Fabien [CEA, DSV, IBM, Service Hospitalier Frederic Joliot, Orsay (France); Universite Paris Sud, INSERM U1023, Orsay (France); Universite Lyon 1, Creatis, CNRS UMR 5220, INSERM U630, INSA Lyon, Lyon (France); Boutin, Herve [CEA, DSV, IBM, Service Hospitalier Frederic Joliot, Orsay (France); Universite Paris Sud, INSERM U1023, Orsay (France); University of Manchester, Faculty of Life Sciences, Manchester (United Kingdom); Camp, Nadja van; Tavitian, Bertrand [CEA, DSV, IBM, Service Hospitalier Frederic Joliot, Orsay (France); Universite Paris Sud, INSERM U1023, Orsay (France); Thominiaux, Cyrille; Dolle, Frederic [CEA, DSV, IBM, Service Hospitalier Frederic Joliot, Orsay (France); Hantraye, Philippe [CEA, DSV, IBM, MIRCEN, Fontenay-aux-Roses (France); Rivron, Luc [Sanofi-Aventis, GMPK-Global Isotope Chemistry and Metabolite Synthesis Department (ICMS), Paris (France); Marguet, Frank; Castel, Marie-Noelle; Rooney, Thomas; Benavides, Jesus [Sanofi-Aventis, CNS Department, Paris (France)

    2011-03-15

    Neuroinflammation is involved in neurological disorders through the activation of microglial cells. Imaging of neuroinflammation with radioligands for the translocator protein (18 kDa) (TSPO) could prove to be an attractive biomarker for disease diagnosis and therapeutic evaluation. The indoleacetamide-derived 7-chloro-N,N,5-trimethyl-4-oxo-3-phenyl-3,5-dihydro-4H-pyridazino[4,5-b]indole-1-acetamide, SSR180575, is a selective high-affinity TSPO ligand in human and rodents with neuroprotective effects. Here we report the radiolabelling of SSR180575 with {sup 11}C and in vitro and in vivo imaging in an acute model of neuroinflammation in rats. The image contrast and the binding of [{sup 11}C]SSR180575 are higher than that obtained with the isoquinoline-based TSPO radioligand, [{sup 11}C]PK11195. Competition studies demonstrate that [{sup 11}C]SSR180575 has high specific binding for the TSPO. [{sup 11}C]SSR180575 is the first PET radioligand for the TSPO based on an indoleacetamide scaffold designed for imaging neuroinflammation in animal models and in the clinic. (orig.)

  6. Trapping of NAPQI, the intermediate toxic paracetamol metabolite, by aqueous sulfide (S²⁻) and analysis by GC-MS/MS.

    Science.gov (United States)

    Trettin, Arne; Batkai, Sandor; Thum, Thomas; Jordan, Jens; Tsikas, Dimitrios

    2014-07-15

    NAPQI, i.e., N-acetyl-p-benzoquinone imine, is considered the toxic metabolite of the widely used analgesic drug paracetamol (acetaminophen, APAP). Due to its high reactivity towards nucleophiles both in low- and high-molecular-mass biomolecules, NAPQI is hardly detectable in its native form. Upon conjugation with glutathione, NAPQI is finally excreted in the urine as the paracetamol mercapturic acid. Thus, determination of paracetamol mercapturate may provide a measure of in vivo NAPQI formation. In this work, we propose the use of Na2S in aqueous solution to trap NAPQI and to analyze the reaction product, i.e., 3-thio-paracetamol, together with paracetamol by GC-MS/MS in the electron-capture negative-ion chemical ionization mode after solvent extraction with ethyl acetate and derivatization with pentafluorobenzyl bromide. In mechanistic studies, we used newly synthesized N-acetyl-p-[2,3,5,6-(2)H4]benzoquinone imine (d4-NAPQI). In quantitative analyses, N-(4-hydroxyphenyl)-[2,3,5,6-(2)H4]acetamide (d4-APAP) was used as the internal standard both for NAPQI and APAP. 3-Thio-d3-paracetamol, prepared from d4-NAPQI and Na2S, may also be useful as an internal standard. We showed NAPQI in vitro formation from APAP by recombinant cyclooxygenase-1 as well as by dog liver homogenate. In vivo formation of NAPQI was demonstrated in mice given paracetamol intraperitoneally (about 150 mg/kg).

  7. Biodegradation and detoxification of textile dye Disperse Red 54 by Brevibacillus laterosporus and determination of its metabolic fate.

    Science.gov (United States)

    Kurade, Mayur B; Waghmode, Tatoba R; Khandare, Rahul V; Jeon, Byong-Hun; Govindwar, Sanjay P

    2016-04-01

    Bioremediation is one of the milestones achieved by the biotechnological innovations. It is generating superior results in waste management such as removal of textile dyes, which are considered xenobiotic compounds and recalcitrant to biodegradation. In the present bioremedial approach, Brevibacillus laterosporus was used as an effective microbial tool to decolorize disperse dye Disperse Red 54 (DR54). Under optimized conditions (pH 7, 40°C), B. laterosporus led to 100% decolorization of DR54 (at 50 mg L(-1)) within 48 h. Yeast extract and peptone, supplemented in medium enhanced the decolorization efficiency of the bacterium. During the decolorization process, activities of enzymes responsible for decolorization, such as tyrosinase, veratryl alcohol oxidase and NADH--DCIP reductase were induced by 1.32-, 1.51- and 4.37-fold, respectively. The completely different chromatographic/spectroscopic spectrum of metabolites obtained after decolorization confirmed the biodegradation of DR54 as showed by High pressure liquid chromatography, High pressure thin layer chromatography and Fourier transform infrared spectroscopy. Gas chromatography-Mass spectroscopy studies suggested the parent dye was biodegraded into simple final product, N-(1λ(3)-chlorinin-2-yl)acetamide. Phytotoxicity study suggested that the metabolites obtained after biodegradation of DR54 were non-toxic as compared to the untreated dye signifying the detoxification of the DR54 by B. laterosporus.

  8. [Analytic evaluation of potential nootropic agents].

    Science.gov (United States)

    Opatrilová, R; Sokolová, P

    2004-01-01

    The paper deals with analytical evaluation of newly prepared substances, derivatives of N-(4-alkoxy-phenyl)-2-(2-oxo-azepan-1-yl)-acetamide. The substances are a homological series (methyl- to hexyl-). The purity of the substances was verified by thin-layer adsorption chromatography, and the principal physical characteristics--melting point and solubility--were determined. Experimental determination of the partition coefficient, extraction of the substances between two liquids miscible to a limited degree (n-octanol--water), determination of RM values by means of TLC partition chromatography (glass plates DC-Fertigplatten RP-8 F254S), determination of the capacity factor by means of HPLC (column C18 Plaris), and calculation by means of computer programmes were employed to determine the lipophilicity of this series of substances. The antiradical activity of the substances was evaluated by the method of extinguishing the stable radical 2,2-diphenyl-1-picryl-hydrazyl. Ascorbic acid, in which an antiradical effect had been demonstrated, was used for the sake of comparison. The substances show a certain activity, but they do not reach the antioxidative effect of ascorbic acid.

  9. Molecular docking studies on potential PPAR-γ agonist from Rhizophora apiculata

    Directory of Open Access Journals (Sweden)

    Gurudeeban Selvaraj

    2014-08-01

    Full Text Available Peroxisome proliferator-activated receptor gamma (PPARγ agonists are beneficial in the management of diabetes by increasing insulin sensitivity and inhibiting hepatic gluconeogenesis. The aim of the present study was to isolate and evaluate PPAR-γ agonist property of phytocompounds from Rhizophora apiculata using in silico approach. 30 g powdered leaves of R. apiculata extracted through acid-base method and subjected to GC-MS analysis. GC-MS results identified 18 phytocompounds, among those major peaks were 1-adamantyl-p-methylbenzalimine, clivorin, 4-butyl pyridine, 1-oxide, acetamide and p-aminodiethylaniline. In silico analysis of major compounds on human PPAR-γ protein was determined by AutoDock 4.0. Compared to thiazolidinediones, R. apiculata derived ligands acts as a potential agonist with binding energy -4.41, -5.29, -5.28 and -4.27 kcal/mol respectively. The molecular interaction of ligands was at residues of TYR473, ILE326, ARG288, HIS323 and ARG 288 to activate the action of PPAR-γ protein.

  10. Long-term tillage effects on soil metolachlor sorption and desorption behavior.

    Science.gov (United States)

    Ding, Guangwei; Novak, Jeffrey M; Herbert, Stephen; Xing, Baoshan

    2002-09-01

    Sorption and desorption are two important processes that influence the amount of pesticides retained by soils. However, the detailed sorption mechanisms as influenced by soil tillage management are unclear. This study examined the sorption and desorption characteristics of metolachlor [2-chloro-N-(2-ethyl-6-methyphenyl)-N-(2-methoxy-1-methylethyl)-acetamide] using the soil samples collected from the long-term conservation tillage (CnT) and conventional tillage (CT) research plots established in 1979 in Darlinton, SC. Humic acid (HA) and humin were extracted from the soils and used in the sorption experiments along with the whole soil samples. The sorption experiments were conducted using a batch-equilibration method. Three sequential desorption rinses were carried out following the sorption experiments. By comparing metolachlor sorption and desorption results we observed hysteresis for all soil samples and their organic matter fractions. Sorption nonlinearity (N) and hysteresis were dependent on the structure and composition of soil organic matter (SOM), e.g., Freundlich isotherm exponents (N) of HA and humin from CnT were higher than those of CT treatment, which may be related to high aromaticity of SOM fractions in CT treatment. Sorption capacity (K'f) was positively correlated with soil organic carbon (SOC) content. These results show that long-term tillage management can greatly affect metolachlor sorption and desorption behavior probably by qualitative differences in the structural characteristics of the humic substances.

  11. Gas Permeability and Selectivity of Synthesized Diethanol Amine-Polysulfone/Polyvinylacetate Blend Membranes

    Directory of Open Access Journals (Sweden)

    Asim Mushtaq

    2014-08-01

    Full Text Available The control of anthropogenic carbon dioxide release is one of the most challenging environmental problem faced by developing countries, as the interfering of atmospheric carbon dioxide level and climate revolutionize. An rising technology is the membrane gas separation, which is more dense, energy efficient and possibly more economical than past technologies, such as solvent absorption. Amine has a greater efficiency for removal of carbon dioxide. The blending technique not only provides improved chemical and thermal stability but is also efficient enough to improve the perm-selective properties with economical viability. In this study, research will be carried out to study the gas permeability behavior of glassy Polysulfone and Polyvinyl acetate rubbery polymeric blend membranes with diethanol amine. Polymeric amine blend membranes with different blending ratios were prepared in dimethyl acetamide solvent, flat sheet membrane were developed with enhance properties. We were studied PSU/PVAc blend with DEA amine using a gas permeability application for CO2 and CH4 at different feed pressures.

  12. Efecto de diferentes plaguicidas sobre el crecimiento de Azotobacter chroococcum

    Directory of Open Access Journals (Sweden)

    Diego Rivera

    2010-06-01

    dichlorovinyl-2,2-dimethylcyclopropane carboxylate (RS-cyano-3-phenoxybenzyl; S-metolachlor:(S-2-chloro-N-(2-ethyl-6-methyl-phenyl-N-(2-methoxy-1-methyl-ethyl-acetamide; Fluometuron: 1,1-dimethyl-3 (alpha, alpha, alpha-trifluoro-m-tolyl urea and Glyphosate: (N-(phosphonomethyl glycine on the viability of biological inoculant Monibac ® - Corpoica whose active ingredient is based on non-symbiotic diazotrophic bacteria Azotobacter chroococcum AC1, applying the minimum inhibitory concentration and compatibility techniques. The results demonstrated the susceptibility of the organism Cypermethrin 50% and when it is mixed with other pesticides in the rate used in the field regularly. It was found that there were no significant effects (P< 0,05 of pesticides (Carboxin, Thiram, Imidacloprid, S-metolachlor, Fluometuron and Glyphosate under the different concentrations tested suggesting that this bacterium is able to tolerate these chemicals by different physiological mechanisms without affecting their growth in laboratory level. Key words: Azotobacter chroococcum, agrochemicals, bacteria, biofertilizer, inhibition

  13. In vitro determination of carcinogenicity of sixty-four compounds using a bovine papillomavirus DNA-carrying C3H/10T(1/2) cell line.

    Science.gov (United States)

    Kowalski, L A; Laitinen, A M; Mortazavi-Asl, B; Wee, R K; Erb, H E; Assi, K P; Madden, Z

    2000-01-01

    A new in vitro test for predicting rodent carcinogenicity is evaluated against a testing database of 64 chemicals including both genotoxic and nongenotoxic carcinogens and carcinogens that normally require addition of an S-9 microsomal fraction for detection in the bacterial mutagenicity assay. The assay uses focus formation in a stable, bovine papillomavirus type 1 (BPV-1) DNA carrying C3H/10T(1/2) mouse embryo fibroblast cell line (T1) that does not require transfection, infection with virus, isolation of primary cells from animals, or addition of a microsomal fraction. Of a total database of 64 compounds, 92% of the carcinogens, promoters, or noncarcinogens were correctly predicted. Based on previously reported results, the test of bacterial mutagenicity would have correctly predicted 58% of carcinogens, promoters or noncarcinogens and the Syrian hamster embryo test would have correctly predicted 87% of carcinogens, promoters, or noncarcinogens of this database. Of carcinogens that normally require addition of an S-9 fraction, T1 cells correctly predicted rodent carcinogenicity of polyaromatic hydrocarbons, aflatoxins, azo-compounds, nitrosamines, and hydrazine without the addition of an S-9 fraction. Of nongenotoxic carcinogens, T1 cells correctly predicted diethylstilbestroel, diethylhexylphthalate, acetamides, alkyl halides, ethyl carbamate, and phorbol ester tumour promoters.

  14. Permeability of commercial solvents through living human skin

    DEFF Research Database (Denmark)

    Ursin, C; Hansen, C M; Van Dyk, J W;

    1995-01-01

    rate. For other solvents this was not necessary, so the un-normalized data were used. High [3H]water permeation rate also was used as a criterion for "defective" skin samples that gave erroneous permeability rates, especially for solvents having slow permeability. The linearity of the steady state data...... was characterized by calculation of the "percent error of the slope." The following permeability rates (g/m2h) of single solvents were measured: dimethyl sulfoxide (DMSO), 176; N-methyl-2-pyrrolidone, 171; dimethyl acetamide, 107; methyl ethyl ketone, 53; methylene chloride, 24; [3H]water, 14.8; ethanol, 11.......3; butyl acetate, 1.6; gamma-butyrolactone, 1.1; toluene, 0.8; propylene carbonate, 0.7; and sulfolane, 0.2. The effect of [3H]water saturation on the shape of the presteady state portion of the permeation curve was determined and found to be very dependent on the solvent. The permeability of mixtures...

  15. Thermal analysis and structural characterization of chitinous exoskeleton from two marine invertebrates

    Energy Technology Data Exchange (ETDEWEB)

    Juárez-de la Rosa, B.A., E-mail: balej05@yahoo.com.mx [Laboratory of Natural Polymers, CIAD – Coordinación Guaymas, Carretera al Varadero Nacional km. 6.6, Col. Las Playitas, 85480 Guaymas, Sonora (Mexico); Applied Physics Department, CINVESTAV-IPN Unidad Mérida, Carretera antigua a Progreso, km. 6. Apdo, Postal 73, Cordemex, 97310 Mérida, Yucatan (Mexico); May-Crespo, J.; Quintana-Owen, P.; Gónzalez-Gómez, W.S. [Applied Physics Department, CINVESTAV-IPN Unidad Mérida, Carretera antigua a Progreso, km. 6. Apdo, Postal 73, Cordemex, 97310 Mérida, Yucatan (Mexico); Yañez-Limón, J.M. [Materials and Engineering Science, CINVESTAV-IPN, Unidad Querétaro, Libramiento Norponiente No. 2000, Fracc. Real de Juriquilla, 76230 Santiago de Querétaro, Querétaro (Mexico); Alvarado-Gil, J.J., E-mail: jjag@mda.cinvestav.mx [Applied Physics Department, CINVESTAV-IPN Unidad Mérida, Carretera antigua a Progreso, km. 6. Apdo, Postal 73, Cordemex, 97310 Mérida, Yucatan (Mexico)

    2015-06-20

    Highlights: • Thermal analysis of exoskeletons: Antipathes caribbeana and Limulus polyphemus. • DMTA revealed Limulus has a stronger structure with a stepper glass transition. • DSC measurements exhibited a much larger water holding capacity in Antipathes. • X-ray diffraction analysis shows a higher crystallinity index in Limulus • FTIR showed α-chitin structures and high temperature C–N groups prevalence. - ABSTRACT: Thermomechanical and structural properties of two marine species exoskeletons, Antipathes caribbeana (black coral) and Limulus polyphemus (xiphosure), were studied using dynamic mechanical thermal analysis (DMTA), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). DMTA curves indicate the viscoelastic behavior and glass transition around 255 °C, black coral presented a second transition (175 °C) associated to the acetamide group attached to the α-chitin chain. DSC measurements showed a endothermic peak around 100 °C, with enthalpies of 4.02 and 118.04 J/g, indicating strong differences between exoskeletons respect to their water holding capacity and strength water–polymer interaction. A comparative analysis involving DSC and X-ray diffraction showed that lower values ΔH in xiphosure correspond to a material with a higher crystallinity (30), in contrast black coral exhibits higher values ΔH and a lower crystallinity (19). FTIR confirmed α-chitin based structure, at higher temperature diminishes the amide bands and a new one appears, related to C–N groups.

  16. Confirming anthropogenic influences on the major organic and inorganic constituents of rainwater in an urban area

    Directory of Open Access Journals (Sweden)

    K. Chon

    2015-06-01

    Full Text Available The chemical composition and organic compounds of rainwater were investigated from June to December 2012 at Gwangju in Korea. The volume weighted mean of pH ranged from 3.83 to 8.90 with an average of 5.78. 50 % of rainwater samples had pH values below 5.6. The volume-weighted mean concentration (VWMC of major ions followed the order: Cl− > SO42− > NH4+ > Na+ > NO3− > Ca2+ > Mg2+ > K+. The VWMC of trace metals decreased in the order as follows Zn > Al > Fe > Mn > Pb > Cu > Ni > Cd > Cr. The VWMCs of major ions and trace metals were higher in winter than in summer. The high enrichment factors indicate that Zn, Pb, Cu, and Cd originated predominantly from anthropogenic sources. Factor analysis (principal component analysis indicates the influence of anthropogenic pollutants, sea salt, and crustal materials on the chemical compositions of rainwater. Benzoic acids, 1H-Isoindole-1,3(2H-dione, phthalic anhydride, benzene, acetic acids, 1,2-benzenedicarboxylic acids, benzonitrile, acetaldehyde, and acetamide were the most prominent pyrolysis fragments for rainwater organic compounds identified by pyrolysis gas chromatography/mass spectrometry (Py-GC/MS. The results indicate that anthropogenic sources are the most important factors affecting the organic composition of rainwater in urban area.

  17. Role of Lewis acid additives in a palladium catalyzed directed C-H functionalization reaction of benzohydroxamic acid to isoxazolone.

    Science.gov (United States)

    Athira, C; Sunoj, Raghavan B

    2016-12-20

    Metallic salts as well as protic additives are widely employed in transition metal catalyzed C-H bond functionalization reactions to improve the efficiency of catalytic protocols. In one such example, ZnCl2 and pivalic acid are used as additives in a palladium catalyzed synthesis of isoxazolone from a readily available benzohydroxamic acid under one pot conditions. In this article, we present some important mechanistic insights into the role of ZnCl2 and pivalic acid, gained by using density functional theory (M06) computations. Two interesting modes of action of ZnCl2 are identified in various catalytic steps involved in the formation of isoxazolone. The conventional Lewis acid coordination wherein zinc chloride (ZnCl2·(DMA)) binds to the carbonyl group is found to be more favored in the C-H activation step. However, the participation of a hetero-bimetallic Pd-Zn species is preferred in reductive elimination leading to Caryl-N bond formation. Pivalic acid helps in relay proton transfer in C-H bond activation through a cyclometallation deprotonation (CMD) process. The explicit inclusion of ZnCl2 and solvent N,N-dimethyl acetamide (DMA) stabilizes the transition state and also helps reduce the activation barrier for the C-H bond activation step. The electronic communication between the two metal species is playing a crucial role in stabilizing the Caryl-N bond formation transition state through a Pd-Zn hetero-bimetallic interaction.

  18. Effect of DNA damage caused by cryopreservation of spermatozoa using a modified Single cell gell electrophoresis in the freshwater catfish Pangasianodon hypophthalmus (Fowler, 1936

    Directory of Open Access Journals (Sweden)

    Kuppusamy Umaa Rani

    2014-07-01

    Full Text Available Objective: To detect the integrity of sperm DNA in the catfish Pangasianodon hypophthalmus cryopreserved with Hanks balanced salt solution, 5%-30% dimethyl acetamide (DMA using the single-cell gel electrophoresis in order to test how sperm cryopreservation affected nuclear DNA stability. Methods: Electrophoresis was conducted for 60 min at 130 mA and 15 V. The comet images were analyzed using software CometScore 1.5, and parameters such as comet length, tail length and percentage DNA in the tail were obtained. Then the comet rate and damage coefficient were calculated. Results: There were no significant differences in motility, comet rate and damage coefficient between fresh sperm and cryopreserved sperm stored in 5%, 10%, 15% and 20% DMA, while the sperm cryopreserved with 25% and 30% DMA had lower motility, higher comet length and damage coefficients than those of fresh sperm. Conclusions: There was a positive correlation between comet rate of cryopreserved sperm and the concentration of DMA. The toxicity of cryoprotectant is the main factor for DNA damage in cryopreserved sperm.

  19. Identification, synthesis, isolation and spectral characterization of potential impurities of montelukast sodium.

    Science.gov (United States)

    Saravanan, M; Siva Kumari, K; Pratap Reddy, P; Naidu, M N; Moses Babu, J; Srivastava, Alok Kumar; Lakshmi Kumar, T; Chandra Sekhar, B V V N; Satyanarayana, Bollikonda

    2008-11-04

    During the process development of montelukast sodium, three polar impurities and one non-polar impurity with respect to montelukast sodium were detected by simple reverse phase high-performance liquid chromatography (HPLC). Initially, all the four impurities were identified by the liquid chromatography-mass spectrometry (LC-MS) data and out of four impurities, three have been prepared by the synthetic method and remaining one is isolated by preparative HPLC. Based on the spectral data (IR, (1)H NMR, (13)C NMR and MS), the structure of these impurities 1-4 were characterised as 1-[[[(1R)-1-[3-[(1E)-2-(7-chloro-2-quinolinyl)ethenyl]phenyl-3-[2-(1-hydroxy-1-methylethyl)phenyl]propyl]thio]methyl]cyclopropane acetamide (impurity-1), {1-[1-{3-[2-(7-chloro-quinolin-2-yl)-vinyl]-phenyl}-3-(2-isopropenyl-phenyl)-propylsulfanylmethyl]-cyclopropyl}-acetic acid (impurity-2), 1-[[[(1R)-1-[3-[(1E)-2-(7-chloro-2-quinolinyl)ethyl]phenyl-3-[2-(1-hydroxy-1-methylethyl)phenyl]propyl]thio]methyl]cyclopropaneacetic acid (impurity-3) and 1-[[[(1R)-1-[3-[(1E)-2-(2-quinolinyl)ethenyl]phenyl-3-[2-(1-hydroxy-1-methylethyl)phenyl]propyl]thio]methyl]cyclopropaneacetic acid (impurity-4).

  20. Biodegradation of acrylamide by Enterobacter aerogenes isolated from wastewater in Thailand.

    Science.gov (United States)

    Buranasilp, Kanokhathai; Charoenpanich, Jittima

    2011-01-01

    A widespread use of acrylamide, probably a neurotoxicant and carcinogen, in various industrial processes has led to environmental contamination. Fortunately, some microorganisms are able to derive energy from acrylamide. In the present work, we reported the isolation and characterization of a novel acrylamide-degrading bacterium from domestic wastewater in Chonburi, Thailand. The strain grew well in the presence of acrylamide as 0.5% (W/V), at pH 6.0 to 9.0 and 25 degrees C. Identification based on biochemical characteristics and 16S rRNA gene sequence identified the strain as Enterobacter aerogenes. Degradation of acrylamide to acrylic acid started in the late logarithmic growth phase as a biomass-dependent pattern. Specificity of cell-free supernatant towards amides completely degraded butyramide and urea and 86% of lactamide. Moderate degradation took place in other amides with that by formamide > benzamide > acetamide > cyanoacetamide > propionamide. No degradation was detected in the reactions of N,N-methylene bisacrylamide, sodium azide, thioacetamide, and iodoacetamide. These results highlighted the potential of this bacterium in the cleanup of acrylamide/amide in the environment.

  1. Bio-Inspired Nitrile Hydration by Peptidic Ligands Based on L-Cysteine, L-Methionine or L-Penicillamine and Pyridine-2,6-dicarboxylic Acid

    Directory of Open Access Journals (Sweden)

    Cillian Byrne

    2014-12-01

    Full Text Available Nitrile hydratase (NHase, EC 4.2.1.84 is a metalloenzyme which catalyses the conversion of nitriles to amides. The high efficiency and broad substrate range of NHase have led to the successful application of this enzyme as a biocatalyst in the industrial syntheses of acrylamide and nicotinamide and in the bioremediation of nitrile waste. Crystal structures of both cobalt(III- and iron(III-dependent NHases reveal an unusual metal binding motif made up from six sequential amino acids and comprising two amide nitrogens from the peptide backbone and three cysteine-derived sulfur ligands, each at a different oxidation state (thiolate, sulfenate and sulfinate. Based on the active site geometry revealed by these crystal structures, we have designed a series of small-molecule ligands which integrate essential features of the NHase metal binding motif into a readily accessible peptide environment. We report the synthesis of ligands based on a pyridine-2,6-dicarboxylic acid scaffold and L-cysteine, L-S-methylcysteine, L-methionine or L-penicillamine. These ligands have been combined with cobalt(III and iron(III and tested as catalysts for biomimetic nitrile hydration. The highest levels of activity are observed with the L-penicillamine ligand which, in combination with cobalt(III, converts acetonitrile to acetamide at 1.25 turnovers and benzonitrile to benzamide at 1.20 turnovers.

  2. A novel acylaminoimidazole derivative, WN1316, alleviates disease progression via suppression of glial inflammation in ALS mouse model.

    Directory of Open Access Journals (Sweden)

    Kazunori Tanaka

    Full Text Available Amyotrophic lateral sclerosis (ALS is an adult-onset motor neuron degenerative disease. Given that oxidative stress and resulting chronic neuronal inflammation are thought to be central pathogenic, anti-oxidative agents and modulators of neuronal inflammation could be potential therapies for ALS. We report here that the novel small molecular compound, 2-[mesityl(methylamino]-N-[4-(pyridin-2-yl-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316 selectively suppresses oxidative stress-induced cell death and neuronal inflammation in the late-stage ALS mice. WN1316 has high blood-brain-barrier permeability and water solubility, and boosts both neuronal apoptosis inhibitory protein (NAIP and NF-E2-related factor 2 (Nrf2 which governed glutathione (GSH-related anti-oxidation pathway protecting motor neurons against oxidative injuries. Post-onset oral administration of low dose (1-100 µg/kg/day WN1316 in ALS(SOD1(H46R and ALS(SOD1(G93A mice resulted in sustained improved motor function and post onset survival rate. Immunohistochemical analysis revealed less DNA oxidative damage and motor neuronal inflammation as well as repression of both microgliosis and astrocytosis, concomitant down regulation of interleukin-1β and inducible nitric oxide synthase, and preservation of the motoneurons in anterior horn of lumbar spinal cord and skeletal muscle (quadriceps femoris. Thus, WN1316 would be a novel therapeutic agent for ALS.

  3. Efficient Synthesis of Novel Pyridine-Based Derivatives via Suzuki Cross-Coupling Reaction of Commercially Available 5-Bromo-2-methylpyridin-3-amine: Quantum Mechanical Investigations and Biological Activities.

    Science.gov (United States)

    Ahmad, Gulraiz; Rasool, Nasir; Ikram, Hafiz Mansoor; Gul Khan, Samreen; Mahmood, Tariq; Ayub, Khurshid; Zubair, Muhammad; Al-Zahrani, Eman; Ali Rana, Usman; Akhtar, Muhammad Nadeem; Alitheen, Noorjahan Banu

    2017-01-27

    The present study describes palladium-catalyzed one pot Suzuki cross-coupling reaction to synthesize a series of novel pyridine derivatives 2a-2i, 4a-4i. In brief, Suzuki cross-coupling reaction of 5-bromo-2-methylpyridin-3-amine (1) directly or via N-[5-bromo-2-methylpyridine-3-yl]acetamide (3) with several arylboronic acids produced these novel pyridine derivatives in moderate to good yield. Density functional theory (DFT) studies were carried out for the pyridine derivatives 2a-2i and 4a-4i by using B3LYP/6-31G(d,p) basis with the help of GAUSSIAN 09 suite programme. The frontier molecular orbitals analysis, reactivity indices, molecular electrostatic potential and dipole measurements with the help of DFT methods, described the possible reaction pathways and potential candidates as chiral dopants for liquid crystals. The anti-thrombolytic, biofilm inhibition and haemolytic activities of pyridine derivatives were also investigated. In particular, the compound 4b exhibited the highest percentage lysis value (41.32%) against clot formation in human blood among all newly synthesized compounds. In addition, the compound 4f was found to be the most potent against Escherichia coli with an inhibition value of 91.95%. The rest of the pyridine derivatives displayed moderate biological activities.

  4. Silver complexes of 1,2,4-triazole derived N-heterocyclic carbenes: Synthesis, structure and reactivity studies

    Indian Academy of Sciences (India)

    Chandrakanta Dash; Mobin M Shaikh; Prasenjit Ghosh

    2011-03-01

    Two silver(I) complexes {[1-R-4-(-t4-butylacetamido)-1,2,4-triazol-5-ylidene]2Ag}+ Cl− [R = Et (1b), -Pr (2b)] of /-functionalized N-heterocyclic carbenes derived from 1,2,4-triazoles are reported. The silver complexes, 1b and 2b, have been synthesized from the reaction of the /-functionalized triazolium chloride salts namely, 1-R-4-(N-t-butylacetamido)-1,2,4-triazolium chloride [R = Et (1a), -Pr (2a)] by treatment with Ag2O in 53-56% yield. The 1,2,4-triazolium chloride salts 1a and 2a were prepared by the alkylation reaction of 1-R-1,2,4-triazole (R = Et, -Pr) with --butyl-2-chloro acetamide in 47-63% yield. The molecular structures of the silver(I) complexes, 1b and 2b, have been determined by X-ray diffraction studies. The density functional theory studies on the silver 1b and 2b complexes suggest that the 1,2,4-triazole derived N-heterocyclic carbenes to be strong −donating ligands similar to the now much recognized imidazolebased N-heterocyclic carbenes. The reactivity studies with (SMe2)AuCl and (SMe2)CuBr indicated the silver complexes, 1b and 2b, to be good transmetallating agents.

  5. Preparation and characterization of regenerated cellulose membranes from natural cotton fiber

    Directory of Open Access Journals (Sweden)

    Yanjuan CAO

    2015-06-01

    Full Text Available A series of organic solutions with different cellulose concentrations are prepared by dissolving natural cotton fibers in lithium chloride/dimethyl acetamide (LiCl/DMAC solvent system after the activation of cotton fibers. Under different coagulating bath, the regenerated cellulose membranes are formed in two kinds of coagulation baths, and two coating methods including high-speed spin technique (KW-4A spin coating machine and low-speed scraping (AFA-Ⅱ Film Applicator are selected in this paper. The macromolecular structure, mechanical properties, crystallinity, thermal stability and wetting property of the regenerated cellulose membrane are characterized by Scanning Electron Microscope(SEM, Fourier Transform Infrared Spectroscopy (FT-IR,X-ray diffraction (XRD, Thermogravimetric analysis (TG and contacting angle tester. The effects of mass fraction, coagulation bath type, membrane forming process on the regenerated membrane properties are investigated. Experimental results show that the performance of regenerated cellulose membrane is relatively excellent under the condition of using the KW-4A high-speed spin method, water coagulation bath, and when mass fraction of cellulose is 3.5%. The crystallinity of the regenerated cellulose membrane changes a lot compared with natural cotton fibers. The variation trend of thermal stability is similar with that of cotton fiber. But thermal stability is reduced to some degree, while the wetting ability is improved obviously.

  6. Hydrogen Bonding Interaction between Atmospheric Gaseous Amides and Methanol.

    Science.gov (United States)

    Zhao, Hailiang; Tang, Shanshan; Xu, Xiang; Du, Lin

    2016-12-30

    Amides are important atmospheric organic-nitrogen compounds. Hydrogen bonded complexes of methanol (MeOH) with amides (formamide, N-methylformamide, N,N-dimethylformamide, acetamide, N-methylacetamide and N,N-dimethylacetamide) have been investigated. The carbonyl oxygen of the amides behaves as a hydrogen bond acceptor and the NH group of the amides acts as a hydrogen bond donor. The dominant hydrogen bonding interaction occurs between the carbonyl oxygen and the OH group of methanol as well as the interaction between the NH group of amides and the oxygen of methanol. However, the hydrogen bonds between the CH group and the carbonyl oxygen or the oxygen of methanol are also important for the overall stability of the complexes. Comparable red shifts of the C=O, NH- and OH-stretching transitions were found in these MeOH-amide complexes with considerable intensity enhancement. Topological analysis shows that the electron density at the bond critical points of the complexes fall in the range of hydrogen bonding criteria, and the Laplacian of charge density of the O-H∙∙∙O hydrogen bond slightly exceeds the upper value of the Laplacian criteria. The energy decomposition analysis further suggests that the hydrogen bonding interaction energies can be mainly attributed to the electrostatic, exchange and dispersion components.

  7. Improved synthesis of the peripheral benzodiazepine receptor ligand [{sup 11}C]DPA-713 using [{sup 11}C]methyl triflate

    Energy Technology Data Exchange (ETDEWEB)

    Thominiaux, C. [Service Hospitalier Frederic Joliot, Departement de Recherche Medicale, CEA/DSV, 4 place du General Leclerc, F-91401 Orsay (France); Dolle, F. [Service Hospitalier Frederic Joliot, Departement de Recherche Medicale, CEA/DSV, 4 place du General Leclerc, F-91401 Orsay (France); James, M.L. [Department of Pharmacology, University of Sydney, NSW 2006 (Australia)] (and others)

    2006-05-15

    Recently, the pyrazolopyrimidine, [{sup 11}C] N,N-Diethyl-2-[2-(4-methoxyphenyl)-5,7-dimethylpyrazolo [1,5-a]pyrimidin-3-yl]acetamide (DPA-713) has been reported as a new promising marker for the study of peripheral benzodiazepine receptors with positron emission tomography. In the present study, DPA-713 has been labelled from the corresponding nor-analogue using [{sup 11}C]methyl triflate (CH{sub 3}OTf). Conditions for HPLC were also modified to include physiological saline (aq. 0.9% NaCl)/ethanol:60/40 as mobile phase making it suitable for injection. The total time of radiosynthesis, including HPLC purification, was 18-20 min. This reported synthesis of [{sup 11}C]DPA-713, using [{sup 11}C]CH{sub 3}OTf, resulted in an improved radiochemical yield (30-38%) compared to [{sup 11}C]methyl iodide (CH{sub 3}I) (9) with a simpler purification method. This ultimately enhances the potential of [{sup 11}C]DPA-713 for further pharmacological and clinical evaluation. These improvements make this radioligand more suitable for automated synthesis which is of benefit where multi-dose preparations and repeated syntheses of radioligand are required.

  8. Sensitivity of transitions in internal rotor molecules to a possible variation of the proton-to-electron mass ratio

    Energy Technology Data Exchange (ETDEWEB)

    Jansen, Paul; Ubachs, Wim; Bethlem, Hendrick L. [Institute for Lasers, Life and Biophotonics, VU University Amsterdam, De Boelelaan 1081, NL-1081 HV Amsterdam (Netherlands); Kleiner, Isabelle [Laboratoire Interuniversitaire des Systemes Atmospheriques (LISA), CNRS UMR 7583 et Universites Paris 7 et Paris Est, 61 avenue du General de Gaulle, FR-94010 Creteil Cedex (France); Xu, Li-Hong [Department of Physics and Centre for Laser, Atomic, and Molecular Sciences, University of New Brunswick, Saint John, New Brunswick, Canada E2L 4L5 (Canada)

    2011-12-15

    Recently, methanol was identified as a sensitive target system to probe variations of the proton-to-electron mass ratio {mu}[Jansen et al., Phys. Rev. Lett. 106, 100801 (2011)]. The high sensitivity of methanol originates from the interplay between overall rotation and hindered internal rotation of the molecule; that is, transitions that convert internal rotation energy into overall rotation energy, or vice versa, have an enhanced sensitivity coefficient, K{sub {mu}}. As internal rotation is a common phenomenon in polyatomic molecules, it is likely that other molecules display similar or even larger effects. In this paper we generalize the concepts that form the foundation of the high sensitivity in methanol and use this to construct an approximate model which makes it possible to estimate the sensitivities of transitions in internal rotor molecules with C{sub 3v} symmetry, without performing a full calculation of energy levels. We find that a reliable estimate of transition sensitivities can be obtained from the three rotational constants (A, B, and C) and three torsional constants (F, V{sub 3}, and {rho}). This model is verified by comparing obtained sensitivities for methanol, acetaldehyde, acetamide, methyl formate, and acetic acid with a full analysis of the molecular Hamiltonian. Of the molecules considered, methanol is by far the most suitable candidate for laboratory and cosmological tests searching for a possible variation of {mu}.

  9. Synthesis Organonitrogen Compounds from Patchouli Alcohol Through Ritter Reaction with Acetonitrile and Its Toxicity to Artemia salina Leach.

    Directory of Open Access Journals (Sweden)

    Khoirun Nisyak

    2013-03-01

    Full Text Available Patchouli oil contains a compound with biological activities to human body called the patchouli alcohol that can be further developed in medical field. This research aimed to synthesize organonitrogen compound from patchouli alcohol through Ritter reaction with acetonitrile and discover its toxicity towards Artemia salina Leach. The isolation of patchouli alcohol from patchouli oil using fractional distillation under reduced pressure method. The synthesis of organonitrogen compound is done at room temperature with the mol ratio of patchouli alcohol: acetonitrile: sulfuric acid is 1:1,5:4 for 24 hours. The result showed that the amount of patchouli alcohol produced from fractional distillation is 65,25%. The main product yielded from the synthesis between patchouli alcohol and acetonitrile through Ritter reaction is 36,93 % of N-(4,8a,9,9-tetramethyl decahydro-1,6-methanonaphtalene-1-yl acetamide. Starting material used have LC50 of 77,39 ppm. The product of synthesis have higher toxicity level than starting material, which have LC50 value is 10,39 ppm with the potential as medical compounds.

  10. Evaluation of the structural, electronic, topological and vibrational properties of N-(3,4-dimethoxybenzyl)-hexadecanamide isolated from Maca (Lepidium meyenii) using different spectroscopic techniques

    Science.gov (United States)

    Chain, Fernando; Iramain, Maximiliano Alberto; Grau, Alfredo; Catalán, César A. N.; Brandán, Silvia Antonia

    2017-01-01

    N-(3,4-dimethoxybenzyl)-hexadecanamide (DMH) was characterized by using Fourier Transform infrared (FT-IR) and Raman (FT-Raman), Ultraviolet- Visible (UV-Visible) and Hydrogen and Carbon Nuclear Magnetic Resonance (1H and 13C NMR) spectroscopies. The structural, electronic, topological and vibrational properties were evaluated in gas phase and in n-hexane employing ONIOM and self-consistent force field (SCRF) calculations. The atomic charges, molecular electrostatic potentials, stabilization energies and topological properties of DMH were analyzed and compared with those calculated for N-(3,4-dimethoxybenzyl)-acetamide (DMA) in order to evaluate the effect of the side chain on the properties of DMH. The reactivity and behavior of this alkamide were predicted by using the gap energies and some descriptors. Force fields and the corresponding force constants were reported for DMA only in gas phase and n-hexane due to the high number of vibration normal modes showed by DMH, while the complete vibrational assignments are presented for DMA and both forms of DMH. The comparisons between the experimental FTIR, FT-Raman, UV-Visible and 1H and 13C NMR spectra with the corresponding theoretical ones showed a reasonable concordance.

  11. Advanced Development and Characterization of DEA Amine-Polysulfone/Polyvinylacetate Blend Membranes

    Directory of Open Access Journals (Sweden)

    Asim Mushtaq

    2014-09-01

    Full Text Available Membrane technology effectively separates CO2 from CH4 and has been practiced for many years but requires membranes with high selectivity and permeability. Different approaches are employed to improve membrane performance and it is soon possible to develop a blended polymeric membrane that separates high pressure gas streams at the point of processing pressure. However, glassy polymers suffer a lack of permeability causing their performance to drop as an upper bound trade-off but highly selective and rubbery polymers have high permeability with low selectivity. As an amine solution is capable of purifying naturally acidic gas, blending glassy, rubbery polymers with amines-specifically, polysulfone and polyvinyl acetate with diethanol amine in dimethyl acetamide as solvent-we developed flat sheet membranes with desirable properties. As it is now possible to acquire amine-polymer blends with more desirable properties by mixing with a miscible polymer, it is essential to observe factors that affect the polymer's miscibility with amines. Hence, we also analyzed the effects of blend ratios on different properties. Blended membranes of different ratios were synthesized and their functional groups were characterized by Fourier Transformed Infra-Red spectroscopy (FTIR. We then employed Thermal Gravimetric Analysis (TGA to describe weight loss and Field Emission Scanning Electron Microscopy (FESEM to determine respective morphologies.

  12. ucb L059, a novel anti-convulsant drug: pharmacological profile in animals.

    Science.gov (United States)

    Gower, A J; Noyer, M; Verloes, R; Gobert, J; Wülfert, E

    1992-11-10

    The anticonvulsant activity of ucb L059 ((S)-alpha-ethyl-2-oxo-pyrrolidine acetamide) was evaluated in a range of animal models. ucb L059 was active after oral and intraperitoneal administration in both rats and mice, with a unique profile of action incorporating features in common with several different types of antiepileptic drugs. The compound was active, with ED50 values generally within the range of 5.0-30.0 mg/kg, in inhibiting audiogenic seizures, electrically induced convulsions and convulsions induced chemically by pentylenetetrazole (PTZ), bicuculline, picrotoxin and N-methyl-D-aspartate (NMDA). ucb L059 retarded the development of PTZ-induced kindling in mice and reduced PTZ-induced EEG spike wave discharge in rats. The R enantiomer, ucb L060, had low intrinsic anticonvulsant activity, showing the stereospecificity of action of the molecule although the actual mechanism of action remains unknown. Neurotoxicity, evaluated with an Irwin-type observation test, the rotarod test and open-field exploration, was minimal, with only mild sedation being observed, even at doses 50-100 times higher than the anticonvulsant doses; at pharmacologically active doses, the animals appeared calm but slightly more active. ucb L059 thus presents as an orally active, safe, broad-spectrum anticonvulsant agent, with potential antiepileptogenic and anti-absence actions.

  13. Deformation micromechanics of all-cellulose nanocomposites: comparing matrix and reinforcing components.

    Science.gov (United States)

    Pullawan, Tanittha; Wilkinson, Arthur N; Zhang, Lina N; Eichhorn, Stephen J

    2014-01-16

    All-cellulose nanocomposites, comprising two different forms of cellulose nanowhiskers dispersed in two different matrix systems, are produced. Acid hydrolysis of both tunicate (T-CNWs) and cotton cellulose (CNWs) is carried out to produce the nanowhiskers. These nanowhiskers are then dispersed in a cellulose matrix material, produced using two dissolution methods; namely lithium chloride/N,N-dimethyl acetamide (LiCl/DMAc) and sodium hydroxide/urea (NaOH/urea). Crystallinity of both nanocomposite systems increases with the addition of nanowhiskers up to a volume fraction of 15 v/v%, after which a plateau is reached. Stress-transfer mechanisms, between the matrix and the nanowhiskers in both of these nanocomposites are reported. This is achieved by following both the mechanical deformation of the materials, and by following the molecular deformation of both the nanowhiskers and matrix phases using Raman spectroscopy. In order to carry out the latter of these analyses, two spectral peaks are used which correspond to different crystal allomorphs; cellulose-I for the nanowhiskers and cellulose-II for the matrix. It is shown that composites comprising a LiCl/DMAc based matrix perform better than NaOH/urea based systems, the T-CNWs provide better reinforcement than CNWs and that an optimum loading of nanowhiskers (at 15 v/v%) is required to obtain maximum tensile strength and modulus.

  14. Ani9, A Novel Potent Small-Molecule ANO1 Inhibitor with Negligible Effect on ANO2.

    Directory of Open Access Journals (Sweden)

    Yohan Seo

    Full Text Available Anoctamin1 (ANO1/transmembrane protein 16A (TMEM16A, a calcium-activated chloride channel (CaCC, is involved in many physiological functions such as fluid secretion, smooth muscle contraction, nociception and cancer progression. To date, only a few ANO1 inhibitors have been described, and these have low potency and selectivity for ANO1. Here, we performed a high-throughput screening to identify highly potent and selective small molecule inhibitors of ANO1. Three novel ANO1 inhibitors were discovered from screening of 54,400 synthetic small molecules, and they were found to fully block ANO1 channel activity with an IC50 < 3 μM. Electrophysiological analysis revealed that the most potent inhibitor, 2-(4-chloro-2-methylphenoxy-N-[(2-methoxyphenylmethylideneamino]-acetamide (Ani9, completely inhibited ANO1 chloride current with submicromolar potency. Notably, unlike previous small-molecule ANO1 inhibitors identified to date, Ani9 displayed high selectivity for ANO1 as compared to ANO2, which shares a high amino acid homology to ANO1. In addition, Ani9 did not affect the intracellular calcium signaling and CFTR chloride channel activity. Our results suggest that Ani9 may be a useful pharmacological tool for studying ANO1 and a potential development candidate for drug therapy of cancer, hypertension, pain, diarrhea and asthma.

  15. Synthesis and applications of chitosan mercaptanes as heavy metal retention agent.

    Science.gov (United States)

    Cárdenas, G; Orlando, P; Edelio, T

    2001-01-10

    Chitosan, poly-beta(1-->4)-2 amino-2-deoxy-D-Glucopyranose is a biopolymer obtained by extensive deacetylation of chitin [poly-beta(1-->4)-2-acetamide-2-deoxy-D-Glucopyranose], main constituent of crustacean shells. The present study was carried out using crab shells from nylon shrimps (Heterocarpus reedi). Despite the abundance of raw material in our environment, little work has been published in this field using derivatives. The main goal of this work is to develop a good method to prepare chitosan mercaptanes derivatives using mercaptoacetic acid and 1-chloro-2,3-epoxy propane propionic acid. The evaluation of the retention capacities using several concentrations of copper and mercury solutions with concentrations ranging from 10 to 104 ppm at pH 2.5 and 4.5 are tested. A comparison of the absorption isotherms with Langmuir isotherms is also reported. Full characterization of the derivatives was carried out using FTIR, elemental analysis and TGA. The morphology of chitosan and derivatives is compared before and after treating polymers with mercury and copper ions.

  16. A3 Adenosine receptors mediate oligodendrocyte death and ischemic damage to optic nerve.

    Science.gov (United States)

    González-Fernández, Estíbaliz; Sánchez-Gómez, María Victoria; Pérez-Samartín, Alberto; Arellano, Rogelio O; Matute, Carlos

    2014-02-01

    Adenosine receptor activation is involved in myelination and in apoptotic pathways linked to neurodegenerative diseases. In this study, we investigated the effects of adenosine receptor activation in the viability of oligodendrocytes of the rat optic nerve. Selective activation of A3 receptors in pure cultures of oligodendrocytes caused concentration-dependent apoptotic and necrotic death which was preceded by oxidative stress and mitochondrial membrane depolarization. Oligodendrocyte apoptosis induced by A3 receptor activation was caspase-dependent and caspase-independent. In addition to dissociated cultures, incubation of optic nerves ex vivo with adenosine and the A3 receptor agonist 2-CI-IB-MECA(1-[2-Chloro-6-[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl]-1-deoxy-N-methyl-b-D-ribofuranuronamide)-induced caspase-3 activation, oligodendrocyte damage, and myelin loss, effects which were prevented by the presence of caffeine and the A3 receptor antagonist MRS 1220 (N-[9-Chloro-2-(2-furanyl)[1,2,4]-triazolo [1,5-c]quinazolin-5-yl]benzene acetamide). Finally, ischemia-induced injury and functional loss to the optic nerve was attenuated by blocking A3 receptors. Together, these results indicate that adenosine may trigger oligodendrocyte death via activation of A3 receptors and suggest that this mechanism contributes to optic nerve and white matter ischemic damage.

  17. Influence of pine or oak wood on the degradation of alachlor and metalaxyl in soil.

    Science.gov (United States)

    Rodríguez-Cruz, M Sonia; Marín-Benito, Jesús M; Ordax, José M; Azejjel, Hanane; Sánchez-Martín, María J

    2012-03-01

    The objective of this work was to study the influence pine or oak wood added to soil as an amendment (5% w/w) had on the degradation rate of two pesticides, alachlor and metalaxyl, with different hydrophobic character. The formation of pesticide metabolites and the soil dehydrogenase activity in non-amended and amended soil samples were also monitored. The degradation of metalaxyl followed first-order kinetics, while the degradation of alachlor followed first-order or biphasic kinetics in the soil samples studied. The results indicated that the degradation rate was slower for metalaxyl than for alachlor, and for both pesticides followed the order: pine amended soil metalaxyl metabolites (2-[(2,6-dimethylphenyl)-methoxyacetylamino]-propionic acid and N-(2,6-dimethylphenyl)-2-methoxy-acetamide) were detected during the incubation period. Soil dehydrogenase activity recorded close values in non-amended and amended soil treated with alachlor, but it was higher in wood amended soil treated with metalaxyl. Pine and oak wood increase the immobilization of the pesticides studied, but they also limit their bioavailability in soil by decreasing their degradation rate in amended soil. Copyright © 2010 Elsevier Ltd. All rights reserved.

  18. A new approach of microalgal biomass pretreatment using deep eutectic solvents for enhanced lipid recovery for biodiesel production.

    Science.gov (United States)

    Lu, Weidong; Alam, Md Asraful; Pan, Ying; Wu, Jingcheng; Wang, Zhongming; Yuan, Zhenhong

    2016-10-01

    The biomass of Chlorella sp. was pretreated with three different aqueous deep eutectic solvents (aDESs), i.e. aqueous choline chloride-oxalic acid (aCh-O), aqueous choline chloride-ethylene glycol (aCh-EG) and aqueous urea-acetamide (aU-A). The effect of aDESs pretreatment of microalgae biomass was evaluated in terms of lipid recovery rate, total carbohydrate content, fatty acid composition, and thermal chemical behavior of biomass. Results indicated that, lipid recovery rate was increased from 52.03% of untreated biomass to 80.90%, 66.92%, and 75.26% of the biomass treated by aCh-O, aCh-EG and aU-A, respectively. However, there were no major changes observed in fatty acid profiles of both untreated and treated biomass, specifically palmitic acid, palmitoleic acid and stearic acid under various pretreatments. Furthermore, characterizations of untreated and treated biomass were carried out using Fourier transform infrared (FTIR), thermogravimetry analysis (TGA) and scanning electron microscope (SEM) to understand the enhanced lipids recovery.

  19. Absolute rate constants for hydrogen atom transfer from tertiary amides to the cumyloxyl radical: evaluating the role of stereoelectronic effects.

    Science.gov (United States)

    Salamone, Michela; Milan, Michela; DiLabio, Gino A; Bietti, Massimo

    2014-08-01

    A time-resolved kinetic study of the hydrogen atom transfer (HAT) reactions from a series of alkanamides to the cumyloxyl radical (CumO(•)) was carried out. With N,N-dialkylformamides HAT preferentially occurs from the formyl C-H bond, while in N-formylpyrrolidine HAT mostly occurs from the ring α-C-H bonds. With the acetamides and the alkanamides almost exclusive HAT from the C-H bonds that are α to nitrogen was observed. The results obtained show that alignment between the C-H bond being broken and the amide π-system can lead to significant increases in the HAT rate constant (kH). This finding points toward the important role of stereoelectronic effects on the HAT reactivity and selectivity. The highest kH values were measured for the reactions of CumO(•) with N-acylpyrrolidines. These substrates have ring α-C-H bonds that are held in a conformation that is optimally aligned with the amide π-system, thus allowing for the relatively facile HAT reaction. The lowest kH value was measured for the reaction of N,N-diisobutylacetamide, wherein the steric bulk associated with the N-isobutyl groups increases the energy barrier required to reach the most suitable conformation for HAT. The experimental results are well supported by the computed BDEs for the C-H bonds of the most representative substrates.

  20. Facile Synthesis of New Aromatic Polyamides Based on 1,2-Dihydro-2-(4-carboxylphenyl)-4-[4-(4-carboxyl- phenoxy)-3-methylphenyl]phthalazin-1-one

    Institute of Scientific and Technical Information of China (English)

    程琳; 应磊; 杨小玲; 蹇锡高

    2005-01-01

    A new monomer diacid, 1,2-dihydro-2-(4-carboxylphenyl)-4-[4-(4-carboxylphenoxy)-3-methylphenyl]phtha-lazin-1-one (3), was synthesized through the aromatic nucleophilic substitution reaction of a readily available unsymmetrical phthalazinone 1 bisphenol-like with p-chlorobenzonitrile in the presence of potassium carbonate in N,N-dimethylacetamide and alkaline hydrolysis. The diacid could be directly polymerized with various aromatic diamines 4a-4e using triphenyl phosphite and pyridine as condensing agents to give five new aromatic poly(ether amide)s 5a-5e containing the kink non-coplanar heterocyclic units with inherent viscosities of 1.30-1.54 dL/g.The polymers were readily soluble in a variety of solvents such as N,N-dimethylformamide (DMF), N,N-dimethyl-acetamide (DMA), dimethylsulfoxide (DMSO), N-methyl-2-pyrrolidinone (NMP), and even in m-cresol and pyridine (Py). The transparent, flexible and tough films could be formed by solution casting. The glass transition tem-peratures Tg were in the range of 286-317℃.

  1. Relative solvation free energies calculated using an ab initio QM/MM-based free energy perturbation method: dependence of results on simulation length.

    Science.gov (United States)

    Reddy, M Rami; Erion, Mark D

    2009-12-01

    Molecular dynamics (MD) simulations in conjunction with thermodynamic perturbation approach was used to calculate relative solvation free energies of five pairs of small molecules, namely; (1) methanol to ethane, (2) acetone to acetamide, (3) phenol to benzene, (4) 1,1,1 trichloroethane to ethane, and (5) phenylalanine to isoleucine. Two studies were performed to evaluate the dependence of the convergence of these calculations on MD simulation length and starting configuration. In the first study, each transformation started from the same well-equilibrated configuration and the simulation length was varied from 230 to 2,540 ps. The results indicated that for transformations involving small structural changes, a simulation length of 860 ps is sufficient to obtain satisfactory convergence. In contrast, transformations involving relatively large structural changes, such as phenylalanine to isoleucine, require a significantly longer simulation length (>2,540 ps) to obtain satisfactory convergence. In the second study, the transformation was completed starting from three different configurations and using in each case 860 ps of MD simulation. The results from this study suggest that performing one long simulation may be better than averaging results from three different simulations using a shorter simulation length and three different starting configurations.

  2. NAD deamidation "a new reaction" by an enzyme from Aspergillus terreus DSM 826.

    Science.gov (United States)

    Elzainy, Tahany A; Ali, Thanaa H

    2005-02-01

    NAD deamidation is a non-previously recognized reaction. This reaction has been found to be catalyzed by extracts of Aspergillus terreus DSM 826. Conversion of NAD to the biosynthetic intermediate, deamido NAD, by these extracts, at the optimum pH and temperature did not exceed about 55 of the amount of the substrate added. Completion of the reaction was achieved when the extracts were pre-heated at 50 degrees C for 15 min in absence of the substrate. In a very similar manner, the extracts catalyzed hydrolytic cleavage of the amide linkages of different biomolecules such as nicotinamide, nicotinamide riboside, nicotinamide mononucleotide, L-glutamine, L-asparagine and acetamide. Polyacrylamide was also deamidated under the same conditions. In addition, complete dephosphorylation of the dinucleotide molecule was also effected by the same extracts. Separation of the NAD deamidating enzyme from the NAD dephosphorylating enzyme was achieved on using either DEAE - Sephadex A-25 or Sephadex G-200 column chromatography. The obtained phosphohydrolase-free-deamidase showed optimum activity at pH 8 of 0.1 M phosphate buffer and 50 degrees C. It exhibited broad substrate specificity and hyperbolic substrate saturation kinetics. It was isosterically inhibited by the product of its activity and this inhibition was prevented by heating the extracts at 50 degrees C for 15 min. Its activity was not affected in presence of sodium fluoride, partially inhibited in presence of magnesium chloride and was retained in the freezer for some months.

  3. Composition and mechanisms analysis of aromatic telechelic oligomers by mass spectroscopy; Analyse de la composition et de mecanismes de polymerisation d`oligomeres telecheliques aromatiques par spectrometrie de masse

    Energy Technology Data Exchange (ETDEWEB)

    Damerval, V.

    1997-10-22

    The aim of this work was to apply mass spectrometry, on the one hand to the characterization of telechelic oligo-imides with oxazoline and lactane end-caps and, on the other hand to the determination of the thermal reticulation mechanism of nadimides. First bis-oxazoline and buslactane end-capped, oligomers used to form blocks copolymers were studied by liquid secondary ion mass spectroscopy (LSIMS) and Matrix-assisted laser desorption ionization time of flight spectroscopy (MALDI-TOF). An acetamide end-cap by-product was detected. Then the analysis was modified to avoid the formation of this by-product which was unable to copolymerize. Secondly, to circumvent the experimental difficulties related to crosslinked networks, the study of the thermal polymerization of nadimides was performed ones (LSIMS, electroscopy, MALDI-TOF) led to the determination of the polynadimide structure. Thanks to MS/MS studies the nature of the linkages and the structure of the end-caps were established. Finally, this work evidenced the opportunity to use mass spectrometry to analyze synthetic polymers. (author) 222 refs.

  4. (Acetonitrile{2-[bis(pyridin-2-ylmethyl-κ2Namino-κN]-N-(2,6-dimethylphenylacetamide-κO}(perchlorato-κOzinc (acetonitrile{2-[bis(pyridin-2-ylmethyl-κ2Namino-κN]-N-(2,6-dimethylphenylacetamide-κO}zinc tris(perchlorate

    Directory of Open Access Journals (Sweden)

    Ove Alexander Høgmoen Åstrand

    2013-02-01

    Full Text Available In the title salt, [Zn(C22H24N4O(CH3CN][Zn(ClO4(C22H24N4O(CH3CN](ClO43, two differently coordinated zinc cations occur. In the first complex, the metal ion is coordinated by the N,N′,N′′,O-tetradentate acetamide ligand and an acetonitrile N atom, generating an approximate trigonal–bipyramidal coordination geometry, with the O atom in an equatorial site and the acetonitrile N atom in an axial site. In the second complex ion, a perchlorate ion is also bonded to the zinc ion, generating a distorted trans-ZnO2N4 octahedron. Of the uncoordinating perchlorate ions, one lies on a crystallographic twofold axis and one lies close to a twofold axis and has a site occupancy of 0.5. N—H...O and N—H...(O,O hydrogen bonds are observed in the crystal. Disordered solvent molecules occupy about 11% of the unit-cell volume; their contribution to the scattering was removed with the SQUEEZE routine of the PLATON program [Spek (2009. Acta Cryst. D65, 148–155.].

  5. Modafinil decreases anxiety-like behaviour in zebrafish

    Science.gov (United States)

    Johnson, Adrian

    2017-01-01

    Modafinil (2-((diphenylmethyl)sulfinyl)acetamide), a selective dopamine and norepinephrine transporter inhibitor, is most commonly prescribed for narcolepsy but has gained recent interest for treating a variety of disorders. Zebrafish (Danio rerio) are becoming a model of choice for pharmacological and behavioural research. To investigate the behavioural effects of modafinil on anxiety, we administered doses of 0, 2, 20, and 200 mg/L for 30 minutes then tested zebrafish in the novel approach test. In this test, the fish was placed into a circular arena with a novel object in the center and motion-tracking software was used to quantify the time the fish spent in the outer area of the arena (thigmotaxis zone), middle third of the arena (transition zone) and center of the arena, as well as total distance traveled, immobility and meandering. Modafinil caused a decrease in time spent in the thigmotaxis zone and increased time spent in the transition zone across all doses. Modafinil did not significantly alter the time spent in the center zone (near the novel object), the distance moved, meandering, or the duration of time spent immobile. We also validated this test as a measure of anxiety with the administration of ethanol (1%) which decreased time spent in the thigmotaxis zone and increased time spent in the transition zone. These results suggest that modafinil decreases anxiety-like behaviour in zebrafish. PMID:28229024

  6. Intercalation of paracetamol into the hydrotalcite-like host

    Science.gov (United States)

    Kovanda, František; Maryšková, Zuzana; Kovář, Petr

    2011-12-01

    Hydrotalcite-like compounds are often used as host structures for intercalation of various anionic species. The product intercalated with the nonionic, water-soluble pharmaceuticals paracetamol, N-(4-hydroxyphenyl)acetamide, was prepared by rehydration of the Mg-Al mixed oxide obtained by calcination of hydrotalcite-like precursor at 500 °C. The successful intercalation of paracetamol molecules into the interlayer space was confirmed by powder X-ray diffraction and infrared spectroscopy measurements. Molecular simulations showed that the phenolic hydroxyl groups of paracetamol interact with hydroxide sheets of the host via the hydroxyl groups of the positively charged sites of Al-containing octahedra; the interlayer water molecules are located mostly near the hydroxide sheets. The arrangement of paracetamol molecules in the interlayer is rather disordered and interactions between neighboring molecules cause their tilting towards the hydroxide sheets. Dissolution tests in various media showed slower release of paracetamol intercalated in the hydrotalcite-like host in comparison with tablets containing the powdered pharmaceuticals.

  7. New benzo[d]thiazol-2-yl-aminoacetamides as potential anticonvulsants: synthesis, activity and prediction of molecular properties.

    Science.gov (United States)

    Ali, Ruhi; Siddiqui, Nadeem

    2015-04-01

    A series of N-(substituted-2-oxo-4-phenylazetidin-1-yl)-2-((6-substitutedbenzo[d]thiazol-2-yl)amino)acetamide derivatives were synthesized using pharmacophoric features with aromatic hydrophobic aryl ring (A), NH-C=O as hydrogen bonding domain, the nitrogen atom as electron donor (D), and phenyl as distal aryl ring (C). The synthesized molecules were initially screened for anticonvulsant activity using the maximal electroshock seizure (MES) test and the subcutaneous pentylenetetrazole test in albino mice. An acute neurotoxicity study on the synthesized molecules was also carried out using the rotarod test. The results of these tests revealed that two compounds, 5b and 5q, showed promising activity with ED50 values of 15.4 and 18.6 mg/kg and protective indices of 20.7 and 34.9 in the MES test, respectively, which are found to be approximately fourfold higher than those of the standard drugs phenytoin (6.9) and carbamazepine (8.1). These molecules may act as lead of the designed scheme. The pharmacokinetic profiles of all the synthesized compounds were estimated using Molinspiration software. None of the compounds violated Lipinski's "rule of five". The possible structure-activity relationship was discussed. In conclusion, this manuscript shows that the developed model has a highly prognostic power for the further investigation of better benzothiazole derivatives for future discovery and development.

  8. Prebiotic Organic Matter from the Center of the Galaxy

    Science.gov (United States)

    Halfen, DeWayne; Ziurys, Lucy M.

    2016-06-01

    The origins of life on Earth must have begun with simple organic compounds. A plausible source of such prebiotic molecules was the interstellar medium (ISM). Of the over 160 molecules that have been identified in interstellar gas, about half have been discovered in one source, Sagittarius B2(N), located in the Galactic Center. This giant molecular cloud is also home to many large organic species observed in the ISM. How complex these species can become is unknown. In order to accurately establish an inventory of potentially, prebiotic organic molecules, we completed a continuous spectral-line survey of Sgr B2(N) at the confusion limit using the Arizona Radio Observatory facilities: the Kitt Peak 12 m and the Submillimeter Telescope. The survey covers the 1, 2, and 3 mm atmospheric windows in the range 68 - 280 GHz, and about 15,000 individual spectral lines have been observed. Seventy-four molecules have been identified in the data, including several potential prebiotic species, such as glycolaldehyde, acetamide, and methyl isocyanate. These molecules are relatively abundant in Sgr B2(N), with fractional abundances of f ~ 10-10 - 10-12 relative to H2. Current results of this survey will be presented, along with its implications for interstellar organic chemistry and prebiotic synthesis. A comparison with organics found in comets and meteorites will also be discussed.

  9. 2-Phenyl-imidazo[1,2-a]pyridine compounds containing hydrophilic groups as potent and selective ligands for peripheral benzodiazepine receptors: synthesis, binding affinity and electrophysiological studies.

    Science.gov (United States)

    Denora, Nunzio; Laquintana, Valentino; Pisu, Maria Giuseppina; Dore, Riccardo; Murru, Luca; Latrofa, Andrea; Trapani, Giuseppe; Sanna, Enrico

    2008-11-13

    A series of imidazopyridine acetamides were synthesized to evaluate the effects of structural changes at both central (CBRs) and peripheral benzodiazepine receptors (PBRs). These changes include the introduction of polar substituents or ionizable functional groups at the 2- and 8-position of the imidazopyridine skeleton. The results suggest that substituents endowed with hydrogen bonding acceptor and/or donor properties in the para position of the phenyl ring lead to high affinity for PBR. In electrophysiological studies, it was found that compounds 9, 12, 13, and 28 markedly enhanced GABA-evoked Cl (-) currents in Xenopus oocytes expressing alpha 1beta 2gamma 2 GABA A receptors. The capability of flumazenil to reduce the stimulatory effect exerted by compound 9 supports the conclusion that the modulatory effects of the examined compounds occur involving the CBR. The ability of compound 16 to increase GABA A receptor-mediated miniature inhibitory postsynaptic currents in CA1 pyramidal neurons is indicative of its ability to stimulate the local synthesis and secretion of neurosteroids.

  10. Paracetamol degradation intermediates and toxicity during photo-Fenton treatment using different iron species.

    Science.gov (United States)

    Trovó, Alam G; Pupo Nogueira, Raquel F; Agüera, Ana; Fernandez-Alba, Amadeo R; Malato, Sixto

    2012-10-15

    The photo-Fenton degradation of paracetamol (PCT) was evaluated using FeSO(4) and the iron complex potassium ferrioxalate (FeOx) as iron source under simulated solar light. The efficiency of the degradation process was evaluated considering the decay of PCT and total organic carbon concentration and the generation of carboxylic acids, ammonium and nitrate, expressed as total nitrogen. The results showed that the degradation was favored in the presence of FeSO(4) in relation to FeOx. The higher concentration of hydroxylated intermediates generated in the presence of FeSO(4) in relation to FeOx probably enhanced the reduction of Fe(III) to Fe(II) improving the degradation efficiency. The degradation products were determined using liquid chromatography electrospray time-of-flight mass spectrometry. Although at different concentrations, the same intermediates were generated using either FeSO(4) or FeOx, which were mainly products of hydroxylation reactions and acetamide. The toxicity of the sample for Vibrio fischeri and Daphnia magna decreased from 100% to less than 40% during photo-Fenton treatment in the presence of both iron species, except for D. magna in the presence of FeOx due to the toxicity of oxalate to this organism. The considerable decrease of the sample toxicity during photo-Fenton treatment using FeSO(4) indicates a safe application of the process for the removal of this pharmaceutical.

  11. Synthesis and radioiodination of di-iodo-Evan's blue via isotopic exchange reaction in the molten state and evaluation of the kinetics

    Energy Technology Data Exchange (ETDEWEB)

    El-Azony, K.M. [Research Center Juelich (Germany). Inst. of Nuclear Chemistry]|[Hot Lab. Center, Cairo (Egypt). Radioactive Isotopes and Generators Dept.; Bier, D.; Coenen, H.H. [Research Center Juelich (Germany). Inst. of Nuclear Chemistry

    2004-07-01

    Many aryl halides were synthesized from aryl amines such as iodo-trypan, iodo-methylene blue and iodo-toluidine. Methylene blue and toludine blue are phenothiazinium dyes and were used to localize parathyroid glands visually during surgery. Radioiodination of these compounds by using iodine-123 analogues for scintgraphic localization of parathyroids was reported. Radiolabelled dyes administered may also localize in tumor tissues. Evan's blue dye was used to study altered sarcolemmal permeability in dystrophic muscle fibers, and in animals to study muscular dystrophy. In this work Diiodo-Evan's blue was synthesized via Sandmeyer reaction and characterized by mass spectrum analysis. A procedure for labelling DIEB with Na{sup 131}I via isotopic exchange in molten medium was developed. The labelling conditions studied for the isotopic exchange of {sup 131}I-for-I in DIEB included the effect of temperature and solvents (melt of acetamide, benzoic and pivalic acid). Kinetic studies were performed to obtain [{sup 131}I] DIEB with more reliable reaction conditions. Quality control for the final product ([{sup 131}I] DIEB) was performed by HPLC. (orig.)

  12. Characterization of a Novel Butachlor Biodegradation Pathway and Cloning of the Debutoxylase (Dbo) Gene Responsible for Debutoxylation of Butachlor in Bacillus sp. hys-1.

    Science.gov (United States)

    Gao, Yang; Jin, Lei; Shi, Hui; Chu, Zhangjie

    2015-09-30

    Bacillus sp. strain hys-1, which was isolated from active sludge, could degrade >90% butachlor at a concentration of 100 mg/L within 7 days. The present work revealed that strain hys-1 could mineralize butachlor via the following pathway: butachlor was initially metabolized to 2-chloro-N-(2,6-diethylphenyl)-N-methylacetamide by debutoxylation and then transformed to form 2-chloro-N-(2,6-diethylphenyl)acetamide by N-demethylation. Subsequently, it was converted to 2,6-diethylaniline and further mineralized into CO2 and H2O. In addition, the catalytic efficiency of crude cell extracts descended as follows: alachlor > acetochlor > butachlor. Furthermore, a novel 744 bp gene responsible for transforming butachlor into 2-chloro-N-(2,6-diethylphenyl)-N-methylacetamide was cloned from strain hys-1 and the encoding debutoxylase was designated Dbo. Then Dbo was expressed in Escherichia coli BL21 (DE3) and purified using Ni-nitrilotriacetic acid affinity chromatography. Dbo displayed the highest activity against butachlor at pH 6.5 and 30 °C. Metal ions played an important role in Dbo activity. To the best of the authors' knowledge, this is the first report that strain hys-1 can mineralize butachlor by a novel metabolic mechanism and the first identification of a gene encoding butachlor debutoxylase.

  13. Syntrophic biodegradation of butachlor by Mycobacterium sp. J7A and Sphingobium sp. J7B isolated from rice paddy soil.

    Science.gov (United States)

    Kim, Nam Hyun; Kim, Dong-Uk; Kim, Ijung; Ka, Jong-Ok

    2013-07-01

    Two bacterial strains involved in syntrophic degradation of chloroacetamide herbicide butachlor were isolated from a rice paddy soil. Analysis of 16S rRNA gene sequences indicated that the two isolates were related to members of the genera Mycobacterium and Sphingobium, respectively. Thus, a pair consisted of Mycobacterium sp. J7A and Sphingobium sp. J7B could rapidly degrade butachlor (100 mg L(-1)) at 28 °C within 24 h, while each isolate alone was not able to completely degrade butachlor. The isolate Mycobacterium sp. J7A was observed to grow slightly on butachlor, possibly utilizing the alkyl side chain of butachlor as its carbon and energy source, but the isolate Sphingobium sp. J7B alone could not grow on butachlor at all. Gas chromatography-mass spectrometry on catabolic intermediates revealed that the strain J7A produced and accumulated 2-chloro-N-(2,6-diethylphenyl) acetamide (CDEPA) during growth on butachlor. This intermediate was not further degraded by strain J7A, but strain J7B was observed to be able to completely degrade and grow on it through 2,6-diethylaniline (DEA). The results showed that butachlor was completely degraded by the two isolates by syntrophic metabolism, in which strain Mycobacterium sp. J7A degraded butachlor to CDEPA, which was subsequently degraded by strain Sphingobium sp. J7B through DEA.

  14. Difficulties in Laboratory Studies and Astronomical Observations of Organic Molecules: Hydroxyacetone and Lactic Acid

    Science.gov (United States)

    Apponi, A. J.; Brewster, M. A.; Hoy, J.; Ziurys, L. M.

    2006-01-01

    For the past 35 years, radio astronomy has revealed a rich organic chemistry in the interstellar gas, which is exceptionally complex towards active star-forming regions. New solar systems condense out of this gas and may influence the evolution of life on newly formed planets. Much of the biologically important functionality is present among the some 130 gas-phase molecules found to date, including alcohols, aldehydes, ketones, acids, amines, amides and even the simplest sugar - glycolaldehyde. Still, many unidentified interstellar radio signals remain, and their identification relies on further laboratory study. The molecules hydroxyacetone and lactic acid are relatively small organic molecules, but possess rather complex rotational spectra owing to their high asymmetry. Hydroxyacetone is particularly problematic because it possess a very low barrier to internal rotation, and exhibits strong coupling of the free-rotor states with the overall rotation of the molecule. As in the case of acetamide, a full decomposition method was employed to order the resultant eigenstates onto normal asymmetric top eigenvectors.

  15. [Discrimination of patients with Xiao-Chaihu Tang syndrome using 1H NMR metabonomics and partial least square analysis].

    Science.gov (United States)

    Xing, Jie; Yuan, Shu-chun; Sun, Hui-min; Fan, Ma-li; Li, Zhen-yu; Qin, Xue-mei

    2015-08-01

    1H NMR metabonomics approach was used to reveal the chemical difference of urine between patients with Xiao-Chaihu Tang syndrome (XCHTS) and healthy participants (HP). The partial least square method was used to establish a model to distinguish the patients with Xiao-Chaihu-Tang syndrome from the healthy controls. Thirty-four endogenous metabolites were identified in the 1H NMR spectrum, and orthogonal partial least squares discriminant analysis showed the urine of patients with Xiao-Chaihu Tang syndrome and healthy participants could be separated clearly. It is indicated that the metabolic profiling of patients with Xiao-Chaihu Tang syndrome was changed obviously. Fifteen metabolites were found by S-pot of OPLS-DA and VIP value. The contents of leucine, formic acid, glycine, hippuric acid and uracil increased in the urine of patients, while threonine, 2-hydroxyisobutyrate, acetamide, 2-oxoglutarate, citric acid, dimethylamine, malonic acid, betaine, trimethylamine oxide, phenylacetyl glycine, and uridine decreased. These metabolites involve the intestinal microbial balance, energy metabolism and amino acid metabolism pathways, which is related with the major symptom of Xiao-Chaihu Tang syndrome. The patients with Xiao-Chaihu Tang syndrome could be identified and predicted correctly using the established partial least squares model. This study could be served as the basis for the accurate diagnostic and reasonable administration of Xiao-Chaihu-Tang syndrome.

  16. In silico modification of oseltamivir as neuraminidase inhibitor of influenza A virus subtype H1N1

    Institute of Scientific and Technical Information of China (English)

    Usman Sumo Friend Tambunan; Rizky Archintya Rachmania; Arli Aditya Parikesit

    2015-01-01

    This research focused on the modification of the functional groups of oseltamivir as neuraminidase inhibitor against influenza A virus subtype H1N1.Interactions of three of the best ligands were evaluated in the hydrated state using molecular dynamics simulation at two different temperatures.The docking result showed that AD3BF2D ligand (N-[(1S,6R)-5-amino-5-{[(2R,3S,4S)-3,4-dihydroxy-4-(hydroxymethyl) tetrahydrofuran-2-yl]oxy}-4-formylcyclohex-3-en-l-yl]acetamide-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate) had better binding energy values than standard oseltamivir.AD3BF2D had several interactions,including hydrogen bonds,with the residues in the catalytic site of neuraminidase as identified by molecular dynamics simulation.The results showed that AD3BF2D ligand can be used as a good candidate for neuraminidase inhibitor to cope with influenza A virus subtype H1N1.

  17. Synthesis, DNA-binding, DNA-photonuclease profiling and antimicrobial activity of novel tetra-aza macrocyclic Ni(II), Co(II) and Cu(II) complexes constrained by thiadiazole.

    Science.gov (United States)

    Vinay Kumar, B; Bhojya Naik, H S; Girija, D; Sharath, N; Pradeepa, S M; Joy Hoskeri, H; Prabhakara, M C

    2012-08-01

    A new tetra-aza macrocyclic ligand, L (C(24)H(16)N(12)O(2)S(4)) and its complexes of type, [MLCl(2)] and [CuL]Cl(2) (where M=Ni(II), Co(II); L=N,N'-(benzene-1,3-diyldi-1,3,4-thiadiazole-5,2-diyl)bis{2-[(5-benzene-1,3-diyl-1,3,4-thiadiazol-2-yl)amino]acetamide}) were synthesized and characterized by the spectral and analytical techniques. An octahedral geometry has been proposed for Ni(II) and Co(II) complexes while Cu(II) complex exhibit a square planar geometry. All the synthesized metal complexes were screened for their in vitro antimicrobial activity against selected species of pathogenic bacteria and fungi. The binding property of the complexes with CT-DNA was studied by absorption spectral analysis, followed by viscosity measurement and thermal denaturation studies. The photo induced cleavage studies revealed that the complexes possess photonuclease property against pUC19 DNA under UV-visible irradiation.

  18. Simultaneous LC/ESI-MS separation method for the enantioseparation of some new anticonvulsant drugs.

    Science.gov (United States)

    Walczak, Maria; Pekala, Elzbieta; Waszkielewicz, Anna M; Marona, Henryk

    2014-03-01

    A sensitive and specific method for the simultaneous determination of the enantiomeric purity of 2,6-dimethylphenoxyacetyl derivatives as trans or cis racemic and enantiomeric forms with 2- or 4-aminocyclohexanol moiety (1, 2, 3, 6) and their amine analogs (8, 9) was developed. The compounds studied are known for their anticonvulsant activity and the most interesting pharmacological results were those for (±)-trans-2-(2,6-dimethylphenoxy)-N-(2-hydroxycyclohexyl)acetamide (1) as well as (±)-trans-2-[(2,6-dimethylphenoxy)ethyl]aminocyclohexanol (8). The analytical method for determining the enantiomeric purity of the compounds studied is based on direct separation of the analytes using a chiral stationary phase (Chiralpak AS column). The mass spectrometric analysis was done on a coupled liquid chromatograph-mass spectrometer system with an electrospray ionization source (LC/ESI-MS). For the compounds 1, 8, and 9, the method allows an excellent separation of enantiomers, with a resolution higher than 3.2, and a tailing factor of less than 1.67 with a final enantiomer purity better than 97.5%. © 2014 Wiley Periodicals, Inc.

  19. Radiolabelled molecules for imaging the translocator protein (18 kDa) using positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Dolle, F.; Luus, C.; Reynolds, A.; Kassiou, M. [CEA, Institut d' Imagerie BioMedicale, Service Hospitalier Frederic Joliot, Orsay (France)

    2009-07-01

    The translocator protein (18 kDa) (TSPO), formerly known as the peripheral benzodiazepine receptor (PBR), was originally identified as an alternate binding site for the central benzodiazepine receptor (CBR) ligand, diazepam, in the periphery, but has now been distinguished as a novel site. The TSPO is ubiquitously expressed in peripheral tissues but only minimally in the healthy brain and increased levels of TSPO expression have been noted in neuro inflammatory conditions such as Alzheimer's disease, Parkinson's disease and stroke. This increase in TSPO expression has been reported to coincide with the process of micro-glial activation, whereby the brain's intrinsic immune system becomes active. Therefore, by using recently developed high affinity, selective TSPO ligands in conjunction with functional imaging modalities such as positron emission tomography (PET), it becomes possible to study the process of micro-glial activation in the living brain. A number of high affinity ligands, the majority of which are C, N-substituted acetamide derivatives, have been successfully radiolabelled and used in in vivo studies of the TSPO and the process of micro-glial activation. This review highlights recent achievements (up to December 2008) in the field of functional imaging of the TSPO as well as the radio-syntheses involved in such studies. (authors)

  20. [{sup 11}C]DAA1106: radiosynthesis and in vivo binding to peripheral benzodiazepine receptors in mouse brain

    Energy Technology Data Exchange (ETDEWEB)

    Zhang Mingrong E-mail: zhang@nirs.go.jp; Kida, Takayo; Noguchi, Junko; Furutsuka, Kenji; Maeda, Jun; Suhara, Tetsuya; Suzuki, Kazutoshi

    2003-05-01

    DAA1106 (N-(2,5-Dimethoxybenzyl)-N-(5-fluoro-2-phenoxyphenyl)acetamide), is a potent and selective ligand for peripheral benzodiazepine receptors (PBR) in mitochondrial fractions of rat (K{sub i}=0.043 nM) and monkey (K{sub i}=0.188 nM) brains. This compound was labeled by [{sup 11}C]methylation of a corresponding desmethyl precursor (DAA1123) with [{sup 11}C]CH{sub 3}I in the presence of NaH, with a 72{+-}16% (corrected for decay) incorporation yield of radioactivity. After HPLC purification, [{sup 11}C]DAA1106 was obtained with {>=}98% radiochemical purity and specific activity of 90-156 GBq/{mu}mol at the end of synthesis. After iv injection of [{sup 11}C]DAA1106 into mice, high accumulations of radioactivity were found in the olfactory bulb and cerebellum, the high PBR density regions in the brain. Coinjection of [{sup 11}C]DAA1106 with unlabeled DAA1106 and PBR-selective PK11195 displayed a significant reduction of radioactivity, suggesting a high specific binding of [{sup 11}C]DAA1106 to PBR. Although this tracer was rapidly metabolized in the plasma, only [{sup 11}C]DAA1106 was detected in the brain tissues, suggesting the specific binding in the brain due to the tracer itself. These findings revealed that [{sup 11}C]DAA1106 is a potential and selective positron emitting radioligand for PBR.

  1. Recycle and synthesis of LiCoO2 from incisors bound of Li-ion batteries

    Institute of Scientific and Technical Information of China (English)

    LIU Yun-jian; HU Qi-yang; LI Xin-hai; WANG Zhi-xing; GUO Hua-jun

    2006-01-01

    A new LiCoO2 recovery technology of Li-ion battery was studied. LiCoO2 was initially separated from the Al foil with dimethyl acetamide(DMAC), and then the polyvinylidene fluoride(PVDF) and carbon powders in the active material were eliminated by high temperature calcining. The content of the elements in the recovered powder was analyzed. The structure and morphology of the resulted samples were observed by XRD and SEM. Then the Li2CO3 was added in the recycled powder to adjust the Li/Co molar ratio to 1. The new LiCoO2 was synthesized by calcining at 850 ℃ for 12 h in air. The well-crystallized single phase LiCoO2 without Co3O4 phase was obtained. The recycle-synthesized LiCoO2 powders have good characteristics as a cathode active material in terms of charge-discharge capacity and cycling performance.

  2. Preparation and characterization of nanocomposite polymer electrolytes poly(vinylidone fluoride)/nanoclay

    Energy Technology Data Exchange (ETDEWEB)

    Rahmawati, Suci A.; Sulistyaningsih,; Putro, Alviansyah Z. A.; Widyanto, Nugroho F.; Jumari, Arif; Purwanto, Agus; Dyartanti, Endah R., E-mail: endahrd@uns.ac.id [Research Group of Battery & Advanced Material, Department of Chemical Engineering, Sebelas Maret University, Jl. Ir. Sutami 36 A Kentingan, Surakarta Indonesia 57126 (Indonesia)

    2016-02-08

    Polymer electrolytes are defined as semi solid electrolytes used as separator in lithium ion battery. Separator used as medium for transfer ions and to prevent electrical short circuits in battery cells. To obtain the optimal battery performance, separator with high porosity and electrolyte uptake is required. This can reduce the resistance in the transfer of ions between cathode and anode. The main objective of this work is to investigate the impact of different solvent (Dimethyl acetamide (DMAc), N-methyl-2-pyrrolidone (NMP) and dimethyl formamide (DMF)), pore forming agent poly(vinylpyrolidone) (PVP) and nanoclay as filler in addition of membrane using phase inversion method on the morphology, porosity, electrolyte uptake and degree of crystallinity. The membrane was prepared by the phase inversion method by adding PVP and Nanoclay using different solvents. The phase inversion method was prepared by dissolving Nanoclay and PVP in solvent for 1-2 hours, and then add the PVDF with stirring for 4 hours at 60°C. The membranes were characterized by porosity test, electrolyte uptake test, scanning electron microscope (SEM), and X-ray diffraction (XRD). The results showed that DMAc as solvent gives the highest value of porosity and electrolyte uptake. The addition of nanoclay and PVP enlarge the size of the pores and reduce the degree of crystallinity. So, the usage of DMAc as solvent is better than NMP or DMF.

  3. Searching for novel scaffold of triazole non-nucleoside inhibitors of HIV-1 reverse transcriptase.

    Science.gov (United States)

    Frączek, Tomasz; Paneth, Agata; Kamiński, Rafał; Krakowiak, Agnieszka; Paneth, Piotr

    2016-01-01

    Azoles are a promising class of the new generation of HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs). From thousands of reported compounds, many possess the same basic structure of an aryl substituted azole ring linked by a thioglycolamide chain with another aromatic ring. In order to find novel extensions for this basic scaffold, we explored the 5-position substitution pattern of triazole NNRTIs using molecular docking followed by the synthesis of selected compounds. We found that heterocyclic substituents in the 5-position of the triazole ring are detrimental to the inhibitory activity of compounds with four-membered thioglycolamide linker and this substitution seems to be viable only for compounds with shorter two-membered linker. Promising compound, N-(4-carboxy-2-chlorophenyl)-2-((4-benzyl-5-methyl-4H-1,2,4-triazol-3-yl)sulfanyl)acetamide, with potent inhibitory activity and acceptable aqueous solubility has been identified in this study that could serve as lead scaffold for the development of novel water-soluble salts of triazole NNRTIs.

  4. TSPO Imaging in Glioblastoma Multiforme

    DEFF Research Database (Denmark)

    Jensen, Per; Feng, Ling; Law, Ian

    2015-01-01

    -CLINDE is superior to (18)F-FET in predicting progression of glioblastoma multiforme (GBM) at follow-up. METHODS: Three patients with World Health Organization grade IV GBM were scanned with (123)I-CLINDE SPECT, (18)F-FET PET, and gadolinium-enhanced MR imaging. Molecular imaging data were compared with follow......UNLABELLED: Here we compare translocator protein (TSPO) imaging using 6-chloro-2-(4'-(123)I-iodophenyl)-3-(N,N-diethyl)-imidazo[1,2-a]pyridine-3-acetamide SPECT ((123)I-CLINDE) and amino acid transport imaging using O-(2-(18)F-fluoroethyl)-l-tyrosine PET ((18)F-FET) and investigate whether (123)I......-up gadolinium-enhanced MR images or contrast-enhanced CT scans. RESULTS: The percentage overlap between volumes of interest (VOIs) of increased (18)F-FET uptake and (123)I-CLINDE binding was variable (12%-42%). The percentage overlap of MR imaging baseline VOIs was greater for (18)F-FET (79%-93%) than (123)I...

  5. Amide bond cleavage initiated by coordination with transition metal ions and tuned by an auxiliary ligand.

    Science.gov (United States)

    Yang, Yongpo; Lu, Chunxin; Wang, Hailong; Liu, Xiaoming

    2016-06-21

    The reaction of ligand , N,N-bis(pyridin-2-ylmethyl)acetamide, with five transition metal salts, FeCl3·6H2O, CuCl2·2H2O, Cu(ClO4)2·6H2O, ZnCl2 and K2PtCl4/KI, produced five metal complexes, [(μ-O)(FeClL')(FeCl3)] (), [CuLCl2] (), [CuBPA(ClO4)(CHCN)] ClO4 (), [ZnLCl2] () and [PtLI2] (), where = 1-(2,4,5-tri(pyridin-2-yl)-3-(pyridin-2-ylmethyl)imidazolidin-1-yl)ethanone which formed in situ, and BPA = bis(pyridin-2-ylmethyl)amine. The ligand and complexes were characterized by a variety of spectroscopic techniques including X-ray single crystal diffraction where applicable. Depending on the metal ion and auxiliary ligand of the complex, the acetyl group of the ligand could be either intact or cleaved. When ferric chloride hexahydrate was used, the deacetylation proceeded even further and a novel heterocyclic compound () was formed in situ. A possible mechanism was proposed for the formation of the heterocyclic compound found in complex . Our results indicate that to cleave effectively an amide bond, it is essential for a metal centre to bind to the amide bond and the metal centre is of sufficient Lewis acidity.

  6. Fine-tuning alkyne cycloadditions: Insights into photochemistry responsible for the double-strand DNA cleavage via structural perturbations in diaryl alkyne conjugates

    Directory of Open Access Journals (Sweden)

    Igor V. Alabugin

    2011-06-01

    Full Text Available Hybrid molecules combining photoactivated aryl acetylenes and a dicationic lysine moiety cause the most efficient double-strand (ds DNA cleavage known to date for a small molecule. In order to test the connection between the alkylating ability and the DNA-damaging properties of these compounds, we investigated the photoreactivity of three isomeric aryl–tetrafluoropyridinyl (TFP alkynes with amide substituents in different positions (o-, m-, and p- toward a model π-system. Reactions with 1,4-cyclohexadiene (1,4-CHD were used to probe the alkylating properties of the triplet excited states in these three isomers whilst Stern–Volmer quenching experiments were used to investigate the kinetics of photoinduced electron transfer (PET. The three analogous isomeric lysine conjugates cleaved DNA with different efficiencies (34, 15, and 0% of ds DNA cleavage for p-, m-, and o-substituted lysine conjugates, respectively consistent with the alkylating ability of the respective acetamides. The significant protecting effect of the hydroxyl radical and singlet oxygen scavengers to DNA cleavage was shown only with m-lysine conjugate. All three isomeric lysine conjugates inhibited human melanoma cell growth under photoactivation: The p-conjugate had the lowest CC50 (50% cell cytotoxicity value of 1.49 × 10−7 M.

  7. Hsp90 C-terminal inhibitors exhibit antimigratory activity by disrupting the Hsp90α/Aha1 complex in PC3-MM2 cells.

    Science.gov (United States)

    Ghosh, Suman; Shinogle, Heather E; Garg, Gaurav; Vielhauer, George A; Holzbeierlein, Jeffrey M; Dobrowsky, Rick T; Blagg, Brian S J

    2015-02-20

    Human Hsp90 isoforms are molecular chaperones that are often up-regulated in malignances and represent a primary target for Hsp90 inhibitors undergoing clinical evaluation. Hsp90α is a stress-inducible isoform of Hsp90 that plays a significant role in apoptosis and metastasis. Though Hsp90α is secreted into the extracellular space under metastatic conditions, its role in cancer biology is poorly understood. We report that Hsp90α associates with the Aha1 co-chaperone and found this complex to localize in secretory vesicles and at the leading edge of migrating cells. Knockdown of Hsp90α resulted in a defect in cell migration. The functional role of Hsp90α/Aha1 was studied by treating the cells with various novobiocin-based Hsp90 C-terminal inhibitors. These inhibitors disrupted the Hsp90α/Aha1 complex, caused a cytoplasmic redistribution of Hsp90α and Aha1, and decreased cell migration. Structure-function studies determined that disruption of Hsp90α/Aha1 association and inhibition of cell migration correlated with the presence of a benzamide side chain, since an acetamide substituted analog was less effective. Our results show that disruption of Hsp90α/Aha1 interactions with novobiocin-based Hsp90 C-terminal inhibitors may limit the metastatic potential of tumors.

  8. [Cloning and analysis of a new aliphatic amidase gene from Rhodococcus erythropolis TA37].

    Science.gov (United States)

    Lavrov, K V; Karpova, I Yu; Epremyan, A S; Yanenko, A S

    2014-10-01

    A new aliphatic amidase gene (ami), having a level of similarity with the nearest homologs of no more than 77%, was identified in the Rhodococcus erythropolis TA37 strain, which is able to hydrolyze a wide range of amides. The amidase gene was cloned within a 3.7 kb chromosomal locus, which also contains putative acetyl-CoA ligase and ABC-type transportergenes. The structure of this locus in the R. erythropolis TA37 strain differs from the structure of loci in other Rhodococcus strains. The amidase gene is expressed in Escherichia coli cells. It was demonstrated that amidase (generated in the recombinant strain) efficiently hydrolyzes acetamide (aliphatic anmide) and does not use 4'-nitroacetanilide (N-substituted amide) as a substrate. Insertional inactivation of the amidase gene in the R. erythropolis TA37 strain results in a considerable decrease (by at least 6-7 times) in basal amidase activity, indicating functional amidase activity in the R. erythropolis TA37 strain.

  9. A new acylamidase from Rhodococcus erythropolis TA37 can hydrolyze N-substituted amides.

    Science.gov (United States)

    Lavrov, K V; Zalunin, I A; Kotlova, E K; Yanenko, A S

    2010-08-01

    A new acylamidase was isolated from Rhodococcus erythropolis TA37 and characterized. N-Substituted acrylamides (isopropyl acrylamide, N,N-dimethyl-aminopropyl acrylamide, and methylene-bis-acrylamide), acid para-nitroanilides (4'-nitroacetanilide, Gly-pNA, Ala-pNA, Leu-pNA), and N-acetyl derivatives of glycine, alanine, and leucine are good substrates for this enzyme. Aliphatic amides (acetamide, acrylamide, isobutyramide, n-butyramide, and valeramide) are also used as substrates but with less efficiency. The enzyme subunit mass by SDS-PAGE is 55 kDa. Maximal activity is exhibited at pH 7-8 and 55°C. The enzyme is stable for 15 h at 22°C and for 0.5 h at 45°C. The Michaelis constant (K(m)) is 0.25 mM with Gly-pNA and 0.55 mM with Ala-pNA. The acylamidase activity is suppressed by inhibitors of serine proteases (phenylmethylsulfonyl fluoride and diisopropyl fluorophosphate) but is not suppressed by inhibitors of aliphatic amidases (acetaldehyde and nitrophenyl disulfides). The N-terminal amino acid sequence of the acylamidase is highly homologous to those of two putative amidases detected from sequenced R. erythropolis genomes. It is suggested that the acylamidase together with the detected homologs forms a new class within the amidase signature family.

  10. Amidation reaction of eugenyl oxyacetate ethyl ester with 1,3 diaminopropane

    Science.gov (United States)

    Suryanti, V.; Wibowo, F. R.; Kusumaningsih, T.; Wibowo, A. H.; Khumaidah, S. A.; Wijayanti, L. A.

    2016-04-01

    Eugenol having various substituents on the aromatic ring (hydroxy, methoxy and allyl) are useful for starting material in synthesizing of its derivatives. Eugenol derivatives have shown wide future potential applications in many areas, especially as future drugs against many diseases. The aim of this work was to synthesize an amide of eugenol derivative. The starting material used was eugenol from clove oil and the reaction was conducted in 3 step reactions to give the final product. Firstly, eugenol was converted into eugenyl oxyacetate [2-(4-allyl-2-methoxyphenoxy) acetic acid] as a white crystal with 70.5% yield, which was then esterified with ethanol to have eugenyl oxyacetate ethyl ester [ethyl 2-(4-allyl-2-methoxyphenoxy) acetate] as brown liquid in 75.7%. The last step was the reaction between eugenyl oxyacetate ethyl ester and 1,3 diaminopropane to give 2-(4-allyl-2-methoxyphenoxy)-N-(3-aminopropyl) acetamide as a brown powder with 71.6% yield, where the amidation reaction was occurred.

  11. Transition metal cations extraction by ester and ketone derivatives of chromogenic azocalix[4]arenes.

    Science.gov (United States)

    Ak, Metin; Taban, Deniz; Deligöz, Hasalettin

    2008-06-15

    The molecule of azocalix[n]arene is a macrocyclic used effectively in the complexation of the heavy metal pollutants (like silver and mercury). In this work, our main aim is to prepare new chromogenic azocalix[n]arene molecules to elaborate an extractant with high extractant selectivity for metal ions able to detect this type of pollutant. The solvent extraction properties of four acetyls, four methyl ketones and four benzoyls derivatives from azocalix[4]arenes which were prepared by linking 4-ethyl, 4-n-butyl, 4-acetamid anilin and 2-aminothiazol to calix[4]arene through a diazo-coupling reaction, the alkaline earth (Sr2+) and the transition (Ag+, Hg2+, Co2+, Ni2+, Cu2+, Zn2+, Cd2+, Cr3+) metal cations have been determined by extraction studies with metal picrates. Both ketones are better extractants than esters, and show a strong preference for Ag+, while Cu2+ and Cr3+ are the most extracted cation with the esters. Both acetyl and benzoyl esters are good carriers for Ag+ and Hg2+.

  12. Quantitative assays of the amount of diethylenetriaminepentaacetic acid conjugated to water-soluble polymers using isothermal titration calorimetry and colorimetry.

    Science.gov (United States)

    Gouin, S; Winnik, F M

    2001-01-01

    The level of conjugation of diethylenetriaminepentaacetic acid (DTPA) to the polysaccharide sodium hyaluronan (HA) has been measured by a colorimetric assay, isothermal titration calorimetry (ITC), and (1)H NMR spectroscopy. The colorimetric assay is based on the red shift, upon complexation with gadolinium ion (Gd3+), of the wavelength of maximum absorption of the dye arsenazo III. It can be performed in a few minutes using as little as 10 microg of polymer with a detection limit of approximately 0.03 mmol of DTPA (gram of polymer)-1. The ITC measurements yield values of the amount of DTPA linked to HA identical to those obtained by colorimetry. The levels of DTPA conjugation calculated by integration of signals at 3.1-3.2 ppm (DTPA protons) and at 2.0 ppm (HA acetamide protons) in the 1H NMR spectrum of HA-DTPA are consistently overestimated by a factor of approximately 2, compared to the data obtained by ITC and colorimetry. The longer relaxation times of protons of the polymer backbone, compared to those of protons attached to the freely moving DTPA side-chains may account for the discrepancy.

  13. Gas chromatographic method for the determination of lumefantrine in antimalarial finished pharmaceutical products

    Directory of Open Access Journals (Sweden)

    Sultan Suleman

    2015-09-01

    Full Text Available A simple method has been developed and validated for quantitative determination of lumefantrine in antimalarial finished pharmaceutical products using gas chromatography coupled to flame ionization detector. Lumefantrine was silylated with N,O–bis(trimethyl-silyltrifluoro-acetamide at 70°C for 30 minutes, and chromatographic separation was conducted on a fused silica capillary (HP-5, 30 m length × 0.32 mm i.d., 0.25 μm film thickness column. Evaluation of the method within analytical quality-by-design principles, including a central composite face-centered design for the sample derivatization process and Plackett–Burman robustness verification of the chromatographic conditions, indicated that the method has acceptable specificity toward excipients and degradants, accuracy [mean recovery = 99.5%, relative standard deviation (RSD = 1.0%], linearity (=0.9986, precision (intraday = 96.1% of the label claim, RSD = 0.9%; interday = 96.3% label claim, RSD = 0.9%, and high sensitivity with detection limits of 0.01 μg/mL. The developed method was successfully applied to analyze the lumefantrine content of marketed fixed-dose combination antimalarial finished pharmaceutical products.

  14. Free and bound aroma compounds characterization by GC-MS of Negroamaro wine as affected by soil management.

    Science.gov (United States)

    Toci, Aline T; Crupi, Pasquale; Gambacorta, Giuseppe; Dipalmo, Tiziana; Antonacci, Donato; Coletta, Antonio

    2012-09-01

    Negroamaro is an autochthonous wine grape variety of Southern Italy, which is becoming very important for the Italian wine market. The wine aroma is primary affected by the chemical composition of grapes, which can be influenced also by agronomic practices such as soil management. In this study, the free and bound aroma characterization was performed by gas chromatography-mass spectrometry analyses, and the influence of two soil managements (cover cropping and soil tillage) was evaluated. A total of 40 volatile compounds were observed in the wine samples. Alcohols (55.7 mg/L), fatty acids (7.0 mg/L) and esters (6.6 mg/L) were found as the main classes in Negroamaro wine. The results showed that the aroma composition of Negroamaro wine was positively affected by soil tillage probably because of the higher water stress (ψ(s)) recorded in the vines from this treatment. Indeed, among the free volatile compounds, higher contents of esters, carboxylic acids, alcohols, phenolics and acetamides together with lower contents of sulfurs compounds were found in soil tillage wine. Conversely, no difference was observed in glycoside volatile compounds.

  15. Preferential binding of growth inhibitory prostaglandins by the target protein of a carcinogen

    Energy Technology Data Exchange (ETDEWEB)

    Khan, S.H.; Sorof, S. (Fox Chase Cancer Center, Philadelphia, PA (United States))

    1990-12-01

    Liver fatty acid binding protein (L-FABP) is the principal target protein of the hepatic carcinogen N-(2-fluorenyl)acetamide (2-acetylaminofluorene) in rat liver. In addition, the cyclopentenone prostaglandins (PG), PGA, PGJ{sub 2}, and {Delta}{sup 12}-PGJ{sub 2}, inhibit the growth of many cell types in vitro. This report describes the preferential binding of the growth inhibitory prostaglandins by L-FABP and the reversible inhibition of thymidine incorporation into DNA by PGA{sub 2} and {Delta}{sup 12}-PGJ{sub 2} in primary cultures of purified rat hepatocytes. As a model ligand, ({sup 3}H)PGA{sub 1} bound to L-FABP specifically, reversibly, rapidly, and with high affinity. Its dissociation constants were 134 nM (high affinity) and 3.6 {mu}M (low affinity). The high-affinity finding of ({sup 3}H)PGA{sup 1} correlated with their growth inhibitory activities reported previously and here. The in vitro actions of L-FABP are compatible with those of a specific and dissociable carrier of growth inhibitory prostaglandins in rat hepatocytes and suggest that the carcinogen may usurp the cellular machinery of the growth inhibitory prostaglandins.

  16. Expression, purification and functional characterization of AmiA of acetamidase operon of Mycobacterium smegmatis.

    Science.gov (United States)

    Sundararaman, Balaji; Palaniyandi, Kannan; Venkatesan, Arunkumar; Narayanan, Sujatha

    2014-11-01

    Regulation of gene expression is one of the mechanisms of virulence in pathogenic organisms. In this context, we would like to understand the gene regulation of acetamidase enzyme of Mycobacterium smegmatis, which is the first reported inducible enzyme in mycobacteria. The acetamidase is highly inducible and the expression of this enzyme is increased 100-fold when the substrate acetamide is added. The acetamidase structural gene (amiE) is found immediately downstream of three predicted open reading frames (ORFs). Three of these genes along with a divergently expressed ORF are predicted to form an operon and involved in the regulation of acetamidase enzyme. Here we report expression, purification and functional characterization of AmiA which is one of these predicted ORFs. Electrophoretic mobility shift assays showed that AmiA binds to the region between the amiA and amiD near the predicted promoter (P2). Over-expression of AmiA significantly lowered the expression of acetamidase compared to the wild type as demonstrated by qRT-PCR and SDS-PAGE. We conclude that AmiA binds near P2 promoter and acts as a repressor in the regulation of acetamidase operon. The described work is a further step forward toward broadening the knowledge on understanding of the complex gene regulatory mechanism of Mycobacterium sp.

  17. Stimulant effect of nitric oxide generator and roxatidine on mucin biosynthesis of rat gastric oxyntic mucosa.

    Science.gov (United States)

    Ichikawa, T; Ishihara, K; Kusakabe, T; Kawakami, T; Hotta, K

    1999-01-01

    Although the involvement of nitric oxide (NO) in an increasing gastric mucus metabolism has been reported, information on whether or not its activation is limited to the specific mucus-producing cells is lacking. In this paper, we report the effect of the exogenous NO-donor, isosorbide dinitrate (ISDN), and second-generation histamine H2 receptor antagonist roxatidine (2-acetoxy-N-(3-[m-(1-piperidinylmethyl)phenoxy]propyl)acetamide hydrochloride) which is demonstrated to accelerate the mucin metabolism mediated by endogenous NO, on the mucin biosynthesis in distinct sites and layers of the rat gastric mucosa using an organ culture technique. Radiolabeled mucin was obtained from the tissue of full-thickness and the deep corpus layer, and the antrum of the rat stomach incubated for 5 hr with [3H]glucosamine(GlcN) in vitro. With the addition of ISDN to the culture medium, 3H-labeled mucin in the full-thickness corpus mucosa increased to 124-145% of the control (proxatidine stimulated the mucin biosynthesis in the full-thickness corpus mucosa, but not in the gland mucous cell layer. These results suggest that the stimulation of the mucin biosynthesis mediated by NO is restricted to the surface mucous cells of the rat gastric oxyntic mucosa.

  18. 2-acylamino-5-nitro-1,3-thiazoles: preparation and in vitro bioevaluation against four neglected protozoan parasites.

    Science.gov (United States)

    Nava-Zuazo, Carlos; Chávez-Silva, Fabiola; Moo-Puc, Rosa; Chan-Bacab, Manuel Jesús; Ortega-Morales, Benjamín Otto; Moreno-Díaz, Hermenegilda; Díaz-Coutiño, Daniel; Hernández-Núñez, Emanuel; Navarrete-Vázquez, Gabriel

    2014-03-01

    The 2-acylamino-5-nitro-1,3-thiazole derivatives (1-14) were prepared using a one step reaction. All compounds were tested in vitro against four neglected protozoan parasites (Giardia intestinalis, Trichomonas vaginalis, Leishmania amazonensis and Trypanosoma cruzi). Acetamide (9), valeroylamide (10), benzamide (12), methylcarbamate (13) and ethyloxamate (14) derivatives were the most active compounds against G. intestinalis and T. vaginalis, showing nanomolar inhibition. Compound 13 (IC50=10nM), was 536-times more active than metronidazole, and 121-fold more effective than nitazoxanide against G. intestinalis. Compound 14 was 29-times more active than metronidazole and 6.5-fold more potent than nitazoxanide against T. vaginalis. Ureic derivatives 2, 3 and 5 showed moderate activity against L. amazonensis. None of them were active against T. cruzi. Ligand efficiency indexes analysis revealed higher intrinsic quality of the most active 2-acylamino derivatives than nitazoxanide and metronidazole. In silico toxicity profile was also computed for the most active compounds. A very low in vitro mammalian cytotoxicity was obtained for 13 and 14, showing selectivity indexes (SI) of 246,300 and 141,500, respectively. Nitazoxanide showed an excellent leishmanicidal and trypanocidal effect, repurposing this drug as potential new antikinetoplastid parasite compound.

  19. Cytochrome P450 1 enzyme inhibition and anticancer potential of chromene amides from Amyris plumieri.

    Science.gov (United States)

    Badal, S; Williams, S A; Huang, G; Francis, S; Vedantam, P; Vendantam, P; Dunbar, O; Jacobs, H; Tzeng, T J; Gangemi, J; Delgoda, R

    2011-03-01

    Cytochrome P450 (CYP) enzyme inhibitory properties of six chromenylated amide compounds (CAs) from Amyris plumieri are described. Inhibition of CYP microsomes (CYP1A1, CYP1A2, CYP1B1, CYP2D6, CYP3A4 and CYP2C19) was monitored using a fluorescent assay. Potent inhibition was found against CYP1A1 with IC(50) and K(i) for CA1 (acetamide), being the lowest at 1.547 ± 1.0 μM and 0.37 μM respectively, displaying non-competitive kinetics. The selectivity for CYP1A1 was increased in CA3 (butanamide), which also exhibited cytotoxicity against breast cancer cells, MCF7 with an IC(50) of 47.46 ± 1.62 μM. Structure-activity relationship studies provide insight at a molecular level for CAs with implications in chemoprevention and chemotherapy. Copyright © 2010 Elsevier B.V. All rights reserved.

  20. Thermodynamic and Acoustic Study on Molecular Interactions in Certain Binary Liquid Systems Involving Ethyl Benzoate

    Directory of Open Access Journals (Sweden)

    B. Nagarjun

    2013-01-01

    Full Text Available Speeds of sound and density for binary mixtures of ethyl benzoate (EB with N,N-dimethylformamide (NNDMF, N,N-dimethyl acetamide (NNDMAc, and N,N-dimethylaniline (NNDMA were measured as a function of mole fraction at temperatures 303.15, 308.15 K, 313.15 K, and 318.15 K and atmospheric pressure. From the experimental data, adiabatic compressibility (βad, intermolecular free length (Lf, and molar volume (V have been computed. The excess values of the above parameters were also evaluated and discussed in light of molecular interactions. Deviation in adiabatic compressibilities and excess intermolecular free length (LfE are found to be negative over the molefraction of ethyl benzoate indicating the presence of strong interactions between the molecules. The negative excess molar volume VE values are attributed to strong dipole-dipole interactions between unlike molecules in the mixtures. The binary data of Δβad, VE, and LfE were correlated as a function of molefraction by using the Redlich-Kister equation.

  1. Orchid-associated bacteria produce indole-3-acetic acid, promote seed germination, and increase their microbial yield in response to exogenous auxin.

    Science.gov (United States)

    Tsavkelova, Elena A; Cherdyntseva, Tatiana A; Klimova, Svetlana Yu; Shestakov, Andrey I; Botina, Svetlana G; Netrusov, Alexander I

    2007-12-01

    Germination of orchid seeds is a complex process. In this paper we focus on interactions between the host-plant and its bacterial partners via indole-3-acetic acid (IAA). Originally isolated from the roots of the epiphytic orchid Dendrobium moschatum, the strains of Rhizobium, Microbacterium, Sphingomonas, and Mycobacterium genera were among the most active IAA producers. Addition of exogenous tryptophan significantly enhanced auxin formation both in mineral and complex media. The presence of IAA and indole-3-acetaldehyde was confirmed by HPLC. Indole-3-pyruvic and indole-3-lactic acids were also detected in supernatants of culture filtrates of Sphingomonas sp., Rhizobium sp., and Microbacterium sp., while indole-3-acetamide was identified only in Mycobacterium sp. Some concentration- and strain-dependent effects of exogenous IAA on bacterial development were also established. Treatment of the cultures with 10 and 100 microg/ml of auxin resulted in an increase in microbial yield. None of the investigated strains was able to utilize IAA as a source of carbon and energy. Furthermore, inoculation of D. moschatum seeds with Sphingomonas sp. and Mycobacterium sp. resulted in considerable enhancement of orchid seeds germination. This growth-promoting activity was observed in the absence of any plant growth stimulators or mycorrhizal fungi, usually required for orchid germination.

  2. The Cytotoxic Constituents from Marine-derived Streptomyces 3320#

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    The present work studies the chemical constituents from marine-derived streptomyces 3320# and their antitumor activities. The n-BuOH extract of the ferment broth of 3320# was chromatographed on silica gel, Sephadex LH-20, ODS columns and HPLC to separate the compounds with antitoumor activities. Their structures were identified using IR, UV, NMR, MS spectroscopic techniques and compared with published data. The antitumor activities of the isolates were assayed using SRB method and flow cytometry assay, accompanied with the morphological observation of the cells under light microscope against mammalian tsFT210 cells. Ten compounds, cyclo-(Ala-Leu) 1, cyclo-(Ala-Ile) 2, cyclo-(Ala-Val) 3, cyclo-(Phe- Pro) 4, cyclo-(Phe-Gly) 5, cyclo-(Leu-Pro) 6, 1-methyl-1, 2, 3, 4-tetrahydro-β-carboline-3-carboxylic acid 7, N-(4-hydroxyphenethyl) acetamide 8, 4-methyoxy-1-(2-hydroxy) ethylbenzene 9 and uridine 10, were isolated from the ferment broth of streptomyces 3320#. Among them, compounds 6, 7, 8 and 10 showed potent cytotoxicity against the tsFT210 cell with the IC50 values of 3 . 6, 7 . 2, 5 . 2 and 1 . 6 mmol L - 1, respectively. Compounds 8, 10 also exhibited apoptosis inducing activity under 2 . 0 mmol L - 1. Compounds 6, 7, 8 and 10 are the principle bioactive constituents responsible for the antitumor activities of marine streptomyces 3320# . Compound 7 was isolated from this species for the first time.

  3. Discovery of a selective kinase inhibitor (TAK-632) targeting pan-RAF inhibition: design, synthesis, and biological evaluation of C-7-substituted 1,3-benzothiazole derivatives.

    Science.gov (United States)

    Okaniwa, Masanori; Hirose, Masaaki; Arita, Takeo; Yabuki, Masato; Nakamura, Akito; Takagi, Terufumi; Kawamoto, Tomohiro; Uchiyama, Noriko; Sumita, Akihiko; Tsutsumi, Shunichirou; Tottori, Tsuneaki; Inui, Yoshitaka; Sang, Bi-Ching; Yano, Jason; Aertgeerts, Kathleen; Yoshida, Sei; Ishikawa, Tomoyasu

    2013-08-22

    With the aim of discovering a selective kinase inhibitor targeting pan-RAF kinase inhibition, we designed novel 1,3-benzothiazole derivatives based on our thiazolo[5,4-b]pyridine class RAF/VEGFR2 inhibitor 1 and developed a regioselective cyclization methodology for the C-7-substituted 1,3-benzothiazole scaffold utilizing meta-substituted anilines. Eventually, we selected 7-cyano derivative 8B (TAK-632) as a development candidate and confirmed its binding mode by cocrystal structure with BRAF. Accommodation of the 7-cyano group into the BRAF-selectivity pocket and the 3-(trifluoromethyl)phenyl acetamide moiety into the hydrophobic back pocket of BRAF in the DFG-out conformation contributed to enhanced RAF potency and selectivity vs VEGFR2. Reflecting its potent pan-RAF inhibition and slow off-rate profile, 8B demonstrated significant cellular activity against mutated BRAF or mutated NRAS cancer cell lines. Furthermore, in both A375 (BRAF(V600E)) and HMVII (NRAS(Q61K)) xenograft models in rats, 8B demonstrated regressive antitumor efficacy by twice daily, 14-day repetitive administration without significant body weight loss.

  4. Photodegradation of acetochlor in water and UV photoproducts identified by mass spectrometry

    Institute of Scientific and Technical Information of China (English)

    ZHENG He-hui; YE Chang-ming

    2003-01-01

    The sunlight photodegradation half-lives of 20 mg/L acetochlor were 151, 154 and 169 days in de-ionized water, river water and paddy water, respectively. When exposed to ultraviolet (UV) light, acetochlor in aqueous solution was rapidly degraded. The half-lives were 7.1, 10.1, and 11. 5 min in de-ionized water, river water and paddy water, respectively. Photoproducts of acetochlor were identified by gas chromatography/mass spectrometry(GC/MS) and found at least twelve photoproducts resulted from dechlorination with subsequent hydroxylation and cyclization processes. The chemical structures of ten photoproducts were presumed on the basis of mass spectrum interpretation and literature data. Photoproducts are identified as 2-ethyl-6-methylaniline; N, N-diethylaniline; 4,8-dimethyl-2-oxo-1, 2, 3,4- tetrahydroquinoline; 2-oxo-N-(2-ethyl-6-methylphenyl)-N-(ethoxymethyl) acetamide; N-(ethoxymethyl)-2′-ethyl-6′-methylformanilide; 1-hydroxyacetyl-2-ethoxyl-7-ethylind ole; 8-ethyl-1-ethoxymethyl-2-oxo-1, 2, 3, 4-tetrahydroquinoline; 4, 8-dimethyl-1-ethoxymethyl-2-oxo-1, 2, 3, 4-tetrahydroquinoline; 2-hydroxy-2′-ethyl-6′-methyl-N-(ethoxymethyl) acetanilide and a compound related to acetochlor. The other two photoproducts were detected by GC/MS although their chemical structure was unknown.

  5. Stereoselective synthesis and structure-affinity relationships of bicyclic kappa receptor agonists.

    Science.gov (United States)

    Kracht, Daniel; Rack, Elisabeth; Schepmann, Dirk; Fröhlich, Roland; Wünsch, Bernhard

    2010-01-07

    Reductive amination of the bicyclic ketone 4 led diastereoselectively to endo-configured amines, which were transformed into the amides 7-10. The synthesis of the diastereomers 25 with an exo-configured amino moiety at position 6 was only successful after deactivation of both N-atoms of the 1,4-diazabicyclo[3.3.1]nonane system. The N-1-oxide 19 with an N-4-tosyl moiety was the crucial intermediate, which allows SN2 substitution with NaN3 under inversion of the configuration at position 6. Whereas the endo-configured pyrrolidine 7a (WMS-1302) revealed a kappa receptor affinity of 73 nM, the exo-configured diastereomer 25a was almost inactive at the kappa receptor (Ki > 1 microM). Replacement of the 3,4-dichlorophenylacetyl residue by other acyl and sulfonyl residues showed that it is essential for high kappa affinity. The kappa receptor affinities of the conformationally constrained pyrrolidines 7a and 25a were correlated with the dihedral angle N(pyrrolidine)-C-C-N(acetamide). A systematic conformational analysis of the potent but flexible kappa agonist 2 showed that a dihedral angle of 168 degrees (as in 25a) is energetically more disfavored than a dihedral angle of 58 degrees (7a). However, even the conformation with a dihedral angle of 58 degrees does not represent an energy minimum, which might explain the reduced kappa affinity of 7a.

  6. HPLC assay for the determination of PD 117,302, a Kappa analgesic, and its application to disposition studies in rats

    Energy Technology Data Exchange (ETDEWEB)

    Young, R.M.; Chang, T.

    1986-03-01

    PD 117,302-2 (I) trans-(+)-N-methyl-N-(2-(1-pyrrolidinyl) cyclohexyl)benzo(b)thiophene-4-acetamide, monohydrochloride is a new Kappa analgesic. To facilitate preclinical development, an HPLC assay was developed. (I) and an internal standard were extracted from alkalinized rat plasma with CH/sub 2/Cl/sub 2/. HPLC was performed on a Waters Nova-Pak C/sub 18/ column (3.9 mm x 15 cm) using 0.5% triethylamine in 50:50 CH/sub 3/CN/0.05M NH/sub 4/H/sub 2/PO/sub 4/ (pH 6.7) at a flow rate of 2 ml/min. UV absorbancy was monitored at 237 nm. Calibration curves were linear over a range of 80-4000 ng/ml. Within-day precision ranged 0.1-9.0% and between-day precision ranged 3.1-7.6%. /sup 14/C-(I) given orally (10 mg/kg) was completely absorbed and extensively metabolized. Elimination t 1/2 of (I) averaged 2 hr. Fecal and urinary /sup 14/C recoveries accounted for 54-76% and 9-12% of the dose, respectively. No intact drug was found in feces, indicating that the high fecal /sup 14/C recovery was due to the presence of metabolites(s) rather than poor absorption.

  7. Effect of successive alkylation of N,N-dialkyl amides on the complexation behavior of uranium and thorium: solvent extraction, small angle neutron scattering, and computational studies.

    Science.gov (United States)

    Verma, Parveen Kumar; Pathak, Priyanath N; Kumari, Neelam; Sadhu, Biswajit; Sundararajan, Mahesh; Aswal, Vinod Kumar; Mohapatra, Prasanta Kumar

    2014-12-11

    The effect of successive alkylation of the Cα atom adjacent to the carbonyl group in N,N-dialkyl amides (i.e., di(2-ethylhexyl)acetamide (D2EHAA), di(2-ethylhexyl)propionamide (D2EHPRA), di(2-ethylhexyl)isobutyramide (D2EHIBA), and di(2-ethylhexyl)pivalamide (D2EHPVA)) on the extraction behavior of hexavalent uranium (U(VI)) and tetravalent thorium (Th(IV)) ions has been investigated. These studies show that the extraction of Th(IV) is significantly suppressed compared to that of U(VI) with increased branching at the Cα atom adjacent to the carbonyl group. Small angle neutron scattering (SANS) studies showed an increased aggregation tendency in the presence of nitric acid and metal ions. D2EHAA showed more aggregation compared to its branched homologues, which explains its capacity for higher extraction of metal ions. These experimental observations were further supported by density function theory calculations, which provided structural evidence of differential binding affinities of these extractants for uranyl cations. The complexation process is primarily controlled by steric and electronic effects. Quantum chemical calculations showed that local hardness and polarizability can be extremely useful inputs for designing novel extractants relevant to a nuclear fuel cycle.

  8. Use of Bacterial Indicators for Contamination in Drinking Water of Qom, Iran

    Science.gov (United States)

    Shamabadi, N.; Ebrahimi, M.

    This study is performed to investigate the bacterial contamination of the water resources and the pipeline networks of the city. Faecal coliforms (such as Escherichia coli (E. coli) as the most important indicator of water contamination), non-faecal coliforms and Pseudomonas aeruginosa (which have recently been introduced as a new indicator of water contamination) as well as the number of phototrophic bacteria are examined. Samples collected from all wells, a big reservoir supplying big part of the city=s water (called Khordad 15 Dam), main pipeline networks, settling and resting reservoirs and finally treated water consumed by people under a sterile condition. The results showed 25% of samples from main water resources of Qom city were contaminated with confirm but no contamination detected in treated water. 16.7% of were samples were contaminated with Pseudomonas aeruginosa after subculturing to Acetamid broth, but 11.8% of treated water samples confirmed to be contaminated with this bacterium in the second subculture. Although the results of this study demonstrated the potential threats of bacterial contamination (such as coliforms) in water resources, Qom=s fresh water is safe and water treatment facilities there work quietly efficient and remove all coliform contaminations. The appearance of Pseudomonas aeruginosa contamination in drinking water is a sign of pipeline network cracks and erosions which require new efforts to repair and renew them.

  9. Simultaneous determination of compounds in Septalen pellets by derivative spectrophotometry

    Directory of Open Access Journals (Sweden)

    ANDJELIJA MALENOVIC

    2000-06-01

    Full Text Available In this paper, a second-derivative spectrophotometric method of assaying Septalen pellets (Krka, Novo Mesto, Slovenia, which contain lidocaine 1 mg, and cetrimonium bromide 2 mg, is described. Lidocaine, 2-(diethylamino-N-(2,6-dimethyl-phenyl-acetamide, is a local anesthetic with pronounced antiarhythmic and anticonvulsant properties. Cetrimonium bromide, N,N,N-trimethyl-l-hexadecanaminium bromide, is a topical antiseptic and cleansing agent. Lidocaine was determined at 250 nm using the "zero crossing" technique because the signals of centrimonium bromide and the colour ingredient are zero at this wavelength. Cetrimonium bromide was determined by correction of the peak amplitude at 215 nm according to lidocaine. In choosing the optimal magnitudes for the simultaneous determination of both drugs, the following criteria were considered: (1 the linearity of the calibration graphs as given by the correlation coefficients, (2 the intercept, (3 the sensitivity as given by the regression coefficient, (4 the degree of interference in the derivative measurement by the presence of the other compound, as given by the relative percent error and by the relative recovery, and (5 the reproducibility, as given by the coefficient of variation, calculated by recording the second-derivative spectra.

  10. Biotherapeutic potential and mechanisms of action of colchicine.

    Science.gov (United States)

    Dubey, Kashyap Kumar; Kumar, Punit; Labrou, Nikolaos E; Shukla, Pratyoosh

    2017-12-01

    Cancer is a clinical situation caused by uncontrolled cell division and is responsible for a large number of deaths worldwide. Colchicine is a classical antimitotic, tubulin-binding agent (TBA) which is being explored for its antitumor activities, although its tubulin-binding ability leads to some toxicity toward normal cells proliferation. Colchicine derivatives are considered as potent antitumor compounds with less toxicity compared to colchicine. Derivatives with substituted functional groups at A-ring (methoxy), B-ring (acetamide) or C-ring (methoxy) have been synthesized via chemical and microbial routes and show modified bioactivities and altered tropolonic functionality. Earlier reports, in combination with our group's research findings, suggest that microbial biotransformation is an efficient choice for the production of bioactive colchicine derivatives. This route has gained significant interest in the mass production of regio-specific, cost-effective, safe and eco-friendly derivatives. The present review paper critically analyzes and discusses the development and application of colchicine derivatives as a potent antitumor molecule and their production through a microbial transformation process. The information provided in this review might assist in the stimulation of new ideas regarding the development of alternative therapeutic agent(s) for cancer treatment.

  11. Recent updates on glucokinase activators for the treatment of type 2 diabetes mellitus.

    Science.gov (United States)

    Grewal, Ajmer Singh; Sekhon, Bhupinder Singh; Lather, Viney

    2014-01-01

    Glucose-phosphorylating enzyme, glucokinase (GK) plays a major role in glucose homeostasis primarily through its regulatory actions in pancreatic β-cells and liver hepatocytes. Conversion of glucose to glucose-6-phosphate by GK promotes glycogen synthesis in liver hepatocytes, and insulin release in the pancreatic β-cells. Small molecules called glucokinase activators (GKAs) which bind to an allosteric activator site of the GK enzyme have indeed been discovered and developed, and thus hold great promise as new, effective and safe antidiabetic agents. GKAs enhance the catalytic activity of GK and promising clinical trials in humans demonstrated that they are highly useful in the treatment of type 2 diabetes mellitus. Most of the reported GKAs include amide derivatives like benzamides, acrylamides, carboxamides, acetamides and acrylamides. Examples include Piragliatin, AZD1656, AZD6370, R1440 GKA2, GKA 50, YH GKA, PSN 010, and LY2121260. Recent findings on GKAs including lead compounds and overview of current hypothesis on mechanism of GK activation along with summary of the recently published patents as well as the GKAs of natural origin are reported in the present review.

  12. Biodegradation of acrylamide by Enterobacter aerogenes isolated from wastewater in Thailand

    Institute of Scientific and Technical Information of China (English)

    Kanokhathai Buranasilp; Jittima Charoenpanich

    2011-01-01

    A widespread use of acrylamide, probably a neurotoxicant and carcinogen, in various industrial processes has led to environmental contamination. Fortunately, some microorganisms are able to derive energy from acrylamide. In the present work, we reported the isolation and characterization of a novel acrylamide-degrading bacterium from domestic wastewater in Chonburi, Thailand. The strain grew well in the presence of acrylamide as 0.5% (W/V), at pH 6.0 to 9.0 and 25℃. Identification based on biochemical characteristics and 16S rRNA gene sequence identified the strain as Enterobacter aerogenes. Degradation of acrylamide to acrylic acid started in the late logarithmic growth phase as a biomass-dependent pattern. Specificity of cell-free supernatant towards amides completely degraded butyramide and urea and 86% of lactamide. Moderate degradation took place in other amides with that by formamide > benzamide > acetamide > cyanoacetamide > propionamide. No degradation was detected in the reactions of N,N-methylene bisacrylamide, sodium azide, thioacetamide, and iodoacetamide. These results highlighted the potential of this bacterium in the cleanup of acrylamide/amide in the environment.

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

    Science.gov (United States)

    Krátký, Martin; Vinšová, Jarmila; Stolaříková, Jiřina

    2017-03-15

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

  14. Efficient Synthesis of Novel Pyridine-Based Derivatives via Suzuki Cross-Coupling Reaction of Commercially Available 5-Bromo-2-methylpyridin-3-amine: Quantum Mechanical Investigations and Biological Activities

    Directory of Open Access Journals (Sweden)

    Gulraiz Ahmad

    2017-01-01

    Full Text Available The present study describes palladium-catalyzed one pot Suzuki cross-coupling reaction to synthesize a series of novel pyridine derivatives 2a–2i, 4a–4i. In brief, Suzuki cross-coupling reaction of 5-bromo-2-methylpyridin-3-amine (1 directly or via N-[5-bromo-2-methylpyridine-3-yl]acetamide (3 with several arylboronic acids produced these novel pyridine derivatives in moderate to good yield. Density functional theory (DFT studies were carried out for the pyridine derivatives 2a–2i and 4a–4i by using B3LYP/6-31G(d,p basis with the help of GAUSSIAN 09 suite programme. The frontier molecular orbitals analysis, reactivity indices, molecular electrostatic potential and dipole measurements with the help of DFT methods, described the possible reaction pathways and potential candidates as chiral dopants for liquid crystals. The anti-thrombolytic, biofilm inhibition and haemolytic activities of pyridine derivatives were also investigated. In particular, the compound 4b exhibited the highest percentage lysis value (41.32% against clot formation in human blood among all newly synthesized compounds. In addition, the compound 4f was found to be the most potent against Escherichia coli with an inhibition value of 91.95%. The rest of the pyridine derivatives displayed moderate biological activities.

  15. Solubility of β-cyclodextrin in different mixed solvents

    Institute of Scientific and Technical Information of China (English)

    Yu Yong; Li Jiguang; Sun Yan; Liang Qianqing; Peng Xiaoming; Liu Yansheng; Hu Yufeng

    2008-01-01

    The solubility of β-cyclodextrin(β-CD)in ionic liquid/N,N-dimethyl-acetamide(IL/DMAC)mixed solvent and in LiCl/DMAC mixed solvent was investigated at 323.15 K and 353.15 K.The results showed that the solubility of β-CD in IL/DMAC system increased with increasing temperature,but decreased in LiCl/DMAC system.β-CD had the highest solubility in IL/DMAC system with[Cl]- or[Br]- anions.The solubility of β-CD in LiCl/DMAC system was lower than that in IL/DMAC system with [Cl]- or[Br]- anions but higher than that in IL/DMAC system with weak-coordinated anions(e.g[BF4]- or[PF6]-).The effects of substituent groups(benzyl and butyl)of cation and the structure of cations on β-cyclodextrin solubility were also investigated.

  16. Interfacial thermodynamics of water and six other liquid solvents.

    Science.gov (United States)

    Pascal, Tod A; Goddard, William A

    2014-06-05

    We examine the thermodynamics of the liquid-vapor interface by direct calculation of the surface entropy, enthalpy, and free energy from extensive molecular dynamics simulations using the two-phase thermodynamics (2PT) method. Results for water, acetonitrile, cyclohexane, dimethyl sulfoxide, hexanol, N-methyl acetamide, and toluene are presented. We validate our approach by predicting the interfacial surface tensions (IFT--excess surface free energy per unit area) in excellent agreement with the mechanical calculations using Kirkwood-Buff theory. Additionally, we evaluate the temperature dependence of the IFT of water as described by the TIP4P/2005, SPC/Ew, TIP3P, and mW classical water models. We find that the TIP4P/2005 and SPC/Ew water models do a reasonable job of describing the interfacial thermodynamics; however, the TIP3P and mW are quite poor. We find that the underprediction of the experimental IFT at 298 K by these water models results from understructured surface molecules whose binding energies are too weak. Finally, we performed depth profiles of the interfacial thermodynamics which revealed long tails that extend far into what would be considered bulk from standard Gibbs theory. In fact, we find a nonmonotonic interfacial free energy profile for water, a unique feature that could have important consequences for the absorption of ions and other small molecules.

  17. Characterization of the hydrogen bond in molecular systems of biological interest by neutron scattering; Caracterisation de la liaison hydrogene dans des systemes moleculaires d'interet biologique par diffusion de neutrons

    Energy Technology Data Exchange (ETDEWEB)

    Cavillon, F

    2004-10-15

    This work presents a methodology for the analysis of the scattering spectra of neutrons on molecular liquids. This method is based on the adjustment of the molecular form factor concerning great momentum transfer. The subtraction of the intra-molecular contributions gives access to information on inter-molecular interactions such as the hydrogen bond. 3 systems with increasing levels of difficulty have been studied: the ammonia molecule, the N-methyl-formamide (NMF) and the N-methyl-acetamide (NMA). The value we get for the N-D intermolecular distance of the liquid ammonia molecule is 1.7 angstrom, this value is different from the value generally admitted (2.3 angstrom) but we have validated it by studying the isotopic substitution N{sup 14}/N{sup 15}. The adjustment to the NMF is obtained with a good accuracy but the characterization of the hydrogen bound is more delicate to infer. A preliminary study of the NMA molecule shows that this method can give relevant results on complex molecules.

  18. Selectable genes for transformation of the fungal plant pathogen Glomerella cingulata f. sp. phaseoli (Colletotrichum lindemuthianum).

    Science.gov (United States)

    Rodriguez, R J; Yoder, O C

    1987-01-01

    Glomerella cingulata f. sp. phaseoli (Gcp) was transformed using either of two selectable markers: the amdS + gene of Aspergillus nidulans, which encodes acetamidase and permits growth on acetamide as the sole nitrogen source and the hygBR gene of Escherichia coli which encodes hygromycin B (Hy) phosphotransferase and permits growth in the presence of the antibiotic Hy. The amdS+ gene functioned in Gcp under control of A. nidulans regulatory signals and hygBR was expressed after fusion to a promoter from Cochliobolus heterostrophus, another filamentous ascomycete. Protoplasts to be transformed were generated with the digestive enzyme complex Novozym 234 and then were exposed to plasmid DNA in the presence of 10 mM CaCl2 and polyethylene glycol. Transformation occurred by integration of single or multiple copies of either the amdS+ or hygBR plasmid into the fungal genome. There was no evidence of autonomous plasmid replication. Transformants were mitotically stable on selective and nonselective media. However, transforming DNA in hygBR transformants was observed to occasionally rearrange during nonselective growth, resulting in fewer copies of the plasmid per genome. These transformants were capable of infecting bean (Phaseolus vulgaris), the Gcp host plant, and after recovery from infected tissue were found to have retained both the transforming DNA unrearranged in their genomes and the Hy resistance phenotype. All single-conidial cultures derived from both amdS+ and hygBR transformants had the transplanted phenotype, suggesting that transformants were homokaryons.

  19. TRPA1 contributes to cold hypersensitivity.

    Science.gov (United States)

    del Camino, Donato; Murphy, Sarah; Heiry, Melissa; Barrett, Lee B; Earley, Taryn J; Cook, Colby A; Petrus, Matt J; Zhao, Michael; D'Amours, Marc; Deering, Nate; Brenner, Gary J; Costigan, Michael; Hayward, Neil J; Chong, Jayhong A; Fanger, Christopher M; Woolf, Clifford J; Patapoutian, Ardem; Moran, Magdalene M

    2010-11-10

    TRPA1 is a nonselective cation channel expressed by nociceptors. Although it is widely accepted that TRPA1 serves as a broad irritancy receptor for a variety of reactive chemicals, its role in cold sensation remains controversial. Here, we demonstrate that mild cooling markedly increases agonist-evoked rat TRPA1 currents. In the absence of an agonist, even noxious cold only increases current amplitude slightly. These results suggest that TRPA1 is a key mediator of cold hypersensitivity in pathological conditions in which reactive oxygen species and proinflammatory activators of the channel are present, but likely plays a comparatively minor role in acute cold sensation. Supporting this, cold hypersensitivity can be induced in wild-type but not Trpa1(-/-) mice by subcutaneous administration of a TRPA1 agonist. Furthermore, the selective TRPA1 antagonist HC-030031 [2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide] reduces cold hypersensitivity in rodent models of inflammatory and neuropathic pain.

  20. Imaging of peripheral-type benzodiazepine receptor in tumor: carbon ion irradiation reduced the uptake of a positron emission tomography ligand [11C]DAC in tumor.

    Science.gov (United States)

    Yamasaki, Tomoteru; Koike, Sachiko; Hatori, Akiko; Yanamoto, Kazuhiko; Kawamura, Kazunori; Yui, Joji; Kumata, Katsushi; Ando, Koichi; Zhang, Ming-Rong

    2010-01-01

    We aimed to determine the effect of carbon ion irradiation on the uptake of N-benzyl-N-11C-methyl-2-(7-methyl-8-oxo-2-phenyl-7,8-dihydro-9H-purin-9-yl)acetamide ([(11)C]DAC), a positron emission tomography (PET) ligand for the peripheral-type benzodiazepine receptor (PBR), in tumor cells and tumor-bearing mice. Spontaneous murine fibrosarcoma (NFSa) cells were implanted into the right hind legs of syngeneic C3H male mice. Conditioning irradiation with 290 MeV/u carbon ions was delivered to the 7- to 8-mm tumors In vitro uptake of [(11)C]DAC was measured in single NFSa cells isolated from NFSa-bearing mice after irradiation. In vivo biodistribution of [(11)C]DAC in NFSa-bearing mice was determined by small animal PET scanning and dissection. In vitro autoradiography was performed using tumor sections prepared from mice after PET scanning. In vitro and in vivo uptake of [(11)C]DAC in single NFSa cells and NFSa-bearing mice was significantly reduced by carbon ion irradiation. The decrease in [(11)C]DAC uptake in the tumor sections was mainly due to the change in PBR expression. In conclusion, [(11)C]DAC PET responded to the change in PBR expression in tumors caused by carbon ion irradiation in this study. Thus, [(11)C]DAC is a promising predictor for evaluating the effect of carbon ion radiotherapy.

  1. Crystal structure of oxamyl

    Directory of Open Access Journals (Sweden)

    Eunjin Kwon

    2016-12-01

    Full Text Available The title compound, C7H13N3O3S [systematic name: (Z-methyl 2-dimethylamino-N-(methylcarbamoyloxy-2-oxoethanimidothioate], is an oxime carbamate acaride, insecticide and nematicide. The asymmetric unit comprises two independent molecules, A and B. The dihedral angles between the mean planes [r.m.s. deviations = 0.0017 (A and 0.0016 Å (B] of the acetamide and oxyimino groups are 88.80 (8° for A and 87.05 (8° for B. In the crystal, N/C—H...O hydrogen bonds link adjacent molecules, forming chains along the a axis. The chains are further linked by C—H...O hydrogen bonds, resulting in a three-dimensional network with alternating rows of A and B molecules in the bc plane stacked along the a-axis direction. The structure was refined as an inversion twin with a final BASF parameter of 0.16 (9.

  2. Synergistic effects of ethosomes and chemical enhancers on enhancement of naloxone permeation through human skin.

    Science.gov (United States)

    Xu, D H; Zhang, Q; Feng, X; Xu, X; Liang, W Q

    2007-04-01

    The purpose of this study was to investigate the effects of ethosomes, chemical enhancers and their binary combination on the in vitro permeability enhancement of naloxone through human skin. Franz diffusion cells were used for the percutaneous absorption studies. Propylene glycol (PG), N,N-dimethyl formamide (N,N-DMF), N,N-dimethyl acetamide (N,N-DMA), dimethyl sulfoxide (DMSO), Azone and polyethylene glycol 400 (PEG400), were chosen as the chemical enhancers. Naloxone ethosomes showed 11.68 times increase in steady-state flux compared to phosphate buffered solution (PBS). Ethosomes in combination with chemical enhancers synergistically increased (p ethosomal form dramatically enhanced the skin permeation of naloxone in vitro compared with ethosomes (steady-state flux: 96.75 +/- 5.70 microg x cm(-2) x h(-1) vs 20.56 +/- 1.67 microg x cm(-2) x h(-1)). Ethosomal carrier and enhancers accumulated in the skin after 24 h were greater than that of PBS.

  3. Synthesis and nootropic activity of some 2,3-dihydro-1H-isoindol-1-one derivatives structurally related with piracetam.

    Science.gov (United States)

    Reyes, Adelfo; Huerta, Leticia; Alfaro, Marisol; Navarrete, Andrés

    2010-11-01

    Three 2,3-dihydro-1H-isoindol-1-ones structurally related with piracetam (=2-oxopyrrolidine-1-acetamide) have been synthesized and tested for their nootropic effects in the passive avoidance test in mice. Compounds (RS)-2, (R,R)-3, and (R,S)-3 were obtained in good yields in only two steps starting from methyl DL-phthaloylalanine. Compound (RS)-2 exhibited nootropic activity at lower doses than piracetam, used as reference drug, but it showed lower efficacy. Whereas diastereoisomers (R,R)-3 and (R,S)-3 were as potent as piracetam to revert amnesia induced by scopolamine, (R,S)-3 showed lower efficacy than (R,R)-3. Only (R,R)-3 showed myorelaxant effect at doses of 10 and 30 mg/kg; other compounds did not exhibit any anticonvulsant, sedative, myorelaxant, or impaired motor-coordination effect in mice. These synthesized 2,3-dihydro-1H-isoindol-1-one derivatives constitute a new kind of nootropic compounds.

  4. Piracetam and TRH analogues antagonise inhibition by barbiturates, diazepam, melatonin and galanin of human erythrocyte D-glucose transport

    Science.gov (United States)

    Naftalin, Richard J; Cunningham, Philip; Afzal-Ahmed, Iram

    2004-01-01

    Nootropic drugs increase glucose uptake into anaesthetised brain and into Alzheimer's diseased brain. Thyrotropin-releasing hormone, TRH, which has a chemical structure similar to nootropics increases cerebellar uptake of glucose in murine rolling ataxia. This paper shows that nootropic drugs like piracetam (2-oxo 1 pyrrolidine acetamide) and levetiracetam and neuropeptides like TRH antagonise the inhibition of glucose transport by barbiturates, diazepam, melatonin and endogenous neuropeptide galanin in human erythrocytes in vitro. The potencies of nootropic drugs in opposing scopolamine-induced memory loss correlate with their potencies in antagonising pentobarbital inhibition of erythrocyte glucose transport in vitro (PPiracetam and TRH have no direct effects on net glucose transport, but competitively antagonise hypnotic drug inhibition of glucose transport. Other nootropics, like aniracetam and levetiracetam, while antagonising pentobarbital action, also inhibit glucose transport. Analeptics like bemigride and methamphetamine are more potent inhibitors of glucose transport than antagonists of hypnotic action on glucose transport. There are similarities between amino-acid sequences in human glucose transport protein isoform 1 (GLUT1) and the benzodiazepine-binding domains of GABAA (gamma amino butyric acid) receptor subunits. Mapped on a 3D template of GLUT1, these homologies suggest that the site of diazepam and piracetam interaction is a pocket outside the central hydrophilic pore region. Nootropic pyrrolidone antagonism of hypnotic drug inhibition of glucose transport in vitro may be an analogue of TRH antagonism of galanin-induced narcosis. PMID:15148255

  5. Response surface method (RSM) for optimization of ionic conductivity of membranes polymer electrolyte poly (vinylidene fluoride) (PVDF) with polyvinyl pyrrolidone (PVP) as pore forming agent

    Science.gov (United States)

    Dyartanti, E. R.; Susanto, H.; Widiasa, I. N.; Purwanto, A.

    2017-06-01

    The Membranes Polymer Gel Electrolyte (MPGEs) based poly (vinylidene fluoride) (PVDF) was prepared by a phase inversion method using polyvinyl pyrrolidone (PVP) as a pore-forming agent and N, N-dimethyl acetamide (DMAc) as a solvent and water as non solvet. The membranes were then soaked in 1 M lithium hexafluorophosphate (LiPF6) in ethylene carbonate (EC) / dimethyl carbonate (DMC) / Diethyl carbonate (DEC) (4:2:4 %vol) solution in order to prepare polymer electrolyte membranes. The MPEGs PVDF/PVP/Nanoclay was applied using central composite design (CCD) experimental design to obtain a quantitative relationship between selected membranes prepared parameters namely (PVDF, PVP as pore forming agent and nanoclay filler concentration) and Ionic conductivity MPEGs. The model was used to find the optimum ionic conductivity from polymer electrolyte membranes. The polymer electrolyte membranes show good ionic conductivity on the order of 6.3 - 8.7 x 10-3 S cm-1 at the ambient temperatures. The ionic conductivity tended to increase with PVP and nanoclay concentration and decrease with PVDF composition. The model predicted the maximum ionic conductivity of 8.47 x 10-3 S cm-1 when the PVDF, PVP and nanoclay concentration were set at 8.01 %, 8.04 % and 10.12%, respectively. The first section in your paper.

  6. Cytokinins of the Developing Mango Fruit : Isolation, Identification, and Changes in Levels during Maturation.

    Science.gov (United States)

    Chen, W S

    1983-02-01

    The cytokinin activity has been isolated and identified from extracts of immature mango (Mangifera indica L.) seeds. The structures of zeatin, zeatin riboside, and N(6)-(Delta(2)-isopentenyl)adenine riboside were confirmed on the basis of their chromatographic behavior and mass spectra of trimethylsilyl derivatives. Both trans and cis isomers of zeatin and zeatin riboside were also identified by the retention times of high performance liquid chromatography. In addition, an unidentified compound appeared to be a cytokinin glucoside.The concentration of cytokinins in the panicle and pulp of mango reached a maximum 5 to 10 days after full bloom and decreased rapidly thereafter. The cytokinin level in the seed remained high until the 28th day after full bloom. The quantity of cytokinins in pulp per fruit increased from the 10th day after full bloom, the maximum being attained around the 50th day after full bloom. Similarly, the amount of cytokinins per seed increased from the 10th day after full bloom, reaching a peak on the 40th day and decreasing gradually thereafter.A high percentage of fruit set in mango was persistently maintained by supplying 6-benzylaminopurine (1.5 x 10(3) micromolar) onto the panicle at the anthesis stage and by supplying gibberellic acid (7.2 x 10(2) micromolar) and naphthalene acetamide (3.1 x 10 micromolar) at the young fruit stage.

  7. A comparison of the alpha and gamma radiolysis of CMPO

    Energy Technology Data Exchange (ETDEWEB)

    Bruce J. Mincher; Stephen P. Mezyk; Gary Groenewold; Gracy Elias

    2011-06-01

    The radiation chemistry of CMPO has been investigated using a combination of irradiation and analytical techniques. The {alpha}-, and {gamma}-irradiation of CMPO resulted in identical degradation rates (G-value, in {mu}mol Gy{sup -1}) for both radiation types, despite the difference in their linear energy transfer (LET). Similarly, variations in {gamma}-ray dose rates did not affect the degradation rate of CMPO. The solvent extraction behavior was different for the two radiation types, however. Gamma-irradiation resulted in steadily increasing distribution ratios for both forward and stripping extractions, with respect to increasing absorbed radiation dose. This was true for samples irradiated as a neat organic solution, or irradiated in contact with the acidic aqueous phase. In contrast, {alpha}-irradiated samples showed a rapid drop in distribution ratios for forward and stripping extractions, followed by essentially constant distribution ratios at higher absorbed doses. These differences in extraction behavior are reconciled by mass spectrometric examination of CMPO decomposition products under the different irradiation sources. Irradiation by {gamma}-rays resulted in the rupture of phosphoryl-methylene bonds with the production of phosphinic acid products. These species are expected to be complexing agents for americium that would result in higher distribution ratios. Irradiation by {alpha}-sources appeared to favor rupture of carbamoyl-methylene bonds with the production of less deleterious acetamide products.

  8. Urearetics: a small molecule screen yields nanomolar potency inhibitors of urea transporter UT-B.

    Science.gov (United States)

    Levin, Marc H; de la Fuente, Ricardo; Verkman, A S

    2007-02-01

    Functional studies in knockout mice indicate a critical role for urea transporters (UTs) in the urinary concentrating mechanism and in renal urea clearance. However, potent and specific urea transport blockers have not been available. Here, we used high-throughput screening to discover high-affinity, small molecule inhibitors of the UT-B urea transporter. A collection of 50,000 diverse, drug-like compounds was screened using a human erythrocyte lysis assay based on UT-B-facilitated acetamide transport. Primary screening yielded approximately 30 UT-B inhibitors belonging to the phenylsulfoxyoxazole, benzenesulfonanilide, phthalazinamine, and aminobenzimidazole chemical classes. Screening of approximately 700 structurally similar analogs gave many active compounds, the most potent of which inhibited UT-B urea transport with an EC50 of approximately 10 nM, and approximately 100% inhibition at higher concentrations. Phenylsulfoxyoxazoles and phthalazinamines also blocked rodent UT-B and had good UT-B vs. UT-A specificity. The UT-B inhibitors did not reduce aquaporin-1 (AQP1)-facilitated water transport. In AQP1-null erythrocytes, "chemical UT-B knockout" by UT-B inhibitors reduced by approximately 3-fold UT-B-mediated water transport, supporting an aqueous pore pathway through UT-B. UT-B inhibitors represent a new class of diuretics, "urearetics," which are predicted to increase renal water and solute clearance in water-retaining states.

  9. The Effect of Electrolyte Additives upon the Lithium Kinetics of Li-Ion Cells Containing MCMB and LiNi(x)Co(1-x)O2 Electrodes and Exposed to High Temperatures

    Science.gov (United States)

    Smart, M. C.; Ratnakumar, B. V.; Gozdz, A. S.; Mani, S.

    2009-01-01

    With the intent of improving the performance of lithium-ion cells at high temperatures, we have investigated the use of a number of electrolyte additives in experimental MCMB- Li(x)Ni(y)Co(1-y)O2 cells, which were exposed to temperatures as high as 80 C. In the present work, we have evaluated the use of a number of additives, namely vinylene carbonate (VC), dimethyl acetamide (DMAc), and mono-fluoroethylene carbonate (FEC), in an electrolyte solution anticipated to perform well at warm temperature (i.e., 1.0M LiPF6 in EC+EMC (50:50 v/v %). In addition, we have explored the use of novel electrolyte additives, namely lithium oxalate and lithium tetraborate. In addition to determining the capacity and power losses at various temperatures sustained as a result of high temperature cycling (cycling performed at 60 and 80 C), the three-electrode MCMB-Li(x)Ni(y)Co(1-y)O2 cells (lithium reference) enabled us to study the impact of high temperature storage upon the solid electrolyte interphase (SEI) film characteristics on carbon anodes (MCMB-based materials), metal oxide cathodes, and the subsequent impact upon electrode kinetics.

  10. Lead evaluation of tetrahydroquinolines as nonsteroidal selective androgen receptor modulators for the treatment of osteoporosis.

    Science.gov (United States)

    Nagata, Naoya; Furuya, Kazuyuki; Oguro, Nao; Nishiyama, Daisuke; Kawai, Kentaro; Yamamoto, Noriko; Ohyabu, Yuki; Satsukawa, Masahiro; Miyakawa, Motonori

    2014-01-01

    Tetrahydroquinoline (THQ) was deemed to be a suitable scaffold for our nonsteroidal selective androgen receptor modulator (SARM) concept. We adapted the strategy of switching the antagonist function of cyano-group-containing THQ (CN-THQ) to the agonist function and optimized CN-THQ as an orally available drug candidate with suitable pharmacological and ADME profiles. Based on binding mode analyses and synthetic accessibility, we designed and synthesized a compound that possesses a para-substituted aromatic ring attached through an amide linker. The long-tail THQ derivative 6-acetamido-N-(2-(8-cyano-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinolin-4-yl)-2-methylpropyl)nicotinamide (1 d), which bears a para-acetamide-substituted aromatic group, showed an appropriate in vitro biological profile, as expected. We considered that the large conformational change at Trp741 of the androgen receptor (AR) and the hydrogen bond between 1 d and helix 12 of the AR could maintain the structure of the AR in its agonist form; indeed, 1 d displays strong AR agonistic activity. Furthermore, 1 d showed an appropriate in vivo profile for use as an orally available SARM, displaying clear tissue selectivity, with a separation between its desirable osteoanabolic effect on femoral bone mineral density and its undesirable virilizing effects on the uterus and clitoral gland in a female osteoporosis model.

  11. Concomitant pseudopolymorphs of 10-deacetyl baccatin III.

    Science.gov (United States)

    Tatini, Lakshmi Kumar; Rao, N Someswara; Khan, Muzaffar; Peraka, Krishna Sumanth; Reddy, K V S R Krishna

    2013-06-01

    Three new solvates [mono-dimethyl sulfoxide (mono-DMSO), mono-dimethyl acetamide (mono-DMA) and mono-dimethyl formamide (mono-DMF)] of 10-Deacetyl baccatin III, were generated by slow evaporation in DMSO, DMF, and DMSO/DMA (1:1) solvent systems respectively. Two concomitant forms mono-DMSO(a new form) and di-DMSO (a known form) were obtained in the DMSO solvent system. Yet two other concomitant forms mono-DMA (a new form) and di-DMSO (a known form) were obtained in DMSO/DMA (1:1) solvent system. A fourth solvate mono-DMF (a new form) was crystallized in unimolar ratio using DMF as a solvent. These solvates were characterized using powder X-ray diffraction, differential scanning calorimeter, thermogravimetric analysis (TGA), and spectroscopic [(13)C solid-state nuclear magnetic spectroscopy, solution (1)H NMR, and Fourier transform infrared] techniques. The interactions between host and guest molecules were elucitated by single-crystal X-ray diffraction data. In all the cases, guest molecules are connected to the host molecules by O-H∙∙∙O hydrogen bonds. A remarkable difference in the desolvation onset temperatures of di- and mono-DMSO solvates was observed which was also featured by a corresponding weight loss during TGA analysis.

  12. Array of Love-wave sensors based on quartz/Novolac to detect CWA simulants.

    Science.gov (United States)

    Matatagui, D; Fontecha, J; Fernández, M J; Aleixandre, M; Gràcia, I; Cané, C; Horrillo, M C

    2011-09-15

    An array of Love-wave sensors based on quartz and Novolac has been developed to detect chemical warfare agents (CWAs). These weapons are a risk for human health due to their efficiency and high lethality; therefore an early and clear detection is of enormous importance for the people safety. Love-wave devices realized on quartz as piezoelectric substrate and Novolac as guiding layer have been used to make up an array of six sensors, which have been coated with specific polymers by spin coating. The CWAs are very dangerous and for safety reasons their well known simulants have been used: dimethylmethyl phosphonate (DMMP), dipropyleneglycol methyl ether (DPGME), dimethylmethyl acetamide (DMA), dichloroethane (DCE), dichloromethane (DCM) and dichloropentane (DCP). The array has been exposed to these CWA simulants detecting very low concentrations, such as 25 ppb of DMMP, a simulant of nerve agent sarin. Finally, principal component analysis (PCA) as data pre-processing and discrimination technique, and probabilistic neural networks (PNN) as patterns classification technique have been applied. The performance of the sensor array has shown stability, accuracy, high sensitivity and good selectivity to these simulants.

  13. Synthesis, molecular docking, and biological evaluation of some novel hydrazones and pyrazole derivatives as anti-inflammatory agents.

    Science.gov (United States)

    Mohammed, Khaled O; Nissan, Yassin M

    2014-10-01

    2-Hydrazinyl-N-(4-sulfamoylphenyl)acetamide 3 was the key intermediate for the synthesis of novel hydrazones 4-10 and pyrazole derivatives 11-17. All compounds were tested for their in vivo anti-inflammatory activity and their ability to inhibit the production of PGE(2) in serum samples of rats. IC(50) values for the most active compounds for inhibition of COX-1 and COX-2 enzymes were determined in vitro, and they were also tested for their ulcerogenic effect. Molecular docking was performed on the active site of COX-2 to predict their mode of binding to the amino acids. Most of the synthesized compounds showed good anti-inflammatory activity especially compounds 3, 4, 8, 9, 15, and 17 which showed better activity than diclofenac as the reference drug. Compounds 3, 8, 9, 13, and 15-17 were less ulcerogenic than indomethacine as the reference drug. Most of the synthesized compounds interacted with Tyr 385 and Ser 530 in molecular docking study with additional hydrogen bond for compound 17. Compound 17 showed good selectivity index value of 11.1 for COX-1/COX-2 inhibition in vitro.

  14. A facile approach for high surface area electrospun TiO2 nanostructures for photovoltaic and photocatalytic applications.

    Science.gov (United States)

    Arun, T A; Madhavan, Asha Anish; Chacko, Daya K; Anjusree, G S; Deepak, T G; Thomas, Sara; Nair, Shantikumar V; Nair, A Sreekumaran

    2014-03-28

    A rice-shaped TiO2-ZnO composite was prepared by electrospinning a mixture comprising the precursors of TiO2 and ZnO in polyvinyl acetate polymer dissolved in N,N-dimethyl acetamide. The electrospun nanofibers upon heat treatment in air resulted in collapse of the continuous fiber morphology and the formation of the rice-shaped TiO2-ZnO composite. The TiO2-ZnO composite was then treated with dilute acetic acid under hydrothermal conditions to etch ZnO from the TiO2-ZnO composite to get coral-shaped anisotropic TiO2. The structural anisotropy of TiO2 produced by the selective etching of ZnO resulted in a high surface area of 148 m(2) g(-1) for the TiO2. The initial and final materials were characterized by scanning electron microscopy, transmission electron microscopy, Raman and XPS spectroscopies, powder X-ray diffraction and BET surface area measurements. The utility of the anisotropic TiO2 in photovoltaics and photocatalysis was explored. Dye-sensitized solar cells fabricated using the TiO2 showed a conversion efficiency of 6.54% as against 4.8% for a control experiment with the rice-shaped TiO2. The anisotropic TiO2 also showed good photocatalysis in the degradation of methyl orange dye and phenol.

  15. Structure and properties of PVDF membrane with PES-C addition via thermally induced phase separation process

    Science.gov (United States)

    Wu, Lishun; Sun, Junfen

    2014-12-01

    Polyvinylidene fluoride (PVDF) membrane and PVDF membrane with phenolphthalein polyethersulfone (PES-C) addition were prepared via thermally induced phase separation (TIPS) method by using diphenyl carbonate (DPC) and dimethyl acetamide (DMAc) as mixed diluents. The effects of coagulation temperature and pre-evaporation time on structure and properties of membranes were studied. The changes of sewage flux in MBR and the attenuation coefficient of sewage flux were investigated. The resistance distributions of PVDF and PVDF/PES-C membranes were compared by resistance analysis. Membrane composition and structure were characterized by ATR-FTIR, TGA, SEM and AFM. The foulant on membranes was analyzed by FTIR. The contact angle of PVDF/PES-C membrane was lower than that of PVDF membrane. A thinner skin layer and a porous cellular support layer formed in PVDF/PES-C membrane and resulted in a higher porosity and pure water flux. The pure water flux and porosity of PVDF/PES-C membrane increased with rising coagulation temperature and decreased with extending pre-evaporation time. The flux attenuation coefficient, the cake layer resistance and internal fouling resistance of PVDF/PES-C membrane in MBR were smaller than those of PVDF membrane in MBR. The FTIR spectrum of foulant on membrane indicated that the foulant on PVDF/PES-C membrane was mostly composed of protein and polysaccharide, while the foulant on pure PVDF membrane included biopolymer clusters besides protein and polysaccharide.

  16. Probing the Reactivity of the Ce═O Multiple Bond in a Cerium(IV) Oxo Complex.

    Science.gov (United States)

    So, Yat-Ming; Li, Yang; Au-Yeung, Ka-Chun; Wang, Guo-Cang; Wong, Kang-Long; Sung, Herman H Y; Arnold, Polly L; Williams, Ian D; Lin, Zhenyang; Leung, Wa-Hung

    2016-10-17

    The reactivity of the cerium(IV) oxo complex [(LOEt)2Ce(IV)(═O)(H2O)]·MeC(O)NH2 (1; LOEt(-) = [CoCp{P(O)(OEt)2}3](-), where Cp = η(5)-C5H5) toward electrophiles and Brønsted acids has been investigated. The treatment of 1 with acetic anhydride afforded the diacetate complex [Ce(IV)(LOEt)2(O2CMe)2] (2). The reaction of 1 with B(C6F5)3 yielded [Ce(IV)(LOEt)2(Me2CONH2)2][B(C6F5)3(OH)]2 (3), in which the [B(C6F5)3(OH)](-) anions are H-bonded to the O-bound acetamide ligands. The treatment of 1 with HCl and HNO3 afforded [Ce(IV)(LOEt)2Cl2] and [Ce(IV)(LOEt)2(NO3)2], respectively. Protonation of 1 with triflic acid (HOTf) gave the diaqua complex [Ce(IV)(LOEt)2(H2O)2](OTf)2 (4), in which the triflate anions are H-bonded to the two aqua ligands. The treatment of 1 with phenol afforded the phenoxide complex [Ce(IV)(LOEt)2(OPh)2] (5). The oxo-bridged bimetallic complex [(LOEt)2(Me2CONH2)Ce(IV)(O)NaLOEt] (6) with the Ce-Ooxo and Na-Ooxo distances of 1.953(4) and 2.341(4) Å, respectively, was obtained from the reaction of 1 with [NaLOEt]. Density functional theory calculations showed that the model complex [(LOMe)2Ce(IV)(Me2CONH2)(O)NaLOMe] (6A; LOMe(-) = [CoCp{P(O)(OMe)2}3](-)) contains a polarized Ce═O multiple bond. The energy for dissociation of the {NaLOMe} fragment from 6A in acetonitrile was calculated to be +33.7 kcal/mol, which is higher than that for dissociation of the H-bonded acetamide from [(LOMe)2Ce(IV)(═O)(H2O)]·MeC(O)NH2 (1A) (calculated to be +17.4 kcal/mol). In hexanes containing trace water, complex 1 decomposed readily to a mixture of a tetranuclear cerium(IV) oxo cluster, [Ce(IV)4(LOEt)4(μ4-O)(μ2-O)4(μ2-OH)2] (7), and a cerium(III) complex, [Ce(III)(LOEt)2(H2O)2][LOEt] [8(LOEt)], whereas the cerium/sodium oxo complex 6 is stable under the same conditions. The crystal structures of 3, 4·H2O, 6, and 8(LOEt) have been determined.

  17. Overview of VOC emissions and chemistry from PTR-TOF-MS measurements during the SusKat-ABC campaign: high acetaldehyde, isoprene and isocyanic acid in wintertime air of the Kathmandu Valley

    Science.gov (United States)

    Sarkar, Chinmoy; Sinha, Vinayak; Kumar, Vinod; Rupakheti, Maheswar; Panday, Arnico; Mahata, Khadak S.; Rupakheti, Dipesh; Kathayat, Bhogendra; Lawrence, Mark G.

    2016-03-01

    The Kathmandu Valley in Nepal suffers from severe wintertime air pollution. Volatile organic compounds (VOCs) are key constituents of air pollution, though their specific role in the valley is poorly understood due to insufficient data. During the SusKat-ABC (Sustainable Atmosphere for the Kathmandu Valley-Atmospheric Brown Clouds) field campaign conducted in Nepal in the winter of 2012-2013, a comprehensive study was carried out to characterise the chemical composition of ambient Kathmandu air, including the determination of speciated VOCs, by deploying a proton transfer reaction time-of-flight mass spectrometer (PTR-TOF-MS) - the first such deployment in South Asia. In the study, 71 ion peaks (for which measured ambient concentrations exceeded the 2σ detection limit) were detected in the PTR-TOF-MS mass scan data, highlighting the chemical complexity of ambient air in the valley. Of the 71 species, 37 were found to have campaign average concentrations greater than 200 ppt and were identified based on their spectral characteristics, ambient diel profiles and correlation with specific emission tracers as a result of the high mass resolution (m / Δm > 4200) and temporal resolution (1 min) of the PTR-TOF-MS. The concentration ranking in the average VOC mixing ratios during our wintertime deployment was acetaldehyde (8.8 ppb) > methanol (7.4 ppb) > acetone + propanal (4.2 ppb) > benzene (2.7 ppb) > toluene (1.5 ppb) > isoprene (1.1 ppb) > acetonitrile (1.1 ppb) > C8-aromatics ( ˜ 1 ppb) > furan ( ˜ 0.5 ppb) > C9-aromatics (0.4 ppb). Distinct diel profiles were observed for the nominal isobaric compounds isoprene (m / z = 69.070) and furan (m / z = 69.033). Comparison with wintertime measurements from several locations elsewhere in the world showed mixing ratios of acetaldehyde ( ˜ 9 ppb), acetonitrile ( ˜ 1 ppb) and isoprene ( ˜ 1 ppb) to be among the highest reported to date. Two "new" ambient compounds, namely formamide (m / z = 46.029) and acetamide (m / z

  18. Photophysical studies on the interaction of amides with Bovine Serum Albumin (BSA) in aqueous solution: Fluorescence quenching and protein unfolding

    Energy Technology Data Exchange (ETDEWEB)

    Kumaran, R., E-mail: kumaranwau@rediffmail.com [Department of Chemistry, Dwaraka Doss Goverdhan Doss Vaishnav College, Arumbakkam, Chennai 600106 (India); Ramamurthy, P. [National Centre for Ultrafast Processes, University of Madras, Sekhizar Campus, Taramani, Chennai 600113 (India)

    2014-04-15

    Addition. of amides containing a H-CO(NH{sub 2}) or CH{sub 3}-CO(NH{sub 2}) framework to BSA results in a fluorescence quenching. On the contrary, fluorescence enhancement with a shift in the emission maximum towards the blue region is observed on the addition of dimethylformamide (DMF) (H-CON(CH{sub 3}){sub 2}). Fluorescence quenching accompanied initially with a shift towards the blue region and a subsequent red shift in the emission maximum of BSA is observed on the addition of formamide (H-CO(NH{sub 2})), whereas a shift in the emission maximum only towards the red region results on the addition of acetamide (CH{sub 3}-CONH{sub 2}). Steady state emission spectral studies reveal that amides that possess a free NH{sub 2} and N(CH{sub 3}){sub 2} moiety result in fluorescence quenching and enhancement of BSA respectively. The 3D contour spectral studies of BSA with formamide exhibit a shift in the emission towards the red region accompanied with fluorescence quenching, which indicates that the tryptophan residues of the BSA are exposed to a more polar environment. Circular Dichroism (CD) studies of BSA with amides resulted in a gradual decrease in the α-helical content of BSA at 208 nm, which confirms that there is a conformational change in the native structure of BSA. Time-resolved fluorescence studies illustrate that the extent of buried trytophan moieties exposed to the aqueous phase on the addition of amides follows the order DMF<acetamide

  19. Criopreservação do sêmen testicular do teleósteo piau-açu Leporimus macrocephalus Testicular sperm cryopreservation of the teleost 'piau-açu' Leporinus macrocephalus

    Directory of Open Access Journals (Sweden)

    R.I.M.A. Ribeiro

    2003-02-01

    Full Text Available Avaliaram-se metodologias de criopreservação para o sêmen do piau-açu Leporinus macrocephalus (Teleostei, Anostomidae. O volume de sêmen coletado diretamente dos testículos de seis peixes (446,7±165,1g de peso corporal foi de 0,4±0,2 ml. Testou-se a toxicidade dos crioprotetores dimetilsulfóxido (DMSO, dimetilacetamida, propilenoglicol, etilenoglicol e metanol nas concentrações de 5%, 10% e 15%. DMSO, dimetilacetamida e propilenoglicol foram os menos tóxicos e, por isso, utilizados na criopreservação do sêmen. Para este teste, o sêmen foi diluído 1:8 (v:v em soluções de cada crioprotetor(8,9%, concentração final às quais adicionaram-se gema de ovo de galinha (8,9%, concentração final, glicose (5% e água destilada (75%. A mistura foi então envasada em palhetas de 5ml de capacidade e imediatamente colocada em botijão de vapor de nitrogênio líquido. A taxa de motilidade espermática pós-descongelamento mais alta (40,8± 13,6 % foi obtida com sêmen criopreservado em diluente contendo DMSO e ativado em solução de NaHCO3 119mM. A taxa de fertilização, correspondente a 84,3±9,4% do controle, foi obtida com ovócitos de piau-açu fertilizados com sêmen congelado em solução de DMSO (8%, concentração final.Methods for cryopreservation of 'piau-açu' Leporinus macrocephalus (Teleostei, Anostomidae sperm were evaluated. Sperm collected directly from the testes of six fish (446.7±165.1g of body weight yielded 0.4±0.2 ml. The toxicity of the cryoprotectants dimethyl sulphoxide (DMSO, dimethyl acetamide, propylene glycol, ethylene glycol and methanol, at concentrations of 5%, 10% and 15%, was tested. DMSO, dimethyl acetamide and propylene glycol were the least toxic and were used to freeze the sperm. Sperm was diluted 1:8 (v:v in solutions made of 8.9% (final concentration of one of those crioprotectants to which 8.9% (final concentration of chicken yolk egg, 5% glucose and 75% distilled water were added. The mixture

  20. Highly selective luminescent nanostructures for mitochondrial imaging and targeting

    Science.gov (United States)

    Fanizza, E.; Iacobazzi, R. M.; Laquintana, V.; Valente, G.; Caliandro, G.; Striccoli, M.; Agostiano, A.; Cutrignelli, A.; Lopedota, A.; Curri, M. L.; Franco, M.; Depalo, N.; Denora, N.

    2016-02-01

    Here a luminescent hybrid nanostructure based on functionalized quantum dots (QDs) is used as a fluorescent imaging agent able to target selectively mitochondria thanks to the molecular recognition of the translocator protein (TSPO). The selective targeting of such an 18 kDa protein mainly located in the outer mitochondrial membrane and overexpressed in several pathological states including neurodegenerative diseases and cancers may provide valuable information for the early diagnosis and therapy of human disorders. In particular, the rational design of amino functionalized luminescent silica coated QD nanoparticles (QD@SiO2 NPs) provides a versatile nanoplatform to anchor a potent and selective TSPO ligand, characterized by a 2-phenyl-imidazo[1,2-a]pyridine acetamide structure along with a derivatizable carboxylic end group, useful to conjugate the TSPO ligand and achieve TSPO-QD@SiO2 NPs by means of a covalent amide bond. The colloidal stability and optical properties of the proposed nanomaterials are comprehensively investigated and their potential as mitochondrial imaging agents is fully assessed. Sub-cellular fractionation, together with confocal laser scanning fluorescence microscopy and co-localization analysis of targeted TSPO-QD@SiO2 NPs in C6 glioma cells overexpressing the TSPO, proves the great potential of these multifunctional nanosystems as in vitro selective mitochondrial imaging agents.Here a luminescent hybrid nanostructure based on functionalized quantum dots (QDs) is used as a fluorescent imaging agent able to target selectively mitochondria thanks to the molecular recognition of the translocator protein (TSPO). The selective targeting of such an 18 kDa protein mainly located in the outer mitochondrial membrane and overexpressed in several pathological states including neurodegenerative diseases and cancers may provide valuable information for the early diagnosis and therapy of human disorders. In particular, the rational design of amino

  1. Rotational spectroscopy, tentative interstellar detection, and chemical modeling of N-methylformamide

    Science.gov (United States)

    Belloche, A.; Meshcheryakov, A. A.; Garrod, R. T.; Ilyushin, V. V.; Alekseev, E. A.; Motiyenko, R. A.; Margulès, L.; Müller, H. S. P.; Menten, K. M.

    2017-05-01

    unsaturated molecule methyl isocyanate (CH3NCO), but only slightly less abundant than acetamide (CH3CONH2). We also report the tentative detection of the 15N isotopolog of formamide (15NH2CHO) toward Sgr B2(N2). The chemical models indicate that the efficient formation of HNCO via NH + CO on grains is a necessary step in the achievement of the observed gas-phase abundance of CH3NCO. Production of CH3NHCHO may plausibly occur on grains either through the direct addition of functional-group radicals or through the hydrogenation of CH3NCO. Conclusions: Provided the detection of N-methylformamide is confirmed, the only slight underabundance of this molecule compared to its more stable structural isomer acetamide and the sensitivity of the model abundances to the chemical kinetics parameters suggest that the formation of these two molecules is controlled by kinetics rather than thermal equilibrium. Full Tables 2 and 3 are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/601/A49

  2. Synthesis, characterization and luminescence properties of rare earth complexes with a new biphenylamide

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Yan-Ling, E-mail: guoyl2004@163.com [School of Nuclear Science and Technology, Lanzhou University, Lanzhou 730000 (China); Dou, Wei; Wang, Yu-Jiao; Zhou, Xiao-Yan; Liu, Wei-Sheng [College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000 (China)

    2013-03-15

    A new amide-based ligand derived from biphenyl, N,N-dibenzyl-2-{l_brace}2 Prime -[(dibenzylcarbamoyl)-methoxy]-biphenyl-2-yloxy{r_brace} -acetamide (L), and its complexes of rare earth picrates were synthesized. The complexes were characterized by elemental analysis, IR, {sup 1}H NMR, UV-Vis spectra and conductivity measurements. Under the excitation, the europium(III) complex exhibited characteristic emissions of europium. The luminescence properties of the europium(III) complex in solid state and in CHCl{sub 3}, acetone, acetonitrile and DMF were investigated. The lifetime of the {sup 5}D{sub 0} level of the Eu{sup 3+} ion in the complex is 0.68 ms. The quantum yield {Phi} of the europium picrate complex was found to be 2.54 Multiplication-Sign 10{sup -3} with quinine sulfate as reference. The lowest triplet state energy level of the ligand indicates that the triplet state energy level of the ligand matches better to the resonance level of Eu(III) than Tb(III) ion. - Highlights: Black-Right-Pointing-Pointer Synthesis of a new amide type podand and its lanthanide picrate complexes. Black-Right-Pointing-Pointer Characterization was done by elemental analysis, conductivity, IR, {sup 1}H NMR and UV-Vis. Black-Right-Pointing-Pointer Luminescence properties of Eu{sup 3+} complex were analyzed. Black-Right-Pointing-Pointer Triplet state energy level of ligand matches better to the resonance level of Eu{sup 3+} than Tb{sup 3+} ion.

  3. A concise synthesis of 1,4-dihydro-[1,4]diazepine-5,7-dione, a novel 7-TM receptor ligand core structure with melanocortin receptor agonist activity.

    Science.gov (United States)

    Szewczyk, Jerzy R; Laudeman, Chris P; Sammond, Doug M; Villeneuve, Manon; Minick, Douglas J; Grizzle, Mary K; Daniels, Alejandro J; Andrews, John L; Ignar, Diane M

    2010-03-01

    Finding small non-peptide molecules for G protein-coupled receptors (GPCR) whose endogenous ligands are peptides, is a very important task for medicinal chemists. Over the years, compounds mimicking peptide structures have been discovered, and scaffolds emulating peptide backbones have been designed. In our work on GPCR ligands, including cholecystokinin receptor-1 (CCKR-1) agonists, we have employed benzodiazepines as a core structure. Looking for ways to reduce molecular weight and possibly improve physical properties of GPCR ligands, we embarked on the search for molecules providing similar scaffolds to the benzodiazepine with lower molecular weight. One of our target core structures was 1,4-dihydro-[1,4]diazepine-5,7-dione. There was not, however, a known synthetic route to such molecules. Here we report the discovery of a simple and concise method for synthesis of 2-[6-(1H-indazol-3-ylmethyl)-5,7-dioxo-4-phenyl-4,5,6,7-tetrahydro-[1,4]diazepin-1-yl]-N-isopropyl-N-phenyl-acetamide as an example of a compound containing the tetrahydrodiazepine-5,7-dione core. Compounds from this series were tested in numerous GPCR assays and demonstrated activity at melanocortin 1 and 4 receptors (MC1R and MC4R). Selected compounds from this series were tested in vivo in Peptide YY (PYY)-induced food intake. Compounds dosed by intracerebroventricular and oral routes reduced PYY-induced food intake and this effect was reversed by the cyclic peptide MC4R antagonist SHU9119.

  4. A Small-Molecule Inhibitor of Lin28.

    Science.gov (United States)

    Roos, Martina; Pradère, Ugo; Ngondo, Richard P; Behera, Alok; Allegrini, Sara; Civenni, Gianluca; Zagalak, Julian A; Marchand, Jean-Rémy; Menzi, Mirjam; Towbin, Harry; Scheuermann, Jörg; Neri, Dario; Caflisch, Amedeo; Catapano, Carlo V; Ciaudo, Constance; Hall, Jonathan

    2016-10-21

    New discoveries in RNA biology underscore a need for chemical tools to clarify their roles in pathophysiological mechanisms. In certain cancers, synthesis of the let-7 microRNA tumor suppressor is blocked by an RNA binding protein (RBP) Lin28, which docks onto a conserved sequence in let-7 precursor RNA molecules and prevents their maturation. Thus, the Lin28/let-7 interaction might be an attractive drug target, if not for the well-known difficulty in targeting RNA-protein interactions with drugs. Here, we describe a protein/RNA FRET assay using a GFP-Lin28 donor and a black-hole quencher (BHQ)-labeled let-7 acceptor, a fluorescent protein/quencher combination which is rarely used in screening despite favorable spectral properties. We tested 16 000 molecules and identified N-methyl-N-[3-(3-methyl[1,2,4]triazolo[4,3-b]pyridazin-6-yl)phenyl]acetamide, which blocked the Lin28/let-7 interaction, rescued let-7 processing and function in Lin28-expressing cancer cells, induced differentiation of mouse embryonic stem cells, and reduced tumor-sphere formation by 22Rv1 and Huh7 cells. A biotinylated derivative captured Lin28 from cell lysates consistent with an on-target mechanism in cells, though the compound also showed some activity against bromodomains in selectivity assays. The Lin28/let-7 axis is presently of high interest not only for its role as a bistable switch in stem-cell biology but also because of its prominent roles in numerous diseases. We anticipate that much can be learned from the use of this first reported small molecule antagonist of Lin28, including the potential of the Lin28/let-7 interaction as a new drug target for selected cancers. Furthermore, this approach to assay development may be used to identify antagonists of other RBP/RNA interactions suspected to be operative in pathophysiological mechanisms.

  5. Synthesis and Antimicrobial Activity of Some Derivatives on the Basis (7-hydroxy-2-oxo-2H-chromen-4-yl-acetic Acid Hydrazide

    Directory of Open Access Journals (Sweden)

    Elizabeth Has-Schon

    2006-03-01

    Full Text Available (7-Hydroxy-2-oxo-2H-chromen-4-yl-acetic acid hydrazide (2 was prepared from (7-hydroxy-2-oxo-2H-chromen-4-yl-acetic acid ethyl ester (1 and 100% hydrazine hydrate. Compound 2, is the key intermediate for the synthesis of several series of new compounds such as Schiff’s bases 3a-l, formic acid N'-[2-(7-hydroxy-2-oxo-2H- chromen-4-ylacetyl] hydrazide (4, acetic acid N'-[2-(7-hydroxy-2-oxo-2H-chromen-4- yl-acetyl] hydrazide (5, (7-hydroxy-2-oxo-2H-chromen-4-yl-acetic acid N'-[2-(4- hydroxy-2-oxo-2H-chromen-3-yl-2-oxoethyl] hydrazide (6, 4-phenyl-1-(7-hydroxy-2- oxo-2H-chromen- 4-acetyl thiosemicarbazide (7, ethyl 3-{2-[2-(7-hydroxy-2-oxo-2H- chromen-4-yl-acetyl]hydrazono}butanoate (8, (7-hydroxy-2-oxo-2H-chromen-4-yl- acetic acid N'-[(4-trifluoromethylphenyliminomethyl] hydrazide (9 and (7-hydroxy-2- oxo-2H-chromen-4-ylacetic acid N'-[(2,3,4-trifluorophenylimino-methyl] hydrazide (10. Cyclo- condensation of compound 2 with pentane-2,4-dione gave 4-[2-(3,5- dimethyl-1H-pyrazol-1-yl-2-oxoethyl]-7-hydroxy-2H-chromen-2-one (11, while with carbon disulfide it afforded 7-hydroxy-4-[(5-mercapto-1,3,4-oxadiazol-2-ylmethyl]-2H- chromen-2-one (12 and with potassium isothiocyanate it gave 7-hydroxy-4-[(5- mercapto-4H-1,2,4-triazol-3-ylmethyl]-2H-chromen-2-one (14. Compound 7 was cyclized to afford 2-(7-hydroxy-2-oxo-2H-chromen-4-yl-N ́-(4-oxo-2-phenylimino- thiazolidin-3-yl acetamide (15.

  6. Alternative Radioligands for Investigating the Molecular Pharmacology of Melatonin Receptors.

    Science.gov (United States)

    Legros, Céline; Brasseur, Chantal; Delagrange, Philippe; Ducrot, Pierre; Nosjean, Olivier; Boutin, Jean A

    2016-03-01

    Melatonin exerts a variety of physiologic activities that are mainly relayed through the melatonin receptors MT1 and MT2 Low expressions of these receptors in tissues have led to widespread experimental use of the agonist 2-[(125)I]-iodomelatonin as a substitute for melatonin. We describe three iodinated ligands: 2-(2-[(2-iodo-4,5-dimethoxyphenyl)methyl]-4,5-dimethoxy phenyl) (DIV880) and (2-iodo-N-2-[5-methoxy-2-(naphthalen-1-yl)-1H-pyrrolo[3,2-b]pyridine-3-yl])acetamide (S70254), which are specific ligands at MT2 receptors, and N-[2-(5-methoxy-1H-indol-3-yl)ethyl]iodoacetamide (SD6), an analog of 2-[(125)I]-iodomelatonin with slightly different characteristics. Here, we further characterized these new ligands with regards to their molecular pharmacology. We performed binding experiments, saturation assays, association/dissociation rate measurements, and autoradiography using sheep and rat tissues and recombinant cell lines. Our results showed that [(125)I]-S70254 is receptor, and can be used with both cells and tissue. This radioligand can be used in autoradiography. Similarly, DIV880, a partial agonist [43% of melatonin on guanosine 5'-3-O-(thio)triphosphate binding assay], selective for MT2, can be used as a tool to selectively describe the pharmacology of this receptor in tissue samples. The molecular pharmacology of both human melatonin receptors MT1 and MT2, using a series of 24 ligands at these receptors and the new radioligands, did not lead to noticeable variations in the profiles. For the first time, we described radiolabeled tools that are specific for one of the melatonin receptors (MT2). These tools are amenable to binding experiments and to autoradiography using sheep or rat tissues. These specific tools will permit better understanding of the role and implication in physiopathologic processes of the melatonin receptors.

  7. Life cycle assessment of corn-based ethanol production in Argentina.

    Science.gov (United States)

    Pieragostini, Carla; Aguirre, Pío; Mussati, Miguel C

    2014-02-15

    The promotion of biofuels as energy for transportation in the world is mainly driven by the perspective of oil depletion, the concerns about energy security and global warming. In Argentina, the legislation has imposed the use of biofuels in blend with fossil fuels (5 to 10%) in the transport sector. The aim of this paper is to assess the environmental impact of corn-based ethanol production in the province of Santa Fe in Argentina based on the life cycle assessment methodology. The studied system includes from raw materials production to anhydrous ethanol production using dry milling technology. The system is divided into two subsystems: agricultural system and refinery system. The treatment of stillage is considered as well as the use of co-products (distiller's dried grains with solubles), but the use and/or application of the produced biofuel is not analyzed: a cradle-to-gate analysis is presented. As functional unit, 1MJ of anhydrous ethanol at biorefinery is chosen. Two life cycle impact assessment methods are selected to perform the study: Eco-indicator 99 and ReCiPe. SimaPro is the life cycle assessment software used. The influence of the perspectives on the model is analyzed by sensitivity analysis for both methods. The two selected methods identify the same relevant processes. The use of fertilizers and resources, seeds production, harvesting process, corn drying, and phosphorus fertilizers and acetamide-anillide-compounds production are the most relevant processes in agricultural system. For refinery system, corn production, supplied heat and burned natural gas result in the higher contributions. The use of distiller's dried grains with solubles has an important positive environmental impact.

  8. Microbial toxicity and characterization of DNAN (bio)transformation product mixtures.

    Science.gov (United States)

    Olivares, Christopher I; Sierra-Alvarez, Reyes; Alvarez-Nieto, Cristina; Abrell, Leif; Chorover, Jon; Field, Jim A

    2016-07-01

    2,4-Dinitroanisole (DNAN) is an emerging insensitive munitions compound. It undergoes rapid (bio)transformation in soils and anaerobic sludge. The primary transformation pathway catalyzed by a combination of biotic and abiotic factors is nitrogroup reduction followed by coupling of reactive intermediates to form azo-dimers. Additional pathways include N-acetylation and O-demethoxylation. Toxicity due to (bio)transformation products of DNAN has received little attention. In this study, the toxicity of DNAN (bio)transformation monomer products and azo-dimer and trimer surrogates to acetoclastic methanogens and the marine bioluminescent bacterium, Allivibrio fischeri, were evaluated. Methanogens were severely inhibited by 3-nitro-4-methoxyaniline (MENA), with a 50%-inhibiting concentration (IC50) of 25 μM, which is more toxic than DNAN with the same assay, but posed a lower toxicity to Allivibrio fischeri (IC50 = 219 μM). On the other hand, N-(5-amino-2-methoxyphenyl) acetamide (Ac-DAAN) was the least inhibitory test-compound for both microbial targets. Azo-dimer and trimer surrogates were very highly toxic to both microbial systems, with a toxicity similar or stronger than that of DNAN. A semi-quantitative LC-QTOF-MS method was employed to determine product mixture profiles at different stages of biotransformation, and compared with the microbial toxicity of the product-mixtures formed. Methanogenic toxicity increased due to putative reactive nitroso-intermediates as DNAN was reduced. However, the inhibition later attenuated as dimers became the predominant products in the mixtures. In contrast, A. fischeri tolerated the initial biotransformation products but were highly inhibited by the predominant azo-dimer products formed at longer incubation times, suggesting these ultimate products are more toxic than DNAN.

  9. Kinetics of the Oxidation of D-Glucose and Cellobiose by Acidic Solution of N-Bromoacetamide Using Transition Metal Complex Species,[RuCl3(H2O)2OH]-,as Catalyst

    Institute of Scientific and Technical Information of China (English)

    SINGH,Ashok Kumar; SRIVASTAVA,Jaya; SRIVASTAVA,Shalini; RAHMANI,Shahla

    2008-01-01

    The kinetics of Ru(Ⅲ)-catalyzed and Hg(Ⅱ)-co-catalyzed oxidation of D-glucose (Glc) and cellobiose (Cel) by N-bromoacetamide (NBA) in the presence of perchloric acid at 40 ℃ have been investigated.The reactions exhibit the first order kinetics with respect to NBA,but tend towards the zeroth order to higher NBA.The reactions are the first order with respect to Ru(Ⅲ) and are fractional positive order with respect to [reducing sugar].Positive effect of Cl- and Hg(Oac)2 on the rate of reaction is also evident in the oxidation of both reducing sugars.A negative effect of variation of H+ and acetamide was observed whereas the ionic strength (μ) of the medium had no influence on the oxidation rate.The rate of reaction decreased with the increase in dielectric constant and this enabled the computation of dAB,the size of the activated complex.Various activation parameters have been evaluated and suitable explanation for the formation of the most reactive activated complex has been given.The main products of the oxidation are the corresponding arabinonic acid and formic acid.HOBr and [RuCl3(H2O)2OH]- were postulated as the reactive species of oxidant and catalyst respectively.A common mechanism,consistent with the kinetic data and supported by the observed effect of ionic strength,dielectric constant and multiple regression analysis,has been proposed.Formation of complex species such as [RuCl3·S·(H2O)OH]- and RuCl3·S·OHgBr·OH during the course of reaction was fully supported by kinetic and spectral evidences.

  10. Pharmacokinetics and Disposition of the Thiouracil Derivative PF-06282999, an Orally Bioavailable, Irreversible Inactivator of Myeloperoxidase Enzyme, Across Animals and Humans.

    Science.gov (United States)

    Dong, Jennifer Q; Varma, Manthena V; Wolford, Angela; Ryder, Tim; Di, Li; Feng, Bo; Terra, Steven G; Sagawa, Kazuko; Kalgutkar, Amit S

    2016-02-01

    The thiouracil derivative PF-06282999 [2-(6-(5-chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide] is an irreversible inactivator of myeloperoxidase and is currently in clinical trials for the potential treatment of cardiovascular diseases. Concerns over idiosyncratic toxicity arising from bioactivation of the thiouracil motif to reactive species in the liver have been largely mitigated through the physicochemical (molecular weight, lipophilicity, and topological polar surface area) characteristics of PF-06282999, which generally favor elimination via nonmetabolic routes. To test this hypothesis, pharmacokinetics and disposition studies were initiated with PF-06282999 using animals and in vitro assays, with the ultimate goal of predicting human pharmacokinetics and elimination mechanisms. Consistent with its physicochemical properties, PF-06282999 was resistant to metabolic turnover from liver microsomes and hepatocytes from animals and humans and was devoid of cytochrome P450 inhibition. In vitro transport studies suggested moderate intestinal permeability and minimal transporter-mediated hepatobiliary disposition. PF-06282999 demonstrated moderate plasma protein binding across all of the species. Pharmacokinetics in preclinical species characterized by low to moderate plasma clearances, good oral bioavailability at 3- to 5-mg/kg doses, and renal clearance as the projected major clearance mechanism in humans. Human pharmacokinetic predictions using single-species scaling of dog and/or monkey pharmacokinetics were consistent with the parameters observed in the first-in-human study, conducted in healthy volunteers at a dose range of 20-200 mg PF-06282999. In summary, disposition characteristics of PF-06282999 were relatively similar across preclinical species and humans, with renal excretion of the unchanged parent emerging as the principal clearance mechanism in humans, which was anticipated based on its physicochemical properties and

  11. In Silico Analog Design for Terbinafine Against Trichophyton rubrum: A Preliminary Study.

    Science.gov (United States)

    Karumuri, Sudha; Singh, Puneet Kumar; Shukla, Pratyoosh

    2015-09-01

    The diseases caused by dermatophytes are common among several other infections which cause serious threat to human health. It is evident that enzyme squalene epoxidase is responsible for prolonged dermatophyte infection and it is appealing to note that this enzyme is also responsible for fatty acid synthesis in these groups of fungi. In the present study, terbinafine drug which targets enzyme squalene epoxidase has been explored to design its various novel analogues. The present study suggests that many more prominent drug analogues could be constituted which may be crucial towards designing new drug candidates. In the present study, we have designed a series of such analogues viz. [(2E)-6,6-dimethylhept-2-en-4-yn-1-yl](methyl)(naphthalen-1-ylmethyl)amine, N-[8-({[(2E)-6,6-dimethylhept-2-en-4-yn-1-yl](methyl)amino}methyl)naphthalen-1-yl]-2-(sulfoamino) acetamide, {[4-(dihydroxyamino)-8-({[(2E)-6,6-dimethylhept-2-en-4-yn-1-yl](methyl)amino}methyl)naphthalen-1-yl]sulfanyl}methanol and (R)-{[4-({[(2E,6R)-6,7-dimethyloct-2-en-4-yn-1-yl](methyl)amino}methyl)-5-[(hydroxysulfamoyl)amino]naphthalen-1-yl]amino}sulfinic acid. Moreover, further by molecular docking approach the binding between enzyme and designed analogues was further analysed. The present preliminary report suggested a considerably good docking interaction score of -338.75 kcal/mol between terbinafine and squalene epoxidase from Trichophyton rubrum. This preliminary study implies that few designed candidate ligands can be effectual towards the activity of this enzyme and can play crucial role in pathogenesis control of T. rubrum.

  12. A benzimidazole derivative exhibiting antitumor activity blocks EGFR and HER2 activity and upregulates DR5 in breast cancer cells.

    Science.gov (United States)

    Chu, B; Liu, F; Li, L; Ding, C; Chen, K; Sun, Q; Shen, Z; Tan, Y; Tan, C; Jiang, Y

    2015-03-12

    Aberrant expression or function of epidermal growth factor receptor (EGFR) or the closely related human epidermal growth factor receptor 2 (HER2) can promote cell proliferation and survival, thereby contributing to tumorigenesis. Specific antibodies and low-molecular-weight tyrosine kinase inhibitors of both proteins are currently in clinical trials for cancer treatment. Benzimidazole derivatives possess diverse biological activities, including antitumor activity. However, the anticancer mechanism of 5a (a 2-aryl benzimidazole compound; 2-chloro-N-(2-p-tolyl-1H-benzo[d]imidazol-5-yl)acetamide, C(16)H(14)ClN(3)O, MW299), a novel 2-aryl benzimidazole derivative, toward breast cancer is largely unknown. Here, we demonstrate that 5a potently inhibited both EGFR and HER2 activity by reducing EGFR and HER2 tyrosine phosphorylation and preventing downstream activation of PI3K/Akt and MEK/Erk pathways in vitro and in vivo. We also show that 5a inhibited the phosphorylation of FOXO and promoted FOXO translocation from the cytoplasm into the nucleus, resulting in the G1-phase cell cycle arrest and apoptosis. Moreover, 5a potently induced apoptosis via the c-Jun N-terminal kinase (JNK)-mediated death receptor 5 upregulation in breast cancer cells. The antitumor activity of 5a was consistent with additional results demonstrating that 5a significantly reduced tumor volume in nude mice in vivo. Analysis of the primary breast cancer cell lines with HER2 overexpression further confirmed that 5a significantly inhibited Akt Ser473 and Bad Ser136 phosphorylation and reduced cyclin D3 expression. On the basis of our findings, further development of this 2-aryl benzimidazole derivative, a new class of multitarget anticancer agents, is warranted and represents a novel strategy for improving breast cancer treatment.

  13. Determination cytotoxicity of [1,2,4]triazolo[4,3-a]-pyrazine derivatives

    Directory of Open Access Journals (Sweden)

    Кристина Юріївна Куликовська

    2015-11-01

    Full Text Available With test systems CellTiter-Glo was determined the cytotoxicity of series N7-aryl/benzyl-3-tioxo-2,3-dihydro-7Н-[1,2,4]triazolo-[4,3-а]pyrazin-8-ones, their 3-S- acetamides and 3-S-benzyl derivatives. The synthesis of the compounds performed based on the previously developed and published scheme. Structure and purity of the compounds proved with 1H-NMR and element analysis.Methods. The method is based on determining the number of viable cells in culture by intensity of luminescence mixture of cell suspension of prostate cancer Du145, solution of the substance and CellTiter-Glo reagent. Tubercidin and taxol were used as reference drugs. The parameter СK50, that has been set according to a study, describes the ability of analyzed substances induce cell death.Results. Cytotoxic concentration of synthesized 3-substituted N7-aryl/benzyl-2,3-dihydro-7Н-[1,2,4]triazolo-[4,3-а]pyrazine-8-ones not exceed the maximum concentration of compounds, which were tested, and was above 30 mkM. This demonstrates the complete absence of negative impact of these substances on cells of prostate cancer Du145.Conclusions. Found that these compounds do not exhibit toxic effects on living cells, making the actual possibility of developing new effective and safe drugs on their base. Also inappropriate to search anticancer drugs among of the N7-aryl/benzyl-2,3-dihydro-7Н-[1,2,4]triazolo-[4,3-а]pyrazine-8-one derivatives

  14. Ship-in-a-bottle CMPO in MIL-101(Cr) for selective uranium recovery from aqueous streams through adsorption

    Energy Technology Data Exchange (ETDEWEB)

    De Decker, Jeroen [Department of Inorganic and Physical Chemistry, Center for Ordered Materials, Organometallics, and Catalysis (COMOC), Ghent University, Krijgslaan 281-S3, 9000 Ghent (Belgium); Folens, Karel [Laboratory of Analytical Chemistry and Applied Ecochemistry, Ghent University, Coupure Links 653, 9000 Ghent (Belgium); De Clercq, Jeriffa [Department of Materials, Textiles, and Chemical Engineering, Industrial Catalysis and Adsorption Technology (INCAT), Ghent University, Valentin, Vaerwyckweg 1, 9000 Ghent (Belgium); Meledina, Maria; Van Tendeloo, Gustaaf [EMAT, University of Antwerp, Groenenborgerlaan 171, 2020 Antwerp (Belgium); Du Laing, Gijs [Laboratory of Analytical Chemistry and Applied Ecochemistry, Ghent University, Coupure Links 653, 9000 Ghent (Belgium); Van Der Voort, Pascal, E-mail: pascal.vandervoort@ugent.be [Department of Inorganic and Physical Chemistry, Center for Ordered Materials, Organometallics, and Catalysis (COMOC), Ghent University, Krijgslaan 281-S3, 9000 Ghent (Belgium)

    2017-08-05

    Highlights: • Highly stable metal-organic framework, MIL-101(Cr), for uses in aqueous, acidic adsorption. • Uranium recovery from low concentration acidic solutions. • One-step ship-around-the-bottle synthetic approach to incorporate CMPO in MIL-101(Cr). • Highly selective U(VI) adsorbent in competition with a high variety of metals, incl. rare earths and transition metals. • Regenerable and reusable adsorbent via 0.1 M nitric acid stripping. - Abstract: Mesoporous MIL-101(Cr) is used as host for a ship-in-a-bottle type adsorbent for selective U(VI) recovery from aqueous environments. The acid-resistant cage-type MOF is built in-situ around N,N-Diisobutyl-2-(octylphenylphosphoryl)acetamide (CMPO), a sterically demanding ligand with high U(VI) affinity. This one-step procedure yields an adsorbent which is an ideal compromise between homogeneous and heterogeneous systems, where the ligand can act freely within the pores of MIL-101, without leaching, while the adsorbent is easy separable and reusable. The adsorbent was characterized by XRD, FTIR spectroscopy, nitrogen adsorption, XRF, ADF-STEM and EDX, to confirm and quantify the successful encapsulation of the CMPO in MIL-101, and the preservation of the host. Adsorption experiments with a central focus on U(VI) recovery were performed. Very high selectivity for U(VI) was observed, while competitive metal adsorption (rare earths, transition metals...) was almost negligible. The adsorption capacity was calculated at 5.32 mg U/g (pH 3) and 27.99 mg U/g (pH 4), by fitting equilibrium data to the Langmuir model. Adsorption kinetics correlated to the pseudo-second-order model, where more than 95% of maximum uptake is achieved within 375 min. The adsorbed U(VI) is easily recovered by desorption in 0.1 M HNO{sub 3}. Three adsorption/desorption cycles were performed.

  15. Holistic assessment of occurrence and fate of metolachlor within environmental compartments of agricultural watersheds

    Science.gov (United States)

    Rose, Claire E.; Coupe, Richard H.; Capel, Paul D.; Webb, Richard M.

    2017-01-01

    Background: Metolachlor [(RS)-2-Chloro-N-(2-ethyl-6-methyl-phenyl)-N-(1-methoxypropan-2-yl)acetamide] and two degradates (metolachlor ethane-sulfonic acid and metolachlor oxanilic acid) are commonly observed in surface and groundwater. The behavior and fate of these compounds were examined over a 12-year period in seven agricultural watersheds in the United States. They were quantified in air, rain, streams, overland flow, groundwater, soil water, subsurface drain water, and water at the stream/groundwater interface. The compounds were frequently detected in surface and groundwater associated with agricultural areas. A mass budget approach, based on all available data from the study and literature, was used to determine a percentage-wise generalized distribution and fate of applied parent metolachlor in typical agricultural environments.Results: In these watersheds, about 90% of applied metolachlor was taken up by plants or degraded, 10% volatilized, and 0.3% returned as rainfall. One percent was transported to surface water, while an equal amount infiltrated into the unsaturated zone soil water. < 0.02% reached the groundwater. Subsurface flow paths resulted in greater degradation of metolachlor because degradation reactions had more time to proceed.Conclusions: An understanding of the residence times of water in the different environmental compartments, and the important processes affecting metolachlor as it is transported along flowpaths among the environmental compartments allows for a degree of predictability of metolachlor's fate. Degradates with long half-lives can be used (in a limited capacity) as tracers of metolachlor, because of their persistence and widespread occurrence in the environment.

  16. The genome of cultivated sweet potato contains Agrobacterium T-DNAs with expressed genes: An example of a naturally transgenic food crop.

    Science.gov (United States)

    Kyndt, Tina; Quispe, Dora; Zhai, Hong; Jarret, Robert; Ghislain, Marc; Liu, Qingchang; Gheysen, Godelieve; Kreuze, Jan F

    2015-05-05

    Agrobacterium rhizogenes and Agrobacterium tumefaciens are plant pathogenic bacteria capable of transferring DNA fragments [transfer DNA (T-DNA)] bearing functional genes into the host plant genome. This naturally occurring mechanism has been adapted by plant biotechnologists to develop genetically modified crops that today are grown on more than 10% of the world's arable land, although their use can result in considerable controversy. While assembling small interfering RNAs, or siRNAs, of sweet potato plants for metagenomic analysis, sequences homologous to T-DNA sequences from Agrobacterium spp. were discovered. Simple and quantitative PCR, Southern blotting, genome walking, and bacterial artificial chromosome library screening and sequencing unambiguously demonstrated that two different T-DNA regions (IbT-DNA1 and IbT-DNA2) are present in the cultivated sweet potato (Ipomoea batatas [L.] Lam.) genome and that these foreign genes are expressed at detectable levels in different tissues of the sweet potato plant. IbT-DNA1 was found to contain four open reading frames (ORFs) homologous to the tryptophan-2-monooxygenase (iaaM), indole-3-acetamide hydrolase (iaaH), C-protein (C-prot), and agrocinopine synthase (Acs) genes of Agrobacterium spp. IbT-DNA1 was detected in all 291 cultigens examined, but not in close wild relatives. IbT-DNA2 contained at least five ORFs with significant homology to the ORF14, ORF17n, rooting locus (Rol)B/RolC, ORF13, and ORF18/ORF17n genes of A. rhizogenes. IbT-DNA2 was detected in 45 of 217 genotypes that included both cultivated and wild species. Our finding, that sweet potato is naturally transgenic while being a widely and traditionally consumed food crop, could affect the current consumer distrust of the safety of transgenic food crops.

  17. Synthesis, Density Functional Theory (DFT, Urease Inhibition and Antimicrobial Activities of 5-Aryl Thiophenes Bearing Sulphonylacetamide Moieties

    Directory of Open Access Journals (Sweden)

    Mnaza Noreen

    2015-11-01

    Full Text Available A variety of novel 5-aryl thiophenes 4a–g containing sulphonylacetamide (sulfacetamide groups were synthesized in appreciable yields via Pd[0] Suzuki cross coupling reactions. The structures of these newly synthesized compounds were determined using spectral data and elemental analysis. Density functional theory (DFT studies were performed using the B3LYP/6-31G (d, p basis set to gain insight into their structural properties. Frontier molecular orbital (FMOs analysis of all compounds 4a–g was computed at the same level of theory to get an idea about their kinetic stability. The molecular electrostatic potential (MEP mapping over the entire stabilized geometries of the molecules indicated the reactive sites. First hyperpolarizability analysis (nonlinear optical response were simulated at the B3LYP/6-31G (d, p level of theory as well. The compounds were further evaluated for their promising antibacterial and anti-urease activities. In this case, the antibacterial activities were estimated by the agar well diffusion method, whereas the anti-urease activities of these compounds were determined using the indophenol method by quantifying the evolved ammonia produced. The results revealed that all the sulfacetamide derivatives displayed antibacterial activity against Bacillus subtiles, Escherichia coli, Staphylococcus aureus, Shigella dysenteriae, Salmonella typhae, Pseudomonas aeruginosa at various concentrations. Furthermore, the compound 4g N-((5-(4-chlorophenylthiophen-2-ylsulfonyl acetamide showed excellent urease inhibition with percentage inhibition activity ~46.23 ± 0.11 at 15 µg/mL with IC50 17.1 µg/mL. Moreover, some other compounds 4a–f also exhibited very good inhibition against urease enzyme.

  18. Synthesis, Density Functional Theory (DFT), Urease Inhibition and Antimicrobial Activities of 5-Aryl Thiophenes Bearing Sulphonylacetamide Moieties.

    Science.gov (United States)

    Noreen, Mnaza; Rasool, Nasir; Gull, Yasmeen; Zubair, Muhammad; Mahmood, Tariq; Ayub, Khurshid; Nasim, Faiz-Ul-Hassan; Yaqoob, Asma; Zia-Ul-Haq, Muhammad; de Feo, Vincenzo

    2015-11-05

    A variety of novel 5-aryl thiophenes 4a-g containing sulphonylacetamide (sulfacetamide) groups were synthesized in appreciable yields via Pd[0] Suzuki cross coupling reactions. The structures of these newly synthesized compounds were determined using spectral data and elemental analysis. Density functional theory (DFT) studies were performed using the B3LYP/6-31G (d, p) basis set to gain insight into their structural properties. Frontier molecular orbital (FMOs) analysis of all compounds 4a-g was computed at the same level of theory to get an idea about their kinetic stability. The molecular electrostatic potential (MEP) mapping over the entire stabilized geometries of the molecules indicated the reactive sites. First hyperpolarizability analysis (nonlinear optical response) were simulated at the B3LYP/6-31G (d, p) level of theory as well. The compounds were further evaluated for their promising antibacterial and anti-urease activities. In this case, the antibacterial activities were estimated by the agar well diffusion method, whereas the anti-urease activities of these compounds were determined using the indophenol method by quantifying the evolved ammonia produced. The results revealed that all the sulfacetamide derivatives displayed antibacterial activity against Bacillus subtiles, Escherichia coli, Staphylococcus aureus, Shigella dysenteriae, Salmonella typhae, Pseudomonas aeruginosa at various concentrations. Furthermore, the compound 4g N-((5-(4-chlorophenyl)thiophen-2-yl)sulfonyl) acetamide showed excellent urease inhibition with percentage inhibition activity ~46.23 ± 0.11 at 15 µg/mL with IC50 17.1 µg/mL. Moreover, some other compounds 4a-f also exhibited very good inhibition against urease enzyme.

  19. Evaluation of CLINDE as potent translocator protein (18 kDa) SPECT radiotracer reflecting the degree of neuroinflammation in a rat model of microglial activation

    Energy Technology Data Exchange (ETDEWEB)

    Arlicot, Nicolas; Duval, Stephanie; Guilloteau, Denis; Chalon, Sylvie [Inserm, U930, Tours (France); Universite Francois Rabelais, Tours (France); CHRU de Tours, Tours (France); Katsifis, Andrew; Mattner, Filomena [Australian Nuclear Science and Technology Organisation, Radiopharmaceuticals Research Institute, Sydney (Australia); Garreau, Lucette; Vergote, Jackie; Bodard, Sylvie [Inserm, U930, Tours (France); Universite Francois Rabelais, Tours (France)

    2008-12-15

    The translocator protein (TSPO; 18 kDa), the new name of the peripheral-type benzodiazepine receptor, is localised in mitochondria of glial cells and expressed in very low concentrations in normal brain. Their expression rises after microglial activation following brain injury. Accordingly, TSPO are potential targets to evaluate neuroinflammatory changes in a variety of CNS disorders. To date, only a few effective tools are available to explore TSPO by SPECT. We characterised here 6-chloro-2-(4'iodophenyl)-3-(N,N-diethyl)-imidazo[1,2-a]pyridine-3-acetamide or CLINDE in a rat model with different stages of excitotoxic lesion. Excitotoxicity was induced in male Wistar rats by unilateral intrastriatal injection of different amounts of quinolinic acid (75, 150 or 300 nmol). Six days later, two groups of rats (n = 5-6/group) were i.v. injected with [{sup 125}I]-CLINDE (0.4 MBq); one group being pre-injected with PK11195 (5 mg/kg). Brains were removed 30 min after tracer injection and the radioactivity of cerebral areas measured. Complementary ex vivo autoradiography, in vitro autoradiography ([{sup 3}H]-PK11195) and immunohistochemical studies (OX-42) were performed on brain sections. In the control group, [{sup 125}I]-CLINDE binding was significantly higher (p < 0.001) in lesioned than that in intact side. This binding disappeared in rats pre-treated with PK11195 (p<0.001), showing specific binding of CLINDE to TSPO. Ex vivo and in vitro autoradiographic studies and immunohistochemistry were consistent with this, revealing a spatial correspondence between radioactivity signal and activated microglia. Regression analysis yielded a positive relation between the ligand binding and the degree of neuroinflammation. These results demonstrate that CLINDE is suitable for TSPO in vivo SPECT imaging to explore their involvement in neurodegenerative disorders associated with microglial activation. (orig.)

  20. Evaluation of [{sup 11}C]-DAA1106 for imaging and quantification of neuroinflammation in a rat model of herpes encephalitis

    Energy Technology Data Exchange (ETDEWEB)

    Doorduin, Janine [Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, PO Box 30.001, 9700 RB Groningen (Netherlands)], E-mail: j.doorduin@ngmb.umcg.nl; Klein, Hans C. [Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, PO Box 30.001, 9700 RB Groningen (Netherlands); University Center of Psychiatry, University Medical Center Groningen, University of Groningen, PO Box 30.001, 9700 RB Groningen (Netherlands); Jong, Johan R. de; Dierckx, Rudi A.; Vries, Erik F.J. de [Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, PO Box 30.001, 9700 RB Groningen (Netherlands)

    2010-01-15

    Introduction: Many neurological and psychiatric disorders are associated with neuroinflammation. Positron emission tomography (PET) with [{sup 11}C]-PK11195 can be used to study neuroinflammation in these disorders. However, [{sup 11}C]-PK11195 may not be sensitive enough to visualize mild neuroinflammation. As a potentially more sensitive PET tracer for neuroinflammation, [{sup 11}C]-N-(2,5-dimethoxybenzyl)-N-(4-fluoro-2-phenoxyphenyl)-acetamide (DAA1106) was evaluated in a rat model of herpes encephalitis. Methods: Male Wistar rats were intranasally inoculated with HSV-1 (HSE) or phosphate-buffered saline (control). At Day 6 or Day 7 after inoculation, small-animal [{sup 11}C]-DAA1106 PET scans were acquired, followed by ex vivo biodistribution. Arterial blood sampling was performed for quantification of uptake. Results: In HSE rats, a significantly higher ex vivo, but not in vivo, uptake of [{sup 11}C]-DAA1106 was found in almost all examined brain areas (24-71%, P<.05), when compared to control rats. Pretreatment with unlabeled PK11195 effectively reduced [{sup 11}C]-DAA1106 uptake in HSE rats (54-84%; P<.001). The plasma and brain time-activity curves showed rapid uptake of [{sup 11}C]-DAA1106 into tissue. The data showed a good fit to the Logan analysis but could not be fitted to a two-tissue compartment model. Conclusions: [{sup 11}C]-DAA1106 showed a high and specific ex vivo uptake in the encephalitic rat brain. However, neuroinflammation could not be demonstrated in vivo by [{sup 11}C]-DAA1106 PET. Quantification of the uptake of [{sup 11}C]-DAA1106 using plasma sampling is not optimal, due to rapid tissue uptake, slow tissue clearance and low plasma activity.

  1. Tafuketide, a phylogeny-guided discovery of a new polyketide from Talaromyces funiculosus Salicorn 58.

    Science.gov (United States)

    Guo, Jia; Ran, Huomiao; Zeng, Jie; Liu, Dong; Xin, Zhihong

    2016-06-01

    A phylogeny-guided approach was applied to screen endophytic fungi containing type I polyketide synthase (PKS I) biosynthetic gene sequences and aimed to correlate genotype to chemotype for the discovery of novel bioactive polyketides. Salicorn 58, which was identified as Talaromyces funiculosus based on its internal transcribed spacer (ITS) and ribosomal large-subunit (LSU) DNA sequences, showed significant target bands. A chemical investigation of the culture of Salicorn 58 was allowed for the isolation of a new polyketide, Talafun (1), and a new natural product, N-(2'-hydroxy-3'-octadecenoyl)-9-methyl-4,8-sphingadienin (2), together with six known compounds, including chrodrimanin A (3), chrodrimanin B (4), N-(4-hydroxy-2-methoxyphenyl) acetamide (5), butyl β-glucose (6), 3β,15β-dihydroxyl-(22E, 24R)-ergosta-5,8(14),22-trien-7-dione (7), and (3β,5a,8a,22E)-5,8-epidioxyergosta-6,22-dien-3-ol (8). Their chemical structures were elucidated by extensive spectroscopic analysis and electro circular dichroism (ECD) spectrum calculations. Antioxidant experiments revealed that compound 5 showed strong ABTS(+) radical scavenging activity with an IC50 value of 11.43 ± 1.61 μM and potent ferric reducing activity (FRAP assay) with FRAP value of 187.52 ± 2.97. Antimicrobial assays revealed that compounds 1 and 4 showed high levels of selectivity toward Escherichia coli with MIC values of 18 ± 0.40 and 43 ± 0.52 μM, respectively. Compounds 2 and 3 exhibited broad-spectrum antimicrobial activity against Staphylococcus aureus, Mycobacterium smegmatis, Micrococcus tetragenus, Mycobacterium phlei, and E. coli, respectively. The results from the current research highlight the advantage of phylogeny-guided pipeline for the screening of new polyketides from endophytic fungi containing PKS I genes.

  2. Cell-Cell Communication in Yeast Using Auxin Biosynthesis and Auxin Responsive CRISPR Transcription Factors.

    Science.gov (United States)

    Khakhar, Arjun; Bolten, Nicholas J; Nemhauser, Jennifer; Klavins, Eric

    2016-04-15

    An engineering framework for synthetic multicellular systems requires a programmable means of cell-cell communication. Such a communication system would enable complex behaviors, such as pattern formation, division of labor in synthetic microbial communities, and improved modularity in synthetic circuits. However, it remains challenging to build synthetic cellular communication systems in eukaryotes due to a lack of molecular modules that are orthogonal to the host machinery, easy to reconfigure, and scalable. Here, we present a novel cell-to-cell communication system in Saccharomyces cerevisiae (yeast) based on CRISPR transcription factors and the plant hormone auxin that exhibits several of these features. Specifically, we engineered a sender strain of yeast that converts indole-3-acetamide (IAM) into auxin via the enzyme iaaH from Agrobacterium tumefaciens. To sense auxin and regulate transcription in a receiver strain, we engineered a reconfigurable library of auxin-degradable CRISPR transcription factors (ADCTFs). Auxin-induced degradation is achieved through fusion of an auxin-sensitive degron (from IAA corepressors) to the CRISPR TF and coexpression with an auxin F-box protein. Mirroring the tunability of auxin perception in plants, our family of ADCTFs exhibits a broad range of auxin sensitivities. We characterized the kinetics and steady-state behavior of the sender and receiver independently as well as in cocultures where both cell types were exposed to IAM. In the presence of IAM, auxin is produced by the sender cell and triggers deactivation of reporter expression in the receiver cell. The result is an orthogonal, rewireable, tunable, and, arguably, scalable cell-cell communication system for yeast and other eukaryotic cells.

  3. Determination of tumour hypoxia with the PET tracer [{sup 18}F]EF3: improvement of the tumour-to-background ratio in a mouse tumour model

    Energy Technology Data Exchange (ETDEWEB)

    Christian, Nicolas; Bol, Anne; Bast, Marc de; Labar, Daniel; Lee, John; Mahy, Pierre; Gregoire, Vincent [Universite Catholique de Louvain, Center for Molecular Imaging and Experimental Radiotherapy, Brussels (Belgium)

    2007-09-15

    The 2-(2-nitroimidazol-1-yl)-N-(3,3,3-trifluoropropyl)acetamide (EF3) is a 2-nitroimidazole derivative which undergoes bioreductive activation under hypoxic conditions. Using the PET tracer [{sup 18}F]EF3 in mice, tumour-to-muscle ratios ranging from 1.3 to 3.5 were observed. This study investigated the impact of various interventions aimed at increasing [{sup 18}F]EF3 elimination, thus potentially increasing the tumour-to-noise ratio in mice, by increasing the renal filtration rate (spironolactone, furosemide), decreasing tubular re-absorption (metronidazole, ornidazole, amino acid solution) or stimulating gastro-intestinal elimination (phenobarbital). C3H mice were injected i.v. with an average of 12.95 MBq of [{sup 18}F]EF3. Drugs were injected i.v. 15 min before the tracer or daily 4 days prior to the experiment (phenobarbital). Anaesthetised mice were imaged from 30 to 300 min with a dedicated animal PET (Mosaic, Philips). Regions of interest were delineated around the tumour, bladder, heart, liver and leg muscle. Radioactivity was expressed as a percentage of injected activity per gram of tissue. Ornidazole decreased the urinary excretion and increased the liver uptake of [{sup 18}F]EF3, but without causing any changes in the other organs. Phenobarbital significantly increased the liver concentration and decreased radioactivity in blood and muscle without affecting the tracer uptake in tumour. Consequently, a small but non-significant increase in tumour-to-noise ratio was observed. Although some effects were observed with other drugs, they did not modify the tumour-to-noise ratio. Only phenobarbital induced a trend toward an increased tumour-to-noise ratio that could possibly be tested in the clinical situation. (orig.)

  4. Synthesis and pharmacological evaluation of new (indol-3-yl)alkylamides and alkylamines acting as potential serotonin uptake inhibitors.

    Science.gov (United States)

    Fouchard, F; Menciu, C; Duflos, M; Le Baut, G; Lambrey, B; Mourgues, M; Perrissoud, D

    1999-02-01

    A series of new indolylalkylamides 3-18 and alkylamines 19-26 has been prepared in the search of novel 5-hydroxytryptamine (5-HT) uptake inhibitors. Synthesis of N-2,3 or 4-pyridinyl-(indol-3-yl) acetamides and propionamides 3-10 was achieved starting from the corresponding Ph3P/BrCCl3 or DCC-activated acids. Reduction of the pyridine nucleus led to the N-piperidinylalkylamides 15-18 via the tetrahydropyridinyl derivatives 11-14, and LiAlH4 reduction afforded the desired amines 19-26. The affinity of these compounds for 5-HT and also dopamine (DA) and noradrenaline (NA) uptake sites was measured. Among the 16 studied amides only N-(methylpiperidin-3-yl)-(indol-3-yl) propionamide 16 exhibited a moderate 5-HT uptake inhibitory effect: 38% at 10 mu mol/l. In contrast the N-pyridinyl-(indol-3-yl)alkylamines 19-26 exerted high inhibition at this concentration and two of them, 23 and 24, remained very efficient at 0.1 mu mol/l. Optimal activity was observed in the 4-pyridinyl subseries and was compatible with variation (n = 1, 2) of the length of the interspacing alkylamino chain. Although 23 and 24 were about 17-fold less active than indalpine as 5-HT uptake inhibitors, they demonstrated, like indalpine, excellent selectivity for the 5-HT uptake site versus the DA uptake site. Both amines inhibited tetrabenazine-induced hypothermia and potentiated 5-HTP-induced behavioural effects in mice. The absence of 3,4-dioxyphenylalanine (dopa)-induced behavioural effects with compound 24 suggests possible antidepressant activity through selective inhibition of central neuronal serotonin uptake and/or increased monoamine release.

  5. 含羟基活性基团的聚酰亚胺制备和表征%Preparation and Properties of Polyimides from Diamino Containing Hydroxyl Group, 4,4′-Diamino-4″-Hydroxytriphenylmethan

    Institute of Scientific and Technical Information of China (English)

    路庆华; 李梅; 陶萍; 莫海燕; 魏少华; 王宗光

    2001-01-01

    合成了一种4,4′-二氨基-4″-羟基三苯甲烷的二胺单体,用该单体分别和芳香性二酐、酯环二酐以及含氟二酐制备了三种含羟基聚酰亚胺,并对其溶解性能和热性能进行了初步研究.发现含羟基二胺单体和含氟二酐生成的聚酰亚胺能溶解在极性非质子溶剂中,且显示出良好的耐热性能,这种聚酰亚胺可通过羟基引入功能基团制备功能性聚酰亚胺.%4,4′-diamino-4″-hydroxyphenyl-triphenylmethan was synthesized and polyhydroxyimides (PHI) based on this diamine and benzophenone-3,3′4,4′-tetracarboxylic acid dianhydride (BTDA), 1,2,4-tricarboxy-3-carboxymethylcyclopentane(TCAAH), hexafluoroisopropylidene 2,2-bis(phthalic acid anhydride) (6FDA) were prepared by solution polycondensation followed by thermal cyclization in refluxing xylene. PHI from 6FDA and DHTM is soluble in aprotonic polar organic solvents such as N-methyl 2-pyrrolidone, N,N-dimethyl acetamide, it has glass transition temperature of 248°C and thermal decomposition temperature above 500°C.

  6. Prebiotic chemical evolution in the astrophysical context.

    Science.gov (United States)

    Ziurys, L M; Adande, G R; Edwards, J L; Schmidt, D R; Halfen, D T; Woolf, N J

    2015-06-01

    An ever increasing amount of molecular material is being discovered in the interstellar medium, associated with the birth and death of stars and planetary systems. Radio and millimeter-wave astronomical observations, made possible by high-resolution laboratory spectroscopy, uniquely trace the history of gas-phase molecules with biogenic elements. Using a combination of both disciplines, the full extent of the cycling of molecular matter, from circumstellar ejecta of dying stars - objects which expel large amounts of carbon - to nascent solar systems, has been investigated. Such stellar ejecta have been found to exhibit a rich and varied chemical content. Observations demonstrate that this molecular material is passed onto planetary nebulae, the final phase of stellar evolution. Here the star sheds almost its entire original mass, becoming an ultraviolet-emitting white dwarf. Molecules such as H2CO, HCN, HCO(+), and CCH are present in significant concentrations across the entire age span of such nebulae. These data suggest that gas-phase polyatomic, carbon-containing molecules survive the planetary nebula phase and subsequently are transported into the interstellar medium, seeding the chemistry of diffuse and then dense clouds. The extent of the chemical complexity in dense clouds is unknown, hindered by the high spectral line density. Organic species such as acetamide and methyl amine are present in such objects, and NH2CHO has a wide Galactic distribution. However, organophosphorus compounds have not yet been detected in dense clouds. Based on carbon and nitrogen isotope ratios, molecular material from the ISM appears to become incorporated into solar system planetesimals. It is therefore likely that interstellar synthesis influences prebiotic chemistry on planet surfaces.

  7. Effect of the primary cooling rate on the motility and fertility of frozen-thawed rabbit spermatozoa

    Directory of Open Access Journals (Sweden)

    Tatsuhiro Maeda

    2012-07-01

    Full Text Available In the present study, we examined the effect of primary cooling rates on the motility and fertility of frozen-thawed rabbit spermatozoa. Rabbit semen diluted with an egg-yolk acetamide extender was cooled from room temperature to 5°C at four different rates (-0.1, -0.2, -0.4, -0.8°C/min as a primary cooling step, then semen was frozen in liquid nitrogen vapour. After thawing, sperm cooled at -0.1°C/min showed the highest motility (40.7 ± 7.3%; there were no significant differences between the motilities of the -0.1, -0.2, and -0.4°C/min groups. The motility of frozen-thawed sperm cooled at -0.8°C/min (29.2 ± 6.8% was significantly lower than that of sperm cooled at -0.1 and -0.2°C/min. The viability (-0.1°C/min, 38.1 ± 4.0%; -0.8°C/min, 24.3 ± 7.3% of frozen-thawed sperm was closely related to its motility (-0.1°C/min, 36.7 ± 7.2%; -0.8°C/min, 22.3 ± 4.7%. Quality of post-thaw motile sperm cooled at different rates was estimated by comparing the fertilisation ability of the -0.1 and -0.8°C/min groups following artificial insemination. There were no significant differences in pregnancy rates and mean litter sizes. These data suggest that cooling rabbit semen at rates ranging from -0.1 to -0.8°C/min affects the viability but not the fertilisation capacity of motile spermatozoa after thawing.

  8. Self-repairable polymeric networks: Synthesis and network design

    Science.gov (United States)

    Ghosh, Biswajit

    This dissertation describes the design, synthesis and development of a new class of polymeric networks that exhibit self-repairing properties under UV exposure. It consists of two parts: (a) modification and synthesis of oxetane (OXE), and oxolane (OXO) substituted chitosan (CHI) macromonomer, and (b) design, and synthesis of self-repairing polyurethane (PUR) networks consisting of modified chitosan. Unmodified CHI consisting of acetamide (-NHCOCH3), primary hydroxyl (-OH), and amine (-NH2) functional groups were reacted with OXE or OXO compounds under basic conditions in order to substitute the 1° --OH groups, and at the same time, convert -NHCOCH 3 functionalities into -NH2 groups, while maintaining their un-reacted form to generate OXE/OXO-substituted CHI macromonomer. These substituted CHI macromonomers were incorporated within the PUR backbone by reacting with trifunctional isocyanate in the presence of polyethylene glycol (PEG) and dibutyl tin dilaurate catalyst (DBTDL). Utilizing spectroscopic analysis combined with optical microscopy, these studies showed that the kinetics of self-repair depends on the stoichiometry of the individual entities as well as the time required for self-repairing to occur decrease with increasing OXE quantity within the network. Internal reflection infrared imaging (IRIRI) of OXE/OXO-CHI-PUR networks as well as Raman and Fourier transform IR (FT-IR) studies of OXE/OXO-CHI macromonomers revealed that cationic OXE/OXO ring opening, free radical polyurea (PUA)-to-PUR conversion, along with chair-to-boat conformational changes of CHI backbone are responsible for repairing the damaged network. The network remodeling process, investigated by utilizing micro-thermal analyzer (muTA), revealed that mechanical damage generates small fragments or oligomers within the scratch, therefore glass transition temperature (Tg) decreases, and under UV exposure cross-linking reactions propagate from the bottom of the scratch to the top resulting in

  9. Atmospheric pressure ionization-tandem mass spectrometry of the phenicol drug family.

    Science.gov (United States)

    Alechaga, Élida; Moyano, Encarnación; Galceran, M Teresa

    2013-11-01

    In this work, the mass spectrometry behaviour of the veterinary drug family of phenicols, including chloramphenicol (CAP) and its related compounds thiamphenicol (TAP), florfenicol (FF) and FF amine (FFA), was studied. Several atmospheric pressure ionization sources, electrospray (ESI), atmospheric pressure chemical ionization and atmospheric pressure photoionization were compared. In all atmospheric pressure ionization sources, CAP, TAP and FF were ionized in both positive and negative modes; while for the metabolite FFA, only positive ionization was possible. In general, in positive mode, [M + H](+) dominated the mass spectrum for FFA, while the other compounds, CAP, TAP and FF, with lower proton affinity showed intense adducts with species present in the mobile phase. In negative mode, ESI and atmospheric pressure photoionization showed the deprotonated molecule [M-H](-), while atmospheric pressure chemical ionization provided the radical molecular ion by electron capture. All these ions were characterized by tandem mass spectrometry using the combined information obtained by multistage mass spectrometry and high-resolution mass spectrometry in a quadrupole-Orbitrap instrument. In general, the fragmentation occurred via cyclization and losses or fragmentation of the N-(alkyl)acetamide group, and common fragmentation pathways were established for this family of compounds. A new chemical structure for the product ion at m/z 257 for CAP, on the basis of the MS(3) and MS(4) spectra is proposed. Thermally assisted ESI and selected reaction monitoring are proposed for the determination of these compounds by ultra high-performance liquid chromatography coupled to tandem mass spectrometry, achieving instrumental detection limits down to 0.1 pg. Copyright © 2013 John Wiley & Sons, Ltd.

  10. Monotherapy for partial epilepsy: focus on levetiracetam

    Directory of Open Access Journals (Sweden)

    Antonio Gambardella

    2008-03-01

    Full Text Available Antonio Gambardella1,2, Angelo Labate1,2, Eleonora Colosimo1, Roberta Ambrosio1, Aldo Quattrone1,21Institute of Neurology, University Magna Græcia, Catanzaro, Italy; 2Institute of Neurological Sciences, National Research Council, Piano Lago di Mangone, Cosenza, ItalyAbstract: Levetiracetam (LEV, the S-enantiomer of alpha-ethyl-2-oxo-1-pyrollidine acetamide, is a recently licensed antiepileptic drug (AED for adjunctive therapy of partial seizures. Its mechanism of action is uncertain but it exhibits a unique profile of anticonvulsant activity in models of chronic epilepsy. Five randomized, double-blind, placebo-controlled trials enrolling adult or pediatric patients with refractory partial epilepsy have demonstrated the efficacy of LEV as adjunctive therapy, with a responder rate (≥50% reduction in seizure frequency of 28%–45%. Long-term efficacy studies suggest retention rates of 60% after one year, with 13% of patients seizure-free for 6 months of the study and 8% seizure-free for 1 year. More recent studies illustrated successful conversion to monotherapy in patients with refractory epilepsy, and its effectiveness as a single agent in partial epilepsy. LEV has also efficacy in generalized epilepsies. Adverse effects of LEV, including somnolence, lethargy, and dizziness, are generally mild and their occurrence rate seems to be not significantly different from that observed in placebo groups. LEV also has no clinically significant pharmacokinetic interactions with other AEDs, or with commonly prescribed medications. The combination of effective antiepileptic properties with a relatively mild adverse effect profile makes LEV an attractive therapy for partial seizures.Keywords: levetiracetam, partial epilepsy, antiepileptic drugs

  11. Combining bifunctional chelator with (3 + 2)-cycloaddition approaches: synthesis of dual-function technetium complexes.

    Science.gov (United States)

    Braband, Henrik; Imstepf, Sebastian; Benz, Michael; Spingler, Bernhard; Alberto, Roger

    2012-04-02

    A new concept for the synthesis of dual-functionalized technetium (Tc) compounds is presented, on the basis of the reactivity of fac-{Tc(VII)O(3)}(+) complexes. The concept combines the "classical" bifunctional chelator (BFC) approach with the new ligand centered labeling strategy of fac-{TcO(3)}(+) complexes with alkenes ((3 + 2)-cycloaddition approach). To evidence this concept, fac-{(99)TcO(3)}(+) model complexes containing functionalized 1,4,7-triazacyclononane (tacn) derivatives N-benzyl-2-(1,4,7-triazonan-1-yl)acetamide (tacn-ba) and 2,2',2″-(1,4,7-triazonane-1,4,7-triyl)triacetic acid (nota·3H) were synthesized and characterized. Whereas [(99)TcO(3)(tacn-ba)](+) [2](+) can be synthesized following a established oxidation procedure starting from the Tc(V) complex [(99)TcO(glyc)(tacn-ba)](+) [1](+), a new synthetic pathway for the synthesis of [(99)TcO(3)(nota)](2-) [5](2-) had to be developed, starting from [(99)Tc(nota·3H)(CO)(3)](+) [4](+) and using sodium perborate tetrahydrate (NaBO(3)·4H(2)O) as oxidizing reagent. While [(99)TcO(3)(nota)](2-) [5](2-) is a very attractive candidate for the development of trisubstituted novel multifunctional radioprobes, (3 + 2)-cycloaddition reactions of [(99)TcO(3)(tacn-ba)](+) [2](+) with 4-vinylbenzenesulfonate (styrene-SO(3)(-)) demonstrated the suitability of monosubstituted tacn derivatives for the new mixed "BFC-(3 + 2)-cycloaddition" approach. Kinetic studies of this reaction lead to the conclusion that the alteration of the electronic structure of the nitrogen donors by, e.g., alkylation can be used to tune the rate of the (3 + 2)-cycloaddition.

  12. Lanthanide mixed-ligand complexes of the [Ln(CAPh)3(Phen)] and [LaxEu1-x(CAPh)3(Phen)] (CAPh = carbacylamidophosphate) type. A comparative study of their spectral properties.

    Science.gov (United States)

    Litsis, Olena O; Ovchynnikov, Vladimir A; Scherbatskii, Vasyl P; Nedilko, Sergiy G; Sliva, Tatiana Yu; Dyakonenko, Viktoriya V; Shishkin, Oleg V; Davydov, Valentine I; Gawryszewska, Paula; Amirkhanov, Vladimir M

    2015-09-21

    A series of complexes Ln(Pip)3(Phen) (Ln(iii) = La, Ce-Nd, Sm-Lu, Y; HPip (CAPh type ligand) = 2,2,2-trichloro-N-(dipiperidin-1-yl-phosphoryl)acetamide, Phen = 1,10-phenanthroline) has been synthesized. The lanthanum(iii) doped europium(iii) complexes ([LaxEu1-x(Pip)3(Phen)], x = 0.99, 0.95, 0.50) have been obtained by the co-crystallization method. The complexes have been characterized by means of X-ray diffraction, IR, (1)H and (31)P-NMR and absorption spectroscopy. Emission and excitation luminescence spectra were recorded at 295 and 77 K. The lifetime values (τ) for the emission of all europium complexes were determined. The (5)D0 luminescence quantum efficiency is 73-89%. The symmetries of the nearest europium surrounding in pure and doped complexes were evaluated from the Stark splitting of (5)D0-(7)FJ transitions. Crystal structures of [Ln(Pip)3(Phen)] (Ln = Nd (1), Eu (2) and Tb (3)) have been determined. Lattice parameters of the [Ln(Pip)3(Phen)] (Ln = Tb, Yb) and the doped [LaxEu1-x(Pip)3(Phen)] (x = 0.99, 0.95, 0.50) complexes have been measured. The presence of four polymorphs within a number of rare earth elements has been estimated: two in triclinic (Ln1 = La, Nd; Ln2 = Eu), one in the monoclinic (Ln3 = Tb) and one in the rhombic (Ln4 = Tb, Yb) symmetry. Complex 3 can be obtained in two crystal modifications: monoclinic and orthorhombic ones.

  13. Characterization of Disopyramide derivative ADD424042 as a non-cardiotoxic neuronal sodium channel blocker with broad-spectrum anticonvulsant activity in rodent seizure models.

    Science.gov (United States)

    Król, Marek; Ufnal, Marcin; Szulczyk, Bartłomiej; Podsadni, Piotr; Drapała, Adrian; Turło, Jadwiga; Dawidowski, Maciej

    2016-01-01

    It was reported that antiarrhythmic drugs (AADs) can be useful in controlling refractory seizures in humans or in enhancing the action of antiepileptic drugs (AEDs) in animal models. Disopyramide phosphate (DISO) is an AAD that blocks sodium channels in cardiac myocytes. We evaluated a DISO derivative, 2-(2-chlorophenyl)-2-(pyridin-2-yl)acetamide (ADD424042) for its anticonvulsant activity in a battery of rodent models of epileptic seizures. The compound displayed a broad spectrum of activity in the 'classical' models as well as in the models of pharmacoresistant seizures. Furthermore, ADD424042 showed good therapeutic indices between the anticonvulsant activity and the motor impairment. On the contrary, no anticonvulsant effects but severe lethality were observed in the primary anticonvulsant testing of the parent DISO. By performing the whole-cell voltage-clamp experiments in dispersed cortical neurons we demonstrated that ADD424042 decreased the maximal amplitude of voltage-gated sodium channels with an IC50 value in nM range. Moreover, the compound enhanced use-dependent block and decreased excitability in pyramidal neurons in the current-clamp experiments in cortical slices. Importantly, we found that ADD424042 possessed either no, or very small cardiotoxic effect. In contrast to DISO, ADD424042 did not produce any apparent changes in electrocardiogram (ECG) and arterial blood pressure recordings. ADD424042 had no effect on QT and corrected QT intervals, at a dose which was 15 times higher than ED50 for the anticonvulsant effect in the MES model. Taken together, these data suggest that ADD424042 has the potential to become a lead structure for novel broadly acting AEDs with wide margin of cardiac safety.

  14. Hydrophilic polysulfone film prepared from polyethylene glycol monomethylether via coupling graft

    Science.gov (United States)

    Du, Ruikui; Gao, Baojiao; Li, Yanbin

    2013-06-01

    In the presence of acid-acceptor Na2CO3, the nucleophilic substitution between chloromethylated polysulfone (CMPSF) and polyethylene glycol monomethylether (PEGME) was conducted. Polyethylene glycol (PEG) was coupling-grafted onto the side chains of polysulfone (PSF) so that the graft copolymer PSF-g-PEG was prepared and the hydrophilic modification of polysulfone membrane material was realized. The chemical structure of PSF-g-PEG was characterized by FTIR and 1H NMR. The influence of the main factors on the coupling graft reaction was investigated. The water static contact angle of PSF-g-PEG membrane was determined and its property of resisting protein pollution was examined by using bovine serum albumin (BSA) as a model protein. The experimental results show that the coupling graft reaction between CMPSF and PEGME can proceed successfully, and the reaction of chloromethyl groups of CMPSF with the hydroxyl end groups of PEGME is a typical SN1 nucleophilic substitution reaction. The polarity of the solvents and the reaction temperature greatly influence the reaction. The suitable solvent is dimethyl acetamide with stronger polarity and 70 °C is a suitable reaction temperature. After reaction of 36 h, the grafting degree of PEG can reach 48 g/100 g and the product yield is about 73.6%. The contact angle of PSF-g-PEG membrane declines rapidly with the increase of PEG grafting degree, displaying the obvious enhancement of the hydrophilicity. The adsorption capacity of BSA on PSF-g-PEG membrane decreases remarkably with the increase of PEG grafting degree, showing excellent antifouling ability of PSF-g-PEG membrane for proteins.

  15. Semi- and thiosemicarbazide Mn(II) complexes: Characterization, DFT and biological studies

    Science.gov (United States)

    Yousef, T. A.; Alduaij, O. K.; Ahmed, Sara F.; Abu El-Reash, G. M.; El-Gammal, O. A.

    2016-09-01

    One NO and two NOS donor ligands have been prepared by addition ethanolic suspension of 2-hydrazino-2-oxo-N-phenyl-acetamide to phenyl isocyanate (H2PAPS), phenyl isothiocyanate (H2PAPT) and benzoyl isothiocyanate (H2PABT). The Mn (II) complexes were prepared from the chloride salt and characterized by conventional techniques. The isolated complexes were assigned the formulaes, [Mn(HPAPS)2], [Mn(HPAPT)Cl] and [Mn(HPABT)Cl(H2O)2], respectively. The IR study of ligands and their complexes shows that H2PAPS behaves as a mononegative tridentate via both CO of hydrazide moiety in keto and deprotonated enol form and CN (azomethine) due to enolization of CO cyanate moiety without deprotonation. H2PAPT behaves as mononegative tridentate via CO of hydrazide moiety, deprotonated thiol CS and NH group. Finally H2PABT behaves as mononegative tridentate via deprotonated enolized CO of hydrazide moiety, CO of benzoyl moiety and NH group. The IR spectra of ligands from DFT calculations are compared with those obtained experimentally. Also, HOMO, LUMO, the bond lengths, bond angles, and dipole moments have been calculated. The calculated HOMO-LUMO energy gap reveals that charge transfer occurs within the molecule. The binding energy values display the high stability of complexes. The kinetic and thermodynamic parameters were determined by Coats-Redfern and Horowitz-Metzger methods. The antibacterial activities were also tested against Bacillus subtilis and Escherichia coli bacteria. Finally, the antitumor activities of the Ligands and their Mn(II) complexes have been evaluated against liver (HePG2) and breast (MCF-7) cancer cells.

  16. Deceptive Ceropegia dolichophylla fools its kleptoparasitic fly pollinators with exceptional floral scent

    Directory of Open Access Journals (Sweden)

    Annemarie eHeiduk

    2015-07-01

    Full Text Available Ceropegia species (Apocynaceae have deceptive pitfall flowers and exploit small flies as pollinators, supposedly by chemical mimicry. Only preliminary data on the composition of flower scents are available for a single species so far, and the mimicry system is not yet understood in any species.We collected data on basic pollination aspects of C. dolichophylla, analyzed floral scent by gas chromatography linked to mass spectrometry, identified electrophysiologically active scent components by gas chromatography coupled with electroantennographic detection, and determined compounds responsible for pollinator attraction in bioassays. We found that flowers of C. dolichophylla are visited by small flies of several taxa. Only Milichiidae and Chloropidae carried pollinaria and are, thus, pollinators. The pollen transfer efficiency at two different sites was 2 % and 4 %, respectively. The floral scent was dominated by spiroacetals, mainly (2S,6R,8S-8-methyl-2-propyl-1,7-dioxaspiro[5.5]undecane, n-tridecane, and N-(3-methylbutylacetamide. This spiroacetal and the acetamide elicited the most intense electrophysiological responses in fly antennae, and bioassays confirmed the capability of the spiroacetal in eliciting behavioral responses in pollinators. Most flies, determined as pollinators of C. dolichophylla, are kleptoparasites. They exploit insect prey of predatory arthropods as food source to which they are attracted by volatiles. 8-Methyl-2-propyl-1,7-dioxaspiro[5.5]undecane and N-(3-methylbutylacetamide have not been identified before as volatiles of other plants, however, they are known as insect volatiles. Both compounds occur in the venom glands of paper wasps, a potential food source for the pollinators of C. dolichophylla. We propose that C. dolichophylla shows a kleptomyiophilous pollination strategy. It mimics insect related odors to exploit the food-seeking behavior of its kleptoparasitic pollinators.

  17. Experimental and theoretical study of 4-formyl pyrrole derived aroylhydrazones

    Science.gov (United States)

    Rawat, Poonam; Singh, R. N.

    2015-03-01

    Two new 4-formyl pyrrole derived aroylhydrazones (3a, b) from ethyl 4-formyl-3,5-dimetyl-1H-pyrrole-2-carboxylate and aroylhydrazides (3,5-dinitrobenzohydrazide/2-hydrazinocarbonyl-N-phenyl-acetamide) have been synthesized and characterized by various spectroscopic techniques 1H NMR, Mass, UV-Visible and FT-IR. The calculated thermodynamic parameters show that the formation of 3a as spontaneous, whereas 3b as non-spontaneous. TD-DFT has been used to calculate the absorption wavelengths, oscillator strength (f) and the nature of electronic excitations. Natural bond orbital (NBO) analysis has been carried out to explore the various conjugative and hyperconjugative interactions and their second order stabilization energy (E(2)) within monomer and its dimer. The dimer formation of 3a, 3b due to result of intermolecular hydrogen bonding N1sbnd H30⋯O84, N1sbnd H28⋯O60 is obvious in 1H NMR, NBO and FT-IR as down field chemical shifts, n(O84) → σ∗(N1sbnd H30), n(O60) → σ∗(N1sbnd H28) interactions, vibrational red shifts, respectively. To determine the strength and nature of hydrogen bonding, topological parameters at bond critical points (BCP) have been analyzed by 'Quantum theory of Atoms in molecules' (QTAIM) in detail. The global electrophilicity index (ω) has been calculated to determine the relative electrophilic strength of molecules. The local reactivity descriptors analyses such as Fukui functions (fk+, fk-), local softnesses (sk+, sk-) and electrophilicity indices (ωk+, ωk-) have been performed to determine the reactive sites within molecules. The first hyperpolarizabilities (β0) of 3a, b have been computed to evaluate the non-linear optical (NLO) response of the investigated molecules.

  18. Pd(II)-catalysed and Hg(II)-co-catalysed oxidation of D-glucose and D-fructose by N-bromoacetamide in the presence of perchloric acid: a kinetic and mechanistic study.

    Science.gov (United States)

    Singh, Ashok Kumar; Srivastava, Jaya; Rahmani, Shahla; Singh, Vineeta

    2006-02-27

    The kinetics of Pd(II)-catalysed and Hg(II)-co-catalysed oxidation of D-glucose (Glc) and D-fructose (Fru) by N-bromoacetamide (NBA) in the presence of perchloric acid using mercury(II) acetate as a scavenger for Br- ions have been studied. The results show first-order kinetics with respect to NBA at low concentrations, tending to zero order at high concentrations. First-order kinetics with respect to Pd(II) and inverse fractional order in Cl- ions throughout their variation have also been noted. The observed direct proportionality between the first-order rate constant (k1) and the reducing sugar concentration shows departure from the straight line only at very higher concentration of sugar. Addition of acetamide (NHA) decreases the first-order rate constant while the oxidation rate is not influenced by the change in the ionic strength (mu) of the medium. Variation of [Hg(OAc)2] shows a positive effect on the rate of reaction. The observed negative effect in H+ at lower concentrations tends to an insignificant effect at its higher concentrations. The first-order rate constant decreases with an increase in the dielectric constant of the medium. The various activation parameters have also been evaluated. The products of the reactions were identified as arabinonic acid and formic acid for both the hexoses. A plausible mechanism involving HOBr as the reactive oxidising species, Hg(II) as co-catalyst, and [PdCl3.S]-1 as the reactive Pd(II)-sugar complex in the rate-controlling step is proposed.

  19. Degradation of 2,6-di-tert-butylphenol by an isolated high-efficiency bacterium strain.

    Science.gov (United States)

    Zhang, Ya-lei; Fang, Zhen-wei; Xu, De-qiang; Xiao, Yi-ping; Zhao, Jian-fu; Qiang, Zhi-min

    2005-01-01

    An aerobic bacterium strain, F-3-4, capable of effectively degrading 2, 6-ditert-butylphenol (2, 6-DTBP), was isolated and screened out from an acrylic fiber wastewater and the biofilm in the wastewater treatment facilities. This strain was identified as Alcaligenes sp. through morphological, physiological and biochemical examinations. After cultivation, the strain was enhanced by 26.3% in its degradation capacity for 2,6-DTBP. Results indicated that the strain was able to utilize 2,6-DTBP, lysine, lactamine, citrate, n-utenedioic acid and malic acid as the sole carbon and energy source, alkalinize acetamide, asparagine, L-histidine, acetate, citrate and propionate, but failed to utilize glucose, D-fructose, D-seminose, D-xylose, serine and phenylalanine as the sole carbon and energy source. The optimal growth conditions were determined to be: temperature 37 degrees C, pH 7.0, inoculum size 0.1% and shaker rotary speed 250 r/min. Under the optimal conditions, the degradation kinetics of 2,6-DTBP with an initial concentration of 100 mg/L was studied. Results indicated that 62.4% of 2,6-DTBP was removed after 11 d. The degradation kinetics could be expressed by Eckenfelder equation with a half life of 9.38 d. In addition, the initial concentration of 2,6-DTBP played an important role on the degradation ability of the strain. The maximum initial concentration of 2,6-DTBP was determined to be 200 mg/L. Above this level, the strain was overloaded and exhibited significant inhibition.

  20. Endophytic Paecilomyces formosus LHL10 Augments Glycine max L. Adaptation to Ni-Contamination through Affecting Endogenous Phytohormones and Oxidative Stress.

    Science.gov (United States)

    Bilal, Saqib; Khan, Abdul L; Shahzad, Raheem; Asaf, Sajjad; Kang, Sang-Mo; Lee, In-Jung

    2017-01-01

    This study investigated the Ni-removal efficiency of phytohormone-producing endophytic fungi Penicillium janthinellum, Paecilomyces formosus, Exophiala sp., and Preussia sp. Among four different endophytes, P. formosus LHL10 was able to tolerate up to 1 mM Ni in contaminated media as compared to copper and cadmium. P. formosus LHL10 was further assessed for its potential to enhance the phytoremediation of Glycine max (soybean) in response to dose-dependent increases in soil Ni (0.5, 1.0, and 5.0 mM). Inoculation with P. formosus LHL10 significantly increased plant biomass and growth attributes as compared to non-inoculated control plants with or without Ni contamination. LHL10 enhanced the translocation of Ni from the root to the shoot as compared to the control. In addition, P. formosus LHL10 modulated the physio-chemical apparatus of soybean plants during Ni-contamination by reducing lipid peroxidation and the accumulation of linolenic acid, glutathione, peroxidase, polyphenol oxidase, catalase, and superoxide dismutase. Stress-responsive phytohormones such as abscisic acid and jasmonic acid were significantly down-regulated in fungal-inoculated soybean plants under Ni stress. LHL10 Ni-remediation potential can be attributed to its phytohormonal synthesis related genetic makeup. RT-PCR analysis showed the expression of indole-3-acetamide hydrolase, aldehyde dehydrogenase for indole-acetic acid and geranylgeranyl-diphosphate synthase, ent-kaurene oxidase (P450-4), C13-oxidase (P450-3) for gibberellins synthesis. In conclusion, the inoculation of P. formosus can significantly improve plant growth in Ni-polluted soils, and assist in improving the phytoremediation abilities of economically important crops.