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Sample records for acetamide

  1. 40 CFR 721.285 - Acetamide, N-[4-(pentyloxy)phenyl]-, acetamide, N-[2-nitro-4-(pentyloxy)phenyl]-, and acetamide...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Acetamide, N- -, acetamide, N- -, and acetamide, N- -. 721.285 Section 721.285 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.285 Acetamide, N- -, acetamide, N- -, and acetamide, N- -. (a)...

  2. 40 CFR 721.285 - Acetamide, N-[4-(pentyloxy)phenyl]-, acetamide, N-[2-nitro-4-(pentyloxy)phenyl]-, and acetamide...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Acetamide, N- -, acetamide, N- -, and acetamide, N- -. 721.285 Section 721.285 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.285 Acetamide, N- -, acetamide, N- -, and acetamide, N- -. (a)...

  3. Orientational Jumps in (Acetamide + Electrolyte) Deep Eutectics: Anion Dependence.

    PubMed

    Das, Suman; Biswas, Ranjit; Mukherjee, Biswaroop

    2015-08-27

    All-atom molecular dynamics simulations have been carried out to investigate orientation jumps of acetamide molecules in three different ionic deep eutectics made of acetamide (CH3CONH2) and lithium salts of bromide (Br(–)), nitrate (NO3(–)) and perchlorate (ClO4(–)) at approximately 80:20 mole ratio and 303 K. Orientational jumps have been dissected into acetamide–acetamide and acetamide–ion catagories. Simulated jump characteristics register a considerable dependence on the anion identity. For example, large angle jumps are relatively less frequent in the presence of NO3(–) than in the presence of the other two anions. Distribution of jump angles for rotation of acetamide molecules hydrogen bonded (H-bonded) to anions has been found to be bimodal in the presence of Br(–) and is qualitatively different from the other two cases. Estimated energy barrier for orientation jumps of these acetamide molecules (H-bonded to anions) differ by a factor of ∼2 between NO3(–) and ClO4(–), the barrier height for the latter being lower and ∼0.5kBT. Relative radial and angular displacements during jumps describe the sequence ClO(4)– > NO3(–) > Br(–) and follow a reverse viscosity trend. Jump barrier for acetamide–acetamide pairs reflects weak dependence on anion identity and remains closer to the magnitude (∼0.7kBT) found for orientation jumps in molten acetamide. Jump time distributions exhibit a power law dependence of the type, P(tjump) ∝ A(tjump/τ)(−β), with both β and τ showing substantial anion dependence. The latter suggests the presence of dynamic heterogeneity in these systems and supports earlier conclusions from time-resolved fluorescence measurements.

  4. Silylated derivatives OF N-(2-hydroxyphenyl)acetamide: Synthesis and structure

    NASA Astrophysics Data System (ADS)

    Nikonov, Alexey Yu.; Sterkhova, Irina V.; Lazarev, Igor M.; Albanov, Alexander I.; Lazareva, Natalya F.

    2016-10-01

    The N-(2-(trimethylsilyloxy)phenyl)acetamide 1 was synthesized via reaction of N-(2-hydroxyphenyl)acetamide with chlorotrimethylsilane. Transsilylation of new compound 1 by chloro(chloromethyl)dimethylsilane leads to 4-acetyl-2,2-dimethyl-3,4-dihydro-2H-1,4,2-benzoxazasiline 3. The structures of the new compounds were investigated by 1H, 13C and 29Si NMR spectroscopy, X-ray single-crystal analysis, FTIR spectroscopy and DFT methods.

  5. Photoinduced intermolecular dynamics and subsequent fragmentation in VUV-ionized acetamide clusters

    NASA Astrophysics Data System (ADS)

    Tarkanovskaja, Marta; Kooser, Kuno; Levola, Helena; Nõmmiste, Ergo; Kukk, Edwin

    2016-09-01

    Photofragmentation of small gas-phase acetamide clusters (CH3CONH2)n (n ≤ 10) produced by a supersonic expansion source has been studied using time-of-flight ion mass spectroscopy combined with tunable vacuum-ultraviolet (VUV) synchrotron radiation. Fragmentation channels of acetamide clusters under VUV photoionization resulting in protonated and ammoniated clusters formation were identified with the discussion about the preceding intramolecular rearrangements. Acetamide-2,2,2-d3 clusters were also studied in an experiment with a gas discharge lamp as a VUV light source; comparison with the main experiment gave insights into the mechanism of formation of protonated acetamide clusters, indicating that proton transfer from amino group plays a dominant role in that process. Geometry of the acetamide dimer was discussed and the most stable arrangement was concluded to be achieved when subunits of the dimer are connected via two N—H⋯O —C hydrogen bonds. Also, the influence of the photon energy on the stability of the clusters and their fragmentation channels has been examined.

  6. Density functional theory study of the local molecular properties of acetamide derivatives as anti-HIV drugs

    PubMed Central

    Oftadeh, M.; Mahani, N. Madadi; Hamadanian, M.

    2013-01-01

    Accurate quantum chemical computations based on density functional theory (DFT) were performed on the series of 2-(4-(naphthalen-2-yl)-1,2,3-thiadiazol-5-ylthio)-N-acetamide (TTA) derivatives. The local reactivity of the acetamide derivatives as anti-HIV drugs were studied in terms of Fukui functions in the framework of DFT. The results based on the basis set superposition error (BSSE) corrections showed that the mechanism of bond formation between the acetamide derivatives and tyrosine as a biological molecule occurs mainly through nitrogen atoms. The intramolecular interaction energies between the acetamide derivatives and tyrosine were calculated and the nature of the intermolecular interaction was revealed by natural bond orbital charge (NBO) analysis. The results suggest that acetamide derivatives with bromophenyl and nitrophenyl substitutions are the most potent as anti-HIV drugs. PMID:24082898

  7. 40 CFR 721.275 - Halogenated-N-(2-propenyl)-N-(substituted phenyl) acetamide.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Halogenated-N-(2-propenyl)-N... New Uses for Specific Chemical Substances § 721.275 Halogenated-N-(2-propenyl)-N-(substituted phenyl... identified generically as halogenated-N-(2-propenyl)-N-(substituted phenyl) acetamide (P-83-1085) is...

  8. 40 CFR 721.275 - Halogenated-N-(2-propenyl)-N-(substituted phenyl) acetamide.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Halogenated-N-(2-propenyl)-N... New Uses for Specific Chemical Substances § 721.275 Halogenated-N-(2-propenyl)-N-(substituted phenyl... identified generically as halogenated-N-(2-propenyl)-N-(substituted phenyl) acetamide (P-83-1085) is...

  9. 40 CFR 721.275 - Halogenated-N-(2-propenyl)-N-(substituted phenyl) acetamide.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Halogenated-N-(2-propenyl)-N... New Uses for Specific Chemical Substances § 721.275 Halogenated-N-(2-propenyl)-N-(substituted phenyl... identified generically as halogenated-N-(2-propenyl)-N-(substituted phenyl) acetamide (P-83-1085) is...

  10. 40 CFR 721.225 - 2-Chloro-N-methyl-N-substituted acetamide (generic name).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false 2-Chloro-N-methyl-N-substituted... Specific Chemical Substances § 721.225 2-Chloro-N-methyl-N-substituted acetamide (generic name). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance...

  11. 40 CFR 721.225 - 2-Chloro-N-methyl-N-substituted acetamide (generic name).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false 2-Chloro-N-methyl-N-substituted... Specific Chemical Substances § 721.225 2-Chloro-N-methyl-N-substituted acetamide (generic name). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance...

  12. 40 CFR 721.275 - Halogenated-N-(2-propenyl)-N-(substituted phenyl) acetamide.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Halogenated-N-(2-propenyl)-N... New Uses for Specific Chemical Substances § 721.275 Halogenated-N-(2-propenyl)-N-(substituted phenyl... identified generically as halogenated-N-(2-propenyl)-N-(substituted phenyl) acetamide (P-83-1085) is...

  13. 40 CFR 721.225 - 2-Chloro-N-methyl-N-substituted acetamide (generic name).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false 2-Chloro-N-methyl-N-substituted... Specific Chemical Substances § 721.225 2-Chloro-N-methyl-N-substituted acetamide (generic name). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance...

  14. 40 CFR 721.225 - 2-Chloro-N-methyl-N-substituted acetamide (generic name).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false 2-Chloro-N-methyl-N-substituted... Specific Chemical Substances § 721.225 2-Chloro-N-methyl-N-substituted acetamide (generic name). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance...

  15. 40 CFR 721.275 - Halogenated-N-(2-propenyl)-N-(substituted phenyl) acetamide.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Halogenated-N-(2-propenyl)-N... New Uses for Specific Chemical Substances § 721.275 Halogenated-N-(2-propenyl)-N-(substituted phenyl... identified generically as halogenated-N-(2-propenyl)-N-(substituted phenyl) acetamide (P-83-1085) is...

  16. Amino and Acetamide Functional Group Effects on the Ionization and Fragmentation of Sugar Chains in Positive-Ion Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Yamagaki, Tohru; Sugahara, Kohtaro; Watanabe, Takehiro

    2014-01-01

    To elucidate the influence of amino (-NH2) and acetamide (-NHCOCH3, -NAc) groups in sugar chains on their ionization and fragmentation, cycloamyloses (cyclodextrins, CyDs) and lacto-oligosaccharide are analyzed by MALDI TOF/TOF and ESI Q-TOF mass spectrometry. CyD derivatives substituted by amino or acetamide groups are ideal analytes to extract the function group effects, which are amino-CyD with one hexosamine (HexNH2) and acetamide-CyD with one N-acetyl hexosamine (HexNAc). Interestingly, the relative ion intensities and isotope-like patterns in their product ion spectra depend on the functional groups and ion forms of sugar chains. Consequently, the results indicate that a proton (H+) localizes on the amino group of the amino sugar, and that the proton (H+) induces their fragmentation. Sodium cation (Na+) attachment is independent from amino group and exerts no influence on their fragmentation patterns in amino group except for mono- and disaccharide fragment ions because there is the possibility of the reducing end effect. In contrast, a sodium cation localizes much more frequently on the acetamide group in acetamide-CyDs because the chemical species with HexNAc are stable. Thus, their ions with HexNAc are abundant. These results are consistent with the fragmentation of lacto-neo- N-tetraose and maltotetraose, suggesting that a sodium cation generally localizes much more frequently on the acetamide group in sugar chains.

  17. Discovery of phenyl acetamides as potent and selective GPR119 agonists.

    PubMed

    Zhu, Cheng; Wang, Liping; Zhu, Yuping; Guo, Zack Zhiqiang; Liu, Ping; Hu, Zhiyong; Szewczyk, Jason W; Kang, Ling; Chicchi, Gary; Ehrhardt, Anka; Woods, Andrea; Seo, Toru; Woods, Morgan; van Heek, Margaret; Dingley, Karen H; Pang, Jianmei; Salituro, Gino M; Powell, Joyce; Terebetski, Jenna L; Hornak, Viktor; Campeau, Louis-Charles; Orr, Robert K; Ujjainwalla, Feroze; Miller, Michael; Stamford, Andrew; Wood, Harold B; Kowalski, Timothy; Nargund, Ravi P; Edmondson, Scott D

    2017-03-01

    The paper describes the SAR/SPR studies that led to the discovery of phenoxy cyclopropyl phenyl acetamide derivatives as potent and selective GPR119 agonists. Based on a cis cyclopropane scaffold discovered previously, phenyl acetamides such as compound 17 were found to have excellent GPR119 potency and improved physicochemical properties. Pharmacokinetic data of compound 17 in rat, dog and rhesus will be described. Compound 17 was suitable for QD dosing based on its predicted human half-life, and its projected human dose was much lower than that of the recently reported structurally-related benzyloxy compound 2. Compound 17 was selected as a tool compound candidate for NHP (Non-Human Primate) efficacy studies.

  18. Novel isocyanide-based three-component one-pot synthesis of cyanophenylamino-acetamide derivatives.

    PubMed

    Shaabani, Ahmad; Maleki, Ali; Mofakham, Hamid; Khavasi, Hamid Reza

    2008-01-01

    A one-pot multicomponent synthesis of a novel class of cyanophenylamino-acetamides through the conversion of primary amides to the corresponding nitriles, starting from simple and readily available inputs including 2-aminobenzamide, an aldehyde, and an isocyanide in the presence of p-toluenesulfonic acid as a catalyst, in excellent yields at room temperature in ethanol as a green reaction medium is described.

  19. Synthesis and evaluation of 3-ylideneoxindole acetamides as potent anticancer agents.

    PubMed

    Chiou, Chun-Tang; Lee, Wei-Chun; Liao, Jiahn-Haur; Cheng, Jing-Jy; Lin, Lie-Chwen; Chen, Chih-Yu; Song, Jen-Shin; Wu, Ming-Hsien; Shia, Kak-Shan; Li, Wen-Tai

    2015-06-15

    Indirubin, an active component in the traditional Chinese medicine formula Danggui Longhui Wan, shows promising anticancer effects. Meisoindigo is an analog derived from indirubin, which is less toxic and appears to be even more potent against cancer. In considering meisoindigo as a structural template for the development of new drugs, we designed and synthesized a series of 3-ylideneoxindole acetamides as novel anticancer agents. The acetamides were then evaluated for in vitro and in vivo anticancer activities. The 3-ylideneoxindole acetamides were found to have better anticancer activity than was indirubin-3'-oxime in several cancer cell lines and also displayed a spectrum of activity similar to that of the drug candidate roscovitine, a CDK inhibitor. Among the 3-ylideneoxindole acetamides, compound 10 showed particularly good efficacy. Cell cycle analysis further revealed that compound 10 arrested cells in the G1 phase and caused an increase in the sub-G1 population, indicating that the apoptosis pathway had been induced. In addition, exposure of cells to compound 10 led to the upregulation of the cell-cycle regulator cyclin D1, which was sustained at a high level. In contrast, the same compound induced a short-term elevation in the level of cyclin E, which was followed by a rapid decrease and the attenuation of Rb phosphorylation. Furthermore, a docking model suggests that compound 10 binds to the active site of CDK4. In testing the therapeutic potency of compound 10 on CT26-xenografted BALB/c mice, a significant reduction in tumor size comparable to that of cisplatin was found when administrated via the i.p. route. The mice presented no loss of body weight, indicating that this compound possesses low toxicity. In the future, we are planning in vivo investigations of these new active anticancer agents to better elucidate active mechanisms at the cellular level and thus benefit the development of anticancer therapies.

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

    NASA Astrophysics Data System (ADS)

    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.

  1. Acetamide herbicides and their degradation products in ground water and surface water of the United States, 1993-2003

    USGS Publications Warehouse

    Scribner, Elisabeth A.; Dietze, Julie E.; Thurman, Michael

    2004-01-01

    During 1993 through 2003, the U.S. Geological Survey conducted a number of studies to investigate and document the occurrence, fate, and transport of acetamide herbicides and their degradation products in ground and surface water. As part of these studies, approximately 5,100 water samples were collected and analyzed for the acetamide parent herbicides acetochlor, alachlor, dimethenamid, flufenacet, and metolachlor and their degradation products ethanesulfonic acid, oxanilic acid, and sulfinyl acetic acid. During this period, various analytical methods were developed to detect and measure concentrations of acetamide herbicides and their degradation products in ground water and surface water. Results showed that the degradation products of acetamide herbicides in ground water were detected more frequently and occurred at higher concentrations than their parent compounds. Further study showed that the acetamide herbicides and their degradation products were detected more frequently in surface water than in ground water. In general, the parent compounds were detected at similar or greater frequencies than the degradation products in surface water. The developed methods and data were valuable for acquiring information about the occurrence, fate, and transport of the herbicides and their degradation products and the importance of analyzing for both parent compounds and their degradate products in water-quality studies.

  2. N-[4-(2-Propyn-1-yl-oxy)phen-yl]acetamide.

    PubMed

    Belay, Yonas H; Kinfe, Henok H; Muller, Alfred

    2012-11-01

    The title compound, C(11)H(11)NO(2), was synthesized by chemoselective N-acetyl-ation of 4-amino-phenol followed by reaction with propargyl bromide in the presence of K(2)CO(3). the acetamide and propyn-1-yloxy substituents form dihedral angles of 18.31 (6) and 7.01 (10)°, respectively, with the benzene ring. In the crystal, mol-ecules are linked by N-H⋯O hydrogen bonds into chains along [010]. C-H⋯O and C-H⋯π inter-actions also occur.

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

    SciTech Connect

    Pailloux, Sylvie; Binyamin, Iris; Kim, Sung-jun; Deck, Lorraine M.; Rapko, Brian M.; Hay, Benjamin; Duesler, Eileen N.; Paine, Robert T.

    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.

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

    SciTech Connect

    Redondo, Pilar; Barrientos, Carmen; Largo, Antonio

    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.

  5. Peptide Bond Formation through Gas-phase Reactions in the Interstellar Medium: Formamide and Acetamide as Prototypes

    NASA Astrophysics Data System (ADS)

    Redondo, Pilar; Barrientos, Carmen; Largo, Antonio

    2014-09-01

    A theoretical study of the reactions of NH_4+ with formaldehyde and CH_5+ 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.

  6. Solution-phase parallel synthesis of acyclic nucleoside libraries of purine, pyrimidine, and triazole acetamides.

    PubMed

    Pathak, Ashish K; Pathak, Vibha; Reynolds, Robert C

    2014-09-08

    Molecular diversity plays a pivotal role in modern drug discovery against phenotypic or enzyme-based targets using high throughput screening technology. Under the auspices of the Pilot Scale Library Program of the NIH Roadmap Initiative, we produced and report herein a diverse library of 181 purine, pyrimidine, and 1,2,4-triazole-N-acetamide analogues which were prepared in a parallel high throughput solution-phase reaction format. A set of assorted amines were reacted with several nucleic acid N-acetic acids utilizing HATU as the coupling reagent to produce diverse acyclic nucleoside N-acetamide analogues. These reactions were performed using 24 well reaction blocks and an automatic reagent-dispensing platform under inert atmosphere. The targeted compounds were purified on an automated purification system using solid sample loading prepacked cartridges and prepacked silica gel columns. All compounds were characterized by NMR and HRMS, and were analyzed for purity by HPLC before submission to the Molecular Libraries Small Molecule Repository (MLSMR) at NIH. Initial screening through the Molecular Libraries Probe Production Centers Network (MLPCN) program, indicates that several analogues showed diverse and interesting biological activities.

  7. Growth and characterization of new organic nonlinear optical crystal (R)-2-cyano-N-(1-phenylethyl) acetamide

    SciTech Connect

    Hemaraju, B. C.; Gnana Prakash, A. P.; Madhukar, B. S.; Bhadregowda, D. G.

    2014-04-24

    (R)-2-Cyano-N-(1-phenylethyl) acetamide (RCNPA) single crystals were grown by slow evaporation of the aqueous solution at room temperature (300K) using ethanol. The grown crystals were characterized by single crystal X-ray diffraction, powder X-ray diffraction, FTIR, UV-Vis-NIR transmittance, scanning electron microscopy (SEM) and powder second harmonic generation (SHG)

  8. The Microwave Spectrum of Monodeuterated Acetamide CH_2DC(=O)NH_2

    NASA Astrophysics Data System (ADS)

    Konov, I. A.; Coudert, L. H.; Gutle, C.; Huet, T. R.; Margulès, L.; Motiyenko, R. A.; Møllendal, H.; Guillemin, J.-C.

    2014-06-01

    Acetamide is an oblate asymmetric top displaying almost free internal rotation of its methyl group. The microwave spectrum of the normal species (CH_3C(=O)NH_2) has already been studied and a value of only 25 wn was retrieved for the height of the potential barrier hindering the internal rotation. No spectroscopic results are available about the monodeutared species with a partially deuterated CH_2D methyl group which will be the subject of the present talk. The effects of deuteration on the hindering potential will be investigated first. They lead to qualitative changes of the hindering potential no longer resembling that of the normal species and displaying several inequivalent minima. A determination of the torsional potential will be attempted through an analysis of the microwave spectrum of the monodeuterated species in which torsion-rotation energies are calculated with the approach developed for monodeuterated methanol, accounting for the torsion-rotation Coriolis coupling and for the dependence of the inertia tensor on the torsional angle. A low temperature spectrum, recorded with the MB-FTMW spectrometer in Lille, has already been analyzed and 14 transitions could be assigned up to J=6. Room temperature spectra have also been recorded in the 7-91 and 150-165 GHz frequency ranges and more than 100 transitions have been assigned up to J=16 for the ground torsional state. In the paper, deuteration effects will be discussed and we hope to assign a sufficient number of microwave transitions in order to obtain the first quantitative information about the hindering potential of monodeuterated acetamide. Ilyushin, Alekseev, Dyubko, Kleiner, and Hougen, J. Molec. Spectrosc. 227 (2004) 115 Lauvergnat, Coudert, Klee, and Smirnov, J. Molec. Spectrosc. 256 (2009) 204 Margulès, Coudert, Møllendal, Guillemin, Huet and Janečková, J. Molec. Spectrosc. 254 (2009) 55 Coudert, Zemouli, Motiyenko, Margulès, and Klee, J. Chem. Phys. 140 (2014) 064307

  9. 2-(Quinolin-4-yloxy)acetamides Are Active against Drug-Susceptible and Drug-Resistant Mycobacterium tuberculosis Strains

    PubMed Central

    2016-01-01

    2-(Quinolin-4-yloxy)acetamides have been described as potent in vitro inhibitors of Mycobacterium tuberculosis growth. Herein, additional chemical modifications of lead compounds were carried out, yielding highly potent antitubercular agents with minimum inhibitory concentration (MIC) values as low as 0.05 μM. Further, the synthesized compounds were active against drug-resistant strains and were devoid of apparent toxicity to Vero and HaCat cells (IC50s ≥ 20 μM). In addition, the 2-(quinolin-4-yloxy)acetamides showed intracellular activity against the bacilli in infected macrophages with action similar to rifampin, low risk of drug–drug interactions, and no sign of cardiac toxicity in zebrafish (Danio rerio) at 1 and 5 μM. Therefore, these data indicate that this class of compounds may furnish candidates for future development to, hopefully, provide drug alternatives for tuberculosis treatment. PMID:26985307

  10. Acetamide hydrolyzing activity of Bacillus megaterium F-8 with bioremediation potential: optimization of production and reaction conditions.

    PubMed

    Sogani, Monika; Bakre, Prakash P; Mathur, Nupur; Sharma, Pratibha; Bhatnagar, Pradeep

    2014-01-01

    Bacillus megaterium F-8 exhibited an intracellular acetamide hydrolyzing activity (AHA) when cultivated in modified nutrient broth with 3% tryptone, 1.5% yeast extract, and 0.5% sodium chloride, at pH 7.2, 45 °C for 24 h. Maximum AHA was recorded in the culture containing 0.1 M of sodium phosphate buffer, (pH 7.5) at 45 °C for 20 min with 0.2 % of acetonitrile and resting cells of B. megaterium F-8 equivalent to 0.2 ml culture broth. This activity was stable up to 55 °C and was completely inactivated at or above 60 °C. Maximum acyl transferase activity (ATA) was recorded in the reaction medium containing 0.1 M of potassium phosphate buffer, (pH 8.0) at 55 °C for 5 min with 0.85 mM of acetamide as acyl donor and hydroxylamine hydrochloride as acyl acceptor and resting cells of B. megaterium F-8 equivalent to 0.94 mg cells (dry weight basis). This activity was stable up to 60 °C and a rapid decline in enzyme activity was recorded above it. Under the optimized conditions, this organism hydrolyzed various nitriles and amides such as propionitrile, propionamide, caprolactam, acetamide, and acrylamide to corresponding acids. Acyl group transfer capability of this organism was used for the production of acetohydroxamic acid. ATA of B. megaterium F-8 showed broad substrate specificity such as for acetamide followed by propionamide, acrylamide, and lactamide. This amide hydrolyzing and amidotransferase activity of B. megaterium F-8 has potential applications in enzymatic synthesis of hydroxamic acids and bioremediation of nitriles and amides contaminated soil and water system.

  11. Changes in concentrations of triazine and acetamide herbicides by bank filtration, ozonation, and chlorination in a public water supply

    USGS Publications Warehouse

    Verstraeten, Ingrid M.; Thurman, E.M.; Lindsey, M.E.; Lee, E.C.; Smith, R.D.

    2002-01-01

    The changes in triazine and acetamide concentrations in water during natural and artificial treatment by bank filtration, ozonation, filtration, and chlorination were measured at the well field and drinking water treatment plant of Lincoln, Nebraska, USA. The city's groundwater supply is affected by induced infiltration and transport of triazines and acetamide herbicides from the Platte River in late spring and early summer. The objective of the study was to evaluate the effect of infiltration and treatment on the presence of triazines and acetamides in drinking water. Samples of river water, well water, and public supply water at various stages of water treatment were collected from 1997-1999 during spring-runoff when the presence of herbicides in the Platte River is largest. In 1999, parent compounds were reduced by 76% of the concentration present in river water (33% by bank filtration, 41% by ozonation, and 1.5% by chlorination). Metabolites of herbicides for which analytical techniques existed were reduced by 21% (plus 26% by bank filtration, minus 23% by ozonation, and minus 24% by chlorination). However, increases in concentrations of specific metabolite compounds were identified after bank filtration and ozonation. After bank filtration, increases in cyanazine amide, cyanazine acid, and deethylcyanazine acid were identified. After ozonation, concentrations of deisopropylatrazine, deethylatrazine, didealkylatrazine, atrazine amide-I, hydroxydeethylatrazine, hydroxydeisopopylatrazine, deethylcyanazine acid, and deethylcyanazine increased. Concentrations of cyanazine acid and ethanesulfonic and oxanilic acids of acetamides decreased during ozonation. Our findings suggest that bank filtration and ozonation of water in part can shift the assessment of risk to human health associated with the consumption of the water from the parent compounds to their degradation products.

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

    PubMed

    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.

  13. A triclinic polymorph of N-[4-(4-methyl-benzene-sulfonamido)-phenyl-sulfon-yl]acetamide.

    PubMed

    Hayat, Khizar; Asghar, Muhammad Nadeem; Tahir, M Nawaz; Shafiq, Muhammad; Ahmad, Dildar

    2012-04-01

    In the asymmetric unit of the title compound, C(15)H(16)N(2)O(5)S(2), there are two symmetry-independent mol-ecules which adopt similar conformations, with dihedral angles between the aromatic rings of 59.30 (8) and 61.81 (8)°, and dihedral angles between acetamide group and the benzene ring of 77.08 (10) and 78.40 (10)°. Each type of mol-ecule forms similar one-dimensional polymeric structures extending along the b axis via N-H⋯O hydrogen bonds. These hydrogen bonds generate two types of centrosymmetric motifs, R(2) (2)(8) and R(2) (2)(20). Moreover C-H⋯O inter-actions assemble the mol-ecules into a three-dimensional framework. The crystal structure was determined from a non-merohedral twin [ratio of the twin components = 0.322 (4):0.678 (4)].

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

    PubMed Central

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

    2012-01-01

    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 IC50 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 (IC50 = 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 (IC50 = 280 nM) provides a new lead that incorporates an adamantyl group surrogate and should enable further series diversification. PMID:23040895

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

    PubMed

    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.

  16. A HPLC method for the quantification of butyramide and acetamide at ppb levels in hydrogeothermal waters

    SciTech Connect

    Gracy Elias; Earl D. Mattson; Jessica E. Little

    2012-01-01

    A quantitative analytical method to determine butyramide and acetamide concentrations at the low ppb levels in geothermal waters has been developed. The analytes are concentrated in a preparation step by evaporation and analyzed using HPLC-UV. Chromatographic separation is achieved isocratically with a RP C-18 column using a 30 mM phosphate buffer solution with 5 mM heptane sulfonic acid and methanol (98:2 ratio) as the mobile phase. Absorbance is measured at 200 nm. The limit of detection (LOD) for BA and AA were 2.0 {mu}g L{sup -1} and 2.5 {mu}g L{sup -1}, respectively. The limit of quantification (LOQ) for BA and AA were 5.7 {mu}g L{sup -1} and 7.7 {mu}g L{sup -1}, respectively, at the detection wavelength of 200 nm. Attaining these levels of quantification better allows these amides to be used as thermally reactive tracers in low-temperature hydrogeothermal systems.

  17. Dielectric Relaxations of (Acetamide + Electrolyte) Deep Eutectic Solvents in the Frequency Window, 0.2 ≤ ν/GHz ≤ 50: Anion and Cation Dependence.

    PubMed

    Mukherjee, Kallol; Das, Anuradha; Choudhury, Samiran; Barman, Anjan; Biswas, Ranjit

    2015-06-25

    Dielectric relaxation (DR) measurements in the frequency range 0.2 ≤ ν/GHz ≤ 50 have been carried out for neat molten acetamide and six different (acetamide + electrolyte) deep eutectic solvents (DESs) for investigating ion effects on DR dynamics in these ionic DESs. Electrolytes used are lithium salts of bromide (LiBr), nitrate (LiNO3), and perchlorate (LiClO4); sodium salts of perchlorate (NaClO4) and thiocyante (NaSCN); and potassium thiocyanate (KSCN). With these electrolytes acetamide forms DESs approximately at an 80:20 mol ratio. Simultaneous fits to the measured permittivity (ε′) and loss (ε″) spectra of these DESs at ∼293 K require a sum of four Debye (4-D) processes with relaxation times spread over picosecond to nanosecond regime. In contrast, DR spectra for neat molten acetamide (∼354 K) depict 2-D relaxation with time constants ∼50 ps and ∼5 ps. For both the neat and ionic systems, the undetected dispersion, ε∞ – n(D)2, remains to be ∼3–4. Upon comparison, measured DR dynamics reveal pronounced anion and cation effects. Estimated static dielectric constants (ε0) from fits for these DESs cover the range 12 < ε0 < 30 and are remarkably lower than that (ε0 ∼ 64) measured for molten acetamide at ∼354 K. Hydrodynamic effective rotation volumes (Veff) estimated from the slowest DR relaxation time constants vary with ion identity and are much smaller than the molecular volume of acetamide. This decrease of ε0 and Veff is attributed respectively to the pinning of acetamide molecules by ions and orientation jumps and undetected portion to the limited frequency coverage employed in these measurements

  18. [Factors affecting formation of THMs during dissolved organic nitrogen acetamide chlorination in drinking water].

    PubMed

    Chu, Wen-Hai; Gao, Nai-Yun; Zhao, Shi-Jia; Li, Qing-Song

    2009-05-15

    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.

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

    PubMed

    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

  20. Crystal structures of two C,N-disubstituted acetamides: 2-(4-chloro­phen­yl)-N-(2-iodo­phen­yl)acetamide and 2-(4-chloro­phen­yl)-N-(pyrazin-2-yl)acetamide

    PubMed Central

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

    2016-01-01

    In the crystal of 2-(4-chloro­phen­yl)-N-(2-iodo­phen­yl)acetamide, C14H11ClINO, mol­ecules are linked by a combination of N—H⋯O and C—H⋯O hydrogen bonds to form a C(4)C(4)[R 2 1(7)] chain of rings and chains of this type are linked by a combination of C—Cl⋯π(arene) and C—I⋯π(arene) inter­actions to form deeply puckered twofold inter­woven sheets. In the crystal of 2-(4-chloro­phen­yl)-N-(pyrazin-2-yl)acetamide, C12H10ClN3O, mol­ecules are linked into complex sheets by N—H⋯N, C—H⋯N and C—H⋯O hydrogen bonds, and by C—H⋯π(arene) inter­actions. PMID:27920915

  1. Regioselective formation of 2,4,5-trisubstituted oxazoles through transition-metal free heterocyclization of 1,3-diynes with N,O-bis(trimethylsiyl)acetamide.

    PubMed

    Zhang, Liang; Zhao, Xiaoming

    2015-01-16

    Transition-metal free heterocyclization reaction of 1,3-diynes with N,O-bis(trimethylsiyl)acetamide was accomplished in the presence of t-BuOK and acetonitrile at 120 °C. This method regioselectively gave 2,4,5-trisubstituted oxazoles in yields up to 97%.

  2. Collective dynamic dipole moment and orientation fluctuations, cooperative hydrogen bond relaxations, and their connections to dielectric relaxation in ionic acetamide deep eutectics: Microscopic insight from simulations

    NASA Astrophysics Data System (ADS)

    Das, Suman; Biswas, Ranjit; Mukherjee, Biswaroop

    2016-08-01

    The paper reports a detailed simulation study on collective reorientational relaxation, cooperative hydrogen bond (H-bond) fluctuations, and their connections to dielectric relaxation (DR) in deep eutectic solvents made of acetamide and three uni-univalent electrolytes, lithium nitrate (LiNO3), lithium bromide (LiBr), and lithium perchlorate (LiClO4). Because cooperative H-bond fluctuations and ion migration complicate the straightforward interpretation of measured DR timescales in terms of molecular dipolar rotations for these conducting media which support extensive intra- and inter-species H-bonding, one needs to separate out the individual components from the overall relaxation for examining the microscopic origin of various timescales. The present study does so and finds that reorientation of ion-complexed acetamide molecules generates relaxation timescales that are in sub-nanosecond to nanosecond range. This explains in molecular terms the nanosecond timescales reported by recent giga-Hertz DR measurements. Interestingly, the simulated survival timescale for the acetamide-Li+ complex has been found to be a few tens of nanosecond, suggesting such a cation-complexed species may be responsible for a similar timescale reported by mega-Hertz DR measurements of acetamide/potassium thiocyanate deep eutectics near room temperature. The issue of collective versus single particle relaxation is discussed, and jump waiting time distributions are determined. Dependence on anion-identity in each of the cases has been examined. In short, the present study demonstrates that assumption of nano-sized domain formation is not required for explaining the DR detected nanosecond and longer timescales in these media.

  3. Collective dynamic dipole moment and orientation fluctuations, cooperative hydrogen bond relaxations, and their connections to dielectric relaxation in ionic acetamide deep eutectics: Microscopic insight from simulations.

    PubMed

    Das, Suman; Biswas, Ranjit; Mukherjee, Biswaroop

    2016-08-28

    The paper reports a detailed simulation study on collective reorientational relaxation, cooperative hydrogen bond (H-bond) fluctuations, and their connections to dielectric relaxation (DR) in deep eutectic solvents made of acetamide and three uni-univalent electrolytes, lithium nitrate (LiNO3), lithium bromide (LiBr), and lithium perchlorate (LiClO4). Because cooperative H-bond fluctuations and ion migration complicate the straightforward interpretation of measured DR timescales in terms of molecular dipolar rotations for these conducting media which support extensive intra- and inter-species H-bonding, one needs to separate out the individual components from the overall relaxation for examining the microscopic origin of various timescales. The present study does so and finds that reorientation of ion-complexed acetamide molecules generates relaxation timescales that are in sub-nanosecond to nanosecond range. This explains in molecular terms the nanosecond timescales reported by recent giga-Hertz DR measurements. Interestingly, the simulated survival timescale for the acetamide-Li(+) complex has been found to be a few tens of nanosecond, suggesting such a cation-complexed species may be responsible for a similar timescale reported by mega-Hertz DR measurements of acetamide/potassium thiocyanate deep eutectics near room temperature. The issue of collective versus single particle relaxation is discussed, and jump waiting time distributions are determined. Dependence on anion-identity in each of the cases has been examined. In short, the present study demonstrates that assumption of nano-sized domain formation is not required for explaining the DR detected nanosecond and longer timescales in these media.

  4. Comparison of the crystal structure and molecular models of N,N-dissobutyl-2-(octylphenylphosphinyl)acetamide(CMPO).

    SciTech Connect

    Rogers, R. D.; Rollins, A. N.; Gatrone, R. C.; Horwitz, E. P.; Chemistry; Northern Illinois Univ.

    1995-01-01

    The crystal structure of N,N-diisobutyl-2-(octylphenylphosphinyl)acetamide, or CMPO was recently determined. The compound crystallizes in the space group P2{sub 1}/c with a=13.446(6),b=22.280(7),c=17.217(7) Angstroms, {beta}=92.07(4) degrees, and D{sub calc}=1.05 g/cm3 for Z=8 @20 C. Molecular mechanics, molecular dynamics, and MNDO calculations were also performed on CMPO utilizing the SYBYL suite of programs. The results from these calculations are compared to the crystal structure and to similar calculations performed on CMPO using ALCHEMY. In general, the results from the calculations agree fairly well with the parameters from the crystal structure.

  5. Thermal phase diagram of acetamide-benzoic acid and benzoic acid-phthalimide binary systems for solar thermal applications

    NASA Astrophysics Data System (ADS)

    Kumar, Rohitash; Kumar, Ravindra; Dixit, Ambesh

    2016-05-01

    Thermal properties of Acetamide (AM) - Benzoic acid (BA) and Benzoic acid (BA) - Phthalimide (PM) binary eutectic systems are theoretically calculated using thermodynamic principles. We found that the binary systems of AM-BA at 67.6 : 32.4 molar ratio, BA-PM at 89.7 : 10.3 molar ratio form eutectic mixtures with melting temperatures ~ 54.5 °C and 114.3 °C respectively. Calculated latent heat of fusion for these eutectic mixtures are 191 kJ/kg and 146.5 kJ/kg respectively. These melting temperatures and heat of fusions of these eutectic mixtures make them suitable for thermal energy storage applications in solar water heating and solar cooking systems.

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

    NASA Astrophysics Data System (ADS)

    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.

  7. Triethylenetetramine penta- and hexa-acetamide ligands and their ytterbium complexes as paraCEST contrast agents for MRI.

    PubMed

    Burdinski, Dirk; Lub, Johan; Pikkemaat, Jeroen A; Moreno Jalón, Diana; Martial, Sophie; Del Pozo Ochoa, Carolina

    2008-08-21

    The ligand triethylenetetramine-N,N,N',N'',N''',N'''-hexaacetamide (ttham) was synthesized with the aim of forming lanthanide complexes suitable as contrast agents for magnetic resonance imaging applications utilizing the chemical exchange-dependent saturation transfer (CEST) effect. It was designed to exclude water molecules from the first coordination sphere and provide a high number of CEST active amide protons per lanthanide ion. The ligand was characterized by its protonation behavior and its complexation properties with ytterbium ions in aqueous solution. The basicity of the ttham backbone amine protons decreases in the order N(central(1)) > N(terminal(1)) > N(terminal(2)) > N(central(2)), as deduced from NMR titration experiments and from a comparison of its protonation constants with those of two ttham derivatives, in which either a terminal (N-benzyl-triethylenetetramine-N,N',N'',N''',N'''-pentaacetamide, 1bttpam) or a central acetamide group (N'-benzyl-triethylenetetramine-N,N,N'',N''',N'''-pentaacetamide, 4bttpam) is substituted with a benzyl group. This protonation sequence results from the combined influence of inductive effects, the intramolecular hydrogen bonding network, and the Coulomb repulsion between protonated ammonium groups. The ytterbium complex of ttham, [Yb(ttham)]Cl(3), is coordinatively frustrated. Due to steric constraints, in addition to the four backbone nitrogen atoms, only three of the four symmetry-equivalent terminal acetamide donors can coordinate simultaneously to the ytterbium ion, and the dangling fourth one exchanges quickly with the other three. The ytterbium complexes of a total of five ligands (ttham, 1bttpam, 4bttpam, 2,2',2''-triaminotriethylaminehexaacetamide (ttaham), and diethylenetriamine-N,N,N',N'',N''-pentaacetamide (dtpam)) were studied with respect to their CEST properties. In solution, all of these complexes have a low symmetry. The presence of multiple magnetically different amide groups in each complex

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

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

    2016-09-01

    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 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.

  10. 2-(4-Chloro-3,3,7-trimethyl-2,3-dihydro-1H-indol-2-yl-idene)-2-cyano-acetamide.

    PubMed

    Helliwell, Madeleine; Baradarani, Mehdi M; Alyari, Maryam; Afghan, Arash; Joule, John A

    2012-01-01

    Reaction of 2-(4-chloro-3,3,7-trimethyl-2,3-dihydro-1H-indol-2-yl-idene)propane-dial with hydroxyl-amine gives the title compound, C(14)H(14)ClN(3)O, in which the ring N atom is essentially planar [sum of angles around the ring N atom = 361°], indicating conjugation with the 2-cyano-acryl-amide unit. The orientation of the acetamide group arises from intra-molecular hydrogen bonding between the indole N-H and carbonyl groups. In the crystal, inversion-related acetamide groups form N-H⋯O hydrogen-bonded dimers in graph-set R(2) (2)(8) motifs, whilst dimers are also formed by pairs of amine-nitrile N-H⋯N hydrogen bonds in R(2) (2)(12) motifs. These inter-actions together generate ribbons that propagate along the b-axis direction.

  11. 2-(2,4-Dioxy-1,2,3,4-Tetrahydropyrimidin-1-yl)-N-(4-Phenoxyphenyl)-Acetamides as a Novel Class of Cytomegalovirus Replication Inhibitors

    PubMed Central

    Babkov, D. A.; Paramonova, M. P.; Ozerov, A. A.; Khandazhinskaya, A. L.; Snoeck, R.; Andrei, G.; Novikov, M. S.

    2015-01-01

    A series of novel uracil derivatives, bearing N-(4-phenoxyphenyl)acetamide moiety at N3 of a pyrimidine ring, has been synthesized. Their antiviral activity has been evaluated. It has been found that the novel compounds possess high inhibitory activity against replication of human cytomegalovirus (AD-169 and Davis strains) in HEL cell cultures. In addition, some of the derivatives proved to be inhibitory against varicella zoster virus. PMID:26798502

  12. Natural bond orbital analysis, electronic structure and vibrational spectral analysis of N-(4-hydroxyl phenyl) acetamide: A density functional theory

    NASA Astrophysics Data System (ADS)

    Govindasamy, P.; Gunasekaran, S.; Ramkumaar, G. R.

    2014-09-01

    The Fourier transform infrared (FT-IR) and FT-Raman spectra of N-(4-hydroxy phenyl) acetamide (N4HPA) of painkiller agent were recorded in the region 4000-450 cm-1 and 4000-50 cm-1 respectively. Density functional theory (DFT) has been used to calculate the optimized geometrical parameter, atomic charges, and vibrational wavenumbers and intensity of the vibrational bands. The computed vibrational wave numbers were compared with the FT-IR and FT-Raman experimental data. The computational calculations at DFT/B3LYP level with 6-31G(d,p), 6-31++G(d,p), 6-311G(d,p) and 6-311++G(d,p) basis sets. The complete vibrational assignments were performed on the basis of the potential energy distribution (PED) of the vibrational modes calculated using Vibrational energy distribution analysis (VEDA 4) program. The oscillator’s strength calculated by TD-DFT and N4HPA is approach complement with the experimental findings. The NMR chemical shifts 13C and 1H were recorded and calculated using the gauge independent atomic orbital (GIAO) method. The molecular electrostatic potential (MESP) and electron density surfaces of the molecule were constructed. The Natural charges and intermolecular contacts have been interpreted using Natural Bond orbital (NBO) analysis the HOMO-LUMO energy gap has been calculated. The thermodynamic properties like entropy, heat capacity and zero vibrational energy have been calculated.

  13. Natural bond orbital analysis, electronic structure and vibrational spectral analysis of N-(4-hydroxyl phenyl) acetamide: a density functional theory.

    PubMed

    Govindasamy, P; Gunasekaran, S; Ramkumaar, G R

    2014-09-15

    The Fourier transform infrared (FT-IR) and FT-Raman spectra of N-(4-hydroxy phenyl) acetamide (N4HPA) of painkiller agent were recorded in the region 4000-450 cm(-1) and 4000-50 cm(-1) respectively. Density functional theory (DFT) has been used to calculate the optimized geometrical parameter, atomic charges, and vibrational wavenumbers and intensity of the vibrational bands. The computed vibrational wave numbers were compared with the FT-IR and FT-Raman experimental data. The computational calculations at DFT/B3LYP level with 6-31G(d,p), 6-31++G(d,p), 6-311G(d,p) and 6-311++G(d,p) basis sets. The complete vibrational assignments were performed on the basis of the potential energy distribution (PED) of the vibrational modes calculated using Vibrational energy distribution analysis (VEDA 4) program. The oscillator's strength calculated by TD-DFT and N4HPA is approach complement with the experimental findings. The NMR chemical shifts 13C and 1H were recorded and calculated using the gauge independent atomic orbital (GIAO) method. The molecular electrostatic potential (MESP) and electron density surfaces of the molecule were constructed. The Natural charges and intermolecular contacts have been interpreted using Natural Bond orbital (NBO) analysis the HOMO-LUMO energy gap has been calculated. The thermodynamic properties like entropy, heat capacity and zero vibrational energy have been calculated.

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

    PubMed Central

    2015-01-01

    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 binding mode, novel thio- and sulfinylacetamide and ethanamine analogues of (±)-1 were synthesized wherein (1) the diphenyl rings were substituted with methyl, trifluoromethyl, and halogen substituents and (2) substituents were added to the terminal amide/amine nitrogen. Halogen substitution of the diphenyl rings of (±)-1 gave several amide analogues with improved binding affinity for DAT and robust selectivity over the serotonin transporter (SERT), whereas affinity improved at SERT over DAT for the p-halo-substituted amine analogues. Molecular docking studies, using a subset of analogues with DAT and SERT homology models, and functional data obtained with DAT (A480T) and SERT (T497A) mutants defined a role for TM10 in the substrate/inhibitor S1 binding sites of DAT and SERT. PMID:24494745

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

    PubMed

    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.

  16. The in vivo melanocytotoxicity and depigmenting potency of N-2,4-acetoxyphenyl thioethyl acetamide in the skin and hair.

    PubMed

    Jimbow, M; Marusyk, H; Jimbow, K

    1995-10-01

    It has been shown previously that N-acetyl-4-S-cysteaminylphenol (N-Ac-4-S-CAP) is a tyrosinase substrate and a potent depigmenting agent of dark skin and black hair. The present study evaluated the depigmenting potency of an acetyl derivative of N-Ac-4-S-CAP, N-2,4-acetoxyphenyl thioethyl acetamide (NAP-TEA) in the skin and hair. We tested for (i) in vitro metabolites in the skin after topical application, and (ii) in vivo depigmenting potency in the skin and hair. We found that NAP-TEA was stable in water, but was converted to N-Ac-4-S-CAP after topical application to human skin. Therefore, although NAP-TEA was not a tyrosinase substrate, it could react with tyrosinase after being converted to N-Ac-4-S-CAP by O-deacetylation in vivo. NAP-TEA produced marked depigmentation of dark skin (Yucatan pig) after daily topical application. When given by intraperitoneal injection, it resulted in complete loss of hair colour (white) grown at the epilated site in adult C57 black mice after daily administration for 10 days, and incomplete loss of coat colour (silver grey) in newborn C57 black mice after a single administration. The depigmentation of the skin and hair was reversible. Split-dopa preparation and electron microscopy indicated that this depigmentation is primarily related to (i) a marked decrease in the number of functioning melanocytes and melanized melanosomes, (ii) a decrease in the number of melanosomes transferred to keratinocytes, and (iii) selective degeneration/inactivation of melanocytes, and deposition of melanin-like material in the Golgi cisternae, coated vesicles and melanosomes, where tyrosinase is reported to be located. We propose the NAP-TEA is converted in vivo to N-Ac-4-S-CAP which, via interaction with tyrosinase, causes reversible depigmentation of the skin and hair.

  17. 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.

    PubMed

    Das, Anuradha; Das, Suman; Biswas, Ranjit

    2015-01-21

    Temperature dependent relaxation dynamics, particle motion characteristics, and heterogeneity aspects of deep eutectic solvents (DESs) made of acetamide (CH3CONH2) and urea (NH2CONH2) have been investigated by employing time-resolved fluorescence measurements and all-atom molecular dynamics simulations. Three different compositions (f) for the mixture [fCH3CONH2 + (1 - f)NH2CONH2] 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 (α2) 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.

  18. 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

    SciTech Connect

    Das, Anuradha; Das, Suman; Biswas, Ranjit

    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.

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

    PubMed

    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.

  20. Discovery and Optimization of N-(4-(3-Aminophenyl)thiazol-2-yl)acetamide as a Novel Scaffold Active against Sensitive and Resistant Cancer Cells.

    PubMed

    Millet, Antoine; Plaisant, Magali; Ronco, Cyril; Cerezo, Michaël; Abbe, Patricia; Jaune, Emilie; Cavazza, Elisa; Rocchi, Stéphane; Benhida, Rachid

    2016-09-22

    Cancer is the second cause of deaths worldwide and is forecasted to affect more that 22 million people in 2020. Despite dramatic improvement in its care over the last two decades, the treatment of resistant forms of cancer is still an unmet challenge. Thus, innovative and efficient treatments are still needed. In this context, we report herein the synthesis and the evaluation of a new class of bioactive molecules belonging to the N-(4-(3-aminophenyl(thiazol-2-yl)acetamide family. Structure-activity relationships could be driven and resulted in the discovery of lead compound 6b. The latter display high in vitro potency against both sensitive and resistant cancer cell lines on three models: melanoma, pancreatic cancer, and chronic myeloid leukemia (CML). 6b leads to cell death by concomitant induction of apoptosis and autophagy, shows good pharmacokinetic properties, and demonstrates a significant reduction of tumor growth in vivo on A375 xenograft model in mice.

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

    NASA Astrophysics Data System (ADS)

    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.

  2. Design, synthesis, pharmacological evaluation and descriptor based similarities study of N,N-diphenyl-2-[4-(substituted phenyl)piperazin-1-yl]acetamides as potential antipsychotics.

    PubMed

    Dash, Radha Charan; Bhosale, Sharad H; Shelke, Suhas M; Suryawanshi, Mugdha R; Mahadik, Kakasaheb R

    2012-11-01

    A series of novel N,N-diphenyl-2-[4-(substituted phenyl)piperazin-1-yl]acetamides was designed, synthesized and evaluated for anti-dopaminergic activity, anti-serotonergic activity and catalepsy induction studies in mice as an approach to novel potential antipsychotic agent. Antipsychotic activity of these compounds in terms of blocking of dopaminergic transmission was evaluated by their ability to inhibit apomorphine induced climbing behavior in mice and antiserotonergic activity of synthesized compounds was assessed by studying inhibition of 5-HTP induced head twitches. All the synthesized compounds were found to exhibit anti-dopaminergic and anti-serotonergic activity in behavioral models. The compound 3f showed better antipsychotic potential among the different synthesized compounds. The descriptor based similarities study for blood brain permeation established a good similarity between the synthesized compounds with standard atypical antipsychotics.

  3. Synthesis, crystal structure and DFT studies of N-(4-acetyl-5,5-dimethyl-4,5-dihydro-1,3,4-thiadiazol-2-yl)acetamide

    NASA Astrophysics Data System (ADS)

    Gautam, P.; Gautam, D.; Chaudhary, R. P.

    2013-12-01

    The title compound N-(4-acetyl-5,5-dimethyl-4,5-dihydro-1,3,4-thiadiazol-2-yl)acetamide ( III) was obtained from the reaction of 2-(propan-2-ylidene)hydrazinecarbothioamide ( II) with acetic anhydride instead of formation of the desired thiosemcarbazide derivative of Meldrum acid. The structures of II and III were established by elemental analysis, IR, NMR, Mass and X-ray crystallographic studies. II crystallizes in triclinic system, sp. gr. Z = 2; III crystallizes in the monoclinic system, sp. gr. P21/ c, Z = 8. Density functional theory (DFT) calculations have been carried out for III. 1H and 13C NMR of III has been calculated and correlated with experimental results.

  4. Synthesis, crystal structure and DFT studies of N-(4-acetyl-5,5-dimethyl-4,5-dihydro-1,3,4-thiadiazol-2-yl)acetamide

    SciTech Connect

    Gautam, P.; Gautam, D.; Chaudhary, R. P.

    2013-12-15

    The title compound N-(4-acetyl-5,5-dimethyl-4,5-dihydro-1,3,4-thiadiazol-2-yl)acetamide (III) was obtained from the reaction of 2-(propan-2-ylidene)hydrazinecarbothioamide (II) with acetic anhydride instead of formation of the desired thiosemcarbazide derivative of Meldrum acid. The structures of II and III were established by elemental analysis, IR, NMR, Mass and X-ray crystallographic studies. II crystallizes in triclinic system, sp. gr. P-bar1 Z = 2; III crystallizes in the monoclinic system, sp. gr. P2{sub 1}/c, Z = 8. Density functional theory (DFT) calculations have been carried out for III. {sup 1}H and {sup 13}C NMR of III has been calculated and correlated with experimental results.

  5. Synthesis, characterization and biological screening of N-substituted derivatives of 5-benzyl-1,3,4-oxadiazole-2yl-2"-sulfanyl acetamide.

    PubMed

    Siddiqui, Sabahat Zahra; Rehman, Azizur; Abbasi, Muhammad Athar; Abbas, Nadia; Khan, Khalid Mohammed; Ashraf, Muhammad; Ejaz, Syeda Abida

    2013-05-01

    A series of new N-substituted derivatives of 5-benzyl-1, 3, 4-oxadiazole-2yl-2"-sulfanyl acetamide (6a-n) were synthesized in three phases. The first phase involved the sequentially converting phenyl acetic acid into ester, hydrazide and finally cyclized in the presence of CS2 to afford 5-benzyl-1, 3, 4-oxadiazole-2-thiol. In the second phase N-substituted-2-bromoacetamides were prepared by reacting substituted amines with bromoacetyl bromide in basic media. In the third phase, 5-benzyl-1,3,4-oxadiazole-2-thiol was stirred with N-substituted-2-bromoacetamides in the presence of N,N-dimethyl formamide (DMF) and sodium hydride (NaH) to get the target compounds. Spectral techniques were used to confirm the structures of synthesized compounds. Synthesized compounds were screened against butyrylcho linesterase (BChE), acetylcholinesterase (AChE), and lipoxygenase enzymes (LOX) and were found to be relatively more active against acetylcholinesterase.

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

    PubMed

    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.

  7. Synthesis, antidepressant evaluation and QSAR studies of novel 2-(5H-[1,2,4]triazino[5,6-b]indol-3-ylthio)-N-(substituted phenyl)acetamides.

    PubMed

    Shelke, Suhas M; Bhosale, Sharad H

    2010-08-01

    In search for novel antidepressants, a series of 2-(5H-[1,2,4]triazino[5,6-b]indol-3-ylthio)-N-(substituted phenyl)acetamides was synthesized and screened for potential antidepressant activity by tail suspension test (TST) in mice. Number of synthesized compounds exhibited impressive antidepressant activity, measured in terms of percentage decrease in immobility duration (%DID). QSAR analysis was also undertaken which correlated three parameters FOSA, PISA, and glob with biological activity.

  8. Microwave-assisted synthesis, structural elucidation and biological assessment of 2-(2-acetamidophenyl)-2-oxo-N phenyl acetamide and N-(2-(2-oxo-2(phenylamino)acetyl)phenyl)propionamide derivatives

    NASA Astrophysics Data System (ADS)

    Ghazzali, Mohamed; El-Faham, Ayman; Abdel-Megeed, Ahmed; Al-Farhan, Khalid

    2012-04-01

    A facile solid-state synthesis of 2-(2-acetamidophenyl)-2-oxo-N phenyl acetamide and N-(2-(2-oxo-2(phenylamino)acetyl)phenyl)propionamide six derivatives has been achieved by microwave promoted condensation of N-acylisatin or N-propionylisatin with various aniline derivatives. The six products were characterized by IR and NMR (H1 and C13). Only two of them, The N-[2-(4-Bromo-phenylaminooxalyl)-phenyl]-propionamide and 2-(2-Acetylamino-phenyl)-2-oxo-N-p-tolyl-acetamide molecular structures were verified by X-ray single-crystal diffraction. The Br⋯Br intermolecular interaction in the crystal structure of N-[2-(4-Bromo-phenylaminooxalyl)-phenyl]-propionamide was evaluated by DFT/B3LYP calculation. The antimicrobial activity was evaluated against eight bacterial strains and two fungal species. The N-[2-(4-Bromo-phenylaminooxalyl)-phenyl]-propionamide and 2-(2-Acetylamino-phenyl)-2-oxo-N-p-tolyl-acetamide exhibit selective high inhibitory effects against Aspergillus niger and Staphylococcus aureus, respectively.

  9. Synthesis of 2-{(5-phenyl-1,3,4-Oxadiazol-2-yl)sulfanyl}-N-substituted acetamides as potential antimicrobial and hemolytic agents.

    PubMed

    Rehman, Aziz-ur; Abbasi, Muhammad Athar; Siddiqui, Sabahat Zahra; Ahmad, Irshad; Shahid, Muhammad; Subhani, Zinayyera

    2016-05-01

    A new series of N-substituted derivatives of 2-{(5-phenyl-1,3,4-Oxadiazol-2-yl)sulfanyl}acetamides was synthesized. The synthesis was carried out by converting benzoic acid (1) into ethyl benzoate (2), benzohydrazide (3) and then 5-pheny-1,3,4-Oxadiazol-2-thiol (4) step by st0ep. The target compounds 6a-p were synthesized by reaction of compound 4 with equimolar ratios of different N-alkyl/aryl substituted 2-bromoacetamide (5a-p) in the presence of DMF and sodium hydride (NaH). The spectral (EI-MS, IR, (1)H-NMR) characterization of all the synthesized compounds reveal their successful synthesis. The compounds were also screened for antimicrobial & hemolytic activity and most of them were found to be active against the selected microbial species at variable extent relative to reference standards. But 6h was the most active against the selected panel of microbes. This series showed less toxicity and may be considered for further biological screening and application trial except 6m, possessing higher cytotoxicity.

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

    SciTech Connect

    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.

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

    PubMed

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

    2008-12-15

    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 x 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.

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

    NASA Astrophysics Data System (ADS)

    Tripathy, Satya N.; Wojnarowska, Zaneta; Knapik, Justyna; Shirota, Hideaki; Biswas, Ranjit; Paluch, Marian

    2015-05-01

    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 (10-1-106 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.

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

    SciTech Connect

    Tripathy, Satya N. Wojnarowska, Zaneta; Knapik, Justyna; Paluch, Marian; Shirota, Hideaki; Biswas, Ranjit

    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.

  14. 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.

    PubMed

    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.

  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.

    PubMed

    Mishra, Pradeep; Kaur, Suneet; Sharma, Amar Nath; Jolly, Ravinder S

    2016-01-01

    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 the best of

  16. 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

    USGS Publications Warehouse

    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

  17. 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

    PubMed Central

    Mishra, Pradeep; Kaur, Suneet; Sharma, Amar Nath; Jolly, Ravinder S.

    2016-01-01

    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 the best of

  18. 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

    PubMed Central

    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

  19. 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

    PubMed Central

    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. PMID:28217364

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

    PubMed

    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 <11% for EtOAc, and 76 to 85% with RSD <7% for QuEChERS. NAAm recoveries ranged from 74 to 102% with RSD 5 15% for mini-Luke, 76 to 97% with RSD <4% for EtOAc, and 76 to 93% with RSD < 5% for QuEChERS. The linearity of the response over two

  1. Substituted 2-[(2-Oxo-2H-[1,2,4]triazino [2,3-c]quinazolin-6-yl)thio]acetamides with Thiazole and Thiadiazole Fragments: Synthesis, Physicochemical Properties, Cytotoxicity, and Anticancer Activity

    PubMed Central

    Kovalenko, Sergey I.; Nosulenko, Inna S.; Voskoboynik, Alexey Yu.; Berest, Galina G.; Antypenko, Lyudmyla N.; Antypenko, Alexey N.; Katsev, Andrey M.

    2012-01-01

    The series of novel N-R-2-[(3-R-2-oxo-2H-[1,2,4]triazino[2,3-c]quinazolin-6-yl)thio]acetamides with thiazole and thiadiazole fragments in a molecule were obtained by alkylation of potassium salts 1.1–1.4 by N-hetaryl-2-chloroacetamides and by aminolysis of activated acids 2.1–2.4 with N,N’-carbonyldiimidazole (CDI). The structures of compounds were determined by IR, 1H NMR, MS, and EI-MS analysis. The results of cytotoxicity evaluated by the bioluminescence inhibition of bacterium Photobacterium leiognathi, Sh1 showed that the compounds have considerable cytotoxicity. The synthesized compounds were tested for anticancer activity in NCI against 60 cell lines. Among the highly active compounds 3.1, 3.2, and 6.5, 2-[(3-methyl-2-oxo-2H-[1,2,4]triazino[2,3-c]quinazolin-6-yl)thio]-N-(1,3-thiazol-2-yl)acetamide (3.1) was found to be the most active anticancer agent against the cell lines of colon cancer (GI50 at 0.41–0.69 μM), melanoma (GI50 0.48–13.50 μM), and ovarian cancer (GI50 0.25–5.01 μM). The structure-activity relationship (SAR-analysis) was discussed. PMID:23264935

  2. 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).

    PubMed

    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.

  3. Low-frequency collective dynamics in deep eutectic solvents of acetamide and electrolytes: a femtosecond Raman-induced Kerr effect spectroscopic study.

    PubMed

    Biswas, Ranjit; Das, Anuradha; Shirota, Hideaki

    2014-10-07

    In this study, we have investigated the ion concentration dependent collective dynamics in two series of deep eutectic solvent (DES) systems by femtosecond Raman-induced Kerr effect spectroscopy, as well as some physical properties, e.g., shear viscosity (η), density (ρ), and surface tension (γ). The DES systems studied here are [0.75CH3CONH2 + 0.25{f KSCN + (1 - f )NaSCN}] and [0.78CH3CONH2 + 0.22{f LiBr + (1 - f )LiNO3}] with f = 0, 0.2, 0.4, 0.6, 0.8, and 1.0. γ of these DES systems shows near insensitivity to f, while ρ shows a moderate dependence on f. Interestingly, η exhibits a strong dependence on f. In the low-frequency Kerr spectra, obtained via the Fourier transform of the collected Kerr transients, a characteristic band at ∼70 cm(-1) is clear in [0.78CH3CONH2 + 0.22{f LiBr + (1 - f )LiNO3}] DES especially at the larger f. The band is attributed to the intermolecular hydrogen bond of acetamide. Because of less depolarized Raman activities of intermolecular/interionic vibrational motions, which are mostly translational (collision-induced or interaction-induced) motions, of spherical ions, the intermolecular hydrogen-bonding band is clearly observed. In contrast, the intermolecular hydrogen-bonding band is buried in the other intermolecular/interionic vibrational motions, which includes translational and reorientational (librational) motions and their cross-terms, in [0.75CH3CONH2 + 0.25{f KSCN + (1 - f )NaSCN}] system. The first moment (M1) of the intermolecular/interionic vibrational band in these DES systems is much higher than that in typical neutral molecular liquids and shows a weak but contrasting dependence on the bulk parameter √γ/ρ. The time constants for picosecond overdamped Kerr transients in both the DES systems, which are obtained on the basis of the analysis fitted by a triexponential function, are rather insensitive to f for both the DES systems, but all the three time constants (fast: ∼1-3 ps; intermediate:

  4. Synthesis and in vitro evaluation of bis-quaternary 2-(hydroxyimino)-N-(pyridin-3-yl)acetamide derivatives as reactivators against sarin and VX inhibited human acetylcholinesterase (hAChE).

    PubMed

    Karade, Hitendra N; Valiveti, Aditya Kapil; Acharya, Jyotiranjan; Kaushik, Mahabir Parshad

    2014-05-01

    A series of bis-quaternary pyridinium derivatives 3a-3i of 2-(hydroxyimino)-N-(pyridin-3-yl)acetamide (2) have been synthesized. The synthesized pyridinium compounds have an amide group in conjugation to the oxime moiety. These compounds were evaluated in vitro for their reactivation efficacy against organophosphorus (OP) nerve agents (NAs) (sarin and VX) inhibited human erythrocyte ghost acetylcholinesterase (hAChE) and compared with the reactivation efficacy of 2-PAM and obidoxime. The pKa values of the synthesized compounds were found closer to the pKa values of 2- and 4-pyridinium oxime reactivators such as 2-PAM and obidoxime. Some of the compounds have shown better reactivation efficacy than 2-PAM, and obidoxime against sarin and VX inhibited AChE.

  5. SYNTHESIS AND BIOLOGICAL EVALUATION OF N-(SUBSTITUTED PHENYL)-2-(5H-[1,2,4]TRIAZINO[5,6-b]INDOL-3-YLSULFANYL)ACETAMIDES AS ANTIMICROBIAL, ANTIDEPRESSANT AND ANTICONVULSANT AGENTS.

    PubMed

    Shruthi, N; Poojary, Boja; Kumar, Vasantha; Prathibha, A; Hussain, Mumtaz Mohammed; Revanasiddappa, B C; Joshi, Himanshu

    2015-01-01

    A new series of N-Aryl-2-(5H-[1,2,4]triazino[5,6-b]indol-3-ylsulfanyl)acetamides were synthesized by condensation of tricyclic compound 2,5-dihydro-3H-[1,2,4]triazino[5,6-b]indole-3-thione with chloro N-phenylacetamides. The tricyclic compound was obtained by condensation of Isatin with thiosemicarbazide. Chloro N-phenylacetamides were obtained from different substituted anilines. Their structures were characterized by IR, 1H NMR, LC-MS and elemental analyses. Newly synthesized compounds were screened for antimicrobial, antidepressant and anticonvulsant activities. Preliminary results indicated that most of the compounds showed lesser MIC value than the standard drug used when tested for antimicrobial activity. Some of the compounds were endowed with very good antidepressant and anticonvulsant activity.

  6. Facile synthesis of SSR180575 and discovery of 7-chloro-N,N,5-trimethyl-4-oxo-3(6-[18F]fluoropyridin-2-yl)-3,5-dihydro-4H-pyridazino[4,5-b]indole-1-acetamide, a potent pyridazinoindole ligand for PET imaging of TSPO in cancer

    PubMed Central

    Cheung, Yiu-Yin; Nickels, Michael L.; Tang, Dewei; Buck, Jason R.

    2014-01-01

    A novel synthesis of the translocator protein (TSPO) ligand 7-chloro-N,N,5-trimethyl-4-oxo-3-phenyl-3,5-dihydro-4H-pyridazino[4,5-b]indole-1-acetamide (SSR180575, 3) was achieved in four steps from commercially available starting materials. Focused structure−activity relationship development about the pyridazinoindole ring at the N3 position led to the discovery of 7-chloro-N,N,5-trimethyl-4-oxo-3(6-fluoropyridin-2-yl)-3,5-dihydro-4H-pyridazino[4,5-b]indole-1-acetamide (14), a novel ligand of comparable affinity. Radiolabeling with fluorine-18 (18F) yielded 7-chloro-N,N,5-trimethyl-4-oxo-3(6-[18F]fluoropyridin-2-yl)-3,5-dihydro-4H-pyridazino[4,5-b]indole-1-acetamide (18F-14) in high radiochemical yield and specific activity. In vivo studies of [18F]-14 revealed this agent as a promising probe for molecular imaging of glioma. PMID:25172419

  7. SAR and identification of 2-(quinolin-4-yloxy)acetamides as Mycobacterium tuberculosis cytochrome bc 1 inhibitors† †The authors declare no competing interests. ‡ ‡Electronic supplementary information (ESI) available: Materials and methods, and characterisation of compounds 10a–f, 11a–x and 5, 9, 12a–12aa. See DOI: 10.1039/c6md00236f Click here for additional data file.

    PubMed Central

    Phummarin, Narisa; Boshoff, Helena I.; Tsang, Patricia S.; Dalton, James; Wiles, Siouxsie; Barry 3rd, Clifton E.

    2016-01-01

    A previous phenotypic screen by GSK identified 2-(quinolin-4-yloxy)acetamides as potent growth inhibitors of Mycobacterium tuberculosis (Mtb). We report the results of a preliminary structure–activity relationship (SAR) study of the compound class which has yielded more potent inhibitors. An Mtb cytochrome bd oxidase deletion mutant (cydKO) was found to be hypersensitive to most members of the compound library, while strains carrying single-nucleotide polymorphisms of the qcrB gene, which encodes a subunit of the menaquinol cytochrome c oxidoreductase (bc 1) complex, were resistant to the library. These results identify that the 2-(quinolin-4-yloxy)acetamide class of Mtb growth inhibitors can be added to the growing number of scaffolds that target the M. tuberculosis bc 1 complex. PMID:28337336

  8. 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.

    PubMed

    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.

  9. 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.

    PubMed

    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.

  10. 40 CFR 721.285 - Acetamide, N-[4-(pentyloxy)phenyl]-, acetamide, N-[2-nitro-4-(pentyloxy)phenyl]-, and acetamide...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for... control technology does not apply. Instead, if the waste stream containing the substance will be treated before release, then the amount of the substance reasonably likely to be removed from the waste stream...

  11. MF498 [N-{[4-(5,9-Diethoxy-6-oxo-6,8-dihydro-7H-pyrrolo[3,4-g]quinolin-7-yl)-3-methylbenzyl]sulfonyl}-2-(2-methoxyphenyl)acetamide], a selective E prostanoid receptor 4 antagonist, relieves joint inflammation and pain in rodent models of rheumatoid and osteoarthritis.

    PubMed

    Clark, Patsy; Rowland, Steven E; Denis, Danielle; Mathieu, Marie-Claude; Stocco, Rino; Poirier, Hugo; Burch, Jason; Han, Yongxin; Audoly, Laurent; Therien, Alex G; Xu, Daigen

    2008-05-01

    Previous evidence has implicated E prostanoid receptor 4 (EP4) in mechanical hyperalgesia induced by subplantar inflammation. However, its role in chronic arthritis remains to be further defined because previous attempts have generated two conflicting lines of evidence, with one showing a marked reduction of arthritis induced by a collagen antibody in mice lacking EP4, but not EP1-EP3, and the other showing no impact of EP4 antagonism on arthritis induced by collagen. Here, we assessed the effect of a novel and selective EP4 antagonist MF498 [N-{[4-(5,9-diethoxy-6-oxo-6,8-dihydro-7H-pyrrolo[3,4-g]quinolin-7-yl)-3-methylbenzyl]sulfonyl}-2-(2-methoxyphenyl)acetamide] on inflammation in adjuvant-induced arthritis (AIA), a rat model for rheumatoid arthritis (RA), and joint pain in a guinea pig model of iodoacetate-induced osteoarthritis (OA). In the AIA model, MF498, but not the antagonist for EP1, MF266-1 [1-(5-{3-[2-(benzyloxy)-5-chlorophenyl]-2-thienyl}pyridin-3-yl)-2,2,2-trifluoroethane-1,1-diol] or EP3 MF266-3 [(2E)-N-[(5-bromo-2-methoxyphenyl)sulfonyl]-3-[5-chloro-2-(2-naphthylmethyl)phenyl]acrylamide], inhibited inflammation, with a similar efficacy as a selective cyclooxygenase 2 (COX-2) inhibitor MF-tricyclic. In addition, MF498 was as effective as an nonsteroidal anti-inflammatory drug, diclofenac, or a selective microsomal prostaglandin E synthase-1 inhibitor, MF63 [2-(6-chloro-1H-phenanthro[9,10-d]imidazol-2-yl)isophthalonitrile], in relieving OA-like pain in guinea pigs. When tested in rat models of gastrointestinal toxicity, the EP4 antagonist was well tolerated, causing no mucosal leakage or erosions. Lastly, we evaluated the renal effect of MF498 in a furosemide-induced diuresis model and demonstrated that the compound displayed a similar renal effect as MF-tricyclic [3-(3,4-difluorophenyl)-4-(4-(methylsulfonyl)phenyl)-2-(5H)-furanone], reducing furosemide-induced natriuresis by approximately 50%. These results not only suggest that EP4 is the major EP

  12. Exemption of Dimethyl Acetamide (DMAC) from Regulation Under PSD Review

    EPA Pesticide Factsheets

    This document may be of assistance in applying the New Source Review (NSR) air permitting regulations including the Prevention of Significant Deterioration (PSD) requirements. This document is part of the NSR Policy and Guidance Database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  13. 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.

    PubMed

    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

  14. 40 CFR 721.225 - 2-Chloro-N-methyl-N-substituted acetamide (generic name).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...) Protection in the workplace. Requirements as specified in § 721.63(a)(1), (a)(3), (b) (concentration set at 1.0 percent), and (c). (ii) Hazard communication program. Requirements as specified in § 721.72 (b)(2... availability of a written hazard communication program and MSDSs do not apply when the written program...

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

    PubMed

    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.

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

    NASA Astrophysics Data System (ADS)

    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.

  17. In situ Determination of Fluoride in Groundwater Using N-Octyl Acetamide with Iron(III)-Thiocyanate Complex

    NASA Astrophysics Data System (ADS)

    Sahin, R.; Tapadia, K.; Sharma, A.

    2016-07-01

    This paper describes the nanodrop spectrophotometric determination of fluoride (F-) in a ground water sample using the organic reagent N-octylacetamide (N-OAA) with iron(III)-thiocyanate complex. The iron(III)-thiocyanate complex was extracted with a chloroform solution of amide (N-phenylacetamide, N-alkylacetamide, alkyl = butyl, phenyl, hexyl, and octyl group). This method is based upon the bleaching effect of fluoride on the red-colored extracted complex of iron(III)-thiocyanate-OAA in chloroform. The absorbance of the extract was measured pre and post F- addition at λmax = 470 nm against the reagent blank. The limit of detection and %RSD of F- was 38 μg/L and ±1.6%. The designed work followed Beer's law between 0.5 to 10 μg/mL with slope, intercept, and correlation coefficient values of -0.1101, 1.116, and -0.997, respectively. Furthermore, the applicability of the present investigation was extended for the determination of F- in a groundwater sample, and the results obtained were compared with those from another reported method.

  18. Comparison of the crystal structure and molecular models of N,N-diisobutyl-2-(octylphenylphosphinyl)acetamide (CMPO)

    SciTech Connect

    Rogers, R.D.; Rollins, A.N.; Gatrone, R.C.; Horwitz, E.P.

    1994-06-01

    The compound crystallizes in the space group P2{sub 1}/c with a=13. 446(6), b=22.280(7) {Angstrom}, b=92.07(4){degrees}, and D{sub calc}=1.05 g/cm{sup 3} for Z=8 (@20{degrees}C). Molecular mechanics, molecular dynamics, and MNDO calculations were also performed on CMPO utilizing the SYBYL{sup 2} suite of programs. Results from these calculations are compared to the crystal structure and to similar calculations performed on CMPO using ALCHEMY. The calculations agree fairly well with the crystal structure.

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

    PubMed

    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.

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

    PubMed

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

    2017-04-21

    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.

  1. Medium decoupling of dynamics at temperatures ~100 K above glass-transition temperature: a case study with (acetamide + lithium bromide/nitrate) melts.

    PubMed

    Guchhait, Biswajit; Daschakraborty, Snehasis; Biswas, Ranjit

    2012-05-07

    Time-resolved fluorescence Stokes shift and anisotropy measurements using a solvation probe in [0.78CH(3)CONH(2) + 0.22{f LiBr + (1-f) LiNO(3)}] melts reveal a strong decoupling of medium dynamics from viscosity. Interestingly, this decoupling has been found to occur at temperatures ∼50-100 K above the glass transition temperatures of the above melt at various anion concentrations (f(LiBr)). The decoupling is reflected via the following fractional viscosity dependence (η) of the measured average solvation and rotation times (<τ(s)> and <τ(r)>, respectively): <τ(x)> ∝ (η∕T)(p) (x being solvation or rotation), with p covering the range, 0.20 < p < 0.70. Although this is very similar to what is known for deeply supercooled liquids, it is very surprising because of the temperature range at which the above decoupling occurs for these molten mixtures. The kinship to the supercooled liquids is further exhibited via p which is always larger for <τ(r)> than for <τ(s)>, indicating a sort of translation-rotation decoupling. Multiple probes have been used in steady state fluorescence measurements to explore the extent of static heterogeneity. Estimated experimental dynamic Stokes shift for coumarin 153 in these mixtures lies in the range, 1000 < Δν(t)/cm(-1) < 1700, and is in semi-quantitative agreement with predictions from our semi-molecular theory. The participation of the fluctuating density modes at various length-scales to the observed solvation times has also been investigated.

  2. Medium decoupling of dynamics at temperatures ˜100 K above glass-transition temperature: A case study with (acetamide + lithium bromide/nitrate) melts

    NASA Astrophysics Data System (ADS)

    Guchhait, Biswajit; Daschakraborty, Snehasis; Biswas, Ranjit

    2012-05-01

    Time-resolved fluorescence Stokes shift and anisotropy measurements using a solvation probe in [0.78CH3CONH2 + 0.22{f LiBr + (1-f) LiNO3}] melts reveal a strong decoupling of medium dynamics from viscosity. Interestingly, this decoupling has been found to occur at temperatures ˜50-100 K above the glass transition temperatures of the above melt at various anion concentrations (fLiBr). The decoupling is reflected via the following fractional viscosity dependence (η) of the measured average solvation and rotation times (⟨τs⟩ and ⟨τr⟩, respectively): ⟨τx⟩ ∝ (η/T)p (x being solvation or rotation), with p covering the range, 0.20 < p < 0.70. Although this is very similar to what is known for deeply supercooled liquids, it is very surprising because of the temperature range at which the above decoupling occurs for these molten mixtures. The kinship to the supercooled liquids is further exhibited via p which is always larger for ⟨τr⟩ than for ⟨τs⟩, indicating a sort of translation-rotation decoupling. Multiple probes have been used in steady state fluorescence measurements to explore the extent of static heterogeneity. Estimated experimental dynamic Stokes shift for coumarin 153 in these mixtures lies in the range, 1000 < Δνt/cm-1 < 1700, and is in semi-quantitative agreement with predictions from our semi-molecular theory. The participation of the fluctuating density modes at various length-scales to the observed solvation times has also been investigated.

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

    PubMed

    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.

  4. Discovery of inhibitors of the mitotic kinase TTK based on N-(3-(3-sulfamoylphenyl)-1H-indazol-5-yl)-acetamides and carboxamides.

    PubMed

    Laufer, Radoslaw; Ng, Grace; Liu, Yong; Patel, Narendra Kumar B; Edwards, Louise G; Lang, Yunhui; Li, Sze-Wan; Feher, Miklos; Awrey, Don E; Leung, Genie; Beletskaya, Irina; Plotnikova, Olga; Mason, Jacqueline M; Hodgson, Richard; Wei, Xin; Mao, Guodong; Luo, Xunyi; Huang, Ping; Green, Erin; Kiarash, Reza; Lin, Dan Chi-Chia; Harris-Brandts, Marees; Ban, Fuqiang; Nadeem, Vincent; Mak, Tak W; Pan, Guohua J; Qiu, Wei; Chirgadze, Nickolay Y; Pauls, Henry W

    2014-09-01

    TTK kinase was identified by in-house siRNA screen and pursued as a tractable, novel target for cancer treatment. A screening campaign and systematic optimization, supported by computer modeling led to an indazole core with key sulfamoylphenyl and acetamido moieties at positions 3 and 5, respectively, establishing a novel chemical class culminating in identification of 72 (CFI-400936). This potent inhibitor of TTK (IC50=3.6nM) demonstrated good activity in cell based assay and selectivity against a panel of human kinases. A co-complex TTK X-ray crystal structure and results of a xenograft study with TTK inhibitors from this class are described.

  5. DEVELOPMENT OF METHOD 535 FOR THE DETERMINATION OF CHLOROACETANILIDE AND OTHER ACETAMIDE HERBICIDE DEGRADATES IN DRINKING WATER BY SOLID PHASE EXTRACTION AND LIQUID CHROMATOGRAPHY/TANDEM MASS SPECTROMETRY

    EPA Science Inventory

    EPA Method 535 has been developed in order to provide a method for the analysis of "Alachlor ESA and other acetanilide degradation products" which are listed on U.S. EPA's 1998 Drinking Water Contaminant Candidate List. Method 535 uses solid phase extraction with a nonporous gr...

  6. Crystal structure of N-[(2S,5R)-4-oxo-2,3-diphenyl-1,3-thia-zinan-5-yl]acetamide 0.375-hydrate.

    PubMed

    Yennawar, Hemant P; Singh, Harnoor; Silverberg, Lee J

    2015-01-01

    The asymmetric unit of the title compound, C18H18N2O2S.0.375H2O, has two independent organic mol-ecules (A and B) and 3/4 of a water mol-ecule distributed over three sites. In mol-ecule A, the 1,3-thia-zine ring is in a boat conformation, with the C atoms at the 2- and 5-positions out of the plane. The angle between the two phenyl rings is 51.70 (12)°. In mol-ecule B, the thia-zine ring is in a half-chair conformation, with the S atom forming the back of the half-chair. The angle between the two phenyl rings is 84.44 (14)°. The A mol-ecule features an intra-molecular N-H⋯O hydrogen bond, which closes an S(5) ring motif. In the crystal, the corresponding N-H grouping of the B mol-ecule participates in an inter-molecular hydrogen bond to the A mol-ecule. The A mol-ecule participates in a C-H⋯O inter-action back to the B mol-ecule, whilst the B mol-ecule features an intra-molecular C-H⋯O link, which generates an S(10) loop.

  7. [Synthesis of two new acetanilide derivatives and their effect on the serum antioxidant vitamins (A, E, and C) and the MDA level in rats].

    PubMed

    Karatas, F; Cansiz, A; Kara, H; Karatepe, M; Koparir, M

    2005-01-01

    Acetanilide derivatives, 2,2'-thiobis[N-(4-nitrophenyl)acetamide] and 2,2'-thiobis[N-(4-chlorophenyl)acetamide], were synthesized and characterized. They were shown to cause a considerable oxidative stress in rats.

  8. Crystal structure of 2-[4(E)-2,6-bis­(4-chloro­phen­yl)-3-ethyl­piperidin-4-yl­idene]acetamide

    PubMed Central

    Priya, K.; Saravanan, K.; Selvanayagam, S.; Kabilan, S.

    2015-01-01

    In the title piperidine derivative, C21H22Cl2N2O, the piperidine ring adopts a chair conformation. The chloro­phenyl rings are oriented at an angle of 45.59 (14)° with respect to each other. In the crystal, mol­ecules are linked via N—H⋯O hydrogen bonds, forming C(4) chains along [100]. The chains are linked by C—H⋯O hydrogen bonds, forming sheets parallel to the ab plane. Within the sheets, there are N—H⋯π inter­actions present. The crystal studied was refined as an inversion twin. PMID:26594551

  9. Synthesis of 2-{2-[(α/β-naphthalen-1-ylsulfonyl)amino]-1,3-thiazol-4-yl} acetamides with 11β-hydroxysteroid dehydrogenase inhibition and in combo antidiabetic activities.

    PubMed

    Navarrete-Vázquez, Gabriel; Morales-Vilchis, Maria Guadalupe; Estrada-Soto, Samuel; Ramírez-Espinosa, Juan José; Hidalgo-Figueroa, Sergio; Nava-Zuazo, Carlos; Tlahuext, Hugo; Leon-Rivera, Ismael; Medina-Franco, José L; López-Vallejo, Fabian; Webster, Scott P; Binnie, Margaret; Ortiz-Andrade, Rolffy; Moreno-Diaz, Hermenegilda

    2014-03-03

    Compounds 1-10 were designed using a bioisosteric approach and were prepared using a short synthetic route. The in vitro inhibitory activity of the compounds against 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) was evaluated. Compounds 5 (α-series) and 10 (β-series) had a moderate inhibitory enzyme activity (55.26% and 67.03% inhibition at 10 μM, respectively) and were as active as BVT.14225 (positive control). Both compounds have a piperidine ring in their structure, but the most active (10) was selected to establish its in vivo antidiabetic effect using a non insulin-dependent diabetes mellitus rat model. The antidiabetic activity of compound 10 was determined at 50 mg/kg single dose in an acute model, and also by short term sub-chronic administration for 5 days. The results indicated a significant decrease of plasma glucose levels, similar than BVT.14225. Additionally, a molecular docking of the most active compounds of each series into the ligand binding pocket of one subunit of human 11β-HSD1 was performed. In this model the oxygen atom of the sulfonamide make hydrogen bond interactions with the catalytic residues Ser170 and Ala172. We also observed important π-π interactions between the naphthyl group and Tyr177.

  10. X-Ray diffraction and vibrational spectroscopic study of 2-chloro-N-{l_brace}4-[3-(2,5-dimethylphenyl)-3-methylcyclobutyl] -thiazol-2-yl{r_brace}-acetamide

    SciTech Connect

    Caliskan, Nezihe Guentepe, Feyizan; Yueksektepe, Cigdem; Cukurovali, Alaaddin; Bueyuekguengoer, Orhan

    2010-12-15

    The title compound C{sub 18}H{sub 21}ClN{sub 2}SO crystallizes with Z = 4 in space group P2{sub 1}/c. The structure of the title compound was characterized by {sup 1}H-NMR, {sup 13}C-NMR, IR and single crystal diffraction. There are an intermolecular N-H-O hydrogen bond and a C-H-{pi} interactions in crystal packing. In addition to the molecular geometry and packing obtained from X-ray experiment, the molecular geometry and vibrational frequencies of the title compound in ground state have been calculated using density functional theory method DFT (B3LYP) with 6-31G (d, p) basis set. Calculated frequencies, bond lengths, angles and dihedral angles are in good agreement with the corresponding experimental data.

  11. A simplified synthesis of the hypoxia imaging agent 2-(2-Nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-[18F]pentafluoropropyl)-acetamide ([18F]EF5)

    PubMed Central

    Chitneni, Satish K.; Bida, Gerald T.; Dewhirst, Mark W.; Zalutsky, Michael R.

    2012-01-01

    Introduction [18F]EF5 is a validated marker for PET imaging of tumor hypoxia. It is prepared by reacting a trifluoroallyl precursor with carrier-added [18F]F2 gas in trifluoroacetic acid (TFA) solvent. We report here an improved radiosynthesis and purification of [18F]EF5 by utilizing an electroformed nickel (Ni) target for [18F] F2 production, and Oasis® HLB cartridges for on-line solid phase extraction of [18F]EF5 prior to HPLC purification. Methods [18F]F2 was produced by deuteron bombardment of neon plus F2 in an Ni target, and bubbled through the radiolabelling precursor solution. Purification was achieved by extracting the contents of the crude reaction mixture onto Oasis HLB cartridges, and subsequently eluted onto a semi-preparative HPLC column for further separation. Purified [18F]EF5 was evaluated in small animal PET studies using HCT116 tumor xenografts in nude mice. Results The electroformed Ni target enabled recovery of >75% of the radioactivity from the cyclotron target, resulting in 16.2±2.2 GBq (438±58 mCi) of [18F]F2 available for the synthesis. Use of Oasis cartridges yielded a less complex mixture for purification. On average, 1140±200 MBq (30.8±5.4 mCi) of [18F]EF5 were collected at EOS. Small animal PET imaging studies showed specific retention of [18F]EF5 in tumors, with tumor-to-muscle ratios of 2.7±0.3 at about 160 min after injection. Conclusion A simple procedure has been developed for the routine synthesis of [18F]EF5 in amounts and purity required for clinical studies. This new method avoids the need for TFA evaporation and also enables facile automation of the synthesis using commercially available radiosynthesis modules. PMID:22727821

  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

    SciTech Connect

    Sharma, R.; Nayak, P. S.; Narayana, B.; Kant, R.

    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. Crystal structure of 2-[(1R,2R,4aS,8aS)-2-hy-droxy-2,5,5,8a-tetra-methyl-deca-hydro-naphthalen-1-yl]-N-(o-tol-yl)acetamide.

    PubMed

    Li, Dang-Dang; Shi, Xin-Wei; Lu, Qiang-Qiang; Li, Sheng-Kun

    2015-10-01

    The title compound, C23H35NO2, is an amide derivative of the lactone (+)-sclareolide, and was synthesized from natural sclareol. In the mol-ecular structure, the two six-membered rings (A and B) of the labdane skeleton are trans-fused, and adopt chair conformations. There is an intra-molecular N-H⋯O hydrogen bond present forming an S(7) ring motif. In the crystal, O-H⋯O hydrogen bonds link the mol-ecules into helical chains propagating along the b-axis direction. The chains are linked via C-H⋯π inter-actions, forming a three-dimensional structure.

  14. 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).

    PubMed

    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.

  15. 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

    SciTech Connect

    Jacobs, Jon; Grum-Tokars, Valerie; Zhou, Ya; Turlington, Mark; Saldanha, S. Adrian; Chase, Peter; Eggler, Aimee; Dawson, Eric S.; Baez-Santos, Yahira M.; Tomar, Sakshi; Mielech, Anna M.; Baker, Susan C.; Lindsley, Craig W.; Hodder, Peter; Mesecar, Andrew; Stauffer, Shaun R.

    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.

  16. N-[(R)-(6-Bromo-2-meth­oxy­quinolin-3-yl)(phen­yl)meth­yl]-N-[(S)-1-(4-meth­oxy­phen­yl)eth­yl]-2-(piperazin-1-yl)acetamide

    PubMed Central

    Yuan, Lei; Wang, Rui; Li, Chang-Yi; Wang, Zhi-Qiang; Sun, Tie-Min

    2011-01-01

    In the title compound, C32H35BrN4O3, the piperazine ring exists in a chair conformation. The quinoline ring system is oriented at dihedral angles of 82.70 (17) and 19.54 (17)° to the phenyl and meth­oxy­phenyl rings, respectively. Weak inter­molecular C—H⋯π inter­actions are present in the crystal structure. PMID:22219953

  17. 40 CFR 180.155 - 1-Naphthaleneacetic acid; tolerances for residues.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... established for the combined residues of the plant growth regulator 1-naphthaleneacetic acid and its... ammonium, sodium, or potassium salts, ethyl ester, and acetamide in or on food commodities as...

  18. HEXIM1 — EDRN Public Portal

    Cancer.gov

    HEXIM1 is an intronless transcriptional regulator which functions as a general RNA polymerase II transcription inhibitor. HEXIM1 expression is induced by hexamethylene-bis-acetamide in vascular smooth muscle cells.

  19. Feasibility study for a secondary Na/S battery

    NASA Technical Reports Server (NTRS)

    Abraham, K. M.; Schiff, R.; Brummer, S. B.

    1979-01-01

    The feasibility of a moderate temperature Na battery was studied. This battery is to operate at a temperature in the range of 100-150 C. Two kinds of cathode were investigated: (1) a soluble S cathode consisting of a solution of Na2Sn in an organic solvent and (2) an insoluble S cathode consisting of a transition metal dichalcogenide in contact with a Na(+)ion conducting electrolyte. Four amide solvents, dimethyl acetamide, diethyl acetamide, N-methyl acetamide and acetamide, were investigated as possible solvents for the soluble S cathode. Results of stability and electrochemical studies using these solvents are presented. The dialkyl substituted amides were found to be superior. Although the alcohol 1,3-cyclohexanediol was found to be stable in the presence of Na2Sn at 130 C, its Na2Sn solutions did not appear to have suitable electrochemical properties.

  20. Antimicrobial Acrylic Fiber

    DTIC Science & Technology

    2006-08-01

    hydantoin). The fibers were extruded from a single solvent, dimenthyl acetamide. The fibers could be chlorinated to produce halamines and thus... chlorine adsorption was shown to be proportional to the specific surface area of the fibers, as might be expected for hydrophobic materials which can react...hydantoin). The fibers were extruded from a single solvent, dimethyl acetamide. The fibers could be chlorinated to produce halamines and thus rendered

  1. Indole-3-Acetic Acid Biosynthesis in Colletotrichum gloeosporioides f. sp. aeschynomene

    PubMed Central

    Robinson, M.; Riov, J.; Sharon, A.

    1998-01-01

    We characterized the biosynthesis of indole-3-acetic acid by the mycoherbicide Colletotrichum gloeosporioides f. sp. aeschynomene. Auxin production was tryptophan dependent. Compounds from the indole-3-acetamide and indole-3-pyruvic acid pathways were detected in culture filtrates. Feeding experiments and in vitro assay confirmed the presence of both pathways. Indole-3-acetamide was the major pathway utilized by the fungus to produce indole-3-acetic acid in culture. PMID:9835603

  2. Biotransformation of 2-Benzoxazolinone and 2-Hydroxy-1,4-Benzoxazin-3-one by Endophytic Fungi Isolated from Aphelandra tetragona

    PubMed Central

    Zikmundová, M.; Drandarov, K.; Bigler, L.; Hesse, M.; Werner, C.

    2002-01-01

    The biotransformation of the phytoanticipins 2-benzoxazolinone (BOA) and 2-hydroxy-1,4-benzoxazin-3-one (HBOA) by four endophytic fungi isolated from Aphelandra tetragona was studied. Using high-performance liquid chromatography-mass spectrometry, several new products of acylation, oxidation, reduction, hydrolysis, and nitration were identified. Fusarium sambucinum detoxified BOA and HBOA to N-(2-hydroxyphenyl)malonamic acid. Plectosporium tabacinum, Gliocladium cibotii, and Chaetosphaeria sp. transformed HBOA to 2-hydroxy-N-(2-hydroxyphenyl)acetamide, N-(2-hydroxyphenyl)acetamide, N-(2-hydroxy-5-nitrophenyl)acetamide, N-(2-hydroxy-3-nitrophenyl)acetamide, 2-amino-3H-phenoxazin-3-one, 2-acetylamino-3H-phenoxazin-3-one, and 2-(N-hydroxy)acetylamino-3H-phenoxazin-3-one. BOA was not degraded by these three fungal isolates. Using 2-hydroxy-N-(2-hydroxyphenyl)[13C2]acetamide, it was shown that the metabolic pathway for HBOA and BOA degradation leads to o-aminophenol as a key intermediate. PMID:12324332

  3. Biotransformation of 2-benzoxazolinone and 2-hydroxy-1,4-benzoxazin-3-one by endophytic fungi isolated from Aphelandra tetragona.

    PubMed

    Zikmundová, M; Drandarov, K; Bigler, L; Hesse, M; Werner, C

    2002-10-01

    The biotransformation of the phytoanticipins 2-benzoxazolinone (BOA) and 2-hydroxy-1,4-benzoxazin-3-one (HBOA) by four endophytic fungi isolated from Aphelandra tetragona was studied. Using high-performance liquid chromatography-mass spectrometry, several new products of acylation, oxidation, reduction, hydrolysis, and nitration were identified. Fusarium sambucinum detoxified BOA and HBOA to N-(2-hydroxyphenyl)malonamic acid. Plectosporium tabacinum, Gliocladium cibotii, and Chaetosphaeria sp. transformed HBOA to 2-hydroxy-N-(2-hydroxyphenyl)acetamide, N-(2-hydroxyphenyl)acetamide, N-(2-hydroxy-5-nitrophenyl)acetamide, N-(2-hydroxy-3-nitrophenyl)acetamide, 2-amino-3H-phenoxazin-3-one, 2-acetylamino-3H-phenoxazin-3-one, and 2-(N-hydroxy)acetylamino-3H-phenoxazin-3-one. BOA was not degraded by these three fungal isolates. Using 2-hydroxy-N-(2-hydroxyphenyl)[(13)C(2)]acetamide, it was shown that the metabolic pathway for HBOA and BOA degradation leads to o-aminophenol as a key intermediate.

  4. The potential of the acetonitrile biodegradation by Mesorhizobium sp. F28.

    PubMed

    Feng, Yun-Shu; Lee, Chi-Mei

    2009-05-30

    Mesorhizobium sp. F28 was used in the NHase/amidase enzyme system to convert acetonitrile into acetamide and acetic acid, and the cells grew with the production of acetic acid. The NHase activity of the strain F28 was 78 U mg(-1)dcw, observed in the conversion of 19.5mM acetonitrile at 0.2h. As the initial pH value was between 6.5 and 8.3, 18.3mM acetonitrile completely converted into acetamide within 2h and the accumulation of acetamide subsequently converted into acetic acid and ammonia within 46h. When 20.3mM acetamide was added in the medium, the conversion rate of acetonitrile was 80% at 2h and the conversion rate of the accumulative acetamide was slightly affected. The concentrations of acetic acid and ammonia were respectively 6.01 and 6.68 mM at 46h. The addition of acetic acid decreased the activities of the NHase and amidase. The conversion rate of acetonitrile was 94% at 9.5h and traces of acetic acid (0.25 mM) and ammonia (0.29 mM) were produced. The effects of product-inhibition indicated that the appropriate operation of bioreactor would be beneficial for Mesorizobium sp. F28 to degrade acetonitrile continuously.

  5. Hydroxylated 2-amino-3H-phenoxazin-3-one derivatives as products of 2-hydroxy-1,4-benzoxazin-3-one (HBOA) biotransformation by Chaetosphaeria sp., an endophytic fungus from Aphelandra tetragona.

    PubMed

    Zikmundová, Martina; Drandarov, Konstantin; Hesse, Manfred; Werner, Christa

    2002-01-01

    The biotransformation of the phytoanticipin HBOA and its major degradation metabolites 2-hydroxy-N-(2-hydroxyphenyl)acetamide (7) and N-(2-hydroxyphenyl)acetamide (8) by Chaetosphaeria sp., an endophytic fungus isolated from Aphelandra tetragona, was studied. Three new metabolites could be identified as 2-amino-7-hydroxy-3H-phenoxazin-3-one (12), 2-acetylamino-7-hydroxy-3H-phenoxazin-3-one (13) and 7-hydroxy-2-(2-hydroxyacetyl)-amino-3H-phenoxazin-3-one (14). Structure elucidation of 12 and 13 was performed by MS, 1H, 13C NMR and 2D NMR techniques and confirmed by chemical transformation.

  6. N-aryl 2-aryloxyacetamides as a new class of fatty acid amide hydrolase (FAAH) inhibitors.

    PubMed

    Sunduru, Naresh; Svensson, Mona; Cipriano, Mariateresa; Marwaha, Sania; Andersson, C David; Svensson, Richard; Fowler, Christopher J; Elofsson, Mikael

    2017-12-01

    Fatty acid amide hydrolase (FAAH) is a promising target for the development of drugs to treat neurological diseases. In search of new FAAH inhibitors, we identified 2-(4-cyclohexylphenoxy)-N-(3-(oxazolo[4,5-b]pyridin-2-yl)phenyl)acetamide, 4g, with an IC50 of 2.6 µM as a chemical starting point for the development of potent FAAH inhibitors. Preliminary hit-to-lead optimisation resulted in 2-(4-phenylphenoxy)-N-(3-(oxazolo[4,5-b]pyridin-2-yl)phenyl)acetamide, 4i, with an IC50 of 0.35 µM.

  7. Degradation of a xenobiotic textile dye, Disperse Brown 118, by Brevibacillus laterosporus.

    PubMed

    Kurade, Mayur B; Waghmode, Tatoba R; Kabra, Akhil N; Govindwar, Sanjay P

    2013-10-01

    The toxic textile dye, Disperse Brown 118, was degraded by Brevibacillus laterosporus. 96% decolorization was achieved within 48 h at pH 7, 40 °C at 50 mg dye l(-1) accompanied by significant increases in the activities of veratryl alcohol oxidase, tyrosinase and NADH-DCIP reductase. HPTLC and FT-IR spectroscopy confirmed biodegradation after dye decolorization. As identified by GC-MS, biodegradation products of Disperse Brown 118 were N-carbamoyl-2-[(8-chloroquinazolin-4-yl)oxy] acetamide and N-carbamoyl-2-(quinazolin-4-yloxy)acetamide which were much less toxic than parent dye as evidenced by phytotoxicity tests.

  8. Enhanced photocurrent generation in bacteriorhodopsin based bio-sensitized solar cells using gel electrolyte.

    PubMed

    Chellamuthu, Jeganathan; Nagaraj, Pavithra; Chidambaram, Sabari Girisun; Sambandam, Anandan; Muthupandian, Ashokkumar

    2016-09-01

    High purity light sensitive photoactive protein Bacteriorhodopsin (BR) was isolated successfully via a simple two phase extraction technique (ATPS) as an alternate method for the tedious sucrose gradient ultracentrifugation procedure (SGU). Bio sensitized solar cells (BSSCs) were fabricated by the integration of BR into TiO2 (photo anode) with acetamide based gel electrolytes and platinum (photo cathode) as a counter electrode. The structural and photoelectrical behaviours of BR and BSSCs were analyzed by Atomic Force Microscopy, Raman spectroscopy, photocurrent and photovoltage (IV) measurement and electrochemical impedance spectroscopy. The short circuit photocurrent (Jsc) and photoelectric conversion efficiency (η) of acetamide based gel electrolyte (AG) (1.08mAcm(-2), 0.49%) are twice higher than that of traditional triiodide based liquid electrolyte (LE) (0.62mAcm(-2), 0.19%). Also, quasi-Fermi level and lifetime of photogenerated electrons in acetamide based gel electrolyte is about four times higher than that observed in traditional triiodide redox electrolyte. A comparison of the observed results with similar BSSCs made of other natural photoactive protein systems shows that BR as sensitizer has better photovoltaic performance. The enhanced photocurrent generation of the BSSC constructed in our study could be due to the interaction of BR with acetamide based modified poly(ethylene)oxide (PEO) gel electrolyte.

  9. Reduction and Acetylation of 2,4-Dinitrotoluene by a Pseudomonas aeruginosa Strain.

    PubMed

    Noguera, D R; Freedman, D L

    1996-07-01

    Aerobic and anoxic biotransformation of 2,4-dinitrotoluene (DNT) was examined by using a Pseudomonas aeruginosa strain isolated from a plant treating propellant manufacturing wastewater. DNT biotransformation in the presence and absence of oxygen was mostly reductive and was representative of the type of cometabolic transformations that occur when a high concentration of an easily degradable carbon source is present. P. aeruginosa reduced both nitro groups on DNT, with the formation of mainly 4-amino-2-nitrotoluene and 2-amino-4-nitrotoluene and small quantities of 2,4-diaminotoluene. Acetylation of the arylamines was a significant reaction. 4-Acetamide-2-nitrotoluene and the novel compounds 2-acetamide-4-nitrotoluene, 4-acetamide-2-aminotoluene, and 2,4-diacetamidetoluene were identified as DNT metabolites. The biotransformation of 2,4-diaminotoluene to 4-acetamide-2-aminotoluene was 24 times faster than abiotic transformation. 2-Nitrotoluene and 4-nitrotoluene were also reduced to their corresponding toluidines and then acetylated. However, the yield of 4-acetamidetoluene was much higher than that of 2-acetamidetoluene, demonstrating that acetylation at the position para to the methyl group was favored.

  10. Reduction and Acetylation of 2,4-Dinitrotoluene by a Pseudomonas aeruginosa Strain

    PubMed Central

    Noguera, D. R.; Freedman, D. L.

    1996-01-01

    Aerobic and anoxic biotransformation of 2,4-dinitrotoluene (DNT) was examined by using a Pseudomonas aeruginosa strain isolated from a plant treating propellant manufacturing wastewater. DNT biotransformation in the presence and absence of oxygen was mostly reductive and was representative of the type of cometabolic transformations that occur when a high concentration of an easily degradable carbon source is present. P. aeruginosa reduced both nitro groups on DNT, with the formation of mainly 4-amino-2-nitrotoluene and 2-amino-4-nitrotoluene and small quantities of 2,4-diaminotoluene. Acetylation of the arylamines was a significant reaction. 4-Acetamide-2-nitrotoluene and the novel compounds 2-acetamide-4-nitrotoluene, 4-acetamide-2-aminotoluene, and 2,4-diacetamidetoluene were identified as DNT metabolites. The biotransformation of 2,4-diaminotoluene to 4-acetamide-2-aminotoluene was 24 times faster than abiotic transformation. 2-Nitrotoluene and 4-nitrotoluene were also reduced to their corresponding toluidines and then acetylated. However, the yield of 4-acetamidetoluene was much higher than that of 2-acetamidetoluene, demonstrating that acetylation at the position para to the methyl group was favored. PMID:16535348

  11. 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)

    EPA Science Inventory

    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...

  12. Regioselective Green Electrochemical Approach to the Synthesis of Nitroacetaminophen Derivatives.

    PubMed

    Salahifar, Eslam; Nematollahi, Davood; Bayat, Mehdi; Mahyari, Amir; Amiri Rudbari, Hadi

    2015-10-02

    A regioselective green synthesis of nitroacetaminophen derivatives was carried out by electrochemical oxidation of acetaminophen, N-(2-hydroxyphenyl)acetamide, and 1-(4-(4-hydroxyphenyl)piperazin-1-yl)ethanone in the presence of nitrite ion as a nucleophile. The present work has led to the development of a reagentless green and facile electrochemical method for the synthesis of some nitroacetaminophen derivatives.

  13. Developing a genetic manipulation system for the Antarctic archaeon, Halorubrum lacusprofundi: investigating acetamidase gene function

    PubMed Central

    Liao, Y.; Williams, T. J.; Walsh, J. C.; Ji, M.; Poljak, A.; Curmi, P. M. G.; Duggin, I. G.; Cavicchioli, R.

    2016-01-01

    No systems have been reported for genetic manipulation of cold-adapted Archaea. Halorubrum lacusprofundi is an important member of Deep Lake, Antarctica (~10% of the population), and is amendable to laboratory cultivation. Here we report the development of a shuttle-vector and targeted gene-knockout system for this species. To investigate the function of acetamidase/formamidase genes, a class of genes not experimentally studied in Archaea, the acetamidase gene, amd3, was disrupted. The wild-type grew on acetamide as a sole source of carbon and nitrogen, but the mutant did not. Acetamidase/formamidase genes were found to form three distinct clades within a broad distribution of Archaea and Bacteria. Genes were present within lineages characterized by aerobic growth in low nutrient environments (e.g. haloarchaea, Starkeya) but absent from lineages containing anaerobes or facultative anaerobes (e.g. methanogens, Epsilonproteobacteria) or parasites of animals and plants (e.g. Chlamydiae). While acetamide is not a well characterized natural substrate, the build-up of plastic pollutants in the environment provides a potential source of introduced acetamide. In view of the extent and pattern of distribution of acetamidase/formamidase sequences within Archaea and Bacteria, we speculate that acetamide from plastics may promote the selection of amd/fmd genes in an increasing number of environmental microorganisms. PMID:27708407

  14. 40 CFR 180.155 - 1-Naphthaleneacetic acid; tolerances for residues.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... (CONTINUED) PESTICIDE PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific... ammonium, sodium, or potassium salts, ethyl ester, and acetamide in or on food commodities as follows: Commodity Parts per million Cherry, sweet 0.1 Fruit, pome, group 11 0.15 Olive 0.7 Orange 0.1 Pineapple1...

  15. 40 CFR 180.503 - Cymoxanil, tolerance for residues.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific Tolerances § 180.503..., cymoxanil, 2-cyano -N- -2-(methoxyimino) acetamide, in or on the following food commodities: Commodity Parts..., subgroup 3-07B 1.1 Potato 0.05 Vegetable, cucurbit, group 9 0.05 Vegetable, fruiting, group 8 0.2 1There...

  16. METHOD DEVELOPMENT FOR ALACHLOR ESA AND OTHER ACENTANILIDE HERBICIDE DEGRADATION PRODUCTS

    EPA Science Inventory

    Introduction: Acetanilide herbicides are frequently applied in the U.S. on crops (corn, soybeans, popcorn, etc.) to control broadleaf and annual weeds. The acetanilide and acetamide herbicides currently registered for use in the U.S. are alachlor, acetochlor, metolachlor, propa...

  17. Iridium-catalyzed selective α-alkylation of unactivated amides with primary alcohols.

    PubMed

    Guo, Le; Liu, Yinghua; Yao, Wubing; Leng, Xuebing; Huang, Zheng

    2013-03-01

    The first α-alkylation of unactivated amides with primary alcohols is described. An effective and robust iridium pincer complex has been developed for selective α-alkylation of tertiary and secondary acetamides involving a "borrowing hydrogen" methodology. The method is compatible with alcohols bearing various functional groups. This presents a convenient and environmentally benign protocol for α-alkylation of amides.

  18. Effect of meteorology and soil condition on metolachlor and atrazine volatilization over a 10 year period

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A 10-year study was conducted to focus on the impact of soil and climatic factors governing herbicide volatilization from an agricultural field. For the first 5 years, metolachlor [2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-1-methylethyl) acetamide] and atrazine [6-chloro-N-ethyl-N’-(1-methyl...

  19. ACETANILIDE HERBICIDE DEGRADATION PRODUCTS BY LC/MS

    EPA Science Inventory

    Acetanilide herbicides are frequently applied in the U.S. on crops (corn, soybeans, popcorn, etc.) to control broadleaf and annual weeds. The acetanilide and acetamide herbicides currently registered for use in the U.S. are alachlor, acetochlor, metolachlor, propachlor, flufen...

  20. Microwave accelerated aza-Claisen rearrangement.

    PubMed

    Gajdosíková, Eva; Martinková, Miroslava; Gonda, Jozef; Conka, Patrik

    2008-11-14

    A study of microwave-induced and standard thermal Overman rearrangement of selected allylic trichloroacetimidates 1a-1f, 6-8 to the corresponding acetamides 2a-2f, 9-11 is reported. The microwave-assisted rearrangement of trifluoroacetimidate 13 is also described. Using this methodology, an efficient access to versatile allylic trihaloacetamides building synthons was established.

  1. Keeping Your Students Awake: Facile Microscale Synthesis of Modafinil, a Modern Anti-Narcoleptic Drug

    ERIC Educational Resources Information Center

    Aktoudianakis, Evangelos; Lin, Rui Jun; Dicks, Andrew P.

    2006-01-01

    An uncomplicated organic synthesis experiment with modafinil that showcases a prevalent modern antinarcoleptic drug as an approach to inspire students to learn real-world relevance is presented. The synthesis and analysis of racemic 2-(diphenylmethyl-sulfinyl)acetamide, (plus or minus)-modafinil, is suitable as a midlevel undergraduate organic…

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

    PubMed

    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.

  3. 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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed Central

    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

  5. (3-Methyl­benzo­nitrile-1κN)-cis-tetra­kis(μ-N-phenyl­acetamidato)-1:2κ4 N:O;1:2κ4 O:N-dirhodium(II)(Rh—Rh)

    PubMed Central

    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

  6. Insights into diastereoisomeric characterization of tetrahydropyridazine amino acid derivatives: crystal structures and gas phase ion chemistry.

    PubMed

    Giorgi, Gianluca; Favi, Gianfranco; Attanasi, Orazio A

    2013-08-14

    Structural, conformational properties, and gas phase reactivity of two representative diastereoisomeric members of a series of α,α-tetrahydropyridazine amino acid derivatives have been investigated by using X-ray crystallography, tandem mass spectrometry and theoretical calculations. Both diastereoisomers show an unusual screw-boat conformation of the tetrahydropyridazine ring. While protonated molecules mainly decompose in the gas phase by loss of acetamide, the main reactivity of the [M + Na](+) species consists of loss of PhNCO followed by acetamide and it is strictly dependent upon the stereochemistry of the parent compound. The most stable energy minimized structures obtained by theoretical calculations are in full agreement with the experimental data and allowed us to rationalize the gas phase reaction pathways.

  7. Radiolysis of paracetamol in dilute aqueous solution

    NASA Astrophysics Data System (ADS)

    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. Synthetic approaches to multifunctional indenes

    PubMed Central

    López-Pérez, Sara; Dinarès, Immaculada

    2011-01-01

    Summary The synthesis of multifunctional indenes with at least two different functional groups has not yet been extensively explored. Among the plausible synthetic routes to 3,5-disubstituted indenes bearing two different functional groups, such as the [3-(aminoethyl)inden-5-yl)]amines, a reasonable pathway involves the (5-nitro-3-indenyl)acetamides as key intermediates. Although several multistep synthetic approaches can be applied to obtain these advanced intermediates, we describe herein their preparation by an aldol-type reaction between 5-nitroindan-1-ones and the lithium salt of N,N-disubstituted acetamides, followed immediately by dehydration with acid. This classical condensation process, which is neither simple nor trivial despite its apparent directness, permits an efficient entry to a variety of indene-based molecular modules, which could be adapted to a range of functionalized indanones. PMID:22238553

  9. Synthesis and antileishmanial activity of 6-mono-substituted and 3,6-di-substituted acridines obtained by acylation of proflavine.

    PubMed

    Di Giorgio, Carole; Shimi, Kamal; Boyer, Gérard; Delmas, Florence; Galy, Jean-Pierre

    2007-10-01

    Two new series of diaminoacridinic derivatives obtained from proflavine and N-(6-amino-3-acridinyl)acetamide were synthesised and assessed for their cytotoxic and antileishmanial activities. Two compounds, N-[6-(acetylamino)-3-acridinyl]acetamide and N-[6-(benzoylamino)-3-acridinyl]benzamide demonstrated highly specific antileishmanial properties against the intracellular amastigote form of the parasite. Structure-activity relationships established that the antiproliferative activity against human cells was greatly enhanced by the presence of a benzoylamino group in 6-mono-substituted acridines, while the presence of two acetylamino or benzoylamino groups in 3,6-di-substituted acridines strongly increased the specificity of the molecules for Leishmania parasite, suggesting that symmetric conformations could preferentially interfere with Leishmania metabolism.

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

    PubMed

    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.

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

    PubMed

    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.

  12. A Method for the Sample Handling and Analysis of Bio-Active Peptides

    DTIC Science & Technology

    1998-05-01

    two disulfide bridges of a-conotoxin GI would be expected to break and the side chain hydrogen on each cysteine would be replaced with an acetamide...peptides in a database. Disulfide bridge reductive alkylation is used to determine the number of cysteines in the peptide as well as the presence of...was 42 ppm. Reductive alkylation indicated the presence of four cysteines and two intramolecular disulfide bridges which was consistent with the

  13. An iron(III)-monoamidate complex catalyst for selective hydroxylation of alkane C-H bonds with hydrogen peroxide.

    PubMed

    Hitomi, Yutaka; Arakawa, Kengo; Funabiki, Takuzo; Kodera, Masahito

    2012-04-02

    Selective oxidation: the success of the title reaction is caused by the strong electron donation from the amidate moiety of the dpaq ligand to the iron center (dpaq=2-[bis(pyridin-2-ylmethyl)]amino-N-quinolin-8-yl-acetamidate). This process facilitates the O-O bond heterolysis of the intermediate Fe(III)OOH species to generate a selective oxidant without forming highly reactive hydroxyl radicals.

  14. 29 CFR 1910.1000 - Air contaminants.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...-86-4 3.5 Carbon dioxide 124-38-9 5000 9000 Carbon disulfide 75-15-0 (2) Carbon monoxide 630-08-0 50...; see Methylal. Dimethyl acetamide 127-19-5 10 35 X Dimethylamine 124-40-3 10 18 Dimethylaminobenzene...-5 0.05 0.2 Hydrogen sulfide 7783-06-4 (2) Hydroquinone 123-31-9 2 Iodine 7553-56-2 (C)0.1 (C)1...

  15. 29 CFR 1910.1000 - Air contaminants.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...-86-4 3.5 Carbon dioxide 124-38-9 5000 9000 Carbon disulfide 75-15-0 (2) Carbon monoxide 630-08-0 50...; see Methylal. Dimethyl acetamide 127-19-5 10 35 X Dimethylamine 124-40-3 10 18 Dimethylaminobenzene...-5 0.05 0.2 Hydrogen sulfide 7783-06-4 (2) Hydroquinone 123-31-9 2 Iodine 7553-56-2 (C)0.1 (C)1...

  16. 29 CFR 1915.1000 - Air contaminants.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... — Carbon dioxide 124-38-9 5000 9000 — Carbon disulfide 75-15-0 20 60 X Carbon monoxide 630-08-0 50 55...-11-7 Dimethoxymethane; see Methylal Dimethyl acetamide 127-19-5 10 35 X Dimethylamine 124-40-3 10 18...-74-6 — 0.1 — Iodine 7553-56-2 (C)0.1 (C)1 — Iron oxide fume 1309-37-1 — 10 — Iron salts (soluble)...

  17. 29 CFR 1910.1000 - Air contaminants.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...-86-4 3.5 Carbon dioxide 124-38-9 5000 9000 Carbon disulfide 75-15-0 (2) Carbon monoxide 630-08-0 50...; see Methylal. Dimethyl acetamide 127-19-5 10 35 X Dimethylamine 124-40-3 10 18 Dimethylaminobenzene...-5 0.05 0.2 Hydrogen sulfide 7783-06-4 (2) Hydroquinone 123-31-9 2 Iodine 7553-56-2 (C)0.1 (C)1...

  18. 29 CFR 1910.1000 - Air contaminants.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...-86-4 3.5 Carbon dioxide 124-38-9 5000 9000 Carbon disulfide 75-15-0 (2) Carbon monoxide 630-08-0 50...; see Methylal. Dimethyl acetamide 127-19-5 10 35 X Dimethylamine 124-40-3 10 18 Dimethylaminobenzene...-5 0.05 0.2 Hydrogen sulfide 7783-06-4 (2) Hydroquinone 123-31-9 2 Iodine 7553-56-2 (C)0.1 (C)1...

  19. 29 CFR 1926.55 - Gases, vapors, fumes, dusts, and mists.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... — 2 — Carbaryl (Sevin) 63-25-2 — 5 — Carbon black 1333-86-4 — 3.5 — Carbon dioxide 124-38-9 5000 9000... Dimethoxymethane; see Methylal Dimethyl acetamide 127-19-5 10 35 X Dimethylamine 124-40-3 10 18... 95-13-6 10 45 — Indium and compounds (as In) 7440-74-6 — 0.1 — Iodine 7553-56-2 (C)0.1 (C)1 —...

  20. 29 CFR 1926.55 - Gases, vapors, fumes, dusts, and mists.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... — 2 — Carbaryl (Sevin) 63-25-2 — 5 — Carbon black 1333-86-4 — 3.5 — Carbon dioxide 124-38-9 5000 9000... Dimethoxymethane; see Methylal Dimethyl acetamide 127-19-5 10 35 X Dimethylamine 124-40-3 10 18... 95-13-6 10 45 — Indium and compounds (as In) 7440-74-6 — 0.1 — Iodine 7553-56-2 (C)0.1 (C)1 —...

  1. 29 CFR 1915.1000 - Air contaminants.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... — Carbon dioxide 124-38-9 5000 9000 — Carbon disulfide 75-15-0 20 60 X Carbon monoxide 630-08-0 50 55...-11-7 Dimethoxymethane; see Methylal Dimethyl acetamide 127-19-5 10 35 X Dimethylamine 124-40-3 10 18...-74-6 — 0.1 — Iodine 7553-56-2 (C)0.1 (C)1 — Iron oxide fume 1309-37-1 — 10 — Iron salts (soluble)...

  2. 29 CFR 1915.1000 - Air contaminants.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... — Carbon dioxide 124-38-9 5000 9000 — Carbon disulfide 75-15-0 20 60 X Carbon monoxide 630-08-0 50 55...-11-7 Dimethoxymethane; see Methylal Dimethyl acetamide 127-19-5 10 35 X Dimethylamine 124-40-3 10 18...-74-6 — 0.1 — Iodine 7553-56-2 (C)0.1 (C)1 — Iron oxide fume 1309-37-1 — 10 — Iron salts (soluble)...

  3. 29 CFR 1910.1000 - Air contaminants.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...-86-4 3.5 Carbon dioxide 124-38-9 5000 9000 Carbon disulfide 75-15-0 (2) Carbon monoxide 630-08-0 50...; see Methylal. Dimethyl acetamide 127-19-5 10 35 X Dimethylamine 124-40-3 10 18 Dimethylaminobenzene...-5 0.05 0.2 Hydrogen sulfide 7783-06-4 (2) Hydroquinone 123-31-9 2 Iodine 7553-56-2 (C)0.1 (C)1...

  4. 29 CFR 1926.55 - Gases, vapors, fumes, dusts, and mists.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... — 2 — Carbaryl (Sevin) 63-25-2 — 5 — Carbon black 1333-86-4 — 3.5 — Carbon dioxide 124-38-9 5000 9000... Dimethoxymethane; see Methylal Dimethyl acetamide 127-19-5 10 35 X Dimethylamine 124-40-3 10 18... 95-13-6 10 45 — Indium and compounds (as In) 7440-74-6 — 0.1 — Iodine 7553-56-2 (C)0.1 (C)1 —...

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

    PubMed

    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.

  6. Scaffold hopping: exploration of acetanilide-containing uracil analogues as potential NNRTIs.

    PubMed

    Babkov, Denis A; Valuev-Elliston, Vladimir T; Paramonova, Maria P; Ozerov, Alexander A; Ivanov, Alexander V; Chizhov, Alexander O; Khandazhinskaya, Anastasia L; Kochetkov, Sergey N; Balzarini, Jan; Daelemans, Dirk; Pannecouque, Christophe; Seley-Radtke, Katherine L; Novikov, Mikhail S

    2015-03-01

    In order to identify novel nonnucleoside inhibitors of HIV-1 reverse transcriptase two series of amide-containing uracil derivatives were designed as hybrids of two scaffolds of previously reported inhibitors. Subsequent biological evaluation confirmed acetamide uracil derivatives 15a-k as selective micromolar NNRTIs with a first generation-like resistance profile. Molecular modeling of the most active compounds 15c and 15i was employed to provide insight on their inhibitory properties and direct future design efforts.

  7. Parametric Binding Images of the TSPO Ligand 18F-DPA-714.

    PubMed

    Golla, Sandeep S V; Boellaard, Ronald; Oikonen, Vesa; Hoffmann, Anja; van Berckel, Bart N M; Windhorst, Albert D; Virta, Jere; Te Beek, Erik T; Groeneveld, Geert Jan; Haaparanta-Solin, Merja; Luoto, Pauliina; Savisto, Nina; Solin, Olof; Valencia, Ray; Thiele, Andrea; Eriksson, Jonas; Schuit, Robert C; Lammertsma, Adriaan A; Rinne, Juha O

    2016-10-01

    (18)F-labeled N,N-diethyl-2-(2-[4-(2-fluoroethoxy)phenyl]-5,7-dimethylpyrazolo[1,5-α]pyrimidine-3-yl)acetamide (DPA-714) is a radioligand for the 18-kDa translocator protein. The purpose of the present study was to identify the best method for generating quantitative parametric images of (18)F-DPA-714 binding.

  8. Synthesis of 9,9'-[1,2-ethanediylbis(oxymethylene)]bis-2-amino-1,9-dihydro-6H-purin-6-one, an impurity of acyclovir.

    PubMed

    Suárez, Rosa M; Matía, Maria Paz; Novella, José Luis; Molina, Andres; Cosme, Antonio; Vaquero, Juan José; Alvarez-Builla, Julio

    2012-07-25

    The synthesis of 9,9'-[1,2-ethanediylbis(oxymethylene)]bis-2-amino-1,9-dihydro-6H-purin-6-one, a minor impurity of acyclovir, is described. Starting with commercial N-(9-acetyl-6-oxo-1H-purin-2-yl)acetamide, the process uses an acid catalysed phase transfer catalysis (PTC) process to produce the selective alkylation at the 9 position of the guanine ring.

  9. JPRS Report, Science & Technology, USSR: Life Sciences

    DTIC Science & Technology

    2007-11-02

    Production [E. I. Perov, L. Yu. Zamytskiy, et al; BIOTEKHNOLOGIYA, Vol 4 No 2, Mar-Apr 88] 7 Bioenergetic and Instrumental Aspects of Energy...hydrolysis of the products at 90°C, the fragments were analyzed by electrophoresis in 8% polyacrylamide gel with 7 M urea and autoradiographed...the synthetic process for simplification and avoidance of side products . Bis(trimethylsilyl)acetamide and trimethylchlorosilane were employed for

  10. Spectroscopy of the amide-I modes of acetanilide

    SciTech Connect

    Bigio, I.J.; Scott, A.C.; Johnston, C.T.

    1989-01-01

    Raman measurements were made on acetanilide (N-phenyl-acetamide). Data are presented of the integrated intensity of the 1650 cm/sup /minus/1/ band as a function of temperature. The experimental procedures and data reduction were highly rigorous and are believed to be to most reliable data available. A concise theory of polaron states is presented and used to interpret the data. 22 refs., 4 figs., 1 tab.

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

    SciTech Connect

    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

    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.

  12. Tough, Soluble, Aromatic, Thermoplastic Copolyimides

    NASA Technical Reports Server (NTRS)

    Bryant, Robert G. (Inventor)

    1998-01-01

    Tough, soluble, aromatic, thermoplastic copolyimides were prepared by reacting 4,4'-oxydiphthalic anhydride, 3,4,3',4'-biphenyltetracarboxylic dianhydride and 3,4'-oxydianiline. These copolyimides were found to be soluble in common amide solvents such as N,N'-dimethyl acetamide, N-methylpyrrolidinone, and dimethylformamide allowing them to be applied as the fully imidized copolymer and to be used to prepare a wide range of articles.

  13. 40 CFR Appendix Vi to Part 265 - Compounds With Henry's Law Constant Less Than 0.1 Y/X

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... chloride 79-44-7 Dimethyldisulfide 624-92-0 Dimethylformamide 68-12-2 1,1-Dimethylhydrazine 57-14-7... 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...

  14. 40 CFR Appendix Vi to Part 265 - Compounds With Henry's Law Constant Less Than 0.1 Y/X

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... chloride 79-44-7 Dimethyldisulfide 624-92-0 Dimethylformamide 68-12-2 1,1-Dimethylhydrazine 57-14-7... 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...

  15. 40 CFR Appendix Vi to Part 265 - Compounds With Henry's Law Constant Less Than 0.1 Y/X

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... chloride 79-44-7 Dimethyldisulfide 624-92-0 Dimethylformamide 68-12-2 1,1-Dimethylhydrazine 57-14-7... 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...

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

    PubMed

    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.

  17. Differential fate of metabolism of a sulfonated azo dye Remazol Orange 3R by plants Aster amellus Linn., Glandularia pulchella (Sweet) Tronc. and their consortium.

    PubMed

    Kabra, Akhil N; Khandare, Rahul V; Waghmode, Tatoba R; Govindwar, Sanjay P

    2011-06-15

    Plant consortium-AG of Aster amellus Linn. and Glandularia pulchella (Sweet) Tronc. showed complete decolorization of a dye Remazol Orange 3R in 36 h, while individually A. amellus and G. pulchella took 72 and 96 h respectively. Individually A. amellus showed induction in the activities of enzymes veratryl alcohol oxidase and DCIP reductase after degradation of the dye while G. pulchella showed induction of laccase and tyrosinase, indicating their involvement in the dye metabolism. Consortium-AG showed induction in the activities of lignin peroxidase, veratryl alcohol oxidase, laccase, tyrosinase and DCIP reductase. Two different sets of induced enzymes from A. amellus and G. pulchella work together in consortium-AG resulting in faster degradation of the dye. The degradation of the dye into different metabolites was confirmed using High Performance Liquid Chromatography and Fourier Transform Infra Red Spectroscopy. Gas Chromatography Mass Spectroscopy analysis identified four metabolites of dye degradation by A. amellus as acetamide, benzene, naphthalene and 3-diazenylnaphthalene-2-sulfonic acid, four metabolites by G. pulchella as acetamide, 3-diazenyl-4-hydroxynaphthalene-2-sulfonic acid, naphthalen-1-ol and (ethylsulfonyl)benzene, while two metabolites by consortium-AG as 2-(phenylsulfonyl)ethanol and N-(naphthalen-2-yl)acetamide. The non-toxic nature of the metabolites of Remazol Orange 3R degradation was revealed by phytotoxicity studies.

  18. Synthesis of azepino[4,5-b]indol-4-ones via MCR/free radical cyclization and in vitro-in silico studies as 5-Ht₆R ligands.

    PubMed

    Rentería-Gómez, Angel; Islas-Jácome, Alejandro; Díaz-Cervantes, Erik; Villaseñor-Granados, Tayde; Robles, Juvencio; Gámez-Montaño, Rocío

    2016-05-01

    A series of nine new 3-acetamide-azepino[4,5-b]indol-4-ones were synthesized in two steps: (i) multicomponent reaction (Ugi-4CR/SN2) and (ii) free radical-mediated cyclization. These compounds, along with their tetrazole-based analogs, were studied in vitro to assess their binding with the 5-hydroxytryptamine type 6 receptor (5-Ht6R). The 3-acetamide-azepino[4,5-b]indol-4-ones displayed moderate affinity, whereas the 3-tetrazolylmethyl-azepino[4,5-b]indol-4-ones affinity values are lower. However, one of the 3-acetamide-azepino[4,5-b]indol-4-ones exhibited a hit value of Ki (211.2nM) to the 5-Ht6R. Minimal-energy structures of one cis-amide and its tetrazole-based analog (calculated by means of the Density Functional Theory) were analyzed to assess some interesting bioisosterism aspects. Interactions and binding energies between all products and the 5-Ht6R were calculated through in silico molecular couplings. Finally, a QSAR model was proposed using the results of the in vitro assays.

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

    NASA Astrophysics Data System (ADS)

    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.

  20. Synthesis and antimicrobial activity of some new diphenylamine derivatives

    PubMed Central

    Kumar, Arvind; Mishra, Arun K.

    2015-01-01

    In search of new leads toward potent antimicrobial agent, an array of novel derivatives of 2-hydrazinyl–N-N, diphenyl acetamide has been synthesized from the chloroacetylation reaction of diphenylamine (DPA). For this, a series of DPA derivatives were prepared by replacing chlorine with hydrazine hydrate in alcoholic medium and 2-hydrazino-N, N-diphenylacetamide was synthesized. The 2-hydrazino-N, N-diphenylacetamide was further subjected to reaction with various aromatic aldehydes in presence of glacial acetic acid in methanol. The synthesized compounds were characterized by their IR, 1HNMR spectral data and elemental analysis. The compounds were screened for antibacterial and antifungal activity by cup plate method. 2-(2-Benzylidenehydrazinyl)-N, N-diphenylacetamide (A1); 2-(2-(3-methylbenzylidene) hydrazinyl)-N, N-diphenyl-acetamide (A5) and 2-(2-(2-nitrobenzylidine) hydrazinyl)-N, N-diphenyl-acetamide compounds (A7) showed significant antimicrobial as well as antifungal activity. Diphenylamine compounds may be explored as potent antimicrobial and antifungal compounds. PMID:25709343

  1. New analytical reagents for the determination of sulfur dioxide and carbon monoxide

    SciTech Connect

    Trump, E.L.

    1987-01-01

    Four solid reagent methods were developed for the determination of sulfur dioxide in air, and one method was developed to measure carbon monoxide. When applied to filter paper with acetamide as the humectant and 4-phenylcyclohexanone as a bisulfite absorbent, oxohydroxybis(8-hydroxyquinolinyl-) vanadium (V) changes from yellow to black in the presence of sulfur dioxide. The three other methods, also on a filter paper support, utilized the reduction of bromate to bromine which then changed 3-,3'-, 5-,5'-tetramethylbenzidine from yellow to blue, phenothiazine from white to green, and 4-dimethylamino-4'-,4/double prime/-dimethoxytriphenylmethanol from colorless to red-purple. Quantitative measurements were made by reflectance spectroscopy. The method for carbon monoxide involved the use of tetrakis (acetamide-) Pd(II) ditetrafluoroborate, sodium iodate, and leuco crystal violet all together on a filter paper support. Carbon monoxide reduced the Pd(II)-acetamide complex to metallic palladium. The metallic palladium then reduced iodate to hypoiodous acid, HOI, which, in turn, oxidized leuco crystal violet to crystal violet. The crystal violet color was then measured by reflectance.

  2. How does lithium oxalyldifluoroborate enable the compatibility of ionic liquids and carbon-based capacitors?

    NASA Astrophysics Data System (ADS)

    Chen, Renjie; Chen, Yan; Xu, Bin; Zhang, Rong; He, Zhouying; Wu, Feng; Li, Li

    2015-02-01

    Lithium oxalyldifluoroborate (LiODFB) has several unique characteristics, such as high ionic conductivity over a wide temperature range and the ability to form and stabilize solid electrolyte interface films on graphite surfaces. A series of binary, room-temperature, molten electrolytes composed of LiODFB and organic compounds with acylamino groups (acetamide, oxazolidinone or OZO) have been synthesized. Fourier-transform infrared (FT-IR) spectroscopy indicates that Cdbnd O and N-H functional groups undergo blue or red shifts upon addition of LiODFB. The electrolytes have excellent thermal stabilities and electrochemical characteristics that allow them to be promising electrolytes for electrochemical double layer capacitors (EDLCs). Here, we examine 1:5 molar ratio LiODFB and acetamide/OZO ionic liquid (IL) electrolytes in EDLCs. IL compatibility with two types of carbon-based electrodes is investigated theoretically and experimentally. We simulate possible structures and ion diameters for the ILs, which must be compatible with pore sizes of the carbon electrodes. Mesoporous activated carbon AC2, with a pore size similar to the ionic diameter of LiODFB-acetamide, has a specific capacitance of 154.2 Fg-1 at 20 m Ag-1. Additionally, typical capacitive and reversibility behaviors can be seen in the charge-discharge curves over 0-2 V. Finally, the EDLCs exhibit good charging/discharging performances.

  3. Design of new heteroscorpionate ligands and their coordinative ability toward Group 4 transition metals; an efficient synthetic route to obtain enantiopure ligands.

    PubMed

    Otero, Antonio; Fernández-Baeza, Juan; Antiñolo, Antonio; Tejeda, Juan; Lara-Sánchez, Agustín; Sánchez-Barba, Luis; Sánchez-Molina, Margarita; Franco, Sonia; López-Solera, Isabel; Rodríguez, Ana M

    2006-09-28

    The reaction of different types of bis(pyrazol-1-yl)methane derivatives with Bu(n)Li and alkyl or aryl-containing-isocyanates or isothiocyanates, some of these as chiral reagents, gives rise to the preparation of new heteroscorpionate ligands in the form of the lithium derivatives [Li(NNE)]2 (1-10), although a similar process with trimethylsilyl isocyanate or isothiocyanate gave the complexes [Li(NCX)(bdmpzs)(THF)](X = O, 11; X = S, 12)[bdmpzs = bis(3,5-dimethylpyrazol-1-yl)trimethylsilylmethane]. Compounds 1-8 reacted with [TiCl4(THF)2] or [MCl4](M = Zr, Hf) to give a series of cationic complexes [MCl3{kappa3-NNE(H)}]Cl (13-36) where the heteroscorpionate ligand contains either an acetamide or thioacetamide group resulting from the protonation of the corresponding acetamidate or thioacetamidate. However, under appropriate experimental conditions neutral Ti complexes were isolated-namely [TiClx(NMe2)3-x(S-mbbpam)](37-39)[S-mbbpam =(S)-(-)-N-alpha-methylbenzyl-2,2-bis(3,5-dimethylpyrazol-1-yl)acetamidate]. Finally, two alkoxide-containing titanium complexes [TiClx(OR)3-x(S-mbbpamH)]Cl (40-41) were also prepared. The structures of these complexes have been determined by spectroscopic methods and, in addition, the X-ray crystal structures of 1, 12, and 19 were also established.

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

    PubMed

    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.

  5. Investigation of Uranyl Nitrate Ion Pairs Complexed with Amide Ligands using Electrospray Ionization Ion Trap Mass Spectrometry and Density Functional Theory

    SciTech Connect

    Gary S. Groenewold; Adriana Dinescu; Michael T. Benson; Garold L. Gresham; Michael J. van Stipdonk

    2011-04-01

    Ion populations formed from electrospray of uranyl nitrate solutions containing different amides vary depending on ligand nucleophilicity and steric crowding at the metal center. The most abundant species were ion pair complexes having the general formula [UO2(NO3)(amide)n=2,3]+, and complexes containing the amide conjugate base, reduced uranyl UO2+, and a 2+ charge were also formed. The formamide experiment produced the greatest diversity of species that stems from weaker amide binding leading to dissociation and subsequent solvent coordination or metal reduction. Experiments using methyl formamide, dimethyl formamide, acetamide, and methyl acetamide produced ion pair and doubly charged complexes that were more abundant, and less abundant complexes containing solvent or reduced uranyl. This pattern is reversed in the dimethylacetamide experiment, which displayed reduced doubly charged complexes and augmented reduced uranyl complexes. DFT investigations of the tris-amide ion pair complexes showed that inter-ligand repulsion distorts the amide ligands out of the uranyl equatorial plane, and that complex stabilities do not increase with increasing amide nucleophilicity. Elimination of an amide ligand largely relieves the interligand repulsion, and the remaining amide ligands become closely aligned with the equatorial plane in the structures of the bis-amide ligands. The studies show that the phenomenological distribution of coordination complexes in a metal-ligand electrospray experiment is a function of both ligand nucleophilicity and interligand repulsion, and that the latter factor begins exerting influence even in the case of relatively small ligands like the substituted methyl-formamide and –acetamide ligands.

  6. Synthesis and psychobiological evaluation of modafinil analogs in mice

    PubMed Central

    2013-01-01

    Background and the purpose of the study Modafinil, a novel wake-promoting agent with low potential for abuse and dependence, has a reliable structure to find some novel derivatives with better activity and lower potential for abuse and risk of dependency. This study was designed to evaluate psychobiological activity of some novel N-aryl modafinil derivatives. Methods Seven novel N-aryl modafinil derivatives were synthesized through three reactions: a) preparation of benzhydrylsulfanyl acetic acid through reaction of benzhydrol with thioglycolic acid, b) formation of desired amide by adding the substituted aniline to activated acid with EDC (1-ethyl-3-(3-dimethyl amino propyl) carbodiimide). This reaction was catalyzed by HOBt (N- hydroxylbenzotriazole), and c) oxidation of sulfur to sulfoxide group with H2O2. Then, their psychobiological effect on the performance of male albino mice were compared to that of modafinil as following: wakefulness by determining the effects of derivatives on phenobarbital-induced loss of the righting reflex (LOPR); exploratory activity by measuring activity in the open field test (OFT); depression by measuring immobility time (IT) during forced swimming test (FST) and the anxiogenic and anxiolytic like effects by using elevated plus-maze test (EPM). All tests were videotaped and analyzed for the frequency and duration of the behaviors during the procedures. Conclusions 2-(Benzhydrylsulfonyl)-N-(4-chlorophenyl)acetamide (4c) showed comparable result in LOPR test. However, all analogs were found to be stimulant except 2-(benzhydrylsulfinyl)-N-phenylacetamide (4a). Also 4c led the most exploratory activity in mice among derivatives. FST results showed that 4a had the longest IT while modafinil, 2-(benzhydrylsulfinyl)-N-(3-chlorophenyl) acetamide (4b) and 2-(benzhydrylsulfinyl)-N-(4-ethylphenyl) acetamide (4d) had the shortest IT. In EPM, all derivatives showed anxiogenic-like behavior since they decreased open arms time and open arms

  7. Elucidation of strain-specific interaction of a GII-4 norovirus with HBGA receptors by site-directed mutagenesis study

    SciTech Connect

    Tan Ming |; Xia Ming; Cao Sheng; Huang Pengwei; Farkas, Tibor |; Meller, Jarek |; Hegde, Rashmi S. |; Li Xuemei; Rao Zihe; Jiang Xi |

    2008-09-30

    Noroviruses interact with histo-blood group antigen (HBGA) receptors in a strain-specific manner probably detecting subtle structural differences in the carbohydrate receptors. The specific recognition of types A and B antigens by various norovirus strains is a typical example. The only difference between the types A and B antigens is the acetamide linked to the terminal galactose of the A but not to the B antigen. The crystal structure of the P dimer of a GII-4 norovirus (VA387) bound to types A and B trisaccharides has elucidated the A/B binding site on the capsid but did not explain the binding specificity of the two antigens. In this study, using site-directed mutagenesis, we have identified three residues on the VA387 capsid that are sterically close to the acetamide and are required for binding to A but not B antigens, indicating that the acetamide determines the binding specificity between the A and B antigens. Further mutational analysis showed that a nearby open cavity may also be involved in binding specificity to HBGAs. In addition, a systematic mutational analysis of residues in and around the binding interface has identified a group of amino acids that are required for binding but do not have direct contact with the carbohydrate antigens, implying that these residues may be involved in the structural integrity of the receptor binding interface. Taken together, our study provides new insights into the carbohydrate/capsid interactions which are a valuable complement to the atomic structures in understanding the virus/host interaction and in the future design of antiviral agents.

  8. Palladium mediated intramolecular multiple C-X/C-H cross coupling and C-H activation: synthesis of carbazole alkaloids calothrixin B and murrayaquinone A.

    PubMed

    Kaliyaperumal, Srinivasan A; Banerjee, Shyamapada; U K, Syam Kumar

    2014-08-28

    Straightforward palladium mediated syntheses of calothrixin B and murrayaquinone A are described. Regioselective palladium mediated intramolecular multiple C-X/C-H cross coupling reaction on N-(4-((2-bromophenyl)amino)-2,5-dimethoxybenzyl)-N-(2-iodophenyl)acetamide followed by CAN oxidation afforded calothrixin B in excellent yield in two steps. A linear synthesis has also been developed for calothrixin B. Utilizing C-H functionalization as well as palladium mediated intramolecular C-X/C-H cross coupling reaction, murrayaquinone A synthesis was achieved. Overall, these synthetic methodologies provide an expedient entry to these biologically active alkaloids in a short reaction sequence.

  9. Characterization and identification of gram-negative, nonfermentative bacteria.

    PubMed Central

    Oberhofer, T R; Rowen, J W; Cunningham, G F

    1977-01-01

    The morphological and physiological characteristics of 593 strains of nonfermentative, gram-negative bacteria are described. A battery of 46 tests was used to identify and differentiate strains representing 8 genera and 31 species of named and group-designated bacteria. Seven selected amides and organic salts were closely examined to determine their usefulness, individually or as a battery, in characterizing and identifying the organisms. Of these, allantoin and acetamide showed the most promise in differentiating the more commonly occurring organisms from biochemically similar species. Susceptiblilty patterns to 12 antimicrobics also proved useful in differentiation, especially among atypical strains. PMID:845246

  10. Space thermal control development

    NASA Technical Reports Server (NTRS)

    Hoover, M. J.; Grodzka, P. G.; Oneill, M. J.

    1971-01-01

    The results of experimental investigations on a number of various phase change materials (PCMs) and PCMs in combination with metals and other materials are reported. The evaluations include the following PCM system performance characteristics: PCM and PCM/filler thermal diffusivities, the effects of long-term thermal cycling, PCM-container compatibility, and catalyst effectiveness and stability. Three PCMs demonstrated performance acceptable enough to be considered for use in prototype aluminum thermal control devices. These three PCMs are lithium nitrate trihydrate with zinc hydroxy nitrate catalyst, acetamide, and myristic acid. Of the fillers tested, aluminum honeycomb filler was found to offer the most increase in system thermal diffusivity.

  11. Two Half-Sandwiched Ruthenium (II) Compounds Containing 5-Fluorouracil Derivatives: Synthesis and Study of DNA Intercalation

    PubMed Central

    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. PMID:25789618

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

    PubMed

    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.

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

    PubMed

    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.

  14. Synthesis of 1,2-amino alcohols by sigmatropic rearrangements of 3-(N-tosylamino)allylic alcohol derivatives.

    PubMed

    Barbazanges, Marion; Meyer, Christophe; Cossy, Janine; Turner, Peter

    2011-04-11

    Sigmatropic rearrangements of 3-(N-tosylamino)allylic alcohol derivatives, a particular subclass of functionalized enamides, have been investigated. Whereas the presence of the nitrogen atom alters the stereochemical outcome of Ireland-Claisen rearrangements of glycolates derived from such substrates, [2,3]-Wittig rearrangements of α-allyloxy acetamides or propargylic ethers derivatives provide access to a wide variety of functionalized 1,2-amino alcohols usually with high levels of stereocontrol, as well as to heterocyclic compounds. The stereoselectivity issues of these rearrangements (1,2-diastereoselectivity, auxiliary-induced diastereoselection, chirality transfer, and double stereodifferentiation) were thoroughly investigated.

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

    NASA Astrophysics Data System (ADS)

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

    2013-07-01

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

  16. Electrostatics in the self-assembly of macromolecular surfactants

    NASA Astrophysics Data System (ADS)

    Mendes, E.; Schädler, V.; Marques, C. M.; Lindner, P.; Wiesner, U.

    1997-12-01

    We report on a small-angle neutron scattering (SANS) study of dilute solutions of neutral and charged polystyrene-polyisoprene (PS-b-PI) diblock copolymers in dimethyl acetamide (DMAc), a polar selective solvent for PS. This is a model macromolecular surfactant system: the low glass temperature of the PI block ensures that thermodynamic equilibrium can be attained; the ionic character of the copolymers is provided by a single sulfonate group at the free chain end of the PI block. The crossover from ionic to non-ionic behaviour is investigated by addition of salt. The results are compared to theoretical predictions for micellization of these model macromolecular systems.

  17. Synthesis and characteristics of polyarylene ether sulfones

    NASA Technical Reports Server (NTRS)

    Viswanathan, R.; Johnson, B. C.; Ward, T. C.; Mcgrath, J. E.

    1981-01-01

    A method utilizing potassium carbonate/dimethyl acetamide, as base and solvent respectively, was used for the synthesis of several homopolymers and copolymers derived from various bisphenols. It is demonstrated that this method deviates from simple second order kinetics; this deviation being due to the heterogeneous nature of the reaction. Also, it is shown that a liquid induced crystallization process can improve the solvent resistance of these polymers. Finally, a Monte Carlo simulation of the triad distribution of monomers in nonequilibrium copolycondensation is discussed.

  18. Forced degradation study of thiocolchicoside: characterization of its degradation products.

    PubMed

    Erika, Del Grosso; Silvio, Aprile; Giorgio, Grosa

    2012-03-05

    Thiocolchicoside (TCC, N-[1,2-dimethoxy-10-methylsulphanyl-9-oxo-3-(3,4,5-trihydroxy-6-hydroxymethyl-tetrahydropyran-2-yloxy)-5,6,7,9-tetrahydro-benzo[a]heptalen-7-yl]-acetamide) was subjected to hydrolytic, oxidative, and photolytic stresses. TCC underwent degradation in acidic, basic, and oxidative conditions, while it was stable toward other stress conditions. The degradation products (DPs) were detected and their separation was achieved on a SGE Wakosil C18RS 5μm (250*4.6 mm; SGE) column employing a gradient LC-MS method for a total time of analysis of 18 min. The mass fragmentation pathways of both thiocolchicoside and its degradation products were established using LC-MS experiments assigning the structures to the DPs. In particular, five DPs were identified as: D1SO (N-[1,2-dimethoxy-10-methylsulphoxide-9-oxo-3-(3,4,5-trihydroxy-6-hydroxymethyl-tetrahydropyran-2-yloxy)-5,6,7,9-tetrahydro-benzo[a]heptalen-7-yl]-acetamide), D1SO(2) (N-[1,2-dimethoxy-10-methylsulphone-9-oxo-3-(3,4,5-trihydroxy-6-hydroxymethyl-tetrahydropyran-2-yloxy)-5,6,7,9-tetrahydro-benzo[a]heptalen-7-yl]-acetamide), D2 ([1,2-dimethoxy-10-methylsulphanyl-9-oxo-3-(3,4,5-trihydroxy-6-hydroxymethyl-tetrahydropyran-2-yloxy)-5,6,7,9-tetrahydro-benzo[a]heptalen-7-yl]-amine), D3 (N-[1,2-dimethoxy-3-hydroxy-10-methylsulphanyl-9-oxo-5,6,7,9-tetrahydro-benzo[a]heptalen-7-yl]-acetamide or 3-O-demethylthiocolchicine), D4 ([1,2-dimethoxy-3-hydroxy-10-methylsulphanyl-9-oxo-5,6,7,9-tetrahydro-benzo[a]heptalen-7-yl]-amine or N-deacetyl-3-O-demethylthiocochicine). Moreover, the structures of DPs were confirmed by synthesis of the reference standards which were fully characterized by MS, NMR, IR analyses. Finally a comprehensive degradation scheme of TCC was proposed allowing to outline D1SO and D3 as the indicators of its stability for oxidative and hydrolytic stress conditions.

  19. Copper-catalyzed direct amination of ortho-functionalized haloarenes with sodium azide as the amino source.

    PubMed

    Zhao, Haibo; Fu, Hua; Qiao, Renzhong

    2010-05-21

    A simple copper-catalyzed direct amination of ortho-functionalized haloarenes (2-halobenzoic acid, 2-halobenzamide, and N-(2-bromophenyl)acetamide derivatives) has been developed with use of NaN(3) as the amino source in ethanol, and the corresponding ortho-functionalized aromatic amines were synthesized in good to excellent yields. The protocol undergoes one-pot Ullmann-type coupling of ortho-functionalized haloarenes with NaN(3) to lead to ortho-functionalized azidoarenes, followed by reduction with ethanol.

  20. Indole-3-acetic acid in plant-microbe interactions.

    PubMed

    Duca, Daiana; Lorv, Janet; Patten, Cheryl L; Rose, David; Glick, Bernard R

    2014-07-01

    Indole-3-acetic acid (IAA) is an important phytohormone with the capacity to control plant development in both beneficial and deleterious ways. The ability to synthesize IAA is an attribute that many bacteria including both plant growth-promoters and phytopathogens possess. There are three main pathways through which IAA is synthesized; the indole-3-pyruvic acid, indole-3-acetamide and indole-3-acetonitrile pathways. This chapter reviews the factors that effect the production of this phytohormone, the role of IAA in bacterial physiology and in plant-microbe interactions including phytostimulation and phytopathogenesis.

  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.

    PubMed

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

    PubMed

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

    2014-08-06

    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.

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

    NASA Astrophysics Data System (ADS)

    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.

  4. Influence of ethylene-oxy spacer group on the activity of linezolid: synthesis of potent antibacterials possessing a thiocarbonyl group.

    PubMed

    Selvakumar, N; Raheem, Mohammed A; Khera, Manoj Kumar; Rajale, Trideep V; Kumar, Magadi Sitaram; Kandepu, Sreenivas; Das, Jagattaran; Rajagopalan, R; Iqbal, Javed; Trehan, Sanjay

    2003-12-01

    The influence of an ethylene-oxy spacer element between the heterocycle and the aromatic ring in linezolid is reported. The introduction of such spacer group generated compounds with inferior antibacterial activity. However, the conversion of the acetamide group present in the linezolid analogues to either thiocarbamate or thioacetamide functionality restored the activity. The synthesis of linezolid analogues possessing the ethylene-oxy spacer group along with SAR studies with different heterocycles and preparation of some thiocarbonyl compounds possessing potent antibacterial property are presented.

  5. A facile method for the preparation of MOM-protected carbamates.

    PubMed

    Barnes, David M; Barkalow, Jufang; Plata, Daniel J

    2009-01-15

    A novel method for the preparation of MOM-protected carbamates is described that avoids the use of MOM-Cl, a regulated carcinogen. The two-step, one-pot procedure generates a reactive N-chloromethyl carbamate that is quenched with methanol to afford MOM-protected carbamates. The process is tolerant of a variety of functionalities, including Boc, sulfonamide, and acetamide protecting groups. Mild conditions for the removal of the MOM group are also described; selective deprotection of the MOM group in the presence of a Boc group has been demonstrated.

  6. Catalytic behaviour in the ring-opening polymerisation of organoaluminiums supported by bulky heteroscorpionate ligands.

    PubMed

    Castro-Osma, Jose A; Alonso-Moreno, Carlos; Lara-Sánchez, Agustín; Otero, Antonio; Fernández-Baeza, Juan; Sánchez-Barba, Luis F; Rodríguez, Ana M

    2015-07-21

    A series of alkyl organoaluminium complexes based on bulky heteroscorpionate ligands were designed as catalysts for the ring-opening polymerisation of cyclic esters. Thus, the treatment of AlX3 (X = Me, Et) with bulky acetamide or thioacetamide heteroscorpionate ligands nbptamH (1) [nbptamH = N-naphthyl-2,2-bis(3,5-dimethylpyrazol-1-yl)thioacetamide], fbpamH (2) [fbpamH = N-fluorenyl-2,2-bis(3,5-dimethylpyrazol-1-yl)acetamide], ptbptamH (3) [ptbptamH = N-phenyl-2,2-bis(3,5-di-tert-butylpyrazol-1-yl)thioacetamide], ntbptamH (4) [ntbptamH = N-naphthyl-2,2-bis(3,5-di-tert-butylpyrazol-1-yl)thioacetamide], ptbpamH (5) [ptbpamH = N-phenyl-2,2-bis(3,5-di-tert-butylpyrazol-1-yl)acetamide] and (S)-mtbpamH (6) [(S)-mtbpamH = (S)-(−)-N-α-methylbenzyl-2,2-bis(3,5-di-tert-butylpyrazol-1-yl)acetamide] for 1 hour at 0 °C afforded the dialkyl aluminium complexes [AlX2{κ(2)-nbptam}] (X = Me 7, Et 8), [AlX2{κ(2)-fbpam}] (X = Me 9, Et 10), [AlX2{κ(2)-ptbptam}] (X = Me 11, Et 12), [AlX2{κ(2)-ntbptam}] (X = Me 13, Et 14), [AlX2{κ2(-)ptbpam}] (X = Me 15, Et 16) and [AlX2{κ(2)-(S)-mtbpam}] (X = Me 17, Et 18). The structures of the complexes were determined by spectroscopic methods and the X-ray crystal structure of 14 was also established. The alkyl-containing aluminium complexes 7–18 can act as efficient single-component initiators for the ring-opening polymerisation of ε-caprolactone and rac-lactide. The polymerisations are living, as evidenced by the narrow polydispersities of the isolated polymers and the linear nature of the number average molecular weight versus conversion plot. Finally, a comparative study of ring-opening polymerisation for new bulky heteroscorpionate aluminium initiators and the less congested aluminium analogues is reported.

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

    DOEpatents

    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.

  8. Genotoxicity studies with the unstable Zeste-White (UZ) system of Drosophila melanogaster: Results with ten carcinogenic compounds

    SciTech Connect

    Batiste-Alentorn, M.; Xamena, N.; Creus, A.; Marcos, R. )

    1991-01-01

    To increase the number of chemicals tested using the Zeste-White (UZ) somatic mutation assay, ten selected carcinogens (acetamide, acrylamide, benzo({alpha})pyrene, cyclophosphamide, diethylstilbestrol, 4-nitroquinoline N-oxide, propyleneimine, safrole, thiourea, and o-toluidine) have been evaluated in this assay. The results show that all the compounds tested produce significant increases in the eye spot frequency at, at least, one of the concentrations assayed, indicating that the Zeste-White assay appears to be highly sensitive to these carcinogenic compounds. That is in agreement with data previously reported by other authors.

  9. Surface-water-quality assessment of the Yakima River basin, Washington; distribution of pesticides and other organic compounds in water, sediment, and aquatic biota, 1987-91; with a section on dissolved organic carbon in the Yakima River basin

    USGS Publications Warehouse

    Rinella, Joseph F.; McKenzie, Stuart W.; Crawford, J. Kent; Foreman, William T.; Fuhrer, Gregory J.; Morace, Jennifer L.; Aiken, George R.

    1999-01-01

    During 1987-91, chemical data were collected for pesticides and other organic compounds in surface water, streambed sediment, suspended sediment, agricultural soil, and aquatic biota to determine the occurrence, distribution, transport, and fate of organic compounds in the Yakima River basin in Washington. The report describes the chemical and physical properties of the compounds most frequently detected in the water column; organochlorine compounds including DDT, organophosphorus compounds, thiocarbamate and sulfite compounds, acetamide and triazine compounds, and chlorophenoxy-acetic acid and benzoic compounds. Concentrations are evaluated relative to chronic-toxicity water quality criteria and guidelines for the protection of human health and freshwater aquatic life.

  10. Crystal structure of 2-cyano-N-(furan-2-ylmeth­yl)-3-(3-nitro­phen­yl)propanamide

    PubMed Central

    Subhadramma, Shivanna; Siddaraju, Budanur Papaiah; Chandra, Naveen; Saravanan, Janardhanan; Gayathri, Dasararaju

    2015-01-01

    In the title compound, C15H11N3O4, the acetamide group is inclined to the furan ring by 66.5 (1)°. The dihedral angle between the furan ring and the benzene ring is 66.8 (1)°. In the crystal, mol­ecules are linked by pairs of N—H⋯N hydrogen bonds, forming inversion dimers with an R 2 2(12) ring motif. The dimers are linked via two pairs of C—H⋯O hydrogen bonds to the same acceptor oxygen atom, enclosing R 2 1(6) ring motifs, forming chains along the [101] direction. PMID:26396801

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

    PubMed

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

    2014-01-24

    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.

  12. Submersible Packaging Techniques

    DTIC Science & Technology

    1989-07-01

    Chloride V,F Aluminum Sulfate B,E,N Borax B,E Amines E Boric Acid B,E Ammonia (Anhydrous/liquid) E,B Boron Fluids (HEF) V,F Ammonium Carbonate E,N Brake...Elastomer/Fluid Compatibilities. Fluid Code Fluid cad& Acetaldhyde E Animal Oil BV,F Acetamide B,E,N Aqua Regia E,F Acetic Acid E Aroclor V Acetic...Anhydride N,E Arsenic Acid F,E Acetone E Askarel V,B,F Acetophenone E Asphalt V,K Acetyl Acetone E Barium Chloride B,E Acetyl Chloride V,E Barium Hydroxide B

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

    PubMed

    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.

  14. Alkyl Chlorides as Hydrogen Bond Acceptors

    SciTech Connect

    Nadas, Janos I; Vukovic, Sinisa; Hay, Benjamin

    2012-01-01

    To gain an understanding of the role of an alkyl chloride as a hydrogen bond acceptor, geometries and interaction energies were calculated at the MP2/aug-cc-pVDZ level of theory for complexes between ethyl chloride and representative hydrogen donor groups. The results establish that these donors, which include hydrogen cyanide, methanol, nitrobenzene, pyrrole, acetamide, and N-methylurea, form X-H {hor_ellipsis} Cl hydrogen bonds (X = C, N, O) of weak to moderate strength, with {Delta}E values ranging from -2.8 to -5.3 kcal/mol.

  15. Crystal structure of 4-acetamido-benzoic acid monohydrate.

    PubMed

    Cai, Wen-Juan; Chi, Shao-Ming; Kou, Jun-Feng; Liu, Feng-Yi

    2014-11-01

    In the title compound, C9H9NO3·H2O, the plane of the acetamide group is oriented at 20.52 (8)° with respect to the benzene ring, whereas the plane of the carb-oxy-lic acid group is essentially coplanar with the benzene ring [maximum deviation = 0.033 (1) Å]. In the crystal, classical O-H⋯O and N-H⋯O hydrogen bonds and weak C-H⋯O hydrogen bonds link the organic mol-ecules and water mol-ecules of crystallization into a three-dimensional supra-molecular architecture.

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

    PubMed Central

    Ichikawa, Takafumi; Ishihara, Kazuhiko; Saigenji, Katsunori; Hotta, Kyoko

    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 striatum. [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. 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. 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). Ranitidine at 10−4 M did not suppress the roxatidine-induced increase in [3H]glucosamine incorporation into mucin. 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 (5×10−3 M). These results suggest that the cardinal chemical features of roxatidine for the activation of

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

    PubMed

    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.

  18. Synthesis and characterisation of bis-cyclen based dinuclear lanthanide complexes.

    PubMed

    Gunnlaugsson, Thorfinnur; Harte, Andrew J

    2006-04-21

    The design and synthesis of several bis-macrocyclic cyclen (1,4,7,10-tetraazacyclododecane) ligands and their corresponding lanthanum or europium complexes is described; these dinuclear lanthanide systems were made by connecting two macrocyclic cyclen moieties through a rigid, covalent, p-xylylenediamide bridge or a flexible aliphatic hexane bridge. These ligands were subsequently functionalised with six acetamide pendant arms (CONR1R2: R1 = R2 = H or CH3, or R1 = H, R2 = CH3). The corresponding lanthanide bis-complexes were then formed by reaction with La(III) and Eu(III) triflates, yielding overall cationic (+VI charged) complexes.

  19. Substituted Tetrahydroisoquinolines as Selective Antagonists for the Orexin 1 Receptor

    PubMed Central

    Perrey, David A.; German, Nadezhda A.; Gilmour, Brian P.; Li, Jun-Xu; Harris, Danni L.; Thomas, Brian F.; Zhang, Yanan

    2013-01-01

    Increasing evidence implicates the orexin 1 (OX1) receptor in reward processes, suggesting OX1 antagonism could be therapeutic in drug addiction. In a program to develop an OX1 selective antagonist, we designed and synthesized a series of substituted tetrahydroisoquinolines and determined their potency in OX1 and OX2 calcium mobilization assays. Structure-activity relationship (SAR) studies revealed limited steric tolerance and preference for electron deficiency at the 7-position. Pyridylmethyl groups were shown to be optimal for activity at the acetamide position. Computational studies resulted in a pharmacophore model and confirmed the SAR results. Compound 72 significantly attenuated the development of place preference for cocaine in rats. PMID:23941044

  20. Mimicking the intradiol catechol cleavage activity of catechol dioxygenase by high-spin iron(III) complexes of a new class of a facially bound [N2O] ligand.

    PubMed

    Panda, Manas K; John, Alex; Shaikh, Mobin M; Ghosh, Prasenjit

    2008-12-15

    A series of high-spin iron(III) complexes, {N-R-2-[(pyridin-2-ylmethyl)amino]acetamide}FeCl(3) [R = mesityl (1b), 2,6-Et(2)C(6)H(3) (2b), and 2,6-i-Pr(2)C(6)H(3) (3b)], that functionally emulate the intradiol catechol dioxygenase enzyme are reported. In particular, these enzyme mimics, 1b, 2b, and 3b, which utilized molecular oxygen in carrying out the intradiol catechol cleavage of 3,5-di-tert-butylcatechol with high regioselectivity (ca. 81-85%) at room temperature under ambient conditions, were designed by employing a new class of a facially bound [N(2)O] ligand, namely, N-R-2-[(pyridin-2-ylmethyl)amino]acetamide [R = mesityl (1a), 2,6-Et(2)C(6)H(3) (2a), and 2,6-i-Pr(2)C(6)H(3) (3a)]. The density functional theory studies revealed that the intradiol catechol cleavage reaction proceeded by an iron(III) peroxo intermediate that underwent 1,2-Criegee rearrangement to yield the intradiol catechol cleaved products analogous to the native enzyme.

  1. Synthesis, NMR conformational analysis and pharmacological evaluation of 7,7a,13,14-tetrahydro-6H-cyclobuta[b]pyrimido[1,2-a:3,4-a']diindole analogues as melatonin receptor ligands.

    PubMed

    Attia, Mohamed I; Güclü, Deniz; Hertlein, Barbara; Julius, Justin; Witt-Enderby, Paula A; Zlotos, Darius P

    2007-07-07

    A structure for the self-condensation product of 2-(1H-indol-2-yl)ethyl tosylate 2a, previously proposed as 6,7,14,15-tetrahydro-15aH-azocino[1,2-a:6,5-b]diindole 3a, was revised based on the (13)C-2D-INADEQUATE experiment, and proved to be 7,7a,13,14-tetrahydro-6H-cyclobuta[b]pyrimido[1,2-a:3,4-a']diindole 4a. A mechanism for the unexpected formation of this novel hexacyclic heterocycle was proposed and its NMR solution structure was elucidated. Five derivatives of the title ring skeleton 12-16 designed as melatonin receptor ligands were synthesized and their affinities for the human MT(1) and MT(2) receptors were determined. Both butyramides 13 and 15, as well as the non-methoxy acetamide 12 exhibited micromolar binding affinities for both receptors being slightly MT(2) selective. The methoxy acetamide 14 showed the best pharmacological profile exhibiting a five times higher affinity for MT(1) (K(i) = 49 nM) than for MT(2) (K(i) = 246 nM) receptor.

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

    NASA Astrophysics Data System (ADS)

    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.

  3. Electrochemical stability of organic electrolytes in supercapacitors: Spectroscopy and gas analysis of decomposition products

    NASA Astrophysics Data System (ADS)

    Kurzweil, P.; Chwistek, M.

    The fundamental aging mechanisms in double-layer capacitors based on alkylammonium electrolytes in acetonitrile were clarified for the first time. After abusive testing at cell voltages above 4 V, ultracapacitors cast out a crystalline mass of residual electrolyte, organic acids, acetamide, aromatics, and polymer compounds. The mixture could be reproduced by electrolysis. The decomposition products of active carbon electrodes and electrolyte solution after a heat treatment at 70 °C were identified by infrared and ultraviolet spectroscopy, liquid and headspace GC-MS, thermogravimetric analysis, and X-ray diffraction. The alkylammonium cation is destroyed by the elimination of ethene. The fluoroborate anion works as source of fluoride and hydrogenfluoride, and boric acid derivates. Acetonitrile forms acetamide, acetic and fluoroacetic acid, and derivates thereof. Due to the catalytic activity of the electrode, heterocyclic compounds are generated in the liquid phase. The etched aluminium support under the active carbon layer is locally destroyed by fluorination. Exploring novel electrolytes, ionic liquids were characterized by impedance spectroscopy.

  4. Characterization of Four Bifunctional Plant IAM/PAM-Amidohydrolases Capable of Contributing to Auxin Biosynthesis

    PubMed Central

    Sánchez-Parra, Beatriz; Frerigmann, Henning; Pérez Alonso, Marta-Marina; Carrasco Loba, Víctor; Jost, Ricarda; Hentrich, Mathias; Pollmann, Stephan

    2014-01-01

    Amidases [EC 3.5.1.4] capable of converting indole-3-acetamide (IAM) into the major plant growth hormone indole-3-acetic acid (IAA) are assumed to be involved in auxin de novo biosynthesis. With the emerging amount of genomics data, it was possible to identify over forty proteins with substantial homology to the already characterized amidases from Arabidopsis and tobacco. The observed high conservation of amidase-like proteins throughout the plant kingdom may suggest an important role of theses enzymes in plant development. Here, we report cloning and functional analysis of four, thus far, uncharacterized plant amidases from Oryza sativa, Sorghum bicolor, Medicago truncatula, and Populus trichocarpa. Intriguingly, we were able to demonstrate that the examined amidases are also capable of converting phenyl-2-acetamide (PAM) into phenyl-2-acetic acid (PAA), an auxin endogenous to several plant species including Arabidopsis. Furthermore, we compared the subcellular localization of the enzymes to that of Arabidopsis AMI1, providing further evidence for similar enzymatic functions. Our results point to the presence of a presumably conserved pathway of auxin biosynthesis via IAM, as amidases, both of monocot, and dicot origins, were analyzed. PMID:27135507

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

    PubMed

    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.

  6. Design, synthesis, and examination of neuron protective properties of alkenylated and amidated dehydro-silybin derivatives.

    PubMed

    Yang, Lei Xiang; Huang, Ke Xin; Li, Hai Bo; Gong, Jing Xu; Wang, Feng; Feng, Yu Bing; Tao, Qiao Feng; Wu, Yi Hang; Li, Xiao Kun; Wu, Xiu Mei; Zeng, Su; Spencer, Shawn; Zhao, Yu; Qu, Jia

    2009-12-10

    A series of C7-O- and C20-O-amidated 2,3-dehydrosilybin (DHS) derivatives ((+/-)-1a-f and (+/-)-2), as well as a set of alkenylated DHS analogues ((+/-)-4a-f), were designed and de novo synthesized. A diesteric derivative of DHS ((+/-)-3) and two C23 esterified DHS analogues ((+/-)-5a and (+/-)-5b) were also prepared for comparison. The cell viability of PC12 cells, Fe(2+) chelation, lipid peroxidation (LPO), free radical scavenging, and xanthine oxidase inhibition models were utilized to evaluate their antioxidative and neuron protective properties. The study revealed that the diether at C7-OH and C20-OH as well as the monoether at C7-OH, which possess aliphatic substituted acetamides, demonstrated more potent LPO inhibition and Fe(2+) chelation compared to DHS and quercetin. Conversely, the diallyl ether at C7-OH and C20-OH was more potent in protection of PC12 cells against H(2)O(2)-induced injury than DHS and quercetin. Overall, the more lipophilic alkenylated DHS analogues were better performing neuroprotective agents than the acetamidated derivatives. The results in this study would be beneficial for optimizing the therapeutic potential of lignoflavonoids, especially in neurodegenerative disorders such as Alzheimer's and Parkinson's disease.

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

    PubMed

    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.

  8. Novel chromatographic separation and carbon solid-phase extraction of acetanilide herbicide degradation products.

    PubMed

    Shoemaker, Jody A

    2002-01-01

    One acetamide and 5 acetanilide herbicides are currently registered for use in the United States. Over the past several years, ethanesulfonic acid (ESA) and oxanilic acid (OA) degradation products of these acetanilide/acetamide herbicides have been found in U.S. ground waters and surface waters. Alachlor ESA and other acetanilide degradation products are listed on the U.S. Environmental Protection Agency's (EPA) 1998 Drinking Water Contaminant Candidate List. Consequently, EPA is interested in obtaining national occurrence data for these contaminants in drinking water. EPA currently does not have a method for determining these acetanilide degradation products in drinking water; therefore, a research method is being developed using liquid chromatography/negative ion electrospray/mass spectrometry with solid-phase extraction (SPE). A novel chromatographic separation of the acetochlor/alachlor ESA and OA structural isomers was developed which uses an ammonium acetate-methanol gradient combined with heating the analytical column to 70 degrees C. Twelve acetanilide degradates were extracted by SPE from 100 mL water samples using carbon cartridges with mean recoveries >90% and relative standard deviations < or =16%.

  9. Occurrence and transport of acetochlor in streams of the Mississippi River Basin

    USGS Publications Warehouse

    Clark, G.M.; Goolsby, D.A.

    1999-01-01

    The herbicide acetochlor [2-chloro-N-(ethoxymethyl)-N-(2-ethyl-6- methylphenyl) acetamide] was first used on corn (Zea mays L.) in the USA during the growing season of 1994. By 1996, it was the third most heavily used corn herbicide in the midwestern USA. During the growing season of 1997, 78% of 375 samples collected at 32 stream sites in the Mississippi River Basin contained detectable concentrations of acetochlor. However, concentrations in only 2% of the samples exceeded 2 ??g/L, the maximum annual average concentration allowable in public water supplies derived primarily from surface water. The largest acetochlor concentrations were detected in streams draining basins in parts of Illinois, Indiana, and Iowa. The median concentration of acetochlor in streams was about 10% that of atrazine (6- chloro-N-ethyl-N-isopropyl-1,3,5-triazine-2,4-diamine), about 25% that of metolachlor [2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-1-methylethyl) acetamide], about 50% that of cyanazine [2-[[4-chloro-6-(ethylamino)-1,3,5- triazin-2-yl]amino]-2-methylpropionitrile], and about threefold that of alachlor [2-chloro-2',6'-diethyl-N-(methoxymethyl) acetanilide]. Load estimates indicate that, during the growing season of 1997, agricultural subbasins draining areas of Illinois, Indiana, and Iowa contributed about 37000 kg, or 74%, of the 50 000 kg of acetochlor measured in streams of the Mississippi River Basin.

  10. Oxidation of amino groups by hydroxyl radicals in relation to the oxidation degree of the alpha-carbon.

    PubMed

    Leitner, N Karpel Vel; Berger, P; Legube, B

    2002-07-15

    Nitrogen organic compounds constitute a large class of aqueous pollutants. These compounds include not only azoic structures, nitrogen heterocycles, and nitrous groups but also amides and amines. This work consisted in studying the OH* induced oxidation of simple primary amines in dilute aqueous solution with special attention to mineralization of the nitrogen group as a function of the nature of the alpha-carbon. H2O2/UV and gamma-irradiation processes were used for the production of OH* radicals, and the molecules studied were one alpha-amino acid i.e., glycine (HOOCCH2NH2), and two primary amides i.e., acetamide (CH3CONH2) and oxamic acid (HOOCCONH2). It was shown that the oxidation of glycine leads to the formation of ammonia, whereas the acetamide molecule is first oxidized into oxamic acid ending in complete mineralization with production of nitrates. Reaction mechanisms are proposed which account for the observed inorganic nitrogen end product depending on the oxidation degree of the carbon atoms of the molecules. It follows that the present study will allow for prediction of the fate of nitrogen resulting from the oxidation of primary amino groups by OH* radicals.

  11. Can the unauthorised use of ceftiofur be detected in poultry?

    PubMed

    Heinrich, Katharina; Chan, Danny; Fussell, Richard J; Kay, Jack F; Sharman, Matthew

    2013-01-01

    Ceftiofur is a third-generation cephalosporin antibiotic used to treat cattle and swine for bacterial infection of the respiratory tract. It is not authorised for use in poultry within the European Union. Due to the complexity of the chemistry and metabolism of ceftiofur, maximum residue limits (MRLs) are based on desfuroylceftiofur (DFC) equivalents after chemical conversion of all compounds that have an intact ß-lactam ring. In practice the DFC is usually stabilised as the acetamide (desfuroylceftiofur acetamide - DFCA) for analysis. Because of recent evidence of off-label use in the European Union, a policy need emerged to develop a cost-effective method for the detection of ceftiofur residues in poultry tissues. One-day-old chicks were each dosed subcutaneously with ceftiofur and samples taken from day 1 to day 44 post-dosing. Residues of ceftiofur parent compound were detected in whole chicks, wing feathers and faeces. On the basis of this finding it was decided to evaluate ceftiofur parent, as the marker, instead of proceeding with the time-consuming conversion to DFCA. Expected metabolites, DFC and desfuroylceftiofur cysteine disulfide (DCCD), were not detected in whole chicks, muscle or liver, but DFC was found in wing feathers. These results indicate that determination of ceftiofur parent compound in either whole chicks or possibly wing feathers and faeces may allow the detection of the misuse of ceftiofur.

  12. Design, synthesis and biological evaluation of a novel series of peripheral-selective noradrenaline reuptake inhibitor.

    PubMed

    Fujimori, Ikuo; Yukawa, Tomoya; Kamei, Taku; Nakada, Yoshihisa; Sakauchi, Nobuki; Yamada, Masami; Ohba, Yusuke; Takiguchi, Maiko; Kuno, Masako; Kamo, Izumi; Nakagawa, Hideyuki; Hamada, Teruki; Igari, Tomoko; Okuda, Teruaki; Yamamoto, Satoshi; Tsukamoto, Tetsuya; Ishichi, Yuji; Ueno, Hiroyuki

    2015-08-01

    Centrally acting noradrenaline reuptake inhibitor (NRI) is reportedly effective for patients with stress urinary incontinence (SUI) by increasing urethral closure in the clinical Phase IIa study with esreboxetine. Noradrenaline transporters are expressed in both central and peripheral nervous systems and the contribution of each site to efficacy has not been clarified. This report describes the development of a series of peripheral-selective 7-phenyl-1,4-oxazepane NRIs to investigate the contribution of the peripheral site to increasing urethral resistance in rats. (6S,7R)-1,4-Oxazepane derivative 7 exhibited noradrenaline transporter inhibition with high selectivity against inhibitions of serotonin and dopamine transporters. A replacement of hydroxyl with acetamide group contributed to enhancement of peripheral selectivity by increasing molecular polarity. Compound 12, N-{[(6S,7R)-7-(3,4-dichlorophenyl)-1,4-oxazepan-6-yl]methyl}acetamide 0.5 fumarate, which showed effectively no brain penetration in rats, increased urethral resistance in a dose-dependent manner and exhibited a maximal effect on par with esreboxetine. These results demonstrate that the urethral resistance-increasing effects of NRI in rats are mainly caused by the inhibition of noradrenaline transporters in the peripheral sites.

  13. 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.

    PubMed

    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.

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

    PubMed

    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.

  15. Synthesis of dense energetic materials. Annual report

    SciTech Connect

    Coon, C.

    1982-07-01

    The objective of the research described in the report is to synthesize new, dense, stable, highly energetic materials which will ultimately be a candidates for improved explosive and propellant formulations. Following strict guidelines pertaining to energy, density, stability, etc. Specific target molecules were chosen that appear to possess the improved properties desired for new energetic materials. This report summarizes research on the synthesis of these target materials from February 1981 to January 1982. The following compounds were synthesized: 5,5'-diamino-3,3'-bioxadiazole(1,2,4); 5,5'-bis(trichloromethyl)-3,3'-di(1,2,4-oxadiazole); 3,3'-bi(1,2,4-oxadiazole); ethylene tetranitramine (ETNA); N,N-bis(methoxymethyl)acetamide; N,N-bis(chloromethyl)acetamide; 7,8-dimethylglycoluril; Synthesis of 3,9-Di(t-butyl)-13,14-dimethyl-tetracyclo-(5,5,2,0/sup 5/ /sup 13/ 0/sup 11/ /sup 14/)-1,3,5,7,9,11-hexaaza-6,12-dioxotetradecane.

  16. Production of the Phytohormone Indole-3-Acetic Acid by Estuarine Species of the Genus Vibrio▿

    PubMed Central

    Gutierrez, Casandra K.; Matsui, George Y.; Lincoln, David E.; Lovell, Charles R.

    2009-01-01

    Strains of Vibrio spp. isolated from roots of the estuarine grasses Spartina alterniflora and Juncus roemerianus produce the phytohormone indole-3-acetic acid (IAA). The colorimetric Salkowski assay was used for initial screening of IAA production. Gas chromatography-mass spectroscopy (GC-MS) was then employed to confirm and quantify IAA production. The accuracy of IAA quantification by the Salkowski assay was examined by comparison to GC-MS assay values. Indole-3-acetamide, an intermediate in IAA biosynthesis by the indole-3-acetamide pathway, was also identified by GC-MS. Multilocus sequence typing of concatenated 16S rRNA, recA, and rpoA genes was used for phylogenetic analysis of environmental isolates within the genus Vibrio. Eight Vibrio type strains and five additional species-level clades containing a total of 16 environmental isolates and representing five presumptive new species were identified as IAA-producing Vibrio species. Six additional environmental isolates similar to four of the Vibrio type strains were also IAA producers. To our knowledge, this is the first report of IAA production by species of the genus Vibrio or by bacteria isolated from an estuarine environment. PMID:19218411

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

    PubMed Central

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

    2016-01-01

    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 < 0.05). Moreover, N-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 < 0.05). Results suggested that glutamine and N-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. PMID:27527211

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

    PubMed

    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.

  19. Major herbicides in ground water: results from the National Water-Quality Assessment.

    PubMed

    Barbash, J E; Thelin, G P; Kolpin, D W; Gilliom, R J

    2001-01-01

    To improve understanding of the factors affecting pesticide occurrence in ground water, patterns of detection were examined for selected herbicides, based primarily on results from the National Water-Quality Assessment (NAWQA) program. The NAWQA data were derived from 2,227 sites (wells and springs) sampled in 20 major hydrologic basins across the USA from 1993 to 1995. Results are presented for six high-use herbicides--atrazine (2-chloro-4-ethylamino-6-isopropylamino-s-triazine), cyanazine (2-[4-chloro-6-ethylamino-1,3,5triazin-2-yl]amino]-2-methylpropionitrile), simazine (2-chloro-4,6-bis-[ethylamino]-s-triazine), alachlor (2-chloro-N-[2,6-diethylphenyl]-N-[methoxymethyl]acetamide), acetochlor (2-chloro-N-[ethoxymethyl]-N-[2-ethyl-6-methylphenyl]acetamide), and metolachlor (2-chloro-N-[2-ethyl-6-methylphenyl]-N-[2-methoxylethyl]acetamide)--as well as for prometon (2,4-bis[isopropylamino]-6-methoxy-s-triazine), a nonagricultural herbicide detected frequently during the study. Concentrations were <1 microg L(-1) at 98% of the sites with detections, but exceeded drinking-water criteria (for atrazine) at two sites. In urban areas, frequencies of detection (at or above 0.01 microg L(-1)) of atrazine, cyanazine, simazine, alachlor, and metolachlor in shallow ground water were positively correlated with their nonagricultural use nationwide (P < 0.05). Among different agricultural areas, frequencies of detection were positively correlated with nearby agricultural use for atrazine, cyanazine, alachlor, and metolachlor, but not simazine. Multivariate analysis demonstrated that for these five herbicides, frequencies of detection beneath agricultural areas were positively correlated with their agricultural use and persistence in aerobic soil. Acetochlor, an agricultural herbicide first registered in 1994 for use in the USA, was detected in shallow ground water by 1995, consistent with previous field-scale studies indicating that some pesticides may be detected in ground

  20. Substitutions of Thr-103-Ile and Trp-138-Gly in amidase from Pseudomonas aeruginosa are responsible for altered kinetic properties and enzyme instability.

    PubMed

    Karmali, A; Pacheco, R; Tata, R; Brown, P

    2001-03-01

    Pseudomonas aeruginosa Ph1 is a mutant strain derived from strain AI3. The strain AI3 is able to use acetanilide as a carbon source through a mutation (T103I) in the amiE gene that encodes an aliphatic amidase (EC 3.5.1.4). The mutations in the amiE gene have been identified (Thr103Ile and Trp138Gly) by direct sequencing of PCR-amplified mutant gene from strain Ph1 and confirmed by sequencing the cloned PCR-amplified gene. Site-directed mutagenesis was used to alter the wild-type amidase gene at position 138 for Gly. The wild-type and mutant amidase genes (W138G, T103I-W138G, and T103I) were cloned into an expression vector and these enzymes were purified by affinity chromatography on epoxy-activated Sepharose 6B-acetamide/phenylacetamide followed by gel filtration chromatography. Altered amidases revealed several differences in kinetic properties, namely, in substrate specificity, sensitivity to urea, optimum pH, and enzyme stability, compared with the wild-type enzyme. The W138G enzyme acted on acetamide, acrylamide, phenylacetamide, and p-nitrophenylacetamide, whereas the double mutant (W138G and T103I) amidase acted only on p-nitrophenylacetamide and phenylacetamide. On the other hand, the T103I enzyme acted on p-nitroacetanilide and acetamide. The heat stability of altered enzymes revealed that they were less thermostable than the wild-type enzyme, as the mutant (W138G and W138G-T103I) enzymes exhibited t1/2 values of 7.0 and 1.5 min at 55 degrees C, respectively. The double substitution T103I and W138G on the amidase molecule was responsible for increased instability due to a conformational change in the enzyme molecule as detected by monoclonal antibodies. This conformational change in altered amidase did not alter its M(r) value and monoclonal antibodies reacted differently with the active and inactive T103I-W138G amidase.

  1. Major herbicides in ground water: Results from the National Water-Quality Assessment

    USGS Publications Warehouse

    Barbash, J.E.; Thelin, G.P.; Kolpin, D.W.; Gilliom, R.J.

    2001-01-01

    To improve understanding of the factors affecting pesticide occurrence in ground water, patterns of detection were examined for selected herbicides, based primarily on results from the National Water-Quality Assessment (NAWQA) program. The NAWQA data were derived from 2227 sites (wells and springs) sampled in 20 major hydrologic basins across the USA from 1993 to 1995. Results are presented for six high-use herbicides - atrazine (2-chloro-4-ethylamino-6-iso-propylamino-s-triazine), cyanazine (2-[4-chloro-6-ethylamino-l,3,5-triazin-2-yl]amino]-2-methylpropionitrile), simazine (2-chloro-4,6-bis[ethylamino]-s-triazine), alachlor (2-chloro-N-[2,6-diethylphenyl]-N-[methoxymethyl]acetamide), acetochlor (2-chloro-N-[ethoxymethyl]. N-[2-ethyl-6-methylphenyl]acetamide), and metolachlor (2-chloro-N-[2-ethyl-6-methylphenyl]-N-[2-methoxy-l- methylethyl]acetamide) - as well as for prometon (2,4-bis[isopropylamino]-6-methoxy-s-triazine), a nonagricultural herbicide detected frequently during the study. Concentrations were <1 ??g L-1 at 98% of the sites with detections, but exceeded drinking-water criteria (for atrazine) at two sites. In urban areas, frequencies of detection (at or above 0.01 ??g L-1) of atrazine, cyanazine, simazine, alachlor, and metolachlor in shallow ground water were positively correlated with their nonagricultural use nationwide (P < 0.05). Among different agricultural areas, frequencies of detection were positively correlated with nearby agricultural use for atrazine, cyanazine, alachlor, and metolachlor, but not simazine. Multivariate analysis demonstrated that for these five herbicides, frequencies of detection beneath agricultural areas were positively correlated with their agricultural use and persistence in aerobic soil. Acetochlor, an agricultural herbicide first registered in 1994 for use in the USA, was detected in shallow ground water by 1995, consistent with previous field-scale studies indicating that some pesticides may be detected in ground

  2. Synthesis and Characterization of Two Cyanoxime Ligands, Their Precursors, and Light Insensitive Antimicrobial Silver(I) Cyanoximates.

    PubMed Central

    Riddles, Courtney N.; Whited, Mark; Lotlikar, Shalaka R.; Still, Korey; Patrauchan, Marianna; Silchenko, Svitlana; Gerasimchuk, Nikolay

    2014-01-01

    High-yield syntheses of N-piperidine-cyanacetamide (1), N-morpholyl-cyanacetamide (4) and their oxime derivatives N-piperidine-2-cyano-2-oximino-acetamide (HPiPCO, 2) and N-morpholyc-2-cyano-2-oximino-acetamide (HMCO, 5) were developed using two-step preparations. At first, the reactions of neat cyanoacetic acid esters and the respective cyclic secondary amines such as piperideine and morpholine afforded pure cyanacetamides, which were converted into cyanoximes at room temperature using the nitrosation reaction with gaseous CH3ONO. The synthesized compounds were investigated by means of IR, 1H, 13C and UV-visible spectroscopy. Crystal structures of two starting substituted cyan-acetamides and two target cyanoximes were determined. Silver(I) complexes of AgL composition (L = PipCO, 3; MCO, 6) were prepared in high yield. Both metal complexes are thermally stable above 100oC, and remarkably stable to high intensity visible light. The stability of dried AgL compounds towards short wavelength UV-radiation (a frequently used germicidal light) was examined using diffusion reflectance spectroscopy. Both complexes demonstrate slow photoreduction within ~3 hrs, observable as a gradual color change and darkening due to the formation of fine (nano-scale) particles of metallic silver. The complex Ag(MCO), 6, is about 2.6 times less stable towards UV-radiation than its more lypophyllic analog Ag(PipCO), 3. Antimicrobial and biofilm growth inhibition properties of the prepared solid acrylate-based polymeric composites containing embedded silver(I) cyanoximates were investigated using three human pathogens: P. aeruginosa PAO1 (wound isolate), S. aureus NRS70 (methicillin resistant respiratory isolate), and S. mutans UA159 (cariogenic dental isolate). Studies showed that both 3 and 6 compounds completely abolished the growth of PAO1 at 0.5 weight % concentration, and the growth of UA159 and NRS70 at 1% concentration. Moreover, data demonstrates that complexes 3 and 6 also inhibit

  3. 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.

    PubMed

    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 < 0.05) in plasma. Compared with the diquat group, the arginine + diquat group had significantly higher levels of citrate, creatinine, homogentisate, and α-ketoglutarate while lower levels of acetamide, citrulline, ethanol, glycine, isobutyrate, lactate, malonate, methymalonate, N-acetylglutamate, N-methylnicotinamide, propionate, and β-glucose (P < 0.05) in urine. Compared with the diquat group, the N-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

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

    PubMed

    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.

  5. Poly (vinylidene fluoride-co-hexafluoropropylene)/polybenzimidazole blend nanofiber supported Nafion membranes for direct methanol fuel cells

    NASA Astrophysics Data System (ADS)

    Wang, Shih-Hua; Lin, Hsiu-Li

    2014-07-01

    This article presents preparation of poly (vinylidene fluoride-co-hexafluoropropylene) (PVdF-co-HFP) and polybenzimidazole (PBI) blend electrospun nanofiber (PVFP-BI) films from N,N‧-dimethyl acetamide (DMAc)/acetone mixture solutions. Using the PVFP-BI nanofiber film (thickness ∼13-15 μm) as a supporting material for impregnating Nafion resin solution, Nafion/PVFP-BI composite membranes (thickness ∼50 μm) are prepared and direct methanol fuel cell (DMFC) tests are performed. Better DMFC performance of the Nafion/PVFP-BI composite membrane than the commercial Nafion-117 (thickness ∼175 μm) and Nafion-212 (thickness ∼50 μm) membranes when blending with 5-10 wt.% of PBI in the PVFP-BI nanofiber support film is demonstrated.

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

    NASA Astrophysics Data System (ADS)

    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.

  7. Isolation and characterisation of degradation impurities in the cefazolin sodium drug substance.

    PubMed

    Sivakumar, Balasubramanian; Parthasarathy, Kannabiran; Murugan, Raman; Jeyasudha, Ramajeyabalan; Murugan, Saravanan; Saranghdar, Rajendira Janardhan

    2013-01-01

    Two unknown impurities were detected in the cefazolin sodium bulk drug substance using gradient reversed-phase high-performance liquid chromategraphy (HPLC). These impurities were isolated by preparative HPLC and characterized by using spectroscopic techniques like LC-MS, LC-MS/MS, 1D, 2D NMR, and FT-IR. Based on the spectral data, the impurities have been characterized as N-(2,2-dihydroxyethyl)-2-(1H-tetrazol-1-yl)acetamide (Impurity-I) and 2-{carboxy[(1H-tetrazol-1-ylacetyl)amino]methyl}-5-methylidene-5,6-dihydro-2H-1,3-thiazine-4-carboxylic acid (Impurity-II). The structures of these impurities were also established unambiguously by co-injection into HPLC to confirm the retention time. To the best of our knowledge, these two impurities were not reported elsewhere.

  8. Phenols and lignans from Chenopodium album.

    PubMed

    Cutillo, Francesca; DellaGreca, Marina; Gionti, Melania; Previtera, Lucio; Zarrelli, Armando

    2006-01-01

    Cinnamic acid, 4-hydroxy-cinnamic acid, ferulic acid, methyl ferulate, sinapic acid, methyl 3-(4-hydroxy-3-methoxyphenyl)propanoate, 4-(1-hydroxyethyl)-2-methoxyphenol, vanillyl alcohol, 4-(hydroxymethyl)-2-methoxyphenol, 4-hydroxy-3-methoxybenzoic acid, 4-vinylphenol, 4-methylbenzaldehyde, N-[2-(1H-indol-3-yl)ethyl]acetamide, pinoresinol, syringaresinol, lariciresinol, 5,5'-dimethoxy-lariciresinol, threo-guaiacylglycerol-3-beta-4-syringaresinol ether and two new sesquilignans, namely, threo-guaiacylglycerol-alpha-O-methyl-beta-O-4-syringaresinol ether and threo-syringylglycerol-alpha-O-methyl-beta-O-4-syringaresinol ether, were isolated and identified as components of Chenopodium album. Constitutions were established on the basis of spectroscopic data, including two-dimensional NMR analyses.

  9. Structural, electronic, thermodynamical and charge transfer properties of Chloramphenicol Palmitate using vibrational spectroscopy and DFT calculations

    NASA Astrophysics Data System (ADS)

    Mishra, Rashmi; Srivastava, Anubha; Sharma, Anamika; Tandon, Poonam; Baraldi, Cecilia; Gamberini, Maria Christina

    2013-01-01

    The global problem of advancing bacterial resistance to newer drugs has led to renewed interest in the use of Chloramphenicol Palmitate (C27H42Cl2N2O6) [Palmitic acid alpha ester with D-threo-(-),2-dichloro-N-(beta-hydroxy-alpha-(hydroxymethyl)-p-nitrophenethyl)acetamide also known as Detereopal]. The characterization of the three polymorphic forms of Chloramphenicol Palmitate (CPP) was done spectroscopically by employing FT-IR and FT-Raman techniques. The equilibrium geometry, various bonding features, and harmonic wavenumbers have been investigated for most stable form A with the help of DFT calculations and a good correlation was found between experimental data and theoretical values. Electronic properties have been analyzed employing TD-DFT for both gaseous and solvent phase. The theoretical calculation of thermodynamical properties along with NBO analysis has also been performed to have a deep insight into the molecule for further applications.

  10. Crystal structure of mandipropamid.

    PubMed

    Park, Hyunjin; Kim, Jineun; Kang, Gihaeng; Kim, Tae Ho

    2015-10-01

    In the title compound, C23H22ClNO4 (systematic name: (RS)-2-(4-chloro-phen-yl)-N-{2-[3-meth-oxy-4-(prop-2-yn-1-yl-oxy)phen-yl]eth-yl}-2-(prop-2-yn-yloxy)acetamide), an amide fungicide, the dihedral angle between the chloro-benzene and benzene rings is 65.36 (6)°. In the crystal, N-H⋯O hydrogen bonds lead to zigzag supra-molecular chains along the c axis (glide symmetry). These are connected into layers by C-H⋯O and C-H⋯π inter-actions; the layers stack along the a axis with no specific inter-molecular inter-actions between them.

  11. Polyimidazoles via aromatic nucleophilic displacement

    NASA Technical Reports Server (NTRS)

    Connell, John W. (Inventor); Hergenrother, Paul M. (Inventor)

    1992-01-01

    Polyimidazoles (PI) are prepared by the aromatic nucleophilic displacement reaction of di(hydroxyphenyl) imidazole monomers with activated aromatic dihalides or activated aromatic dinitro compounds. The reactions are carried out in polar aprotic solvents such as N,N-dimethyl acetamide, sulfolane, N-methylpyrrolidinone, dimethylsulfoxide, or diphenylsulfone using alkali metal bases such as potassium carbonate at elevated temperatures under nitrogen. The di(hydroxyphenyl) imidazole monomers are prepared by reacting an aromatic aldehyde with a dimethoxybenzil or by reacting an aromatic dialdehyde with a methoxybenzil in the presence of ammonium acetate. The di(methoxyphenyl) imidazole is subsequently treated with aqueous hydrobromic acid to give the di(hydroxphenyl) imidazole monomer. This synthetic route has provided high molecular weight PI of new chemical structure, is economically and synthetically more favorable than other routes, and allows for facile chemical structure variation due to the availability of a large variety of activated aromatic dihalides and dinitro compounds.

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

    PubMed

    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.

  13. Synthesis, characterization, and differentiation of high energy amine peroxides by MS and vibrational microscopy

    NASA Astrophysics Data System (ADS)

    Peña-Quevedo, Alvaro J.; Mina-Calmide, Nairmen; Rodríguez, Nelmary; Nieves, Deborah; Cody, Robert B.; Hernández-Rivera, Samuel P.

    2006-05-01

    Synthesis and characterization of hexamethelene triperoxide diamine (HMTD), tetramethylene diperoxide dicarbamide (TMDD) and tetramethylene diperoxide acetamide (TMDA) using GC-MS, HPLC-MS, FT-IR and Raman Microscopy has been carried out. The study also centered in the synthesis and characterization of other cyclic amine peroxides, including and different forms of caged peroxides from other diaminoalkanes. Interest also was given to the secondary products of all syntheses and the effect of temperature in the composition mixtures of the preparations. Differentiation spectroscopy and spectrometry studies were also conducted. In these studies the differences in the ν(O-O), ν(N-C), ν(N-H), ν(C-O), δ(CH 3-C) and δ(C-O) bands for Raman and IR were established. For the GC/MS spectrometric studies retention times and fragmentation patterns for GC-MS and GC-FT-IR useful in amine peroxide differentiation were also established.

  14. Spectroscopic investigations of the chiral interactions of metolachlor and its (S)-isomer with lipase and phosphatase.

    PubMed

    Wen, Yue Z; Yuan, Yu L; Chen, Hui; Wang, He L; Liu, Hui J; Kang, Xiao D; Fu, Liu S

    2010-04-01

    Metolachlor [2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-1-methylethyl) acetamide] is a chiral acetanilide herbicide. We investigated its enantioselective interactions, and that of its (S)-isomer, with Penicillium expansum alkaline lipase and phosphatase. UV differential spectroscopy and fluorescence spectrophotometry studies were conducted in phosphate buffered solution at pH 7. Chiral differences in the UV absorption and fluorescence spectra of lipase and phosphatase with metolachlor and its (S)-isomer were detected. The results showed that the interactions of metolachlor and its (S)-isomer with lipase and phosphatase occur statically through complex formation, and enantioselectivity was clearly observed. In addition, both UV absorption and fluorescence spectrophotometry showed that the (S)-isomer interacted more strongly with lipase and phosphatase than metolachlor.

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

    PubMed

    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.

  16. 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)

    NASA Technical Reports Server (NTRS)

    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.

  17. Modeling of peritectic YBa{sub 2}Cu{sub 3}O{sub 7{minus}x} growth using transparent organic analogues

    SciTech Connect

    Terborg, R.; Schmitz, G.J.

    1997-08-01

    Transparent organic analogues were directionally solidified to investigate, via in-situ observation, the peritectic reaction occurring in the YBa{sub 2}Cu{sub 3}O{sub 7{minus}x} YBCO-superconductor system. Nucleation and growth of peritectic and properitectic phases were examined with respect to similarities with the solidification of the YBCO superconductor. The selected organic system, salicylic acid-acetamide, turned out to match the requirements concerning crystal shape, small nucleation rate of the peritectic phase on the properitectic phase, existence of stoichiometric phases with no solubility limits, common and undercooling ability of the peritectic phase. Several features of YBCO growth which were previously deduced only from metallographic cross sections could be verified by direct observation. The organic analogue system will also be used in the future to improve numerical simulations. {copyright} {ital 1997 Materials Research Society.}

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

    PubMed

    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.

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

    PubMed Central

    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

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

    PubMed

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

    2014-07-15

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

  1. Single-drop microextraction followed by in-syringe derivatization and GC-MS detection for the determination of parabens in water and cosmetic products.

    PubMed

    Saraji, Mohammad; Mirmahdieh, Shiva

    2009-04-01

    A single-drop microextraction (SDME) method followed by in-syringe derivatization and GC-MS determination has been developed for analysis of five parabens, including methyl, ethyl, isopropyl, n-propyl and n-butyl paraben in water samples and cosmetic products. N,O-Bis(trimethylsilyl)acetamide (BSA) was used as derivatization reagent. Derivatization reaction was performed inside the syringe barrel using 0.4 microL of BSA. Parameters that affect the derivatization yield such as temperature and time of the reaction were studied. In addition, experimental SDME parameters such as selection of organic solvent, addition of salt, extraction time and extraction temperature were investigated and optimized. The RSD of the method for aqueous samples varied from 8.1 to 13%. The LODs ranged from 0.001 (n-butyl paraben) to 0.015 (methyl paraben) microg/L, and the enrichment factors were between 23 and 150.

  2. The potential of mean force surface for the alanine dipeptide in aqueous solution: a theoretical approach

    NASA Astrophysics Data System (ADS)

    Montgomery Pettitt, B.; Karplus, Martin

    1985-11-01

    Results of an application of integral equation theory to the determination of the intramolecular potential of mean force for the alanine dipeptide. N-methyl alanine acetamide, in aqueous solution are presented. The calculations are based on Ornstein—Zernike-like equations for polar systems with an intramolecular superposition approximation. The solvated free energy surface for the dipeptide as a function of the dihedral angles φ and ψ (Ramachandran plot) is determined and compared with the vaccum surface calculations. Conformations that are essentially forbidden in vaccum are found to be significant in aqueous solution. The solvent contributions to the free energy surface are decomposed into enthalpic and entropic terms. Possible applications and extensions of the method are outlined.

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

    PubMed

    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.

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

    PubMed

    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.

  5. Conformations of polyelectrolyte macromolecules with different charge density in solutions of different ionic strengths

    NASA Astrophysics Data System (ADS)

    Dommes, O. A.; Okatova, O. V.; Pavlov, G. M.

    2016-11-01

    Studies of charged polymer chains are interesting in both fundamental and applied aspects. Especially, polyelectrolytes attract huge attention of researchers due to their ability to form interpolymer complexes with synthetic and biopolymers. The study was carried out on the fractions of hydrophilic copolymers of N-methyl-N-vinyl acetamide and N-methyl-N-vinyl amine hydrochloride of different degrees of polymerization and of different charge density using methods of molecular hydrodynamics. Hydrodynamic and conformational characteristics as well as molar masses of isolated molecules were estimated. In addition, the intrinsic viscosity of fractions was studied at the extreme ionic strengths - in distilled water (∼10-6M) and in 6M NaCl. Scaling relations for intrinsic viscosity, sedimentation and translational diffusion coefficients with molar mass were obtained. Conformational behavior of macromolecules with different linear charge density was compared.

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

    NASA Astrophysics Data System (ADS)

    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.

  7. One-Pot Parallel Synthesis of Alkyl Sulfides, Sulfoxides, and Sulfones.

    PubMed

    Bogolubsky, Andrey V; Moroz, Yurii S; Mykhailiuk, Pavel K; Ostapchuk, Eugeniy N; Rudnichenko, Alexander V; Dmytriv, Yurii V; Bondar, Anna N; Zaporozhets, Olga A; Pipko, Sergey E; Doroschuk, Roman A; Babichenko, Liudmyla N; Konovets, Anzhelika I; Tolmachev, Andrey

    2015-06-08

    A simple and cost-effective one-pot parallel synthesis approach to sulfides, sulfoxides, and sulfones from thiourea was elaborated. The method combines two procedures optimized to the parallel synthesis conditions: alkylation of thiourea with alkyl chlorides and mono or full oxidation of in situ generated sulfides with H2O2 or H2O2-(NH4)2MoO4. The experimental set up required commonly used lab equipment: conventional oven and ultrasonic bath; the work up includes filtration or extraction with chloroform. The method was evaluated on an 81 member library of drug-like sulfides, sulfoxides, and sulfones yielding the compounds on a 30-300 mg scale. A small-scale synthesis of 2-(benzhydrylsulfinyl)acetamide (modafinil) utilizing our approach resulted in similar efficiency to the published procedures.

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

    PubMed

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

    2016-05-03

    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.

  9. Discovery of a potent and orally available acyl-CoA: cholesterol acyltransferase inhibitor as an anti-atherosclerotic agent: (4-phenylcoumarin)acetanilide derivatives.

    PubMed

    Ogino, Masaki; Fukui, Seiji; Nakada, Yoshihisa; Tokunoh, Ryosuke; Itokawa, Shigekazu; Kakoi, Yuichi; Nishimura, Satoshi; Sanada, Tsukasa; Fuse, Hiromitsu; Kubo, Kazuki; Wada, Takeo; Marui, Shogo

    2011-01-01

    Acyl-CoA: cholesterol acyltransferase (ACAT) is an intracellular enzyme that catalyzes cholesterol esterification. ACAT inhibitors are expected to be potent therapeutic agents for the treatment of atherosclerosis. A series of potent ACAT inhibitors based on an (4-phenylcoumarin)acetanilide scaffold was identified. Evaluation of the structure-activity relationships of a substituent on this scaffold, with an emphasis on improving the pharmacokinetic profile led to the discovery of 2-[7-chloro-4-(3-chlorophenyl)-6-methyl-2-oxo-2H-chromen-3-yl]-N-[4-chloro-2-(trifluoromethyl)phenyl]acetamide (23), which exhibited potent ACAT inhibitory activity (IC50=12 nM) and good pharmacokinetic profile in mice. Compound 23 also showed regressive effects on atherosclerotic plaques in apolipoprotein (apo)E knock out (KO) mice at a dose of 0.3 mg/kg per os (p.o.).

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

    PubMed

    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.

  11. 7-Hy­droxy­methyl-2-pivaloyl­amino-1,8-naphthyridine

    PubMed Central

    Fun, Hoong-Kun; Quah, Ching Kheng; Aich, Krishnendu; Das, Sangita; Goswami, Shyamaprosad

    2013-01-01

    In the title compound, C14H17N3O2, the mean plane of the 1,8-naphthyridine ring system (r.m.s deviation = 0.020 Å) forms a dihedral angle of 23.4 (1)° with the acetamide moiety (r.m.s deviation = 0.001 Å). The mol­ecular structure is stabilized by an intra­molecular O—H⋯N hydrogen bond, which generates an S(5) ring motif. In the crystal, mol­ecules are linked into inversion dimers by pairs of N—H⋯O hydrogen bonds, generating 18-membered R 2 2(18) ring motifs. PMID:23634051

  12. Metolachlor and alachlor breakdown product formation patterns in aquatic field mesocosms

    USGS Publications Warehouse

    Graham, W.H.; Graham, D.W.; DeNoyelles, F.; Smith, V.H.; Larive, C.K.; Thurman, E.M.

    1999-01-01

    The transformation of metolachlor [2-chloro-N-(2-ethyl-6-methylphenyl)- N-(2-methoxy-1-methyl)ethyl)acetamide] and alachlor [2-chloro-N-(2,6- diethylphenyl)-N-methoxymethyl)acetamide] in aquatic systems was investigated using outdoor tank mesocosms. Metolachlor and alachlor levels and their ethane sulfonic acid (ESA) and oxanillic acid breakdown products were monitored over time under five experimental treatments (each in quadruplicate). Background water conditions were identical in all treatments with each treatment differing based on the level and type(s) of herbicide present. Treatments included a noherbicide control, 10 ??g/L metolachlor, 25 ??g/L metolachlor, 25 ??g/L alachlor, and 25 ??g/L alachlor plus 25 ??g/L metolachlor in combination. The experiment was initiated by adding herbicide(s) to the units to the target concentrations; herbicide and breakdown product levels and other chemical parameters were then monitored for 85 days. In general, metolachlor half-lives were longer than alachlor half-lives under all treatments, although the differences were not statistically significant. Metolachlor half-lives (??95% confidence limits) ranged from 33.0 d (??14.1 d) to 46.2 d (??40.0 d), whereas alachlor half- lives ranged from 18.7 d (??3.5 d) to 21.0 d (??6.5 d) for different treatments. Formation patterns of ESA were similar in all treatments, whereas oxanillic acid formation differed for the two herbicides. Alachlor oxanillic acid was produced in larger quantities than metolachlor oxanillic acid and either ESA under equivalent conditions. Our results suggest that the transformation pathways for alachlor and metolachlor in aquatic systems are similar and resemble the acetochlor pathway in soils proposed by Feng (Pestic. Biochem. Physiol. 1991, 34, 136); however, the oxanillic acid branch of the pathway is favored for alachlor as compared with metolachlor.The transformation of metolachlor [2-chloro-N-(2-ethyl-6-methylphenyl)-N- (2-methoxy-1-methylethy)acetamide

  13. Minimization of a Protein–DNA Dimerizer

    PubMed Central

    Stafford, Ryan L.; Arndt, Hans-Dieter; Brezinski, Mary L.; Ansari, Aseem Z.; Dervan, Peter B.

    2011-01-01

    A protein–DNA dimerizer constructed from a DNA-binding polyamide and the peptide FYPWMKG facilitates the binding of a natural transcription factor Exd to an adjacent DNA site. The Exd binding domain can be reduced to a dipeptide WM attached to the polyamide through an ε-aminohexanoic acid linker with retention of protein–DNA dimerizer activity. Screening a library of analogues indicated that the tryptophan indole moiety is more important than methionine’s side chain or the N-terminal acetamide. Remarkably, switching the stereochemistry of the tryptophan residue (l to d) stabilizes the dimerizer•Exd•DNA ternary complex at 37 °C. These observations provide design principles for artificial transcription factors that may function in concert with the cellular regulatory circuitry. PMID:17290996

  14. Novel poly(methyl methacrylate)-based semi-interpenetrating polyelectrolyte gels for rechargeable lithium batteries

    NASA Astrophysics Data System (ADS)

    Kalapala, Saibabu; Easteal, Allan J.

    Novel semi-interpenetrating polymer gel electrolytes designed for use in rechargeable lithium polymer batteries are synthesised from methyl methacrylate and the lithium salt of 2-acrylamido-2-methylpropanesulfonic acid (LiAMPS). The gels are made by first synthesising linear chains of poly(LiAMPS) by free radical polymerisation of LiAMPS dissolved in dimethyl acetamide (DMA) or DMA/ethylene carbonate mixtures, then co-polymerisation of methyl methacrylate and a cross-linking monomer (tetraethyleneglycol diacrylate) to form the semi-interpenetrating network. The electrical conductivity of the gels is determined as a function of LiAMPS and methyl methacrylate (MMA) concentrations, cross-link density, and solvent composition. The conductivity ( σ) is found to be in the range 0.2 ≤ σ ≤ 0.8 mS cm -1 at ambient temperature (20 ± 1 °C).

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

    PubMed

    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.

  16. Development of dynamic kinetic resolution on large scale for (±)-1-phenylethylamine.

    PubMed

    Thalén, Lisa K; Bäckvall, Jan-E

    2010-09-13

    Candida antarctica lipase B (CALB) and racemization catalyst 4 were combined in the dynamic kinetic resolution (DKR) of (±)-1-phenylethylamine (1). Several reaction parameters have been investigated to modify the method for application on multigram scale. A comparison of isopropyl acetate and alkyl methoxyacetates as acyl donors was carried out. It was found that lower catalyst loadings could be used to obtain (R)-2-methoxy-N-(1-phenylethyl)acetamide (3) in good yield and high ee when alkyl methoxyacetates were used as acyl donors compared to when isopropyl acetate was used as the acyl donor. The catalyst loading could be decreased to 1.25 mol % Ru-catalyst 4 and 10 mg CALB per mmol 1 when alkyl methoxyacetates were used as the acyl donor.

  17. 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)

    NASA Technical Reports Server (NTRS)

    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.

  18. A rapid and efficient determination of natural estrogens in soils by pressurised liquid extraction and gas chromatography-mass spectrometry.

    PubMed

    Beck, Josefine; Totsche, Kai Uwe; Kögel-Knabner, Ingrid

    2008-03-01

    We present a new analytical procedure for the extraction and determination of natural estrogens in soils based on pressurised liquid extraction and GC-MS determination. After testing twelve solvents, acetone proved to be the most efficient extractant. The optimum extraction temperature is 60 degrees C. Soil extracts have to be purified and concentrated by C-18 solid phase extraction. The dried extracts are derivatised by N-methyl-N-(trimethylsilyl)trifluoro-acetamide before measurement by GC-MS. Recoveries of 79-103% with relative standard deviations

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

    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.

  1. Biotransformation studies of textile dye Remazol Orange 3R.

    PubMed

    Surwase, Swati V; Deshpande, Krutika K; Phugare, Swapnil S; Jadhav, Jyoti P

    2013-08-01

    In the present study, biotransformation of Remazol Orange 3R (RO3R) was studied using well-known bacterial isolate Pseudomonas aeruginosa strain BCH. The dye was decolorized up to 98 % within 15 min. The induction in the level of various oxidoreductive enzymes viz. laccase, tyrosinase, veratryl alcohol oxidase and DCIP reductase were observed in the cells obtained after decolorization of RO3R, which supports their role in decolorization. The metabolites of RO3R obtained after biodegradation were identified and characterized by various analytical techniques viz, HPLC, FTIR, and GC-MS. The RO3R was transformed to the N-(7 amino 8 hydroxy-napthalen-2yl) actamide (m/z, 198), Acetamide (m/z, 59) and Napthalen-1-ol (m/z, 144).

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

    NASA Astrophysics Data System (ADS)

    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.

  3. Effect of chronic piracetam on age-related changes of cross-maze exploration in mice.

    PubMed

    Salimov, R; Salimova, N; Shvets, L; Shvets, N

    1995-11-01

    Normal aging is known to deteriorate memory, spatial orientation, and perceptual recognition. Experiment 1 examined behavioral manifestations of aging by using a cross-maze exploration test in 2-, 6-, and 10-month-old hybrid mice (CBA x C57BL). A decrease in explorative patrolling and an increase in arm reentries, a latency to start and a total time of exploration were found in 10-month-old mice. In Experiment 2, administration of the cognition enhancer piracetam (2-oxo-1-pirrolidone acetamide) (400 mg/kg, IP, once a day for 10 days) enhanced arm patrolling and decreased reentries in 10-month-old mice to the level displayed by the 2-month-old animals. The results suggest that the cross-maze test may be useful for a preliminary screening of antisenescent drugs.

  4. Lethal or protective effects of prolonged treatment with hypoxic cell sensitizers

    SciTech Connect

    Edgren, M.R.

    1995-12-31

    AK-2123 [N-(2-methoxyethyl)-2-(3-nitro-1-triazolyl)acetamide] is a hypoxic cell radiosensitizer which is currently being tested in several oncology clinics and which has a lower toxicity than misonidazole (MISO) in vivo. The positive experiences reported recently certainly warrant further clinical evaluations. The experimental observations reported so far need further experimental studies to clarify the sensitization mechanism, especially as recent intratumoral strategies used in the clinical administration of the sensitizers can result in a large local concentration of the drug that may persist for a prolonged period of time between and after radiation exposures. Model experiments in vitro using V79 cells were performed with AK-2123 under these conditions. Misonidazole (MISO) and metronidazole (METRO), well known hypoxic cell radiosensitizers, were used for comparison of the effects. Clonogenic survival and induction and repair of DNA damage were used as end-points.

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

    PubMed

    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.

  6. Identification of auxins by a chemical genomics approach

    PubMed Central

    Christian, May; Hannah, William B.; Lüthen, Hartwig; Jones, Alan M.

    2008-01-01

    Thirteen auxenic compounds were discovered in a screen of 10 000 compounds for auxin-like activity in Arabidopsis roots. One of the most potent substances was 2-(4-chloro-2-methylphenoxy)-N-(4-H-1,2,4-triazol-3-yl)acetamide (WH7) which shares similar structure to the known auxenic herbicide 2,4-dichlorophenoxyacetic acid (2,4-D). A selected set of 20 analogues of WH7 was used to provide detailed information about the structure–activity relationship based on their efficacy at inhibiting and stimulating root and shoot growth, respectively, and at induction of gene expression. It was shown that WH7 acts in a genetically defined auxin pathway. These small molecules will extend the arsenal of substances that can be used to define auxin perception site(s) and to dissect subsequent signalling events. PMID:18515827

  7. Identification of auxins by a chemical genomics approach.

    PubMed

    Christian, May; Hannah, William B; Lüthen, Hartwig; Jones, Alan M

    2008-01-01

    Thirteen auxenic compounds were discovered in a screen of 10 000 compounds for auxin-like activity in Arabidopsis roots. One of the most potent substances was 2-(4-chloro-2-methylphenoxy)-N-(4-H-1,2,4-triazol-3-yl)acetamide (WH7) which shares similar structure to the known auxenic herbicide 2,4-dichlorophenoxyacetic acid (2,4-D). A selected set of 20 analogues of WH7 was used to provide detailed information about the structure-activity relationship based on their efficacy at inhibiting and stimulating root and shoot growth, respectively, and at induction of gene expression. It was shown that WH7 acts in a genetically defined auxin pathway. These small molecules will extend the arsenal of substances that can be used to define auxin perception site(s) and to dissect subsequent signalling events.

  8. Simultaneous Detection of Cadmium, Copper, and Lead using A Carbon Paste Electrode Modified with Carbamoylphosphonic Acid Self-Assembled Monolayer on Mesoporous Silica (SAMMS)

    SciTech Connect

    Yantasee, Wassana ); Lin, Yuehe ); Fryxell, Glen E. ); Busche, Brad J. )

    2004-01-30

    A new sensor was developed for simultaneous detection of cadmium (Cd2+), copper (Cu2+), and lead (Pb2+), based on the voltammetric response at a carbon paste electrode modified with carbamoylphosphonic acid (acetamide phosphonic acid) self-assembled monolayer on mesoporous silica (Ac-Phos SAMMS). The adsorptive stripping voltammetry technique involves preconcentration of the metal ions onto Ac-Phos SAMMS under an open circuit, then electrolysis of the preconcentrated species, followed by a square wave potential sweep towards positive values. Factors affecting the preconcentration process were investigated. The voltammetric responses increased linearly with the preconcentration time from 1 to 30 minutes or with metal ion concentrations ranging from 10 to 200 ppb. The responses also evolved in the same fashion as adsorption isotherm in the pH range of 2-6. The metal detection limits were 10 ppb after 2 minutes preconcentration and improved to 0.5 ppb after 20 minutes preconcentration.

  9. Felinine stability in the presence of selected urine compounds.

    PubMed

    Rutherfurd, S M; Kitson, T M; Woolhouse, A D; McGrath, M C; Hendriks, W H

    2007-02-01

    The stability of felinine, an amino acid present in feline urine, was investigated. Synthetic felinine was unstable in the urine of a selection of mammals. Felinine was found to stable in feline urine in which urea had been degraded. Synthetic felinine was found to react specifically with urea and did not react with urea analogues such as biuret or thiourea or other nucleophilic compounds such as ammonia which is more nucleophilic or acetamide and water which are less nucleophilic than urea. The reaction of urea and felinine was independent of pH over the range of 3-10. Urea did not react with N-acetyl-felinine suggesting a felinine N-terminal interaction with urea. Mass spectral analysis of the reaction products showed the presence of carbamylated felinine and fragmentation ions derived from carbamyl-felinine. The physiological relevance of felinine carbamylation is yet to be determined.

  10. Crystal and molecular structure of an (S)-(+)-enantiomer of modafinil, a novel wake-promoting agent.

    PubMed

    In, Yasuko; Tomoo, Koji; Ishida, Toshimasa; Sakamoto, Yasuhiko

    2004-10-01

    The (+)-enantiomer of modafinil [(RS)-2-(diphenylmethylsulfinyl)acetamide], a novel wake-promoting agent, was clarified to be S-configuration by X-ray crystal structure analysis. The crystal consists of two crystallographically independent conformers that are different at the torsion angles around the sulfinylacetamide moiety, and this results from the molecular packing requirement to form a two-dimensional hydrogen-bonding network via neighboring amide groups in the crystal. The crystal structure is characterized by the formation of alternative hydrophobic and hydrophilic layers, which are formed among the symmetry-translated assemblies of diphenylmethyl and sulfinylacetamide moieties, respectively. The spatial orientation between the diphenyl and amide groups is believed to be important for the activity of modafinil.

  11. CONDENSED MATTER: STRUCTURE, MECHANICAL AND THERMAL PROPERTIES: Microstructure and Corrosion Performance of Carbonitriding Layers on Cast Iron by Plasma Electrolytic Carbonitriding

    NASA Astrophysics Data System (ADS)

    Pang, Hua; Lv, Guo-Hua; Chen, Huan; Wang, Xin-Quan; Zhang, Gu-Ling; Yang, Si-Ze

    2009-08-01

    The surface carbonitriding of cast iron is investigated in an aqueous solution of acetamide and glycerin. Microstructure, chemical and phase composition and corrosion performance of the carbonitriding layers are investigated by scanning electron microscopy, energy dispersive spectroscopy and x-ray diffraction, as well as potentiodynamic polarization testing. X-ray diffraction results show that the carbonitriding coatings are composed of martensite, austenite(γ-Fe), Fe2C, Fe3C, Fe5C2, FeN and in-Fe2-3N. After the plasma electrolytic carbonitriding treatment the corrosion resistance of cast iron is clearly improved compared to the substrate, and the coatings produced at 350 V for 30s give the best corrosion resistance.

  12. Tough soluble aromatic thermoplastic copolyimides

    NASA Technical Reports Server (NTRS)

    Bryant, Robert G. (Inventor)

    2000-01-01

    Tough, soluble, aromatic, thermoplastic copolyimides were prepared by reacting 4,4'-oxydiphthalic anhydride, 3,4,3',4'-biphenyltetracarboxylic dianhydride and 3,4'-oxydianiline. Alternatively, these copolyimides may be prepared by reacting 4,4'-oxydiphthalic anhydride with 3,4,3',4'-biphenyltetracarboxylic dianhydride and 3,4'-oxydiisocyanate. Also, the copolyimide may be prepared by reacting the corresponding tetra acid and ester precursors of 4,4'-oxydiphthalic anhydride and 3,4,3',4'-biphenyltetracarboxylic dianhydride with 3,4'-oxydianiline. These copolyimides were found to be soluble in common amide solvents such as N,N'-dimethyl acetamide, N-methylpyrrolidinone, and dimethylformamide allowing them to be applied as the fully imidized copolymer and to be used to prepare a wide range of articles.

  13. Development and Validation of Transferable Amide I Vibrational Frequency Maps for Peptides

    PubMed Central

    Wang, L.; Middleton, C. T.; Zanni, M. T.; Skinner, J. L.

    2012-01-01

    Infrared (IR) spectroscopy of the amide I band has been widely utilized for the analysis of peptides and proteins. Theoretical modeling of IR spectra of proteins requires an accurate and efficient description of the amide I frequencies. In this paper, amide I frequency maps for protein backbone and side chain groups are developed from experimental spectra and vibrational lifetimes of N-methylacetamide and acetamide in different solvents. The frequency maps, along with established nearest-neighbor frequency shift and coupling schemes, are then applied to a variety of peptides in aqueous solution and reproduce experimental spectra well. The frequency maps are designed to be transferable to different environments; therefore, they can be used for heterogeneous systems, such as membrane proteins. PMID:21405034

  14. Reaction pathways and free energy profiles for spontaneous hydrolysis of urea and tetramethylurea: Unexpected substituent effects

    PubMed Central

    Yao, Min; Tu, Wenlong; Chen, Xi; Zhan, Chang-Guo

    2013-01-01

    It has been difficult to directly measure the spontaneous hydrolysis rate of urea and, thus, 1,1,3,3-tetramethylurea (Me4U) was used as a model to determine the “experimental” rate constant for urea hydrolysis. The use of Me4U was based on an assumption that the rate of urea hydrolysis should be 2.8 times that of Me4U hydrolysis because the rate of acetamide hydrolysis is 2.8 times that of N,N-dimethyl-acetamide hydrolysis. The present first-principles electronic-structure calculations on the competing non-enzymatic hydrolysis pathways have demonstrated that the dominant pathway is the neutral hydrolysis via the CN addition for both urea (when pH<~11.6) and Me4U (regardless of pH), unlike the non-enzymatic hydrolysis of amides where alkaline hydrolysis is dominant. Based on the computational data, the substituent shift of free energy barrier calculated for the neutral hydrolysis is remarkably different from that for the alkaline hydrolysis, and the rate constant for the urea hydrolysis should be ~1.3×109-fold lower than that (4.2×10−12 s−1) measured for the Me4U hydrolysis. As a result, the rate enhancement and catalytic proficiency of urease should be 1.2×1025 and 3×1027 M−1, respectively, suggesting that urease surpasses proteases and all other enzymes in its power to enhance the rate of reaction. All of the computational results are consistent with available experimental data for Me4U, suggesting that the computational prediction for urea is reliable. PMID:24097048

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

    PubMed Central

    Rami, Chirag; Patel, Laxmanbhai; Patel, Chhaganbhai N.; Parmar, Jayshree P.

    2013-01-01

    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 (1H 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 (r2pred) 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. PMID:24302836

  16. Synthesis of novel selenium-containing sulfa drugs and their antibacterial activities.

    PubMed

    Abdel-Hafez, Sh H

    2010-01-01

    Synthesis of 3-[4-(N-substituted sulfamoyl)phenyl]-3,4-dihydro-4-oxo-7,9-dimethylpyrido[3',2':4,5]selenolo[3,2-d]pyrimidines, 7-[4-(N-substituted sulfamoyl)phenyl]-7,8-dihydro-8-oxo-3,4-diphenylpyrimido[4',5':4,5]selenolo [2,3-c]pyridazines and 1-[4-(N-substituted sulfamoyl)phenyl]-1,11-dihydro-11-oxo-4-methylpyrimido[4',5':4,5]selenolo[2,3-b]quinolines is reported. 4-Amino-N-pyrimidine-2-ylbenzene sulfonamide (a), 4-amino-N-(2,6-dimetnylpyrimidin-4-yl)benzene sulfonamide (b), N-[(4-aminophenyl)sulfonyl] acetamide (c) with N-ethoxymethyleneamino of selenolo pyridine, selenolo pyridazine and selenolo quinoline derivatives respectively were obtained starting from 1-amino-N-substituted sulfanilamides. Spectroscopic data (IR, (1)H NMR, (13)C NMR and Mass spectral) confirmed the structure of the newly synthesized compounds. Substituted pyrimidines, pyridazines and quinolines were screened for antibacterial activity against gram-positive and gram-negative bacteria. Selenolo derivative of N-[(4-aminophenyl)sulfonyl] acetamide (substitutent of sulfacetamide c) showed strong bactericidal effect against all the tested organisms. Selenolo[3,2-d]pyrimidin (substitutent a) showed a good bactericidal effect against Serratia marcescens, Staphylococcus aureus and Escherichia coli. Compounds Selenolo[2,3-c]pyridazine (substitutent b), Selenolo[2,3-b]quinoline(substitutents c)) exhibited a moderate bactericidal effect against Serratia marcescens. None of the synthesized selenopyridazines has a considerable antimicrobial activity against the tested organisms. The minimum inhibitory concentration (MIC) of the most active compound - 3-[4-(N-acetyl sulfamoyl)phenyl]-3,4-dihydro-4-oxo-7,9-dimethylpyrido[3',2':4,5]selenolo [3,2-d]pyrimidine was 10 mg mL(-1).

  17. Interaction and dynamics of (alkylamide + electrolyte) deep eutectics: dependence on alkyl chain-length, temperature, and anion identity.

    PubMed

    Guchhait, Biswajit; Das, Suman; Daschakraborty, Snehasis; Biswas, Ranjit

    2014-03-14

    Here we investigate the solute-medium interaction and solute-centered dynamics in (RCONH2 + LiX) deep eutectics (DEs) via carrying out time-resolved fluorescence measurements and all-atom molecular dynamics simulations at various temperatures. Alkylamides (RCONH2) considered are acetamide (CH3CONH2), propionamide (CH3CH2CONH2), and butyramide (CH3CH2CH2CONH2); the electrolytes (LiX) are lithium perchlorate (LiClO4), lithium bromide (LiBr), and lithium nitrate (LiNO3). Differential scanning calorimetric measurements reveal glass transition temperatures (T(g)) of these DEs are ~195 K and show a very weak dependence on alkyl chain-length and electrolyte identity. Time-resolved and steady state fluorescence measurements with these DEs have been carried out at six-to-nine different temperatures that are ~100-150 K above their individual T(g)s. Four different solute probes providing a good spread of fluorescence lifetimes have been employed in steady state measurements, revealing strong excitation wavelength dependence of probe fluorescence emission peak frequencies. Extent of this dependence, which shows sensitivity to anion identity, has been found to increase with increase of amide chain-length and decrease of probe lifetime. Time-resolved measurements reveal strong fractional power dependence of average rates for solute solvation and rotation with fraction power being relatively smaller (stronger viscosity decoupling) for DEs containing longer amide and larger (weaker decoupling) for DEs containing perchlorate anion. Representative all-atom molecular dynamics simulations of (CH3CONH2 + LiX) DEs at different temperatures reveal strongly stretched exponential relaxation of wavevector dependent acetamide self dynamic structure factor with time constants dependent both on ion identity and temperature, providing justification for explaining the fluorescence results in terms of temporal heterogeneity and amide clustering in these multi-component melts.

  18. Herbicide and nitrate distribution in central Iowa rainfall

    SciTech Connect

    Hatfield, J.L.; Prueger, J.H.; Pfeiffer, R.L.; Wesley, C.K.

    1996-03-01

    Herbicides are detected in rainfall; however, these are a small fraction of the total applied. This study was designed to evaluate monthly and annual variation in atrazine (6-chloro-N-ethyl-N{prime}-(1-methylethyl)-1,3,5-triazine-2,4-diamine), alachlor (2-chloro-N-(2,6-diethylphenyl)-N-(methoxymethyl)acetamide), metolachlor (2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-1-methylethyl)acetamide), and NO{sub 3}-N concentrations in rainfall over Walnut Creek watershed south of Ames, IA. The study began in 1991 and continued through 1994. Within the watershed, two wet/dry precipitation samplers were positioned 4 km apart. Detections varied during the year with >90% of the herbicide detections occurring in April through early July. Concentrations varied among events from nondetectable amounts to concentrations of 154 {mu}g L{sup {minus}1}, which occurred when atrazine was applied during an extremely humid day immediately followed by rainfall of <10 mm that washed spray drift from the atmosphere. This was a local scale phenomenon, because the other collector had a more typical concentration of 1.7 {mu}g L{sup {minus}1} with an 8-mm rainfall. VAriation between the two collectors suggests that local scale meteorological processes affect herbicide movement. Yearly atrazine deposition totals were >100 {mu}g m{sup {minus}2} representing <0.1% of the amount applied. Nitrate-N concentrations in precipitation were uniformly distributed throughout the year and without annual variation in the concentrations. Deposition rates of NO{sub 3}-N were about 1.2 g m{sup {minus}2}. Annual loading onto the watershed was about 25% of the amount applied from all forms of N fertilizers. Movement and rates of deposition provide an understanding of the processes and magnitude of the impact of agriculture on the environment. 7 refs., 5 figs., 3 tabs.

  19. Prebiotic chemistry: chemical evolution of organics on the primitive Earth under simulated prebiotic conditions.

    PubMed

    Dondi, Daniele; Merli, Daniele; Pretali, Luca; Fagnoni, Maurizio; Albini, Angelo; Serpone, Nick

    2007-11-01

    A series of prebiotic mixtures of simple molecules, sources of C, H, N, and O, were examined under conditions that may have prevailed during the Hadean eon (4.6-3.8 billion years), namely an oxygen-free atmosphere and a significant UV radiation flux over a large wavelength range due to the absence of an ozone layer. Mixtures contained a C source (methanol, acetone or other ketones), a N source (ammonia or methylamine), and an O source (water) at various molar ratios of C : H : N : O. When subjected to UV light or heated for periods of 7 to 45 days under an argon atmosphere, they yielded a narrow product distribution of a few principal compounds. Different initial conditions produced different distributions. The nature of the products was ascertained by gas chromatographic-mass spectral analysis (GC-MS). UVC irradiation of an aqueous methanol-ammonia-water prebiotic mixture for 14 days under low UV dose (6 x 10(-2) Einstein) produced methylisourea, hexamethylenetetramine (HMT), methyl-HMT and hydroxy-HMT, whereas under high UV dose (45 days; 1.9 x 10(-1) Einstein) yielded only HMT. By contrast, the prebiotic mixture composed of acetone-ammonia-water produced five principal species with acetamide as the major component; thermally the same mixture produced a different product distribution of four principal species. UVC irradiation of the CH(3)CN-NH(3)-H(2)O prebiotic mixture for 7 days gave mostly trimethyl-s-triazine, whereas in the presence of two metal oxides (TiO(2) or Fe(2)O(3)) also produced some HMT; the thermal process yielded only acetamide.

  20. Structural variation in copper(I) complexes with pyridylmethylamide ligands: structural analysis with a new four-coordinate geometry index, tau4.

    PubMed

    Yang, Lei; Powell, Douglas R; Houser, Robert P

    2007-03-07

    Four Cu(I) complexes were synthesized with a family of pyridylmethylamide ligands, HL(R) [HL(R) = N-(2-pyridylmethyl)acetamide, R = null; 2,2-dimethyl-N-(2-pyridylmethyl)propionamide, R = Me(3); 2,2,2-triphenyl-N-(2-pyridylmethyl)acetamide, R = Ph(3))]. Complexes 1-3 were synthesized from the respective ligand and [Cu(CH(3)CN)(4)]PF(6) in a 2 : 1 molar ratio: [Cu(HL)(2)]PF(6) (1), [Cu(2)(HL(Me3))(4)](PF(6))(2) (2), [Cu(HL(Ph3))(2)]PF(6) (3). Complex 4, [Cu(HL)(CH(3)CN)(PPh(3))]PF(6), was synthesized from the reaction of HL with [Cu(CH(3)CN)(4)]PF(6) and PPh(3) in a 1 : 1 : 1 molar ratio. X-Ray crystal structures reveal that complexes 1, 3 and 4 are mononuclear Cu(I) species, while complex 2 is a Cu(I) dimer. The copper ions are four-coordinate with geometries ranging from distorted tetrahedral to seesaw in 1, 2, and 4. Complexes 1 and 2 are very air sensitive and they display similar electrochemical properties. The coordination geometry of complex 3 is nearly linear, two-coordinate. Complex 3 is exceptionally stable with respect to oxidation in the air, and its cyclic voltammetry shows no oxidation wave in the range of 0-1.5 V. The unusual inertness of complex 3 towards oxidation is attributed to the protection from bulky triphenyl substituent of the HL(Ph3) ligand. A new geometric parameter for four-coordinate compounds, tau(4), is proposed as an improved, simple metric for quantitatively evaluating the geometry of four-coordinate complexes and compounds.

  1. Surface water-ground water interaction: Herbicide transport into municipal collector wells

    USGS Publications Warehouse

    Verstraeten, Ingrid M.; Carr, J.D.; Steele, G.V.; Thurman, E.M.; Bastian, K.C.; Dormedy, D.F.

    1999-01-01

    During spring runoff events, herbicides in the Platte River are transported through an alluvial aquifer into collector wells located on an island in the river in 6 to 7 d. During two spring runoff events in 1995 and 1996, atrazine [2-chloro-4-ethylamino-6-isopropylamino-s-triazine] concentrations in water from these wells reached approximately 7 ??g/L, 70 times more than the background concentration in ground water. Concentrations of herbicides and metabolites in the collector wells generally were one-half to one-fifth the concentrations of herbicides in the river for atrazine, alachlor [2-chloro-2'-6'-diethyl-N-(methoxymethyl)-acetanilide], alachlor ethane-sulfonic acid (ESA) [2-((2,6-diethylphenyl) (methoxymethyl)amino)-2- oxoethane-sulfonic acid], metolachlor [2-chloro-N-(2-ethyl-6-methylphenyl)-N- (2-methoxy-1-methylethyl)acetamide], cyanazine [2-((4-chloro-6-(ethyl-amino)- 1,3,5 triazin-2-yl)-amino)-2-methylpropionitrile], and acetochlor [2-chloro- N-(ethoxymethyl)-N-(2-ethyl-6methyl-phenyl) acetamide], suggesting that 20 to 50% river water could be present in the water from the collector wells, assuming no degradation. The effect of the river on the quality of water from the collector wells can be reduced through selective management of horizontal laterals of the collector wells. The quality of the water from the collector wells is dependent on the (i) selection of the collector well used, (ii) number and selection of laterals used, (iii) chemical characteristics of the contaminant, and (iv) relative mixing of the Platte River and a major upstream tributary.

  2. Transport characteristics of urea transporter-B.

    PubMed

    Yang, Baoxue

    2014-01-01

    UT-B represents the major urea transporter in erythrocytes, in addition to being expressed in kidney descending vasa recta, brain, spleen, ureter, bladder, and testis. Expression of urea transporter UT-B confers high urea permeability to mammalian erythrocytes. Erythrocyte membranes are also permeable to various urea analogues, suggesting common transport pathways for urea and structurally similar solutes. UT-B is highly permeable to urea and the chemical analogues formamide, acetamide, methylurea, methylformamide, ammonium carbamate, and acrylamide, each with a Ps > 5.0 × 10(-6) cm/s at 10 °C. The amides formamide, acetamide, acrylamide, and butyramide efficiently diffuse across lipid bilayers. The urea analogues dimethylurea, acryalmide, methylurea, thiourea, and methylformamide inhibit UT-B-mediated urea transport by >60 % by a pore-blocking mechanism. UT-B is also a water channel in erythrocytes and has a single-channel water permeability that is similar to aquaporin-1. Whether UT-B is an NH3 channel still needs further study. Urea permeability (Purea) in erythrocytes differs between different mammals. Carnivores (dog, fox, cat) exhibit high Purea. In contrast, herbivores (cow, donkey, sheep) show much lower Purea. Erythrocyte Purea in human and pig (omnivores) was intermediate. Rodents and lagomorphs (mouse, rat, rabbit) have Purea intermediate between carnivores and omnivores. Birds that do not excrete urea and do not express UT-B in their erythrocytes have very low values. In contrast to Purea, water permeability is relatively similar in all mammals studied. This chapter will provide information about the transporter characteristics of UT-B.

  3. The Role of Ganglioside GM1 in Cellular Internalization Mechanisms of Poly(amidoamine) Dendrimers

    PubMed Central

    Hong, Seungpyo; Rattan, Rahul; Majoros, István J.; Mullen, Douglas G.; Peters, Jennifer L.; Shi, Xiangyang; Bielinska, Anna U.; Blanco, Luz; Orr, Bradford G.; Baker, James R.; Holl, Mark M. Banaszak

    2015-01-01

    Generation 7 (G7) poly(amidoamine) (PAMAM) dendrimers with amine, acetamide, and carboxylate end groups were prepared to investigate polymer/cell membrane interactions in vitro. G7 PAMAM dendrimers were used in this study because higher generation of dendrimers are more effective in permeabilization of cell plasma membranes and in the formation of nanoscale holes in supported lipid bilayers than smaller, lower generation dendrimers. Dendrimer-based conjugates were characterized by 1H NMR, UV/Vis spectroscopy, GPC, HPLC, and CE. Positively charged amine-terminated G7 dendrimers (G7-NH2) were observed to internalize into KB, Rat2 and C6 cells at a 200 nM concentration. By way of contrast, neither negatively charged G7 carboxylate-terminated dendrimers (G7-COOH) nor neutral acetamide-terminated G7 dendrimers (G7-Ac) associated with the cell plasma membrane or internalized under similar conditions. A series of in vitro experiments employing endocytic markers cholera toxin subunit B (CTB), transferrin, and GM1-pyrene were performed to further investigate mechanisms of dendrimer internalization into cells. G7-NH2 dendrimers co-localized with CTB, however, experiments with C6 cells indicated that internalization of G7-NH2 was not ganglioside GM1 dependent. The G7/CTB co-localization was thus ascribed to an artifact of direct interaction between the two species. The presence of GM1 in the membrane also had no effect upon XTT assays of cell viability or lactate dehydrogenase (LDH) assays of membrane permeability. PMID:19583240

  4. 35Cl NQR and Structural Studies of Chloroacetanilides C6H3Cl2NHCOCH3-xClx, 1 ≤ x ≤ 3

    NASA Astrophysics Data System (ADS)

    Groke, Dirk; Dou, Shi-Qi; Weiss, Alarich

    1992-02-01

    The temperature dependence of 35Cl NQR frequencies and the phase transition behaviour of chloroacetanilides (N-[2,6-dichlorophenyl]-2-chloroacetamide, -2,2-dichloroacetamide, -2,2,2-trichloroacetamide) were investigated. The crystal structure determination of N-[2,6-dichlorophenyl]- 2-chloroacetamide leads to the following: a = 1893.8 pm, b = 1110.7 pm, c = 472.1 pm, space group P212121 = D24 with Z = 4 molecules per unit cell. The arrangement of the molecules and their geometry is comparable to the high temperature phase of the acetyl compound N-[2,6-dichlorophenyl]- acetamide. For N-[2,6-diclorophenyl]-2,2,2-trichloroacetamide it was found: a = 1016.6 pm, b = 1194.3 pm, c = 1006.7 pm, ß= 101.79°, space group P21/c = C52h, Z = 4. The structure is similar to the low temperature phase of N-[2,6-dichlorophenyl]-acetamide. Parallelism between the temperature dependence of the 35C1 NQR lines of the CCl3 group and the X-ray diffraction results concerning the different behaviour of the chlorine atoms was observed. The structures of the compounds show intermolecular hydrogen bonding of the N - H • • • O - C type. The phenyl group and the HNCO function are nearly planar. A bleaching out of several 35Cl NQR lines at a temperature far below the melting point of the substances was observed. The different types of chlorine atoms (aromatic, chloromethyl) can be distinguished by their temperature coefficients of the 35Cl NQR frequencies. All the resonances found show normal "Bayer" temperature behaviour. N-[2,6-dichlorophenyl]-2,2-diehloroacetamide shows several solid phases. One stable low temperature phase and an instable high temperature phase (at room temperature) were observed. The different phases were detected by means of 35Cl NQR spectroscopy and thermal analysis

  5. Validation of a liquid chromatography-high-resolution mass spectrometry method for the analysis of ceftiofur in poultry muscle, kidneys and plasma: A unique accuracy profile for each and every matrix.

    PubMed

    Mompelat, Sophie; Fourmond, Marie-Pierre; Laurentie, Michel; Verdon, Eric; Hurtaud-Pessel, Dominique; Abjean, Jean-Pierre

    2015-08-14

    A robust, selective and specific liquid chromatography-high resolution mass spectrometry (LC-HRMS) method was developed for the quantification of total residues of ceftiofur, an antibiotic belonging to the 3rd generation cephalosporins in plasma, muscle and kidney of poultry. Ceftiofur and conjugates in samples were firstly hydrolyzed with dithioerythritol into desfuroylceftiofur, which was then stabilized by derivatization with iodoacetamide into desfuroylceftiofur acetamide. Sample were then submitted to a solid phase extraction followed the accurate mass analysis of desfuroylceftiofur acetamide by LC-HRMS in full scan mode using a linear trap quadrupole (LTQ)-Orbitrap mass spectrometer with a resolving power 60,000 full width at half maximum (FWHM). The method was fully validated over a dosing range between 100 and 2000 μg kg(-1) (or μg L(-1)) using the total error approach. Accuracy profiles a graphical decision-making tool were built by computing results of validation procedure with acceptance limits set at ±60%, and β-expectation tolerance intervals, i.e. the interval assuming to contain a β % of future measurements (β=90% in this study). Total measurement error including trueness, repeatability and intermediate precision were evaluated. Relative bias of trueness was never exceeding the threshold of 6% in all matrices at all level of concentration. The mean relative standard deviation for repeatability was lower than 16% at all levels of concentration for all matrices; the mean relative standard deviation for intermediate precision was lower than 25% at all levels of concentration for all matrices. This validation approach proved that the method is reliable for the quantification in each and every matrix (i.e. plasma, kidneys and muscle of chicken) thanks to only one single regression model (i.e. linear) obtained from external calibration standards (without matrix) with deuterated labelled internal standard. The developed method was applied during a

  6. Solid state structure and solution thermodynamics of three-centered hydrogen bonds (O∙∙∙H∙∙∙O) using N-(2-benzoyl-phenyl) oxalyl derivatives as model compounds.

    PubMed

    Gómez-Castro, Carlos Z; Padilla-Martínez, Itzia I; García-Báez, Efrén V; Castrejón-Flores, José L; Peraza-Campos, Ana L; Martínez-Martínez, Francisco J

    2014-09-12

    Intramolecular hydrogen bond (HB) formation was analyzed in the model compounds N-(2-benzoylphenyl)acetamide, N-(2-benzoylphenyl)oxalamate and N1,N2-bis(2-benzoylphenyl)oxalamide. The formation of three-center hydrogen bonds in oxalyl derivatives was demonstrated in the solid state by the X-ray diffraction analysis of the geometric parameters associated with the molecular structures. The solvent effect on the chemical shift of H6 [δH6(DMSO-d6)-δH6(CDCl3)] and Δδ(ΝΗ)/ΔT measurements, in DMSO-d6 as solvent, have been used to establish the energetics associated with intramolecular hydrogen bonding. Two center intramolecular HB is not allowed in N-(2-benzoylphenyl)acetamide either in the solid state or in DMSO-d6 solution because of the unfavorable steric effects of the o-benzoyl group. The estimated ΔHº and ΔSº values for the hydrogen bonding disruption by DMSO-d6 of 28.3(0.1) kJ·mol-1 and 69.1(0.4) J·mol-1·K-1 for oxalamide, are in agreement with intramolecular three-center hydrogen bonding in solution. In the solid, the benzoyl group contributes to develop 1-D and 2-D crystal networks, through C-H∙∙∙A (A = O, π) and dipolar C=O∙∙∙A (A = CO, π) interactions, in oxalyl derivatives. To the best of our knowledge, this is the first example where three-center hydrogen bond is claimed to overcome steric constraints.

  7. Syntheses of 5-phenyl-2-pyridinamine, a possibly carcinogenic pyrolysis product of phenylalanine, and some of its putative metabolites.

    PubMed

    Stavenuiter, J F; Verrips-Kroon, M; Bos, E J; Westra, J G

    1985-01-01

    5-Phenyl-2-pyridinamine (PPA) is a pyrolysis product of phenylalanine, the presence of which has been demonstrated in broiled sardines. Since PPA is mutagenic in the Ames test and is structurally related to the aminobiphenyls, it has to be considered as potentially carcinogenic. In this study procedures for the synthesis of PPA and its possible metabolites were developed to make them available for biological studies. PPA was synthesized in one step from 2,5-pyridinediamine. However, this method is only suitable for the preparation of small amounts. Larger quantities were synthesized starting from 5-nitro-2-pyridinamine in four steps. PPA was also prepared via a six-step synthesis, starting from 6-amino-3-pyridinecarboxamide. This route was also used for the synthesis of tritiated PPA [( 3H]PPA) and 2-nitro-5-phenylpyridine, the latter being the precursor of the two putative proximate carcinogenic metabolites, viz. the hydroxylamine and the hydroxamic acid of PPA. In the course of these multi-step syntheses a new method for the preparation of unsymmetrical biaryls was worked out. The following possible metabolites were also synthesized: N-(5-phenyl-2-pyridinyl)acetamide in the course of the synthesis of PPA starting from 5-nitro-2-pyridinamine, and both 5-(4-hydroxyphenyl)-2-pyridinamine (4'-OH-PPA) and N-[5-(4-hydroxyphenyl)-2-pyridinyl]acetamide starting from 5-(4-aminophenyl)-2-pyridinamine. After incubation of PPA in suspensions of freshly isolated hepatocytes from rats pretreated with polychlorinated biphenyls (Aroclor 1254) or PPA itself, the presence of 4'-OH-PPA was demonstrated.

  8. Theme-Based Bidisciplinary Chemistry Laboratory Modules

    NASA Astrophysics Data System (ADS)

    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

  9. Identification of a small-molecule inhibitor of HIV-1 assembly that targets the phosphatidylinositol (4,5)-bisphosphate binding site of the HIV-1 matrix protein.

    PubMed

    Zentner, Isaac; Sierra, Luz-Jeannette; Fraser, Ayesha K; Maciunas, Lina; Mankowski, Marie K; Vinnik, Andrei; Fedichev, Peter; Ptak, Roger G; Martín-García, Julio; Cocklin, Simon

    2013-03-01

    The development of drug resistance remains a critical problem for current HIV-1 antiviral therapies, creating a need for new inhibitors of HIV-1 replication. We previously reported on a novel anti-HIV-1 compound, N(2)-(phenoxyacetyl)-N-[4-(1-piperidinylcarbonyl)benzyl]glycinamide (14), that binds to the highly conserved phosphatidylinositol (4,5)-bisphosphate (PI(4,5)P(2)) binding pocket of the HIV-1 matrix (MA) protein. In this study, we re-evaluate the hits from the virtual screen used to identify compound 14 and test them directly in an HIV-1 replication assay using primary human peripheral blood mononuclear cells. This study resulted in the identification of three new compounds with antiviral activity; 2-(4-{[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]methyl})-1-piperazinyl)-N-(4-methylphenyl)acetamide (7), 3-(2-ethoxyphenyl)-5-[[4-(4-nitrophenyl)piperazin-1-yl]methyl]-1,2,4-oxadiazole (17), and N-[4-ethoxy-3-(1-piperidinylsulfonyl)phenyl]-2-(imidazo[2,1-b][1,3]thiazol-6-yl)acetamide (18), with compound 7 being the most potent of these hits. Mechanistic studies on 7 demonstrated that it directly interacts with and functions through HIV-1 MA. In accordance with our drug target, compound 7 competes with PI(4,5)P(2) for MA binding and, as a result, diminishes the production of new virus. Mutation of residues within the PI(4,5)P(2) binding site of MA decreased the antiviral effect of compound 7. Additionally, compound 7 displays a broadly neutralizing anti-HIV activity, with IC(50) values of 7.5-15.6 μM for the group M isolates tested. Taken together, these results point towards a novel chemical probe that can be used to more closely study the biological role of MA and could, through further optimization, lead to a new class of anti-HIV-1 therapeutics.

  10. Cross-modulation and molecular interaction at the Cav3.3 protein between the endogenous lipids and the T-type calcium channel antagonist TTA-A2.

    PubMed

    Cazade, Magali; Nuss, Cindy E; Bidaud, Isabelle; Renger, John J; Uebele, Victor N; Lory, Philippe; Chemin, Jean

    2014-02-01

    T-type calcium channels (T/Ca(v)3-channels) are implicated in various physiologic and pathophysiologic processes such as epilepsy, sleep disorders, hypertension, and cancer. T-channels are the target of endogenous signaling lipids including the endocannabinoid anandamide, the ω3-fatty acids, and the lipoamino-acids. However, the precise molecular mechanism by which these molecules inhibit T-current is unknown. In this study, we provided a detailed electrophysiologic and pharmacologic analysis indicating that the effects of the major N-acyl derivatives on the Ca(v)3.3 current share many similarities with those of TTA-A2 [(R)-2-(4-cyclopropylphenyl)-N-(1-(5-(2,2,2-trifluoroethoxy)pyridin-2-yl)ethyl)acetamide], a synthetic T-channel inhibitor. Using radioactive binding assays with the TTA-A2 derivative [(3)H]TTA-A1 [(R)-2-(4-(tert-butyl)phenyl)-N-(1-(5-methoxypyridin-2-yl)ethyl)acetamide], we demonstrated that polyunsaturated lipids, which inhibit the Ca(v)3.3 current, as NAGly (N-arachidonoyl glycine), NASer (N-arachidonoyl-l-serine), anandamide, NADA (N-arachidonoyl dopamine), NATau (N-arachidonoyl taurine), and NA-5HT (N-arachidonoyl serotonin), all displaced [(3)H]TTA-A1 binding to membranes prepared from cells expressing Ca(v)3.3, with Ki in a micromolar or submicromolar range. In contrast, lipids with a saturated alkyl chain, as N-arachidoyl glycine and N-arachidoyl ethanolamine, which did not inhibit the Ca(v)3.3 current, had no effect on [(3)H]TTA-A1 binding. Accordingly, bio-active lipids occluded TTA-A2 effect on Ca(v)3.3 current. In addition, TTA-Q4 [(S)-4-(6-chloro-4-cyclopropyl-3-(2,2-difluoroethyl)-2-oxo-1,2,3,4-tetrahydroquinazolin-4-yl)benzonitrile], a positive allosteric modulator of [(3)H]TTA-A1 binding and TTA-A2 functional inhibition, acted in a synergistic manner to increase lipid-induced inhibition of the Ca(v)3.3 current. Overall, our results demonstrate a common molecular mechanism for the synthetic T-channel inhibitors and the endogenous

  11. Nitrogen Metabolism and Growth Enhancement in Tomato Plants Challenged with Trichoderma harzianum Expressing the Aspergillus nidulans Acetamidase amdS Gene.

    PubMed

    Domínguez, Sara; Rubio, M Belén; Cardoza, Rosa E; Gutiérrez, Santiago; Nicolás, Carlos; Bettiol, Wagner; Hermosa, Rosa; Monte, Enrique

    2016-01-01

    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 Trichoderma 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

  12. Nitrogen Metabolism and Growth Enhancement in Tomato Plants Challenged with Trichoderma harzianum Expressing the Aspergillus nidulans Acetamidase amdS Gene

    PubMed Central

    Domínguez, Sara; Rubio, M. Belén; Cardoza, Rosa E.; Gutiérrez, Santiago; Nicolás, Carlos; Bettiol, Wagner; Hermosa, Rosa; Monte, Enrique

    2016-01-01

    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 Trichoderma 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

  13. Gallium(III) complexes of NOTA-bis (phosphonate) conjugates as PET radiotracers for bone imaging.

    PubMed

    Holub, Jan; Meckel, Marian; Kubíček, Vojtěch; Rösch, Frank; Hermann, Petr

    2015-01-01

    Ligands with geminal bis(phosphonic acid) appended to 1,4,7-triazacyclonone-1,4-diacetic acid fragment through acetamide (NOTAM(BP) ) or methylenephosphinate (NO2AP(BP) ) spacers designed for (68) Ga were prepared. Ga(III) complexation is much faster for ligand with methylenephosphinate spacer than that with acetamide one, in both chemical (high reactant concentrations) and radiolabeling studies with no-carrier-added (68) Ga. For both ligands, formation of Ga(III) complex was slower than that with NOTA owing to the strong out-of-cage binding of bis(phosphonate) group. Radiolabeling was efficient and fast only above 60 °C and in a narrow acidity region (pH ~3). At higher temperature, hydrolysis of amide bond of the carboxamide-bis(phosphonate) conjugate was observed during complexation reaction leading to Ga-NOTA complex. In vitro sorption studies confirmed effective binding of the (68) Ga complexes to hydroxyapatite being comparable with that found for common bis(phosphonate) drugs such as pamindronate. Selective bone uptake was confirmed in healthy rats by biodistribution studies ex vivo and by positron emission tomography imaging in vivo. Bone uptake was very high, with SUV (standardized uptake value) of 6.19 ± 1.27 for [(68) Ga]NO2AP(BP) ) at 60 min p.i., which is superior to uptake of (68) Ga-DOTA-based bis(phosphonates) and [(18) F]NaF reported earlier (SUV of 4.63 ± 0.38 and SUV of 4.87 ± 0.32 for [(68) Ga]DO3AP(BP) and [(18) F]NaF, respectively, at 60 min p.i.). Coincidently, accumulation in soft tissue is generally low (e.g. for kidneys SUV of 0.26 ± 0.09 for [(68) Ga]NO2AP(BP) at 60 min p.i.), revealing the new (68) Ga complexes as ideal tracers for noninvasive, fast and quantitative imaging of calcified tissue and for metastatic lesions using PET or PET/CT.

  14. Enhanced tumor retention of radioiodinated anti-epidermal growth factor receptor antibody using novel bifunctional iodination linker for radioimmunotherapy

    PubMed Central

    KIM, EUN JUNG; KIM, BYOUNG SOO; CHOI, DAN BEE; CHI, SUNG-GIL; CHOI, TAE HYUN

    2016-01-01

    Radioimmunotherapy (RIT) uses an antibody labeled with a radionuclide to deliver cytotoxic radiation to a target tumor cells. Radioiodine is most commonly employed to prepare radiolabeled proteins (antibodies, peptides) for in vitro and in vivo applications. A major shortcoming of radioiodinated proteins prepared by direct labeling methods is their deiodination in vivo. For the preparation of more stable radioiodinated antibodies, we developed a new linker (N-(4-isothiocyanatobenzyl)-2-(3-(tributylstannyl)phenyl) acetamide (IBPA). This study evaluated the usefulness of IBPA as a linker for the stable radioiodinated internalizing antibody, cetuximab. Directly labeled cetuximab ([125I]-cetuximab) was prepared by the chloramine T method. To prepare indirectly labeled cetuximab using IBPA ([125I]-IBPA-cetuximab), IBPA was radioiodinated using chloramine-T to give N-(4-isothiocyanatobenzyl)-2-(3-[125I]phenyl)acetamide ([125I]-IBPA), which was purified by high performance liquid chromatography. [125I]-IBPA was then conjugated to cetuximab. In vitro target binding and internalizing assays were performed in PC9, LS174T, and FaDu cell lines. In vivo planar images were obtained using an Inveon SPECT scanner 3, 24, 48, and 168 h after i.v. injection of [125I]-cetuximab or [125I]-IBPA-cetuximab in athymic mice bearing LS174T tumor xenografts. Specific binding and internalized radioactivity of [125I]-IBPA-cetuximab were higher than those of [125I]-cetuximab in PC9, LS174T, and FaDu cell lines. In planar images scant radioactivity was evident in thyroid glands after injection of [125I]-IBPA-cetuximab, while a high level of radioactivity was present in thyroid glands after injection of [125I]-cetuximab. Tumor uptake value of [125I]-IBPA-cetuximab was higher than that of [125I]-cetuximab for up to 168 h. [125I]-IBPA-cetuximab is stable and resistant to deiodination in vivo. IBPA is a promising bi-functional linker for radioiodination of internalizing monoclonal antibodies for in

  15. New macrocyclic terbium(III) complex for use in RNA footprinting experiments.

    PubMed

    Belousoff, Matthew J; Ung, Phuc; Forsyth, Craig M; Tor, Yitzhak; Spiccia, Leone; Graham, Bim

    2009-01-28

    Reaction of terbium triflate with a heptadentate ligand derivative of cyclen, L1 = 2-[7-ethyl-4,10-bis(isopropylcarbamoylmethyl)-1,4,7,10-tetraazacyclododec-1-yl]-N-isopropyl-acetamide, produced a new synthetic ribonuclease, [Tb(L1)(OTf)(OH(2))](OTf)(2).MeCN (C1). X-ray crystal structure analysis indicates that the terbium(III) center in C1 is 9-coordinate, with a capped square-antiprism geometry. While the terbium(III) center is tightly bound by the L1 ligand, two of the coordination sites are occupied by labile water and triflate ligands. In water, the triflate ligand is likely to be displaced, forming [Tb(L1)(OH(2))(2)](3+), which is able to effectively promote RNA cleavage. This complex greatly accelerates the rate of intramolecular transesterification of an activated model RNA phosphodiester, uridine-3'-p-nitrophenylphosphate (UpNP), with k(obs) = 5.5(1) x 10(-2) s(-1) at 21 degrees C and pH 7.5, corresponding to an apparent second-order rate constant of 277(5) M(-1) s(-1). By contrast, the analogous complex of an octadentate derivative of cyclen featuring only a single labile coordination site, [Tb(L2)(OH(2))](OTf)(3) (C2), where L2 = 2-[4,7,10-tris(isopropylcarbamoylmethyl)-1,4,7,10-tetraazacyclododec-1-yl]-N-isopropyl-acetamide, is inactive. [Tb(L1)(OH(2))(2)](3+) is also capable of hydrolyzing short transcripts of the HIV-1 transactivation response (TAR) element, HIV-1 dimerization initiation site (DIS) and ribosomal A-site, as well as formyl methionine tRNA (tRNA(fMet)), albeit at a considerably slower rate than UpNP transesterification (k(obs) = 2.78(8) x 10(-5) s(-1) for TAR cleavage at 37 degrees C, pH 6.5, corresponding to an apparent second-order rate constant of 0.56(2) M(-1)s(-1)). Cleavage is concentrated at the single-stranded "bulge" regions of these RNA motifs. Exploiting this selectivity, [Tb(L1)(OH(2))(2)](3+) was successfully employed in footprinting experiments, in which binding of the Tat peptide and neomycin B to the bulge region of the

  16. Overview of VOC emissions and chemistry from PTR-TOF-MS measurements during the SusKat-ABC campaign: high acetaldehyde, ketene, isoprene and isocyanic acid in wintertime air of the Kathmandu Valley

    NASA Astrophysics Data System (ADS)

    Sarkar, C.; Sinha, V.; Kumar, V.; Rupakheti, M.; Panday, A. K.; Mahata, K.; Rupakheti, D.; Kathayat, B.; Lawrence, M. G.

    2015-12-01

    During SusKat-ABC (Sustainable Atmosphere for the Kathmandu Valley-Atmospheric Brown Clouds) field campaign conducted in the winter of 2012-2013, a comprehensive study was carried out to characterize the chemical composition of ambient Kathmandu air for speciated VOCs by deploying a Proton Transfer Reaction Time of Flight Mass Spectrometer (PTR-TOF-MS), the first time to be deployed in South Asia. Due to its high mass resolution (m/Δm > 4200) and temporal resolution (1 minute), 71 ion peaks were detected in the PTR-TOF-MS mass scan data, highlighting the chemical complexity of ambient air in the Valley. Of the 71, 38 species were found to have campaign average concentrations > 200 ppt and were identified based on their spectral characteristics, ambient diel profiles and correlation with specific emission tracers. Distinct diel profiles were observed for the nominal isobaric compounds isoprene (m/z=69.070) and furan (m/z=69.033). Comparison with several sites elsewhere in the world showed mixing ratios of acetaldehyde (~ 9 ppb), acetonitrile (~1 ppb) and isoprene (~ 1 ppb) to be among the highest measured anywhere in the world. Two "new" ambient compounds namely, methanamide (m/z = 46.029) and acetamide (m/z=60.051) which can photochemically produce isocyanic acid in the atmosphere, are reported in this study alongwith nitromethane (a tracer for diesel exhaust) and ketene (a very reactive compound). Two distinct periods were identified during the campaign based on high daytime biogenic emissions of isoprene even in winter and biomass fired brick kiln emissions of acetonitrile, benzene and isocyanic acid. Biomass burning and biomass fired brick kiln emissions were found to be the dominant source for compounds such as propyne, propene, benzene and propanenitrile which correlated strongly with biomass burning tracer acetonitrile (r2 > 0.7). The calculated total VOC OH reactivity was dominated by acetaldehyde (20.1%), ketene (ethenone) (17.1%), isoprene (16.8 %) and

  17. Investigation of the Mechanism of Electron Capture and Electron Transfer Dissociation of Peptides with a Covalently Attached Free Radical Hydrogen Atom Scavenger.

    PubMed

    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

  18. Outsmarted by nootropics? An investigation into the thermal degradation of modafinil, modafinic acid, adrafinil, CRL-40,940 and CRL-40,941 in the GC injector: formation of 1,1,2,2-tetraphenylethane and its tetra fluoro analogue.

    PubMed

    Dowling, Geraldine; Kavanagh, Pierce V; Talbot, Brian; O'Brien, John; Hessman, Gary; McLaughlin, Gavin; Twamley, Brendan; Brandt, Simon D

    2016-12-08

    2-[(Diphenylmethyl)sulfinyl]acetamide (modafinil) is commonly prescribed for the treatment of narcolepsy. Increasing popularity and off-label use as a cognitive enhancer has resulted in a reputation as an intelligence boosting 'wonder drug'. Common alternatives available from online shops and other retail outlets include 2-[(diphenylmethyl)sulfinyl]-N-hydroxyacetamide (adrafinil), 2-{[bis(4-fluorophenyl)methyl]sulfinyl}acetamide (CRL-40,940), 2-{[bis(4-fluorophenyl)methyl]sulfinyl}-N-hydroxyacetamide (CRL-40,941), and N-methyl-4,4-difluoro-modafinil (modafiendz), respectively. Gas chromatography-mass spectrometry (GC-MS) is a common tool used in forensic and clinical analysis but there is a potential for inducing analysis-related ambiguities. This study reports on the thermal degradation of modafinil, modafinic acid, adrafinil, CRL-40,940, and CRL-40,941 due to exposure to the heated GC injection port dissolved in a variety of solvents. Key degradation products common to modafinil, modafinic acid, and adrafinil analysis included diphenylmethanol and 1,1,2,2-tetraphenylethane (TPE), the latter of which was verified by its synthesis and characterization by x-ray crystallography. The investigated compounds were also characterized by (1) H and (13) C NMR. Diphenylmethane and thiobenzophenone were also identified in some instances. TPE formation was suggested to involve the generation of a benzhydrylium ion and its reaction with the sulfoxide oxygen of the parent compound to give an oxysulfonium intermediate. Correspondingly, the fluorinated TPE analogue was formed during heat-induced degradation of modafiendz, CRL-40,940 and CRL-40,941, respectively. When a mixture of modafinil (non-fluorinated) and modafiendz (fluorinated) were subjected to GC analysis, 4,4'-(2,2-diphenylethane-1,1-diyl)bis(fluorobenzene) was detected as a third cross reaction product in addition to the two expected TPE analogues. These observations served as a reminder that the seemingly

  19. Interaction and dynamics of (alkylamide + electrolyte) deep eutectics: Dependence on alkyl chain-length, temperature, and anion identity

    SciTech Connect

    Guchhait, Biswajit; Das, Suman; Daschakraborty, Snehasis; Biswas, Ranjit

    2014-03-14

    Here we investigate the solute-medium interaction and solute-centered dynamics in (RCONH{sub 2} + LiX) deep eutectics (DEs) via carrying out time-resolved fluorescence measurements and all-atom molecular dynamics simulations at various temperatures. Alkylamides (RCONH{sub 2}) considered are acetamide (CH{sub 3}CONH{sub 2}), propionamide (CH{sub 3}CH{sub 2}CONH{sub 2}), and butyramide (CH{sub 3}CH{sub 2}CH{sub 2}CONH{sub 2}); the electrolytes (LiX) are lithium perchlorate (LiClO{sub 4}), lithium bromide (LiBr), and lithium nitrate (LiNO{sub 3}). Differential scanning calorimetric measurements reveal glass transition temperatures (T{sub g}) of these DEs are ∼195 K and show a very weak dependence on alkyl chain-length and electrolyte identity. Time-resolved and steady state fluorescence measurements with these DEs have been carried out at six-to-nine different temperatures that are ∼100–150 K above their individual T{sub g}s. Four different solute probes providing a good spread of fluorescence lifetimes have been employed in steady state measurements, revealing strong excitation wavelength dependence of probe fluorescence emission peak frequencies. Extent of this dependence, which shows sensitivity to anion identity, has been found to increase with increase of amide chain-length and decrease of probe lifetime. Time-resolved measurements reveal strong fractional power dependence of average rates for solute solvation and rotation with fraction power being relatively smaller (stronger viscosity decoupling) for DEs containing longer amide and larger (weaker decoupling) for DEs containing perchlorate anion. Representative all-atom molecular dynamics simulations of (CH{sub 3}CONH{sub 2} + LiX) DEs at different temperatures reveal strongly stretched exponential relaxation of wavevector dependent acetamide self dynamic structure factor with time constants dependent both on ion identity and temperature, providing justification for explaining the fluorescence results in

  20. Hydrologic and land-use factors associated with herbicides and nitrate in near-surface aquifers

    USGS Publications Warehouse

    Burkart, Michael R.; Kolpin, Dana W.

    1993-01-01

    Selected herbicides, atrazine (2-chloro-4-ethylamino-6-isopropylamino-s-triazine) metabolites, and NO−3 were examined in near-surface unconsolidated and bedrock aquifers in the midcontinental USA to study the hydrogeologic, spatial, and seasonal distribution of these contaminants. Groundwater samples were collected from 303 wells during the spring and late summer of 1991. At least one herbicide or atrazine metabolite was detected in 24% of the samples collected for herbicide analysis (reporting limit 0.05 µg/L). No herbicide concentration exceeded the USEPA's maximum contaminant level (MCL) or health advisory level. The most frequently detected compound was the at razine metabolite deethylatrazine [2-amino-4-chloro-6-(isopropylamino)-s-triazine] followed by atrazine, deisopropylatrazine [2-amino-4-chloro-6-(ethylamino)-s-triazine], prometon (2,4-bis(isopropylamino)-6-methyoxy-s-triazine), metolachlor [2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-1methylethyl)acetamide], alachlor [2-chloro-N-(2,6-diethylphenyl)-N-(methoxymethyl)acetamide], metribuzin [4-amino-6-(tert-butyl)-3-methylthio-as-triazine-5(4H)-one], simazine [2-chloro-4,6-bis(ethylamino)-s-triazine], and cyanazine [2-[[4-chloro-6-(ethylamino)-1,3,5-triazin-2-yl]amino]-2-methylpropionitrile]. Nitrite plus nitrate, as nitrogen (N), exceeding 3.0 mg/L (excess NO−3), was found in 29% of the samples, and 6% had −3exceeding the MCL of 10 mg/L. Ammonium as N was detected in excess of 0.01 mg/L in 78% of the samples. A nonlinear increase in the frequency of atrazine detection occurred with decreases in reporting limit. The frequency of atrazine residue detection (atrazine + deethylatrazine + deisopropylatrazine) was 25% greater than for atrazine alone. Herbicide detections and excess NO−3 were notably lacking in the eastern part of the study region where it was estimated that herbicide and fertilizer use were among the largest in the region. Prometon, the second most frequently detected herbicide

  1. Inhibition of HIF-1{alpha} activity by BP-1 ameliorates adjuvant induced arthritis in rats

    SciTech Connect

    Shankar, J.; Thippegowda, P.B.; Kanum, S.A.

    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.

  2. 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

    NASA Technical Reports Server (NTRS)

    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.

  3. Alkylation of a bioinspired high spin Ni(II)N{sub 3}S{sub 2} complex with bifunctional reagents

    SciTech Connect

    Chohan, B. S.

    2013-12-15

    Crystal structures of two S-alkylated complexes generated from the reaction of iodoacetamide and iodoethanol with an air and moisture sensitive high spin Ni(II) pentacoordinate triaminodithiolate complex, 1 are determined by X-ray structure analysis. Crystals of complex 2, [NiC{sub 16}H{sub 31}N{sub 5}O{sub 2}S{sub 2}]I{sub 2}, are triclinic, sp. gr. P-bar1 , Z = 2. Crystals of complex 3, [NiC{sub 16}H{sub 28}N{sub 3}O{sub 2}S{sub 2}]I{sub 2}, are monoclinic, sp. gr. P2{sub 1}/c, Z = 4. Structures of complexes 2 and 3 are very similar: one of the S-acetamide (2) or S-ethanol (3) groups coordinates to the Ni center through the oxygen atom forming N{sub 3}S{sub 2}O hexacoordination; the other group remains unbound to the Ni and left dangling. Crystal packing shows that complexes 2 and 3 interact with the iodide counterions, and that only complex 2 interact with neighboring molecules; some of these close intermolecular contacts include H-bonding interactions.

  4. Production, purification and characterization of laccase from Pleurotus ostreatus grown on tomato pomace.

    PubMed

    Freixo, Maria do Rosário; Karmali, Amin; Arteiro, José Maria

    2012-01-01

    A strain of Pleurotus ostreatus was grown in tomato pomace as sole carbon source for production of laccase. The culture of P. ostreatus revealed a peak of laccase activity (147 U/L of fermentation broth) on the 4th day of culture with a specific activity of 2.8 U/mg protein. Differential chromatographic behaviour of laccase was investigated on affinity chromatographic matrices containing either urea, acetamide, ethanolamine or IDA as affinity ligands. Laccase exhibited retention on such affinity matrices and it was purified on a Sepharose 6B-BDGE-urea column with final enzyme recoveries of about 60%, specific activity of 6.0 and 18.0 U/mg protein and purification factors in the range of 14-46. It was also possible to demonstrate that metal-free laccase did not adsorb to Sepharose 6B-BDGE-urea column which suggests that adsorption of native laccase on this affinity matrix was apparently due to the specific interaction of carbonyl groups available on the matrix with the active site Cu (II) ions of laccase. The kinetic parameters (V(max), K(m), K(cat), and K(cat)/K(m)) of the purified enzyme for several substrates were determined as well as laccase stability and optimum pH and temperature of enzyme activity. This is the first report describing the production of laccase from P. ostreatus grown on tomato pomace and purification of this enzyme based on affinity matrix containing urea as affinity ligand.

  5. 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.

    PubMed

    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.

  6. Expression, purification and functional characterization of AmiA of acetamidase operon of Mycobacterium smegmatis.

    PubMed

    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.

  7. Removal of Heavy Metals from Aqueous Solution Using Novel Nanoengineered Sorbents: Self-Assembled Carbamoylphosphonic Acids on Mesoporous Silica

    SciTech Connect

    Yantasee, Wassana; Lin, Yuehe; Fryxell, Glen E.; Busche, Brad J.; Birnbaum, Jerome C.

    2003-08-01

    Self-assembled monolayers of carbamoylphosphonic acids (acetamide phosphonic acid and propionamide phosphonic acid) on mesoporous silica supports were studied as potential absorbents for heavy and transition metal ions in aqueous wastes. The adsorption capacity, selectivity, and kinetics of the materials in sequestering metal ions, including Cd2+, Co2+, Cu2+, Cr3+, Pb2+, Ni2+, Zn2+, and Mn2+, were measured in batch experiments with excess sodium ion. The solution pH ranged from 2.2 to 5.5. The kinetics study shows that the adsorption reached equilibrium in seconds, indicating that there is little resistance to mass transfer, intraparticle diffusion, and surface chemical reaction. The competitive adsorption study found the phosphonic acid-SAMMS to have an affinity for divalent metal ions in decreasing order of Pb2+ > Cu2+ > Mn2+ > Cd2+ > Zn2+ > Co2+ > Ni2+. The measured Cd2+ adsorption isotherm was of the Langmuirian type and had a saturation binding capacity of 0.32 mmol/g.

  8. Hypoxia imaging agents labeled with positron emitters.

    PubMed

    Hoigebazar, Lathika; Jeong, Jae Min

    2013-01-01

    Imaging hypoxia using positron emission tomography (PET) is of great importance for therapy of cancer. [(18)F]Fluoromisonidazole (FMISO) was the first PET agent for hypoxia imaging, and various radiolabeled nitroimidazole derivatives such as [(18)F]fluoroerythronitroimidazole (FETNIM), [(18)F]1-α-D: -(2-deoxy-2-fluoroarabinofuranosyl)-2-nitroimidazole (FAZA), [(18)F]2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl) acetamide (EF-5), and [(18)F]fluoroetanidazole (FETA) have been developed successively. To overcome the high cost of cyclotron installation, (68)Ga-labeled nitroimidazole derivatives also have been developed. Another important hypoxia imaging agent is (64)Cu-diacetyl-bis(N (4)-methylthiosemicarbazone) ((64)Cu-ATSM), which can distribute in cancer tissue rapidly due to high lipophilicity. However, its application is limited due to high cost of radionuclide production. Although various hypoxia imaging agents have been reported and tested, hypoxia PET images still have to be improved, because of the low blood flow in hypoxic tissues and resulting low uptake of the agents.

  9. Electrospun Gallium Nitride Nanofibers (abstract)

    NASA Astrophysics Data System (ADS)

    Meléndez, Anamaris; Morales, Kristle; Ramos, Idalia; Campo, Eva; Santiago, Jorge J.

    2009-04-01

    The high thermal conductivity and wide bandgap of gallium nitride (GaN) are desirable characteristics in optoelectronics and sensing applications. In comparison to thin films and powders, in the nanofiber morphology the sensitivity of GaN is expected to increase as the exposed area (proportional to the length) increases. In this work we present electrospinning as a novel technique in the fabrication of GaN nanofibers. Electrospinning, invented in the 1930s, is a simple, inexpensive, and rapid technique to produce microscopically long ultrafine fibers. GaN nanofibers are produced using gallium nitrate and dimethyl-acetamide as precursors. After electrospinning, thermal decomposition under an inert atmosphere is used to pyrolyze the polymer. To complete the preparation, the nanofibers are sintered in a tube furnace under a NH3 flow. Both scanning electron microscopy and profilometry show that the process produces continuous and uniform fibers with diameters ranging from 20 to a few hundred nanometers, and lengths of up to a few centimeters. X-ray diffraction (XRD) analysis shows the development of GaN nanofibers with hexagonal wurtzite structure. Future work includes additional characterization using transmission electron microscopy and XRD to understand the role of precursors and nitridation in nanofiber synthesis, and the use of single nanofibers for the construction of optical and gas sensing devices.

  10. [Identification of narcotics in urine by capillary gas chromatography].

    PubMed

    Akalaev, A N; Shpagin, M G; Shabolenko, V P; Kovalenko, A E

    2004-01-01

    It is demonstrated that gas chromatography with quartz capillary columns (QCC) and with cross-sewn SE-52 by polysiloxane provides for the possibility to divide and identify, in human urine, 16 narcotic substances of the amphetamine, 1.4-benzodiazepine, morphine and other groups. The suggested extraction method makes it possible to isolate the above compounds from urine simultaneously and, after derivatization, to determine them by gas chromatography (GC) with programmed temperature within one stage analysis session. GC tests were performed on 2 both foreign and Russian QCC with SE-52. There is a description of 2 methods of how to obtain the trifluor-acetyl derivatives (TFA-derivatives) by using trifluor-acetate anhydride and N-methyl-bis-trifluor-acetamide. The limit of detecting the TFA-derivatives was 1-2 ng for the plasma-ionizing detector. The extraction method as well as the positive and negative aspects of using the TFA-derivatives are under discussion. The method of gas-chromatography/mass-spectrometry confirms that the positive results of radioreceptor assay are verified by GC in 92% of cases.

  11. A comparison of the alpha and gamma radiolysis of CMPO

    SciTech Connect

    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.

  12. Opioid-dopamine interaction in planaria: a behavioral study.

    PubMed

    Passarelli, F; Merante, A; Pontieri, F E; Margotta, V; Venturini, G; Palladini, G

    1999-09-01

    The behavioral response of planaria to the exposure to selective opioid agonists was studied. The mu agonist [d-ala2, N-methyl-Phe4,Gly5-ol]enkephalin (DAMGO) and the 6 agonist [D-Pen2, D-Pen5]enkephalin (DPDPE) failed to alter motor activity at all doses tested. Low doses of the selective kappa agonist (+/-)-trans-U-50-trans-3,4-dichloro-N-methyl-N[2-(1-pyrrodinyl)-cyclohexyl]benzene acetamide methasulphonate (U50, 488) and bremazocine-HCl increased motor activity leading to C-like position (CLP) and screw-like hyperkinesia (SLH). These changes were identical to those seen previously with the exposure to D2 or D1 dopamine receptor agonists, respectively. Higher doses of kappa agonists produced the enhancement of CLP and SLH together with robust snake-like movements (SLM). This latter response, that was typical of stimulation of kappa opioid receptors, was blocked by co-exposure to naloxone or the selective kappa antagonist Nor-binaltorphimine (Nor-BNI). Finally, co-exposure to sulpiride or SH-23390 respectively blocked the CLP or SLH response produced by U50,488 or bremazocine. Our data indicate the presence of kappa opioid receptors in planaria and suggest the functional interaction between the opioid and dopamine system in this simple animal model.

  13. Concomitant pseudopolymorphs of 10-deacetyl baccatin III.

    PubMed

    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.

  14. Sensitivity of transitions in internal rotor molecules to a possible variation of the proton-to-electron mass ratio

    NASA Astrophysics Data System (ADS)

    Jansen, Paul; Kleiner, Isabelle; Xu, Li-Hong; Ubachs, Wim; Bethlem, Hendrick L.

    2011-12-01

    Recently, methanol was identified as a sensitive target system to probe variations of the proton-to-electron mass ratio μ [Jansen , Phys. Rev. Lett.PRLTAO0031-900710.1103/PhysRevLett.106.100801 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, Kμ. 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 C3v 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, V3, and ρ). 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 μ.

  15. Sensitivity of Transitions in Internal Rotor Molecules to a Possible Variation of the Proton-To Mass Ratio

    NASA Astrophysics Data System (ADS)

    Jansen, P.; Ubachs, W.; Bethlem, H. L.; Kleiner, I.; Xu, L.-H.

    2013-06-01

    Recently, methanol was identified as a sensitive target system to probe variations of the proton-to-electron mass ratio. The high sensitivity of methanol originates from the interplay between overall rotation and hindered internal rotation of the molecule and it gives rise to a large enhancement of the sensitivity coefficient,K_{μ}. In this talk we will remind the general concepts that form the foundation of the high sensitivity in methanol and the approximate model which allows to estimate the sensitivities of transitions in internal rotor molecules with C_{3v} symmetry, without performing a full calculation of energy levels. We will show some examples by comparing obtained sensitivities for methanol, acetaldehyde, acetamide, methyl formate and acetic acid with a full analysis using the molecular Hamiltonian. The talk will give some details about how we obtain the energy levels from the BELGI code. From the molecules considered, methanol appears to be the most suitable candidate for laboratory and cosmological tests searching for a possible variation of μ. Jansen et al. Phys. Rev. Lett 106, 100801 (2011)}

  16. Imaging of peripheral-type benzodiazepine receptor in tumor: carbon ion irradiation reduced the uptake of a positron emission tomography ligand [11C]DAC in tumor.

    PubMed

    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.

  17. NAD deamidation "a new reaction" by an enzyme from Aspergillus terreus DSM 826.

    PubMed

    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.

  18. Alkylation of a bioinspired high spin Ni(II)N3S2 complex with bifunctional reagents

    NASA Astrophysics Data System (ADS)

    Chohan, B. S.

    2013-12-01

    Crystal structures of two S-alkylated complexes generated from the reaction of iodoacetamide and iodoethanol with an air and moisture sensitive high spin Ni(II) pentacoordinate triaminodithiolate complex, 1 are determined by X-ray structure analysis. Crystals of complex 2, [NiC16H31N5O2S2]I2, are triclinic, sp. gr. , Z = 2. Crystals of complex 3, [NiC16H28N3O2S2]I2, are monoclinic, sp. gr. P21/ c, Z = 4. Structures of complexes 2 and 3 are very similar: one of the S-acetamide ( 2) or S-ethanol ( 3) groups coordinates to the Ni center through the oxygen atom forming N3S2O hexacoordination; the other group remains unbound to the Ni and left dangling. Crystal packing shows that complexes 2 and 3 interact with the iodide counterions, and that only complex 2 interact with neighboring molecules; some of these close intermolecular contacts include H-bonding interactions.

  19. Hydrogen Bonding Interaction between Atmospheric Gaseous Amides and Methanol

    PubMed Central

    Zhao, Hailiang; Tang, Shanshan; Xu, Xiang; Du, Lin

    2016-01-01

    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. PMID:28042825

  20. Trapping of NAPQI, the intermediate toxic paracetamol metabolite, by aqueous sulfide (S²⁻) and analysis by GC-MS/MS.

    PubMed

    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).

  1. Intercalation of paracetamol into the hydrotalcite-like host

    NASA Astrophysics Data System (ADS)

    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.

  2. In silico modification of oseltamivir as neuraminidase inhibitor of influenza A virus subtype H1N1

    PubMed Central

    Tambunan, Usman Sumo Friend; Rachmania, Rizky Archintya; Parikesit, Arli Aditya

    2015-01-01

    Abstract 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-1-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. PMID:25859271

  3. Synergistic effects of ethosomes and chemical enhancers on enhancement of naloxone permeation through human skin.

    PubMed

    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 < 0.05) in vitro flux of naloxone. Azone 3% + PG7% pretreated in 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.

  4. Radiosynthesis, In Vivo Biological Evaluation, and Imaging of Brain Lesions with [123I]-CLINME, a New SPECT Tracer for the Translocator Protein

    PubMed Central

    Mattner, F.; Quinlivan, M.; Greguric, I.; Pham, T.; Liu, X.; Jackson, T.; Berghofer, P.; Fookes, C. J. R.; Dikic, B.; Gregoire, M.-C.; Dolle, F.; Katsifis, A.

    2015-01-01

    The high affinity translocator protein (TSPO) ligand 6-chloro-2-(4′-iodophenyl)-3-(N,N-methylethyl)imidazo[1,2-a]pyridine-3-acetamide (CLINME) was radiolabelled with iodine-123 and assessed for its sensitivity for the TSPO in rodents. Moreover neuroinflammatory changes on a unilateral excitotoxic lesion rat model were detected using SPECT imaging. [123I]-CLINME was prepared in 70–80% radiochemical yield. The uptake of [123I]-CLINME was evaluated in rats by biodistribution, competition, and metabolite studies. The unilateral excitotoxic lesion was performed by injection of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid unilaterally into the striatum. The striatum lesion was confirmed and correlated with TSPO expression in astrocytes and activated microglia by immunohistochemistry and autoradiography. In vivo studies with [123I]-CLINME indicated a biodistribution pattern consistent with TPSO distribution and the competition studies with PK11195 and Ro 5-4864 showed that [123I]-CLINME is selective for this site. The metabolite study showed that the extractable radioactivity was unchanged [123I]-CLINME in organs which expresses TSPO. SPECT/CT imaging on the unilateral excitotoxic lesion indicated that the mean ratio uptake in striatum (lesion : nonlesion) was 2.2. Moreover, TSPO changes observed by SPECT imaging were confirmed by immunofluorescence, immunochemistry, and autoradiography. These results indicated that [123I]-CLINME is a promising candidate for the quantification and visualization of TPSO expression in activated astroglia using SPECT. PMID:26199457

  5. Persistence of sister chromatid exchanges and in vitro morphological transformation of Syrian hamster fetal cells by chemical and physical carcinogens

    SciTech Connect

    Popescu, N.C.; Amsbaugh, S.C.; DiPaolo, J.A.

    1985-11-01

    The induction of neoplastic cell transformation is closely associated with DNA alterations which occur shortly after carcinogen exposure. Sister chromatid exchange (SCE) formation is a sensitive indicator of carcinogen-DNA interaction and correlates with the induction of morphological cell transformation. The persistence of lesions generating SCE produced by chemical and physical carcinogens and its relevance to the induction of morphologic transformation was evaluated in coordinated experiments with cultured Syrian hamster fetal cells (HFC). Exponentially growing HFC were exposed for 1 h to benzo(a)pyrene (BP), methyl-methanesulfonate (MMS), cis-platinum (II) diaminedichloride (cis Pt II), N-methyl-N'-nitrosourea (MNU), mitomycin C (MMC), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), N-acetoxy-2-fluorenyl-acetamide (AcAAF) or u.v. light irradiated. SCE analysis demonstrates that for a period of 48 h after carcinogen exposure, during which time the cells undergo at least four replicative cycles, DNA damage generating SCE induced by all chemical carcinogens either persisted or was partially removed, whereas u.v.-induced lesions were completely removed. An elevated SCE frequency persisted after two additional cell cycles after treatment with BP, AcAAF or MMC without increased cell lethality as compared to other carcinogens whose lesions were completely eliminated during the same period.

  6. 7-Substituted-pyrrolo[3,2-d]pyrimidine-2,4-dione derivatives as antagonists of the transient receptor potential ankyrin 1 (TRPA1) channel: a promising approach for treating pain and inflammation.

    PubMed

    Baraldi, Pier Giovanni; Romagnoli, Romeo; Saponaro, Giulia; Aghazadeh Tabrizi, Mojgan; Baraldi, Stefania; Pedretti, Pamela; Fusi, Camilla; Nassini, Romina; Materazzi, Serena; Geppetti, Pierangelo; Preti, Delia

    2012-03-01

    The transient receptor potential ankyrin 1 (TRPA1) channel is activated by a series of by-products of oxidative/nitrative stress, produced under inflammatory conditions or in the case of tissue damage, thus generating inflammatory and neuropathic pain and neurogenic inflammatory responses. These findings have identified TRPA1 as an emerging opportunity for the design and synthesis of selective inhibitors as potential analgesic and antiinflammatory agents. Herein we present the synthesis and functional evaluation of a new series of 7-substituted-1,3-dimethyl-1,5-dihydro-pyrrolo[3,2-d]pyrimidine-2,4-dione derivatives designed as TRPA1 antagonists. A small library of compounds has been built by the introduction of differently substituted N(7)-phenylacetamide or N(7)-[4-(substituted-phenyl)-thiazol-2-yl]-acetamide chains. All the synthesized compounds were assayed to evaluate their ability to block acrolein-mediated activation of native human and rat TRPA1 channels employing a fluorometric calcium imaging assay. Our study led us to the identification of compound 3h which showed considerably improved potency (IC(50)=400nM) against human TRPA1 with regard to some of the most representative antagonists previously reported and integrated in our screening program as reference compounds. In addition, 3h proved to maintain its efficacy toward rTRPA1, which designates it as a possible candidate for future evaluation of in vivo efficacy in rodent animal model of inflammatory and neuropathic pain.

  7. Crystal structure of oxam­yl

    PubMed Central

    Kwon, Eunjin; Park, Ki-Min; Park, Hyunjin; Kim, Tae Ho

    2016-01-01

    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). PMID:27980838

  8. (1)H NMR-based metabolomics study on a goldfish model of Parkinson's disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).

    PubMed

    Lu, Zhaoguang; Wang, Junsong; Li, Minghui; Liu, Qingwang; Wei, Dandan; Yang, Minghua; Kong, Lingyi

    2014-11-05

    A goldfish (Carassius auratus) model of Parkinson's disease (PD) was constructed by a single dose of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) according to previously reported methods. Global metabolite changes in brain of the MPTP induced goldfish model of PD were investigated. (1)H NMR-based metabolomics combined with various statistical methods such as orthogonal partial least squares discriminant analysis (OPLS-DA) and two-dimensional statistical total correlation spectroscopy (2D-STOCSY) found significant increase of leucine, isoleucine, valine, alanine, alanylalanine, creatinine, myo-inositol, 18:2 fatty acid, total fatty acids, arachic alcohol, taurine and significant decrease of N-acetylaspartate, (phospho)creatine, (phospho)choline, betaine, glutamine, 3-hexenedioate, acetamide, malonate, isocitrate, scyllo-inositol, phosphatidylcholines, cholesterols, n-3 fatty acids, polyunsaturated fatty acids (PUFAs) in brain of MPTP induced PD goldfish. These disturbed metabolite levels were involved in oxidative stress, energy failure, neuronal cell injury and death, consistent with those observed in clinical PD patients, and rodents and primates model of PD, indicating that the acute MPTP model of goldfish was an ideal and valuable model for PD research. In addition, several unusual metabolites in brain were significantly changed between MPTP induced PD and control goldfish, which might also play an important role in the pathogenesis of PD. This study also demonstrated the applicability and potential of (1)H NMR-based metabolomics approach for evaluation of animal models of disease induced by chemicals, such as MPTP-induced PD goldfish.

  9. Growth and development, and auxin polar transport of transgenic Arabidopsis under simulated microgravity conditions on a three-dimensional clinostat.

    PubMed

    Shimazu, Toru; Miyamoto, Kensuke; Ueda, Junichi

    2003-12-01

    Growth and development, and auxin polar transport in Arabidopsis thaliana transformed with iaaH gene were studied under simulated microgravity conditions on a three-dimensional (3-D) clinostat. Simulated microgravity conditions on a 3-D clinostat did not affect the number of rosette leaves but promoted the growth and development (fresh weight of plant and the elongation of flower stalk) of transformants. Final growth of transformants under simulated microgravity conditions on a 3-D clinostat was almost equivalent to that grown on 1 g conditions in the presence of 1 micromoles IAM (indole-3-acetamide). The activities of auxin polar transport in the segments of flower stalk (inflorescence axis) of transformants grown on 1 g conditions were significantly promoted by the addition of IAM. Interestingly, simulated microgravity conditions on a 3-D clinostat also promoted the activities of auxin polar transport of transformants grown on the medium with or without IAM. Based on the results in this study, transgenic plants may not have an efficient homeostatic mechanism for the control of growth and development, and auxin polar transport activity in microgravity conditions in space.

  10. A Novel Acylaminoimidazole Derivative, WN1316, Alleviates Disease Progression via Suppression of Glial Inflammation in ALS Mouse Model

    PubMed Central

    Yanagisawa, Yoshiko; Yasutake, Kaori; Inoue, Satoshi; Hirayama, Noriaki; Ikeda, Joh-E

    2014-01-01

    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(methyl)amino]-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(SOD1H46R) and ALS(SOD1G93A) 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. PMID:24498180

  11. Study of the Differential Activity of Thrombin Inhibitors Using Docking, QSAR, Molecular Dynamics, and MM-GBSA.

    PubMed

    Mena-Ulecia, Karel; Tiznado, William; Caballero, Julio

    2015-01-01

    Non-peptidic thrombin inhibitors (TIs; 177 compounds) with diverse groups at motifs P1 (such as oxyguanidine, amidinohydrazone, amidine, amidinopiperidine), P2 (such as cyanofluorophenylacetamide, 2-(2-chloro-6-fluorophenyl)acetamide), and P3 (such as phenylethyl, arylsulfonate groups) were studied using molecular modeling to analyze their interactions with S1, S2, and S3 subsites of the thrombin binding site. Firstly, a protocol combining docking and three dimensional quantitative structure-activity relationship was performed. We described the orientations and preferred active conformations of the studied inhibitors, and derived a predictive CoMSIA model including steric, donor hydrogen bond, and acceptor hydrogen bond fields. Secondly, the dynamic behaviors of some selected TIs (compounds 26, 133, 147, 149, 162, and 177 in this manuscript) that contain different molecular features and different activities were analyzed by creating the solvated models and using molecular dynamics (MD) simulations. We used the conformational structures derived from MD to accomplish binding free energetic calculations using MM-GBSA. With this analysis, we theorized about the effect of van der Waals contacts, electrostatic interactions and solvation in the potency of TIs. In general, the contents reported in this article help to understand the physical and chemical characteristics of thrombin-inhibitor complexes.

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

    NASA Astrophysics Data System (ADS)

    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.

  13. Role of Lewis acid additives in a palladium catalyzed directed C-H functionalization reaction of benzohydroxamic acid to isoxazolone.

    PubMed

    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.

  14. A new approach of microalgal biomass pretreatment using deep eutectic solvents for enhanced lipid recovery for biodiesel production.

    PubMed

    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.

  15. New insights into the primary phototransformation of acetaminophen by UV/H2O2: photo-Fries rearrangement versus hydroxyl radical induced hydroxylation.

    PubMed

    Feng, Shixiang; Zhang, Xu; Liu, Yanxiang

    2015-12-01

    The phototransformation of acetaminophen (APAP) by UV/H2O2 in deionized water and sewage treatment plant (STP) effluents was studied systematically by a combination of analysis of the reaction intermediates and kinetic study. 1-(2-amino-5-hydroxyphenyl)ethanone (P1) and the reported N-(3,4-dihydroxyphenyl)acetamide (P2) were identified as the main transformation intermediates during the transformation of APAP by UV/H2O2. There was no influence of OH on the formation kinetics of P1, while its decay was promoted. The formation and decay kinetics of P2 were accelerated by increases in the concentration of OH. The second-order rate constants for the reaction of OH with APAP, P1, and P2 were 3.9 × 10(9), 8.1 × 10(9), and 4.7 × 10(9) M(-1) s(-1), respectively. The kinetic study indicated that the main transformation of APAP also included transformation to 1,4-hydroquinone, although the accumulated concentration of 1,4-hydroquinone was quite low. The presence of anions (Cl(-), HCO3(-)/CO3(2-) NO2(-)/NO3(-)), humic acid, commercial drug components or adjuvants, and dissolved organic matters in STP effluents not only changed the transformation kinetics of APAP, but also altered the distribution of the intermediates. The kinetics and pathway of APAP transformation in STP effluent were markedly different from those in deionized water.

  16. Deformation micromechanics of all-cellulose nanocomposites: comparing matrix and reinforcing components.

    PubMed

    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.

  17. Selective Inhibition of KCC2 Leads to Hyperexcitability and Epileptiform Discharges in Hippocampal Slices and In Vivo

    PubMed Central

    Sivakumaran, Sudhir; Cardarelli, Ross A.; Maguire, Jamie; Kelley, Matt R.; Silayeva, Liliya; Morrow, Danielle H.; Mukherjee, Jayanta; Moore, Yvonne E.; Mather, Robert J.; Duggan, Mark E.; Brandon, Nicholas J.; Dunlop, John; Zicha, Stephen

    2015-01-01

    GABAA receptors form Cl− permeable channels that mediate the majority of fast synaptic inhibition in the brain. The K+/Cl− cotransporter KCC2 is the main mechanism by which neurons establish low intracellular Cl− levels, which is thought to enable GABAergic inhibitory control of neuronal activity. However, the widely used KCC2 inhibitor furosemide is nonselective with antiseizure efficacy in slices and in vivo, leading to a conflicting scheme of how KCC2 influences GABAergic control of neuronal synchronization. Here we used the selective KCC2 inhibitor VU0463271 [N-cyclopropyl-N-(4-methyl-2-thiazolyl)-2-[(6-phenyl-3-pyridazinyl)thio]acetamide] to investigate the influence of KCC2 function. Application of VU0463271 caused a reversible depolarizing shift in EGABA values and increased spiking of cultured hippocampal neurons. Application of VU0463271 to mouse hippocampal slices under low-Mg2+ conditions induced unremitting recurrent epileptiform discharges. Finally, microinfusion of VU0463271 alone directly into the mouse dorsal hippocampus rapidly caused epileptiform discharges. Our findings indicated that KCC2 function was a critical inhibitory factor ex vivo and in vivo. PMID:26019342

  18. Inhibition of cholinesterase activity by soil extracts and predicted environmental concentrations (PEC) to select relevant pesticides in polluted soils.

    PubMed

    Meza, Juan C Sanchez; Perez, Pedro Avila; Salin, Manuel Borja; Salazar, Victor F Pacheco; Lapoint, Tom

    2010-04-01

    The correlation of predicted environmental concentrations (PEC) with cholinesterase activity inhibition detected in soil extracts was determined. PEC was derived from organophosphate (OP) and carbamate (CA) compounds applied to a flower crop area. Samples of surface soil (0 - 30 cm in depth) and subsurface soil (30 to 60 cm in depth) were taken from a flower crop area in which OP pesticides such as acephate ((RS)-N-[methoxy(methylthio)phosphinoyl]acetamide), dimethoate (2-dimethoxyphosphinothioylthio-N-methylacetamide) and methyl parathion (O,O-dimethyl O-4-nitrophenyl phosphorothioate), and CA pesticides such as carbendazim (methyl benzimidazol-2-ylcarbamate), carbofuran (2,3-dihydro-2,2-dimethylbenzofuran-7-yl methylcarbamate) and methomyl (S-methyl (EZ)-N-(methylcarbamoyloxy) thioacetimidate) were applied for two years. Weekly loads of these pesticides were registered to estimate the annual load of each compound. Physicochemical analysis and relative inhibition of cholinesterasic activity were measured for each soil sample. PEC values were estimated with Pesticide Analytical Model (PESTAN), a leach model, for each pesticide using soil sample data obtained from physicochemical analysis. From all pesticides tested, only acephate and methomyl showed a significant correlation (p < 0.01) between PEC values and inhibition cholinesterase activity of soil extracts. These results suggest that inhibition of cholinesterase activity observed in soil extracts is produced mainly by these two pesticides. Further studies could be developed to measure acephate and methomyl concentrations to reduce their environmental impact.

  19. Preparation of polyvinylidene fluoride/cellulose acetate blend membrane with polyethylene glycol additive for apple juice clarification

    NASA Astrophysics Data System (ADS)

    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.

  20. Metabolite gene regulation of the L-arabinose operon in Escherichia coli with indoleacetic acid and other indole derivatives.

    PubMed

    Kline, E L; Brown, C S; Bankaitis, V; Montefiori, D C; Craig, K

    1980-04-01

    The ability of indole derivatives to facilitate RNA polymerase transcription of the L-arabinose operon in Escherichia coli was shown to require the catabolite activator protein (CAP) as well as the araC gene product. Adenosine 3',5'-monophosphate (cAMP) was not obligatory for araBAD transcription when the cells were grown in the presence of 1 mM indole-3-acetic acid or in the presence of indole-3-acetamide, indole-3-propionic acid, indole-3-butyric acid, or 5-hydroxyindole-3-acetic acid. However, these indole derivatives were unable to circumvent the cAMP requirement for the induction of the lactose and the maltose operons. Catabolic repression occurred when glucose was added to cells grown in the presence of L-arabinose and 1 mM indoleacetic acid or 1 mM cAMP. This effect was reversed at higher concentrations of indoleacetic acid or cAMP. The induction and the catabolite repression phenomena were quantitated by measuring the differential rate of synthesis of L-arabinose isomerase (the araA gene product). These results indicated that indole metabolites from various living systems may regulate gene expression and may be involved in "metabolite gene regulation."

  1. A novel series of thiosemicarbazone drugs: From synthesis to structure

    NASA Astrophysics Data System (ADS)

    Ebrahimi, Hossein Pasha; Hadi, Jabbar S.; Alsalim, Tahseen A.; Ghali, Thaer S.; Bolandnazar, Zeinab

    2015-02-01

    A new series of thiosemicarbazones (TSCs) and their 1,3,4-thiadiazolines (TDZs) containing acetamide group have been synthesized from thiosemicarbazide compounds by the reaction of TSCs with cyclic ketones as well as aromatic aldehydes. The structures of newly synthesized 1,3,4-thiadiazole derivatives obtained by heterocyclization of the TSCs with acetic anhydride were experimentally characterized by spectral methods using IR, 1H NMR, 13C NMR and mass spectroscopic methods. Furthermore, the structural, thermodynamic, and electronic properties of the studied compounds were also studied theoretically by performing Density Functional Theory (DFT) to access reliable results to the experimental values. The molecular geometry, the highest occupied molecular orbital (HOMO), the lowest unoccupied molecular orbital (LUMO) and Mulliken atomic charges of the studied compounds have been calculated at the B3LYP method and standard 6-31+G(d,p) basis set starting from optimized geometry. The theoretical 13C chemical shift results were also calculated using the gauge independent atomic orbital (GIAO) approach and their respective linear correlations were obtained.

  2. Characterization and differentiation of high energy amine peroxides by direct analysis in real time TOF/MS

    NASA Astrophysics Data System (ADS)

    Peña-Quevedo, Alvaro J.; Cody, Robert; Mina-Camilde, Nairmen; Ramos, Mildred; Hernández-Rivera, Samuel P.

    2007-04-01

    Characterization of hexamethelene triperoxide diamine (HMTD), tetramethylene diperoxide dicarbamide (TMDD) and tetramethylene diperoxide acetamide (TMDA) has been carried out using Direct Analysis in Real Time/Time of Flight Mass Spectrometry (DART-TOF/MS). The study also centered in the detection of their precursors such as hexamine and formaldehyde. Analysis of the compounds by GC-MS was also conducted. HMTD shows a clear peak at 209 m/z that allowed its detection in standard solutions and lab made standards. TATP samples with deuterium enrichment are being analyzed to compare results that could differentiate from HMTD and similar substances. All samples were characterized by Raman and FT-IR to confirm the DART results. Some of the vibrations observed were in the ν(O-O), ν(N-C), ν(N-H), ν(C-O), δ(CH 3-C) and δ(C-O). Development methodology for trace detection was compared with GC/MS and HPLC-MS results previously presented for HMTD and TATP.

  3. Effect of Acid Treatment of Plant Cuticles on Sorption of Selected Auxins 1

    PubMed Central

    Shafer, Warren E.; Bukovac, Martin J.

    1987-01-01

    Sorption characteristics of 2-(1-naphthyl)acetic acid (NAA), 2-(1-naphthyl)acetamide (NAAm), and 2,4-dichlorophenoxyacetic acid (2,4-D) were determined for cuticles enzymically isolated from mature tomato (Lycopersicon esculentum Mill. cv Sprinter) and pepper (Capsicum annuum L.) fruit. Sorption equilibrium for NAA and 2,4-D by tomato cuticular membranes (CM) and dewaxed cuticular membranes (DCM) was achieved within 24 hours at 25°C. The average K (partition coefficient) values for NAA in tomato CM and DCM were 166 and 204, respectively, whereas the corresponding K values for 2,4-D were 292 and 383, respectively. Sorption equilibrium for 2,4-D and NAA in pepper cuticles was not achieved after 18 and 63 days, respectively. Sorption equilibrium for NAAm in tomato and pepper CM and DCM was attained within 48 hours. Acid pretreatment (2.0 n HCl, 10 minutes) had no effect on NAA, 2,4-D, or NAAm sorption by tomato CM and DCM, or on NAAm sorption by pepper CM and DCM. Acid pretreatment of pepper CM and DCM led to slightly lower KpH (apparent partition coefficient) values for both NAA and 2,4-D. More significantly, sorption equilibrium for NAA and 2,4-D in pepper CM and DCM was achieved within 24 hours after acid treatment. PMID:16665302

  4. Indole signaling and (micro)algal auxins decrease the virulence of Vibrio campbellii, a major pathogen of aquatic organisms.

    PubMed

    Yang, Qian; Pande, Gde Sasmita Julyantoro; Wang, Zheng; Lin, Baochuan; Rubin, Robert A; Vora, Gary J; Defoirdt, Tom

    2017-03-02

    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, we investigated the impact of indole signaling on the virulence of Vibrio campbellii. 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 signaling was found to interact with the stress sigma factor RpoS. Together with our 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, we found that the auxins indole-3-acetic acid and indole-3-acetamide, which are 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. This article is protected by copyright. All rights reserved.

  5. Acetochlor in the hydrologic system in the midwestern United States, 1994

    USGS Publications Warehouse

    Kolpin, D.W.; Nations, B.K.; Goolsby, D.A.; Thurman, E.M.

    1996-01-01

    The herbicide acetochlor [2-chloro-N-(ethoxymethyl)-N-(2-ethyl-6-methylphenyl)acetamide] was given conditional registration in the United States by the U.S. Environmental Protection Agency in March 1994. This registration provided a rare opportunity to investigate the occurrence of a pesticide during its first season of extensive use in the midwestern United States. Water samples collected and analyzed by the U.S. Geological Survey during 1994 documented the distribution of acetochlor in the hydrologic system; it was detected in 29% of the rain samples from four sites in Iowa, 17% of the stream samples from 51 sites across nine states, and 0% of the groundwater samples from 38 wells across eight states. Acetochlor exhibited concentration increases in rain and streams following its application to corn in the midwestern United States, with 75% of the rainwater and 35% of the stream samples having acetochlor detected during this time period. Acetochlor concentrations in rain decreased as the growing season progressed. Based on the limited data collected for this study, it is anticipated that acetochlor concentrations will have a seasonal pattern in rain and streams similar to those of other acetanilide herbicides examined. Possible explanations for the absence of acetochlor in groundwater for this study include the rapid degradation of acetochlor in the soil zone, insufficient time for this first extensive use of acetochlor to have reached the aquifers sampled, and the possible lack of acetochlor use in the recharge areas for the wells examined.

  6. Synthesis and nootropic activity of some 2,3-dihydro-1H-isoindol-1-one derivatives structurally related with piracetam.

    PubMed

    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.

  7. Putting Tuberculosis (TB) To Rest: Transformation of the Sleep Aid, Ambien, and “Anagrams” Generated Potent Antituberculosis Agents

    PubMed Central

    2015-01-01

    Zolpidem (Ambien, 1) is an imidazo[1,2-a]pyridine-3-acetamide and an approved drug for the treatment of insomnia. As medicinal chemists enamored by how structure imparts biological function, we found it to have strikingly similar structure to the antitubercular imidazo[1,2-a]pyridine-3-carboxyamides. Zolpidem was found to have antituberculosis activity (MIC of 10–50 μM) when screened against replicating Mycobacterium tuberculosis (Mtb) H37Rv. Manipulation of the Zolpidem structure, notably, to structural isomers (“anagrams”), attains remarkably improved potency (5, MIC of 0.004 μM) and impressive potency against clinically relevant drug-sensitive, multi- and extensively drug-resistant Mtb strains (MIC < 0.03 μM). Zolpidem anagrams and analogues were synthesized and evaluated for their antitubercular potency, toxicity, and spectrum of activity against nontubercular mycobacteria and Gram-positive and Gram-negative bacteria. These efforts toward the rational design of isomeric anagrams of a well-known sleep aid underscore the possibility that further optimization of the imidazo[1,2-a]pyridine core may well “put TB to rest”. PMID:25984566

  8. 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

    NASA Astrophysics Data System (ADS)

    Vinay Kumar, B.; Bhojya Naik, H. S.; Girija, D.; Sharath, N.; Pradeepa, S. M.; Joy Hoskeri, H.; Prabhakara, M. C.

    A new tetra-aza macrocyclic ligand, L (C24H16N12O2S4) and its complexes of type, [MLCl2] and [CuL]Cl2 (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.

  9. Effects of anthropogenic inputs on the organic quality of urbanized streams.

    PubMed

    Kalscheur, Kathryn N; Penskar, Rebecca R; Daley, Allison D; Pechauer, Shannon M; Kelly, John J; Peterson, Christopher G; Gray, Kimberly A

    2012-05-15

    Due to arid conditions, population growth, and anthropogenic impacts from agricultural and urban development, wastewater effluent makes up an increasingly large percentage of surface water supplies promoting concerns about the potential ecological and human health effects associated with the organic quality of surface waters receiving treated wastewater discharge. Anthropogenic inputs alter the quality and quantity of organic carbon and also affect the ability of aquatic ecosystems to retain or transform carbon and other nutrients. In this paper, we use pyrolysis-GC/MS (Py-GC/MS) as a tool to examine whether the dissolved organic carbon (DOC) in suburban streams influenced by anthropogenic inputs displays an organic signature that is structurally different from natural organic material (NOM). Py-GC/MS was not only able to differentiate among stream sites that received discharge from upstream wastewater treatment plants and those that did not, but also distinguished stream sites influenced significantly by storm water. Distinct organic signatures were evident in stream waters with upstream wastewater treatment plant discharges regardless of the distance from effluent discharge, indicative of the persistent nature of effluent-derived organic material (EfOM). The pyrolysis fragments of 3-methyl-pyridine, 2-methyl-pyridine, pyrrole, and acetamide were identified as indicators of EfOM, supporting previous research that has suggested that protein and aminosugar derivitives are possible wastewater markers. Furthermore, pyrolysis fragments associated with soil polycarboxylic acids correlated highly with stream sites having the least anthropogenic influences.

  10. ucb L059, a novel anti-convulsant drug: pharmacological profile in animals.

    PubMed

    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.

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

    NASA Astrophysics Data System (ADS)

    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_a<10 could be fitted within experimental accuracy. The rotational spectra of both molecules were analyzed using modified version of the RAM36 code, taking nuclear quadrupole hyperfine coupling into account. Details of the new study and problems encountered in the analysis will be discussed. Part of this work was done within the Ukrainian-French CNRS-PICS 6051 project.

  12. Radiosynthesis and evaluation of [11C]EMPA as a potential PET tracer for orexin 2 receptors.

    PubMed

    Wang, Changning; Moseley, Christian K; Carlin, Stephen M; Wilson, Colin M; Neelamegam, Ramesh; Hooker, Jacob M

    2013-06-01

    EMPA is a selective antagonist of orexin 2 (OX2) receptors. Previous literature with [(3)H]-EMPA suggest that it may be used as an imaging agent for OX2 receptors; however, brain penetration is known to be modest. To evaluate the potential of EMPA as a PET radiotracer in non-human primate (as a step to imaging in man), we radiolabeled EMPA with carbon-11. Radiosynthesis of [(11)C]N-ethyl-2-(N-(6-methoxypyridin-3-yl)-2-methylphenylsulfonamido)-N-(pyridin-3-ylmethyl)acetamide ([(11)C]EMPA), and evaluation as a potential PET tracer for OX2 receptors is described. Synthesis of an appropriate non-radioactive O-desmethyl precursor was achieved from EMPA with sodium iodide and chlorotrimethylsilane. Selective O-methylation using [(11)C]CH3I in the presence of cesium carbonate in DMSO at room temp afforded [(11)C]EMPA in 1.5-2.5% yield (non-decay corrected relative to trapped [(11)C]CH3I at EOS) with ≥95% chemical and radiochemical purities. The total synthesis time was 34-36min from EOB. Studies in rodent suggested that uptake in tissue was dominated by nonspecific binding. However, [(11)C]EMPA also showed poor uptake in both rats and baboon as measured with PET imaging.

  13. Production of induced secondary metabolites by a co-culture of sponge-associated actinomycetes, Actinokineospora sp. EG49 and Nocardiopsis sp. RV163.

    PubMed

    Dashti, Yousef; Grkovic, Tanja; Abdelmohsen, Usama Ramadan; Hentschel, Ute; Quinn, Ronald J

    2014-05-22

    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.

  14. Enthused research on DNA-binding and DNA-cleavage aptitude of mixed ligand metal complexes

    NASA Astrophysics Data System (ADS)

    Mahalakshmi, Rajkumar; Raman, Natarajan

    2013-08-01

    Five new Mn(II), Co(II), Ni(II), Cu(II) and Zn(II) mixed ligand complexes have been synthesized using a Schiff base precursor (obtained by the condensation of N-(4-aminophenyl)acetamide and 4-chlorobenzaldehyde) as main ligand and 1,10-phenanthroline as co-ligand. They have been characterized by microanalytical data, IR, UV-Vis, magnetic moment values, conductivity and electrochemical measurements. The spectral data reveal that all the complexes exhibit octahedral geometry. The high electrical conductance of the complexes supports their electrolytic nature. The monomeric nature of the complexes has been assessed from their magnetic susceptibility values. These complexes are better antimicrobial active agents than the free ligands. DNA (CT) binding properties of these complexes have been explored by UV-Vis., viscosity measurements, cyclic voltammetry, and differential pulse voltammetry measurements. The oxidative cleavage activity of the complexes has been studied using supercoiled pUC19 DNA by gel electrophoresis. The experimental results show that the complexes are good intercalators.

  15. Effects of Block Length and Membrane Processing Conditions on the Morphology and Properties of Perfluorosulfonated Poly(arylene ether sulfone) Multiblock Copolymer Membranes for PEMFC.

    PubMed

    Assumma, Luca; Nguyen, Huu-Dat; Iojoiu, Cristina; Lyonnard, Sandrine; Mercier, Régis; Espuche, Eliane

    2015-07-01

    Perfluorosulfonated poly(arylene ether sulfone) multiblock copolymers have been shown to be promising as proton exchange membranes. The commonly used approach for preparation of the membrane is solvent casting; the properties of the resulting membranes are very dependent on the membrane processing conditions. In this paper, we study the effects of block length, selectivity of the solvent, and thermal treatment on the membrane properties such as morphology, water uptake, and ionic conductivity. DiMethylSulfOxide (DMSO), and DiMethylAcetamide (DMAc) were selected as casting solvents based on the Flory-Huggins parameter calculated by inversion gas chromatography (IGC). It was found that the solvent selectivity has a mild impact on the mean size of the ionic domains and the expansion upon swelling, while it dramatically affects the supramolecular ordering of the blocks. The membranes cast from DMSO exhibit more interconnected ionic clusters yielding higher conductivities and water uptake as compared to membranes cast from DMAc. A 10-fold increase in proton conductivity was achieved after thermal annealing of membranes at 150 °C, and the ionomers with longer block lengths show conductivities similar to Nafion at 80 °C and low relative humidity (30%).

  16. GC-MS analysis of bioactive compounds in the methanol extract of Clerodendrum viscosum leaves

    PubMed Central

    Ghosh, Goutam; Panda, Pritipadma; Rath, Meera; Pal, Abhisek; Sharma, Tripti; Das, Debajyoti

    2015-01-01

    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(1H)Pyrimidinone,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. PMID:25598644

  17. TRPA1 contributes to cold hypersensitivity.

    PubMed

    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.

  18. Cytokinins of the Developing Mango Fruit : Isolation, Identification, and Changes in Levels during Maturation.

    PubMed

    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.

  19. Significant changes in the photo-reactivity of TiO2 in the presence of a capped natural dissolved organic matter layer.

    PubMed

    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.

  20. High temperature two component explosive

    DOEpatents

    Mars, James E.; Poole, Donald R.; Schmidt, Eckart W.; Wang, Charles

    1981-01-01

    A two component, high temperature, thermally stable explosive composition comprises a liquid or low melting oxidizer and a liquid or low melting organic fuel. The oxidizer and fuel in admixture are incapable of substantial spontaneous exothermic reaction at temperatures on the order of 475.degree. K. At temperatures on the order of 475.degree. K., the oxidizer and fuel in admixture have an activation energy of at least about 40 kcal/mol. As a result of the high activation energy, the preferred explosive compositions are nondetonable as solids at ambient temperature, and become detonable only when heated beyond the melting point. Preferable oxidizers are selected from alkali or alkaline earth metal nitrates, nitrites, perchlorates, and/or mixtures thereof. Preferred fuels are organic compounds having polar hydrophilic groups. The most preferred fuels are guanidinium nitrate, acetamide and mixtures of the two. Most preferred oxidizers are eutectic mixtures of lithium nitrate, potassium nitrate and sodium nitrate, of sodium nitrite, sodium nitrate and potassium nitrate, and of potassium nitrate, calcium nitrate and sodium nitrate.

  1. A novel nanostructure of cadmium oxide synthesized by mechanochemical method

    SciTech Connect

    Tadjarodi, A.; Imani, M.

    2011-11-15

    Highlights: {yields} A novel nanostructure of CdO was synthesized by mechanochemical reaction followed by calcination. {yields} Mechanochemical method is a simple and low-cost to synthesize nanomaterials. {yields} The obtained precursor was characterized by FT-IR, NMR techniques and elemental analysis. {yields} SEM images showed cauliflower-like shape of sample with components average diameter of 68 nm. {yields} The rods and tubes bundles with single crystalline nature were revealed by ED pattern and TEM images. -- Abstract: Cauliflower-like cadmium oxide (CdO) nanostructure was synthesized by mechanochemical reaction followed calcination procedure. Cadmium acetate dihydrate and acetamide were used as reagents and the resulting precursor was calcinated at 450 {sup o}C for 2 h in air. The structures of the precursor and resultant product of the heating treatment were characterized using Fourier transform infrared (FT-IR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy and elemental analysis, X-ray powder diffraction (XRD), energy-dispersive X-ray spectroscopy analysis (EDX), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and electron diffraction pattern (ED). SEM and TEM images revealed the cauliflower-like morphology of the sample. This structure includes the bundles of rods and tubes in nanoscale, which combine with each other and form the resulting morphology with the average diameter, 68 nm of the components. ED pattern indicated the single crystal nature of the formed bundles.

  2. Study of the Differential Activity of Thrombin Inhibitors Using Docking, QSAR, Molecular Dynamics, and MM-GBSA

    PubMed Central

    Mena-Ulecia, Karel; Tiznado, William; Caballero, Julio

    2015-01-01

    Non-peptidic thrombin inhibitors (TIs; 177 compounds) with diverse groups at motifs P1 (such as oxyguanidine, amidinohydrazone, amidine, amidinopiperidine), P2 (such as cyanofluorophenylacetamide, 2-(2-chloro-6-fluorophenyl)acetamide), and P3 (such as phenylethyl, arylsulfonate groups) were studied using molecular modeling to analyze their interactions with S1, S2, and S3 subsites of the thrombin binding site. Firstly, a protocol combining docking and three dimensional quantitative structure–activity relationship was performed. We described the orientations and preferred active conformations of the studied inhibitors, and derived a predictive CoMSIA model including steric, donor hydrogen bond, and acceptor hydrogen bond fields. Secondly, the dynamic behaviors of some selected TIs (compounds 26, 133, 147, 149, 162, and 177 in this manuscript) that contain different molecular features and different activities were analyzed by creating the solvated models and using molecular dynamics (MD) simulations. We used the conformational structures derived from MD to accomplish binding free energetic calculations using MM-GBSA. With this analysis, we theorized about the effect of van der Waals contacts, electrostatic interactions and solvation in the potency of TIs. In general, the contents reported in this article help to understand the physical and chemical characteristics of thrombin-inhibitor complexes. PMID:26599107

  3. Evaluation of the structural, electronic, topological and vibrational properties of N-(3,4-dimethoxybenzyl)-hexadecanamide isolated from Maca (Lepidium meyenii) using different spectroscopic techniques

    NASA Astrophysics Data System (ADS)

    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.

  4. A facile approach for high surface area electrospun TiO2 nanostructures for photovoltaic and photocatalytic applications.

    PubMed

    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.

  5. Repurposing the Open Access Malaria Box To Discover Potent Inhibitors of Toxoplasma gondii and Entamoeba histolytica

    PubMed Central

    Fokou, Patrick V. T.; Tchokouaha, Lauve R. Y.; Spangenberg, Thomas; Mfopa, Alvine N.; Kouipou, Ruffin M. T.; Mbouna, Cedric J.; Donfack, Valerie F. Donkeng; Zollo, Paul H. A.

    2014-01-01

    Toxoplasmosis and amebiasis are important public health concerns worldwide. The drugs currently available to control these diseases have proven limitations. Therefore, innovative approaches should be adopted to identify and develop new leads from novel scaffolds exhibiting novel modes of action. In this paper, we describe results from the screening of compounds in the Medicines for Malaria Venture (MMV) open access Malaria Box in a search for new anti-Toxoplasma and anti-Entamoeba agents. Standard in vitro phenotypic screening procedures were adopted to assess their biological activities. Seven anti-Toxoplasma compounds with a 50% inhibitory concentration (IC50) of <5 μM and selectivity indexes (SI) of >6 were identified. The most interesting compound was MMV007791, a piperazine acetamide, which has an IC50 of 0.19 μM and a selectivity index of >157. Also, we identified two compounds, MMV666600 and MMV006861, with modest activities against Entamoeba histolytica, with IC50s of 10.66 μM and 15.58 μM, respectively. The anti-Toxoplasma compounds identified in this study belong to scaffold types different from those of currently used drugs, underscoring their novelty and potential as starting points for the development of new antitoxoplasmosis drugs with novel modes of action. PMID:25049259

  6. Synthesis and Antimicrobial Evaluation of Some Novel Thiazole, Pyridone, Pyrazole, Chromene, Hydrazone Derivatives Bearing a Biologically Active Sulfonamide Moiety

    PubMed Central

    Darwish, Elham S.; Abdel Fattah, Azza M.; Attaby, Fawzy A.; Al-Shayea, Oqba N.

    2014-01-01

    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. PMID:24445259

  7. Occurrence of selected pesticides and their metabolites in near-surface aquifers of the midwestern United States

    USGS Publications Warehouse

    Kolpin, D.W.; Michael, Thurman E.; Goolsby, D.A.

    1996-01-01

    The occurrence and distribution of selected pesticides and their metabolites were investigated through the collection of 837 water-quality samples from 303 wells across the Midwest. Results of this study showed that five of the six most frequently detected compounds were pesticide metabolites. Thus, it was common for a metabolite to be found more frequently in groundwater than its parent compound. The metabolite alachlor ethanesulfonic acid (alachlor-ESA; 2-[(2,6-diethylphenyl)(methoxymethyl)amino]-2-oxoethanesulfonic acid) was detected almost 10 times as frequently and at much higher concentrations than its parent compound alachlor (2-chloro-2‘,6‘-diethyl-N-(methoxymethyl)acetamide). The median detectable atrazine (2-chloro-4-ethylamino-6- isopropylamino-s-triazine) concentration was almost half that of atrazine residue (atrazine plus the two atrazine metabolites analyzed). Cyanazine amide [2-chloro-4-(1-carbamoyl-1-methylethylamino)-6-ethylamino-s-triazine] was detected almost twice as frequently as cyanazine (2-chloro-4-ethylamino-6-methylpropionitrileamino-s-triazine). Results show that information on pesticide metabolites is necessary to understand the environmental fate of pesticides. Consequently, if pesticide metabolites are not quantified, the effects of chemical use on groundwater quality would be substantially underestimated. Thus, continued research is needed to identify major degradation pathways for all pesticides and to develop analytical methods to determine their concentrations in water and other environmental media.

  8. Hydrophobic interaction of organic chemicals with microtubule assembly in vitro.

    PubMed

    Stoiber, Thomas; Unger, Eberhard; Dorn, Susanne B; Degen, Gisela H; Bolt, Hermann M

    2008-09-01

    A recent concept connecting the lipophilicity of organic chemicals with their genotoxicity on a chromosomal level implies that the lipophilic character of organic chemicals determines a certain background of chromosomal genotoxicity that can be addressed as "non-specific". This is opposed to compounds with more "specific" modes of action. Such mechanisms influence the processes of karyokinesis and cytokinesis. A critical partial process for the chromosomal segregation is the dynamics of assembly and disassembly of microtubules. To broaden the present database for such interactions, chemicals were selected based on their lipophilicity (log P between -1.5 and +1.0) and on hints from the literature pointing to possibilities of interaction with the tubulin-microtubule system. Thus, acetamide, acrylamide, methylmethane sulfonate, acetonitrile, acrylonitrile and cyclohexanone were assessed as to their potencies to influence the dynamic processes of microtubule assembly and disassembly in a cell-free system in vitro. These compounds covered a range of log P between -1.5 and 1.0, complementary to compounds investigated earlier. The entire body of data supports the general concept that hydrophobic interactions are connected with non-specific processes, which contribute to a background genotoxicity on a chromosomal level. It also points to the dynamics of microtubule assembly and disassembly as a decisive partial process involved.

  9. Cold-adapted and rhizosphere-competent strain of Rahnella sp. with broad-spectrum plant growth-promotion potential.

    PubMed

    Vyas, Pratibha; Joshi, Robin; Sharma, K C; Rahi, Praveen; Gulati, Ashu; Gulati, Arvind

    2010-12-01

    A phosphate-solubilizing bacterial strain isolated from Hippophae rhamnoides rhizosphere was identified as Rahnella sp. based on its phenotypic features and 16S rRNA gene sequence. The bacterial strain showed the growth characteristics of a cold-adapted psychrotroph, with the multiple plant growth-promoting traits of inorganic and organic phosphate solubilization, 1-aminocyclopropane-1- carboxylate-deaminase activity, ammonia generation, and siderophore production. The strain also produced indole- 3-acetic acid, indole-3-acetaldehyde, indole-3-acetamide, indole-3-acetonitrile, indole-3-lactic acid, and indole-3- pyruvic acid in tryptophan-supplemented nutrient broth. Gluconic, citric and isocitric acids were the major organic acids detected during tricalcium phosphate solubilization. A rifampicin-resistant mutant of the strain exhibited high rhizosphere competence without disturbance to the resident microbial populations in pea rhizosphere. Seed bacterization with a charcoal-based inoculum significantly increased growth in barley, chickpea, pea, and maize under the controlled environment. Microplot testing of the inoculum at two different locations in pea also showed significant increase in growth and yield. The attributes of coldtolerance, high rhizosphere competence, and broad-spectrum plant growth-promoting activity exhibited the potential of Rahnella sp. BIHB 783 for increasing agriculture productivity.

  10. Array of Love-wave sensors based on quartz/Novolac to detect CWA simulants.

    PubMed

    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.

  11. Label-free impedimetric sensor for a ribonucleic acid oligomer specific to hepatitis C virus at a self-assembled monolayer-covered electrode.

    PubMed

    Park, Jin-Young; Lee, Yoon-suk; Chang, Byoung-Yong; Kim, Byeang Hyean; Jeon, Sangmin; Park, Su-Moon

    2010-10-01

    A ribonucleic acid (RNA) sensor based on hybridization of its peptide nucleic acid (PNA) molecule with a target RNA oligomer of the internal ribosome entry site sequence specific to the hepatitis C virus (HCV) and the electrochemical impedance detection is described. This RNA is one of the most conservative molecules of the whole HCV RNA genome. The ammonium ion terminated PNA molecule was immobilized via its host-guest interactions with the diaza crown ring of 3-thiophene-acetamide-diaza-18-crown-6 synthesized by a simple two-step method, which forms a well-defined self-assembled monolayer (SAM) on gold. Hybridization events of the probe PNA with the target RNA were monitored by measuring charge-transfer resistances for the Fe(CN)(6)(3-/4-) redox probe using Fourier transform electrochemical impedance spectroscopy. The ratio of the resistances of the SAM-covered electrode measured before and after hybridization increased linearly with log[RNA] in the rat liver lysate with a detection limit of about 23 pM.

  12. Proton and gallium(III) binding properties of a biologically active salicylidene acylhydrazide.

    PubMed

    Hakobyan, Shoghik; Boily, Jean-François; Ramstedt, Madeleine

    2014-09-01

    Bacterial biofilm formation causes a range of problems in our society, especially in health care. Salicylidene acylhydrazides (hydrazones) are promising antivirulence drugs targeting secretion systems used during bacterial infection of host cells. When mixed with the gallium ion they become especially potent as bacterial and biofilm growth-suppressing agents, although the mechanisms through which this occurs are not fully understood. At the base of this uncertainty lies the nature of hydrazone-metal interactions. This study addresses this issue by resolving the equilibrium speciation of hydrazone-gallium aqueous solutions. The protonation constants of the target 2-oxo-2-[N-(2,4,6-trihydroxy-benzylidene)-hydrazino]-acetamide (ME0163) hydrazone species and of its 2,4,6-trihydroxybenzaldehyde and oxamic acid hydrazide building blocks were determined by UV-visible spectrophotometry to achieve this goal. These studies show that the hydrazone is an excessively strong complexing agent for gallium and that its antivirulence properties are predominantly ascribed to monomeric 1:1Ga-ME0163 complexes of various Ga hydrolysis and ME0163 protonation states. The chelation of Ga(III) to the hydrazone also increased the stability of the compounds against acid-induced hydrolysis, making this group of compounds very interesting for biological applications where the Fe-antagonist action of both Ga(III) and the hydrazone can be combined for enhanced biological effect.

  13. Ani9, A Novel Potent Small-Molecule ANO1 Inhibitor with Negligible Effect on ANO2

    PubMed Central

    Seo, Yohan; Lee, Ho K.; Park, Jinhong; Jeon, Dong-kyu; Jo, Sungwoo; Jo, Minjae; Namkung, Wan

    2016-01-01

    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-methoxyphenyl)methylideneamino]-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. PMID:27219012

  14. Biodegradation of acrylamide by Enterobacter aerogenes isolated from wastewater in Thailand.

    PubMed

    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.

  15. 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.

    PubMed

    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.

  16. Synthesis of oligomers of β-l-arabinofuranosides of (4R)-4-hydroxy-l-proline relevant to the mugwort pollen allergen, Art v 1.

    PubMed

    Xie, Ning; Taylor, Carol M

    2014-08-15

    An efficient, convergent solution phase synthesis of monomer, dimer, trimer and tetramer of the β-l-arabinofuranosylated hydroxyproline (β-l-Araf-Hyp) glycocluster is described. This motif constitutes the carbohydrate-specific epitope of Art v 1, the major allergen of mugwort pollen. While a single monomeric unit was proposed at the outset, poor yields for the seemingly trivial steps of end-capping to replace protecting groups with N-terminal acetamides and C-terminal methyl amides led to the introduction of N-terminal, central and C-terminal β-l-Araf-Hyp building blocks. Dimer 2 was obtained in 60% yield by coupling of two monomers, followed by hydrogenolysis of benzyl ether protecting groups. Trimer 3 was obtained in 35% yield via a [2 + 1] coupling and tetramer 4 in 15% yield via a [2 + 2] fragment condensation. Circular dichroism spectra show that monomer 1 displays no organized structure, whereas compounds 2-4 show a strong negative band at 200 nm and a weak positive band at ∼220 mn, as is characteristic of the polyproline II helix.

  17. Absolute rate constants for hydrogen atom transfer from tertiary amides to the cumyloxyl radical: evaluating the role of stereoelectronic effects.

    PubMed

    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.

  18. Bond dissociation energies of solvated silver(I)-amide complexes: competitive threshold collision-induced dissociations and calculations.

    PubMed

    Romanov, Vladimir; Siu, Chi-Kit; Verkerk, Udo H; Hopkinson, Alan C; Siu, K W Michael

    2010-07-08

    Using competitive threshold collision-induced dissociation (TCID) measurements, experimental bond dissociation energies have been evaluated for the water, methanol, and acetonitrile adducts of silver(I)-amide complexes. The influence of the solvent molecules on the binding energy of silver(I) to acetamide, N-methylacetamide, and N,N-dimethylacetamide was investigated. Experimental results show that solvents decrease the amide binding energy by 4-6 kcal mol(-1). Using density functional theory (DFT), binding energies were evaluated using nine functionals, after full geometry optimizations with the ECP28MWB basis set for silver and the 6-311++G(2df,2pd) basis set for the other atomic constituents of the ligands. In addition, calculations employing the DZVP basis set for Ag and DZVP2 for C, H, N, and O atoms at the B3LYP and MP2 levels of theory were used to investigate the influence of the basis set on the theoretical bond energies. A comparison of the experimental and theoretical silver(I)-ligand bond dissociation energies enables an assessment of the limitations in the basis sets and functionals in describing the energetics of the metal-solvent interaction and the metal-amide interaction. No single functional/basis set combination was found capable of predicting binding energies with a sufficiently high level of accuracy for the silver(I)-amide solvent complexes.

  19. Binding energies of the silver ion to alcohols and amides: a theoretical and experimental study.

    PubMed

    Romanov, Vladimir; Siu, Chi-Kit; Verkerk, Udo H; El Aribi, Houssain; Hopkinson, Alan C; Siu, K W Michael

    2008-10-30

    The silver ion binding energies to alcohols (methanol, ethanol, n-propanol, i-propanol, and n-butanol) and to amides (acetamide, N-methylacetamide, N, N-dimethylacetamide, formamide, N-methylformamide, and N, N-dimethylformamide) have been calculated using density functional theory (DFT) and measured using the threshold collision-induced dissociation (TCID) method. For DFT, the combined basis sets of ECP28MWB for silver and 6-311++G(2df,2pd) for the other atoms were found to be optimal using a series of test calculations on Ag (+) binding to methanol and to formamide. In addition, the Ag (+) binding energies of all ligands were evaluated with nine functionals after full geometric optimizations. TCID binding energies were measured using a triple quadrupole mass spectrometer. Reasonable to good agreements were obtained between the calculated and experimental silver(I) binding energies. Ligation of Ag (+) to the alcohols was primarily via the oxygen, although n-propanol and n-butanol exhibited additional, bidentate coordination via the CH hydrogens. By contrast, silver(I) binding to the amides was all monodentate via the carbonyl oxygen. There appears to be strong correlations between the binding energies and the polarizabilities of the ligands.

  20. High solute rejecting membranes for reverse osmosis: Polyetheramide hydrazide

    SciTech Connect

    Bindal, R.C.; Ramachandhran, V.; Misra, B.M.; Ramani, M.P.S. )

    1991-01-01

    Synthesis of benzhydrazide polymers and determination of reverse osmosis properties of their membranes were reported earlier. Their performance was not adequate for seawater desalination or for high radioactive decontamination factors (DF). The same hydrazide polymers modified by incorporation of additional monomers with ether linkages were synthesized by low temperature polycondensation of freshly prepared m-amino benzhydrazide, p-amino benzhydrazide, and 4,4{prime}-diamino diphenyl ether, with isophthaloyl chloride and terephthaloyl chloride in dimethyl acetamide solvent. A series of film-forming polymers prepared by altering the molar ratios of the reacting monomers were characterized in terms of percent moisture regain, inherent viscosity, solubility parameters, and interfacial sorption characteristics. Asymmetric membranes prepared from these polymer samples were characterized in terms of the pure water permeability constant and the solute transport parameter, and were tested for their reverse osmosis performance. An optimum mole ratio of reaching monomers has been identified for the synthesis of polymer and the resulting membrane offered the best performance for reverse osmosis (salt rejection as high as 99.4% for 3.5% sodium chloride solution). The incorporation of aromatic ether linkages in the polyamide benzhydrazide polymeric chains appears to alter the polar and nonpolar character of the bulk polymer, and also the membrane solution interface characteristics, resulting in enhanced solute separation. These membranes appear to be potential candidates for single-stage seawater desalination and also for a variety of industrial effluent treatment applications for significantly high DF radioactive effluent treatment.

  1. Investigation of chemical transformations of thiophenylglycoside of muramyl dipeptide on the fumed silica surface using TPD-MS, FTIR spectroscopy and ES IT MS

    NASA Astrophysics Data System (ADS)

    Azizova, Liana R.; Kulik, Tetiana V.; Palianytsia, Borys B.; Zemlyakov, Aleksandr E.; Tsikalova, Viktoriya N.; Chirva, Vasiliy Ya

    2014-05-01

    In this study, chemical transformations of benzyl ester of О-(phenyl-2-acetamido-2,3-dideoxy-1-thio-β- d-glucopyranoside-3-yl)- d-lactoyl- l-alanyl- d-isoglutamine (SPhMDPOBn) on the fumed silica surface were examined, and the surface complex structure was characterized by temperature-programmed desorption mass spectrometry (TPD-MS), infrared spectroscopy (FTIR) and electrospray ion trap mass spectrometry (ES IT MS). Stages of pyrolysis of SPhMDPOBn in pristine state and on the silica surface have been determined. Probably, hydrogen-bonded complex forms between silanol surface groups and the C = O group of the acetamide moiety NH-(CH3)-C = O…H-O-Si≡. The thermal transformations of such hydrogen-bonded complex result in pyrolysis of SPhMDPOBn immobilized on the silica surface under TPD-MS conditions. The shifts ∆ ν of amide I band (measured from 1,626 to 1,639 cm-l for SPhMDPOBn in pristine state) of 33 and 35 cm-l which occurred when SPhMDPOBn was immobilized on the silica surface may be caused by a weakening of the intramolecular hydrogen bonding of the SPhMDPOBn because the interaction with the silica surface as hydrogen bond with silanol groups is weaker than that in associates.

  2. Preresonance Raman single-crystal measurements of electronic transition moment orientations in N-acetylglycinamide

    SciTech Connect

    Pajcini, V.; Asher, S.A.

    1999-12-01

    The authors have examined electronic coupling between the two amide electronic transitions in a dipeptide and have found strong excitonic interactions in a case where the amide planes are almost perpendicular. The absorption and resonance Raman spectra of N-methylacetamide (NMA) and acetamide (AM) are compared to that of the dipeptide N-acetylglycinamide (NAGA), which is composed of linked primary and secondary amides. The authors measured the transition moment magnitudes of each of these species and also determined the orientation of the preresonance Raman tensor of NAGA in a single crystal. From these single-crystal tensor values, the NAGA diagonal Raman tensor orientations were calculated and compared to those expected for unperturbed primary and secondary amides oriented as in the NAGA crystal. Because the primary and secondary amide III vibrations are vibrationally uncoupled and nonoverlapping, their intensities can be used to determine the contributions to their resonance enhancement from the coupled NAGA electronic transitions. The Raman tensor major axes of the primary and secondary amide III and amide I vibrations do not lie in their corresponding amide planes, indicating excitonically coupled states which mix the primary and secondary amide transitions. These results are relevant to the understanding of amide coupling in peptides and proteins; the NAGA crystal conformation is similar to that of a type I {beta}-turn in peptides and proteins, with the amide planes nearly perpendicular to each other (dihedral angle 85{degree}).

  3. The behavior and bioactivity of imazaquin in soils

    SciTech Connect

    McKinnon, E.J.

    1989-01-01

    Laboratory studies were conducted to determine the adsorption and relative mobility of {sup 14}C-labelled imazaquin (2-(4,5-dihydro-4-methyl-4-(1-methylethyl)-5-oxo-1H-imadazol-2-yl)-3-quinolinecarboxylic acid) and {sup 14}C labelled metolachlor (2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-1-methylethyl) acetamide) on Norfolk sand loan (Typic Paleudult), Rion sandy clay loam (Typic Hapludult), Cape Fear sandy clay loam (Typic Umbraquult) and Webster clay loam (Typic Hapluquoll). Imazaquin was more mobile than metolachlor on all four soils. Soils high in humic matter content retained between 45 and 48% of the applied imazaquin and 93 and 97% of the applied metolachlor. The relative order of mobility of imazaquin in the soils was Rion = Norfolk > Cape Fear = Webster. The order for metolachlor in the soils was Rion > Norfolk > Cape Fear > Webster. Adsorption of imazaquin and metolachlor was inversely related to their mobility in the soil columns. Adsorption of imazaquin increased as the suspension pH decreased.

  4. Use of NMR-Based Metabolomics To Chemically Characterize the Roasting Process of Chicory Root.

    PubMed

    Wei, Feifei; Furihata, Kazuo; Zhang, Mimin; Miyakawa, Takuya; Tanokura, Masaru

    2016-08-16

    Roasted chicory root (Cichorium intybus) has been widely accepted as the most important coffee substitute. In this study, a nuclear magnetic resonance (NMR)-based comprehensive analysis was performed to monitor the substantial changes in the composition of chicory root during the roasting process. A detailed signal assignment of dried raw and roasted chicory roots was carried out using (1)H, (13)C, (1)H-(1)H DQF-COSY, (1)H-(13)C edited-HSQC, (1)H-(13)C CT-HMBC, and (1)H-(13)C HSQC-TOCSY NMR spectra. On the basis of the signal assignments, 36 NMR-visible components were monitored simultaneously during roasting. Inulins, sucrose, and most of the amino acids were largely degraded during the roasting process, whereas monosaccharides decreased at the beginning and then increased until the dark roasting stage. Acetamide, 5-hydroxymethylfurfural, di-d-fructose dianhydride, and norfuraneol were newly formed during roasting. Furthermore, a principal component analysis score plot indicated that similar chemical composition profiles could be achieved by roasting the chicory root either at a higher firepower for a shorter time or at a lower firepower for a longer time.

  5. Synthesis and evaluation of amide side-chain modified Agomelatine analogues as potential antidepressant-like agents.

    PubMed

    Chang, Ying; Pi, Weiyi; Ang, Wei; Liu, Yuanyuan; Li, Chunlong; Zheng, Jiajia; Xiong, Li; Yang, Tao; Luo, Youfu

    2014-04-01

    In this work, nineteen analogues of Agomelatine were readily synthesized through structural modification of the acetamide side-chain starting from the key common intermediate 2-(7-methoxynaphthalen-1-yl) ethanamine (3), which was prepared from commercially available compound 2-(7-methoxynaphthalen-1-yl) acetonitrile (2) in two steps. Corticosterone-induced PC12 pheochromocytoma cells phenotypic in vitro model was utilized to evaluate their potential antidepression activities. Imide compound 4a and acylamino carboxylic acid analogue 5b showed good protective effects on traumatic PC12 cells with protection rates of 34.2% and 23.2%, respectively. Further in vivo assessments in C57 mice FST (forced swim test) model demonstrated that compound 4a significantly reduced the immobility time of the tested subjects, indicating antidepressant-like activity. Preliminary toxicity assays conducted on human normal liver L02 cells and embryonic kidney 293 cells suggested a relatively low safety risk for compound 4a compared with the marketed drugs Agomelatine and Fluoxetine. The promising antidepressant-like efficacy of compound 4a, together with the relatively low toxicity to the normal tested cells and high liability of diffusion through the blood-brain barrier (BBB), presents us insights of exploration of me-better drug candidates of Agomelatine.

  6. 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.

    PubMed

    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.

  7. 6-Methyl-2,4-Disubstituted Pyridazin-3(2H)-ones: A Novel Class of Small-Molecule Agonists for Formyl Peptide Receptors

    PubMed Central

    Cilibrizzi, Agostino; Quinn, Mark T.; Kirpotina, Liliya N.; Schepetkin, Igor A; Holderness, Jeff; Ye, Richard D.; Rabiet, Marie-Josephe; Biancalani, Claudio; Cesari, Nicoletta; Graziano, Alessia; Vergelli, Claudia; Pieretti, Stefano; Piaz, Vittorio Dal; Giovannoni, Maria Paola

    2010-01-01

    Following a ligand-based drug design approach, a potent mixed formyl peptide receptor 1 (FPR1) and formyl peptide receptor-like 1 (FPRL1) agonist (14a) and a potent and specific FPRL1 agonist (14x) were identified. These compounds belong to a large series of pyridazin-3(2H)-one derivatives substituted with a methyl group at position 6 and a methoxy benzyl at position 4. At position 2, an acetamide side chain is essential for activity. Likewise, the presence of lipophilic and/or electronegative substituents in the position para to the aryl group at the end of the chain plays a critical role for activity. Affinity for FPR1 receptors was evaluated by measuring intracellular calcium flux in HL-60 cells transfected with FPR1, FPRL1, and FPRL2. Agonists were able to activate intracellular calcium mobilization and chemotaxis in human neutrophils. The most potent chemotactic agent (EC50 = 0.6 μM) was the mixed FPR/FPRL1 agonist 14h. PMID:19639995

  8. Value-added organonitrogen chemicals evolution from the pyrolysis of chitin and chitosan.

    PubMed

    Liu, Chao; Zhang, Huiyan; Xiao, Rui; Wu, Shubin

    2017-01-20

    Thermogravimetric characteristics of chitin and chitosan and their potentials to produce value-added organonitrogen chemicals were separately evaluated via TG/DSC-FTIR and Py-GC/MS. Results shown that chitin had the better thermal stability and higher activation energy than chitosan because of the abundant acetamido group. Furthermore, the dominated volatilization in active pyrolysis of chitin contributed to its endothermic property, whereas the charring in chitosan led to the exothermal. During fast pyrolysis, the acetamido group in chitin and chitosan was converted into acetic acid or acetamide. Typical products from chitosan pyrolysis were aza-heterocyclic chemicals, i.e. pyridines, pyrazines, and pyrroles, with the total selectivity of 50.50% at 600°C. Herein, selectivity of pyrazine compounds was up to 22.99%. These aza-heterocyclic chemicals came from the nucleophilic addition reaction of primary amine and carbonyl. However, main reaction during chitin pyrolysis was ring-opening degradation, which led to the formation of acetamido chemicals, especially acetamido acetaldehyde with the highest selectivity of 27.27% at 450°C. In summary, chitosan had the potential to produce aza-heterocyclic chemicals, and chitin to acetamido chemicals.

  9. Difficulties in Laboratory Studies and Astronomical Observations of Organic Molecules: Hydroxyacetone and Lactic Acid

    NASA Technical Reports Server (NTRS)

    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.

  10. Dialkylmethyl-2-(N,N-diisobutyl)acetamidoammonium iodide as a ruthenium selective ligand from nitric acid medium.

    PubMed

    Sharma, Shikha; Ghosh, Sunil K; Sharma, Joti N

    2015-09-15

    A new class of quaternary ammonium iodide based ligands with 2-(N,N-diisobutyl)acetamide as an alkyl appendage have been designed, synthesized and tested for their ability to extract ruthenium selectively from nitric acid medium. The 2-(N,N-diisobutyl)acetamido ammonium iodide with two propyl and a methyl substituents showed best results for the recovery of ruthenium. The optimized concentration of the solvent was found to be 0.2M in 30% isodecyl alcohol/n-dodecane. The stoichiometry of the complex was ascertained by slope analysis method and was found to be 1:1 with respect to ligand L(+)I(-) and Ru(NO)(NO3)3. Ruthenium formed an adduct of structure LRu(NO)(NO3)3 I in the extraction medium. Iodide ion played an important role in the formation of the stable and extractable complex of ruthenium. No extraction was observed when iodide was replaced by nitrate anion in the ligand. The ligand also showed good selectivity for ruthenium in the presence of other metal ions commonly found in nitric acid solutions of nuclear waste.

  11. Synthesis and NMR Analysis of a Conformationally Controlled β-Turn Mimetic Torsion Balance.

    PubMed

    Lypson, Alyssa B; Wilcox, Craig S

    2017-01-20

    The molecular torsion balance concept was applied to a new conformationally controlled scaffold and synthesized to accurately evaluate pairwise amino acid interactions in an antiparallel β-sheet motif. The scaffold's core design combines (ortho-tolyl)amide and o,o,o'-trisubstituted biphenyl structural units to provide a geometry better-suited for intramolecular hydrogen bonding. Like the dibenzodiazocine hinge of the traditional torsion balance, the (ortho-tolyl)amide unit offers restricted rotation around an N-aryl bond. The resulting two-state folding model is a powerful template for measuring hydrogen bond stability between two competing sequences. The aim of this study was to improve the alignment between the amino acid sequences attached to the upper and lower aromatic rings in order to promote hydrogen bond formation at the correct distance and antiparallel orientation. Bromine substituents were introduced ortho to the upper side chains and compared to a control to test our hypothesis. Hydrogen bond formation has been identified between the NH amide proton of the upper side chain (proton donor) and glycine acetamide of the lower side chain (proton acceptor).

  12. [Auxin production by Klebsiella planticola strain TSKhA-91 and Its Effect of development of cucumber (Cucumis sativus L.) Seeds].

    PubMed

    Blinkov, E A; Tsavkelova, E A; Selitskaia, O V

    2014-01-01

    Capacity of Klebsiella planticola strain TSJhA-91 for synthesis of indolyl-3-acetic acid (IAA) and other auxins was studied. The qualitative and quantitative composition of these compounds depends on the presence of exogeneous tryptophan and on the nitrogen source. The highest IAA yield was obtained at the stationary phase of growth. Addition of L-tryptophan to the medium resulted in a significant increase (up to 85.5 microg/mL) of auxin biosynthesis, especially in the presence of nitrates. Thin-layer chromatography revealed that the indole-3-acetamide pathway was not active in this strain. The biological activity of auxins was confirmed by plant assay with the kidney bean cuttings; the height of root formation and rdot number increased 16- and 6-fold, respectively. Under conditions of low-temperature stress, protective effect of K. planticola TSKhA-91 on development of cucumbers (Cucumissativus L.) seeds, including stimulation of germi- nation and root formation by its seeds were shown.

  13. Improving degradation of paracetamol by integrating gamma radiation and Fenton processes.

    PubMed

    Cruz-González, Germán; Rivas-Ortiz, Iram B; González-Labrada, Katia; Rapado-Paneque, Manuel; Chávez-Ardanza, Armando; Nuevas-Paz, Lauro; Jáuregui-Haza, Ulises J

    2016-10-14

    Degradation of paracetamol (N-(4-hydroxiphenyl)acetamide) in aqueous solution by gamma radiation, gamma radiation/H2O2 and gamma radiation/Fenton processes was studied. Parameters affecting the radiolysis of paracetamol such as radiation dose, initial concentration of pollutant, pH and initial oxidant concentration were investigated. Gamma radiation was performed using a (60)Co source irradiator. Paracetamol degradation and mineralization increased with increasing absorbed radiation dose, but decreased with increasing initial concentration of the drug in aqueous solution. The addition of H2O2 resulted in an increased effect on irradiation-driven paracetamol degradation in comparison with the performance of the irradiation-driven process alone: paracetamol removal increased from 48.9% in the absence of H2O2 to 95.2% for H2O2 concentration of 41.7 mmol/L. However, the best results were obtained with gamma radiation/Fenton process with 100% of the drug removal at 5 kGy, for optimal H2O2 and Fe(2+) concentrations at 13.9 and 2.3 mmol/L, respectively, with a high mineralization of 63.7%. These results suggest gamma radiation/H2O2 and gamma radiation/Fenton processes as promising methods for paracetamol degradation in polluted wastewaters.

  14. Enhanced oil recovery profile control with crosslinked anionic acrylamide copolymer gels

    SciTech Connect

    Mitchell, T.O.

    1992-01-07

    This patent describes an aqueous crosslinked acrylamide copolymer gel formed in the absence of a partial hydrolysis step. It comprises water; a viscosifying amount of anionic acrylamide copolymer of high weight-average molecular weight produced by copolymerizing an aqueous mixture of monomers comprising about 5 to 95 weight percent of 2-acrylamido-2-methylpropanesulfonic acid; about 2 to 95 weight percent of N-vinyl-N-methyl acetamide; and about 5 to 93 weight percent of acrylamide, the copolymer having a weight-average molecular weight of at least 5 {times} 10{sup 6} and able to form a stable crosslinked gel without first subjecting the copolymer to a partial hydrolysis step; a crosslinking agent selected from the group consisting of transition metal ions, phenolic resins and amino resins wherein the crosslinking agent is present in an amount sufficient to cause gelation of the aqueous solution of the anionic acrylamide copolymer of high weight-average molecular weight and produce the crosslinked gel.

  15. Characterization and profiling of phenolic amides from Cortex Lycii by ultra-high performance liquid chromatography coupled with LTQ-Orbitrap mass spectrometry.

    PubMed

    Zhang, Jingxian; Guan, Shuhong; Sun, Jianghao; Liu, Tian; Chen, Pei; Feng, Ruihong; Chen, Xin; Wu, Wanying; Yang, Min; Guo, De-An

    2015-01-01

    Cortex Lycii, the root bark of Lycium chinense Mill. or Lycium barbarum L., is a frequently used traditional Chinese medicine. Phytochemical studies have shown that phenolic amides are not only characteristic compounds but also abundant ones in this plant. In the present study, an effective method was developed for structural characterization of phenolic amides from Cortex Lycii by ultra-high performance liquid chromatography coupled with linear ion trap Orbitrap tandem mass spectrometry. The fragmentation of 14 compounds including six cinnamic acid amides, six neolignanamides, and two lignanamides were studied systematically for the first time. It was found that, in the positive ion mode, neutral loss of the tyramide moiety (137 Da) or N-(4-aminobutyl)acetamide moiety (130 Da) were characteristic for these compounds. At least 54 phenolic amides were detected in the extract and 48 of them were characterized, among which 14 known compounds were identified unambiguously by comparing the retention time and mass spectra with those of reference compounds, and 34 components were tentatively identified based on the fragmentation patterns, exact mass, UV spectra, as well as retention time. Fifteen compounds were characterized as potential new ones. Additionally, the developed method was applied to analyze eight batches of samples collected from the northwest of China, and it was found that cinnamic acid amides were the main type of phenolic amides in Cortex Lycii. In conclusion, the identification of these chemicals provided essential data for further phytochemical studies, metabolites identification, and the quality control of Cortex Lycii.

  16. Analysis of glucosinolates, isothiocyanates, and amine degradation products in vegetable extracts and blood plasma by LC-MS/MS.

    PubMed

    Song, Lijiang; Morrison, John J; Botting, Nigel P; Thornalley, Paul J

    2005-12-15

    Dietary glucosinolates are under intensive investigation as precursors of cancer-preventive isothiocyanates. Quantitation of the dose and bioavailability of glucosinolates and isothiocyanates requires a comprehensive analysis of the major dietary glucosinolates, isothiocyanates, and related metabolites. We report a liquid chromatography with tandem mass spectrometric detection (LC-MS/MS) analytical method for the comprehensive analysis of the seven major dietary glucosinolates, related isothiocyanates, and putative amine degradation products. The parent glucosinolates were sinigrin, gluconapin, progoitrin, glucoiberin, glucoraphanin, glucoalyssin, and gluconasturtiin. The LC-MS/MS analysis method for these compounds was developed and validated; a standard addition analysis protocol was used generally to avoid the requirement for stable isotopic standards. Where stable isotopic standards were available, internal standardization with these gave estimates in agreement with those obtained by the standard addition analysis protocol. For glucosinolates, negative ion electrospray LC-MS/MS analysis was performed. Isothiocyanates and amines were prederivatized to the corresponding thiourea and N-acetamides, respectively, and were quantified by positive ion electrospray LC-MS/MS. The limits of detection were 0.5-2 pmol; the recoveries for glucosinolates, isothiocyanates, and amines were 85-90%, 50-85%, and 60-70%, respectively; and the intra- and interbatch coefficients of variation were 1-4% and 3-10%, respectively. These methods provide facile access to comprehensive analytical data on the major dietary glucosinolates and related metabolites to quantify inputs and metabolic formation of these compounds in cancer prevention and related studies.

  17. [Analytic evaluation of potential nootropic agents].

    PubMed

    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.

  18. Yellow nutsedge (Cyperus esculentus L. ) control with herbicides: the role of tuberization

    SciTech Connect

    Pereira, W.

    1985-01-01

    Trials were carried out under greenhouse, growth chamber, laboratory, outdoor pot, and field conditions to characterize stages of yellow nutsedge tuberization and to investigate the influence of herbicides. The effects of herbicides on tuberization and phytotoxicity at several growth stages, as well as on sprouting, growth characteristics, and survival of new tubers were determined. Tuberization was a continuous process, but was modulated by plant age and environmental conditions. The growth stage that included the time of first tuber initiation was the best for applying glyphosate (N-(phosphonomethyl)glycine) and oxyfluorfen (2-chloro-1-(3-ethoxy-4-nitrophenoxy)-4-(trifluromethyl)benzene). Plant-age and length of period after spraying influenced glyphosate and oxyfluorfen absorption and translocation. Addition of unlabelled oxyfluorfen as a tank mixture can glyphosate increased absorption of /sup 14/C-glyphosate to 27% after 1 day and 46% after 8 days and increased translocation into other plant parts. Timing of postemergence herbicide applications relative to tuberization is crucial for overall control of yellow nutsedge. When soil applied herbicides were compared in the field, consecutive applications of dichlobenil (2,6-dichlorobenzonitrile) and metolachlor (2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-1-methylethyl)acetamide) for two years provided the best control of nutsedge.

  19. Ammoxidation of Lignocellulosic Materials: Formation of Nonheterocyclic Nitrogenous Compounds from Monosaccharides

    PubMed Central

    2013-01-01

    Ammoxidized technical lignins are valuable soil-improving materials that share many similarities with native terrestrial humic substances. In contrast to lignins, the chemical fate of carbohydrates as typical minor constituents of technical lignins during the ammoxidation processes has not been thoroughly investigated. Recently, we reported the formation of N-heterocyclic, ecotoxic compounds (OECD test 201) from both monosaccharides (d-glucose, d-xylose) and polysaccharides (cellulose, xylan) under ammoxidation conditions and showed that monosaccharides are a source more critical than polysaccharides in this respect. GC/MS-derivatization analysis of the crude product mixtures revealed that ammoxidation of carbohydrates which resembles the conditions encountered in nonenzymatical browning of foodstuff affords also a multitude of nonheterocyclic nitrogenous compounds such as aminosugars, glycosylamines, ammonium salts of aldonic, deoxyaldonic, oxalic and carbaminic acids, urea, acetamide, α-hydroxyamides, and even minor amounts of α-amino acids. d-Glucose and d-xylose afforded largely similar product patterns which differed from each other only for those products that were formed under preservation of the chain integrity and stereoconfiguration of the respective monosaccharide. The kinetics and reaction pathways involved in the formation of the different classes of nitrogenous compounds under ammoxidation conditions are discussed. PMID:23967905

  20. Toxicity Assessment of Expired Pesticides to Green Algae Pseudokirchneriella subcapitata

    PubMed Central

    Satyavani, G.; Chandrasehar, G.; Varma, K. Krishna; Goparaju, A.; Ayyappan, S.; Reddy, P. Neelakanta; Murthy, P. Balakrishna

    2012-01-01

    In order to investigate the effect of expired pesticides on the yield and growth rate of green algae Pseudokirchneriella subcapitata, a study was conducted as per the Organisation for Economic Cooperation and Development (OECD) guideline number 201. Fifteen expired pesticide formulations, most commonly used in Indian agriculture, were tested in comparison with their unexpired counterparts. The expired pesticide formulations studied belonged to various class and functional groups: organophosphate, pyrethroid-based insecticides; azole-based fungicides; acetamide, propionate, acetic acid-based herbicides; fungicides mixtures containing two actives—azole and dithiocarbamate. The toxicity endpoints of yield (EyC50: 0–72 h) and growth rate (ErC50: 0–72 h) of Pseudokirchneriella subcapitata for each pesticide formulation (both expired and unexpired pesticides) were determined statistically using TOXSTAT 3.5 version software. The results pointed out that some expired pesticide formulations exhibited higher toxicity to tested algal species, as compared to the corresponding unexpired pesticides. These data thus stress the need for greater care to dispose expired pesticides to water bodies, to avoid the effects on aquatic ecospecies tested. PMID:23762633

  1. The cytotoxic constituents from marine-derived streptomyces 3320#

    NASA Astrophysics Data System (ADS)

    Ren, Hong; Gu, Qianqun; Cui, Chengbin; Zhu, Weiming

    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.

  2. Synthesis and anticancer effects evaluation of 1-alkyl-3-(6-(2-methoxy-3-sulfonylaminopyridin-5-yl)benzo[d]thiazol-2-yl)urea as anticancer agents with low toxicity.

    PubMed

    Xie, Xiao-Xiao; Li, Huan; Wang, Juan; Mao, Shuai; Xin, Min-Hang; Lu, She-Min; Mei, Qi-Bing; Zhang, San-Qi

    2015-10-01

    As a PI3K and mTOR dual inhibitor, N-(2-chloro-5-(2-acetylaminobenzo[d]thiazol-6-yl)pyridin-3-yl)-4-fluorophenylsulfonamide displays toxicity when orally administrated. In the present study, alkylurea moiety replaced the acetamide group in the compound and a series of 1-alkyl-3-(6-(2,3-disubstituted pyridin-5-yl)benzo[d]thiazol-2-yl)urea derivatives were synthesized. The antiproliferative activities of the synthesized compounds in vitro were evaluated against HCT116, MCF-7, U87 MG and A549 cell lines. The compounds with potent antiproliferative activity were tested for their acute oral toxicity and inhibitory activity against PI3Ks and mTORC1. The results indicate that the compound attached a 2-(dialkylamino)ethylurea moiety at the 2-positeion of benzothiazole can retain the antiproliferative activity and inhibitory activity against PI3K and mTOR. In addition, their acute oral toxicity reduced dramatically. Moreover, compound 2f can effectively inhibit tumor growth in a mice S180 homograft model. These findings suggest that 1-(2-dialkylaminoethyl)-3-(6-(2-methoxy-3-sulfonylaminopyridin-5-yl)benzo[d]thiazol-2-yl)urea derivatives can serve as potent PI3K inhibitors and anticancer agents with low toxicity.

  3. Lead Development of Thiazolylsulfonamides with Carbonic Anhydrase Inhibitory Action.

    PubMed

    Carta, Fabrizio; Birkmann, Alexander; Pfaff, Tamara; Buschmann, Helmut; Schwab, Wilfried; Zimmermann, Holger; Maresca, Alfonso; Supuran, Claudiu T

    2017-03-17

    A series of congeners structurally related to pritelivir, N-[5-(aminosulfonyl)-4-methyl-1,3-thiazol-2-yl]-N-methyl-2-[4-(2-pyridinyl)phenyl]acetamide, a helicase-primase inhibitor for the treatment of herpes simplex virus infections, was prepared. The synthesized primary and secondary sulfonamides were investigated as inhibitors of six physiologically and pharmacologically relevant human (h) carbonic anhydrase (hCA, EC 4.2.1.1) isoforms, the cytosolic enzymes hCA I and II, the mitochondrial ones hCA VA and VB, and the transmembrane, tumor associated hCA IX and XII. Low nanomolar inhibition KI values were detected for all of them, with a very interesting and well-defined structure-activity relationship. As many CAs are involved in serious pathologies, among which are cancer, obesity, epilepsy, glaucoma, etc., sulfonamide inhibitors as those reported here may be of interest as drug candidates. Furthermore, pritelivir itself is an effective inhibitor of some CAs, also inhibiting whole blood enzymes from several mammalian species, which may be a favorable pharmacokinetic feature of the drug which can be transported throughout the body bound to blood CA I and II.

  4. Fungal fermentation of whey incorporated with certain supplements for the production of proteases.

    PubMed

    Ashour, S A; el-Shora, H M; Metwally, M; Habib, S A

    1996-01-01

    The pattern and the extent of formation of proteases and secretion varied with the fungus, age and/or the nature of the co-supplement. Addition of yeast extract induced the best yield of proteases from both Aspergillus niger and A. terreus. Proteases from A. niger were highly induced by glutamic acid, alanine or albumin, with minor differences, whereas gelatin, peptone, aspartic acid, casein or acetamide stimulated the accumulation of proteases in the culture medium of A. terreus. Galactose stimulated the yield of the enzyme particularly with A. terreus while most C-supplements inhibited such processes, more prominently in the presence of cellulose or starch. Incorporation of nicotinic acid and wheat bran initiated the maximum productivity of proteases from A. niger and A. terreus, respectively. Co+2 and Cu+2 highly stimulated the output of proteases from A. niger and A. terreus, respectively. Co+2 and Ca+2 stimulated the enzyme activity of alkaline and acid proteases from A. terreus and acid proteases from A. niger. The other six cations and DTT inhibited variably the three proteases particularly alkaline proteases from A. terreus indicating that proteases from various sources even from closely related species showed different properties.

  5. Synthesis of new iso-C-nucleoside analogues from 2-(methyl 2-O-benzyl-4,6-O-benzylidene-3-deoxy-alpha-D-altropyranosid-3-yl)ethanal.

    PubMed

    Otero, Iran; Feist, Holger; Herrera, Lidcay; Michalik, Manfred; Quincoces, José; Peseke, Klaus

    2005-03-21

    Treatment of 2-(methyl 2-O-benzyl-4,6-O-benzylidene-3-deoxy-alpha-D-altropyranosid-3-yl)ethanal with malononitrile, cyanoacetamide and 2-cyano-N-(4-methoxyphenyl)acetamide, respectively, in the presence of aluminium oxide yielded 2-cyano-4-(methyl 2-O-benzyl-4,6-O-benzylidene-3-deoxy-alpha-D-altropyranosid-3-yl)crotonic acid derivatives. Cyclization with sulfur and triethylamine was performed to synthesize the 2-amino-5-(methyl 2-O-benzyl-4,6-O-benzylidene-3-deoxy-alpha-D-altropyranosid-3-yl)thiophene-3-carbonic acid derivatives, which were treated with triethyl orthoformate/ammonia and triethyl orthoformate, respectively, to furnish 6-(methyl 2-O-benzyl-4,6-O-benzylidene-3-deoxy-alpha-D-altropyranosid-3-yl)thieno[2.3-d]pyrimidine derivatives. Deprotection in two steps afforded 2-amino-5-(1,6-anhydro-3-deoxy-beta-D-altropyranos-3-yl)thiophene-3-carbonitrile and 6-(1,6-anhydro-3-deoxy-beta-D-altropyranos-3-yl)thieno[2.3-d]pyrimidine derivatives, respectively.

  6. Molecules with a peptide link in protostellar shocks: a comprehensive study of L1157

    NASA Astrophysics Data System (ADS)

    Mendoza, Edgar; Lefloch, B.; López-Sepulcre, A.; Ceccarelli, C.; Codella, C.; Boechat-Roberty, H. M.; Bachiller, R.

    2014-11-01

    Interstellar molecules with a peptide link (-NH-C(=O)-), like formamide (NH2CHO), acetamide (NH2COCH3) 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 30 m telescope, as part of the ASAI Large Programme. Analysis of the line profiles shows that the emission arises from the outflow cavities associated with B1 and B2. Molecular abundances of ≈(0.4-1.1) × 10-8 and (3.3-8.8) × 10-8 are derived for formamide and isocyanic acid, respectively, from a simple rotational diagram analysis. Conversely, NH2COCH3 was not detected down to a relative abundance of a few ≤10-10. B1 and B2 appear to be among the richest Galactic sources of HNCO and NH2CHO molecules. A tight linear correlation between their abundances is observed, suggesting that the two species are chemically related. Comparison with astrochemical models favours molecule formation on icy grain mantles, with NH2CHO generated from hydrogenation of HNCO.

  7. [Activated Sludge Bacteria Transforming Cyanopyridines and Amides of Pyridinecarboxylic Acids].

    PubMed

    Demakov, V A; Vasil'ev, D M; Maksimova, Yu G; Pavlova, Yu A; Ovechkina, G V; Maksimov, A Yu

    2015-01-01

    Species diversity of bacteria from the activated sludge of Perm biological waste treatment facilities capable of transformation of cyanopyridines and amides of pyridinecarboxylic acids was investigated. Enrichment cultures in mineral media with 3-cyanopyridine as the sole carbon and nitrogen source were used to obtain 32 clones of gram-negative heterotrophic bacteria exhibiting moderate growth on solid and liquid media with 3- and 4-cyanopyridine. Sequencing of the 16S rRNA gene fragments revealed that the clones with homology of at least 99% belonged to the genera Acinetobacte, Alcaligenes, Delftia, Ochrobactrum, Pseudomonas, Stenotrophomonas, and Xanthobacter. PCR analysis showed that 13 out of 32 isolates contained the sequences (-1070 bp) homologous to the nitrilase genes reported previously in Alcaligenes faecalis JM3 (GenBank, D13419.1). Nine clones were capable of nitrile and amide transformation in minimal salt medium. Acinetobacter sp. 11 h and Alcaligenes sp. osv transformed 3-cyanopyridine to nicotinamide, while most of the clones possessed amidase activity (0.5 to 46.3 mmol/(g h) for acetamide and 0.1 to 5.6 mmol/(g h) for nicotinamide). Nicotinamide utilization by strain A. faecalis 2 was shown to result in excretion of a secondary metabolite, which was identified as dodecyl acrylate at 91% probability.

  8. Antiproliferative effects of mitochondria-targeted cationic antioxidants and analogs: Role of mitochondrial bioenergetics and energy-sensing mechanism.

    PubMed

    Cheng, Gang; Zielonka, Jacek; McAllister, Donna; Hardy, Micael; Ouari, Olivier; Joseph, Joy; Dwinell, Michael B; Kalyanaraman, Balaraman

    2015-08-28

    One of the proposed mechanisms for tumor proliferation involves redox signaling mediated by reactive oxygen species such as superoxide and hydrogen peroxide generated at moderate levels. Thus, the antiproliferative and anti-tumor effects of certain antioxidants were attributed to their ability to mitigate intracellular reactive oxygen species (ROS). Recent reports support a role for mitochondrial ROS in stimulating tumor cell proliferation. In this study, we compared the antiproliferative effects and the effects on mitochondrial bioenergetic functions of a mitochondria-targeted cationic carboxyproxyl nitroxide (Mito-CP), exhibiting superoxide dismutase (SOD)-like activity and a synthetic cationic acetamide analog (Mito-CP-Ac) lacking the nitroxide moiety responsible for the SOD activity. Results indicate that both Mito-CP and Mito-CP-Ac potently inhibited tumor cell proliferation. Both compounds altered mitochondrial and glycolytic functions, and intracellular citrate levels. Both Mito-CP and Mito-CP-Ac synergized with 2-deoxy-glucose (2-DG) to deplete intracellular ATP, inhibit cell proliferation and induce apoptosis in pancreatic cancer cells. We conclude that mitochondria-targeted cationic agents inhibit tumor proliferation via modification of mitochondrial bioenergetics pathways rather than by dismutating and detoxifying mitochondrial superoxide.

  9. Development of Photoactivatable Allosteric Modulators for the Chemokine Receptor CXCR3.

    PubMed

    Admas, Tizita Haimanot; Bernat, Viachaslau; Heinrich, Markus R; Tschammer, Nuska

    2016-03-17

    The CXCR3 receptor, a class A G protein-coupled receptor (GPCR), is involved in the regulation and trafficking of various immune cells. CXCR3 antagonists have been proposed to be beneficial for the treatment of a wide range of disorders including but not limited to inflammatory and autoimmune diseases. The structure-based design of CXCR3 ligands remains, however, hampered by a lack of structural information describing in detail the interactions between an allosteric ligand and the receptor. We designed and synthesized photoactivatable probes for the structural and functional characterization, using photoaffinity labeling followed by mass spectrometry, of the CXCR3 allosteric binding pocket of AMG 487 and RAMX3, two potent and selective CXCR3 negative allosteric modulators. Photoaffinity labeling is a common approach to elucidate binding modes of small-molecule ligands of GPCRs through the aid of photoactivatable probes that convert to extremely reactive intermediates upon photolysis. The photolabile probe N-[({1-[3-(4-ethoxyphenyl)-4-oxo-3,4-dihydropyrido[2,3-d]pyrimidin-2-yl]ethyl}-2-[4-fluoro-3-(trifluoromethyl)phenyl]-N-{1-[4-(3-(trifluoromethyl)-3H-diazirin-3-yl]benzyl}piperidin-4-yl)methyl]acetamide (10) showed significant labeling of the CXCR3 receptor (80%) in a [(3) H]RAMX3 radioligand displacement assay. Compound 10 will serve as an important tool compound for the detailed investigation of the binding pocket of CXCR3 by mass spectrometry.

  10. The Interaction between Steroid Hormones and Lipid Monolayers on Water

    PubMed Central

    Gershfeld, N. L.; Muramatsu, M.

    1971-01-01

    The interaction of progesterone, testosterone, androsterone, and etiocholanolone with insoluble lipid films (cholesterol and saturated hydrocarbons containing either alcohol, ester, acetamide, phosphate, amine, or carboxyl groups) was studied. In addition to surface pressure and surface potential measurements of the surface films, radioactive tracers were used to measure the concentration of adsorbed steroid in the lipid films. In general, steroids form mixed films with the insoluble lipid films. Compression of the insoluble lipid films to their most condensed state leads to complete ejection of adsorbed steroid from the surface in all cases except with the amine, for which a small amount of steroid is still retained in the surface. Interactions between the steroids and insoluble lipids are primarily due to van der Waals or dispersion forces; there were no significant contributions from dipole-dipole interactions (except possibly with the amine). Specific interactions between cholesterol and the soluble steroids were not observed. Evidence suggests that low steroid concentrations influence structure of lipid films by altering the hydration layer in the surface film. In contrast to a specific site of action, it is proposed that steroid hormones initiate structural changes in a variety of biological sites; this model of steroid action is consistent with the ubiquity of many steroid hormones. PMID:5120392

  11. Biodegradation and detoxification of textile dye Disperse Red 54 by Brevibacillus laterosporus and determination of its metabolic fate.

    PubMed

    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.

  12. Preparation and characterization of nanocomposite polymer electrolytes poly(vinylidone fluoride)/nanoclay

    SciTech Connect

    Rahmawati, Suci A.; Sulistyaningsih,; Putro, Alviansyah Z. A.; Widyanto, Nugroho F.; Jumari, Arif; Purwanto, Agus; Dyartanti, Endah R.

    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.

  13. Design of experiments and detailed uncertainty analysis to develop and validate a solid-phase microextraction/gas chromatography-mass spectrometry method for the simultaneous analysis of 16 pesticides in water.

    PubMed

    Passeport, Elodie; Guenne, Angeline; Culhaoglu, Tanya; Moreau, Sylvain; Bouyé, Jean-Michel; Tournebize, Julien

    2010-08-13

    A solid-phase microextraction (SPME)/gas chromatography (GC)-mass spectrometry (MS) multiresidue analytical method was developed for 16 pesticides presenting different physicochemical properties including diphenyl ether, triazine, ureas, acetamides, benzofuran, thiocarbamate, pyridine carboxamides, chloronitrile, piperedine, and azoles. Optimization was achieved by means of the design of experiments methodology. Extraction temperature, extraction time, desorption temperature, and NaCl addition were the factors exhibiting the most significant effects on pesticide extraction. Validation was carried out through model adequacy and specificity tests, limits of quantification and detection determination, and full uncertainty assessment on the whole analytical method. Good first- and second-order model adequacy was found for pesticide calibration. LOQs were in the 0.05-0.5 microg L(-1) range and specificity recoveries varied from 75% to 140%. These results were considered acceptable for our research purposes on highly concentrated agricultural flows. Uncertainty calculations accounted for several steps: standard preparation, calibration model selection, and use. On average, real sample concentration uncertainties were lower than 10%, indicating that the analytical method performed very well. Its application to 61 real water samples confirmed the presence of some pesticide concentrations in relation to farmer use, whereas other molecules were usually either not detected or not quantified.

  14. Monotherapy for partial epilepsy: focus on levetiracetam

    PubMed Central

    Gambardella, Antonio; Labate, Angelo; Colosimo, Eleonora; Ambrosio, Roberta; Quattrone, Aldo

    2008-01-01

    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. PMID:18728811

  15. Modafinil decreases anxiety-like behaviour in zebrafish

    PubMed Central

    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

  16. Evaluation of the Tobacco Heating System 2.2. Part 3: Influence of the tobacco blend on the formation of harmful and potentially harmful constituents of the Tobacco Heating System 2.2 aerosol.

    PubMed

    Schaller, Jean-Pierre; Pijnenburg, Johannes P M; Ajithkumar, Anu; Tricker, Anthony R

    2016-11-30

    The Tobacco Heating System (THS2.2), which uses "heat-not-burn" technology, generates an aerosol from tobacco heated to a lower temperature than occurs when smoking a combustible cigarette. The concentrations of harmful and potentially harmful constituents (HPHCs) are significantly lower in THS2.2 mainstream aerosol than in smoke produced by combustible cigarettes. Different tobacco types and 43 tobacco blends were investigated to determine how the blend impacted the overall reductions of HPHCs in the THS2.2 mainstream aerosol. The blend composition had minimal effects on the yields of most HPHCs in the aerosol. Blends containing high proportions of nitrogen-rich tobacco, e.g., air-cured, and some Oriental tobaccos, produced higher acetamide, acrylamide, ammonia, and nitrogen oxide yields than did other blends. Most HPHCs were found to be released mainly through the distillation of HPHCs present in the tobacco plug or after being produced in simple thermal reactions. HPHC concentrations in the THS2.2 aerosol may therefore be further minimized by limiting the use of flue- and fire-cured tobaccos which may be contaminated by HPHCs during the curing process and carefully selecting nitrogen rich tobaccos with low concentrations of endogenous HPHCs for use in the tobacco plug blend.

  17. New benzo[d]thiazol-2-yl-aminoacetamides as potential anticonvulsants: synthesis, activity and prediction of molecular properties.

    PubMed

    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.

  18. Heterogeneous photocatalytic degradation of pesticides using decatungstate intercalated macroporous layered double hydroxides.

    PubMed

    Da Silva, Eliana S; Prevot, Vanessa; Forano, Claude; Wong-Wah-Chung, Pascal; Burrows, Hugh D; Sarakha, Mohamed

    2014-10-01

    Decatungstate W10O32(4-) was efficiently intercalated between the layers of three-dimensionally ordered macroporous Mg2Al-layered double hydroxide. The structural and textural properties of as-prepared intercalated compound were characterized using different solid-state characterization techniques such as X-ray powder diffraction, FTIR and Raman spectroscopies and electronic microscopy. The photocatalytic properties of immobilized W10O32 (4-) within Mg2Al structure were investigated using 2-(1-naphthyl) acetamide (NAD) as a model of pesticide. The influence of different parameters such as amount of catalyst, pH and oxygen concentration were investigated. An optimal NAD degradation was obtained for a photocatalyst concentration of 60 mg l(-1). Under our experimental conditions, this heterogeneous photocatalyst induces photodegradation of 60 % of NAD after 17 h of irradiation at 365 nm and at pH 6.6. Interestingly, pesticide photodegradation leads to the mineralization of substrates to H2O and CO2 and the photocatalyst can be recycled and reused without any loss of activity over four cycles.

  19. Hexim1, a Novel Regulator of Leptin Function, Modulates Obesity and Glucose Disposal

    PubMed Central

    Dhar-Mascareno, Manya; Ramirez, Susan N.; Rozenberg, Inna; Rouille, Yves; Kral, John G.

    2016-01-01

    Leptin triggers signaling events with significant transcriptional responses that are essential to metabolic processes affecting obesity and glucose disposal. We asked whether hexamethylene bis-acetamide inducible-1 (Hexim1), an inhibitor of RNA II polymerase-dependent transcription elongation, regulates leptin-Janus kinase 2 signaling axis in the hypothalamus. We subjected C57BL6 Hexim1 heterozygous (HT) mice to high-fat diet and when compared with wild type, HT mice were resistant to high-fat diet-induced weight gain and remain insulin sensitive. HT mice exhibited increased leptin-pY705Stat3 signaling in the hypothalamus, with normal adipocyte size, increased type I oxidative muscle fiber density, and enhanced glucose transporter 4 expression. We also observed that normal Hexim1 protein level is required to facilitate the expression of CCAAT/enhancer-binding proteins (C/EBPs) required for adipogenesis and inducible suppressor of cytokine signaling 3 (SOCS) expression. Further support on the role of Hexim1 regulating C/EBPs during adipocyte differentiation was shown when HT 3T3L1 fibroblasts failed to undergo adipogenesis. Hexim1 selectively modulates leptin-mediated signal transduction pathways in the hypothalamus, the expression of C/EBPs and peroxisome proliferator-activated receptor-γ (PPAR γ) in skeletal muscle and adipose tissue during the adaptation to metabolic stress. We postulate that Hexim1 might be a novel factor involved in maintaining whole-body energy balance. PMID:26859361

  20. Preparation and characterization of nanocomposite polymer electrolytes poly(vinylidone fluoride)/nanoclay

    NASA Astrophysics Data System (ADS)

    Rahmawati, Suci A.; Sulistyaningsih, Putro, Alviansyah Z. A.; Widyanto, Nugroho F.; Jumari, Arif; Purwanto, Agus; Dyartanti, Endah R.

    2016-02-01

    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.

  1. Utility of liquid chromatography/fast atom bombardment mass spectrometry and liquid chromatography/thermospray mass spectrometry for structure identification of metabolites of a fluorinated herbicide.

    PubMed

    Fujiwara, H; Chott, R C; Solsten, R T

    1992-09-01

    This study demonstrates a useful application of on-line microbore high-performance liquid chromatography (HPLC) fast atom bombardment (FAB) and thermospray (TSP) mass spectrometry techniques for identification of metabolites from the in vitro metabolism of an experimental Monsanto herbicide: 2-chloro-N-(ethoxymethyl-N-[2-methyl-6- (trifluoromethyl)phenyl]acetamide, 'chloroacetanilide'. The microbore HPLC FAB technique on a high-resolution sector mass spectrometer accelerated identification of polar metabolites from the in vitro metabolism study of the herbicide. It provided good chromatographic resolution and excellent FAB sensitivity with strong protonated molecular ions. Scanning high-resolution LC/FAB mass spectrometry also provided molecular formulae for structural elucidation of unknown metabolites. Sample purification and concentration were minimized. Identification of less polar metabolites was carried out using LC/TSP mass spectrometry with a quadrupole mass spectrometer. LC/TSP mass spectrometry provided useful structural information for both polar and less polar metabolites because their spectra showed more fragmentation than FAB spectra. Glutathione conjugation was the major reaction observed during in vitro incubation of the herbicide. Oxidation of the chloroacetanilide by rat liver enzymes was also a significant metabolic reaction. Seven metabolites were identified, of which four were glutathione conjugates.

  2. [Cloning and analysis of a new aliphatic amidase gene from Rhodococcus erythropolis TA37].

    PubMed

    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.

  3. A new acylamidase from Rhodococcus erythropolis TA37 can hydrolyze N-substituted amides.

    PubMed

    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.

  4. Cytokinins of the Developing Mango Fruit 1

    PubMed Central

    Chen, Wen-Shaw

    1983-01-01

    The cytokinin activity has been isolated and identified from extracts of immature mango (Mangifera indica L.) seeds. The structures of zeatin, zeatin riboside, and N6-(Δ2-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 × 103 micromolar) onto the panicle at the anthesis stage and by supplying gibberellic acid (7.2 × 102 micromolar) and naphthalene acetamide (3.1 × 10 micromolar) at the young fruit stage. PMID:16662830

  5. Interfacial thermodynamics of water and six other liquid solvents.

    PubMed

    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.

  6. Development of Small-Molecule Cryptochrome Stabilizer Derivatives as Modulators of the Circadian Clock

    PubMed Central

    Lee, Jae Wook; Hirota, Tsuyoshi; Kumar, Anupriya; Kim, Nam-Jung; Irle, Stephan; Kay, Steve A

    2015-01-01

    Small-molecule probes have been playing prominent roles in furthering our understanding of the molecular underpinnings of the circadian clock. We previously discovered a carbazole derivative, KL001 (N-(3-(9H-carbazol-9-yl)-2-hydroxypropyl)-N-(furan-2-ylmethyl)methanesulfonamide), as a stabilizer of the clock protein cryptochrome (CRY). Herein we describe an extensive structure–activity relationship analysis of KL001 derivatives leading to the development of a highly active derivative: 2-(9H-carbazol-9-yl)-N-(2-chloro-6-cyanophenyl)acetamide (KL044). Subsequent 3D-QSAR analysis identified critical features of KL001 derivatives and provided a molecular-level understanding of their interaction with CRY. The electron-rich carbazole, amide/hydroxy linker, sulfonyl group, and electron-withdrawing nitrile moieties contribute to greater biological activity. The hydrogen bonding interactions with Ser394 and His357 as well as stronger CH–π interactions with Trp290 make KL044 a better binder than KL001. KL044 lengthened the circadian period, repressed Per2 activity, and stabilized CRY in reporter assays with roughly tenfold higher potency than KL001. Altogether, KL044 is a powerful chemical tool to control the function of the circadian clock through its action on CRY. PMID:26174033

  7. Synthesis and structural study of precursors of novel methylsilanediols by IR and Raman spectroscopies, single-crystal X-ray diffraction and DFT calculations.

    PubMed

    Rodríguez Ortega, M P G; Docampo, M L; Thomas, L H; Montejo, M; Marchal Ingraín, A; Wilson, C C; López González, J J

    2014-01-24

    On the way towards the development of a synthetic route aimed at obtaining new methylsilanediol derivatives with an aminocarbonyl group in β to silicon (which may have a potential biological interest), we have synthesized, isolated and purified five diphenylic possible precursors, namely chloromethyl(methyl)diphenylsilane, 2-{[methyl(diphenyl)silyl]methyl}-1H-isoindole-1,3(2H)-dione, N-[(methyl(diphenyl) silanyl)-methyl]-benzamide, N-[(methyl(diphenyl)silyl)-methyl]-acetamide and N-[(methyl(diphenyl)silyl)-methyl]-formamide. The conformational landscape of the five species in this study are explored by means of DFT calculations at the B3LYP/6-311++G(∗∗) level. The theoretical molecular structures predicted are confirmed by the reproduction of their respective IR and Raman spectral profiles, that are completely assigned. Some evidence in the vibrational spectra points to the occurrence of conformational mixtures in the samples. Further, single-crystal X-ray diffraction has allowed the elucidation of the crystalline structure of 2-{[methyl(diphenyl)silyl]methyl}-1H-isoindole-1,3(2H)-dione.

  8. Comparison of fate and transport of isoxaflutole to atrazine and metolachlor in 10 Iowa rivers

    USGS Publications Warehouse

    Meyer, M.T.; Scribner, E.A.; Kalkhoff, S.J.

    2007-01-01

    Isoxaflutole (IXF), a newer low application rate herbicide, was introduced for weed control in corn (Zea mays) to use as an alternative to widely applied herbicides such as atrazine. The transport of IXF in streamwater has not been well-studied. The fate and transport of IXF and two of its degradation products was studied in 10 Iowa rivers during 2004. IXF rapidly degrades to the herbicidally active diketonitrile (DKN), which degrades to a biologically inactive benzoic acid (BA) analogue. IXF was detected in only four, DKN in 56, and BA in 43 of 75 samples. The concentrations of DKN and BA were approximately 2 orders of magnitude less than those of the commonly detected triazine and acetamide herbicides and their degradation products. Concentrations of IXF, DKN, and BA were highest during the May through June postplanting period. The concentration ratio of BA/DKN was similar to the deethylatrazine/atrazine ratio with smaller ratios occurring during May and June. The relative temporal variation of DKN and BA was similar to that observed for atrazine and deethylatrazine. This study shows that low application rate herbicides can have similar temporal transport patterns in streamwater as compared to more widely applied herbicides but at lower concentrations.

  9. Structure and properties of PVDF membrane with PES-C addition via thermally induced phase separation process

    NASA Astrophysics Data System (ADS)

    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.

  10. Growth and characterization of a new nonlinear optical organic crystal: 2,4,6-Trimethylacetanilide

    NASA Astrophysics Data System (ADS)

    Upadhyaya, V.; Prabhu, Sharada G.

    2015-09-01

    A new nonlinear optical organic material, 2,4,6-trimethylacetanilide (246TMAA), also known as N-[2,4,6- trimethylphenyl]acetamide, has been synthesized and grown as a single crystal by the slow evaporation technique by organic solvents. The grown crystals have been characterized by morphology study. The crystals are prismatic. Surface examination shows granular dendritic pattern in optical micrograph. The Scanning Electron Micrograph shows the layered growth of the crystal. The Differential Scanning Calorimeter plot shows no phase change until melting point (219°C). The density of the crystals is 1.1g/cc and the crystals are soft. The crystals are transparent in the visible region and in the ultra-violet region till 280 nm. 246TMAA crystallizes with 2 molecules in a monoclinic unit cell in the noncentrosymmetric point group m, space group Pn. Refractive indices of this optically biaxial crystal along the three crystallophysical axes have been measured at 633 nm. The optical second harmonic generation efficiency of the crystal at 1064 nm is about half that of the urea crystal, measured by powder method using Nd:YAG laser. The results show that the 246TMAA crystal can efficiently be used for up-conversion of infrared radiation into visible green light. The powder X-ray diffraction spectrum of the crystal has been obtained.

  11. Radiation inactivation studies of renal brush border water and urea transport

    SciTech Connect

    Verkman, A.S.; Dix, J.A.; Seifter, J.L.; Skorecki, K.L.; Jung, C.Y.; Ausiello, D.A.

    1985-12-01

    Radiation inactivation was used to determine the nature and molecular weight of water and urea transport pathways in brush border membrane vesicles (BBMV) isolated from rabbit renal cortex. BBMV were frozen to -50 degrees C, irradiated with 1.5 MeV electrons, thawed, and assayed for transport or enzyme activity. The freezing process had no effect on enzyme or transport kinetics. BBMV alkaline phosphatase activity gave linear ln(activity) vs. radiation dose plots with a target size of 68 +/- 3 kDa, similar to previously reported values. Water and solute transport were measured using the stopped-flow light-scattering technique. The rates of acetamide and osmotic water transport did not depend on radiation dose (0-7 Mrad), suggesting that transport of these substances does not require a protein carrier. In contrast, urea and thiourea transport gave linear ln(activity) vs. dose curves with a target size of 125-150 kDa; 400 mM urea inhibited thiourea flux by -50% at 0 and 4.7 Mrad, showing that radiation does not affect inhibitor binding to surviving transporters. These studies suggest that BBMV urea transport requires a membrane protein, whereas osmotic water transport does not.

  12. Amidation reaction of eugenyl oxyacetate ethyl ester with 1,3 diaminopropane

    NASA Astrophysics Data System (ADS)

    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.

  13. Talin Modulation by a Synthetic N-Acylurea Derivative Reduces Angiogenesis in Human Endothelial Cells

    PubMed Central

    Lim, I-Rang; Joo, Hyung Joon; Jeong, Minseon; Kim, Jong-Ho; Choi, Seung-Cheol; Kim, Chungho; Jung, Jong-Wha; Hong, Soon Jun

    2017-01-01

    Talin is a focal adhesion protein that activates integrins and recruits other focal adhesion proteins. Talin regulates the interactions between integrins and the extracellular matrix, which are critical for endothelial cells during angiogenesis. In this study, we successfully synthesized a novel talin modulator, N-((2-(1H-indol-3-yl)ethyl)carbamoyl)-2-(benzo[d][1,3]dioxol-5-yloxy)acetamide, referred to as KCH-1521. KCH-1521 was determined to bind talin and modulate downstream signaling molecules of talin. After 24 h of treatment, KCH-1521 changed the cell morphology of human umbilical vein endothelial cells (HUVECs) and reduced focal adhesion protein expression including vinculin and paxillin. Talin downstream signaling is regulated via focal adhesion kinase (FAK), kinase B (AKT), and extracellular signal-regulated kinase (ERK) pathways, however, treatment with KCH-1521 decreased phosphorylation of FAK, AKT, and ERK, leading to reduction of cell proliferation, survival, and angiogenesis. Interestingly, the expression of various angiogenic genes was significantly decreased after treatment with KCH-1521. Also, in vitro tube forming assay revealed that KCH-1521 reduced angiogenic networks in a time-dependent manner. To investigate the reversibility of its effects, KCH-1521 was removed after treatment. HUVECs recovered their morphology through rearrangement of the cytoskeleton and the expression of angiogenic genes was also recovered. By further optimization and in vivo studies of KCH-1521, a novel drug of talin modulation could be used to achieve therapeutic anti-angiogenesis for vascular diseases and cancers. PMID:28117756

  14. Translation Start Sequences Affect the Efficiency of Silencing of Agrobacterium tumefaciens T-DNA Oncogenes1

    PubMed Central

    Lee, Hyewon; Humann, Jodi L.; Pitrak, Jennifer S.; Cuperus, Josh T.; Parks, T. Dawn; Whistler, Cheryl A.; Mok, Machteld C.; Ream, L. Walt

    2003-01-01

    Agrobacterium tumefaciens oncogenes cause transformed plant cells to overproduce auxin and cytokinin. Two oncogenes encode enzymes that convert tryptophan to indole-3-acetic acid (auxin): iaaM (tryptophan mono-oxygenase) and iaaH (indole-3-acetamide hydrolase). A third oncogene (ipt) encodes AMP isopentenyl transferase, which produces cytokinin (isopentenyl-AMP). Inactivation of ipt and iaaM (or iaaH) abolishes tumorigenesis. Because adequate means do not exist to control crown gall, we created resistant plants by introducing transgenes designed to elicit posttranscriptional gene silencing (PTGS) of iaaM and ipt. Transgenes that elicit silencing trigger sequence-specific destruction of the inducing RNA and messenger RNAs with related sequences. Although PTGS has proven effective against a variety of target genes, we found that a much higher percentage of transgenic lines silenced iaaM than ipt, suggesting that transgene sequences influenced the effectiveness of PTGS. Sequences required for oncogene silencing included a translation start site. A transgene encoding a translatable sense-strand RNA from the 5′ end of iaaM silenced the iaaM oncogene, but deletion of the translation start site abolished the ability of the transgene to silence iaaM. Silencing A. tumefaciens T-DNA oncogenes is a new and effective method to produce plants resistant to crown gall disease. PMID:12972655

  15. Structural, DFT and biological studies on Cr(III) complexes of semi and thiosemicarbazide ligands derived from diketo hydrazide

    NASA Astrophysics Data System (ADS)

    Yousef, T. A.; Alduaij, O. K.; Ahmed, Sara F.; Abu El-Reash, G. M.; El-Gammal, O. A.

    2016-12-01

    Three 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 Cr(III) chloride complexes were prepared and characterized by conventional techniques. The data confirmed that the complexes have the following formulaes, [Cr(H2PAPS)Cl3], [Cr(HPAPT)Cl2(H2O)2] and [Cr(HPABT)Cl2(H2O)]. The IR spectra of complexes shows that H2PAPS behaves as neutral tridentate via both CO of hydrazide moiety and Cdbnd N(azomethine) due to enolization of CO isocyanate without deprotonation. H2PAPT suggests the coordination as mononegative bidentate via both CO of hydrazide moiety in keto and deprotonated enolic oxygen atoms. H2PABT act as mononegative tridentate via carbonyl oxygen (Cdbnd O)3, the deprotonated enolic oxygen atom (dbnd Csbnd Osbnd)1 and NH1 groups. The experimental IR data of ligands are compared with those obtained theoretically from DFT calculations. Also, the bond lengths, bond angles, HOMO, LUMO and dipole moments have been calculated. The calculated HOMO-LUMO energy gap reveals that charge transfer occurs within the ligand molecules. The calculated values of binding energies indicates the higher stability of metal complexes than of ligands. Also, the kinetic and thermodynamic parameters for the different thermal degradation steps of the complexes were determined by Coats-Redfern and Horowitz-Metzger methods.

  16. Interaction of 5'-P-sulfonylbenzoyl adenosine with cysteine residues of rat liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase

    SciTech Connect

    El-Maghrabi, M.R.; Lively, M.O.; Pilkis, S.J.

    1987-05-01

    The kinase and bisphosphatase reactions of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase appear to be catalyzed at separate active sites. The kinase site contains 3 cysteinyl residues that are important for sugar phosphate binding but not for ATP binding. These groups are readily alkylated with iodoacetamide which decreases by 15-fold the affinity for Fru 6-P but also increases the maximal velocity of the reaction by the same extent. Incubation of the enzyme with 5'-p-fluorosulfonylbenzoyl adenosine (FSBA), an ATP analog, has no effect on the bisphosphatase activity but inactivates the kinase. The addition of dithiothreitol completely reactivates the kinase, suggesting that the reagent affected sulfhydryl groups critical for sugar phosphate binding and not the ATP site of the enzyme. Similarly, 8-Azido-ATP/UV-photoinactivated enzyme is also reactivated by dithiothreitol and involves the same sulfhydryl groups, since alkylation of the latter with iodoacetamide protects the enzyme from inactivation by FSBA and from 8-azido ATP. Cyanogen bromide cleavage of enzyme that had been alkylated with iodo(I-/sup 14/C)acetamide yielded a 20,000 dalton peptide which contained the three cysteinyl residues. It is concluded that the site of action of ATP analogs to inactivate the kinase are these cysteinyl residues rather than the ATP binding site per se.

  17. Prebiotic Organic Matter from the Center of the Galaxy

    NASA Astrophysics Data System (ADS)

    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.

  18. Ammoxidation of lignocellulosic materials: formation of nonheterocyclic nitrogenous compounds from monosaccharides.

    PubMed

    Klinger, Karl Michael; Liebner, Falk; Hosoya, Takashi; Potthast, Antje; Rosenau, Thomas

    2013-09-25

    Ammoxidized technical lignins are valuable soil-improving materials that share many similarities with native terrestrial humic substances. In contrast to lignins, the chemical fate of carbohydrates as typical minor constituents of technical lignins during the ammoxidation processes has not been thoroughly investigated. Recently, we reported the formation of N-heterocyclic, ecotoxic compounds (OECD test 201) from both monosaccharides (D-glucose, D-xylose) and polysaccharides (cellulose, xylan) under ammoxidation conditions and showed that monosaccharides are a source more critical than polysaccharides in this respect. GC/MS-derivatization analysis of the crude product mixtures revealed that ammoxidation of carbohydrates which resembles the conditions encountered in nonenzymatical browning of foodstuff affords also a multitude of nonheterocyclic nitrogenous compounds such as aminosugars, glycosylamines, ammonium salts of aldonic, deoxyaldonic, oxalic and carbaminic acids, urea, acetamide, α-hydroxyamides, and even minor amounts of α-amino acids. D-glucose and D-xylose afforded largely similar product patterns which differed from each other only for those products that were formed under preservation of the chain integrity and stereoconfiguration of the respective monosaccharide. The kinetics and reaction pathways involved in the formation of the different classes of nitrogenous compounds under ammoxidation conditions are discussed.

  19. Preferential bromide and pesticide movement to tile drains under different cropping practices.

    PubMed

    Fortin, J; Gagnon-Bertrand, E; Vézina, L; Rompré, M

    2002-01-01

    Subsurface drainage systems are useful tools to study chemical leaching in soils. Our objective was to compare the breakthrough behavior of bromide, atrazine (2-chloro-4-ethylamino-6-isopropylamino-s-triazine) and metolachlor [2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-1-methylethyl) acetamid] to tile drains under two fall tillage practices (conventional tillage [CT] with a moldboard plow, and reduced tillage [RT] with a chisel plow) in field plots cultivated with corn (Zea mays L.). Leachate volume were greater in RT than in CT, with no statistical differences. Soil analysis showed that bromide migrated deeper in the soil profile than both herbicides, with little tillage effect. All chemicals were detected in drainage water at the same time and followed an event-driven behavior. Tillage had no effect on atrazine and metolachlor found in drainage water, while bromide concentration peaks were higher in RT than in CT in 1999. Concentration peaks were recorded earlier for atrazine and metolachlor than for bromide. Plots of cumulative relative chemical mass (cumulative mass divided by total mass measured in drainage) as a function of cumulative drainage were mostly linear for bromide, while they were S-shaped for both herbicides. Drainage that corresponded to 50% of relative cumulative mass ranged from 40 to 55% for bromide and from 5 to 28% for both herbicides. Rapid chemical movement to tile drains suggested that preferential flow was important in both CT and RT, and that these tillage practices had little influence on this phenomena.

  20. Effects of nefiracetam on the levels of brain-derived neurotrophic factor and synapsin I mRNA and protein in the hippocampus of microsphere-embolized rats.

    PubMed

    Ando, Tsuyoshi; Takagi, Norio; Takagi, Keiko; Kago, Tomoyuki; Takeo, Satoshi

    2005-01-10

    Our recent study demonstrated that nefiracetam, N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl) acetamide, prevented impairment of the cyclic AMP (cAMP)/cAMP-responsive element binding (CREB) protein signaling pathway in sustained cerebral ischemia. The purpose of the present study was to determine whether nefiracetam has an effect on the expression of brain-derived neurotrophic factor (BDNF) and synapsin I mRNAs that are believed to be produced via CREB, and the alteration in their protein contents in the hippocampus after cerebral ischemia. Sustained cerebral ischemia was induced by injection of 700 microspheres into the right hemisphere of each rat. The rats were treated once daily with 10 mg/kg nefiracetam, p.o., from 15 h after the operation. Treatment with nefiracetam reduced the prolongation of the escape latency in the water maze test on days 7-9 after microsphere embolism-induced sustained cerebral ischemia, suggesting an improvement in the spatial learning function. Microsphere-embolized rats on day 5 showed decreases in BDNF and synapsin I mRNA levels and their protein contents in the ipsilateral hippocampus. Treatment with nefiracetam partially attenuated the decreases. These results suggest that enhancement of BDNF and synapsin I expression by nefiracetam treatment may be, at least in part, due to the improvement in the CREB binding activity, contributing to the prevention of learning and memory dysfunction after sustained cerebral ischemia.

  1. Synthesis and applications of chitosan mercaptanes as heavy metal retention agent.

    PubMed

    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.

  2. Bio-inspired nitrile hydration by peptidic ligands based on L-cysteine, L-methionine or L-penicillamine and pyridine-2,6-dicarboxylic acid.

    PubMed

    Byrne, Cillian; Houlihan, Kate M; Devi, Prarthana; Jensen, Paul; Rutledge, Peter J

    2014-12-12

    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.

  3. 2-acylamino-5-nitro-1,3-thiazoles: preparation and in vitro bioevaluation against four neglected protozoan parasites.

    PubMed

    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.

  4. Purification and properties of beta-N-acetylhexosaminidase from the mollusc Helicella ericetorum Müller.

    PubMed Central

    Calvo, P; Reglero, A; Cabezas, J A

    1978-01-01

    1. A beta-N-acetylhexosaminidase was purified 330-fold from the digestive gland of the terrestrial mollusc Helicella ericetorum Müller. 2. Its pH optimum is 4.5 for both beta-N-acetylglucosaminidase and beta-N-acetylgalactosaminidase activities in two buffer solutions; it is fully stable at 37 degrees C for 2h in the pH range 3.8--4.6 and shows one isoelectric point (pH 4.83). 3. The estimated mol.wt. is between 120,000 and 145,000. 4. The enzyme shows an endo-beta-N-acetylhexosaminidase activity on natural substrates such as ovalbumin, ovomucoid, chondroitin 4-sulphate, chitin and hyaluronic acid. 5. Two forms of the enzyme were separated by preparative polyacrylamide-gel electrophoresis. 6. Km and Vmax. for p-nitrophenyl 2-acetamido-2-deoxy-beta-D-glucopyranoside and p-nitrophenyl 2-acetamide-2-deoxy-beta-D-galactopyranoside are 0.43 mM, 30.1 micronmol of p-nitrophenol/min per mg and 0.19 mM, 8.6 micronmol of p-nitrophenol/min per mg respectively. 7. It is inhibited by Hg2+, Fe3+, acetate, some lactones, N-acetylgalactosamine, N-acetylglucosamine and mannose. 8. Mixed-substrates analysis and Ki values for competitive inhibitors indicated that beta-N-acetylglucosaminidase and beta-N-acetylgalactosaminidase activities are catalysed by the enzyme at the same active site. PMID:33660

  5. Design and in vitro evaluation of transdermal patches based on ibuprofen-loaded electrospun fiber mats.

    PubMed

    Shi, Yongli; Xu, Shuxin; Dong, Anjie; Zhang, Jianhua

    2013-02-01

    To improve the poor compatibility among different components of Drug-in-adhesive type patch, two novel plasters (Drug-in-fiber and Drug-in-adhesive/fiber) were developed based on ibuprofen (IBU)-loaded fiber mats. These fibrous mats were fabricated via electrospinning of cellulose acetate/poly(vinylpyrrolidone) composites in a binary solvent of N,N-dimethyl acetamide/acetone. Physical status studies suggested that Drug-in-fiber could inhibit IBU re-crystallization, but the active ingredients were released at a relatively slow rate due to the dual-resistance of fiber mat and adhesive matrix. To overcome this shortcoming, Drug-in-adhesive/fiber was designed by coupling medicated hydrophilic pressure sensitive adhesive and IBU-loaded fiber mat. This method endowed Drug-in-adhesive/fiber a fast IBU release rate and high permeated drug amount though simulative skins. This design separated enhancer from adhesive matrix, which guaranteed Drug-in-adhesive/fiber excellent adhesion forces. Hence, the plasters based on medicated fiber mats improved the compatibility among patch components.

  6. Characterization of electrospun GaN nanofibers

    NASA Astrophysics Data System (ADS)

    Ramos, Idalia; Melendez, Anamaris; Morales, Kristle; Campo, Eva M.; Santiago-Aviles, Jorge J.

    2010-03-01

    Gallium Nitride shows characteristics pertinent to optoelectronics and gas sensing applications. Nanofibers have been produced using electrospinning and a precursor composed of Gallium (III) Nitrate Hydrate dissolved in Dimethyl-Acetamide and Cellulose Acetate in Acetone and DMA. The resulting nanofibers were sintered at 400C in nitrogen for one hour to decompose the polymer, the furnace atmosphere switched to ammonia and the fibers sintered for periods of 3, 5 and 7 hrs at 900C. They showed morphologies with unclear dependence on processing parameters. X-ray Diffraction revealed the evolution towards wurtzite phase through annealing. From line broadening we estimate a crystalline domain size of about 12 nm. Transmission Electron Microscopy suggests nucleation and growth of X-tallites while Fourier-Transform Infrared Spectroscopy and Ultraviolet-Visible Spectroscopy confirm the material evolution towards crystallinity and the production of wurtzite GaN nanofibers. I-V characteristics of single nanofibers show linearity with increments in conductivity for those fibers ammoniated during longer periods of time. Ongoing efforts aim at improving fabrication, sensing and photoluminescence characterization.

  7. Bioactive brominated metabolites from the natural habitat and tank-maintained cuttings of the Jamaican sponge Aplysina fistularis.

    PubMed

    Gallimore, Winklet A

    2013-06-01

    Cut specimens of the common reef sponge of the Verongid family, Aplysina fistularis, were retained in flow-through seawater tanks over a six-week period to assess the metabolite profile of the sponge when subjected to stress, compare the profile with the source material, and assess the preliminary feasibility of the protocol for sponge culture. The living specimens were harvested, extracted with MeOH/CH₂Cl₂ 1:1, and subjected to column chromatography to identify metabolites. The brominated isoxazoline compounds, aerothionin (1) and 11-oxoaerothionin (2), along with aeroplysinin 2 (3) and 2-(3,5-dibromo-4-hydroxyphenol)acetamide (4), were detected in the cuttings from the tank-maintained sponge. An examination of the metabolite profile of the sponge from the natural habitat showed that the compounds 1 and 2 were present. The identities of all the compounds were ascertained by analysis of the mass-spectral data and NMR spectra (¹H, ¹³C, HMBC, and HSQC) of the compounds, which were compared with reported data. The survival rate was 44% with limited necrosis or exposed skeletal tissue being observed in eight of the 18 cuttings, suggesting that protocol modifications would be required for culturing the sponge.

  8. Purification and characterization of Vibrio parahaemolyticus extracellular chitinase and chitin oligosaccharide deacetylase involved in the production of heterodisaccharide from chitin.

    PubMed

    Kadokura, K; Rokutani, A; Yamamoto, M; Ikegami, T; Sugita, H; Itoi, S; Hakamata, W; Oku, T; Nishio, T

    2007-05-01

    A chitin-degrading bacterial strain, KN1699, isolated from Yatsu dry beach (Narashino, Chiba Prefecture, Japan), was identified as Vibrio parahaemolyticus. Treatment of powdered chitin with crude enzyme solution prepared from the supernatant of KN1699 cultures yielded a disaccharide, beta-D-N-acetylglucosaminyl-(1,4)-D-glucosamine (GlcNAc-GlcN), as the primary chitin degradation product. The extracellular enzymes involved in the production of this heterodisaccharide, chitinase (Pa-Chi; molecular mass, 92 kDa) and chitin oligosaccharide deacetylase (Pa-COD; molecular mass, 46 kDa), were isolated from the crude enzyme solution, and their hydrolysis specificities were elucidated. These studies confirmed that (1) Pa-Chi hydrolyzes chitin to produce (GlcNAc)(2) and (2) Pa-COD hydrolyzes the acetamide group of reducing end GlcNAc residue of (GlcNAc)(2). These findings indicate that GlcNAc-GlcN is produced from chitin by the cooperative hydrolytic reactions of both Pa-Chi and Pa-COD.

  9. Enthused research on DNA-binding and DNA-cleavage aptitude of mixed ligand metal complexes.

    PubMed

    Mahalakshmi, Rajkumar; Raman, Natarajan

    2013-08-01

    Five new Mn(II), Co(II), Ni(II), Cu(II) and Zn(II) mixed ligand complexes have been synthesized using a Schiff base precursor (obtained by the condensation of N-(4-aminophenyl)acetamide and 4-chlorobenzaldehyde) as main ligand and 1,10-phenanthroline as co-ligand. They have been characterized by microanalytical data, IR, UV-Vis, magnetic moment values, conductivity and electrochemical measurements. The spectral data reveal that all the complexes exhibit octahedral geometry. The high electrical conductance of the complexes supports their electrolytic nature. The monomeric nature of the complexes has been assessed from their magnetic susceptibility values. These complexes are better antimicrobial active agents than the free ligands. DNA (CT) binding properties of these complexes have been explored by UV-Vis., viscosity measurements, cyclic voltammetry, and differential pulse voltammetry measurements. The oxidative cleavage activity of the complexes has been studied using supercoiled pUC19 DNA by gel electrophoresis. The experimental results show that the complexes are good intercalators.

  10. The effects of methyl internal rotation and {sup 14}N quadrupole coupling in the microwave spectra of two conformers of N,N-diethylacetamide

    SciTech Connect

    Kannengießer, Raphaela; Klahm, Sebastian; Vinh Lam Nguyen, Ha Lüchow, Arne; Stahl, Wolfgang

    2014-11-28

    The gas phase structures and internal dynamics of N,N-diethylacetamide were determined with very high accuracy using a combination of molecular beam Fourier-transform microwave spectroscopy and quantum chemical calculations at high levels. Conformational studies yielded five stable conformers with C{sub 1} symmetry. The two most energetically favorable conformers, conformer I and II, could be found in the experimental spectrum. For both conformers, quadrupole hyperfine splittings of the {sup 14}N nucleus and torsional fine splittings due to the internal rotation of the acetyl methyl group occurred in the same order of magnitude and were fully assigned. The rotational constants, centrifugal distortion constants as well as the quadrupole coupling constants of the {sup 14}N nucleus were determined and fitted to experimental accuracy. The V{sub 3} potentials were found to be 517.04(13) cm{sup −1} and 619.48(91) cm{sup −1} for conformer I and II, respectively, and compared to the V{sub 3} potentials found in other acetamides. Highly accurate CCSD(T) and DMC calculations were carried out for calculating the barriers to internal rotation in comparison with the experimentally deduced V{sub 3} values.

  11. Regulation of the inner membrane mitochondrial permeability transition by the outer membrane translocator protein (peripheral benzodiazepine receptor).

    PubMed

    Sileikyte, Justina; Petronilli, Valeria; Zulian, Alessandra; Dabbeni-Sala, Federica; Tognon, Giuseppe; Nikolov, Peter; Bernardi, Paolo; Ricchelli, Fernanda

    2011-01-14

    We studied the properties of the permeability transition pore (PTP) in rat liver mitochondria and in mitoplasts retaining inner membrane ultrastructure and energy-linked functions. Like mitochondria, mitoplasts readily underwent a permeability transition following Ca(2+) uptake in a process that maintained sensitivity to cyclosporin A. On the other hand, major differences between mitochondria and mitoplasts emerged in PTP regulation by ligands of the outer membrane translocator protein of 18 kDa, TSPO, formerly known as the peripheral benzodiazepine receptor. Indeed, (i) in mitoplasts, the PTP could not be activated by photo-oxidation after treatment with dicarboxylic porphyrins endowed with protoporphyrin IX configuration, which bind TSPO in intact mitochondria; and (ii) mitoplasts became resistant to the PTP-inducing effects of N,N-dihexyl-2-(4-fluorophenyl)indole-3-acetamide and of other selective ligands of TSPO. Thus, the permeability transition is an inner membrane event that is regulated by the outer membrane through specific interactions with TSPO.

  12. Determination of pyrolysis products of smoked methamphetamine mixed with tobacco by tandem mass spectrometry.

    PubMed

    Lee, M R; Jeng, J; Hsiang, W S; Hwang, B H

    1999-01-01

    This study examines the pyrolysis products of smoked methamphetamine mixed with tobacco that was trapped with a C8 adsorbent cartridge and then detected by gas chromatography-tandem mass spectrometry. According to the results, the mainstream smoke contains 2-methylpropyl-benzene, 2-chloropropyl-benzene, 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one, 3-ethyl-phenol, methamphetamine, dimethylamphetamine, hydroquinone, 3-methyl-5-(1-methylethyl)-methylcarbamate phenol, N-methyl-N-(2-phenylethyl)-acetamide, 4-(3-hydroxy-1-butenyl)-3,5,5-trimethyl-2-cyclohexene-1-one, propanoic acid, N-acetylmethamphetamine, phenyl ester, and furfurylmethylamphetamine. In addition, the compounds in sidestream smoke are 2-propenyl benzene, phenylacetone, methamphetamine, dimethylamphetamine, benzyl methyl ketoxime, 3,4-dihydro-2-naphthalenone, N-folmyamphetamine, N-acetylamphetamine, bibenzyl, N-folmylmethamphetamine, N-acetylmethamphetamine, N-propionymethamphetamine, and furfurylmethylamphetamine. Moreover, the presence of methamphetamine promotes the oxidation of the tobacco components.

  13. Synthesis, molecular docking, and biological evaluation of some novel hydrazones and pyrazole derivatives as anti-inflammatory agents.

    PubMed

    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. Synthesis and Characterization of High Performance Polyimides Containing the Bicyclo(2.2.2)oct-7-ene Ring System

    NASA Technical Reports Server (NTRS)

    Alvarado, M.; Harruna, I. I.; Bota, K. B.

    1997-01-01

    Due to the difficulty in processing polyimides with high temperature stability and good solvent resistance, we have synthesized high performance polyimides with bicyclo(2.2.2)-oct-7-ene ring system which can easily be fabricated into films and fibers and subsequently converted to the more stable aromatic polyimides. In order to improve processability, we prepared two polyimides by reacting 1,4-phenylenediamine and 1,3phenylediamine with bicyclo(2.2.2)-7-octene-2,3,5,6-tetracarboxylic dianhydride. The polyimides were characterized by FTIR, FTNMR, solubility and thermal analysis. Thermogravimetric analysis (TGA) showed that the 1,4-phenylenediamine and 1,3-phenylenediamine containing polyimides were stable up to 460 and 379 C, respectively under nitrogen atmosphere. No melting transitions were observed for both polyimides. The 1,4-phenylenediamine containing polyimide is partially soluble in dimethyl sulfoxide, methane sulfonic acid and soluble in sulfuric acid at room temperature. The 1,3-phenylenediamine containing polyimide is partially soluble in dimethyl sulfoxide, tetramethyl urea, N,N-dimethyl acetamide and soluble in methane sulfonic acid and sulfuric acid.

  15. Effect of Phloretin on Water and Solute Movement in the Toad Bladder

    PubMed Central

    Levine, Sherman; Franki, Nicholas; Hays, Richard M.

    1973-01-01

    It is generally believed that urea crosses the cell membrane through aqueous channels, and that its movement across the membrane is accelerated in the direction of net water flow (solvent drag effect). The present report presents evidence for a vasopressin-sensitive pathway for the movement of urea, other amides, and certain non-amides, which is independent of water flow. Phloretin, when present at 10-4 M concentration in the medium bathing the luminal surface of the toad bladder, strongly inhibits the movement of urea, acetamide, and propionamide across the toad bladder, both in the absence and presence of vasopressin. The vasopressin-stimulated movement of formaldehyde and thiourea is also reduced. Osmotic water flow, on the other hand, is not affected; nor is the movement of ethanol and ethylene glycol, or the net transport of sodium. On the basis of these studies we would conclude that the movement of many, if not all, solutes across the cell membrane is independent of water flow, and that a vasopressin-sensitive carrier may be involved in the transport of certain solutes across the cell membrane. PMID:4703229

  16. The vigilance promoting drug modafinil modulates serotonin transmission in the rat prefrontal cortex and dorsal raphe nucleus. Possible relevance for its postulated antidepressant activity.

    PubMed

    Ferraro, Luca; Antonelli, Tiziana; Beggiato, Sarah; Cristina Tomasini, Maria; Fuxe, Kjell; Tanganelli, Sergio

    2013-04-01

    Modafinil, (RS)-2-(diphenylmethylsulfinyl)acetamide derivative (Modiodal, Provigil), is a vigilance-promoting agent which reduces sleep episodes by improving wakefulness. It is approved by the USA FDA for narcolepsy, shiftwork sleep disorder and obstructive sleep apnoea with residual excessive sleepiness despite optimal use of continuous positive airway pressure. Unlike classical psychostimulants such as amphetamine and amphetamine-like compounds, the awaking effect of modafinil is not associated with a disturbance of nighttime sleep, tolerance, and sensitization. Its precise mechanism of action is still unclear. In animal studies, modafinil and its analogues have been shown to modify dopaminergic, noradrenergic, glutamatergic, GABAergic, serotoninergic, orexinergic, and histaminergic pathways. Besides the approved use in sleep disorders, modafinil has been investigated for the treatment of fatigue, impaired cognition and some symptoms in a number of other disorders. In particular, clinical studies seem to indicate that the drug could be particularly successful in the treatment of depression and its use in major depressive and bipolar disorders, has been suggested. However, the molecular mechanisms underlying this possible effect are still unknown. The present review firstly summarizes the structure-activity relationship studies and the mechanism of action of modafinil and its related compounds. Then, it focuses on data demonstrating that modafinil interacts with serotonin neuronal activity in rat frontal cortex and dorsal raphe nucleus, two brain areas linked together and involved in depression. Preclinical and clinical evidence of a positive interaction between modafinil and classical antidepressant drugs, is also summarized.

  17. Modafinil decreases anxiety-like behaviour in zebrafish.

    PubMed

    Johnson, Adrian; Hamilton, Trevor James

    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.

  18. Guanidinium-based derivatives: searching for new kinase inhibitors.

    PubMed

    Diez-Cecilia, Elena; Kelly, Brendan; Perez, Concepcion; Zisterer, Daniela M; Nevin, Daniel K; Lloyd, David G; Rozas, Isabel

    2014-06-23

    Considering the structural similarities between the kinase inhibitor sorafenib and 4,4'-bis-guanidinium derivatives previously prepared by Rozas and co., which display interesting cytotoxicity in cancer cells, we have studied whether this activity could result from kinase inhibition. Five new families have been prepared consisting of unsubstituted and aryl-substituted 3,4'-bis-guanidiniums, 3,4'-bis-2-aminoimidazolinium and 3-acetamide-4'-(4-chloro-3-trifluoromethylphenyl)guanidinium derivatives. Cytotoxicity (measuring the IC50 values) and apoptosis studies in human HL-60 promyelocytic leukemia cells were carried out for these compounds. Additionally, their potential inhibitory effect was explored on a panel of kinases known to be involved in apoptotic pathways. The previously prepared cytotoxic 4,4'-bis-guanidiniums did not inhibit any of these kinases; however, some of the novel 3,4'-substituted derivatives showed a high percentage inhibition of RAF-1/MEK-1, for which the potential mode of binding was evaluated by docking studies. The interesting antitumour properties showed by these compounds open up new exciting lines of investigation for kinase inhibitors as anticancer agents and also highlights the relevance of the guanidinium moiety for protein kinase inhibitors chemical design.

  19. Local Light-Induced Modification of the Inside of Microfluidic Glass Chips.

    PubMed

    Carvalho, Rui Rijo; Pujari, Sidharam P; Lange, Stefanie C; Sen, Rickdeb; Vrouwe, Elwin Xander; Zuilhof, Han

    2016-03-15

    The ability to locally functionalize the surface of glass allows for myriad biomedical and chemical applications. This would be the case if the surface functionalization can be induced using light with wavelengths for which standard glass is almost transparent. To this aim, we present the first example of a photochemical modification of hydrogen-terminated glass (H-glass) with terminal alkenes. Both flat glass surfaces and the inside of glass microchannels were modified with a well-defined, covalently attached organic monolayer using a range of wavelengths, including sub-band-gap 302 nm ultraviolet light. A detailed characterization thereof was conducted by measurements of the static water contact angle, X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and scanning Auger microscopy (SAM). Germanium attenuated total reflection Fourier transform infrared (GATR-FTIR) indicates that the mechanism of the surface modification proceeds via an anti-Markovnikov substitution. Reacting H-glass with 10-trifluoro-acetamide-1-decene (TFAAD) followed by basic hydrolysis affords the corresponding primary amine-terminated monolayer, enabling additional functionalization of the substrate. Furthermore, we show the successful formation of a photopatterned amine layer by the specific attachment of fluorescent nanoparticles in very discrete regions. Finally, a microchannel was photochemically patterned with a functional linker allowing for surface-directed liquid flow. These results demonstrate that H-glass can be modified with a functional tailor-made organic monolayer, has highly tunable wetting properties, and displays significant potential for further applications.

  20. 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.

    PubMed

    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.

  1. Highly selective luminescent nanostructures for mitochondrial imaging and targeting

    NASA Astrophysics Data System (ADS)

    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

  2. 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

    NASA Astrophysics Data System (ADS)

    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

  3. 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

    NASA Astrophysics Data System (ADS)

    Sarkar, C.; Sinha, V.; Kumar, V.; Rupakheti, M.; Panday, A.; Mahata, K. S.; Rupakheti, D.; Kathayat, B.; Lawrence, M. G.

    2015-09-01

    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 characterize 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. 71 ion peaks (for which measured ambient concentrations exceeded the 2 σ 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 highest average VOC mixing ratios during the measurement period were (in rank order): acetaldehyde (8.8 ppb), methanol (7.4 ppb), acetone (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), and 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 till date. Two "new" ambient compounds namely, formamide (m/z = 46.029) and acetamide (m/z = 60.051), which can photochemically produce isocyanic

  4. 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.

    PubMed

    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

  5. A2B adenosine receptors stimulate IL-6 production in primary murine microglia through p38 MAPK kinase pathway.

    PubMed

    Merighi, Stefania; Bencivenni, Serena; Vincenzi, Fabrizio; Varani, Katia; Borea, Pier Andrea; Gessi, Stefania

    2017-03-01

    The hallmark of neuroinflammation is the activation of microglia, the immunocompetent cells of the CNS, releasing a number of proinflammatory mediators implicated in the pathogenesis of neuronal diseases. Adenosine is an ubiquitous autacoid regulating several microglia functions through four receptor subtypes named A1, A2A, A2B and A3 (ARs), that represent good targets to suppress inflammation occurring in CNS. Here we investigated the potential role of ARs in the modulation of IL-6 secretion and cell proliferation in primary microglial cells. The A2BAR agonist 2-[[6-Amino-3,5-dicyano-4-[4-(cyclopropylmethoxy)phenyl]-2-pyridinyl]thio]-acetamide (BAY60-6583) stimulated IL-6 increase under normoxia and hypoxia, in a dose- and time-dependent way. In cells incubated with the blockers of phospholipase C (PLC), protein kinase C epsilon (PKC-ε) and PKC delta (PKC-δ) the IL-6 increase due to A2BAR activation was strongly reduced, whilst it was not affected by the inhibitor of adenylyl cyclase (AC). Investigation of cellular signalling involved in the A2BAR effect revealed that only the inhibitor of p38 mitogen activated protein kinase (MAPK) was able to block the agonist's effect on IL-6 secretion, whilst inhibitors of pERK1/2, JNK1/2 MAPKs and Akt were not. Stimulation of p38 by BAY60-6583 was A2BAR-dependent, through a pathway affecting PLC, PKC-ε and PKC-δ but not AC, in both normoxia and hypoxia. Finally, BAY60-6583 increased microglial cell proliferation involving A2BAR, PLC, PKC-ε, PKC-δ and p38 signalling. In conclusion, A2BARs activation increased IL-6 secretion and cell proliferation in murine primary microglial cells, through PLC, PKC-ε, PKC-δ and p38 pathways, thus suggesting their involvement in microglial activation and neuroinflammation.

  6. Intercalation of paracetamol into the hydrotalcite-like host

    SciTech Connect

    Kovanda, Frantisek; Maryskova, Zuzana; Kovar, Petr

    2011-12-15

    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 Degree-Sign 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. - Graphical abstract: Molecular simulations showed disordered arrangement of paracetamol molecules in the interlayer; most of the interlayer water molecules are located near the hydroxide sheets. Black-Small-Square Highlights: Black-Right-Pointing-Pointer Paracetamol was intercalated in Mg-Al hydrotalcite-like host by rehydration/reconstruction procedure. Black-Right-Pointing-Pointer Paracetamol phenolic groups interact with positively charged sites in hydroxide sheets. Black-Right-Pointing-Pointer Molecular simulations showed disordered arrangement of guest molecules in the interlayer. Black-Right-Pointing-Pointer Slower release of paracetamol intercalated in the hydrotalcite-like host was observed.

  7. Functional Sorbents for Selective Capture of Plutonium, Americium, Uranium, and Thorium in Blood

    SciTech Connect

    Yantasee, Wassana; Sangvanich, Thanapon; Creim, Jeffrey A.; Pattamakomsan, Kanda; Wiacek, Robert J.; Fryxell, Glen E.; Addleman, Raymond S.; Timchalk, Charles

    2010-09-01

    Nano-engineered solid sorbents for chelation of actinides (239Pu, 241Am, uranium, thorium) from human blood were developed and evaluated in vitro. These sorbents, known as the self-assembled monolayer on mesoporous supports (SAMMSTM), are hybrid materials created from attachment of organic moieties onto extremely high surface area mesoporous silica. The organic moieties known to be effective at capturing actinides including three isomers of hydroxypyridinone, diphosphonic acid, acetamide phosphonic acid, glycinyl urea, and diethylenetriamine pentaacetate analog were evaluated. SAMMS are being reported elsewhere as potential candidates for orally administered drug for radionuclide decorporation. Herein, actinide decorporation of SAMMS in blood were evaluated to assess their viability for sorbent hemoperfusion in renal insufficient patients, whose kidney clear radionuclides at very slow rate. Sorption affinity (Kd), sorption rate, selectivity, and stability of SAMMS were measured in batch contact experiments. An isomer of hydroxypyridinone (3,4-HOPO) on SAMMS demonstrated the highest affinity for decorporation of all four actinides and outperformed the DTPA analog on SAMMS and on commercial resins by a factor of 103-fold in term of affinity. A fifty percent reduction of actinides in blood was achieved within minutes with no evidence of protein fouling and material leaching in blood after 24 hr of contact time. Less than 0.4 wt.% of Si was dissolved from 3,4-HOPO-SAMMS across the pH of 0 to 8. The engineered form of SAMMS (bead format) was further evaluated in a 100-fold scaled-down hemoperfusion device and showed no blood clotting after 2 hr. A 0.2 g of SAMMS could reduce 50 wt.% of 100 ppb uranium in 50 mL of plasma in just 18 min and that of 500 dpm mL-1 in just 24 min. 3,4-HOPO-SAMMS has a long shelf-life in air and at room temperature for at least 8 years, indicating their feasibility for stockpiling in preparedness for emergency.

  8. Regulatory interactions between quorum-sensing, auxin, cytokinin, and the Hrp regulon in relation to gall formation and epiphytic fitness of Pantoea agglomerans pv. gypsophilae.

    PubMed

    Chalupowicz, Laura; Barash, Isaac; Panijel, Mary; Sessa, Guido; Manulis-Sasson, Shulamit

    2009-07-01

    Gall formation by Pantoea agglomerans pv. gypsophilae is controlled by hrp/hrc genes, phytohormones, and the quorum-sensing (QS) regulatory system. The interactions between these three components were investigated. Disruption of the QS genes pagI and pagR and deletion of both substantially reduced the transcription levels of the hrp regulatory genes hrpXY, hrpS, and hrpL, as determined by quantitative reverse-transcriptase polymerase chain reaction. Expression of hrpL in planta was inhibited by addition of 20 microM or higher concentrations of the QS signal C(4)-HSL. The pagR and hrpL mutants caused an equivalent reduction of 1.3 orders in bacterial multiplication on bean leaves, suggesting possible mediation of the QS effect on epiphytic fitness of P. agglomerans pv. gypsophilae by the hrp regulatory system. indole-3-acetic acid (IAA) and cytokinin significantly affected the expression of the QS and hrp regulatory genes. Transcription of pagI, pagR, hrpL, and hrpS in planta was substantially reduced in iaaH mutant (disrupted in IAA biosynthesis via the indole-3-acetamide pathway) and etz mutant (disrupted in cytokinin biosynthesis). In contrast, the ipdC mutant (disrupted in IAA biosynthesis via the indole-3-pyruvate pathway) substantially increased expression of pagI, pagR, hrpL, and hrpS. Results presented suggest the involvement of IAA and cytokinins in regulation of the QS system and hrp regulatory genes.

  9. In vivo quantification of calcitonin gene-related peptide receptor occupancy by telcagepant in rhesus monkey and human brain using the positron emission tomography tracer [11C]MK-4232.

    PubMed

    Hostetler, Eric D; Joshi, Aniket D; Sanabria-Bohórquez, Sandra; Fan, Hong; Zeng, Zhizhen; Purcell, Mona; Gantert, Liza; Riffel, Kerry; Williams, Mangay; O'Malley, Stacey; Miller, Patricia; Selnick, Harold G; Gallicchio, Steven N; Bell, Ian M; Salvatore, Christopher A; Kane, Stefanie A; Li, Chi-Chung; Hargreaves, Richard J; de Groot, Tjibbe; Bormans, Guy; Van Hecken, Anne; Derdelinckx, Inge; de Hoon, Jan; Reynders, Tom; Declercq, Ruben; De Lepeleire, Inge; Kennedy, W P; Blanchard, Rebecca; Marcantonio, Eugene E; Sur, Cyrille; Cook, Jacquelynn J; Van Laere, Koen; Evelhoch, Jeffrey L

    2013-11-01

    Calcitonin gene-related peptide (CGRP) is a potent neuropeptide whose agonist interaction with the CGRP receptor (CGRP-R) in the periphery promotes vasodilation, neurogenic inflammation and trigeminovascular sensory activation. This process is implicated in the cause of migraine headaches, and CGRP-R antagonists in clinical development have proven effective in treating migraine-related pain in humans. CGRP-R is expressed on blood vessel smooth muscle and sensory trigeminal neurons and fibers in the periphery as well as in the central nervous system. However, it is not clear what role the inhibition of central CGRP-R plays in migraine pain relief. To this end, the CGRP-R positron emission tomography (PET) tracer [(11)C]MK-4232 (2-[(8R)-8-(3,5-difluorophenyl)-6,8-[6-(11)C]dimethyl-10-oxo-6,9-diazaspiro[4.5]decan-9-yl]-N-[(2R)-2'-oxospiro[1,3-dihydroindene-2,3'-1H-pyrrolo[2,3-b]pyridine]-5-yl]acetamide) was discovered and developed for use in clinical PET studies. In rhesus monkeys and humans, [(11)C]MK-4232 displayed rapid brain uptake and a regional brain distribution consistent with the known distribution of CGRP-R. Monkey PET studies with [(11)C]MK-4232 after intravenous dosing with CGRP-R antagonists validated the ability of [(11)C]MK-4232 to detect changes in CGRP-R occupancy in proportion to drug plasma concentration. Application of [(11)C]MK-4232 in human PET studies revealed that telcagepant achieved only low receptor occupancy at an efficacious dose (140 mg PO). Therefore, it is unlikely that antagonism of central CGRP-R is required for migraine efficacy. However, it is not known whether high central CGRP-R antagonism may provide additional therapeutic benefit.

  10. Semi- and thiosemicarbazide Mn(II) complexes: Characterization, DFT and biological studies

    NASA Astrophysics Data System (ADS)

    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.

  11. An integrated in silico 3D model-driven discovery of a novel, potent, and selective amidosulfonamide 5-HT1A agonist (PRX-00023) for the treatment of anxiety and depression.

    PubMed

    Becker, Oren M; Dhanoa, Dale S; Marantz, Yael; Chen, Dongli; Shacham, Sharon; Cheruku, Srinivasa; Heifetz, Alexander; Mohanty, Pradyumna; Fichman, Merav; Sharadendu, Anurag; Nudelman, Raphael; Kauffman, Michael; Noiman, Silvia

    2006-06-01

    We report the discovery of a novel, potent, and selective amidosulfonamide nonazapirone 5-HT1A agonist for the treatment of anxiety and depression, which is now in Phase III clinical trials for generalized anxiety disorder (GAD). The discovery of 20m (PRX-00023), N-{3-[4-(4-cyclohexylmethanesulfonylaminobutyl)piperazin-1-yl]phenyl}acetamide, and its backup compounds, followed a new paradigm, driving the entire discovery process with in silico methods and seamlessly integrating computational chemistry with medicinal chemistry, which led to a very rapid discovery timeline. The program reached clinical trials within less than 2 years from initiation, spending less than 6 months in lead optimization with only 31 compounds synthesized. In this paper we detail the entire discovery process, which started with modeling the 3D structure of 5-HT1A using the PREDICT methodology, and then performing in silico screening on that structure leading to the discovery of a 1 nM lead compound (8). The lead compound was optimized following a strategy devised based on in silico 3D models and realized through an in silico-driven optimization process, rapidly overcoming selectivity issues (affinity to 5-HT1A vs alpha1-adrenergic receptor) and potential cardiovascular issues (hERG binding), leading to a clinical compound. Finally we report key in vivo preclinical and Phase I clinical data for 20m tolerability, pharmacokinetics, and pharmacodynamics and show that these favorable results are a direct outcome of the properties that were ascribed to the compound during the rational structure-based discovery process. We believe that this is one of the first examples for a Phase III drug candidate that was discovered and optimized, from start to finish, using in silico model-based methods as the primary tool.

  12. Structure, composition, physical properties, and turnover of proliferated peroxisomes. A study of the trophic effects of Su-13437 on rat liver

    PubMed Central

    Leighton, F.; Coloma, L.; Koenig, C.

    1975-01-01

    Peroxisome proliferation has been induced with 2-methyl-2-(p-[1,2,3,4-tetrahydro-1-naphthyl]-phenoxy)-propionic acid (Su-13437). DNA, protein, cytochrome oxidase, glucose-6-phosphatase, and acid phosphatase concentrations remain almost constant. Peroxisomal enzyme activities change to approximately 165%, 50%, 30%, and 0% of the controls for catalase, urate oxidase, L-alpha-hydroxy acid oxidase, and D-amino acid oxidase, respectively. For catalase the change results from a decrease in particle-bound activity and a fivefold increase in soluble activity. The average diameter of peroxisome sections is 0.58 +/- 0.15 mum in controls and 0.73 +/- 0.25 mum after treatment. Therefore, the measured peroxisomal enzymes are highly diluted in proliferated particles. After tissue fractionation, approximately one-half of the normal peroxisomes and all proliferated peroxisomes show matric extraction with ghost formation, but no change in size. In homogenates submitted to mechanical stress, proliferated peroxisomes do not reveal increased fragility; unexpectedly, Su-13437 stabilizes lysosomes. Our results suggest that matrix extraction and increased soluble enzyme activities result from transmembrane passage of peroxisomal proteins. The changes in concentration of peroxisomal oxidases and soluble catalase after Su-13437 allow the calculation of their half-lives. These are the same as those found for total catalase, in normal and treated rats, after allyl isopropyl acetamide: about 1.3 days, a result compatible with peroxisome degradation by autophagy. A sequential increase in liver RNA concentration, [14C]leucine incorporation into DOC-soluble proteins and into immunoprecipitable catalase, and an increase in liver size and peroxisomal volume per gram liver, characterize the trophic effect of the drug used. In males, Su-13437 is more active than CPIB, another peroxisome proliferation-inducing drug; in females, only Su-13437 is active. PMID:406

  13. Discovery of a benzofuran derivative (MBPTA) as a novel ROCK inhibitor that protects against MPP⁺-induced oxidative stress and cell death in SH-SY5Y cells.

    PubMed

    Chong, Cheong-Meng; Shen, Mingyun; Zhou, Zhong-Yan; Pan, Peichen; Hoi, Pui-Man; Li, Shang; Liang, Wang; Ai, Nana; Zhang, Lun-Qing; Li, Cheuk-Wing; Yu, Huidong; Hou, Tingjun; Lee, Simon Ming-Yuen

    2014-09-01

    Parkinson disease (PD) is a neurodegenerative disease with multifactorial etiopathogenesis. The discovery of drug candidates that act on new targets of PD is required to address the varied pathological aspects and modify the disease process. In this study, a small compound, 2-(5-methyl-1-benzofuran-3-yl)-N-(5-propylsulfanyl-1,3,4-thiadiazol-2-yl) acetamide (MBPTA) was identified as a novel Rho-associated protein kinase inhibitor with significant protective effects against 1-methyl-4-phenylpyridinium ion (MPP(+))-induced damage in SH-SY5Y neuroblastoma cells. Further investigation showed that pretreatment of SH-SY5Y cells with MBPTA significantly suppressed MPP(+)-induced cell death by restoring abnormal changes in nuclear morphology, mitochondrial membrane potential, and numerous apoptotic regulators. MBPTA was able to inhibit MPP(+)-induced reactive oxygen species (ROS)/NO generation, overexpression of inducible NO synthase, and activation of NF-κB, indicating the critical role of MBPTA in regulating ROS/NO-mediated cell death. Furthermore, MBPTA was shown to activate PI3K/Akt survival signaling, and its cytoprotective effect was abolished by PI3K and Akt inhibitors. The structural comparison of a series of MBPTA analogs revealed that the benzofuran moiety probably plays a crucial role in the anti-oxidative stress action. Taken together, these results suggest that MBPTA protects against MPP(+)-induced apoptosis in a neuronal cell line through inhibition of ROS/NO generation and activation of PI3K/Akt signaling.

  14. DIRECT DETECTION OF COMPLEX ORGANIC PRODUCTS IN ULTRAVIOLET (Lyα) AND ELECTRON-IRRADIATED ASTROPHYSICAL AND COMETARY ICE ANALOGS USING TWO-STEP LASER ABLATION AND IONIZATION MASS SPECTROMETRY

    SciTech Connect

    Henderson, Bryana L.; Gudipati, Murthy S.

    2015-02-10

    As discovery of complex molecules and ions in our solar system and the interstellar medium has proliferated, several groups have turned to laboratory experiments in an effort to simulate and understand these chemical processes. So far only infrared (IR) and ultraviolet (UV) spectroscopy has been able to directly probe these reactions in ices in their native, low-temperature states. Here we report for the first time results using a complementary technique that harnesses two-step two-color laser ablation and ionization to measure mass spectra of energetically processed astrophysical and cometary ice analogs directly without warming the ices—a method for hands-off in situ ice analysis. Electron bombardment and UV irradiation of H{sub 2}O, CH{sub 3}OH, and NH{sub 3} ices at 5 K and 70 K led to complex irradiation products, including HCO, CH{sub 3}CO, formamide, acetamide, methyl formate, and HCN. Many of these species, whose assignment was also strengthened by isotope labeling studies and correlate with IR-based spectroscopic studies of similar irradiated ices, are important ingredients for the building blocks of life. Some of them have been detected previously via astronomical observations in the interstellar medium and in cometary comae. Other species such as CH{sub 3}CO (acetyl) are yet to be detected in astrophysical ices or interstellar medium. Our studies suggest that electron and UV photon processing of astrophysical ice analogs leads to extensive chemistry even in the coldest reaches of space, and lend support to the theory of comet-impact-induced delivery of complex organics to the inner solar system.

  15. Direct Detection of Complex Organic Products in Ultraviolet (Lyα) and Electron-irradiated Astrophysical and Cometary Ice Analogs Using Two-step Laser Ablation and Ionization Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Henderson, Bryana L.; Gudipati, Murthy S.

    2015-02-01

    As discovery of complex molecules and ions in our solar system and the interstellar medium has proliferated, several groups have turned to laboratory experiments in an effort to simulate and understand these chemical processes. So far only infrared (IR) and ultraviolet (UV) spectroscopy has been able to directly probe these reactions in ices in their native, low-temperature states. Here we report for the first time results using a complementary technique that harnesses two-step two-color laser ablation and ionization to measure mass spectra of energetically processed astrophysical and cometary ice analogs directly without warming the ices—a method for hands-off in situ ice analysis. Electron bombardment and UV irradiation of H2O, CH3OH, and NH3 ices at 5 K and 70 K led to complex irradiation products, including HCO, CH3CO, formamide, acetamide, methyl formate, and HCN. Many of these species, whose assignment was also strengthened by isotope labeling studies and correlate with IR-based spectroscopic studies of similar irradiated ices, are important ingredients for the building blocks of life. Some of them have been detected previously via astronomical observations in the interstellar medium and in cometary comae. Other species such as CH3CO (acetyl) are yet to be detected in astrophysical ices or interstellar medium. Our studies suggest that electron and UV photon processing of astrophysical ice analogs leads to extensive chemistry even in the coldest reaches of space, and lend support to the theory of comet-impact-induced delivery of complex organics to the inner solar system.

  16. [(11)C]DAC-PET for noninvasively monitoring neuroinflammation and immunosuppressive therapy efficacy in rat experimental autoimmune encephalomyelitis model.

    PubMed

    Xie, Lin; Yamasaki, Tomoteru; Ichimaru, Naotsugu; Yui, Joji; Kawamura, Kazunori; Kumata, Katsushi; Hatori, Akiko; Nonomura, Norio; Zhang, Ming-Rong; Li, Xiao-Kang; Takahara, Shiro

    2012-03-01

    Neuroimaging measures have potential for monitoring neuroinflammation to guide treatment before the occurrence of significant functional impairment or irreversible neuronal damage in multiple sclerosis (MS). N-Benzyl-N-methyl-2-(7-[(11)C]methyl-8-oxo-2-phenyl-7,8-dihydro-9H-purin-9-yl) acetamide ([(11)C]DAC), a new developed positron emission tomography (PET) probe for translocator protein 18 kDa (TSPO), has been adopted to evaluate the neuroinflammation and treatment effects of experimental autoimmune encephalomyelitis (EAE), an animal model of MS. [(11)C]DAC-PET enabled visualization of neuroinflammation lesion of EAE by tracing TSPO expression in the spinal cords; the maximal uptake value reached in day 11 and 20 EAE rats with profound inflammatory cell infiltration compared with control, day 0 and 60 EAE rats. Biodistribution studies and in vitro autoradiography confirmed these in vivo imaging results. Doubling immunohistochemical studies showed the infiltration and expansion of CD4+ T cells and CD11b+ microglia; CD68+ macrophages were responsible for the increased TSPO levels visualized by [(11)C]DAC-PET. Furthermore, mRNA level analysis of the cytokines by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) revealed that TSPO+/CD4 T cells, TSPO+ microglia and TSPO+ macrophages in EAE spinal cords were activated and secreted multiple proinflammation cytokines to mediate inflammation lesions of EAE. EAE rats treated with an immunosuppressive agent: 2-amino-2-[2-(4-octylphenyl)ethyl] propane-1,3-diolhydrochloride (FTY720), which exhibited an absence of inflammatory cell infiltrates, displaying a faint radioactive signal compared with the high accumulation of untreated EAE rats. These results indicated that [(11)C] DAC-PET imaging is a sensitive tool for noninvasively monitoring the neuroinflammation response and evaluating therapeutic interventions in EAE.

  17. Inhibition of STAT3 activation by KT-18618 via the disruption of the interaction between JAK3 and STAT3.

    PubMed

    Shin, Dae-Seop; Jung, Seung Nam; Yun, Jieun; Lee, Chang Woo; Han, Dong Cho; Kim, Bumtae; Min, Yong Ki; Kang, Nam Sook; Kwon, Byoung-Mog

    2014-05-01

    The constitutive activation of STAT3 in human cancers causes the abnormal proliferation and survival of cancer cells, and thus, STAT3 is a therapeutic target of antitumor drugs. We screened a small-molecule library of 8600 synthetic compounds from the "Korea Chemical Bank" to identify inhibit STAT3 activity using a cell-based luciferase assay system. KT-18618 ((Z)-N-(4-chlorophenyl)-N-methyl-2-[1,3,3,3,-tetrafluoro-2-(thiophen-2-yl)prop-1-enyloxy]-acetamide) was selected as a novel inhibitor of the JAK/STAT3 pathway. KT-18618 inhibited STAT3 phosphorylation and the expression of STAT3-regulated genes. The inhibition of STAT3 phosphorylation led to the apoptosis of MDA-MB-468 cells. We postulated that the inhibition of the JAK family of proteins or c-Src inhibited STAT3 phosphorylation. Interestingly, the phosphorylation of these kinases was only mildly inhibited, but the phosphorylation of STAT3 was completely inhibited. This result implies that the inhibition of STAT3 phosphorylation by KT-18618 is an independent event that occurs through the phosphorylation of upstream kinases. Co-immunoprecipitation experiments revealed that KT-18618 inhibited the JAK3-STAT3 interaction. Moreover, JAK3 molecules were captured by biotinylated KT-18618, implying that KT-18618 bound to JAK3 molecules. Additionally, 1μM KT-18618 inhibited JAK3 kinase activity by approximately 28% in an in vitro kinase assay. From these results, we suggest that KT-18618 binds to JAK3 molecules and disrupts the JAK3-STAT3 interaction, which leads to the inhibition of STAT3 phosphorylation. KT-18618 is the first inhibitor of the JAK3-STAT3 interaction.

  18. Combining bifunctional chelator with (3 + 2)-cycloaddition approaches: synthesis of dual-function technetium complexes.

    PubMed

    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.

  19. SEPALLATA1/2-suppressed mature apples have low ethylene, high auxin and reduced transcription of ripening-related genes

    PubMed Central

    Schaffer, Robert J.; Ireland, Hilary S.; Ross, John J.; Ling, Toby J.; David, Karine M.

    2012-01-01

    Background and aims Fruit ripening is an important developmental trait in fleshy fruits, making the fruit palatable for seed dispersers. In some fruit species, there is a strong association between auxin concentrations and fruit ripening. We investigated the relationship between auxin concentrations and the onset of ethylene-related ripening in Malus × domestica (apples) at both the hormone and transcriptome levels. Methodology Transgenic apples suppressed for the SEPALLATA1/2 (SEP1/2) class of gene (MADS8/9) that showed severely reduced ripening were compared with untransformed control apples. In each apple type, free indole-3-acetic acid (IAA) concentrations were measured during early ripening. The changes observed in auxin were assessed in light of global changes in gene expression. Principal results It was found that mature MADS8/9-suppressed apples had a higher concentration of free IAA. This was associated with increased expression of the auxin biosynthetic genes in the indole-3-acetamide pathway. Additionally, in the MADS8/9-suppressed apples, there was less expression of the GH3 auxin-conjugating enzymes. A number of genes involved in the auxin-regulated transcription (AUX/IAA and ARF classes of genes) were also observed to change in expression, suggesting a mechanism for signal transduction at the start of ripening. Conclusions The delay in ripening observed in MADS8/9-suppressed apples may be partly due to high auxin concentrations. We propose that, to achieve low auxin associated with fruit maturation, the auxin homeostasis is controlled in a two-pronged manner: (i) by the reduction in biosynthesis and (ii) by an increase in auxin conjugation. This is associated with the change in expression of auxin-signalling genes and the up-regulation of ripening-related genes. PMID:23346344

  20. Hydrophilic prodrug approach for reduced pigment binding and enhanced transscleral retinal delivery of celecoxib.

    PubMed

    Malik, Pradip; Kadam, Rajendra S; Cheruvu, Narayan P S; Kompella, Uday B

    2012-03-05

    Transscleral retinal delivery of celecoxib, an anti-inflammatory and anti-VEGF agent, is restricted by its poor solubility and binding to the melanin pigment in choroid-RPE. The purpose of this study was to develop soluble prodrugs of celecoxib with reduced pigment binding and enhanced retinal delivery. Three hydrophilic amide prodrugs of celecoxib, celecoxib succinamidic acid (CSA), celecoxib maleamidic acid (CMA), and celecoxib acetamide (CAA) were synthesized and characterized for solubility and lipophilicity. In vitro melanin binding to natural melanin (Sepia officinalis) was estimated for all three prodrugs. In vitro transport studies across isolated bovine sclera and sclera-choroid-RPE (SCRPE) were performed. Prodrug with the highest permeability across SCRPE was characterized for metabolism and cytotoxicity and its in vivo transscleral delivery in pigmented rats. Aqueous solubilities of CSA, CMA, and CAA were 300-, 182-, and 76-fold higher, respectively, than celecoxib. Melanin binding affinity and capacity were significantly lower than for celecoxib for all three prodrugs. Rank order for the % in vitro transport across bovine sclera and SCRPE was CSA > CMA ~ CAA ~ celecoxib, with the transport being 8-fold higher for CSA than celecoxib. CSA was further assessed for its metabolic stability and in vivo delivery. CSA showed optimum metabolic stability in all eye tissues with only 10-20% conversion to parent celecoxib in 30 min. Metabolic enzymes responsible for bioconversion included amidases, esterase, and cytochrome P-450. In vivo delivery in pigmented BN rats showed that CSA had 4.7-, 1.4-, 3.3-, 6.0-, and 4.5-fold higher delivery to sclera, choroid-RPE, retina, vitreous, and lens than celecoxib. CSA has no cytotoxicity in ARPE-19 cells in the concentration range of 0.1 to 1000 μM. Celecoxib succinamidic acid, a soluble prodrug of celecoxib with reduced melanin binding, enhances transscleral retinal delivery of celecoxib.