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Sample records for n-substituted aryl compounds

  1. Palladium-Catalyzed Carbonylation of Aryl Bromides with N-Substituted Cyanamides

    DEFF Research Database (Denmark)

    Lian, Zhong; Friis, Stig D.

    2014-01-01

    The palladium(0)-catalyzed three-component coupling reaction of aryl bromides, carbon monoxide, and N-alkyl cyan­amides has been developed employing a two-chamber system with ex situ generation of carbon monoxide from a silacarboxylic acid. The reactions proceeded well and were complete with a reaction time of only five hours leading to the corresponding N-alkyl cyanamides in good yields. The methodology was further extended to 13C isotope labeling of the carbonyl group through the use of a 13CO produced from the corresponding 13C-labeled version of the sila­carboxylic acid.

  2. N-substituted derivatives of 5-(4-chlorophenyl)-1,3,4-oxadiazol-2-yl-2-sulfanyl acetamide as valuable bioactive compounds

    International Nuclear Information System (INIS)

    In the described research work, a new series of N-substituted derivatives of 5-(4-chlorophenyl)-1,3,4-Oxadiazol-2-yl-2-sulfanyl acetamide has been synthesized. The synthesis was carried out by converting 4-chlorobenzoic acid (1) into ethyl 4-chlorobenzoate (2), 4-chlorobenzohydrazide (3) and then 5-(4-chlorophenyl)-1,3,4-Oxadiazol-2-thiol (4) respectively. The target molecules 6a-o were synthesized by reacting compound 4 with different N-alkyl/aryl substituted 2-bromoacetamide (5a-o) in equimolar ratios of using DMF and sodium hydride (NaH). The structure of all the synthesized compounds was confirmed by spectral data like EI-MS, IR and 1H-NMR. The compounds were also analysed for antimicrobial and hemolytic activity and most of them were found active against the selected microbial species at variable extent relative to reference standards. But 6f and 6o were the active against the selected panel of microbes and former was most potent one. This series revealed less toxicity and may consider for further biological screening and application trial except 6g and 6j, exhibiting high cytotoxicity. (author)

  3. N-substituted iminodiacetic acids

    International Nuclear Information System (INIS)

    The chemical preparation of several new N-substituted iminodiacetic acid derivatives are described. These compounds when complexed with sup(99m)Tc provide useful radiopharmaceuticals for the external imaging of the hepatobiliary system. (U.K.)

  4. Synthesis and fungicidal activity of some sulphide derivatives of O-phenyl-N-substituted phenylcarbamates

    OpenAIRE

    Adelowo, F. E.; Ojo, I. A. O.; Amuda, O. S.

    2011-01-01

    Monosulphides of O-phenyl-N-substituted phenylcar- bamates were prepared by the reaction between O- phenyl-N-substituted phenylcarbamates and sulph- ur dichloride while the corresponding disulphides were prepared by the reaction between O-phenyl-N- substituted phenylcarbamates and sulphur monoch- loride. The synthesized compounds were characte-rized by elemental analysis, thin layer chromatogra-phy (TLC), Fourier-transform infrared, 1H and 13C nuclear magnetic resonance spectroscopic techniqu...

  5. Synthesis and In Vitro Antigungal Properties of 4-Aryl-4-Narylamine-1-butenes and Related Compounds

    OpenAIRE

    Urbina, J; Palma, A.(Laboratorio de Instrumentacao e Fisica Experimental de Particulas-LIP, Lisbon, Portugal; Faculdade de Ciências, Universidade de Lisboa, Lisbon, Portugal; Department of Physics, University of Coimbra, Coimbra, Portugal; Centro de Física Nuclear da Universidade de Lisboa, Lisbon, Portugal; Departamento de Fisica, Universidade do Minho, Braga, Portugal; Departamento de Fisica Teorica y del Cosmos and CAFPE, Universidad de Granada, Granada, Spain; Dep Fisica and CEFITEC of Faculdade de Ciencias e Tecnologia, Universidade Nova de Lisboa, Caparica, Portugal); S. López; C. Devia; R. Enriz; S. ZACCHINO; V. Kouznetsov

    2000-01-01

    A new series of 4-aryl and 4-alkyl-4-N-arylamine-1-butenes (homoallylamines) were synthesized and some of them transformed to 4-aryl or alkylquinolines. All of them showed strong antifungal activities against human pathogenic fungi in vitro, being Epidermophyton floccosum the most susceptible species.

  6. Evaluation of the Toxicity of 5-Aryl-2-Aminoimidazole-Based Biofilm Inhibitors against Eukaryotic Cell Lines, Bone Cells and the Nematode Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    Hans Steenackers

    2014-10-01

    Full Text Available Previously, we have synthesized several series of compounds based on the 5-aryl-2-aminoimidazole scaffold, which showed a preventive activity against microbial biofilms. We here studied the cytotoxicity of the most active compounds of each series. First, the cytostatic activity was investigated against a number of tumor cell lines (L1210, CEM and HeLa. A subset of monosubstituted 5-aryl-2-aminoimidazoles showed a moderate safety window, with therapeutic indices (TIs ranging between 3 and 20. Whereas introduction of a (cyclo-alkyl chain at the N1-position strongly reduced the TI, introduction of a (cyclo-alkyl chain or a triazole moiety at the 2N-position increased the TI up to 370. Since a promising application of preventive anti-biofilm agents is their use in anti-biofilm coatings for orthopedic implants, their effects on cell viability and functional behavior of human osteoblasts and bone marrow derived mesenchymal stem cells were tested. The 2N-substituted 5-aryl-2-aminoimidazoles consistently showed the lowest toxicity and allowed survival of the bone cells for up to 4 weeks. Moreover they did not negatively affect the osteogenic differentiation potential of the bone cells. Finally, we examined the effect of the compounds on the survival of Caenorhabditis elegans, which confirmed the higher safety window of 2N-substituted 5-aryl-2-aminoimidazoles.

  7. Synthesis and Fungicidal activity of some sulphide derivatives of O-Ethyl-N-substituted phenylcarbamates

    International Nuclear Information System (INIS)

    Monosulphides of O-ethyl-N-substituted phenylcarbamates were prepared by the reaction between O-ethyl-N-substituted phenylcarbamates and sulphur dichloride, while the corresponding disulphides were prepared by the reaction between O-ethyl-N-substituted phenylcarbamates and sulphur monochloride. The synthesized compounds were characterized by elemental analysis, thin layer chromatography (TLC), Fourier-transform infrared, and /sup 1/H and /sup 13/C nuclear magnetic resonance spectroscopic techniques. In vitro fungicidal assay of these sulphides against Fusarium oxysporum, Aspergillus niger, Aspergillus flavus and Rhizopus stolonifer showed that they had Greater fungicidal activity than their parent carbamates. The synthesized sulphides were more active towards A. Niger and A. flavus. Unlike the parent carbamates, the type of substituents attached to the aromatic nucleus of these sulphides had little or no effect on their fungicidal activity as there was insignificant variation in the fungicidal activity of the monosulphide and the disulphide derivatives of O-ethyl-N-substituted phenylcarbamates. (author)

  8. Synthesis and fungicidal activity of some sulphide derivatives of O-phenyl-N-substituted phenylcarbamates

    Directory of Open Access Journals (Sweden)

    F. E. Adelowo

    2011-11-01

    Full Text Available Monosulphides of O-phenyl-N-substituted phenylcar- bamates were prepared by the reaction between O- phenyl-N-substituted phenylcarbamates and sulph- ur dichloride while the corresponding disulphides were prepared by the reaction between O-phenyl-N- substituted phenylcarbamates and sulphur monoch- loride. The synthesized compounds were characte-rized by elemental analysis, thin layer chromatogra-phy (TLC, Fourier-transform infrared, 1H and 13C nuclear magnetic resonance spectroscopic techniques. In vitro fungicidal assay of these sulphides against Fusarium oxysporum, Aspergillus niger, Aspergillus flavus and Rhizopus stolonifer showed that they were more fungicidal than their parent carbamates. The synthesized sulphides were more active towards As-pergillus niger and Aspergillus flavus. There was little or no variations in the fungicidal activities of the synthesized monosulphides and disulphides of O-phen- yl-N-substituted phenyl carbamates.

  9. A regioselective synthesis of benzopinacolones through aerobic dehydrogenative ?-arylation of the tertiary sp3 C-H bond of 1,1-diphenylketones with aromatic and heteroaromatic compounds.

    Science.gov (United States)

    More, Nagnath Yadav; Jeganmohan, Masilamani

    2015-01-12

    A regioselective synthesis of symmetrical and unsymmetrical benzopinacolones through aerobic dehydrogenative ?-arylation at the tertiary sp(3) C-H bond of substituted 1,1-diphenylketones with aromatic and heteroaromatic compounds, in the presence of K2S2O8 in CF3COOH at room temperature, is described. The reaction is proposed to go via a carbocation intermediate, which could be generated directly from cleavage of the sp(3) C-H bond of 1,1-diphenylketone. Subsequent ?-arylation was achieved at the methene sp(3) carbon atom of the substituted ketone. A variety of substituted aromatic and heteroaromatic compounds were compatible with this reaction. In addition, benzopinacolones were converted into sterically hindered, tetrasubstituted alkenes and polycyclic aromatic compounds. PMID:25394565

  10. Direct Synthesis of 5-Aryl Barbituric Acids by Rhodium(II)-Catalyzed Reactions of Arenes with Diazo Compounds**

    Science.gov (United States)

    Best, Daniel; Burns, David J; Lam, Hon Wai

    2015-01-01

    A commercially available rhodium(II) complex catalyzes the direct arylation of 5-diazobarbituric acids with arenes, allowing straightforward access to 5-aryl barbituric acids. Free N—H groups are tolerated on the barbituric acid, with no complications arising from N—H insertion processes. This method was applied to the concise synthesis of a potent matrix metalloproteinase (MMP) inhibitor. PMID:25959544

  11. Indium(III)-catalyzed synthesis of N-substituted pyrroles under solvent-free conditions

    Scientific Electronic Library Online (English)

    Jiu-Xi, Chen; Miao-Chang, Liu; Xiao-Liang, Yang; Jin-Chang, Ding; Hua-Yue, Wu.

    Full Text Available Vários pirróis N-substituídos foram sintetizados pela reação de ?-dicetonas (R¹C(O)CH2CH2C(O)R²: R¹, R² = Me, Ph) com aminas (RNH2: R = Alkyl, Aryl, TsNH) ou diaminas (1,6-diaminohexano and 1,2-diaminoetano) na presença de tribrometo de índio, tricloreto de índio ou trifluorometanossulfonato de índi [...] o a temperatura ambiente e sem solventes. O protocolo envolve operações simples e os produtos são isolados em excelentes rendimentos (81-98%). Abstract in english A variety of N-substituted pyrroles have been synthesized by reacting ?-diketones (R¹C(O)CH2CH2C(O)R²: R¹, R² = Me, Ph) with amines (RNH2: R=Alkyl, Aryl, TsNH) or diamines (1,6-diaminohexane and 1,2-diaminoethane) in the presence of indium tribromide, indium trichloride or indium trifluoromethanesul [...] fonate at room temperature under solvent-free conditions. The experiment protocol features simple operations, and the products are isolated in high to excellent yields (81-98%).

  12. SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL SCREENING OF VARIOUS N-SUBSTITUTED DERIVATIVES OF SULFONAMIDES

    Directory of Open Access Journals (Sweden)

    AZIZ-UR-REHMAN, WAJEEHA TANVEER, MUHAMMAD ATHAR ABBASI, SUMBAL AFROZ, KHALID MOHAMMED KHAN, MUHAMMAD ASHRAF, AND IFTIKHAR AFZAL

    2011-12-01

    Full Text Available In the present study, a series of N-substituted sulfonamides have been synthesized. The reaction ofbenzene sulfonyl chloride (1 with O-anisidine (2 yielded N-(2-methoxyphenyl benzenesulfonamide (3, which onbromination with bromine in the presence of acetic acid gave N-(4,5-dibromo-2-methoxyphenylbenzenesulfonamide(6. The two products (3 and (6 further on treatment with alkyl halides/acyl halide in the presence of sodium hydrideyielded thirteen different N-substituted sulfonamides. The compounds were characterized by IR, EIMS and 1H-NMRand screened against acetyl cholinesterase, butyryl cholinesterase and lipoxygenase enzymes. The results revealedthat N-butyl-N-(4, 5-dibromo-2-methoxyphenylbenzene sulfonamide (6d and N-pentyl-N-(4,5-dibromo-2-methoxyphenylbenzenesulfonamide (6e exhibited good inhibitory potential against lipoxygenase.

  13. Synthesis, characterization and dynamic NMR studies of a novel chalcone based N-substituted morpholine derivative

    Science.gov (United States)

    Baskar, R.; Baby, C.; Moni, M. S.; Subramanian, K.

    2013-05-01

    The synthesis of a novel chalcone based N-substituted morpholine derivative namely, (E)-1-(biphenyl-4-yl)-3-(4-(5-morpholinopentyloxy) phenyl) prop-2-en-1-one (BMPP), using a two step protocol is reported. The compound is characterized by FTIR, GC-MS and FTNMR spectroscopy techniques. Advanced 2D NMR techniques such as gradient enhanced COSY, HSQC, HMBC and NOESY were employed to establish through-bond and through-space correlations. Dynamic NMR measurements were carried out to obtain the energy barrier to ring inversion of the morpholine moiety.

  14. Synthesis of N-substituted N-nitrosohydroxylamines as inhibitors of mushroom tyrosinase.

    Science.gov (United States)

    Shiino, M; Watanabe, Y; Umezawa, K

    2001-05-01

    A series of N-substituted N-nitrosohydroxylamines including six new compounds were synthesized and examined for inhibition of mushroom tyrosinase. Corresponding hydroxylamines were reacted with n-butyl nitrite to give substituted nitrosohydroxylamines as their ammonium salt. The N-substituted hydroxylamines were prepared from the primary amines via the oxaziridine, or from the carbonyl compounds via the oxime. Most of the nitrosohydroxylamines tested inhibited mushroom tyrosinase. Among them, N-cyclopentyl-N-nitrosohydroxylamine exhibited the most potent activity (IC(50)=0.6 microM), as powerful as that of tropolone, one of the most powerful inhibitors. As removal of nitroso or hydroxyl moiety, the enzyme inhibitory activity was completely diminished. Both N-nitroso group and N-hydroxy group were suggested to be essential for the activity, probably by interacting with the copper ion at the active site of the enzyme. Lineweaver-Burk plotting showed that cupferron was a competitive inhibitor but that N-cyclopentyl-N-nitrosohydroxylamine was not. PMID:11377181

  15. MICROWAVE ASSISTED SYNTHESIS OF FLUORO, CHLORO, 2-N (SUBSTITUTED SCHIFF’S BASES) AMINO BENZOTHIAZOLES FOR THEIR ANTIMICROBIAL AND ANTITUBERCULAR ACTIVITIES

    OpenAIRE

    Hipparagi, Dr S. M.

    2010-01-01

    The present research work is aimed to synthesize a series of various substituted benzothiazole derivatives containing 7-chloro-6-fluoro-N(substituted hydrozones)- benzothiazole.Structures of compounds have been established by means of IR, 1H-NMR and elemental analysis. All the compounds were evaluated foe antibacterial, antifungal and antitubercular activities. Most of the compounds have shown significant antibacterial, antifungal and antitubercular activity when compared with the standard ...

  16. MICROWAVE ASSISTED SYNTHESIS OF FLUORO, CHLORO, 2-N (SUBSTITUTED SCHIFF’S BASES AMINO BENZOTHIAZOLES FOR THEIR ANTIMICROBIAL AND ANTITUBERCULAR ACTIVITIES

    Directory of Open Access Journals (Sweden)

    Dr. S. M. Hipparagi

    2010-05-01

    Full Text Available The present research work is aimed to synthesize a series of various substituted benzothiazole derivatives containing 7-chloro-6-fluoro-N(substituted hydrozones- benzothiazole.Structures of compounds have been established by means of IR, 1H-NMR and elemental analysis. All the compounds were evaluated foe antibacterial, antifungal and antitubercular activities. Most of the compounds have shown significant antibacterial, antifungal and antitubercular activity when compared with the standard drug.

  17. Modern Arylation Methods

    CERN Document Server

    Ackermann, Lutz

    2009-01-01

    Today, arylation methods are belonging to the most important reaction types in organic synthesis. Lutz Ackermann, a young and ambitious professor has gathered a number of top international authors to present the first comprehensive book on the topic. Starting from a historical review, the book covers hot topics like Palladium-catalyzed arylation of N-H and alpha-C-H-acidic Bonds, Copper-catalyzed arylation of N-H and O-H Bonds, direct arylation reactions, carbanion aromatic synthesis, arylation reactions of alkenes, alkynes and much more. This compact source of high quality information is indi

  18. Lewis acid free high speed synthesis of nimesulide-based novel N-substituted cyclic imides

    Scientific Electronic Library Online (English)

    Kavitha, Kankanala; Vangala Ranga, Reddy; Khagga, Mukkanti; Sarbani, Pal.

    1060-10-01

    Full Text Available A primeira síntese de novas imidas cíclicas derivadas de nimessulida foi realizada via reação de uma imina preparada a partir de nimessulida com anidridos apropriados na presença de acetato de sódio. Usando este processo, uma variedade de imidas cíclicas N-substituídas foi preparada em bons rendimen [...] tos em ácido acético glacial. Alguns dos compostos sintetizados mostraram atividades anti-inflamatórias quando testados in vivo. Abstract in english The first synthesis of nimesulide-based novel cyclic imides has been accomplished via the reaction of an amine prepared from nimesulide with appropriate anhydrides in the presence of sodium acetate. Using this process a variety of N-substituted cyclic imides was prepared in good yields in glacial ac [...] etic acid. Some of the compounds synthesized showed anti-inflammatory activities when tested in vivo.

  19. Synthesis, Antiviral and Cytotoxicity Studies of Novel N-substituted Indophenazine Derivatives.

    Science.gov (United States)

    Selvam, P; Lakra, D R; Pannecouque, C; De Clercq, E

    2012-05-01

    A series of novel N-substituted indophenazine derivatives were synthesised and screened for antiviral activity against a panel of human pathogenic viruses. New compounds were synthesised through modifying the N-hydrogen of indophenazine moiety with different substitution and formaldehyde by Mannich reaction. The structure of the synthetic compounds was characterised by means of infra red and nuclear magnetic resonance spectral data. The compound 10H-indolo-2-Amino pyridine [3,2-b] quinoxalines inhibits Herpes simplex virus-1 and vaccinia virus at a concentration of 12 ?g/ml, and the cytotoxicy was found to be 100 ?g/ml. 4-Aminobenzene sulfonamide-10H-indolo [3,2-b] quinoxalines inhibit vaccinia virus at a concentration of 12 ?g/ml and cytotoxicy was found to be 100 ?g/ml. The anti-HIV activities of the new compounds were also screened for in vitro antiviral activity against replication of HIV-1 (IIIB) and HIV-2 (ROD) in MT-4 cells using zidovudine (AZT) as standard. Pthalimide derivative inhibited the replication of HIV-2 (EC(50)=11.60 ?g/ml and CC(50)=61.63 ?g/ml) in MT-4 cells. PMID:23440065

  20. ?-Alkyl and ?-aryl complexes

    International Nuclear Information System (INIS)

    Methods of preparation, solubility, reactivity, as well as molecular and crystal structure of ?-alkyl and ?-aryl complexes of rare earths of different composition are described. Di- and trisubstituted alkyl (aryl)lanthanides, their halogen derivatives of RLnHal type, afe-complexes, complexes of Cp2LnR type and ilide derivatives are considered in particular. 173 refs.; 17 figs.; 12 tabs

  1. Vibrational and electronic spectra of N-aryl ring substituted (Z)-N-(4-amino-5-(4-chlorophenyl)-3-phenylthiazol-2(3H)-ylidene)benzamide compounds

    Science.gov (United States)

    Rao, Y. B. Shankar; Mohan, S. Ram; Veeraiah, V.

    2015-04-01

    In the present paper the vibrational, electronic and nonlinear optical properties of three N-aryl ring substituted (Z)-N-(4-amino-5-(4-chlorophenyl)-3-phenylthiazol-2(3H)-ylidene)benzamide compounds have been investigated by UV-vis, FT-IR and FT-Raman spectroscopic measurements. The electrochemical properties of the compounds were measured by cyclic voltammetry. Density functional theory calculations with B3LYP/6-31 + G(d,p) basis set was used to determine the ground state molecular geometries (bond lengths and bond angles), harmonic vibrational frequencies, infrared intensities and Raman activities of title compounds. Potential energy distributions (PEDs) and normal modes, for the spectral data computed at B3LYP/6-31 + G(d,p) level, have also been obtained from force-field calculations. A comparison of the theoretical spectra and experimental FT-IR and FT-Raman spectra of the title molecule has been made and full vibrational assignments of the observed spectra have been proposed. The substituent effect on the electronic properties of the title compounds were investigated by time-dependent density functional theory calculations.

  2. Novel N-substituted aminobenzamide scaffold derivatives targeting the dipeptidyl peptidase-IV enzyme

    Directory of Open Access Journals (Sweden)

    Al-Balas QA

    2014-01-01

    Full Text Available Qosay A Al-Balas,1 Munia F Sowaileh,1 Mohammad A Hassan,1 Amjad M Qandil,1,2 Karem H Alzoubi,3 Nizar M Mhaidat,3 Ammar M Almaaytah,4 Omar F Khabour51Department of Medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan; 2Pharmaceutical Sciences Department, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia; 3Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan; 4Department of Pharmaceutical Technology, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan; 5Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, Jordan University of Science and Technology, Irbid, JordanBackground: The dipeptidyl peptidase-IV (DPP-IV enzyme is considered a pivotal target for controlling normal blood sugar levels in the body. Incretins secreted in response to ingestion of meals enhance insulin release to the blood, and DPP-IV inactivates these incretins within a short period and stops their action. Inhibition of this enzyme escalates the action of incretins and induces more insulin to achieve better glucose control in diabetic patients. Thus, inhibition of this enzyme will lead to better control of blood sugar levels.Methods: In this study, computer-aided drug design was used to help establish a novel N-substituted aminobenzamide scaffold as a potential inhibitor of DPP-IV. CDOCKER software available from Discovery Studio 3.5 was used to evaluate a series of designed compounds and assess their mode of binding to the active site of the DPP-IV enzyme. The designed compounds were synthesized and tested against a DPP-IV enzyme kit provided by Enzo Life Sciences. The synthesized compounds were characterized using proton and carbon nuclear magnetic resonance, mass spectrometry, infrared spectroscopy, and determination of melting point.Results: Sixty-nine novel compounds having an N-aminobenzamide scaffold were prepared, with full characterization. Ten of these compounds showed more in vitro activity against DPP-IV than the reference compounds, with the most active compounds scoring 38% activity at 100 µM concentration.Conclusion: The N-aminobenzamide scaffold was shown in this study to be a valid scaffold for inhibiting the DPP-IV enzyme. Continuing work could unravel more active compounds possessing the same scaffold.Keywords: diabetes mellitus, dipeptidyl peptidase-IV, aminobenzamide derivatives, hypoglycemic activity, CDOCKER software

  3. Thermolysis of Semicarbazones to the Corresponding Azines Through Reactive N-Substituted Isocyanate Intermediates

    Directory of Open Access Journals (Sweden)

    N. K. Chudgar

    2000-04-01

    Full Text Available Thermolysis of semicarbazones (I to azines (II occurs through reactive N-substituted isocyanate intermediates (Ia which can be converted in situ to carbamates and Nsubstituted ureas.

  4. N-substituted 3-acetyltetramic acid derivatives as antibacterial agents.

    Science.gov (United States)

    Yendapally, Raghunandan; Hurdle, Julian G; Carson, Elizabeth I; Lee, Robin B; Lee, Richard E

    2008-03-13

    In order to expand the structure-activity relationship of tetramic acid molecules with structural similarity to the antibiotic reutericyclin, 22 compounds were synthesized and tested against a panel of clinically relevant bacteria. Key structural changes on the tetramic acid core affected antibacterial activity. Various compounds in the N-alkyl 3-acetyltetramic acid series exhibited good activity against Gram-positive bacterial pathogens including Bacillus anthracis, Propionibacterium acnes, Enterococcus faecalis, and both Methicillin-sensitive and -resistant Staphylococcus aureus. PMID:18281930

  5. Synthesis and Biological Activity of N-Substituted-3-chloro-2-azetidinones

    Directory of Open Access Journals (Sweden)

    Nandini R. Pai

    2007-11-01

    Full Text Available 2-Aminobenzothiazole-6-carboxylic acid (1, on condensation with chloroacetylchloride yielded 2-(2-chloroacetylaminobenzothiazole-6-carboxylic acid (2, which onamination with hydrazine hydrate yielded in turn 2-(2-hydrazinoacetylaminobenzo-thiazole-6-carboxylic acid (3. Compound 3, on condensation with various aromaticaldehydes afforded a series of 2-{2-[N’-(arylidenehydrazino]acetylamino}benzothiazole-6-carboxylic acids 4a-h, which upon dehydrative annulation in the presence ofchloroacetyl chloride and triethylamine yielded 2-{2-[3-chloro-2-(aryl-4-oxoazetidin-1-ylamino]-acetylamino}benzothiazole-6-carboxylic acids 5a-h. The synthesized compounds4a-h and 5a-h were screened for their antibacterial activity against four microorganisms:Staphylococcus aureus (Gram positive, Bacillus subtilis (Gram positive, Psuedomonasaeruginosa (Gram negative and Escherichia coli (Gram negative. They were found toexhibit good to moderate antibacterial activity. The antifungal activity of these compoundswere also tested against three different fungal species. None of them were active againstthe species tested.

  6. Synthesis and Screening of Some New N-Substituted Derivatives of N-(4-Methylpyridin-2-ylbenzenesulfonamides as Potential Antibacterial Agents

    Directory of Open Access Journals (Sweden)

    Aziz-ur-Rehman

    2014-03-01

    Full Text Available The two step synthesis of a series of N-substituted derivatives of N-(4-Methylpyridin-2-ylbenzenesulfonamide with potential antibacterial activity, has been reported. First step includes the synthesis of N-(4-Methylpyridin-2-ylbenzenesulfonamide (3 by reaction of 2-Amino-4-methylpyridine (1 and Benzenesulfonyl chloride (2 in a slightly basic aqueous medium. The molecule 3 was converted to N-Alkyl/aralkyl-N-(4-methylpyridin-2-ylbenzenesulfonamide derivatives, 5a-f, on treatment with alkyl/aralkyl halides, 4a-f, using lithium hydride as activator in N,N-dimethylformamide. The synthesized molecules were well corroborated by 1H-NMR, IR and EI-MS spectral data and evaluated for antibacterial activity against four gram-negative and two gram-positive bacteria. The evaluation results rendered these compounds as moderately good inhibitors and may be employed as therapeutic agent for certain inflammatory ailments.

  7. Comparative effects of antithrombitic and antimycotic N-substituted imidazoles on rat hepatic microsomal steroid and xenobiotic hydroxylases in vitro.

    Science.gov (United States)

    Murray, M; Zaluzny, L

    1988-02-01

    N-Substituted imidazoles have been shown to be potent inhibitors of microsomal mixed-function oxidase activities in vitro and in vivo. In the present study the effects of two antithrombitic (dazmegrel and dazoxiben) and four antimycotic (ketoconazole, econazole, miconazole and clotrimazole) imidazoles on microsomal cytochrome P-450-mediated steroid and xenobiotic hydroxylases were studied in vitro. Despite the presence of the N-substituted imidazole moiety, the antithrombitic agents were essentially non-potent as inhibitors of all of the oxidase activities evaluated. In contrast, the antimycotic drugs were potent inhibitory compounds. Binding studies revealed that all six imidazoles elicited type II optical difference spectra and exhibited relatively high affinity for ferricytochrome P-450 in microsomal suspensions (Ks range 0.26-0.73 microM for the antimycotic agents and 6.5 microM and 21 microM for dazmegrel and dazoxiben, respectively). The structural feature that the antithrombitic compounds share is a carboxylate function so that, at physiological pH, less than 1% of the drug would be present in the unionised form. This functionality is absent from the structures of the antimycotic agents which possess much greater hydrophobic character. Even though the antithrombitic imidazoles elicit type II binding interactions of quite high affinity it would appear from this study that significant inhibition potency does not necessarily follow. The present findings also suggest that interesting differences exist between the active site binding regions in the cytochrome P-450 that catalyse thromboxane synthetase activity and those involved in microsomal drug oxidation. Inhibitor hydrophobicity is clearly an important factor in the inhibition of microsomal cytochromes P-450 whereas effective thromboxane synthetase inhibitors may be quite hydrophilic at physiological pH. PMID:3337742

  8. Synthesis and biological evaluation of N-substituted noscapine analogues.

    Science.gov (United States)

    DeBono, Aaron J; Xie, Jin Han; Ventura, Sabatino; Pouton, Colin W; Capuano, Ben; Scammells, Peter J

    2012-12-01

    Noscapine is a phthalideisoquinoline alkaloid isolated from the opium poppy Papaver somniferum. It has long been used as an antitussive agent, but has more recently been found to possess microtubule-modulating properties and anticancer activity. Herein we report the synthesis and pharmacological evaluation of a series of 6'-substituted noscapine derivatives. To underpin this structure-activity study, an efficient synthesis of N-nornoscapine and its subsequent reduction to the cyclic ether derivative of N-nornoscapine was developed. Reaction of the latter with a range of alkyl halides, acid chlorides, isocyanates, thioisocyanates, and chloroformate reagents resulted in the formation of the corresponding N-alkyl, N-acyl, N-carbamoyl, N-thiocarbamoyl, and N-carbamate derivatives, respectively. The ability of these compounds to inhibit cell proliferation was assessed in cell-cycle cytotoxicity assays using prostate cancer (PC3), breast cancer (MCF-7), and colon cancer (Caco-2) cell lines. Compounds that showed activity in the cell-cycle assay were further evaluated in cell viability assays using PC3 and MCF-7 cells. PMID:23055449

  9. C-Arylation reactions catalyzed by CuO-nanoparticles under ligand free conditions

    OpenAIRE

    Mazaahir Kidwai; Saurav Bhardwaj; Roona Poddar

    2010-01-01

    CuO-nanoparticles were found to be an excellent heterogeneous catalyst for C-arylation of active methylene compounds using various aryl halides. The products were obtained in good to excellent yield. The catalyst can be recovered and reused for four cycles with almost no loss in activity.

  10. Synthesis of N-substituted 6-trifluoromethyl-1,3-oxazinanes

    Energy Technology Data Exchange (ETDEWEB)

    Zanatta, Nilo; Squizani, Adriana M.C.; Fantinel, Leonardo; Nachtigall, Fabiane M.; Borchhardt, Deise M.; Bonacorso, Helio G.; Martins, Marcos A.P. [Santa Maria Univ., RS (Brazil). Dept. de Quimica. Nucleo de Qumica de Heterociclos (NUQUIMHE)]. E-mail: zanatta@base.ufsm.br

    2005-11-15

    The work reports the synthesis of two new series of N-substituted 6-trifluoromethyl-1,3-oxazinanes and N-substituted 6-trifluoromethyl-1,3-oxazinan-2-ones from the cyclization of 4-ylamino-1,1,1-trifluoro-butan-2-ols with formaldehyde and triphosgene, respectively. The 4-ylamino-1,1,1-trifluoro-butan-2-ols were obtained in good yields from the reduction of the parent 4-ylamino-1,1,1-trifluoro-but-3-en-2-ones with hydrogen and 10% Pd/C. (author)

  11. Comparative cytotoxicity of N-substituted N'-(4-imidazole-ethyl)thiourea in precision-cut rat liver slices

    International Nuclear Information System (INIS)

    In order to more rationally design thiourea-containing drugs and drug candidates, specifically thiourea-containing histamine H3 receptor antagonists, it is necessary to develop structure-toxicity relationships (STRs). For this purpose, the cytotoxicity of a series of thiourea-containing compounds was tested in precision-cut rat liver slices. A concentration of 1000 ?M of N-p-bromophenyl, N'-(4-imidazole-ethyl)thiourea (8) or N-p-nitrophenyl, N'-(4-imidazole-ethyl)thiourea (9) was found to cause cytotoxicity, evidenced as LDH leakage, resulting in more than 95% LDH leakage after 6 h. N-p-Methoxyphenyl, N'-(4-imidazole-ethyl)thiourea (6) caused 40.6±19.7% LDH leakage after 6 h. Control levels of cell death (1% methanol as control vehicle) were below 20% in 6 h. After 6 h of exposure, N-p-chlorophenyl, N'-(4-imidazole-ethyl)thiourea (7), 8, and 9 were already found to cause significant cytotoxicity at a concentration of 100 ?M. At 200 ?M, 9 was found to cause significantly more cytotoxicity than 7 and 8. N-Naphthyl, N'-(4-imidazole-ethyl)thiourea (12) was found to cause significant cytotoxicity towards precision-cut rat liver slices after 6 h of exposure to a concentration of 500 ?M. All other N-substituted, N'-(4-imidazole-ethyl)thiourea tested in this study were not found to be cytotoxic towards precision-cut rat liver slices within the 6 h of exposure up to a concentration of 1000 ?M. Intracellular glutathione (GSH) content and mitochondrial MTT reduc content and mitochondrial MTT reduction activity were also examined after exposure of slices to N-substituted, N'-(4-imidazole-ethyl)thiourea. Both of these markers, however, were not found to provide additional information regarding the possible mechanisms of cytotoxicity, i.e. GSH depletion or reduced mitochondrial activity since these markers did not clearly precede LDH leakage. A correlation was found between cytotoxicity towards precision-cut rat liver slices and Vmax/Km values for the formation of sulfenic acids from N-substituted N'-(4-imidazole-ethyl)thiourea by hepatic rat flavin-containing monooxygenases (FMO). The compound with the highest Vmax/Km value for the formation of sulfenic acids, 9, was also the most cytotoxic. Compounds with a significantly lower Vmax/Km value, 7, 8, and 12, were less cytotoxic than 9. Compounds with a Vmax/Km value for the formation of sulfenic acids lower than 0.0788 ml/(min mg) were found not to be cytotoxic towards precision-cut rat liver slices for concentrations up to 1000 ?M at an exposure time of 6 h. It is concluded, from this study, that N-phenyl substituted N'-(4-imidazole-ethyl)thiourea-containing electron-withdrawing p-substituents are cytotoxic towards precision-cut rat liver slices. Cytotoxicity is increased with increasing electron-withdrawing capacity of the p-substituent. A correlation was found to exist between Vmax/Km value for the formation of sulfenic acids by rat liver FMO enzymes and cytotoxicity

  12. Direct N9-arylation of purines with aryl halides

    DEFF Research Database (Denmark)

    Larsen, Anders Foller; Ulven, Trond

    2014-01-01

    An efficient method for N-arylation of purines is reported. The N-arylation is catalysed by Cu(i) and 4,7-bis(2-hydroxyethylamino)-1,10-phenanthroline (BHPhen) in aqueous DMF or ethanol. The reaction generally proceeds with high selectivity for the N(9)-position.

  13. Aryl diazonium salts new coupling agents and surface science

    CERN Document Server

    Chehimi, Mohamed Mehdi

    2012-01-01

    Diazonium compounds are employed as a new class of coupling agents to link polymers, biomacromolecules, and other species (e. g. metallic nanoparticles) to the surface of materials. The resulting high performance materials show improved chemical and physical properties and find widespread applications. The advantage of aryl diazonium salts compared to other surface modifiers lies in their ease of preparation, rapid (electro)reduction, large choice of reactive functional groups, and strong aryl-surface covalent bonding.This unique book summarizes the current knowledge of the surface and

  14. Electrochemical cleavage of aryl ethers promoted by sodium borohydride.

    Science.gov (United States)

    Wu, Wen-Bin; Huang, Jing-Mei

    2014-11-01

    The NaBH4 (or TBABH4)-promoted electrochemically reductive cleavage of aryl C-O bonds in diaryl ethers to produce phenols and arenes with high yields and excellent selectivities at room temperature was reported. Air- and water-tolerable, this process also works on the cleavage of aryl alkyl and benzyl ethers. The application to break the ?-O-4, ?-O-4, and 4-O-5 lignin model compounds is also illustrated, which highlights the advance toward the goal of lignin conversion. PMID:25317950

  15. Solid-Phase Synthesis of N-Substituted Glycine Oligomers (??Peptoids) and Derivatives

    OpenAIRE

    Ouellette, Rodney J; Culf, Adrian S.

    2010-01-01

    Peptoids (N-substituted polyglycines and extended peptoids with variant backbone amino-acid monomer units) are oligomeric synthetic polymers that are becoming a valuable molecular tool in the biosciences. Of particular interest are their applications to the exploration of peptoid secondary structures and drug design. Major advantages of peptoids as research and pharmaceutical tools include the ease and economy of synthesis, highly variable backbone and side-chain chemistry possibilities. At t...

  16. Neat reaction microwave technology for the synthesis of N-substituted-1,4-dihydropyridines

    International Nuclear Information System (INIS)

    Hantzsch synthesis of N-substituted-1,4-dihydropyridines (1,4-DHP) was carried out using an environmentally benign procedure. Neat reactants were subjected to microwave irradiation (MWI) to give the required products in excellent yield. Appreciable results were not obtained when conventional synthesis using neat reactants was carried out. The good yield and rate enhancement observed in the case of microwave irradiation is attributed to the uniform heating effect of microwaves. (author)

  17. Functionality of aryl hydrocarbon receptors (AhR1 and AhR2) of white sturgeon (Acipenser transmontanus) and implications for the risk assessment of dioxin-like compounds.

    Science.gov (United States)

    Doering, Jon A; Farmahin, Reza; Wiseman, Steve; Kennedy, Sean W; Giesy, John P; Hecker, Markus

    2014-07-15

    Worldwide, populations of sturgeons are endangered, and it is hypothesized that anthropogenic chemicals, including dioxin-like compounds (DLCs), might be contributing to the observed declines in populations. DLCs elicit their toxic action through activation of the aryl hydrocarbon receptor (AhR), which is believed to regulate most, if not all, adverse effects associated with exposure to these chemicals. Currently, risk assessment of DLCs in fishes uses toxic equivalency factors (TEFs) developed for the World Health Organization (WHO) that are based on studies of embryo-lethality with salmonids. However, there is a lack of knowledge of the sensitivity of sturgeons to DLCs, and it is uncertain whether TEFs developed by the WHO are protective of these fishes. Sturgeons are evolutionarily distinct from salmonids, and the AhRs of sturgeons differ from those of salmonids. Therefore, this study investigated the sensitivity of white sturgeon (Acipenser transmontanus) to DLCs in vitro via the use of luciferase reporter gene assays using COS-7 cells transfected with AhR1 or AhR2 of white sturgeon. Specifically, activation and relative potencies (RePs) of 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD), 2,3,4,7,8-pentachloro-dibenzofuran, 2,3,7,8-tetrachloro-dibenzofuran, 3,3',4,4',5-pentachlorobiphenyl, 3,3',4,4'-tetrachlorobiphenyl, and 2,3,3',4,4'-pentachlorobiphenyl were determined for each AhR. It was demonstrated that white sturgeon expresses AhR1s and AhR2s that are both activated by DLCs with EC50 values for 2,3,7,8-TCDD that are lower than those of any other AhR of vertebrates tested to date. Both AhRs of white sturgeon had RePs for polychlorinated dibenzofurans more similar to TEFs for birds, while RePs for polychlorinated biphenyls were most similar to TEFs for fishes. Measured concentrations of select DLCs in tissues of white sturgeon from British Columbia, Canada, were used to calculate toxic equivalents (TEQs) by use of TEFs for fishes used by the WHO and TCDD equivalents (TCDD-EQs) via the use of RePs for AhR2 of white sturgeon as determined by transfected COS-7 cells. TCDD-EQs calculated for endangered populations of white sturgeon were approximately 10-fold greater than TEQs and were within ranges known to cause adverse effects in other fishes, including other species of sturgeons. Therefore, TEFs used by the WHO might not adequately protect white sturgeon, illuminating the need for additional investigation into the sensitivity of these fish to DLCs. PMID:24950391

  18. Experimental and theoretical study of [N-substituted] p-aminoazobenzene derivatives as corrosion inhibitors for mild steel in sulfuric acid solution

    Science.gov (United States)

    Shihab, Mehdi Salih; Al-Doori, Hanan Hussien

    2014-11-01

    [N-substituted] p-aminoazobenzene derivatives (1), (2), (3), (4) and (5) were prepared and investigated as corrosion inhibitors for mild steel in 1 M H2SO4 solution by weight loss measurements. It has been observed that the corrosion rate decreases, inhibition efficiencies increase and surface coverage degree increases with increasing inhibitor concentration. Inhibition efficiencies for prepared compounds were ordered: (1) > (2) > (5) > (4) > (3) with the highest inhibiting efficiency of 63% for 10-3 M. The values of ?Gadso are showing physisorption effect for all prepared compounds. Semiempirical molecular orbital calculations for (1), (2), (3), (4) and (5) could be used as a useful tool to obtain information for explaining the nature of interaction between the metal surface and the organic molecule as a corrosion inhibitor.

  19. N-substituted phenothiazine derivatives: how the stability of the neutral and radical cation forms affects overcharge performance in lithium-ion batteries.

    Science.gov (United States)

    Narayana, Kishore Anand; Casselman, Matthew D; Elliott, Corrine F; Ergun, Selin; Parkin, Sean R; Risko, Chad; Odom, Susan A

    2015-04-27

    Phenothiazine and five N-substituted derivatives were evaluated as electrolyte additives for overcharge protection in LiFePO4 /synthetic graphite lithium-ion batteries. We report on the stability and reactivity of both the neutral and radical-cation forms of these six compounds. While three of the compounds show extensive overcharge protection, the remaining three last for only one to a few cycles. UV/Vis studies of redox shuttle stability in the radical cation form are consistent with the overcharge performance: redox shuttles with spectra that show little change over time exhibit extensive overcharge performance, whereas those with changing spectra have limited overcharge protection. In one case, we determined that a C-N bond cleaves upon oxidation, forming the phenothiazine radical cation and leading to premature overcharge protection failure; in another case, poor solubility appears to limit protection. PMID:25504135

  20. A New Synthetic Route to N-Benzyl Carboxamides through the Reverse Reaction of N-Substituted Formamide Deformylase

    OpenAIRE

    Hashimoto, Yoshiteru; Sakashita, Toshihide; Fukatsu, Hiroshi; Sato, Hiroyoshi; Kobayashi, Michihiko

    2014-01-01

    Previously, we isolated a new enzyme, N-substituted formamide deformylase, that catalyzes the hydrolysis of N-substituted formamide to the corresponding amine and formate (H. Fukatsu, Y. Hashimoto, M. Goda, H. Higashibata, and M. Kobayashi, Proc. Natl. Acad. Sci. U. S. A. 101:13726–13731, 2004, doi:10.1073/pnas.0405082101). Here, we discovered that this enzyme catalyzed the reverse reaction, synthesizing N-benzylformamide (NBFA) from benzylamine and formate. The reverse reaction proceeded o...

  1. Synthesis of N-substituted ?-hexonolactams as pharmacological chaperones for the treatment of N370S mutant Gaucher disease.

    OpenAIRE

    Wang, GN; Twigg, G; Butters, TD; Zhang, S.; Zhang, L.; Zhang, LH; Ye, XS

    2012-01-01

    A series of N-substituted ?-hexonolactams have been designed and prepared by a concise route with a tandem ring-expansion reaction as the key step. Some of the N-substituted ?-hexonolactams show better enhancements to N370S mutant ?-glucocerebrosidase activity than NB-DNJ and NN-DNJ. Both the experimental results and computational studies highlight the importance of the carbonyl group for stabilizing protein folds in the mutant enzyme. The structure-activity relationships are also discusse...

  2. Green and selective synthesis of N-substituted amides using water soluble porphyrazinato copper(II) catalyst

    International Nuclear Information System (INIS)

    N, N',N, N'-Tetramethyl tetra-2,3-pyridinoporphyrazinato copper(II) methyl sulfate ([Cu(2,3-tmtppa)](MeSO4)4) efficiently catalyzed the direct conversion of nitriles to N-substituted amides. The one pot selective synthesis of the N-substituted amides from nitriles and primary amines was performed in refluxing H2O. The catalyst was recovered and reused at least four times, maintaining its efficiency. (author)

  3. One-pot synthesis of aryl sulfones from organometallic reagents and iodonium salts.

    Science.gov (United States)

    Margraf, Natalie; Manolikakes, Georg

    2015-03-01

    A transition-metal-free arylation of lithium, magnesium, and zinc sulfinates with diaryliodonium salts is described. The sulfinic acid salts were prepared from the reaction of the corresponding organometallic reagents and sulfur dioxide. Combination of the three single steps (preparation of the organometallic compound, sulfinate formation, and arylation) leads to a one-pot sequence for the synthesis of aryl sulfones from simple starting materials. The chemoselectivity of unsymmetrical diaryliodonium salts has been investigated. Potential and limitations of this method will be discussed. PMID:25650485

  4. Synthesis, growth and characterization of new 1,3,4 -thiadiazole-5-(n-substituted)-sulfonamides cristals

    Scientific Electronic Library Online (English)

    G.E., Camí; M.del C., Ramírez de Arellano; S., Fustero; J.C., Pedregosa.

    2006-12-01

    Full Text Available Nuevas 1,3,4-tiadiazol-5-(N-substituidas)-sulfonamidas, inhibidores de anhidrasa carbónica, fueron obtenidas incorporando los grupos N-ciclohexil, N-benzil and N-[sec-butil], por una síntesis optimizada y monocristales de las mismas fueron crecidos desde alcohol absoluto por evaporación lenta a temp [...] eratura ambiente hasta dimensiones adecuadas para medidas de DRX. Los datos estructurales de estos compuestos monoclínicos son comparados con los de otras fases relacionadas. El grupo sulfonil presenta una geometría tetraédrica distorsionada alrededor del átomo de S. Los diferentes sustituyentes introducidos no producen modificaciones en la estructura del anillo 1,3,4-tiadiazol. El análisis térmico de las tres fases muestra descomposición total a temperaturas por encima del punto de fusión. Los espectros FTIR confirman la formación de los compuestos y es el primer aporte sobre el conocimiento de la unión puente hidrógeno NH...N en estas sulfonamidas. Abstract in english New 1,3,4-thiadiazole-5-(N-substituted)-sulfonamide derivatives incorporating N-cyclohexyl, N-benzyl and N-[sec-butyl] moieties, carbonic anhydrase inhibitors, have been obtained by an optimized synthesis. Single crystals of these sulfonamides have been successfully grown up to suitable dimensions f [...] or X-ray diffraction measurements by slow evaporation of solvent at room temperature. Structural data for these monoclinic compounds are compared with those of related phases. The sulfonyl moiety presents a distorted tetrahedral arrangement around the S atom. The different groups introduced cause no observable modifications of the 1,3,4-thiadiazole ring structure. Thermal analysis show total sample degradation at temperatures higher than that of the melting point of the three phases. The FTIR spectra confirm the compounds formation and provide a first insight on the modes of NH…N hydrogen bond in these sulfonamides.

  5. Smiles Rearrangement Based Practical One-pot Synthesis of N-Alkyl/aryl-6-aminoquinolines from 6-Hydroxylquinoline

    International Nuclear Information System (INIS)

    The C-N coupling protocol reported herein represents a convenient and practical synthesis of N-alkyl/aryl-6-aminoquinolines in a three-step one-pot manner by simple addition of 6-hydroxyquinoline and N-alkyl/aryl-2-chloroacetamides with Cs2CO3 or K2CO3 in DMF at 150 .deg. C via Smiles rearrangement. An electron donating substituent on the nitrogen counterpart would accelerate the rearrangement process to achieve various anilines in good yields. We currently engaged in making a chemical library including multifarious N-substituted-6-aminoquinolines, to be used in the screening for specific AChEI activity. Furthermore, this work extends the scope of preparing different heterocyclic synthons in drug design for various biological activities. Aminoquinolines and their derivatives are important chemical entities that are widely used as pro-drugs and drugs due to their antimicrobial, cytotoxic and anti-malarial activities etc

  6. Some higher N-substituted 1,3-thiazolidine-2,4-diones and 5,5-diphenylhydantoins, their synthesis and corrosion preventive properties in mineral oil medium

    International Nuclear Information System (INIS)

    Highlights: ? N-substituted 5,5-diphenylhydantoins and 1,3-thiazolidine-2,4-diones were prepared. ? All synthesized compounds showed good inhibition effect in oil–water medium. ? The test results were supported with water contact angle measurements and with SEM. ? Inhibition effect of compounds were evidenced by the optical profilometer photos. - Abstract: Some five membered heterocyclic compounds were synthesized by the reaction of 2,4-thiazolidinedione or 5,5-diphenylhydantoin potassium salts with 2-chloro-N-alkylacetamides and alkyl-2-chloroacetates. The structure confirmations of the synthesized compounds were performed by FT-IR, 1H NMR, 13C NMR spectra. The inhibitory effectiveness of the compounds were evaluated against the corrosion of steel strip immersed in water containing paraffin based mineral oil medium in accordance to standard test method. Surface characterization studies of the metal coupons used were performed by SEM analysis and also by the contact angle measurements using the Sessile–Drop method. In addition the 3D image of the metal surface was obtained using optical profilometer. The test results and surface characterization studies showed that all synthesized compounds are excellent corrosion inhibitors in such a water in oil emulsion system.

  7. Some higher N-substituted 1,3-thiazolidine-2,4-diones and 5,5-diphenylhydantoins, their synthesis and corrosion preventive properties in mineral oil medium

    Energy Technology Data Exchange (ETDEWEB)

    Oeztuerk, Serkan, E-mail: serkanozturk@uludag.edu.tr [Department of Chemistry, Faculty of Science and Arts, Uludag University, 16059 Bursa (Turkey); Y Latin-Small-Letter-Dotless-I ld Latin-Small-Letter-Dotless-I r Latin-Small-Letter-Dotless-I m, Ayhan; Cetin, Mehmet [Department of Chemistry, Faculty of Science and Arts, Uludag University, 16059 Bursa (Turkey)

    2013-01-15

    Highlights: Black-Right-Pointing-Pointer N-substituted 5,5-diphenylhydantoins and 1,3-thiazolidine-2,4-diones were prepared. Black-Right-Pointing-Pointer All synthesized compounds showed good inhibition effect in oil-water medium. Black-Right-Pointing-Pointer The test results were supported with water contact angle measurements and with SEM. Black-Right-Pointing-Pointer Inhibition effect of compounds were evidenced by the optical profilometer photos. - Abstract: Some five membered heterocyclic compounds were synthesized by the reaction of 2,4-thiazolidinedione or 5,5-diphenylhydantoin potassium salts with 2-chloro-N-alkylacetamides and alkyl-2-chloroacetates. The structure confirmations of the synthesized compounds were performed by FT-IR, {sup 1}H NMR, {sup 13}C NMR spectra. The inhibitory effectiveness of the compounds were evaluated against the corrosion of steel strip immersed in water containing paraffin based mineral oil medium in accordance to standard test method. Surface characterization studies of the metal coupons used were performed by SEM analysis and also by the contact angle measurements using the Sessile-Drop method. In addition the 3D image of the metal surface was obtained using optical profilometer. The test results and surface characterization studies showed that all synthesized compounds are excellent corrosion inhibitors in such a water in oil emulsion system.

  8. Synthesis of N-substituted 6-trifluoromethyl-1,3-oxazinanes

    Scientific Electronic Library Online (English)

    Nilo, Zanatta; Adriana M. C., Squizani; Leonardo, Fantinel; Fabiane M., Nachtigall; Deise M., Borchhardt; Helio G., Bonacorso; Marcos A. P., Martins.

    1255-12-01

    Full Text Available Este trabalho apresenta a síntese de duas novas séries de 6-trifluormetil-1,3-oxazinanas N-substituídas e 6-trifluormetil-1,3-oxazinan-2-onas N-substituídas, a partir da ciclização de 4-ilamino-1,1,1-trifluor-butan-2-óis com formaldeído e trifosgênio, respectivamente. Os 4-ilamino-1,1,1-trifluor-but [...] an-2-óis foram obtidos através da reação de redução dos precursores 4-ilamino-1,1,1-trifluor-but-3-en-2-onas, utilizando hidrogênio e 10% Pd/C, com bons rendimentos. Abstract in english This work reports the synthesis of two new series of N-substituted 6-trifluoromethyl-1,3-oxazinanes and N-substituted 6-trifluoromethyl-1,3-oxazinan-2-ones from the cyclization of 4-ylamino-1,1,1-trifluoro-butan-2-ols with formaldehyde and triphosgene, respectively. The 4-ylamino-1,1,1-trifluoro-but [...] an-2-ols were obtained in good yields from the reduction of the parent 4-ylamino-1,1,1-trifluoro-but-3-en-2-ones with hydrogen and 10% Pd/C.

  9. Aminocarbonylation of aryl tosylates to carboxamides.

    Science.gov (United States)

    Chung, Seungwon; Sach, Neal; Choi, Chulho; Yang, Xiaojing; Drozda, Susan E; Singer, Robert A; Wright, Stephen W

    2015-06-01

    The palladium - catalyzed aminocarbonylation of aryl tosylates with amines is reported. Suitable conditions were identified by high throughput reaction screening and then further optimized. The substrate scope of the reaction with respect to the aryl tosylate component and the amine component are reported. Competitive aminolysis of the aryl tosylates to afford the amine toluenesulfonamides and the phenol was not observed. PMID:25994500

  10. Palladium-Catalyzed Thiocarbonylation of Aryl, Vinyl, and Benzyl Bromides

    DEFF Research Database (Denmark)

    Burhardt, Mia; Ahlburg, Andreas

    2014-01-01

    A catalytic protocol for synthesis of thioesters from aryl, vinyl, and benzyl bromides as well as benzyl chlorides was developed using only stoichiometric amounts of carbon monoxide, produced from a solid CO precursor inside a two-chamber system. As a catalytic system, the combination of bis(benzonitrile) palladium(II) chloride and Xantphos furnished the highest yields of the desired compounds, along with the weak base, NaOAc, in anisole at 120 °C. The choice of catalytic system as well as solvent turned out to be important in order to ensure a high chemoselectivity in the reaction. Both electron-rich and electron-deficient aryl bromides worked well in this reaction. Addition of 1 equiv of sodium iodide to the reaction improved the chemoselectivity with the electron-deficient aryl bromides. The thiol scope included both aryl and alkyl thiols, including 2-mercaptobenzophenones, whereby a thiocarbonylation followed by a subsequent McMurry coupling yielded differently substituted benzothiophenes. It was demonstrated that the methodology could be applied for (13)C introduction into the thiophene ring.

  11. Electrochemical synthesis and characterization of N-substituted polypyrrole derivatives on nickel

    International Nuclear Information System (INIS)

    1-Dodecylpyrrole (PyCH3) and 12-(pyrrol-1-yl)dodecane-1-thiol (PySH) films have been successfully electrochemically polymerised on a nickel electrode from acetonitrile solutions containing the monomer and the lithium perchlorate as supporting electrolyte. The electrochemical study of the polymer growth has been carried out by cyclic voltammetry (CV) detecting the nickel dissolution during electropolymerisation. Several surface spectroscopic and microscopic techniques have been used to characterize the surface in term of chemical composition and polymer topography. The presence of unbound and unoxidised thiol groups at the PPySH surface has been evidenced together with a very strong adhesion to the nickel substrate. Furthermore, N-substituted pyrrole derivatives exhibited some corrosion protection properties in neutral NaCl medium

  12. Electrochemical synthesis and characterization of N-substituted polypyrrole derivatives on nickel

    Energy Technology Data Exchange (ETDEWEB)

    Lallemand, F.; Auguste, D.; Amato, C.; Hevesi, L.; Delhalle, J.; Mekhalif, Z. [Laboratoire de Chimie et d' Electrochimie des Surfaces, Academie Louvain, Facultes Universitaires Notre-Dame de la Paix, 61, rue de Bruxelles, B-5000 Namur (Belgium)

    2007-03-20

    1-Dodecylpyrrole (PyCH{sub 3}) and 12-(pyrrol-1-yl)dodecane-1-thiol (PySH) films have been successfully electrochemically polymerised on a nickel electrode from acetonitrile solutions containing the monomer and the lithium perchlorate as supporting electrolyte. The electrochemical study of the polymer growth has been carried out by cyclic voltammetry (CV) detecting the nickel dissolution during electropolymerisation. Several surface spectroscopic and microscopic techniques have been used to characterize the surface in term of chemical composition and polymer topography. The presence of unbound and unoxidised thiol groups at the PPySH surface has been evidenced together with a very strong adhesion to the nickel substrate. Furthermore, N-substituted pyrrole derivatives exhibited some corrosion protection properties in neutral NaCl medium. (author)

  13. Synthesis of N-substituted ?-hexonolactams as pharmacological chaperones for the treatment of N370S mutant Gaucher disease.

    Science.gov (United States)

    Wang, Guan-Nan; Twigg, Gabriele; Butters, Terry D; Zhang, Siwei; Zhang, Liangren; Zhang, Li-He; Ye, Xin-Shan

    2012-04-21

    A series of N-substituted ?-hexonolactams have been designed and prepared by a concise route with a tandem ring-expansion reaction as the key step. Some of the N-substituted ?-hexonolactams show better enhancements to N370S mutant ?-glucocerebrosidase activity than NB-DNJ and NN-DNJ. Both the experimental results and computational studies highlight the importance of the carbonyl group for stabilizing protein folds in the mutant enzyme. The structure-activity relationships are also discussed. These novel N-alkylated iminosugars are promising pharmacological chaperones for the treatment of N370S mutant Gaucher disease. PMID:22286559

  14. Green and selective synthesis of N-substituted amides using water soluble porphyrazinato copper(II) catalyst

    Energy Technology Data Exchange (ETDEWEB)

    Ghodsinia, Sara S.E.; Akhlaghinia, Batool; Eshghi, Hossein, E-mail: akhlaghinia@um.ac.ir [Ferdowsi University of Mashhad (Iran, Islamic Republic of). Faculty of Sciences. Department of Chemistry; Safaei, Elham [Institute for Advanced Studies in Basic Sciences (IASBS), Zanjan (Iran, Islamic Republic of). Department of Chemistry

    2013-06-15

    N, N',N{sup ,} N{sup '}-Tetramethyl tetra-2,3-pyridinoporphyrazinato copper(II) methyl sulfate ([Cu(2,3-tmtppa)](MeSO{sub 4}){sub 4}) efficiently catalyzed the direct conversion of nitriles to N-substituted amides. The one pot selective synthesis of the N-substituted amides from nitriles and primary amines was performed in refluxing H{sub 2}O. The catalyst was recovered and reused at least four times, maintaining its efficiency. (author)

  15. Synthesis, characterization and antibacterial activity of halogenated aryl sulfonamides derived from 2-amino-4-chloroanisole

    International Nuclear Information System (INIS)

    In the current work, a number of new N-(5-chloro-2-methoxyphenyl)aryl sulfonamides (3a-e) and N-ethyl/benzyl-N-(5-chloro-2-methoxyphenyl)aryl sulfonamides (6a-e and 7a-e) were synthesized and evaluated for their biological activities. The synthesis was carried out by coupling 2-amino-4-chloroanisole (1) with different aryl sulfonyl chlorides, 2a-e, under dynamic pH control in aqueous medium to form aryl sulfonamides, 3a-e. Further, N-ethyl/benzyl-N-(5-chloro-2-methoxyphenyl)aryl sulfonamides (6a-e and 7a-e) were synthesized by stirring 3a-e with the electrophiles, 4 and 5, in the presence of sodium hydride and N,N-dimethylformamide. The structures of the synthesized compounds were characterized from their spectral data. In addition, the in vitro antibacterial activity of all the target compounds was investigated against Gram-negative and Gram-positive bacteria using ciprofloxacin as a reference drug. Many of these compounds exhibited moderate to good activity and subtle structural changes in the substituents altered the inhibitory properties significantly. (author)

  16. Rh(I)-Catalyzed Direct Arylation of Pyridines and Quinolines

    Energy Technology Data Exchange (ETDEWEB)

    Berman, Ashley; Lewis, Jared; Bergman, Robert; Ellman, Jonathan

    2008-07-29

    The pyridine and quinoline nuclei are privileged scaffolds that occupy a central role in many medicinally relevant compounds. Consequently, methods for their expeditious functionalization are of immediate interest. However, despite the immense importance of transition-metal catalyzed cross-coupling for the functionalization of aromatic scaffolds, general solutions for coupling 2-pyridyl organometallics with aryl halides have only recently been presented. Direct arylation at the ortho position of pyridine would constitute an even more efficient approach because it eliminates the need for the stoichiometric preparation and isolation of 2-pyridyl organometallics. Progress towards this goal has been achieved by activation of the pyridine nucleus for arylation via conversion to the corresponding pyridine N-oxide or N-iminopyridinium ylide. However, this approach necessitates two additional steps: activation of the pyridine or quinoline starting material, and then unmasking the arylated product. The use of pyridines directly would clearly represent the ideal situation both in terms of cost and simplicity. We now wish to document our efforts in this vein, culminating in an operationally simple Rh(I)-catalyzed direct arylation of pyridines and quinolines. We recently developed an electron-rich Rh(I) system for catalytic alkylation at the ortho position of pyridines and quinolines with alkenes. Therefore, we initially focused our attention on the use of similarly electron-rich Rh(I) catalysts for the proposed direct arylation. After screening an array of electron-rich phosphine ligands and Rh(I) salts, only marginal yields (<20%) of the desired product were obtained. Much more efficient was an electron-poor Rh(I) system with [RhCl(CO){sub 2}]{sub 2} as precatalyst (Table 1). For the direct arylation of picoline with 3,5-dimethyl-bromobenzene, addition of P(OiPr){sub 3} afforded a promising 40% yield of the cross coupled product 1a (entry 1). The exclusion of phosphite additive proved even more effective, with the yield of 1a improving to 61% (entry 2). Further enhancement in yield was not observed upon the inclusion of other additives such as MgO (entry 3), various organic bases (entries 4, 5), or a protic acid source (entry 6). Absolute concentration proved very important, with the best results being obtained at relatively high concentrations of the aryl bromide (compare entries 7 and 8). A marginal improvement was observed upon running the reaction with 6 equivalents of 2-methyl pyridine (entry 9). The reaction temperature could also be increased to 175 or 190 C while maintaining reaction yield, to enable the reaction time to be reduced to 24 h (entries 10 and 11). In summary, we have developed a Rh(I)-catalyzed strategy for the direct arylation of pyridines and quinolines. The heterocycle is used without the need for prefunctionalization, and all reaction components are inexpensive and readily available. The strategy represents an expeditious route to an important class of bis(hetero)aryls and should be of broad utility.

  17. Discovery of novel 2-aryl-4-benzoyl-imidazoles targeting the colchicines binding site in tubulin as potential anticancer agents

    OpenAIRE

    Chen, Jianjun; Wang, Zhao; Li, Chien-Ming; Lu, Yan; Vaddady, Pavan K.; Meibohm, Bernd; Dalton, James T.; Miller, Duane D; Li, Wei

    2010-01-01

    A series of 2-aryl-4-benzoyl-imidazoles (ABI) was synthesized as a result of structural modifications based on the previous set of 2-aryl-imidazole-4-carboxylic amide (AICA) derivatives and 4-substituted methoxylbenzoyl-aryl-thiazoles (SMART). The average IC50 of the most active compound (5da) was 15.7 nM. ABI analogs have substantially improved aqueous solubility (48.9 ?g/mL for 5ga vs. 0.909 ?g/mL for SMART-1, 0.137 ?g/mL for paclitaxel, and 1.04 ?g/mL for Combretastatin A4). Mechanism ...

  18. Radioimmunoassay for anileridine, meperidine, and other N-substituted phenylpiperidine carboxylic acid esters

    International Nuclear Information System (INIS)

    Antibodies that bind an 125I-tyramyl derivative of N-succinylanileridine have been produced in animals immunized with N-succinylanileridine-hemocyanin conjugate. Several congeners and metabolites have been tested as competitors of this antigen-antibody reaction. The concentrations (in picomoles) required for 50 percent inhibition have been found to be: anileridine (0.2), meperidine (3.5), piminodine (3.8), diphenoxylate (20.5), normeperidine (20.0), meperidine acid (45,000) and anileridine acid (3,400). Although ester hydrolysis results in changes in inhibiting capacities on the order of 104, major structural changes in the substituent on the nitrogen of the piperidine ring are not readily recognized by the antibody. This radioimmunoassay can be used to study a variety of N-substituted phenylpiperidine carboxylic acid esters by relating the results to the standard curve obtained for the drug under investigation. For all practical purposes, alphaprodine, morphine and methadone do not interfere with the assay

  19. Radioimmunoassay for anileridine, meperidine, and other N-substituted phenylpiperidine carboxylic acid esters

    Energy Technology Data Exchange (ETDEWEB)

    Van Vunakis, H.; Freeman, D.S.; Gjika, H.B.

    1975-10-01

    Antibodies that bind an /sup 125/I-tyramyl derivative of N-succinylanileridine have been produced in animals immunized with N-succinylanileridine-hemocyanin conjugate. Several congeners and metabolites have been tested as competitors of this antigen-antibody reaction. The concentrations (in picomoles) required for 50 percent inhibition have been found to be: anileridine (0.2), meperidine (3.5), piminodine (3.8), diphenoxylate (20.5), normeperidine (20.0), meperidine acid (45,000) and anileridine acid (3,400). Although ester hydrolysis results in changes in inhibiting capacities on the order of 10/sup 4/, major structural changes in the substituent on the nitrogen of the piperidine ring are not readily recognized by the antibody. This radioimmunoassay can be used to study a variety of N-substituted phenylpiperidine carboxylic acid esters by relating the results to the standard curve obtained for the drug under investigation. For all practical purposes, alphaprodine, morphine and methadone do not interfere with the assay.

  20. Chemometric approach in studying of the retention behavior and lipophilicity of potentially biologically active N-substituted-2-phenylacetamide derivatives

    Scientific Electronic Library Online (English)

    Gyöngyi Gy., Vastag; Suzana Lj., Apostolov; Borko M., Matijevi& #263; ; Aleksandar D., Marinkovi& #263; .

    1948-19-01

    Full Text Available A atividade biológica potencial de moléculas depende largamente da sua lipofilicidade. A lipofilicidade de derivados de 2-fenilacetamida N-substituída foi investigada experimentalmente, aplicando cromatografia em camada delgada em fase inversa (RP-TLC em RP 18 F254s) na presença de etanol e de dioxa [...] no, e usando pacotes de software. A fim de estabelecer a dependência entre a lipofilicidade obtida de diferentes formas foram usados análise de regressão linear e métodos multivariados. Agrupamentos aproximadamente semelhantes dos parâmetros lipofílicos e dos compostos testados foram registados no caso de ambos os métodos quimiométricos usados. Todos os resultados obtidos confirmam o fato de que as análises de regressão linear e multivariada aplicadas oferecem oportunidades para comparar os dados sobre a retenção cromatográfica e parâmetros lipofílicos dos derivados de fenilacetamida investigados. Os resultados sugerem que a lipofilicidade das moléculas estudadas depende largamente da natureza dos substituintes ligados ao átomo de nitrogênio e, por outro lado, que as constantes retenção cromatográfica, R M0, determinada pelo método de RP-TLC, são semelhantes à medida padrão de lipofilicidade, log P, o que torna este método adequado para a previsão de lipofilicidade. Abstract in english The potential biological activity of a molecule largely depends on its lipophilicity. The lipophilicity of derivatives of N-substituted-2-phenylacetamide was investigated experimentally, by applying thin-layer chromatography on reversed phase (RP-TLC on RP 18 F254s) in the presence of ethanol and di [...] oxane and by using relevant software packages. In order to establish dependence between lipophilicity obtained in different ways, linear regression analysis and multivariate methods were used. Approximately similar groupings of lipophilic parameters and tested compounds were registered in case of both chemometric methods. The obtained results confirm the fact that the applied linear regression analysis and multivariate analysis provide opportunities for comparing chromatographic retention data and lipophilic parameters of the investigated phenylacetamide derivatives. Results suggest that the lipophilicity of investigated molecules largely depends on the nature of the substituents linked to nitrogen atom and on the other hand that the chromatographic retention constants, R M0, determined by RP-TLC method, are similar to the standard measure of lipophilicity, log P, which makes this method appropriate for predicting lipophilicity.

  1. Discovery of 6-aryl-azabenzimidazoles that inhibit the TBK1/IKK-? kinases.

    Science.gov (United States)

    Johannes, Jeffrey W; Chuaqui, Claudio; Cowen, Scott; Devereaux, Erik; Gingipalli, Lakshmaiah; Molina, Audrey; Wang, Tao; Whitston, David; Wu, Xiaoyun; Zhang, Hai-Jun; Zinda, Michael

    2014-02-15

    The discovery and optimization of a series of 6-aryl-azabenzimidazole inhibitors of TBK1 and IKK-? is described. Various internal azabenzimidazole leads and reported TBK1/IKK-? inhibitors were docked into a TBK1 homology model. The resulting overlays inspired a focused screen of 6-substituted azabenzimidazoles against TBK1/IKK-?. This screen resulted in initial hit compound 3. The TBK1/IKK-? enzyme and cell potency of this compound was further improved using structure guided drug design. Systematic exploration of the C6 aryl group led to compound 19, a potent inhibitor of TBK1 with selectivity against cell cycle kinases CDK2 and Aurora B. Further elaboration and optimization gave compound 25, a single digit nM inhibitor of TBK1. These compounds may serve as in vitro probes to evaluate TBK1/IKK-? as an oncology target. PMID:24462666

  2. Effects of pesticide compounds (chlorothalonil and mancozeb) and benzo[a]pyrene mixture on aryl hydrocarbon receptor, p53 and ubiquitin gene expression levels in haemocytes of soft-shell clams (Mya arenaria).

    Science.gov (United States)

    Pariseau, Julie; McKenna, Patricia; Aboelkhair, Mohammed; Saint-Louis, Richard; Pelletier, Emilien; Davidson, T Jeffrey; Tremblay, Réjean; Berthe, Franck C J; Siah, Ahmed

    2011-11-01

    The aim of this study is to investigate the effects of the pesticides/polycyclic aromatic hydrocarbon mixture on aryl hydrocarbon receptor (AhR), p53 and ubiquitin mRNA level in haemocytes of Mya arenaria exposed to a mixture of chlorothalonil, mancozeb and benzo[a]pyrene (BaP) for 48 and 72 h. AhR, p53 and ubiquitin gene expression levels were quantified using quantitative Real-time PCR. For robust and accurate quantification of transcripts, suitable housekeeping genes were selected from four sets of ribosomal and elongation factors transcripts previously sequenced from Mya arenaria using geNorm open source software. Quantitative Real-time PCR data exhibited a significantly high expression of AhR after 72 h of exposure (P ? 0.05). p53 gene expression seems to be up-regulated by the mixture after 48 h, however not significantly; but the level of p53 mRNA is down-regulated by the xenobiotics between 48 and 72 h after exposure. This study postulates that AhR mRNA levels could be used as an indicator of the exposure of clams' haemocytes to a mixture of xenobiotics such as chlorothalonil, mancozeb and BaP. However, further studies have to be pursued in order to unravel the molecular mechanisms involved in the p53 signaling pathway. PMID:21688059

  3. Palladium-Catalyzed Carbonylative ?-Arylation to ?-Ketonitriles

    DEFF Research Database (Denmark)

    Schranck, Johannes; Burhardt, Mia

    2014-01-01

    A carbonylative ?-arylation process employing unactivated nitriles for the first time is described. The reaction tolerates a range of (hetero)aryl iodides and several nitrile coupling partners. No prefunctionalization of the nitriles is necessary and the resulting ?-ketonitriles are obtained in good to excellent yields. The methodology also allows for a convenient (13) C-labelling of the generated carbonyl moiety.

  4. SYNTHESIS AND ANTIMICROBIAL EVALUATION OF 2-(4-FLUORO BENZYLTHIO-N-(SUBSTITUTED PHENYLPYRIMIDINE-4-AMINES

    Directory of Open Access Journals (Sweden)

    N.M. Goudgaon*, Y. Rohini Reddy and B.U. Sheshikant

    2013-11-01

    Full Text Available Reaction of 4-fluorobenzylchloride with 2-thiouracil (1 gave 2-(4-fluorobenzylthiopyrimidin-4(3H-one (2, which on chlorination with POCl3 furnished 4-chloro-2-(4-fluorobenzylthio-4-chloropyrimidine (3. This intermediate when treated with various substituted anilines gave desired targeted compounds 4(a-k in 50-90% yield. Structural assignments of the synthesized compounds were based on their IR, 1H NMR, Mass and analytical data. The antimicrobial evaluation of newly synthesized compounds was carried out by cup-plate method. The investigation of antimicrobial screening reveals that the compounds 4b, 4g, 4c and 4f showed good activity against bacterial strain B. subtilis. Compounds 4a, 4e, 4b, 4c, 4f, 4g and 4h were active against bacterial strain P. aeruginosa. Compounds 4a and 4c were active against fungul strain A. niger. Compounds 4e, 4b and 4j showed good activity against fungal strain A. flavus. All the synthesized compounds showed excellent antifungal activity against T.viridae. Remaining compounds exhibited moderate to poor activity against bacterial and fungal strains when compared to standard drugs Gentamycin and Fluconazole respectively. So, further we have carried out the antifungal screening of all the synthesized compounds at different concentrations against T. viridae to determine their IC50 values. Compounds 4e, 4b, 4g, 4i, 4d, 4f and 4j have shown better IC50 values.

  5. Optimized Anti-pathogenic Agents Based on Core/Shell Nanostructures and 2-((4-Ethylphenoxyethyl-N-(substituted-phenylcarbamothioyl-benzamides

    Directory of Open Access Journals (Sweden)

    Mariana Carmen Chifiriuc

    2012-10-01

    Full Text Available The purpose of this study was to design a new nanosystem for catheter surface functionalization with an improved resistance to Staphylococcus aureus ATCC 25923 and Pseudomonas aeruginosa ATCC 27853 colonization and subsequent biofilm development. New 2-((4 ethylphenoxymethyl-N-(substituted-phenylcarbamothioyl-benzamides were synthesized and used for coating a core/shell nanostructure. Their chemical structures were elucidated by NMR, IR and elemental analysis, being in agreement with the proposed ones. Fe3O4/C12 of up to 5 nm size had been synthesized with lauric acid as a coating agent and characterized by XRD, FT-IR, TGA, TEM and biological assays. The catheter pieces were coated with the fabricated nanofluid in magnetic field. The microbial adherence ability was investigated in 6 multiwell plates by using culture based methods and Scanning Electron Microscopy (SEM. The nanoparticles coated with the obtained compounds 1a–c inhibited the adherence and biofilm development ability of the S. aureus and P. aeruginosa tested strains on the catheter functionalized surface, as shown by the reduction of viable cell counts and SEM examination of the biofilm architecture. Using the novel core/shell/adsorption-shell to inhibit the microbial adherence could be of a great interest for the biomedical field, opening new directions for the design of film-coated surfaces with improved anti-biofilm properties.

  6. Synthesis and antileishmanial activity of new 1-Aryl-1H-Pyrazole-4- carboximidamides derivatives

    International Nuclear Information System (INIS)

    Chemotherapy for leishmaniasis, diseases caused by protozoa of the genus Leishmania, remains inefficient in several treatments. So there is a need to search for new drugs. In this work, we have synthesized 1-aryl-1H-pyrazole-4-carboximidamides derivatives and evaluated antileishmanial activities in vitro, as well as cytotoxic effects. Structure-activity relationship (SAR) studies were carried out with all the compounds of the series. Compound 2 showed an activity profile that can be improved through medicinal chemistry strategies. (author)

  7. Synthesis and antileishmanial activity of new 1-Aryl-1H-Pyrazole-4- carboximidamides derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Mauricio S. dos; Gomes, Adriana O.; Bernardino, Alice M.R.; Souza, Marcos C. de, E-mail: alicerolim@globo.co [Universidade Federal Fluminense (UFF), Niteroi, RJ (Brazil). Programa de Pos-Graduacao em Quimica Organica; Khan, Misbahul A. [The Islamia University of Bahawalpur (Pakistan). Chemistry Dept.; Brito, Monique A. de [Universidade Federal Fluminense (UFF), Niteroi, RJ (Brazil). Fac. de Farmacia. Lab. de Quimica Medicinal Computacional; Castro, Helena C.; Abreu, Paula A. [Universidade Federal Fluminense (LABioMol/GCM/UFF), Niteroi, RJ (Brazil). Inst. de Biologia. Lab. de Antibioticos, Bioquimica e Modelagem Molecular; Rodrigues, Carlos R. [Universidade Federal do Rio de Janeiro (ModMol/UFRJ), RJ (Brazil). Fac. de Farmacia. Lab. de Modelagem Molecular e QSAR; Leo, Rosa M.M. de; Leon, Leonor L.; Canto-Cavalheiro, Marilene M. [Fundacao Oswaldo Cruz (IOC/FIOCRUZ), Rio de Janeiro, RJ (Brazil). Instituto Oswaldo Cruz. Lab. de Bioquimica de Tripanosomatideos

    2011-07-01

    Chemotherapy for leishmaniasis, diseases caused by protozoa of the genus Leishmania, remains inefficient in several treatments. So there is a need to search for new drugs. In this work, we have synthesized 1-aryl-1H-pyrazole-4-carboximidamides derivatives and evaluated antileishmanial activities in vitro, as well as cytotoxic effects. Structure-activity relationship (SAR) studies were carried out with all the compounds of the series. Compound 2 showed an activity profile that can be improved through medicinal chemistry strategies. (author)

  8. Development of N-substituted quinolinimides, as potential PET tracers for the visualisation of ?-opioid receptors

    International Nuclear Information System (INIS)

    In order to develop radiotracers for in vivo studies of ?-opioid receptors by Positron Emission Tomography (PET) or Single Photon Emission computed Tomography (SPECT), we undertook the synthesis of halogenated analogues (chlorinated and brominated) of compound 12. These analogues were prepared by a convergent synthesis and from these novel structures a halogen exchange reaction has been performed to complete this series. These molecules were tested to determine their in vitro affinity and selectivity toward ? opioid receptors. The compounds 12 and 15 were labelled with carbon-11. The radiosynthesis of compound 12, in weak radioactivity chemistry, was performed first by the Stille reaction and second by a new methodology based on the transfer reaction of [11C]-methyl group. This new methodology used a mono-organotin compound prepared by addition of [11C]-iodomethane onto Lappert's stannylene. The compound [11C]-12 was obtained with 60 and 10% radiochemical yield respectively. In order to produce higher radioactivity quantities, the Stille reaction was automated. The compounds [11C]-12 and [11C]-15 were obtained in 40 minutes with a specific radioactivity ranging from 322 to 747 mCi/?mol. (author)

  9. A new synthetic route to N-benzyl carboxamides through the reverse reaction of N-substituted formamide deformylase.

    Science.gov (United States)

    Hashimoto, Yoshiteru; Sakashita, Toshihide; Fukatsu, Hiroshi; Sato, Hiroyoshi; Kobayashi, Michihiko

    2014-01-01

    Previously, we isolated a new enzyme, N-substituted formamide deformylase, that catalyzes the hydrolysis of N-substituted formamide to the corresponding amine and formate (H. Fukatsu, Y. Hashimoto, M. Goda, H. Higashibata, and M. Kobayashi, Proc. Natl. Acad. Sci. U. S. A. 101:13726-13731, 2004, doi:10.1073/pnas.0405082101). Here, we discovered that this enzyme catalyzed the reverse reaction, synthesizing N-benzylformamide (NBFA) from benzylamine and formate. The reverse reaction proceeded only in the presence of high substrate concentrations. The effects of pH and inhibitors on the reverse reaction were almost the same as those on the forward reaction, suggesting that the forward and reverse reactions are both catalyzed at the same catalytic site. Bisubstrate kinetic analysis using formate and benzylamine and dead-end inhibition studies using a benzylamine analogue, aniline, revealed that the reverse reaction of this enzyme proceeds via an ordered two-substrate, two-product (bi-bi) mechanism in which formate binds first to the enzyme active site, followed by benzylamine binding and the subsequent release of NBFA. To our knowledge, this is the first report of the reverse reaction of an amine-forming deformylase. Surprisingly, analysis of the substrate specificity for acids demonstrated that not only formate, but also acetate and propionate (namely, acids with numbers of carbon atoms ranging from C1 to C3), were active as acid substrates for the reverse reaction. Through this reaction, N-substituted carboxamides, such as NBFA, N-benzylacetamide, and N-benzylpropionamide, were synthesized from benzylamine and the corresponding acid substrates. PMID:24123742

  10. Green and selective synthesis of N-substituted amides using water soluble porphyrazinato copper(II) catalyst

    Scientific Electronic Library Online (English)

    Sara S. E., Ghodsinia; Batool, Akhlaghinia; Elham, Safaei; Hossein, Eshghi.

    2013-06-01

    Full Text Available N,N',N'',N'''-Tetrametil tetra(2,3-piridil)porfirazinato metil sulfato de cobre(II) ([Cu(2,3-tmtppa)](MeSO4)4) catalisou com sucesso a conversão direta de nitrilas a amidas N-substituídas. A síntese seletiva do tipo one pot de amidas N-substituídas a partir de nitrilas e aminas primárias foi realiza [...] da em refluxo de água. O catalisador foi recuperado e reusado no mínimo 4 vezes, mantendo a sua eficiência. Abstract in english N,N',N'',N'''-Tetramethyl tetra-2,3-pyridinoporphyrazinato copper(II) methyl sulfate ([Cu(2,3-tmtppa)](MeSO4)4) efficiently catalyzed the direct conversion of nitriles to N-substituted amides. The one pot selective synthesis of the N-substituted amides from nitriles and primary amines was performed [...] in refluxing H2O. The catalyst was recovered and reused at least four times, maintaining its efficiency.

  11. Antibacterial, antifungal and cytotoxic properties of novel N-substituted sulfonamides from 4-hydroxycoumarin.

    Science.gov (United States)

    Chohan, Zahid H; Shaikh, Ali U; Rauf, Abdul; Supuran, Claudiu T

    2006-12-01

    A new series of 4-({[2, 4-dioxo-2H-chromen-3 (4H)-ylidene] methyl} amino) sulfonamides have been obtained by the condensation reaction of 4-hydroxycoumarin with various sulfonamides (sulfanilamide, sulfaguanidine, p-aminomethyl-sufanilamide, p-aminoethylsufanilamide, sulfathiazole, sulfamethoxazole, sulfamethazine and 4-[(2-amino-4-pyrimidinyl) amino] benzenesulfonamide) in the presence of an excess of ethylorthoformate. These compounds were screened for their in-vitro antibacterial activity against four Gram-negative (E. coli, S. flexneri, P. aeruginosa and S. typhi) and two Gram-positive (B. subtilis and S. aureus) bacterial strains and for in-vitro antifungal activity against T. longifusus, C. albicans, A. flavus, M. canis, F. solani and C. glaberata. Results revealed that a significant antibacterial activity was observed by compounds (4) and (5), (6) and (8) against two Gram-negative, (P. aeruginosa and S. typhi) and two Gram-positive (B. subtilis and S. aureus) species, respectively. Of these (4) was found to be the most active. Similarly, for antifungal activity compounds (3) and (8) showed significant activity against M. canis and, (6) and (8) against F. solani. The brine shrimp bioassay was also carried out to study their in-vitro cytotoxic properties and only two compounds, (4) and (8) possessing LD50 = 2.9072 x 10(-4) and 3.2844 x 10(-4) M, respectively, displayed potent cytotoxic activity against Artemia salina PMID:17252948

  12. Discovery and SARs of Trans-3-Aryl Acrylic Acids and Their Analogs as Novel Anti- Tobacco Mosaic Virus (TMV) Agents

    OpenAIRE

    Wu, Meng; Wang, Ziwen; Meng, Chuisong; Wang, Kailiang; Hu, Yanna; Wang, Lizhong; Wang, Qingmin

    2013-01-01

    A series of trans-3-aryl acrylic acids 1–27 and their derivatives 28–34 were prepared and evaluated for their antiviral activity against tobacco mosaic virus (TMV) for the first time. The bioassay results showed that most of these compounds exhibited good antiviral activity against TMV, of which compounds 1, 5, 6, 20, 27 and 34 exhibited significantly higher activity against TMV than commercial Ribavirin both in vitro and in vivo. Furthermore, these compounds have more simple structure th...

  13. Synthesis and anticancer activity of N-substituted 2-arylquinazolinones bearing trans-stilbene scaffold.

    Science.gov (United States)

    Mahdavi, Mohammad; Pedrood, Keyvan; Safavi, Maliheh; Saeedi, Mina; Pordeli, Mahboobeh; Ardestani, Sussan Kabudanian; Emami, Saeed; Adib, Mehdi; Foroumadi, Alireza; Shafiee, Abbas

    2015-05-01

    A novel series of 2-arylquinazolinones 7a-o bearing trans-stilbene moiety were designed, synthesized, and evaluated against human breast cancer cell lines including human breast adenocarcinoma (MCF-7 and MDA-MB-231) and human ductal breast epithelial tumor (T-47D). Among the tested compounds, the sec-butyl derivative 7h showed the best profile of activity (IC50 < 5 ?M) against all cell lines, being 2-fold more potent than standard drug, etoposide. Our investigation revealed that the cytotoxic activity was significantly affected by N3-alkyl substituents. Furthermore, the morphological analysis by acridine orange/ethidium bromide double staining test and flow cytometry analysis indicated that the prototype compound 7h can induce apoptosis in MCF-7 and MDA-MB-231 cells. PMID:25847767

  14. Synthesis and Biological Activity of N-Substituted-3-chloro-2-azetidinones

    OpenAIRE

    Pai, Nandini R.; Chavan, Ameya A.

    2007-01-01

    2-Aminobenzothiazole-6-carboxylic acid (1), on condensation with chloroacetylchloride yielded 2-(2-chloroacetylamino)benzothiazole-6-carboxylic acid (2), which onamination with hydrazine hydrate yielded in turn 2-(2-hydrazinoacetylamino)benzo-thiazole-6-carboxylic acid (3). Compound 3, on condensation with various aromaticaldehydes afforded a series of 2-{2-[N’-(arylidene)hydrazino]acetylamino}benzothiazole-6-carboxylic acids 4a-h, which upon dehydrative annulation in the presenc...

  15. Synthesis of N-substituted phthalimidoalkyl 1,2,3-triazoles via click chemistry

    Directory of Open Access Journals (Sweden)

    Moara T. da Silva

    2012-06-01

    Full Text Available In the present work, we have developed a facile procedure for synthesis of new N-phthalimidoalkyl 1H-1,2,3-Triazoles (1-4(a-h using DMF, 10 mol% CuI, Et3N and ultrasound energy at room temperature. This protocol furnished 28 new compounds in 20 to 30 min of reaction and moderate-to-excellent yields (64-94%.

  16. Indium-catalyzed annulation of 2-aryl- and 2-heteroarylindoles with propargyl ethers: concise synthesis and photophysical properties of diverse aryl- and heteroaryl-annulated[a]carbazoles.

    Science.gov (United States)

    Tsuchimoto, Teruhisa; Matsubayashi, Hiromichi; Kaneko, Masayoshi; Nagase, Yuta; Miyamura, Takuhiro; Shirakawa, Eiji

    2008-11-26

    Treatment of 2-aryl- and 2-heteroarylindoles with propargyl ethers in the presence of a catalytic amount of indium nonafluorobutanesulfonate [In(ONf)(3)] gave aryl- and heteroaryl-annulated[a]carbazoles in good yields. The synthetically attractive feature is reflected by its applicability to a wide range of 2-aryl- and 2-heteroarylindoles. In the annulation reaction, propargyl ethers act as C3 sources (HC[triple bond]C-CH(2)OR). Among these, two carbon atoms are incorporated into the product as members of a newly constructed aromatic ring and the remaining carbon atom forms a methyl group on the aromatic ring, where the methyl group is always located next to the C3 position of the indole nucleus. The methyl group can be easily removed through SeO(2) oxidation followed by decarbonylation with RhCl(CO)(PPh(3))(2)-Ph(2)P(CH(2))(3)PPh(2) as a catalyst. The new annulation strategy is applicable also to symmetrical dimers such as bithiophene and bifuran derivatives. Mechanistic studies suggest that the first step is addition reaction initiated by regioselective nucleophilic attack of the C3 of 2-aryl- and 2-heteroarylindoles to the internal carbon atom of the C[triple bond]C bond in propargyl ethers. The next stage is ring-closing S(N)2 process kicking out the alkoxy group and then aromatization via a 1,3-hydrogen shift is the final step. The two carbon-carbon bond-forming reactions achieved in one-pot contribute largely to the reduction in the number of steps for the synthesis of aryl- and heteroaryl-annulated[a]carbazoles. Furthermore, utilization of the Fischer indole synthesis for efficient supply of the substrates, 2-aryl- and 2-heteroarylindoles, is another important factor shortening the overall process. The development of the annulation with a wide substrate scope provided a unique opportunity to evaluate photophysical properties of a series of aryl- and heteroaryl-annulated[a]carbazoles. Almost all the compounds evaluated in this study were found to emit purple to green light in the visible region. Some interesting structure-property correlations are also described. PMID:18980318

  17. Pseudopericyclic 1,5- versus Pericyclic 1,4- and 1,6-Electrocyclization in Electron-Poor 4-Aryl-2-azabuta-1,3-dienes: Indole Synthesis from 2H-Azirines and Diazo Compounds.

    Science.gov (United States)

    Novikov, Mikhail S; Khlebnikov, Alexander F; Rostovskii, Nikolai V; Tcyrulnikov, Sergei; Suhanova, Anna A; Zavyalov, Kirill V; Yufit, Dmitry S

    2015-01-01

    Transformations of 2-azabuta-1,3-dienes, formed in Rh2(OAc)4-catalyzed reactions of diazo carbonyl compounds with 2H-azirines, dramatically depend on the nature of substituents. 4,4-Diphenyl-2-azabuta-1,3-dienes with two electron-acceptor substituents at C(1) undergo thermal 1,5-cyclization to give indoles in good yields. The increase in electron-withdrawing ability of C(1)-substituents facilitates the reaction that proceeds via pseudopericyclic 1,5-electrocyclization of 2-azabutadiene into 7aH-indolium ylide followed by prototropic shift. 3,4-Diphenyl-2-azabuta-1,3-dienes, resulting from reaction of 2,3-diphenyl-2H-azirine and diazo compounds, do not produce indoles via 1,5-cyclization due to the trans-configuration of the 4-Ph-group and the nitrogen, but undergo 1,4-cyclization to 2,3-dihydroazetes. 1,6-Cyclization into 2H-1,4-oxazines with participation of the oxygen of ester or amide group at C(1) of corresponding 2-azabuta-1,3-dienes does not take place due to kinetic and thermodynamic reasons. Instead of this, 1,6-electrocyclization with participation of phenyl substituent at C(4) of the 2-azabuta-1,3-dienes, providing isoquinoline derivatives, can occur at elevated temperatures. The DFT-calculations (mPWB1K/6-31+G(d,p)) confirm the dependence of 2-azabuta-1,3-diene transformation type on the nature of substituents. PMID:25436997

  18. Synthesis of novel substituted N-aryl benzamides as hA3G stabilizers and their inhibitory activities against hepatitis C virus replication

    Directory of Open Access Journals (Sweden)

    Yanping Li

    2013-09-01

    Full Text Available A series of novel amino-substituted N-aryl benzamide analogs were synthesized and evaluated for their ability to inhibit hepatitis C virus (HCV replication in acutely infected Huh7.5 cells. Most of the substituted N-aryl benzamide compounds showed convincing anti-HCV activities. Compounds 1f, 1g and 4c exhibited potent anti-replicative activity at low micromolar levels (IC50=1.0–2.0 ?M with selective indices (SI greater than 40. Mechanistic analysis indicated that the active compounds increased intracellular hA3G protein levels and inhibited HCV replication in a dose-dependent manner. The results demonstrate that this series of substituted N-aryl benzamide compounds warrant further investigation as inhibitors of HCV replication.

  19. Novel Synthesis and Anti-HIV-1 Activity of 2-Arylthio-6-benzyl-2,3-dihydro-1H-pyrimidin-4-ones (Aryl S-DABOs)

    DEFF Research Database (Denmark)

    Aly, Youssef L.; Pedersen, Erik Bjerreg.

    2007-01-01

    The synthesis and the anti-HIV-1 activity of a series of 2-arylthio-6-benzyl-2,3-dihydro-1H-pyrimidin-4-ones (aryl S-DABOs) are reported. These compounds were synthesized via a coupling reaction of the corresponding 6-benzyl-2-thiouracils with aryl iodides in the presence of neocuproine hydrate, copper(I) iodide, and sodium tert-butoxide. Target compounds showed moderate activity against HIV-1.

  20. Polymeric media comprising polybenzimidazoles N-substituted with organic-inorganic hybrid moiety

    Science.gov (United States)

    Klaehn, John R. (Idaho Falls, ID) [Idaho Falls, ID; Peterson, Eric S. (Idaho Falls, ID) [Idaho Falls, ID; Wertsching, Alan K. (Idaho Falls, ID) [Idaho Falls, ID; Orme, Christopher J. (Shelley, ID) [Shelley, ID; Luther, Thomas A. (Idaho Falls, ID) [Idaho Falls, ID; Jones, Michael G. (Pocatello, ID) [Pocatello, ID

    2009-12-15

    A PBI compound includes imidazole nitrogens at least a portion of which are substituted with an organic-inorganic hybrid moiety may be included in a separator medium. At least 85% of the imidazole nitrogens may be substituted. The organic-inorganic hybrid moiety may be an organosilane moiety, for example, (R)Me.sub.2SiCH.sub.2-- where R is selected from among methyl, phenyl, vinyl, and allyl. The separatory medium may exhibit an H.sub.2, Ar, N.sub.2, O.sub.2, CH.sub.3, or CO.sub.2 gas permeability greater than the gas permeability of a comparable separatory medium comprising the PBI compound without substitution. The separatory medium may further include an electronically conductive medium and/or ionically conductive medium. The separatory medium may be used as a membrane (semi-permeable, permeable, and non-permeable), a barrier, an ion exhcange media, a filter, a gas chromatography coating (such as stationary phase coating in affinity chromatography), etc.

  1. Cavity ring-down spectroscopy of the 6?3 bands of 15N substituted N2O

    International Nuclear Information System (INIS)

    The 6?3 and ?2+6?3-?2 bands of 15N substituted nitrous oxide isotopologues have been recorded by a continuous-wave cavity ring-down spectrometer (CW-CRDS) operated near 0.8?m. The sensitivity limit was at the level of 1x10-10/cm. In total, 213, 86 and 191 transitions were observed for the 14N15N16O, 15N14N16O and 15N216O isotopologues, respectively. The ro-vibrational spectroscopic parameters of the upper states are determined from least square fitting of the transitions. The absolute line intensities of the 6?3 cold bands have been retrieved by a multi-line fitting procedure from the spectra with an estimated accuracy of 4% for majority of the unblended lines. The vibrational transition dipole moment squared values and the empirical Herman-Wallis coefficients are also presented.

  2. Aryl carbinols as nerve agent probes. Influence of the conjugation on the sensing properties

    OpenAIRE

    Royo Calvo, Santiago; Gotor Candel, Raul Jesús; COSTERO NIETO, ANA MARIA; PARRA ALVAREZ, MARGARITA; GIL GRAU, SALVADOR; Martínez Mañez, Ramón; Sancenón Galarza, Félix

    2012-01-01

    Two new aryl carbinols (1 and 3) have been synthesised and characterised and their ability as OFF-ON probes for the chromogenic detection of the nerve agent simulant in acetonitrile has been tested. In addition compound 2 has been also studied. The carbinols suffered a phosphorylation reaction followed by an elimination process giving rise to the corresponding carbocations. This transformation of the carbinol into the carbocation is responsible for a significant color change. © The Royal Soc...

  3. The Pd-Catalyzed Conversion of Aryl Chlorides, Triflates, and Nonaflates to Nitroaromatics

    Science.gov (United States)

    Fors, Brett P.; Buchwald, Stephen L.

    2009-01-01

    An efficient Pd-catalyst for the transformation of aryl chlorides, triflates and nonaflates to nitroaromatics has been developed. This reaction proceeds under weekly basic conditions and displays a broad scope and excellent functional group compatibility. Moreover, this method allows for the synthesis of aromatic nitro compounds that cannot be accessed efficiently via other nitration protocols. Mechanistic insight into the trasmetallation step of the catalytic process is also reported. PMID:19737014

  4. The Aryl Hydrocarbon Receptor Meets Immunology: Friend or Foe? A Little of Both

    OpenAIRE

    Julliard, Walker; Fechner, John H.; Mezrich, Joshua D.

    2014-01-01

    The aryl hydrocarbon receptor (AHR) has long been studied by toxicologists as a ligand-activated transcription factor that is activated by dioxin and other environmental pollutants such as polycyclic aromatic hydrocarbons (PAHs). The hallmark of AHR activation is the upregulation of the cytochrome P450 enzymes that metabolize many of these toxic compounds. However, recent findings demonstrate that both exogenous and endogenous AHR ligands can alter innate and adaptive immune responses includi...

  5. Synthesis of 2-Aryl benzothiazoles via K2S2O8-mediated oxidative condensation of benzothiazoles with aryl aldehydes.

    Science.gov (United States)

    Yang, Zhiyong; Chen, Xiang; Wang, Sizhuo; Liu, Jidan; Xie, Kai; Wang, Anwei; Tan, Ze

    2012-08-17

    Nontransition metal-catalyzed synthesis of 2-aryl benzothiazoles was achieved through K(2)S(2)O(8)-mediated oxidative condensation of benzothiazoles with aryl aldehydes. The same transformation can also be effected when the aryl aldehydes were replaced with phenylglyoxylic acids. PMID:22835066

  6. Enantioselective alpha-arylation of ketones with aryl triflates catalyzed by difluorphos complexes of palladium and nickel.

    Science.gov (United States)

    Liao, Xuebin; Weng, Zhiqiang; Hartwig, John F

    2008-01-01

    The asymmetric alpha-arylation of ketones with aryl triflates is described, and the use of this electrophile with nickel and palladium catalysts containing a segphos derivative increases substantially the scope of highly enantioselective arylations of ketone enolates. The combination of aryl triflates as reactant, difluorphos as ligand, palladium catalysts for reactions of electron-neutral or electron-rich aryl triflates, and nickel catalysts for reactions of electron-poor aryl triflates led to a series of alpha-arylations of tetralone, indanone, cyclopentanone, and cyclohexanone derivatives. Enantioselectivities ranged from 70% to 98% with 10 examples over 90%. Systematic studies on these alpha-arylations have revealed a number of factors that affect enantioselectivity. Ligands containing biaryl backbones with smaller dihedral angles generate catalysts that react with higher enantioselectivity than related ligands with larger dihedral angles. In addition, faster rates for reactions of aryl triflates versus those for reactions of aryl bromides allow the alpha-arylations of aryl triflates to be conducted at lower temperatures, and this lower temperature improves enantioselectivity. Finally, studies that compare the enantioselectivities of catalytic reactions to those of stoichiometric reactions of isolated [(segphos)Pd(Ar)(Br)], [(segphos)Pd(Ar)(I)], and [(segphos)Ni(C6H4-4-CN)Br] suggest that catalyst decomposition affects enantioselectivity. PMID:18076166

  7. Diphosphine dioxides as extractants for actinides (in connection with the problem of anomalous aryl strengthening of complexes)

    International Nuclear Information System (INIS)

    Extraction study of uranylnitrate, plutonium in trivalent, tetravalent and gexavalent states and trivalent americium, curium, praseodymium and promethium by alkyl, aromatic and mixed diphosphine dioxides is briefly outlined. The influence of diphosphine dioxide structures on their extraction capacity and, in particular, the problem of anomalous aryl strengthening of compounds, both of entropy and binding character, are considered. Perchlorate media, as opposed to nitrate ones, are characteristic for their high distribution coefficients and extraction equilibrium constants. Anomalous aryl strengthening of trivalent lanthanides and actinides can be applied, at the minimum, for solution purifications from the traces of actinides and lanthanides

  8. Aryl Polyphosphonates: Useful Halogen-Free Flame Retardants for Polymers

    Directory of Open Access Journals (Sweden)

    Li Chen

    2010-10-01

    Full Text Available Aryl polyphosphonates (ArPPN have been demonstrated to function in wide applications as flame retardants for different polymer materials, including thermosets, polycarbonate, polyesters and polyamides, particularly due to their satisfactory thermal stability compared to aliphatic flame retardants, and to their desirable flow behavior observed during the processing of polymeric materials. This paper provides a brief overview of the main developments in ArPPN and their derivatives for flame-retarding polymeric materials, primarily based on the authors’ research work and the literature published over the last two decades. The synthetic chemistry of these compounds is discussed along with their thermal stabilities and flame-retardant properties. The possible mechanisms of ArPPN and their derivatives containing hetero elements, which exhibit a synergistic effect with phosphorus, are also discussed.

  9. N-SUBSTITUTION AND á1-ADRENERGIC RECEPTOR AFFINITY OF LAUDANOSINE ANALOGUES

    Directory of Open Access Journals (Sweden)

    PATRICIO ITURRIAGA-VÁSQUEZ

    2006-09-01

    Full Text Available Benzyltetrahydroisoquinoline (BTHIQ molecules are able to adopt widely differing conformations that depend on the presence or absence of N-substituents. To assess the possible role of BTHIQ conformation on the affinity of these compounds for a 1-adrenergic receptors, of interest for the management of hypertension, the racemic N-unsubstituted BTHIQ norlaudanosine and a series of N-alkylated derivatives were assessed for binding to rat brain cortical sites labelled with the radioligand [³H]prazosin. The a 1-adrenergic affinity in this series increased with the bulk of the substituent on the nitrogen atom, from the N-ethyl to the N-propyl analogue. Comparison of these results with published data for related BTHIQs and for the rigid mimics of the fully extended and semi-folded conformations of laudanosine, tetrahydropalmatine and glaucine, suggested that the a 1-adrenergic receptor binding site is able to accommodate either conformation. The presence of a bulky substituent on the nitrogen atom seems to favor receptor binding independently of the favored conformation, and that the orientation in which BTHIQs are bound probably differs depending on the presence or absence of a hydroxyl group at a key position

  10. N-SUBSTITUTION AND á1-ADRENERGIC RECEPTOR AFFINITY OF LAUDANOSINE ANALOGUES

    Scientific Electronic Library Online (English)

    PATRICIO, ITURRIAGA-VÁSQUEZ; BRUCE K, CASSELS; M. DOLORES, IVORRA; M. PILAR, D' OCON.

    2006-09-01

    Full Text Available Benzyltetrahydroisoquinoline (BTHIQ) molecules are able to adopt widely differing conformations that depend on the presence or absence of N-substituents. To assess the possible role of BTHIQ conformation on the affinity of these compounds for a 1-adrenergic receptors, of interest for the management [...] of hypertension, the racemic N-unsubstituted BTHIQ norlaudanosine and a series of N-alkylated derivatives were assessed for binding to rat brain cortical sites labelled with the radioligand [³H]prazosin. The a 1-adrenergic affinity in this series increased with the bulk of the substituent on the nitrogen atom, from the N-ethyl to the N-propyl analogue. Comparison of these results with published data for related BTHIQs and for the rigid mimics of the fully extended and semi-folded conformations of laudanosine, tetrahydropalmatine and glaucine, suggested that the a 1-adrenergic receptor binding site is able to accommodate either conformation. The presence of a bulky substituent on the nitrogen atom seems to favor receptor binding independently of the favored conformation, and that the orientation in which BTHIQs are bound probably differs depending on the presence or absence of a hydroxyl group at a key position

  11. Catalytic asymmetric synthesis of sterically hindered tertiary ?-aryl ketones.

    Science.gov (United States)

    Doran, Robert; Guiry, Patrick J

    2014-10-01

    The catalytic asymmetric synthesis of a series of tertiary ?-aryl cyclopentanones and cyclohexanones has been accomplished via a Pd-catalyzed decarboxylative protonation of the corresponding ?-aryl-?-keto allyl esters. Enantioselectivities of up to 92% ee and 74% ee were achieved for cyclopentanone and cyclohexanone substrates, respectively. The route described gives access to these important structural motifs in moderate to high levels of enantioselectivity. In particular, this is only the second direct approach for the preparation of tertiary ?-aryl cyclopentanones. The synthetic approach allows for simple modification of the aryl group. Significantly, substrates containing sterically hindered aryl groups gave the highest levels of enantioselectivity, and these aryl groups were readily installed by a Pb-mediated arylation of a ?-keto allyl ester. PMID:25233274

  12. Cloning and heterologous expression of two aryl-aldehyde dehydrogenases from the white-rot basidiomycete Phanerochaete chrysosporium

    International Nuclear Information System (INIS)

    We identified two aryl-aldehyde dehydrogenase proteins (PcALDH1 and PcALDH2) from the white-rot basidiomycete Phanerochaete chrysosporium. Both PcALDHs were translationally up-regulated in response to exogenous addition of vanillin, one of the key aromatic compounds in the pathway of lignin degradation by basidiomycetes. To clarify the catalytic functions of PcALDHs, we isolated full-length cDNAs encoding these proteins and heterologously expressed the recombinant enzymes using a pET/Escherichia coli system. The open reading frames of both PcALDH1 and PcALDH2 consisted of 1503 nucleotides. The deduced amino acid sequences of both proteins showed high homologies with aryl-aldehyde dehydrogenases from other organisms and contained ten conserved domains of ALDHs. Moreover, a novel glycine-rich motif 'GxGxxxG' was located at the NAD+-binding site. The recombinant PcALDHs catalyzed dehydrogenation reactions of several aryl-aldehyde compounds, including vanillin, to their corresponding aromatic acids. These results strongly suggested that PcALDHs metabolize aryl-aldehyde compounds generated during fungal degradation of lignin and various aromatic xenobiotics.

  13. Cloning and heterologous expression of two aryl-aldehyde dehydrogenases from the white-rot basidiomycete Phanerochaete chrysosporium

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, Tomofumi [Faculty of Agriculture, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581 (Japan); Fukuoka Institute of Health and Environmental Sciences, 39 Mukaizano, Dazaifu-shi, Fukuoka 818-0135 (Japan); Ichinose, Hirofumi [Faculty of Agriculture, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581 (Japan); Wariishi, Hiroyuki, E-mail: hirowari@agr.kyushu-u.ac.jp [Faculty of Agriculture, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581 (Japan); Bio-Architecture Center, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581 (Japan); Innovation Center for Medical Redox Navigation, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581 (Japan)

    2010-04-09

    We identified two aryl-aldehyde dehydrogenase proteins (PcALDH1 and PcALDH2) from the white-rot basidiomycete Phanerochaete chrysosporium. Both PcALDHs were translationally up-regulated in response to exogenous addition of vanillin, one of the key aromatic compounds in the pathway of lignin degradation by basidiomycetes. To clarify the catalytic functions of PcALDHs, we isolated full-length cDNAs encoding these proteins and heterologously expressed the recombinant enzymes using a pET/Escherichia coli system. The open reading frames of both PcALDH1 and PcALDH2 consisted of 1503 nucleotides. The deduced amino acid sequences of both proteins showed high homologies with aryl-aldehyde dehydrogenases from other organisms and contained ten conserved domains of ALDHs. Moreover, a novel glycine-rich motif 'GxGxxxG' was located at the NAD{sup +}-binding site. The recombinant PcALDHs catalyzed dehydrogenation reactions of several aryl-aldehyde compounds, including vanillin, to their corresponding aromatic acids. These results strongly suggested that PcALDHs metabolize aryl-aldehyde compounds generated during fungal degradation of lignin and various aromatic xenobiotics.

  14. Pd-Catalyzed Synthesis of Ar–SCF3 Compounds Under Mild Conditions**

    OpenAIRE

    Teverovskiy, Georgiy; Surry, David S.; Buchwald, Stephen L.

    2011-01-01

    Good to excellent yields of aryl trifluoromethyl sulfides, which are an important class of compounds in both the pharmaceutical and agrochemical areas, can be achieved under mild conditions by the Pd-catalyzed reaction of aryl bromides with a trifluoromethylthiolate nucleophile (see scheme).

  15. Synthesis of N-substituted Cyclic Hydrocarbons, such as Pyrimidine, in The Ionosphere of Titan

    Science.gov (United States)

    Bera, P. P.; Peverati, R.; Head-Gordon, M.; Lee, T. J.

    2014-12-01

    The instruments on board the CASSINI spacecraft observed large carbonaceous molecules in the upper atmosphere of Titan. How these large polyatomic molecules are synthesized in such exotic conditions is, thus far, unknown. Molecular ions, including positive and negative ions, are in relative abundance in the ionosphere of Titan. Hence, barrierless ion-molecule interactions may play a major role in guiding molecules towards each other and initiating reactions. We study these condensation pathways to determine whether they are a viable means of forming large pure hydrocarbon molecules, and nitrogen-containing carbonaceous chains, stacks, and even cyclic compounds. By employing accurate quantum chemical methods we have investigated the processes of growth, structures, nature of bonding, mechanisms, and spectroscopic properties of the ensuing ionic products after pairing small carbon, hydrogen, and nitrogen-containing molecules with major ions observed in the upper atmosphere of Titan, e.g. C2H5+ and HCNH+. We have also studied the ion-neutral association pathways involving pure-carbon molecules e.g. acetylene, ethylene and other hydrocarbons, and their dissociation fragments in a plasma discharge. We have investigated how nitrogen atoms are incorporated into the carbon ring during growth. Specifically, we explored the mechanisms by which the synthesis of pyrimidine will be feasible in the atmosphere of Titan in conjunction with ion-mobility experiments. We have used accurate ab initio coupled cluster theory, Møller-Plesset perturbation theory, density functional theory, and coupled cluster theory quantum chemical methods together with large correlation consistent basis sets in these investigations. We found that a series of hydrocarbons with a specific stoichiometric composition prefers cyclic molecule formation rather than chains. Some of the association products we investigated have large oscillator strengths for charge-transfer type electronic excitations in the near infrared and visible regions of the electromagnetic spectrum. Our quantum chemistry computations complement well the results from the molecular/ion plasma experiments performed by the Laboratory Astrochemistry groups at Ames.

  16. Synthesis of 2,3-Dioxo-5-(substitutedarylpyrroles and Their 2-Oxo-5-aryl-3-hydrazone Pyrrolidine Derivatives

    Directory of Open Access Journals (Sweden)

    A. S. Hamzah

    2009-01-01

    Full Text Available Some novel2,3-dioxo-5-(substitutedarylpyrroles have been synthesized. Among these, pyrrolidine compound 1b was converted to 2,3-dioxo-5-aryl pyrrolidine 2b. Finally a set of hydrazone derivatives was obtained from the reaction of 2b with various hydrazine salts. The structures of all the new synthesized compounds were confirmed by elemental analyses, IR and 1H-NMR spectra.

  17. Palladium(0)-catalyzed arylative dearomatization of phenols.

    OpenAIRE

    Rousseaux, S.; Garci?a-fortanet, J.; Del Aguila Sanchez, Ma; Buchwald, Sl

    2011-01-01

    The palladium-catalyzed arylative dearomatization of phenols to yield spirocyclohexadienone products in good to excellent yields has been developed. Preliminary results demonstrate that the formation of the spirocyclic all-carbon quaternary center can be accomplished with high levels of enantiocontrol (up to 91% ee).

  18. Formation Routes For Pure and N-substituted Cyclic Hydrocarbon Molecules in The Ionosphere of Titan

    Science.gov (United States)

    Bera, P. P.; Peverati, R.; Head-Gordon, M.; Lee, T. J.

    2013-12-01

    Titan's upper atmosphere contains large carbonaceous molecules as has been observed by the instruments on board the CASSINI spacecraft. How these large polyatomic molecules are synthesized in such exotic conditions is, thus far, unknown. Molecular ions are in relative abundance in the ionosphere of Titan. Hence, barrierless ion-molecule interactions may play a major role in guiding molecules towards each other and initiating reactions. We study these cold condensation pathways to determine whether they are a viable means of forming large pure hydrocarbon molecules, and nitrogen-containing carbonaceous chains, stacks, and even cyclic compounds. By employing accurate quantum chemical methods we have investigated the processes of growth, structures, nature of bonding, mechanisms, and spectroscopic properties of the ensuing ionic products after pairing small carbon, hydrogen, and nitrogen-containing molecules with major ions observed in the upper atmosphere of Titan, e.g. C2H5+ and HCNH+. We have also studied the ion-neutral association pathways involving pure-carbon molecules e.g. acetylene, ethylene and other hydrocarbons, and their dissociation fragments in a plasma discharge. Additionally, we have investigated how nitrogen atoms are incorporated into the carbon ring during growth. We have used accurate ab initio coupled cluster theory, Møller-Plesset perturbation theory and density functional theory quantum chemical methods together with large correlation consistent basis sets in these investigations. We also employed time-dependent density functional theory and equations-of-motion coupled cluster theory to compute electronic excitation energies and oscillator strengths of the products of the ion-molecule reactions. We obtained accurate vibrational frequencies under the harmonic approximation and vibrational intensities using the double harmonic approximation for fundamental molecular vibrations. We identified three types of bonding motifs with strong, moderate, and weak binding energies among the carbonaceous complexes. Both linear and cyclic isomers identified on the potential energy surface of these molecular complexes are expected to form rather easily due to electrostatic interactions. We uncovered that a series of hydrocarbons with a specific stoichiometric composition prefers cyclic molecule formation rather than chains. Some of the association products we investigated have large oscillator strengths for charge-transfer type electronic excitations in the near infrared and visible regions of the electromagnetic spectrum. Our quantum chemistry computations complement well the results from the molecular/ion plasma experiments performed by the Laboratory Astrochemistry groups at Ames. P. P. Bera, Martin Head-Gordon, and Timothy J. Lee Astron & Astrophys. 535, A74, (2011) P. P. Bera, M. Head-Gordon, and T. J. Lee, 15, 2012-2023,Phys. Chem. Chem. Phys. (2013) P. P. Bera, Roberto Peverati, M. Head-Gordon, and Timothy J. Lee, To be submitted (2013)

  19. Synthesis and Fungicidal Activity of Novel Chloro-Containing 1-Aryl-3-oxypyrazoles with an Oximino Ester or Oximino Amide Moiety

    Directory of Open Access Journals (Sweden)

    Yuanyuan Liu

    2014-06-01

    Full Text Available Six novel chloro-containing 1-aryl-3-oxypyrazoles TMa–TMf with an oximino ester or an oximino amide moiety were prepared by the reaction of 1-aryl-1H-pyrazol-3-ols with benzyl bromide. Their structures were characterized by 1H-NMR, 13C-NMR, IR, MS, and elemental analysis. A preliminary in vitro bioassay indicated that compounds TMa, TMe and TMf displayed excellent fungicidal activity against Rhizoctonia solani and could be used as potential lead compounds for further development of novel fungicides.

  20. Synthesis of novel 2-alkoxy-3-amino-3-arylpropan-1-ols and 5-alkoxy-4-aryl-1,3-oxazinanes with antimalarial activity.

    Science.gov (United States)

    D'hooghe, Matthias; Dekeukeleire, Stijn; Mollet, Karen; Lategan, Carmen; Smith, Peter J; Chibale, Kelly; De Kimpe, Norbert

    2009-07-01

    A variety of novel syn-2-alkoxy-3-amino-3-arylpropan-1-ols was prepared through LiAlH(4)-promoted reductive ring-opening of cis-3-alkoxy-4-aryl-beta-lactams in Et(2)O. The latter gamma-aminoalcohols were easily converted into cis-5-alkoxy-4-aryl-1,3-oxazinanes using formaldehyde in THF. Both series of compounds were evaluated against a chloroquine sensitive strain of Plasmodium falciparum (D10), revealing micromolar potency for almost all representatives. Eleven compounds exhibited antimalarial activity with IC(50) values of cytotoxicity at the concentrations tested. PMID:19463002

  1. Microwave Assisted Condensation Reactions of 2-Aryl Hydrazonopropanals with Nucleophilic Reagents and Dimethyl Acetylenedicarboxylate

    OpenAIRE

    Rita M. Borik; Khadijah M. Al-Zaydi

    2007-01-01

    The reaction of methyl ketones 1a-g with dimethylformamide dimethylacetal (DMFDMA) afforded the enaminones 2a-g, which were coupled with diazotized aromatic amines 3a,b to give the corresponding aryl hydrazones 6a-h. Condensation of compounds 6a-h with some aromatic heterocyclic amines afforded iminoarylhydrazones 9a-m. Enaminoazo compounds 12a,b could be obtained from condensation of 6c with secondary amines. The reaction of 6e,h with benzotriazolylacetone yielded 14a,b. Also, the reaction o...

  2. Design, Synthesis and Anti-Tobacco Mosaic Virus (TMV Activity of 5-Chloro-N-(4-cyano-1-aryl-1H-pyrazol-5-yl-1-aryl-3-methyl-1H-pyrazole-4-carboxamide Derivatives

    Directory of Open Access Journals (Sweden)

    Jin-Jing Xiao

    2015-01-01

    Full Text Available A series of novel pyrazole amide derivatives 3a–3p which take TMV PC protein as the target has been designed and synthesized by the reactions of 5-chloro-1-aryl-3-methyl-1H-pyrazole-4-carboxylic acids with 5-amino-1-aryl-1H-pyrazole-4-carbonitriles. All the compounds were characterized by 1H-NMR, mass spectroscopy and elemental analysis. Preliminary bioassays indicated that all the compounds acted against the tobacco mosaic virus (TMV with different in vivo and in vitro modes at 500 ?g/mL and were found to possess promising activity. Especially, compound 3p showed the most potent biological activity against tobacco mosaic virus (TMV compared to ningnanmycin, and a molecular docking study was performed and the binding model revealed that the pyrazole amide moiety was tightly embedded in the binding sites of TMV PC (PDB code: 2OM3.

  3. Infrared study of lignin: Reexamination of aryl-alkyl ether C-O stretching peak assignments

    International Nuclear Information System (INIS)

    Infrared (IR) C-O ether stretching peak assignments of beta- O-4 interunit bonds and methoxyl groups have been assigned by isotope labeling. The Caryl-O peak for both types of ethers was typically found at 1262-1224 cm-1, but syringyl and 3,5-dimethoxyl derivatives gave Caryl-O peaks of 1328-1295 cm-1 and 1254-1204 cm-1. The Caryl-O peak for all ethers was found at 1047-1004 cm-1. These assignments are similar to values reported in general IR tables for aryl-alkyl ethers, except for the unusually high Caryl-O stretch for syringyl and 3,5- dimethoxyl compounds. IR shift tables also often list a peak at 1176 cm-1 associated with the Caryl-O bond of aryl-alkyl ethers. It is doubtful the peaks observed in this region are due to the Caryl-O bond

  4. Electrochemical and Physical properties of N-substituted arylmethylene pyrrole polymers and N-alkylmethine pyrrole copolymers

    International Nuclear Information System (INIS)

    Highlights: •N-Arylmethylene and methine pyrroles were electropolymerised into polymers and copolymers. •N-arylmethylene pyrrole monomers readily formed stable homopyrrole polymer films. •N-alkylmethine pyrrole monomers only formed stable copolymers films with pyrrole. •N-(1,2-dicarboxyethyl)-1H-pyrrole films readily complexed Cu+ or Cd2+ ions under a applied–ve field. -- Abstract: The electrochemical behaviour of N-arylmethylene and N-alkylmethine pyrrole monomers were investigated in their ability to be electropolymerised into polymer and co-polymer films with pyrrole using the techniques of cyclic voltammetry and scanning electron microscopy (SEM). N-substituted arylmethylene pyrrole monomers readily formed homopolymers by the oxidative electropolymerisation of pyrrole monomers by potentiostatic cycling in acetonitrile containing tetrabutylammonium perchlorate. The polymer films formed were brown in appearance and redox active, with the exception of the 1-((4-chlorophenyl)methyl)-1H-pyrrole (1d) which formed a pale yellow film lacking redox activity. The thickness of films produced calculated on the charge consumed followed the order 1e + and Cd2+ ions at a concentration of 1 × 10?4 M under an applied–ve field and to release the metal ion on stepping the potential to zero

  5. PALLADIUM CATALYZED COUPLING OF ARYL HALIDES WITH ARYLHALOSILANES IN AIR AND WATER. (R828129)

    Science.gov (United States)

    In the presence of a palladium catalyst, various aryl halides reacted with arylhalosilanes in aqueous media and under an air atmosphere to give the corresponding unsymmetrical aryl–aryl coupling products conveniently. ...

  6. Discovery and SARs of Trans-3-Aryl Acrylic Acids and Their Analogs as Novel Anti- Tobacco Mosaic Virus (TMV) Agents

    Science.gov (United States)

    Wu, Meng; Wang, Ziwen; Meng, Chuisong; Wang, Kailiang; Hu, Yanna; Wang, Lizhong; Wang, Qingmin

    2013-01-01

    A series of trans-3-aryl acrylic acids 1–27 and their derivatives 28–34 were prepared and evaluated for their antiviral activity against tobacco mosaic virus (TMV) for the first time. The bioassay results showed that most of these compounds exhibited good antiviral activity against TMV, of which compounds 1, 5, 6, 20, 27 and 34 exhibited significantly higher activity against TMV than commercial Ribavirin both in vitro and in vivo. Furthermore, these compounds have more simple structure than commercial Ribavirin, and can be synthesized more efficiently. These new findings demonstrate that trans-3-aryl acrylic acids and their derivatives represent a new template for antiviral studies and could be considered for novel therapy against plant virus infection. PMID:23418574

  7. Palladium-Catalyzed alpha-Arylation of Tetramic Acids

    DEFF Research Database (Denmark)

    Storgaard, Morten; Dorwald, F. Z.

    2009-01-01

    A mild, racemization-free, palladium-Catalyzed alpha-arylation of tetramic acids (2,4-pyrrolidinediones) has been developed. Various amino acid-derived tetramic acids were cleanly arylated by treatment with 2 mol % of Pd(OAc)(2), 4 mol % of a sterically demanding biaryl phosphine, 2.3 equiv of K2CO3 or K3PO4, and aryl chlorides, bromides, or triflates in THF. With conventional heating, conversions >95% could be attained after 1 h at 80 degrees C, whereas microwave-induced heating led to much shorter reaction times (5 min at 110 degrees C). The electron density of the aryl electrophile had no effect on their reactivity: both electron-rich and electron-poor aryl chlorides and bromides or triflates led to good yields. Ortho-substituted aryl halides and heteroaryl halides, however, did not undergo the title reaction.

  8. Design, synthesis, and biological evaluation of benzofuran- and 2,3-dihydrobenzofuran-2-carboxylic acid N-(substituted)phenylamide derivatives as anticancer agents and inhibitors of NF-?B.

    Science.gov (United States)

    Choi, Minho; Jo, Hyeju; Park, Hyun-Jung; Sateesh Kumar, Arepalli; Lee, Joonkwang; Yun, Jieun; Kim, Youngsoo; Han, Sang-Bae; Jung, Jae-Kyung; Cho, Jungsook; Lee, Kiho; Kwak, Jae-Hwan; Lee, Heesoon

    2015-06-15

    With the aim of developing novel scaffolds as anticancer agents and inhibitors of NF-?B activity, 60 novel benzofuran- and 2,3-dihydrobenzofuran-2-carboxylic acid N-(substituted)phenylamide derivatives (1a-s, 2a-k, 3a-s, and 4a-k) were designed and synthesized from the reference lead compound KL-1156, which is an inhibitor of NF-?B translocation to the nucleus in LPS-stimulated RAW 264.7 macrophage cells. The novel benzofuran- and 2,3-dihydrobenzofuran-2-carboxamide derivatives exhibited potent cytotoxic activities (measured by the sulforhodamine B assay) at low micromolar concentrations against six human cancer cell lines: ACHN (renal), HCT15 (colon), MM231 (breast), NUGC-3 (gastric), NCI-H23 (lung), and PC-3 (prostate). In addition, these compounds also inhibited LPS-induced NF-?B transcriptional activity. The +M effect and hydrophobic groups on the N-phenyl ring potentiated the anticancer activity and NF-?B inhibitory activity, respectively. However, according to the results of structure-activity relationship studies, only benzofuran-2-carboxylic acid N-(4'-hydroxy)phenylamide (3m) was the lead scaffold with both an outstanding anticancer activity and NF-?B inhibitory activity. This novel lead scaffold may be helpful for investigation of new anticancer agents that act through inactivation of NF-?B. PMID:25953156

  9. Regio- and stereoselective Pd-catalyzed direct arylation of unactivated sp(3) C(3)-H bonds of tetrahydrofuran and 1,4-benzodioxane systems.

    Science.gov (United States)

    Parella, Ramarao; Babu, Srinivasarao Arulananda

    2015-02-20

    An auxiliary-enabled Pd-catalyzed highly regio- and stereoselective sp(3) C-H activation and the direct arylation of the C3-position of oxygen heterocycles, such as tetrahydrofuran and 1,4-benzodioxane systems, are reported. An efficient stereoselective construction of cis 2,3-disubstituted tetrahydrofuran derivatives (analogues of norlignans) and cis 2,3-disubstituted 1,4-benzodioxane derivatives (analogues of neolignans) is described. The direct C(sp(3))-H arylation of the C3-position of (R)- or (S)- tetrahydrofuran-2-carboxamides furnished the corresponding (2R,3R) and (2S,3S) C3-arylated THF scaffolds as major compounds with very high regio- and diastereoselectivities. The stereochemistry of the products obtained in this work were unambiguously assigned on the basis of the X-ray structure analyses of representative compounds 3b, 3e, 4p, and 7. PMID:25588549

  10. N-Heterocyclic carbene–palladium catalysts for the direct arylation of pyrrole derivatives with aryl chlorides

    Directory of Open Access Journals (Sweden)

    Ismail Özdemir

    2013-02-01

    Full Text Available New Pd–NHC complexes have been synthesized and employed for palladium-catalyzed direct arylation of pyrrole derivatives by using electron-deficient aryl chlorides as coupling partners. The desired coupling products were obtained in moderate to good yields by using 1 mol % of these air-stable palladium complexes. This is an advantage compared to the procedures employing air-sensitive phosphines, which have been previously shown to promote the coupling of aryl chlorides with heteroarenes.

  11. QSAR Studies on N-aryl Derivative Activity Towards Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Kamalakaran Anand Solomon

    2009-04-01

    Full Text Available A Quantitative Structure Activity Relationship (QSAR study has been an attempted on a series of 88 N-aryl derivatives which display varied inhibitory activity towards both acetylcholinesterase (AChE and butyrylcholinesterase (BChE, targets in Alzheimer’s drug discovery. QSAR models were derived for 53 and 61 compounds for each target, respectively, with the aid of genetic function approximation (GFA technique using topological, molecular shape, electronic and structural descriptors. The predictive ability of the QSAR model was evaluated using a test set of 26 compounds for AChE (r2pred = 0.857, (q2 = 0.803 and 20 compounds for BChE (r2 pred = 0.882, (q2 = 0.857. The QSAR models point out that AlogP98, Wiener, Kappa-1-AM, Dipole-Mag, and CHI-1 are the important descriptors effectively describing the bioactivity of the compounds.

  12. Synthesis and Antiviral Bioactivities of 2-Aryl- or 2-Methyl-3-(substituted- Benzalamino-4(3H-quinazolinone Derivatives

    Directory of Open Access Journals (Sweden)

    Zhuo Chen

    2007-12-01

    Full Text Available A simple and general method has been developed for the synthesis of various4(3H-quinazolinone derivatives by the treatment of the appropriate 3-amino-2-aryl-4(3H-quinazolinone with a substituted benzaldehyde in ethanol. The structures of the compoundswere characterized by elemental analysis, IR, 1H-NMR and 13C-NMR spectra. The title 2-aryl- or 2-methyl-3-(substituted-benzalamino-4(3H-quinazolinone compounds III-1~III-31 were found to possess moderate to good antiviral activity. Semi-quantitative PCR andReal Time PCR assays were used to ascertain the target of action of compound III-31against TMV. The studies suggest that III-31 possesses antiviral activity due to inductionof up-regulation of PR-1a and PR-5, thereby inhibiting virus proliferation and movementby enhancement of the activity of some defensive enzyme.

  13. Aryl (meth)acrylates and polymers based on them

    International Nuclear Information System (INIS)

    Data on the synthesis, polymerisation and copolymerisation of aryl (meth)acrylates are generalised and systematised. Chemical and photochemical properties of the polymers and copolymers are considered. Basic directions of practical application of poly[aryl (meth)acrylates] and copolymers are demonstrated. The bibliography includes 449 references.

  14. Mechanism-based inactivation of benzo[a]pyrene hydroxylase by aryl acetylenes and aryl olefins

    International Nuclear Information System (INIS)

    A series of aryl acetylenes and aryl olefins have been examined as substrates and inhibitors of cytochrome P-450 dependent monooxgenases in liver microsomes from 5,6-benzoflavone or phenobarbital pretreated rats. 1-Ethynylpyrene, 3-ethynylperylene, 2-ethynylfluorene, methyl 1-pyrenyl acetylene, cis- and trans-1-(2-bromovinyl)pyrene, and 1-allylpyrene serve as mechanism-based irreversible inactivators (suicide inhibitors) of benzo[a]pyrene hydroxylase, while 1-vinylpyrene and phenyl 1-pyrenyl acetylene do not cause a detectable suicide inhibition of benzo[a]pyrene hydroxylase. The mechanism-based loss of benzo[a]pyrene hydroxylase caused by the aryl acetylenes is not accompanied by a corresponding loss of the P-450 content of the microsomes (suicide destruction). The suicide inhibition by these aryl acetylenes therefore does not involve covalent binding to the heme moiety of the monooxygenase. Nevertheless, in the presence of NADPH, 3H-labeled 1-ethynylpyrene becomes covalently attached to the cytochrome P-450 protein; the measured stoichiometry of binding is one 1-ethynylpyrene per P-450 heme unit. The authors conclude that the inhibition of benzo[a]pyrene hydroxylase produced by 1-ethynylpyrene may be related to the mechanism of suicide inhibition of P-450 activity by chloramphenicol rather than the mechanism of suicide destruction of P-450 previously described for acetylene and propyne

  15. Formation and reaction behaviour of aryl-tellurium(II)-halogenides

    International Nuclear Information System (INIS)

    Aryl-tellurium(II)-haloganides, according to the author's results, can be quite generally prepared by the reaction of equimolar amounts of diaryl-ditellurides and halogen. By using non-polar solvent in which the reaction products are insoluble, the further reaction to aryl-tellurium(IV)-halogenides can be avoided. Aryl-tellurium(II)-halogenides, which so far have been prepared from diaryl-ditellurides and halogen, were subjected to the same reaction conditions as for the conversions of diaryl-ditellurides with aryl-tellurium(IV)-halogenides. Isotope labelling tests clearly showed the intermediary occurence of aryl-tellurium(II)-halogenides in these conversions. The isotope sup(123m)Te was used. (HK/LH)

  16. Synthesis of 5-Dialkyl(aryl)aminomethyl-8-hydroxyquinoline Dansylates as Selective Fluorescent Sensors for Fe3+

    OpenAIRE

    Yaowu Sha; Feng Wang; Ruogu Peng

    2007-01-01

    A series of 5-dialkyl(aryl)aminomethyl-8-hydroxyquinoline dansylates were synthesized and their fluoroionophoric properties toward representative alkali ions, alkaline earth ions and transition metal ions were investigated. Among the selected ions, Fe3+ caused considerable quenching of the fluorescence, while Cr3+ caused quenching to some extent. The absence of any significant fluorescence quenching effects of the other ions examined, especially Fe2+, renders these compounds highly useful Fe3...

  17. [Inhibition of the arachidonic acid cascade by aza-2-aryl-1,4-naphthoquinone derivatives].

    Science.gov (United States)

    Richwien, A; Wurm, G

    2004-12-01

    Inhibition of the arachidonic acid cascade by aza-2-aryl-1,4-naphthoquinone derivatives To find more potent 5-lipoxygenase(LO)-inhibitors than the up to now studied 2-(3,5-di-tert-butyl-4-hydroxyphenyl)-3-hydroxy-1,4-naphthoquinone derivatives the analogous aza-1,4-naphthoquinones 14, 15, 16/17 as well as the 3-bromo precursors 7, 8, 9/10 and 11 were synthesized. The naphtho[2,1-b][1,4]thiazin derivative 21 was included in this investigation as a quinone imine. Beside 5-LO inhibition the influence on 12-LO, COX-1 and cPLA2 was determined to investigate the selectivity of the compounds within the arachidonic acid cascade. To test the biochemical properties human granulocytes (5-LO) and human platelets (12-LO/COX-1 and cPLA2) were used. All 3-bromo compounds inhibit completely the arachidonic acid cascade by blocking the cPLA2. The 3-methoxy derivatives of the quinoline quinones 12 and 13 and the 3-hydroxyisoquinoline mixture 16/17 show 5-LO selectivity. 13 inhibits 5-LO selectively, 12 is a dual 5-LO/COX-1-inhibitor and 16/17 are dual 12-LO/COX-1-inhibitors. To verify the hypothesis that the hydroxylated 2-aryl-1,4-benzoquinone structure is the pharmacophore for 5-LO-inhibition within the class of 2-aryl-1,4-naphtho- and -aza-naphthoquinones the 2-(3,5-di-tert-butyl-4-hydroxyphenyl)-1,4-benzoquinones 24-28 were synthesized. It was shown that the 5-methoxy and 5-hydroxy compounds 24 and 27 are highly selective and potent 5-LO-inhibitors. PMID:15638076

  18. C- versus O-Arylation of an Enol-Lactone Using Potassium tert-butoxide

    Directory of Open Access Journals (Sweden)

    El Moktar Essassi

    2003-05-01

    Full Text Available Abstract: The use of potassium tert-butoxide as the base in arylation reactions of an enollactone with a series of benzyl halides was explored. Our work demonstrates that the ratio of C-arylation to O-arylation varies with the substitution pattern of the aryl halide.

  19. Highly enantioselective Mannich reactions with ?-aryl silyl ketene acetals and imines.

    Science.gov (United States)

    Notte, Gregory T; Baxter Vu, Jenny M; Leighton, James L

    2011-02-18

    Mannich reactions with chiral silicon Lewis acid activated acylhydrazones and ?-aryl silyl ketene acetals and ?-aryl,?-alkyl silyl ketene imines proceed efficiently and with good to excellent levels of both diastereoselectivity and enantioselectivity. The reactions provide access to ?-aryl,?-hydrazido esters and ?-aryl,?-alkyl,?-hydrazido nitriles, which are valuable analogs of ?-amino acids. PMID:21235253

  20. Expression of the Caenorhabditis elegans aryl hydrocarbon receptor ligand binding domain

    OpenAIRE

    Helaly, Ahmed

    2011-01-01

    The Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor, which mediates the potent toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds. AhR is regulated by the ligand-binding domain (LBD) of the AhR, and so determining how the binding of ligand activates AhR is of considerable interest. However, there are no structural data on mammalian AhR LBDs, and expression of the mouse AhR LBD in E. coli yields insoluble protein. Expression in more com...

  1. Design and Synthesis of Some Novel 4-(4-substituted aryl) Semicarbazones as Anticonvulsant Agents

    Science.gov (United States)

    Singh, Anita; Pande, C.; Gahtori, P.; Pandeya, S. N.; Stables, J. P.

    2010-01-01

    In the present study, a series of 4-(4-substituted aryl) semicarbazones were synthesized from substituted anilines and subsequently evaluated for their anticonvulsant activities. The anticonvulsant activities were established by the anticonvulsant drug development (ADD) programme NIH, USA using experimental animal, adult male FCM mice (20–25 g) and adult Sprague-Dawley rats (100–150 g) and screened against electroshock seizure, subcutaneous metrazole and minimal neurotoxicity tests in mice. Compound 7 was found equipotent to carbamazepine in both MES and ScPTZ tests. This study has highlighted the importance of distal alkyl chain which influences the anticonvulsant activity. PMID:21188048

  2. Design and synthesis of some novel 4-(4-substituted aryl semicarbazones as anticonvulsant agents

    Directory of Open Access Journals (Sweden)

    Singh Anita

    2010-01-01

    Full Text Available In the present study, a series of 4-(4-substituted aryl semicarbazones were synthesized from substituted anilines and subsequently evaluated for their anticonvulsant activities. The anticonvulsant activities were established by the anticonvulsant drug development (ADD programme NIH, USA using experimental animal, adult male FCM mice (20-25 g and adult Sprague-Dawley rats (100-150 g and screened against electroshock seizure, subcutaneous metrazole and minimal neurotoxicity tests in mice. Compound 7 was found equipotent to carbamazepine in both MES and ScPTZ tests. This study has highlighted the importance of distal alkyl chain which influences the anticonvulsant activity.

  3. Synthesis, Characterization, Anti-Inflammatory and in Vitro Antimicrobial Activity of Some Novel Alkyl/Aryl Substituted Tertiary Alcohols

    Directory of Open Access Journals (Sweden)

    Rafiuzzaman SaeedulHaq

    2011-12-01

    Full Text Available The synthesis of some novel alkyl/aryl substituted tertiary alcohols was accomplished in two steps. The synthetic route involves preparation of Grignard reagents by treating alkyl/aryl bromides with magnesium turnings in dry ether. Then substituted chalcones were reacted with the Grignard reagents to afford alkyl/aryl substituted tertiary alcohols 1-10. The structures of the synthesized compounds were assigned on the basis of FT-IR, 1H-NMR, 13C-NMR and mass spectroscopic data. The in vivo anti-inflammatory activity of the synthesized compounds was evaluated using the carrageenan-induced hind paw edema method and was compared with that of ibuprofen. Some of the newly synthesized compounds showed promising anti-inflammatory activity. The tertiary alcohols 1-10 were also screened for antibacterial activity against ten bacterial strains using seven Gram-positive and three Gram-negative bacteria and for antifungal activity against Aspergillus Flavus, Aspergillus Niger and Aspergillus pterus. Tertiary alcohols 1-10 were found to exhibit good to excellent antimicrobial activities compared to levofloxacin and fluconazole used as standard drugs.

  4. Cloning, expression and characterization of an aryl-alcohol dehydrogenase from the white-rot fungus Phanerochaete chrysosporium strain BKM-F-1767

    Directory of Open Access Journals (Sweden)

    Yang Dong-Dong

    2012-06-01

    Full Text Available Abstract Background The white-rot fungus Phanerochaete chrysosporium is among the small group of fungi that can degrade lignin to carbon dioxide while leaving the crystalline cellulose untouched. The efficient lignin oxidation system of this fungus requires cyclic redox reactions involving the reduction of aryl-aldehydes to the corresponding alcohols by aryl-alcohol dehydrogenase. However, the biochemical properties of this enzyme have not been extensively studied. These are of most interest for the design of metabolic engineering/synthetic biology strategies in the field of biotechnological applications of this enzyme. Results We report here the cloning of an aryl-alcohol dehydrogenase cDNA from the white-rot fungus Phanerochaete chrysosporium, its expression in Escherichia coli and the biochemical characterization of the encoded GST and His6 tagged protein. The purified recombinant enzyme showed optimal activity at 37°C and at pH 6.4 for the reduction of aryl- and linear aldehydes with NADPH as coenzyme. NADH could also be the electron donor, while having a higher Km (220 ?M compared to that of NADPH (39 ?M. The purified recombinant enzyme was found to be active in the reduction of more than 20 different aryl- and linear aldehydes showing highest specificity for mono- and dimethoxylated Benzaldehyde at positions 3, 4, 3,4 and 3,5. The enzyme was also capable of oxidizing aryl-alcohols with NADP?+?at 30°C and an optimum pH of 10.3 but with 15 to 100-fold lower catalytic efficiency than for the reduction reaction. Conclusions In this work, we have characterized the biochemical properties of an aryl-alcohol dehydrogenase from the white-rot fungus Phanerochaete chrysosporium. We show that this enzyme functions in the reductive sense under physiological conditions and that it displays relatively large substrate specificity with highest activity towards the natural compound Veratraldehyde.

  5. [Synthetic studies on aromatic heterocyclic compounds].

    Science.gov (United States)

    Harayama, Takashi

    2006-08-01

    This review covers the concise synthesis of simple coumarin with salicyl aldehydes and Wittig reagent, and a convenient synthesis of polycyclic aromatic heterocyclic compounds using the aryl-aryl coupling reaction of aryl benzamides and aryl benzoates with a Pd reagent is presented. In the first section, the reactions of salicyl aldehydes with OMe, OH, Br, CO(2)Me, and NO(2) groups with carbethoxymethylenetriphenylphophorane are described. Specifically, the reaction of 3-nitrosalicylaldehyde with amines gave benzoxazoles in moderate yield. In the second section, the syntheses of benzo[c]phenanthridine alkaloids, quinazoline alkaloids, and graphislactones in the Pd-mediated biaryl coupling reaction are described. Moreover, the synthesis of benzonaphthazepine and pyrrolophenanthridine alkaloids utilizing regioselective C-H activation with intramolecular coordination of a benzylamine to Pd is described, and the effects of oxygen substituents in the benzoyl part of benzanilides on the coupling position in its biaryl coupling reaction are presented. An effective Pd reagent for the coupling reaction of aryl tolyflate and arene was developed. PMID:16880715

  6. Improved cellular inhibitors for glycoprotein processing alpha-glucosidases: biological characterisation of alkyl- and arylalkyl-N-substituted deoxynojirimycins

    OpenAIRE

    Alonzi, DS; Dwek, RA; Butters, TD

    2009-01-01

    A series of N-alkyl- and N-arylalkyl-DNJ compounds have been evaluated for their efficacy for inhibition of endoplasmic reticulum resident ?-glucosidases in cells. A recently developed free oligosaccharide (FOS) assay allowed the products of glucosidase inhibition to be quantified and compounds compared for relative inhibitory activity. A N-alkyl chain of one to six carbon atoms provided a flexible linker between deoxynojirimycin (DNJ) and a phenyl, cyclohexyl or cyclopentyl group to explore...

  7. The Suggested Physiologic Aryl Hydrocarbon ReceptorActivator and Cytochrome P4501 Substrate6-Formylindolo[3,2-b]carbazole Is Present in Humans

    OpenAIRE

    Wincent, Emma; Amini, Nahid; Luecke, Sandra; Glatt, Hansruedi; Bergman, Jan; Crescenzi, Carlo; Rannug, Agneta; RANNUG, ULF

    2009-01-01

    Dioxins and other polycyclic aromatic compounds formedduring the combustion of waste and fossil fuels represent a riskto human health, as well as to the well being of our environment.Compounds of this nature exert carcinogenic and endocrinedisruptingeffects in experimental animals by binding to theorphan aryl hydrocarbon receptor (AhR). Understanding themechanism of action of these pollutants, as well as the physiologicalrole(s) of the AhR, requires identification of the endogenousligand(s) o...

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

    Directory of Open Access Journals (Sweden)

    Ondrej Jandourek

    2014-01-01

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

  9. Azo-hydrazone tautomerism of aryl azo pyridone dyes

    Directory of Open Access Journals (Sweden)

    Mirkovi? Jelena M.

    2013-01-01

    Full Text Available In the last three or four decades disperse dyes derived from pyridones (in particular azo pyridone dyes have gained in importance, and are widely used in various fields. These compounds have excellent coloration properties, and are suitable for the dyeing of polyester fabrics. Basic features of these dyes are simplicity of their synthesis by diazotation and azo coupling. They generally have high molar extinction coefficient with medium to high light and wet fastness. The absorption maxima of these dyes show their visible absorption wavelength ranging from yellow to orange, which can be attributed to poorly delocalized electrons in the pyridone ring. However, there are several dyes with deep colors such as red or violet. Pyridone dyes with alkyl and aryl groups in ortho position to azo group show 2-pyridone/2-hydroxypyridine tautomerism, while those containing OH and NHR groups conjugated with the azo group show azo-hydrazone tautomerism. Determining azo-hydrazone tautomerism could be therefore interesting, since the tautomers have different physico-chemical properties and most importantly different coloration. The literature on azo-hydrazone tautomerism, determination of equilibrium position, and investigation of substituent and solvent influence on tautomerism has been summarized in the presented review. The general conclusion is that the equilibrium between two tautomers is influenced by the structure of the compounds and by the solvents used. The tautomeric behavior patterns of the arylazo pyridone dyes in the reviewed literature has been studied using various instrumental techniques, including FT-IR, UV-vis, and NMR spectroscopy. The quantum chemical calculations related to the azo-hydrazon tautomerism have also been included. A large number of pyridone dyes exist in hydrazone form in solid state, while in solvents there is a mixture of tautomers. In addition, the X-ray single-crystal diffraction data analysis of some commercial pyridone dyes has been discussed concluding that they all crystallize in the hydrazone form.

  10. Synthesis and anticonvulsant activity of some potent 5,6-bis aryl 1,2,4-triazines

    OpenAIRE

    Mallikarjuna, B.P.; Suresh Kumar, G.V.; Sastry, B. S.; Nagaraj,; Manohara, K.P.

    2007-01-01

    In the present research, a series of 5,6-bis aryl 1,2,4-triazines 5a~5f were synthesized by condensation of various benzils 4a~4f with aminoguanidine bicarbonate and were screened in vivo, for their anticonvulsant and neurotoxicity studies. Compounds 5a, 5b and 5d were found to be potent molecules of this series, when compared with the reference drugs phenytoin sodium, diazepam and lamotrigine. The structures of these compounds were established by IR, 1H NMR, 13C NMR and mass spectroscopic data.

  11. Synthesis and anticonvulsant activity of some potent 5,6-bis aryl 1,2,4-triazines.

    Science.gov (United States)

    Mallikarjuna, B P; Suresh Kumar, G V; Sastry, B S; Nagaraj; Manohara, K P

    2007-07-01

    In the present research, a series of 5,6-bis aryl 1,2,4-triazines 5a~5f were synthesized by condensation of various benzils 4a~4f with aminoguanidine bicarbonate and were screened in vivo, for their anticonvulsant and neurotoxicity studies. Compounds 5a, 5b and 5d were found to be potent molecules of this series, when compared with the reference drugs phenytoin sodium, diazepam and lamotrigine. The structures of these compounds were established by IR, (1)H NMR, (13)C NMR and mass spectroscopic data. PMID:17674488

  12. Reaction of 3-aryl-2-benzoyloxiranes with alkyl thiocyanates

    International Nuclear Information System (INIS)

    3-Aryl-2-benzoyloxiranes and alkyl thiocyanates in the presence of an equivalent amount of anhydrous AlCl3 form erythro-N-(2-benzoyl-1-aryl-2-chloroethyl)-S-alkyl thiocarbamates and ?-diketones. p-Tolyl- and p-anisyl-2-benzoyl-oxiranes do not react with alkyl thiocyanates, but isomerize to the respective ?-diketones, and form the threo-chlorohydrins in low yield

  13. Selective copper catalysed aromatic N-arylation in water

    DEFF Research Database (Denmark)

    Engel-Andreasen, Jens; Shimpukade, Bharat

    2013-01-01

    4,7-Dipyrrolidinyl-1,10-phenanthroline (DPPhen) was identified as an efficient ligand for copper catalyzed selective arom. N-arylation in water. N-Arylation of indoles, imidazoles and purines proceeds with moderate to excellent yields and complete selectivity over aliph. amines. Aq. medium and the possibility for low metal and ligand loadings give the process a benign environmental profile. [on SciFinder(R)

  14. A convenient catalyst system for microwave accelerated cross-coupling of a range of aryl boronic acids with aryl chlorides

    Directory of Open Access Journals (Sweden)

    Milton Edward J

    2007-05-01

    Full Text Available Abstract A convenient microwave accelerated cross-coupling procedure between aryl chlorides with a range of boronic acids has been developed. An explanation for the low reactivity of highly fluorinated boronic acids in Suzuki coupling is provided.

  15. A room temperature copper catalyzed N-selective arylation of ?-amino alcohols with iodoanilines and aryl iodides

    OpenAIRE

    Das, Priyabrata; De Brabander, Jef K.

    2013-01-01

    An efficient method is described for the synthesis of N-(2-aminophenyl)-2-hydroxyethylamines via a copper catalyzed N-selective arylation of ?-amino alcohols with iodoanilines. The corresponding coupling products are useful intermediates for the synthesis of a variety of N-2-hydroxyethyl-substituted benzimidazoles, benzimidazolones, and iminobenzimidazoles. We found that 2-iodoaniline only arylates certain amino alcohols but not amines lacking a hydroxyl group. We also demonstrate the arylat...

  16. Establishment of a stable aryl hydrocarbon receptor-responsive HepG2 cell line.

    Science.gov (United States)

    Satsu, Hideo; Yoshida, Kazutaka; Mikubo, Ayano; Ogiwara, Haru; Inakuma, Takahiro; Shimizu, Makoto

    2015-08-01

    The aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor. It heterodimerizes with aryl hydrocarbon nuclear translocator, binds to the xenobiotic-responsive element (XRE), and enhances the transcription of genes encoding xenobiotic metabolizing enzymes. AHR also plays important roles in the inhibition of intestinal carcinogenesis and the modulation of gut immunity. It is very important to screen for AHR-activating compounds because those are expected to produce the AHR-mediated physiological functions. Until now, AHR-mediated transcriptional activity represented by the transcriptional activity of CYP1A1 in luciferase assay has been applied as a screening procedure for AHR-activating compounds. However, the AHR-mediated transcriptional activity did not necessarily correspond with the CYP1A1 transcriptional activity. To evaluate AHR-mediated transcriptional activity more specifically, and to screen for AHR-activating compounds, we establish a stable AHR-responsive HepG2 cell line by co-transfection of an AHR expression vector and an AHR-responsive vector (pGL3-XRE) containing a luciferase gene and three tandemly arranged XRE elements into a human hepatoma derived cell line, HepG2. The induction of luciferase activity in the stable AHR-responsive HepG2 cell line by typical AHR activators occurred in time- and concentration-dependent manners. By assessing the AHR target genes CYP1A1, UGT1A1, and ABCG2, an AHR activator-mediated induction was observed at mRNA level. Furthermore, the AHR activator-mediated induction of luciferase activity was positively correlated with the mRNA levels of CYP1A1, UGT1A1, and ABCG2. These findings verified the usefulness of the established stable AHR-responsive HepG2 cell line for the screening of AHR-activating compounds. PMID:24667997

  17. Reductive carbonylation of aryl halides employing a two-chamber reactor : a protocol for the synthesis of aryl aldehydes including 13C- and D-isotope labeling

    DEFF Research Database (Denmark)

    Korsager, Signe; Taaning, Rolf H

    2013-01-01

    A protocol has been developed for conducting the palladium-catalyzed reductive carbonylation of aryl iodides and bromides using 9-methylfluorene-9-carbonyl chloride (COgen) as a source of externally delivered carbon monoxide in a sealed two-chamber system (COware), and potassium formate as the in situ hydride source. The method is tolerant to a wide number of functional groups positioned on the aromatic ring, and it can be exploited for the isotope labeling of the aldehyde group. Hence, reductive carbonylations run with (13)COgen provide a facile access to (13)C-labeled aromatic aldehydes, whereas with DCO2K, the aldehyde is specifically labeled with deuterium. Two examples of double isotopic labeling are also demonstrated. Finally, the method was applied to the specific carbon-13 labeling of the ?-amyloid binding compound, florbetaben.

  18. Advanced hybrid fluoropolymers from the cycloaddition of aryl trifluorovinyl ethers

    Science.gov (United States)

    Ligon, S. Clark, Jr.

    This dissertation discusses the synthesis of aryl trifluorovinyl ethers and their cycloaddition polymerization to give perfluorocyclobutyl (PFCB) polymers. To explore the stereochemistry of these polymers, simple monomfunctional aryl trifluorovinyl ethers were dimerized and the resultant cis and trans isomers were separated. Differences in structure help to improve understanding of the amorphous nature of the bulk PFCB polymeric material. To apply this knowledge, crown ether containing perfluorocyclobutyl (PFCB) polymers were synthesized for use in lithium ion battery applications. While poor solubility has hindered further development of these materials, slight modifications to structure may provide a solution. Also described is a fluorinated aryl vinyl ether and its attempted copolymerization with chlorotrifluoroethylene. While this copolymerization did not yield the desired materials, novel semifluorinated phenol precursors have been utilized in reactions with carboxylic acids to give polyesters and most recently with phosgene like species to give polycarbonates. Next, PFCB polymers were post functionalized with fluoroalkyl tethers to improve oleophobicity and hydrophobicity without decreasing thermal stability or optical clarity. In addition, various silica nanostructures were functionalized with aryl trifluorovinyl ethers. This includes the reaction of aryl silanes to give trifluorovinyl ether functional POSS and their polymerization to provide PFCB hybrid materials. Silane coupling agents were also used to functionalize colloidal silica and fumed silica nanoparticles. These procedures allow excellent dispersion of the silica nanoparticles throughout the fluoropolymer matrix. Finally, the reaction of aryl trifluorovinyl ether with nonfluorinated alkenes and alkynes was explored. In these reactions, the fluorinated olefin adds with the hydrocarbon olefin to give semifluorinated cyclobutanes (SFCB) and with the alkyne to give semifluorinated cyclobutene. The reaction with alkenes has been applied to bis functional acrylates and styrenics to grow SFCB polymers similar to the PFCB polymers. Also, the fluoroolefin was shown to add to multiple alkynes to give six membered ring adducts. These hetero cycloaddition reactions, which occur at temperatures well below those required to add the aryl trifluorovinyl ethers to themselves, provide multiple pathways for the development of new hybrid fluoropolymer materials.

  19. Synthesis and biological evaluation of a novel series of aryl S,N-ketene acetals as antileishmanial agents.

    Science.gov (United States)

    Suryawanshi, S N; Kumar, Santosh; Tiwari, Avinash; Shivahare, Rahul; Chhonker, Yashpal Singh; Pandey, Susmita; Shakya, Nishi; Bhatta, Rabi Sankar; Gupta, Suman

    2013-07-01

    A series of aryl S,N-ketene acetals 7(a-f) was synthesized and evaluated for their in vitro and in vivo antileishmanial activity against Leishmania donovani. All the 6 compounds exhibited significant in vitro activity against intracellular amastigotes of L. donovani with IC50 values ranging from 1.2 to 3.5 ?M and were found promising as compared with reference drugs, sodium stibogluconate (SSG) and paromomycin. On the basis of good selectivity indices (SI), they were further tested for their in vivo potential against L. donovani/hamster model. Two compounds 7a and 7b showed significant inhibition of parasite multiplication, 72% and 83%, respectively. These compounds were comparable with SSG and superior to paromomycin. Preliminary in vitro metabolic investigations were also performed to assess the metabolic stability and in vitro hepatic intrinsic clearance (Clint) of compound 7b in hamster liver microsomes. PMID:23673014

  20. Photoreactive molecular layers containing aryl ester units: Preparation, UV patterning and post-exposure modification

    International Nuclear Information System (INIS)

    The photolithographic modification of thin functional silane layers provides a versatile and powerful means of fabricating functionalized patterned surfaces which can be applied for tuning inorganic surface properties and for modern immobilisation techniques. In this contribution we present the synthesis of a new functional trichloro organosilane bearing photoreactive aryl ester groups and its application in thin silane layers on silicon oxide surfaces. Whereas the trichlorosilyl group acts as anchoring unit to the inorganic surface, the aryl ester group undergoes the photo-Fries rearrangement to yield hydroxyketones upon irradiation with UV-light of 254 nm which leads to a change in chemical reactivity of the surface. By a subsequent reaction with perfluorobutyryl chloride, the photogenerated hydroxy groups yield the corresponding perfluorinated ester compound, which allows further tuning of surface properties. The layer formation as well as the photoreaction and post-modification reaction was monitored by FTIR spectroscopy and X-ray photoelectron spectroscopy (XPS). The thickness of the obtained thin layers was determined by X-ray reflectivity (XRR). Photopatterned surfaces were produced using a contact mask during illumination followed by the post-modification reaction. Friction force microscopy (FFM) revealed the contrast between modified and unmodified regions of the patterned samples.

  1. Tuning Aryl?CH···O Intermolecular Interactions on Pt(111)

    DEFF Research Database (Denmark)

    Demers-Carpentier, Vincent; Laliberte, Marc-Andre?

    2010-01-01

    Scanning tunneling microscopy (STM) data are reported for the room-temperature adsorption of 2,2,2-trifluoroacetophenone (TFAP), 2,2,2-trifluorovinylbenzene (TFVB), octafluoroacetophenone (OFAP), and methyl benzoate (MB) on Pt(111). The objective of the study is to establish the role of aryl?CH···O bonding in forming self-assembled low-nuclearity structures at room temperature and to compare aryl?CH···O bonding by ester and ketone carbonyl functions. The STM images clearly evidence the formation of homochiral dimers and trimers of TFAP, and density functional theory (DFT) calculations reveal aryl?CH···O bonding as the driving force for dimer formation. In contrast to TFAP, chemisorbed TFVB and OFAP do not form such self-assembled structures as they lack carbonyl and aryl?CH groups, respectively. The self-assembly of MB on Pt(111) differs from that of TFAP, in that it can form structures stabilized by one, as distinct from two, aryl?CH···O bonds. The results are discussed with respect to the enantioselective hydrogenation of ?-ketoesters on cinchona modified Pt catalysts.

  2. Carbonates: Eco-friendly Solvents for Palladium-Catalysed Direct Arylation of Heteroaromatics

    OpenAIRE

    Dong, Jia Jia; Roger, Julien; Verrier, Ce?cile; Martin, Thibaut; Le Goff, Ronan; Hoarau, Christophe; Doucet, Henri

    2010-01-01

    The palladium-catalysed direct 2-, 4- or 5-arylation of a wide range of heteroaromatics with aryl halides proceed in moderate to good yields using the eco-friendly solvents carbonates. The best yields were obtained using benzoxazole or thiazole derivatives. The arylation of furan, thiophene, pyrrole, imidazole or isoxazole derivatives was found to require a more elevated reaction temperature.

  3. Synthesis, insecticidal, and acaricidal activities of novel 2-aryl-pyrrole derivatives containing ester groups.

    Science.gov (United States)

    Zhao, Yu; Li, Yongqiang; Ou, Xiaoming; Zhang, Pengxiang; Huang, Zhiqiang; Bi, Fuchun; Huang, Runqiu; Wang, Qingmin

    2008-11-12

    A series of novel 2-aryl-pyrrole derivatives containing ester groups were synthesized, and their structures were characterized by (1)H NMR spectroscopy and elemental analysis. The insecticidal activities against oriental armyworm, mosquito, diamondback moth, green rice leafhopper, and bean aphids and acaricidal activities against spider mite of these new compounds were evaluated. The results of bioassays indicated that some of these title compounds exhibited excellent insecticidal and acaricidal activities. The insecticidal activities against oriental armyworm of compounds IVa, IVd, IVe, IVf, IVg, IVi, IVk, and IVp were equal to commercialized Chlorfenapyr, and the insecticidal activities of most of compounds IVb, IVc, IVd, IVf, IVg, IVj, IVk, IVl, IVs, IVt, IVu, IVw, IVx, IVz, and Chlorfenapyr against mosquito at 0.10 mg kg (-1) were 100%, and the acaricidal activities of compounds IVd, IVe, IVf, IVg, IVh, IVi, and IVk were equal or superior to Chlorfenapyr. Especially, the results indicated that the acaricidal activity of [4-bromo-2-(4-chlorophenyl)-3-cyano-5-(trifluoromethyl)pyrrol-1-yl]methyl 3-methylbutanoate ( IVg) against spider mite was 2.65-fold as high as that of Chlorfenapyr from the value of LC 50. PMID:18937487

  4. Induction of Mouse UDP-Glucuronosyltransferase mRNA Expression in Liver and Intestine by Activators of Aryl-Hydrocarbon Receptor, Constitutive Androstane Receptor, Pregnane X Receptor, Peroxisome Proliferator-Activated Receptor ?, and Nuclear Factor Erythroid 2-Related Factor 2

    OpenAIRE

    Buckley, David B.; Klaassen, Curtis D.

    2009-01-01

    UDP-glucuronosyltransferases (UGTs) catalyze the addition of UDP-glucuronic acid to endo- and xenobiotics, enhancing their water solubility and elimination. Many exogenous compounds, such as microsomal enzyme inducers (MEIs), alter gene expression through xenobiotic-responsive transcription factors, namely, the aryl hydrocarbon receptor (AhR), constitutive androstane receptor (CAR), pregnane X receptor (PXR), peroxisome proliferator-activated receptor ? (PPAR?), and ...

  5. Preparation of radiohalogenated compounds via organotin intermediates

    International Nuclear Information System (INIS)

    The need to prepare specifically radiohalogenated organic compounds rapidly and in high specific activity has stimulated the evaluation of organometallics to achieve this objective. The versatility associated with the preparation of organotin intermediates and their ability to be transformed to the corresponding radiohalogenated derivatives has made them extremely useful in the preparation of a variety of radiodiagnostic and radiotherapeutic agents. The preparation of alkenyl and aryl trialkyl stannanes is reviewed as well as their conversion to radiofluorinated, brominated, iodinated and astatinated products

  6. Synthesis of thiophene oligomers via organotin compounds

    International Nuclear Information System (INIS)

    2-Trimethylstannylterthiophene coupes with functionalized aryl bromides and substituted bromothiophenes in the presence Bis (triphenylphenylphosphine) palladium (II) chloride to give substituted terthiophenes and substituted quaterthiophenes, respectively. Also, 3-trimethylstannylthiophene and 2-trimethylstannylthiophene couple with substituted 2,5-dibromothiophenes to give substituted branched terthiophenes and substituted ?-terthiophenes, respectively. The structures of the new compounds were confirmed by elemental analysis, mass spectrometry, and H-NMR spectral data. (authors). 18 refs., 2 figs

  7. Regioselective synthesis of 6-aryl-benzo[h][1,2,4]-triazolo[5,1-b]quinazoline-7,8-diones as potent antitumoral agents.

    Science.gov (United States)

    Wu, Liqiang; Zhang, Chong; Li, Weilin

    2013-09-01

    Three-component coupling of aldehyde, 2-hydroxy-1,4-naphthoquinone and 3-amino-1,2,4-triazole has been achieved using a catalytic amount of sulfamic acid under solvent free conditions to produce a novel series of 6-aryl-benzo[h][1,2,4]-triazolo[5,1-b]quinazoline-7,8-dione derivatives in good yields and with high regioselectivity. These compounds are found to exhibit potent antitumoral properties. PMID:23871222

  8. Structural, spectroscopic, magnetic and electrochemical studies of monomer N-substituted-sulfanilamide copper (II) complex with 2,2?-bipyridine

    Science.gov (United States)

    Öztürk, Filiz; Bulut, ?clal; Bulut, Ahmet

    2015-03-01

    A novel copper (II) complex of sulfamethazine (4-amino-N-[4,6-dimethyl-2-pyrimidinyl] benzene sulfonamide, Hsmz) ([Cu(smz)2bipy]?0.8H2O; bipy: 2,2?-bipyridine) has been synthesized and characterized by single crystal X-ray diffraction, EPR, IR, UV-vis and electrochemical methods. The single crystal X-ray analysis indicated that the compound crystallizes in the monoclinic space group P21/c with Z = 4. The central copper (II) ion is coordinated by two bidentate sulfamethazine anions through the nitrogen atoms together with one bidentate 2,2?-bipyridine ligand forming the octahedral geometry. The characteristic vibration bands support the X-ray analysis results. The EPR spectral analysis has led to that the ground state wave function of the unpaired electron of copper ion is dx2-y2 (2B1g state) and also indicated that the metal ions are located in distorted octahedral sites (D4h) elongated along the z-axis. The electrochemical studies of the complex were also carried out to determine the active sites of the ligands. The cyclic and square wave voltammetric techniques have been used to determine the complex.

  9. Structural, spectroscopic, magnetic and electrochemical studies of monomer N-substituted-sulfanilamide copper (II) complex with 2,2'-bipyridine.

    Science.gov (United States)

    Öztürk, Filiz; Bulut, ?clal; Bulut, Ahmet

    2015-03-01

    A novel copper (II) complex of sulfamethazine (4-amino-N-[4,6-dimethyl-2-pyrimidinyl] benzene sulfonamide, Hsmz) ([Cu(smz)2bipy]?0.8H2O; bipy: 2,2'-bipyridine) has been synthesized and characterized by single crystal X-ray diffraction, EPR, IR, UV-vis and electrochemical methods. The single crystal X-ray analysis indicated that the compound crystallizes in the monoclinic space group P21/c with Z=4. The central copper (II) ion is coordinated by two bidentate sulfamethazine anions through the nitrogen atoms together with one bidentate 2,2'-bipyridine ligand forming the octahedral geometry. The characteristic vibration bands support the X-ray analysis results. The EPR spectral analysis has led to that the ground state wave function of the unpaired electron of copper ion is [Formula: see text] ((2)B1g state) and also indicated that the metal ions are located in distorted octahedral sites (D4h) elongated along the z-axis. The electrochemical studies of the complex were also carried out to determine the active sites of the ligands. The cyclic and square wave voltammetric techniques have been used to determine the complex. PMID:25459691

  10. Phenyl boron-based compounds as anion receptors for non-aqueous battery electrolytes

    Science.gov (United States)

    Lee, Hung Sui (East Setauket, NY); Yang, Xiao-Qing (Port Jefferson Station, NY); McBreen, James (Bellport, NY); Sun, Xuehui (Middle Island, NY)

    2002-01-01

    Novel fluorinated boronate-based compounds which act as anion receptors in non-aqueous battery electrolytes are provided. When added to non-aqueous battery electrolytes, the fluorinated boronate-based compounds of the invention enhance ionic conductivity and cation transference number of non-aqueous electrolytes. The fluorinated boronate-based anion receptors include different fluorinated alkyl and aryl groups.

  11. Direct synthesis of ?-alkyl N-aryl aza Baylis-Hillman adducts via nitroso-ene reaction.

    Science.gov (United States)

    Murru, Siva; Gallo, August A; Srivastava, Radhey S

    2012-08-17

    A new approach for the direct Fe-catalyzed synthesis of ?-alkyl N-aryl aza Baylis-Hillman (ABH) adducts is reported. This approach involves the formation of a C-N bond via a nitroso-ene reaction. This is a simple, fast, and best alternate method to overcome the substrate scope limitations of the ABH reaction, which converts allyl esters and carbonyl compounds to novel ABH adducts. A variety of arylhydroxylamines reacted with esters, aldehydes, ketone, and nitriles to yield the corresponding products in moderate to excellent yields. PMID:22839650

  12. Substituted N-aryl-6-pyrimidinones: A new class of potent, selective, and orally active p38 MAP kinase inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Devadas, Balekudru; Selness, Shaun R.; Xing, Li; Madsen, Heather M.; Marrufo, Laura D.; Shieh, Huey; Messing, Dean M.; Yang, Jerry Z.; Morgan, Heidi M.; Anderson, Gary D.; Webb, Elizabeth G.; Zhang, Jian; Devraj, Rajesh V.; Monahan, Joseph B. (Pfizer)

    2012-02-28

    A novel series of highly potent and selective p38 MAP kinase inhibitors was developed originating from a substituted N-aryl-6-pyrimidinone scaffold. SAR studies coupled with in vivo evaluations in rat arthritis model culminated in the identification of 10 with excellent oral efficacy. Compound 10 exhibited a significantly enhanced dissolution rate compared to 1, translating to a high oral bioavailability (>90%) in rat. In animal studies 10 inhibited LPS-stimulated production of tumor necrosis factor-{alpha} in a dose-dependent manner and demonstrated robust efficacy comparable to dexamethasone in a rat streptococcal cell wall-induced arthritis model.

  13. Role of the Per/Arnt/Sim Domains in Ligand-dependent Transformation of the Aryl Hydrocarbon Receptor*S?

    OpenAIRE

    Soshilov, Anatoly; Denison, Michael S.

    2008-01-01

    The aryl hydrocarbon receptor (AhR) mediates the toxic and biological effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin and related compounds. In a process termed transformation, ligand binding converts the AhR into its high affinity DNA binding form that represents a dimer of the AhR and Arnt, a closely related nuclear protein. During transformation, protein chaperone Hsp90 is thought to be replaced by Arnt in overlapping binding sites in the basic helix loop helix and P...

  14. Heck Reactions with Aryl Chlorides : Studies of Regio- and Stereoselectivity

    OpenAIRE

    Datta, Gopal K.

    2008-01-01

    Homogeneous palladium-catalyzed Heck vinylation of aryl chlorides was investigated under air using Herrmann’s palladacycle and the P(t-Bu)3-liberating salt [(t-Bu)3PH]BF4. Based on the results, controlled microwave heating was utilized to accelerate model Heck reactions with aryl chlorides down to 30 min employing an electron-poor olefin and a mixture of an ionic liquid and 1,4-dioxane as solvent. For the first time, a highly regioselective general protocol has been developed for palladium-...

  15. Synthesis, Characterization and Biological Screening of Various O-phenyl-N-aryl Carbamates

    International Nuclear Information System (INIS)

    A series of O-phenyl-N-aryl carbamates (3a-i) were synthesized by the reaction of phenyl chloroformate (1) with different aromatic amines (2a-i). The compounds were characterized by IR and 1H-NMR and screened against acetylcholinesterase, butrylcholinesterase and lipoxygenase enzymes. The results revealed that O-phenyl-N-phenyl carbamate (3a) and O-phenyl-N-(3-hydroxyphenyl) carbamate (3e) were active against acetylcholinesterase while O-phenyl-N-benzyl carbamate (3b), O-phenyl-N-(4-hydroxyphenyl) carbamate (3f) and O-phenyl-N-(3-methoxyphenyl) carbamate (3h) exhibited potential inhibitory activity against 5-lipoxygenase. All these carbamates were also assayed for their antimicrobial and hemolytic activities. O-phenyl-N-(2-hydroxyphenyl) carbamate (3d), O-phenyl-N-(4-hydroxyphenyl) carbamate (3f) and O-phenyl-N-(3-methoxyphenyl) carbamate (3h) showed good antimicrobial and hemolytic activity among all the carbamates. (author)

  16. Influence of conjugation axis on the optical and electronic properties of aryl-substituted benzobisoxazoles.

    Science.gov (United States)

    Tlach, Brian C; Tomlinson, Aimée L; Ryno, Alden G; Knoble, Dawn D; Drochner, Dana L; Krager, Kyle J; Jeffries-EL, Malika

    2013-07-01

    Six different 2,6-diethyl-4,8-diarylbenzo[1,2-d:4,5-d']bis(oxazoles) and four different 2,4,6,8-tetraarylbenzobisoxazoles were synthesized in two steps: a Lewis acid catalyzed orthoester cyclization followed by a Suzuki or Stille cross-coupling with various arenes. The influence of aryl group substitution and/or conjugation axis variation on the optical and electronic properties of these benzobis(oxazole) (BBO) compounds was evaluated. Structural modifications could be used to alter the HOMO, LUMO, and band gap over a range of 1.0, 0.5, and 0.5 eV, respectively. However, depending on the location and identity of the substituent, the HOMO level can be altered without significantly impacting the LUMO level. This is supported by the calculated frontier molecular orbitals. Our results indicate that the FMOs and band gaps of benzobisoxazoles can be readily modified either jointly or individually. PMID:23796165

  17. Characterization of Natural Aryl Hydrocarbon Receptor Agonists from Cassia Seed and Rosemary

    Directory of Open Access Journals (Sweden)

    Yoshiaki Amakura

    2014-04-01

    Full Text Available Many recent studies have suggested that activation of the aryl hydrocarbon receptor (AhR reduces immune responses, thus suppressing allergies and autoimmune diseases. In our continuing study on natural AhR agonists in foods, we examined the influence of 37 health food materials on the AhR using a reporter gene assay, and found that aqueous ethanol extracts of cassia seed and rosemary had particularly high AhR activity. To characterize the AhR-activating substances in these samples, the chemical constituents of the respective extracts were identified. From an active ethyl acetate fraction of the cassia seed extract, eight aromatic compounds were isolated. Among these compounds, aurantio-obtusin, an anthraquinone, elicited marked AhR activation. Chromatographic separation of an active ethyl acetate fraction of the rosemary extract gave nine compounds. Among these compounds, cirsimaritin induced AhR activity at 10–102 ?M, and nepitrin and homoplantagenin, which are flavone glucosides, showed marked AhR activation at 10–103 ?M.

  18. Access to 2-(Het)aryl and 2-Styryl Benzoxazoles via Palladium-Catalyzed Aminocarbonylation of Aryl and Vinyl Bromides.

    Science.gov (United States)

    Neumann, Karoline T; Lindhardt, Anders T; Bang-Andersen, Benny; Skrydstrup, Troels

    2015-05-01

    A sequential one-pot procedure for the synthesis of either 2-(hetero)aryl or 2-styryl benzoxazoles is reported, starting from aryl and vinyl bromides, respectively, involving an initial aminocarbonylation with 2-aminophenols as nucleophiles followed by an acid mediated ring closure to generate the heterocycle. The methodology displays a broad substrate scope in moderate to excellent yields and can be exploited for (13)C-isotope labeling. Finally, this carbonylative protocol was applied to the synthesis of a potential Alzheimer's plaque binder and a selective PPAR antagonist including site-specific labeling with (13)C-carbon monoxide. PMID:25879769

  19. Improved synthesis of 3-aryl isoxazoles containing fused aromatic rings

    OpenAIRE

    Mirzaei, Yousef R.; Weaver, Matthew J.; Steiger, Scott A.; Kearns, Alison K.; Gajewski, Mariusz P.; Rider, Kevin C.; Beall, Howard D.; Natale, N. R.

    2012-01-01

    A critical comparison of methods to prepare sterically hindered 3-aryl isoxazoles containing fused aromatic rings using the nitrile oxide cycloaddition (NOC) reveal that modification of the method of Bode, Hachisu, Matsuura, and Suzuki (BHMS), utilizing either triethylamine as base or sodium enolates of the diketone, ketoester, and ketoamide dipolarophiles, respectively, was the method of choice for this transformation.

  20. Nickel-catalyzed monofluoromethylation of aryl boronic acids.

    Science.gov (United States)

    Su, Yi-Ming; Feng, Guang-Shou; Wang, Zhen-Yu; Lan, Quan; Wang, Xi-Sheng

    2015-05-11

    Aryl boronic acids can be monofluoromethylated under nickel catalysis. The utility of this method is demonstrated by the monofluoromethylation of a borylated and acyl-protected derivative of the statin drug ezetimibe. Mechanistic investigations indicate that a fluoromethyl radical is involved in the Ni(I) /Ni(III) catalytic cycle. PMID:25809786

  1. A large perturbation on electronic and photophysical properties of Ir(III) carbene complexes caused by the variation of N-substitution in N,N?-heteroaromatic ligands

    Science.gov (United States)

    Liu, Yuqi; Si, Yanling; Wang, Ying; Wu, Zhijian

    2014-08-01

    DFT/TDDFT investigation was performed on the electronic and photophysical properties of blue-emitting Ir(III) carbene complexes (fpmi)3-xIr(N^N?)x (x = 1, 2) [fpmi = 1-(4-fluorophenyl)-3-methylimidazolin-2-ylidene-C,C2?, N^N? = 2-(1H-pyrazol-5-yl)pyridinato (1a(x = 1)/1a?(x = 2)); 2-(1H-imidazol-5-yl)pyridinato (1b/1b?); 2-(1H-imidazol-2-yl)pyridinato (1c/1c?); 2-(1H-1,2,4-triazol-5-yl)pyridinato (2a/2a?); 2-(1H-1,2,3-triazol-5-yl)pyridinato (2b/2b?); 2-(4H-1,2,4-triazol-3-yl)pyridinato (2c/2c?)]. The absorption intensities and band positions are obviously affected by the variation of N substitution in N^N? ligand. The emission properties show an apparent dependence on the solvent effects, and the N^N? ligand plays an important role in governing the emissive state. The pyrazolyl-pyridyl-based N^N? ligand is considered to be more beneficial for blue OLEDs emitters.

  2. Synthesis of a new N-substituted bis-benzimidazolyl diamide ligand and its trinuclear copper(II) complex: Structural and fluorescence studies

    Science.gov (United States)

    Mahiya, Kuldeep; Mathur, Pavan

    2013-09-01

    The synthesis of a new N-substituted fluorescent probe based on a bis-benzimidazole diamide N2,N2?-bis[(1-(4-methylbenzyl)-benzimidazol-2-yl)methyl]biphenyl-2,2?-dicarboxamide (L1) with a biphenyl spacer group and its trinuclear copper(II) complex [Cu3(L1)3Cl3]?3Cl?3H2O] has been described. X-ray studies shows that the trinuclear complex crystallizes as [{Cu3(L1)3Cl3}2?6Cl?13CH3CN?2H2O] in triclinic space group P-1 with two independent molecules in the asymmetric unit. Each copper(II) adopts a distorted penta-coordinated geometry in each unit. The fluorescence spectra of L1 in methanol show an emission band centered at 300 nm. This band arises due to benzimidazolyl moiety in the ligating system. The diamide L1 in the presence of Fe3+ show the simultaneous ‘quenching' of (300 nm) and ‘enhancement' of (375 nm) emission band. The new emission band at 375 nm is attributed to intra ligand ?-?* transition of the biphenyl moiety. While Cu2+ and Ag+ show only the quenching of the 300 nm band. No such behavior was observed with other metal ions like Ni2+, Co2+, Mn2+, Mg2+, Zn2+ and Pb2+. The quenching constant with Fe3+, Ag+ and Cu2+ are calculated by the Stern-Volmer plots.

  3. COMPUTER AIDED DESIGN AND MOLECULAR DOCKING STUDY OF 1-N-SUBSTITUTED-3, 5-DIPHENYL-2-PYRAZOLINE DERIVATIVES AS COX–2 INHIBITORS

    Directory of Open Access Journals (Sweden)

    M Prasada Rao*, P Srinivasa Rao, Allam Appa Rao and Manda Rama Narasinga Rao

    2013-10-01

    Full Text Available Cyclooxygenase (COX catalyses the first committed step in the synthesis of prostanoids, a large family of arachidonic acid metabolites and major target of non-steroidal anti-inflammatory drugs (NSAIDs. COX-2 is the inducible isoform, rapidly expressed in several cell types in response to pro-inflammatory molecules. The interaction between the polypeptide and its corresponding receptor is highly selective. Therefore, it is of interest to inhibit COX2 in the context of inflammation. It is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process. The structure of COX 2 is screened using SP (Standard Precision method under molecular docking techniques (Computer aided Design with reference to novel 1-N-substituted-3, 5-diphenyl-2-pyrazoline derivatives. Based on their score and energy few ligands are selected to Induced Fit Docking (IFD studies and compared with the existing drug molecules. The result showed that the docked ligands maintain favorable interactions with the active site residues of COX-2.  All docking studies were performed using the molecular modeling software GLIDE of Schrödinger package.

  4. A comparative study of the hydrolysis pathways of substituted aryl phosphoramidate versus aryl thiophosphoramidate derivatives of stavudine.

    Science.gov (United States)

    Venkatachalam, T K; Yu, G; Samuel, P; Qazi, S; Pendergrass, S; Uckun, F M

    2004-08-01

    A comparative study of aryl phosphoramidate and aryl thiophosphoramidate derivatives of 2',3'-didehydro-2',3'-dideoxythymidine (d4T) was performed. The study focused on the nature of the substituents and the influence of a thiophosphoramidate in the structure of these derivatives. The rate of alkaline hydrolysis of these two types of d4T derivatives indicated that replacement of oxygen with sulfur decreases the rate of hydrolysis by twofold. Additionally, the activation energy (E(a)) for the sulfur analogs is comparatively higher than that of the oxygen analogs. Notably, an intermediate was formed in the hydrolysis reaction of the sulfur analogs of d4T that was absent in the case of the oxygen analog, and the tentative structure of the intermediate was proposed based on LC/mass spectroscopy data. Using both HPLC and (31)P-NMR techniques, we identified the hydrolysis product of the phosphoramidate derivatives and were able to show in in vitro studies that porcine liver esterase can hydrolyze the methyl ester portion of the phosphoramidate derivatives. Aryl phosphoramidate derivatives of d4T were 1000-fold more active than the corresponding aryl thiophosphoramidate derivatives, indicating that the energy of activation of hydrolysis of these phosphoramidate derivatives plays a significant role in their biological potency. PMID:15276300

  5. 2-Aryl substituted pyridine C-region analogues of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides as highly potent TRPV1 antagonists.

    Science.gov (United States)

    Ryu, HyungChul; Seo, Sejin; Kim, Myeong Seop; Kim, Mi-Yeon; Kim, Ho Shin; Ann, Jihyae; Tran, Phuong-Thao; Hoang, Van-Hai; Byun, Jieun; Cui, Minghua; Son, Karam; Sharma, Pankaz Kumar; Choi, Sun; Blumberg, Peter M; Frank-Foltyn, Robert; Bahrenberg, Gregor; Koegel, Babette-Yvonne; Christoph, Thomas; Frormann, Sven; Lee, Jeewoo

    2014-08-15

    A series of 2-aryl pyridine C-region derivatives of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides were investigated as hTRPV1 antagonists. Multiple compounds showed highly potent TRPV1 antagonism toward capsaicin comparable to previous lead 7. Among them, compound 9 demonstrated anti-allodynia in a mouse neuropathic pain model and blocked capsaicin-induced hypothermia in a dose-dependent manner. Docking analysis of 9 with our hTRPV1 homology model provided insight into its specific binding mode. PMID:25011915

  6. Ligand-free Pd-catalyzed and copper-assisted C-H arylation of quinazolin-4-ones with aryl iodides under microwave heating.

    Science.gov (United States)

    Laclef, Sylvain; Harari, Marine; Godeau, Julien; Schmitz-Afonso, Isabelle; Bischoff, Laurent; Hoarau, Christophe; Levacher, Vincent; Fruit, Corinne; Besson, Thierry

    2015-04-01

    A microwave-assisted method for the palladium-catalyzed direct arylation of quinazolin-4-one has been developed under copper-assistance. This method is applicable to a wide range of aryl iodides and substituted (2H)-quinazolin-4-ones. This protocol provides a simple and efficient way to synthesize biologically relevant 2-arylquinazolin-4-one backbones. PMID:25781369

  7. A quantitative structure-activity relationship study of novel inhibitors of cyclooxygenase-2: The 5-aryl-2,2-dialkyl-4-phenyl-3(2 Hfuranone derivatives

    Directory of Open Access Journals (Sweden)

    Singh P

    2007-01-01

    Full Text Available The cyclooxygenase-2 enzyme inhibition activity of 5-aryl-2,2-dialkyl-4-phenyl-3(2 H furanone derivatives is quantitatively analyzed through Fujita-Ban and Hansch type of approaches. The analyses have helped to ascertain the role of different substituents in explaining the observed inhibitory activity of these congeners. From both approaches it is revealed that more hydrophobic susbtituents at 4- R1, a non-hydrogen bond acceptor substitutent, preferably a -F substituent, at 3- R1 in 4-phenyl ring of 3(2 H furanone scaffold improve inhibitory action of a compound. The substituents exhibiting collective molecular bulk smaller than spirocyclopentyl at X and Y positions are preferred as these geminal positions seems to be involved in steric interation. Similarly, 4-aminosulfonyl in 5-aryl ring of 3(2 H furanone moiety emerged as a better choice than 4-methylsulfonyl substitution.

  8. High-resolution laser spectroscopy and magnetic effect of the B ˜ 2 E ' ? X ˜ 2 A 2 ' transition of the 15N substituted nitrate radical

    Science.gov (United States)

    Tada, Kohei; Teramoto, Kanon; Ishiwata, Takashi; Hirota, Eizi; Kasahara, Shunji

    2015-03-01

    Rotationally resolved high-resolution fluorescence excitation spectra of the 0-0 band of the B ˜ 2 E ' ? X ˜ 2 A 2 ' transition of the 15N substituted nitrate radical were observed for the first time, by crossing a jet-cooled molecular beam and a single-mode dye laser beam at right angles. Several thousand rotational lines were detected in the 15 080-15 103 cm-1 region. We observed the Zeeman splitting of intense lines up to 360 G in order to obtain secure rotational assignment. Two, nine, and seven rotational line pairs with 0.0248 cm-1 spacing were assigned to the transitions from the X ˜ 2 A 2 ' (?? = 0, k? = 0, N? = 1, J? = 0.5 and 1.5) to the 2 E3 / 2 ' (J' = 1.5), 2 E1 / 2 ' (J' = 0.5), and 2 E1 / 2 ' (J' = 1.5) levels, respectively, based on the ground state combination differences and the Zeeman splitting patterns. The observed spectrum was complicated due to the vibronic coupling between the bright B ˜ 2 E ' (? = 0) state and surrounding dark vibronic states. Some series of rotational lines other than those from the X ˜ 2 A 2 ' (J = 0.5 and 1.5) levels were also assigned by the ground state combination differences and the observed Zeeman splitting. The rotational branch structures were identified, and the molecular constants of the B ˜ 2 E1 / 2 ' (? = 0) state were estimated by a deperturbed analysis to be T0 = 15 098.20(4) cm-1, B = 0.4282(7) cm-1, and DJ = 4 × 10-4 cm-1. In the observed region, both the 2 E1 / 2 ' and 2 E3 / 2 ' spin-orbit components were identified, and the spin-orbit interaction constant of the B ˜ 2 E ' (? = 0) state was estimated to be -12 cm-1 as the lower limit.

  9. Synthesis, Photophysical, Electrochemical, Tumor-Imaging and Phototherapeutic Properties of Purpurinimide-N-substituted Cyanine Dyes Joined with Variable Length of Linkers

    Science.gov (United States)

    Williams, Michael P.A.; Ethirajan, Manivannan; Ohkubo, Kei; Chen, Ping; Pera, Paula; Morgan, Janet; White, William H.

    2011-01-01

    Purpurinimide methyl esters, bearing variable lengths of N-substitutions, were conjugated individually to a cyanine dye with a carboxylic acid functionality. The results obtained from in vitro and in vivo studies showed a significant impact of the linkers joining the phototherapeutic and fluorescence imaging moieties. The photosensitizer-fluorophore conjugate with a PEG linker showed the highest uptake in the liver, whereas the conjugate linked with two carbon units showed excellent tumor-imaging and PDT efficacy at 24 h postinjection. Whole body imaging and biodistribution studies at variable time points portrayed enhanced fluorescent uptake of the conjugates in the tumor compared to the skin. Interestingly the conjugate with the shortest linker and the one joining with two carbon units showed faster clearance from normal organs e. g., liver, kidney, spleen, lung compared to tumors. Both imaging and PDT efficacy of the conjugates were performed in BALB/c mice bearing Colon26 tumors. Compared to the others, the short linker conjugate showed poor tumor fluorescent properties and as a corollary does not exhibit the dual functionality of the photosensitizer-fluorophore conjugate. For this reason, it was not evaluated for in vivo PDT efficacy. However, in Colon26 tumor cells (in vitro), the short linker was highly effective. Among the conjugates with variable linkers, the rate of energy transfer from the purpurinimide moiety to the cyanine moiety increased with deceasing linker length, as examined by femtosecond laser flash photolysis measurements. No electron transfer from the purpurinimide moiety to the singlet excited state of the cyanine moiety or from the singlet excited state of the cyanine moiety to the purpurinimide moiety occurred as indicated by a comparison of transient absorption spectra with spectra of the one-electron oxidized and one-electron reduced species of the conjugate obtained by spectroelectrochemical measurements. PMID:21985310

  10. Synthesis and biological evaluation of aryl isoxazole derivatives as metabotropic glutamate receptor 1 antagonists: a potential treatment for neuropathic pain.

    Science.gov (United States)

    Cho, Gyeong Hi; Kim, TaeHun; Son, Woo Seung; Seo, Seon Hee; Min, Sun-Joon; Cho, Yong Seo; Keum, Gyochang; Jeong, Kyu-Sung; Koh, Hun Yeong; Lee, Jiyoun; Pae, Ae Nim

    2015-03-15

    Glutamate is the major excitatory neurotransmitter and known to activate the metabotropic and ionotropic glutamate receptors in the brain. Among these glutamate receptors, metabotropic glutamate receptor 1 (mGluR1) has been implicated in various brain disorders including anxiety, schizophrenia and chronic pain. Several studies demonstrated that the blockade of mGluR1 signaling reduced pain responses in animal models, suggesting that mGluR1 is a promising target for the treatment of neuropathic pain. In this study, we have developed mGluR1 antagonists with an aryl isoxazole scaffold, and identify several compounds that are orally active in vivo. We believe that these compounds can serve as a useful tool for the investigation of the role of mGluR1 and a promising lead for the potential treatment of neuropathic pain. PMID:25677662

  11. Palladium(II)-catalyzed meta-selective direct arylation of O-?-naphthyl carbamate.

    Science.gov (United States)

    Zhang, Jingchang; Liu, Qingwen; Liu, Xufei; Zhang, Suoqin; Jiang, Pingping; Wang, Yanxiang; Luo, Shengyuan; Li, Yang; Wang, Qifeng

    2015-01-25

    Selective meta-arylation of O-?-naphthyl carbamate has been accomplished using Pd(OAc)2 as a catalyst precursor and K2S2O8 with AgOAc as the oxidant. A range of aryl boronic acids could be introduced in moderate to good yields. Mechanistic investigation shows that the carbamate substituent has a unique effect and the reaction undergoes an ortho-carbometallation/meta-direct arylation process. PMID:25478680

  12. Synthesis of tricyclic heterocycles via a tandem aryl alkylation/heck coupling sequence.

    Science.gov (United States)

    Alberico, Dino; Rudolph, Alena; Lautens, Mark

    2007-02-01

    A norbornene-mediated palladium-catalyzed sequence is described in which two alkyl-aryl bonds and one alkenyl-aryl bond are formed in one pot with use of microwave irradiation. A variety of symmetrical and unsymmetrical oxygen-, nitrogen-, silicon-, and sulfur-containing tricyclic heterocycles were synthesized from a Heck acceptor and an aryl iodide containing two tethered alkyl halides. This approach was further applied to the synthesis of a tricyclic mescaline analogue. PMID:17253794

  13. Salen-Cu(II Complex Catalyzed N-Arylation of Imidazoles under Mild Conditions

    Directory of Open Access Journals (Sweden)

    Yan Liu

    2013-08-01

    Full Text Available Three inexpensive and air-/moisture-stable Salen-Cu complexes 1-3 were evaluated to be a novel class of catalysts for the N-arylation of imidazoles with aryl halides. A variety of aryl iodides, bromides underwent the coupling with imida-zoles, promoted by the complex 3, in moderate to excellent yields without the protection by an inert gas.

  14. Divergent Reaction Pathways for Phenol Arylation by Arynes: Synthesis of Helicenes and 2-Arylphenols

    OpenAIRE

    Truong, Thanh; Daugulis, Olafs

    2012-01-01

    Two reactions of phenols with arynes have been developed. If LiTMP base is employed, arynes generated from aryl chlorides react with phenols to form helicenes. o-Arylation of phenols can be achieved by employing tBuONa base in the presence of AgOAc. Direct arylation of binol was achieved leading to the shortest pathway to o,o’-diarylbinols.

  15. Mechanism of arylating quinone toxicity involving Michael adduct formation and induction of endoplasmic reticulum stress

    OpenAIRE

    Wang, Xinhe; Thomas, Beena; Sachdeva, Rakesh; Arterburn, Linnea; Frye, Lucy; Hatcher, Patrick G.; Cornwell, David G.; Ma, Jiyan

    2006-01-01

    Quinones permeate our biotic environment, contributing to both homeostasis and cytotoxicity. All quinones generate reactive oxygen species through redox cycling, while partially substituted quinones also undergo arylation (Michael adduct formation) yielding covalent bonds with nucleophiles such as cysteinyl thiols. In contrast to reactive oxygen species, the role of arylation in quinone cytotoxicity is not well understood. We found that the arylating quinones, including unsubstituted 1,4-benz...

  16. Ion and molecular recognition using aryl-ethynyl scaffolding.

    Science.gov (United States)

    Vonnegut, Chris L; Tresca, Blakely W; Johnson, Darren W; Haley, Michael M

    2015-03-01

    The aryl-ethynyl linkage has been extensively employed in the construction of hosts for a variety of guests. Uses range from ion detection (e.g., of metal cations in the environment or industrial waste and of anions prevalent in nature), to molecular mimics for biological systems, and to applications targeting future safety issues (such as CO2 capture and indicators for the manufacture of chemical weapons). This Focus Review examines the utilization of the aryl-ethynyl linkage in engineering host molecules for a variety of different guests, and how the alkyne unit plays an integral part as both a rigid scaffolding section in host geometry design as well as a linker to allow conjugative communication between discrete ?-electron systems. PMID:25586943

  17. Synthesis and cross-coupling reactions of imidomethyltrifluoroborates with aryl chlorides

    OpenAIRE

    Devulapally, Rammohan; Fleury-Brégeot, Nicolas; Molander, Gary A.; Seapy, Dave G.

    2012-01-01

    Potassium imidomethyltrifluoroborate salts were efficiently synthesized. Potassium phthalimidomethyl-trifluoroborate was successfully used in Suzuki–Miyaura-like cross-coupling reactions with a variety of aryl chlorides.

  18. Regioselectivity of Arylation of 2,3’-Biquinolyl Dianion

    OpenAIRE

    Yu. I. Smushkevich; I. V. Borovlev; I. V. Aksenova; A. V. Aksenov

    1999-01-01

    The dianion of 2,3’-biquinolyl with aryl- and hetaryl halides forms the products of arylation to 4’-position, which on treatment with alkyl halides or water yield 1’-alkyl-1’,4’dihydro-2,3’-biquinolyls or 4’-aryl-1’,4’-dihydro-2,3’-biquinolyls respectively. The oxidation of the latter leads to 4’-aryl-2,3’-biquinolyls. The cation dependenc...

  19. Synthesis of Novel Aryl(heteroarylsulfonyl Ureas of Possible Biological Interest

    Directory of Open Access Journals (Sweden)

    Maria Gdaniec

    2010-02-01

    Full Text Available The course of reaction of aryl and heteroaryl sulfonamides with diphenylcarbonate (DPC and 4-dimethylaminopyridine (DMAP was found to depend on the pKa of the sulfonamide used. Aryl sulfonamides with pKa ~ 10 gave 4-dimethylamino-pyridinium arylsulfonyl-carbamoylides, while the more acidic heteroaryl sulfonamides (pKa ~ 8 furnished 4-dimethylaminopyridinium heteroarylsulfonyl carbamates. Both the carbamoylides and carbamate salts reacted with aliphatic and aromatic amines with the formation of appropriate aryl(heteroarylsulfonyl ureas, and therefore, can be regarded as safe and stable substitutes of the hazardous and difficult to handle aryl(heteroarylsulfonyl isocyanates.

  20. Ginsenosides Are Novel Naturally-Occurring Aryl Hydrocarbon Receptor Ligands

    OpenAIRE

    Hu, Qin; He, Guochun; Zhao, Jing; Soshilov, Anatoly; DENISON, Michael S.; Zhang, Aiqian; Yin, Huijun; Fraccalvieri, Domenico; Bonati, Laura; Xie, Qunhui; Zhao, Bin

    2013-01-01

    The aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor that mediates many of the biological and toxicological actions of structurally diverse chemicals. In this study, we examined the ability of a series of ginsenosides extracted from ginseng, a traditional Chinese medicine, to bind to and activate/inhibit the AHR and AHR signal transduction. Utilizing a combination of ligand and DNA binding assays, molecular docking and reporter gene analysis, we demonstrated the abil...

  1. Persistent Binding of Ligands to the Aryl Hydrocarbon Receptor

    OpenAIRE

    Bohonowych, Jessica E.; Denison, Michael S.

    2007-01-01

    The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates many of the biological and toxic effects of halogenated aromatic hydrocarbons (HAHs), polycyclic aromatic hydrocarbons (PAHs), and other structurally diverse ligands. While HAHs are several orders of magnitude more potent in producing AhR-dependent biochemical effects than PAHs or other AhR agonists, only the HAHs have been observed to produce AhR-dependent toxicity in vivo. Here we have characterized...

  2. Aryl-l-Aminoacylamidase Activities in Extracts of Streptococcus durans

    OpenAIRE

    Machuga, Edward J.

    1982-01-01

    Two distinct enzymes with aryl-l-aminoacylamidase activity were found in cellular extracts of Streptococcus durans. One of these enzymes was strictly an arylamidase lacking any observable N-terminal exopeptidase activity. The other enzyme functioned as an aminopeptidase capable of catalyzing the hydrolysis of a variety of l-peptide and arylamide substrates. The arylamidase (molecular weight, 80,000) purified 425-fold to homogeneity preferred arylamides containing large hydrophobic side chains...

  3. Synthesis of 3-Aryl Coumarin Derivatives Using Ultrasound

    Directory of Open Access Journals (Sweden)

    Kandasamy Logeeswari

    2013-02-01

    Full Text Available Coumarins occupy an important place in the realm of natural products and synthetic organic chemistry. A fast and highly efficient green method for synthesizing 3-aryl coumarin derivatives from salicylaldehyde and phenyl acetyl chloride in the presence of tetrahydrofuran and K2CO3 using ultrasound irradiation is reported. Ultrasound assisted reactions have resulted in better yields and faster reaction time of the desired products than when prepared under conventional conditions. The resulting coumarin derivatives were characterized by IR spectrum.

  4. Bioelectrochemical investigations of aryl-alcohol oxidase from Pleurotus eryngii

    OpenAIRE

    Munteanu, Florentina-Daniela; Ferreira, Patrícia; Ruiz-Duenas, Francisco J.; Martínez, Angel T.; Paulo, Artur Cavaco

    2008-01-01

    Aryl-alcohol oxidase (AAO) electrochemistry studies, using graphite-modified electrodes, are presented for the first time herein. The increase in current upon injection of the analyzed substrate was shown to be approximated by Michaelis–Menten type dependence. The calculated kinetic constants were used to characterize the native (non-mutated) recombinant AAO expressed in Escherichia coli, as well as the native enzyme and the F501Y and F501A variants expressed in Emericella nidulans. Results f...

  5. Aryl Polyphosphonates: Useful Halogen-Free Flame Retardants for Polymers

    OpenAIRE

    Li Chen; Yu-Zhong Wang

    2010-01-01

    Aryl polyphosphonates (ArPPN) have been demonstrated to function in wide applications as flame retardants for different polymer materials, including thermosets, polycarbonate, polyesters and polyamides, particularly due to their satisfactory thermal stability compared to aliphatic flame retardants, and to their desirable flow behavior observed during the processing of polymeric materials. This paper provides a brief overview of the main developments in ArPPN and their derivatives for flame-re...

  6. Silver-catalyzed direct thiolation of quinones by activation of aryl disulfides to synthesize quinonyl aryl thioethers.

    Science.gov (United States)

    Zhang, Cheng; McClure, Jesse; Chou, C James

    2015-05-15

    A silver-catalyzed coupling reaction of quinones with aryl disulfides for the synthesis of quinonyl aryl thioethers is described. In the presence of AgOAc (0.2 equiv)/dppp (0.24 equiv) as the catalyst, (NH4)2S2O8 (3.0 equiv) as the oxidant, and Bu4NBF4 (1.0 equiv) as the additive, the reaction is simple, provides high yield (up to 88% yield), and possesses a broad substrate scope. The reaction is believed to proceed via direct activation of disulfides evidenced by observation of a metathesis reaction between two different disulfides placed together under the reaction conditions and (13)C NMR spectroscopy analysis. PMID:25894360

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

    Directory of Open Access Journals (Sweden)

    Mustafa M. El-Abadelah

    2009-07-01

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

  8. Microwave Assisted Condensation Reactions of 2-Aryl Hydrazonopropanals with Nucleophilic Reagents and Dimethyl Acetylenedicarboxylate

    Directory of Open Access Journals (Sweden)

    Rita M. Borik

    2007-08-01

    Full Text Available The reaction of methyl ketones 1a-g with dimethylformamide dimethylacetal (DMFDMA afforded the enaminones 2a-g, which were coupled with diazotized aromatic amines 3a,b to give the corresponding aryl hydrazones 6a-h. Condensation of compounds 6a-h with some aromatic heterocyclic amines afforded iminoarylhydrazones 9a-m. Enaminoazo compounds 12a,b could be obtained from condensation of 6c with secondary amines. The reaction of 6e,h with benzotriazolylacetone yielded 14a,b. Also, the reaction of 6a,b,d-f,h with glycine and hippuric acid in acetic anhydride afforded pyridazinone derivatives 17a-f. Synthesis of pyridazine carboxylic acid derivatives 22a,b from the reaction of 6b,e with dimethyl acetylenedicarboxylate (DMAD in the presence of triphenylphosphine at room temperature is also reported. Most of these reactions were conducted under irradiation in a microwave oven in the absence of solvent in an attempt to improve the product yields and to reduce the reaction times.

  9. Synthesis, antiproliferative and anti-inflammatory activities of some novel 6-aryl-2-(p-(methanesulfonyl)phenyl)-4,5-dihydropyridazi-3(2H)-ones.

    Science.gov (United States)

    Ovais, Syed; Javed, Kalim; Yaseen, Shafiya; Bashir, Rafia; Rathore, Pooja; Yaseen, Raed; Hameed, Alhamzah D; Samim, Mohammad

    2013-09-01

    Sixteen new 6-aryl-2-(p-(methanesulfonyl)phenyl)-4,5-dihydropyridazi-3(2H)-ones (2a-p) were synthesized and tested for in vitro anticancer and in vivo anti-inflammatory activities. Eleven (2b, 2d, 2e-j and 2m-p) of the obtained compounds were screened for their antiproliferative activity towards 60 human cancer cell lines by the National Cancer Institute (USA). Compound 2f showed remarkable activity with GI50 less than 1 ?M on 36 human tumor cell lines and has been referred to Biological Evaluation Committee (NCI) for advance study. Compound 2g also displayed promising antiproliferative activity against 20 different cell lines with GI50 less than 1 ?M. Compounds 2k and 2n were found to have a comparable anti-inflammatory activity to that of standard drug etoricoxib in carrageenan-induced rat hind paw edema model at 5 h. PMID:23887055

  10. High-resolution laser spectroscopy and magnetic effect of the B?(2)E(')?X?(2)A2(') transition of the (15)N substituted nitrate radical.

    Science.gov (United States)

    Tada, Kohei; Teramoto, Kanon; Ishiwata, Takashi; Hirota, Eizi; Kasahara, Shunji

    2015-03-21

    Rotationally resolved high-resolution fluorescence excitation spectra of the 0-0 band of the B?(2)E(')?X?(2)A2(') transition of the (15)N substituted nitrate radical were observed for the first time, by crossing a jet-cooled molecular beam and a single-mode dye laser beam at right angles. Several thousand rotational lines were detected in the 15 080-15 103 cm(-1) region. We observed the Zeeman splitting of intense lines up to 360 G in order to obtain secure rotational assignment. Two, nine, and seven rotational line pairs with 0.0248 cm(-1) spacing were assigned to the transitions from the X?(2)A2(') (?? = 0, k? = 0, N? = 1, J? = 0.5 and 1.5) to the (2)E3/2(') (J' = 1.5), (2)E1/2(') (J' = 0.5), and (2)E1/2(') (J' = 1.5) levels, respectively, based on the ground state combination differences and the Zeeman splitting patterns. The observed spectrum was complicated due to the vibronic coupling between the bright B?(2)E(') (? = 0) state and surrounding dark vibronic states. Some series of rotational lines other than those from the X?(2)A2(') (J = 0.5 and 1.5) levels were also assigned by the ground state combination differences and the observed Zeeman splitting. The rotational branch structures were identified, and the molecular constants of the B?(2)E1/2(') (? = 0) state were estimated by a deperturbed analysis to be T0 = 15 098.20(4) cm(-1), B = 0.4282(7) cm(-1), and DJ = 4 × 10(-4) cm(-1). In the observed region, both the (2)E1/2(') and (2)E3/2(') spin-orbit components were identified, and the spin-orbit interaction constant of the B?(2)E(') (? = 0) state was estimated to be -12 cm(-1) as the lower limit. PMID:25796244

  11. Implications of cytochrome 450 isoenzymes, aryl-esterase and oxonase activity in the inhibition of the acetylcholinesterase of Chirostoma jordani treated with phosphorothionate pesticides.

    Science.gov (United States)

    Dzul-Caamal, Ricardo; Domínguez-López, M Lilia; García-Latorre, Ethel; Vega-López, Armando

    2012-10-01

    Organophosphate pesticides must be metabolized by cytochrome-P450 isoenzymes such CYP 2C19 as CYP 3A4 to induce neurotoxicity, but damage apparently depends on the activity of aryl esterases of the oxonase type that are involved in detoxication of these compounds. However, information on this subject is not available in fish. Chirostoma jordani has sustained significant population reductions, probably due to changes in land-use as well as pesticide impact; nevertheless, no specific studies demonstrating this are available. This study shows for the first time that the activity of cytochrome-P450 isoenzymes (CYP 2B6, CYP 2C19, CYP 3A4) in C. jordani is involved in diazinon and chlorpyrifos bioactivation. However, higher toxicity of chlorpyrifos cannot be explained solely because its bioactivation. Differences in toxicity between both pesticides are due to the activity of aryl esterases and oxonases that are responsible for oxon detoxication. Both hepatic enzymes metabolize diazoxon more efficiently than chlorpyrifos oxon. At lethal concentrations, detoxication is particularly important since mortality was lower with diazinon (LC50=1.5 ?g/L) than with chlorpyrifos (LC50=0.17 ?g/L). At sublethal levels, maximum acetylcholinesterase inhibition took place at 4h in both brain and muscle and was of lower magnitude in diazinon-treated fish. This is due to the higher affinity of both aryl esterases for diazoxon, which allows higher detoxication rates and therefore greater recovery of acetylcholinesterase activity. PMID:22835727

  12. Efficient synthesis of new 1-[Alkyl(aryl)]-5-(3,3,3-trihalo-2-oxopropylidene)pyrrolidine-2-ones

    Energy Technology Data Exchange (ETDEWEB)

    Flores, Alex F.C.; Flores, Darlene C.; Oliveira, Graciela; Pizzuti, Lucas; Silva, Rubia M.S. da; Martins, Marcos A.P.; Bonacorso, Helio G. [Universidade Federal de Santa Maria (UFSM), RS (Brazil). Dept. de Quimica. Nucleo de Quimica de Heterociclos (NUQUIMHE)]. E-mail: alexflores@smail.ufsm.br

    2008-07-01

    Reactions of methyl 4-methoxy-6-oxo-7,7,7-trihalo-4-heptenoates 1 and 2 with primary amines RNH{sub 2}, where R = PhCH{sub 2}, PhCH{sub 2}CH{sub 2}, Ph, 4-MeC{sub 6}H{sub 4}, 4-MeOC{sub 6}H{sub 4}, 4-ClC{sub 6}H{sub 4}, 4-BrC{sub 6}H{sub 4}, 2-pyridyl, 5-methyl-3-isoxazolyl, 4-NH{sub 2}C{sub 6}H{sub 4} affording methyl 4-[alkyl(aryl)amino]-6-oxo-7,7,7- trihalo-4-heptenoates 3, 4, in good yields (57-95%), which suffer quantitative intramolecular cyclocondensation to produce 1-alkyl(aryl)-5-(2-oxo-3,3,3-trihalopropylidene)pyrrolidine-2-ones 5, 6, are reported. The structures of the isolated new products were assigned by means of {sup 1}H, {sup 13}C NMR measurements and mass spectrometry. The Z and E configuration of compounds 3d and 5b respectively were established from X-ray crystallography. (author)

  13. Synthesis, Characterization of Cellulose Grafted N-Oxide Reagent and Its Application in Oxidation of Alkyl/Aryl Halides

    Directory of Open Access Journals (Sweden)

    Poonam K. Dhiman

    2011-03-01

    Full Text Available Oxidation of aliphatic and aromatic halides by N-oxide functionalities supported on 4- vinyl pyridine, (4-VP, grafted cellulose is reported in the present manuscript. Synthesis of graft copolymer of cellulose and poly 4-vinyl pyridine, poly(4-VP, has been carried out using ceric ions as redox initiator. Post-grafting treatment of CellO-g-poly (4-VP with 30% H2O2 in acetic acid gives Cellulose-g-poly (4-VP N-oxide, the polymeric supported oxidizing reagent. The polymeric support, CellO-g-poly (4-VP N-oxide, has been used for oxidation reactions of different alkyl / aryl halide such as 1-bromo-3-methyl butane, 2-bromo propane,1-bromo heptane and benzyl chloride. The polymeric reagent was characterized by IR and thermo-gravimetric analysis. The oxidized products were characterized by FTIR and H1NMR spectral methods. The reagent was reused for the oxidation of a fresh alkyl / aryl halides and it was observed that the polymeric reagent oxidizes the compounds successfully but with little lower product yield.

  14. Palladium-catalyzed carbonylative Heck reaction of aryl bromides with vinyl ethers to 3-alkoxy alkenones and pyrazoles.

    Science.gov (United States)

    Schranck, Johannes; Wu, Xiao-Feng; Neumann, Helfried; Beller, Matthias

    2012-04-16

    Three COming together: The first carbonylative Heck coupling reaction of aryl bromides and vinyl ethers leading to 1-aryl-3-alkoxy-2-propen-1-ones has been established (see scheme). Based on this coupling methodology, a novel one-pot synthesis of aryl-substituted pyrazoles was also realized. PMID:22422673

  15. Cu-Catalyzed Arylation of Phenols: Synthesis of Sterically Hindered and Heteroaryl Diaryl Ethers

    OpenAIRE

    Maiti, Debabrata; Buchwald, Stephen L.

    2009-01-01

    Cu-catalyzed O-arylation of phenols with aryl iodides and bromides can be performed under mild condition in DMSO/K3PO4 with use of picolinic acid as the ligand for copper. This method tolerates a variety of functional groups and is effective in the synthesis of hindered diaryl ethers and heteroaryl ethers.

  16. Oxidant-controlled regioselectivity in the oxidative arylation of N-acetylindoles

    OpenAIRE

    Potavathri, Shathaverdhan; Dumas, Ashley S.; Dwight, Timothy A.; Naumiec, Gregory R.; Hammann, Jeffrey M.; DeBoef, Brenton

    2008-01-01

    N-Acetylindoles can be oxidatively coupled with arenes such as benzene or pentafluorobenzene in dioxane. The use of Cu(OAc)2 as the stoichiometric oxidant produces selective arylation at the 3-position of indole while AgOAc produces selective arylation at indole’s 2-position.

  17. Pd-Catalyzed stereospecific allyl-aryl coupling of allylic alcohols with arylboronic acids.

    Science.gov (United States)

    Ye, Jiang; Zhao, Jingming; Xu, Jing; Mao, Yuxue; Zhang, Yong Jian

    2013-10-28

    An efficient method for Pd-catalyzed stereospecific allyl-aryl coupling of allylic alcohols with arylboronic acids has been described. The reactions proceeded smoothly in the presence of Pd2(dba)3·CHCl3 and racemic BINAP under mild and neutral conditions, affording allyl-aryl coupling products in moderate to high yields with excellent stereospecificities. PMID:24025990

  18. Regioselectivity of Arylation of 2,3’-Biquinolyl Dianion

    Directory of Open Access Journals (Sweden)

    Yu. I. Smushkevich

    1999-04-01

    Full Text Available The dianion of 2,3’-biquinolyl with aryl- and hetaryl halides forms the products of arylation to 4’-position, which on treatment with alkyl halides or water yield 1’-alkyl-1’,4’dihydro-2,3’-biquinolyls or 4’-aryl-1’,4’-dihydro-2,3’-biquinolyls respectively. The oxidation of the latter leads to 4’-aryl-2,3’-biquinolyls. The cation dependence of the arylation is shown.

  19. Synthesis of quinoxaline derivatives via condensation of aryl-1,2-diamines with 1,2-diketones using (NH4)6 Mo7 O24 . 4 H2 O as an efficient, mild and reusable catalyst

    International Nuclear Information System (INIS)

    Ammonium heptamolybdate tetrahydrate [(NH4)6Mo7O24.4H2O] efficiently catalyzes the condensation of aryl-1,2-diamines with l,2-diketones in EtOH/H2O as a green media at room temperature to afford quinoxaline derivatives as biologically interesting compounds. Ease of recycling of the catalyst is one of the most advantages of the proposed method

  20. Cyprodinil as an activator of aryl hydrocarbon receptor

    International Nuclear Information System (INIS)

    Highlights: ? Cyprodinil activated the aryl hydrocarbon receptor (AHR). ? Cyprodinil induced nuclear translocation of the AHR, and the expression of CYP1A1. ? Cyprodinil enhanced dexamethasone-induced gene expression. ? Cyprodinil phosphorylated ERK, indicating its deregulation of ERK activity. -- Abstract: Cyprodinil is a pyrimidinamine fungicide, used worldwide by agriculture. It is used to protect fruit plants and vegetables from a wide range of pathogens. Benzo[a]pyrene (BaP) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) are toxic environmental pollutants and are prototypes of aryl hydrocarbon receptor (AHR) ligands. Although the structure of cyprodinil distinctly differs from those of BaP and TCDD, our results show that cyprodinil induced nuclear translocation of the AHR, and induced the transcriptional activity of aryl hydrocarbon response element (AHRE). Cyprodinil induced the expression of cytochrome P450 (CYP) 1A1, a well-known AHR-targeted gene, in ovarian granulosa cells, HO23, and hepatoma cells, Hepa-1c1c7. Its induction did not appear in AHR signal-deficient cells, and was blocked by the AHR antagonist, CH-223191. Cyprodinil decreased AHR expression in HO23 cells, resulting in CYP1A1 expression decreasing after it peaked at 9 h of treatment in HO23 cells. Dexamethasone is a synthetic agonist of glucocorticoids. Cyprodinil enhanced dexamethasone-induced gene expression, and conversely, its induction of CYP1A1 expression was decreased by dexamethasone in HO23 cells, indicating its induction of crosstalk between the AHR and glucocorticoid receptor and its role as a potential endocrine disrupter. In addition to BaP, TCDD, and an AHR agonist, ?-NF, cyprodinil also phosphorylated extracellular signal-regulated kinase (ERK) in HO23 and Hepa-1c1c7 cells, indicating its deregulation of ERK activity. In summary, our results demonstrate that cyprodinil, similar to BaP, acts as an AHR activator, a potential endocrine disrupter, and an ERK disrupter

  1. Synthesis of New Bioactive Sulfur Compounds Bearing Heterocyclic Moiety and Their Analytical Applications

    OpenAIRE

    Mohammad. S. T. Makki; Reda. M. Abdel-Rahman; Mohammad S. El-Shahawi

    2011-01-01

    Some new bioactive sulfur compounds bearing heterocyclic nitrogen moieties such as 3- imino–2-thioxo-4,5-dihydro- thiazolidin – 4-one (3), 3-imino – 2-thioxo -3,4,5,6-tetrahydro-1, 3-thiazine-4, 6- (2 H)dione(4), N- substituted – pyrazol -3,5-dione (10) , 1,3 –disubstituted -2-thioxo-pyrimidin-4,6 –dione (11) and di –(3,5-diaminopyrazolin-1-yl)thioketone (13) derived from dithioc formic acid hydrazide (1) and thiocarbohydrazide (7)were prepared via condensation of compound 1 or 7 with acyclic...

  2. Palladium-Catalyzed C(sp(3) )?H Arylation of N-Boc Benzylalkylamines via a Deprotonative Cross-Coupling Process.

    Science.gov (United States)

    Hussain, Nusrah; Kim, Byeong-Seon; Walsh, Patrick J

    2015-07-27

    Diarylmethylamines are key intermediates and products in the pharmaceutical industry. Herein we disclose a novel method toward the synthesis of these important compounds via C?H functionalization. Presented is a reversible deprotonation of N-Boc benzylalkylamines at the benzylic C?H with in situ arylation by a NiXantPhos-based palladium catalyst (50-93?% yield, 29 examples). The method is also successful with N-Boc-tetrahydroisoquinolines. The advantages of this method are it avoids strong bases, low temperatures, and the need to transmetallate to main group metals for the coupling. PMID:26129922

  3. N-Aryl-6-methoxy-1,2,3,4-tetrahydroquinolines: a Novel Class of Antitumor Agents Targeting the Colchicine Site on Tubulin

    OpenAIRE

    Wang, Xiao-feng; Wang, Sheng-Biao; Ohkoshi, Emika; Wang, Li-Ting; Hamel, Ernest; Qian, Keduo; Susan L. Morris-Natschke; Lee, Kuo-Hsiung; Xie, Lan

    2013-01-01

    Structural optimizations of the prior lead 1a led to the discovery of a series of N-aryl-6-methoxy-1,2,3,4-tetrahydroquinoline derivatives as a novel class of tubulin polymerization inhibitors targeted at the colchicine binding site. The most active compound 6d showed extremely high cytotoxicity against a human tumor cell line panel (A549, KB, KBvin, and DU145) with GI50 values ranging from 1.5 to 1.7 nM, significantly more potent than paclitaxel, especially against the drug-resistant KBvin c...

  4. Syntheses and Biological Activities of 6-Aryl-3-(3-hydroxy- propyl-7H-1,2,4-triazolo[3,4-b][1,3,4]thiadiazines

    Directory of Open Access Journals (Sweden)

    Hai-le Zhang

    2007-03-01

    Full Text Available A series of 6-aryl-3-(3-hydroxypropyl-7H-1,2,4-triazolo[3,4-b][1,3,4]-thia-diazines were synthesized by the reaction of 4-amino-3-(3-hydroxypropyl-5-mercapto-1,2,4-triazole (1 with substituted ω-haloacetophenones. Their structures were confirmed by elemental analysis, IR, 1H-NMR, and 13C-NMR. Tests of plant growth regulating effects showed that the title compounds display remarkable inhibitory activities on the growth of radish and wheat.

  5. Syntheses and Biological Activities of 6-Aryl-3-(3-hydroxy- propyl)-7H-1,2,4-triazolo[3,4-b][1,3,4]thiadiazines

    OpenAIRE

    Hai-le Zhang; An-jiang Zhang; Xian-xing Chen; Li-xue Zhang; Jian-yu Jin

    2007-01-01

    A series of 6-aryl-3-(3-hydroxypropyl)-7H-1,2,4-triazolo[3,4-b][1,3,4]-thia-diazines were synthesized by the reaction of 4-amino-3-(3-hydroxypropyl)-5-mercapto-1,2,4-triazole (1) with substituted ω-haloacetophenones. Their structures were confirmed by elemental analysis, IR, 1H-NMR, and 13C-NMR. Tests of plant growth regulating effects showed that the title compounds display remarkable inhibitory activities on the growth of radish and wheat.

  6. Synthesis, characterization and antibacterial activity of some 5-aryl-1, 3-Diphenyl 1-4, 5-dihydro-1H-Pyrazoles

    International Nuclear Information System (INIS)

    The condensation of acetophenone (I) with arylaldehyde (II) was investigated and the resulting chalcones 2-Arylidene 1-Acetophenone (III) were reacted with phenyl hydrazine and acetic acid to produce substituted 5-aryl-1, 3-diphenyl-4, 5-dihydro-1H-Pyrazoles (IV). The structures of all products were studied by H-NMR, IR, thermal and elemental analysis. Thermo-gravimetric (TG) and differential thermal analysis (DTA) was applied to investigate the thermal behavior and structure of the synthesized compounds. 2-Pyrazolines (IV) exhibited moderate activity against Streptococcus faecalis ATCC 19433, Klebsiella pneumoniae ATCC 13883, Proteus vulgaris ATCC 25922, Shigella sonnei ATCC 25931 and Peseudom oaeruginosa ATCC 27853. (author)

  7. Some higher N-substituted 1,3-thiazolidine-2,4-diones and 5,5-diphenylhydantoins, their synthesis and corrosion preventive properties in mineral oil medium

    Science.gov (United States)

    Öztürk, Serkan; Y?ld?r?m, Ayhan; Çetin, Mehmet

    2013-01-01

    Some five membered heterocyclic compounds were synthesized by the reaction of 2,4-thiazolidinedione or 5,5-diphenylhydantoin potassium salts with 2-chloro-N-alkylacetamides and alkyl-2-chloroacetates. The structure confirmations of the synthesized compounds were performed by FT-IR, 1H NMR, 13C NMR spectra. The inhibitory effectiveness of the compounds were evaluated against the corrosion of steel strip immersed in water containing paraffin based mineral oil medium in accordance to standard test method. Surface characterization studies of the metal coupons used were performed by SEM analysis and also by the contact angle measurements using the Sessile-Drop method. In addition the 3D image of the metal surface was obtained using optical profilometer. The test results and surface characterization studies showed that all synthesized compounds are excellent corrosion inhibitors in such a water in oil emulsion system.

  8. Catalytic arylation methods from the academic lab to industrial processes

    CERN Document Server

    Burke, Anthony J

    2014-01-01

    A current view of the challenging field of catalytic arylation reactions. Clearly structured, the chapters in this one-stop resource are arranged according to the reaction type, and focus on novel, efficient and sustainable processes, rather than the well-known and established cross-coupling methods.The entire contents are written by two authors with academic and industrial expertise to ensure consistent coverage of the latest developments in the field, as well as industrial applications, such as C-H activation, iron and gold-catalyzed coupling reactions, cycloadditions or novel methodologies

  9. Efficient 11C-carbonylation of isolated aryl palladium complexes for PET: application to challenging radiopharmaceutical synthesis.

    Science.gov (United States)

    Andersen, Thomas L; Friis, Stig D; Audrain, Hélène; Nordeman, Patrik; Antoni, Gunnar; Skrydstrup, Troels

    2015-02-01

    We describe the successful implementation of palladium-aryl oxidative addition complexes as stoichiometric reagents in carbonylation reactions with (11)CO to produce structurally challenging, pharmaceutically relevant compounds. This method enables the first (11)C-carbonyl labeling of an approved PET tracer, [(11)C]raclopride, for the dopamine D2/D3 receptor by carbonylation with excellent radiochemical purity and yield. Two other molecules, [(11)C]olaparib and [(11)C]JNJ 31020028, were efficiently labeled in this manner. The technique distinguishes itself from existing methods by the markedly improved purity profiles of the tracer molecules produced and provides access to complex structures in synthetically useful yields, hereby offering a viable alternative to other (11)C-labeling strategies. PMID:25569730

  10. Direct palladium-catalyzed C-4 arylation of tri-substituted furans with aryl chlorides: An efficient access to heteroaromatics

    International Nuclear Information System (INIS)

    A series of functionalized furans were synthesized by way of a palladium -catalyzed coupling reaction of 2,3,5-tri substituted furans with aryl chlorides through C-H bond cleavages at C-4 position. The feature of the reaction was facilitative preparation of furan derivatives with good functional group tolerance. All reactions gave the desired products in moderate to good yields in the presences of BuAd2P and t-BuOK in DMF at 120 .deg. C after 15 h

  11. Application of metalation reactions for synthesis of sulfur/selenium-containing heterocyclic compounds

    OpenAIRE

    Shirani, Hamid

    2009-01-01

    This thesis deals mainly with the synthesis of various sulfur/selenium-containing heterocyclic compounds, many of which include structural features present in several biologically active molecules, with particular emphasis on compounds of synthetic importance, such as indoles, as well as other heteroaromatic species. In the first part, an efficient procedure toward synthesis of new 3-(arylthio)indoles based on reactions of aryl Grignard reagents or lithiated heteroaromat...

  12. Effects of perfluoroalkyl acids on the function of the thyroid hormone and the aryl hydrocarbon receptor

    DEFF Research Database (Denmark)

    Long, Manhai; Ghisari, Mandana

    2013-01-01

    Perfluoroalkyl acids (PFAAs) are perfluorinated compounds that widely exist in the environment and can elicit adverse effects including endocrine disruption in humans and animals. This study investigated the effect of seven PFAAs on the thyroid hormone (TH) system assessing the proliferation of the 3,3',5-triiodo-L-thryonine (T3)-dependent rat pituitary GH3 cells using the T-screen assay and the effect on the aryl hydrocarbon receptor (AhR) transactivation in the AhR-luciferase reporter gene bioassay. A dose-dependent impact on GH3 cells was observed in the range 1?×?10(-9)-1?×?10(-4) M: seven PFAAs (perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), perfluorooctanoic acid, perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnA), and perfluorododecanoic acid (PFDoA)) inhibited the GH3 cell growth, and four PFAAs (PFOS, PFHxS, PFNA, and PFUnA) antagonized the T3-induced GH3 cell proliferation. At the highest test concentration, PFHxS showed a further increase of the T3-induced GH3 growth. Among the seven tested PFAAs, only PFDoA and PFDA elicited an activating effect on the AhR. In conclusion, PFAAs possess in vitro endocrine-disrupting potential by interfering with TH and AhR functions, which need to be taken into consideration when assessing the impact on human health.

  13. Metabolomics Reveals that Aryl Hydrocarbon Receptor Activation by Environmental Chemicals Induces Systemic Metabolic Dysfunction in Mice.

    Science.gov (United States)

    Zhang, Limin; Hatzakis, Emmanuel; Nichols, Robert G; Hao, Ruixin; Correll, Jared; Smith, Philip B; Chiaro, Christopher R; Perdew, Gary H; Patterson, Andrew D

    2015-07-01

    Environmental exposure to dioxins and dioxin-like compounds poses a significant health risk for human health. Developing a better understanding of the mechanisms of toxicity through activation of the aryl hydrocarbon receptor (AHR) is likely to improve the reliability of risk assessment. In this study, the AHR-dependent metabolic response of mice exposed to 2,3,7,8-tetrachlorodibenzofuran (TCDF) was assessed using global (1)H nuclear magnetic resonance (NMR)-based metabolomics and targeted metabolite profiling of extracts obtained from serum and liver. (1)H NMR analyses revealed that TCDF exposure suppressed gluconeogenesis and glycogenolysis, stimulated lipogenesis, and triggered inflammatory gene expression in an Ahr-dependent manner. Targeted analyses using gas chromatography coupled with mass spectrometry showed TCDF treatment altered the ratio of unsaturated/saturated fatty acids. Consistent with this observation, an increase in hepatic expression of stearoyl coenzyme A desaturase 1 was observed. In addition, TCDF exposure resulted in inhibition of de novo fatty acid biosynthesis manifested by down-regulation of acetyl-CoA, malonyl-CoA, and palmitoyl-CoA metabolites and related mRNA levels. In contrast, no significant changes in the levels of glucose and lipid were observed in serum and liver obtained from Ahr-null mice following TCDF treatment, thus strongly supporting the important role of the AHR in mediating the metabolic effects seen following TCDF exposure. PMID:26023891

  14. Polymorphism of the aryl-hydrocarbon receptor gene in intron 10 of human cancers

    Directory of Open Access Journals (Sweden)

    M. Rocas

    2011-11-01

    Full Text Available Polychlorinated dibenzo-p-dioxins (PCDDs and related halogenated aromatic hydrocarbons (e.g., PCDFs, often called "dioxins", are ubiquitously present environmental contaminants. Some of them, notably 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, are among the most toxic synthetic compounds known. The biological effects of dioxins are mediated via the aryl hydrocarbon receptor (AhR. Mutations in the AhR transactivation domain are linked to sensitivity to the acute lethality of TCDD. We present here a study of AhR gene polymorphism in normal and cancer human tissues affecting pre-mRNA splicing in the AhR gene-coding transactivation domain region (exon 10, intron 10, exon 11 region, previously shown to be associated with AhR dysfunction. We tested 126 pairs of normal and cancer tissue samples from liver, lung, stomach, kidney, mucous, breast, and pancreas of 49 males and 77 females (45-70 years of age. We used in vitro splicing assay, RT-PCR and sequencing methods. Our results showed that in an in vitro system it is possible to reconstitute cellular pre-mRNA splicing events. Tested cancer tissues did not contain mutations in the AhR transactivation domain region when the DNA sequences were compared with those from normal tissues. There were also no differences in AhR mRNA splice variants between normal and malignant breast tissues and no polymorphisms in the studied regions or cDNA.

  15. Polymorphism of the aryl-hydrocarbon receptor gene in intron 10 of human cancers

    Scientific Electronic Library Online (English)

    M., Rocas; E., Jakubauskiene; A., Kanopka.

    1112-11-01

    Full Text Available Polychlorinated dibenzo-p-dioxins (PCDDs) and related halogenated aromatic hydrocarbons (e.g., PCDFs), often called "dioxins", are ubiquitously present environmental contaminants. Some of them, notably 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), are among the most toxic synthetic compounds known. Th [...] e biological effects of dioxins are mediated via the aryl hydrocarbon receptor (AhR). Mutations in the AhR transactivation domain are linked to sensitivity to the acute lethality of TCDD. We present here a study of AhR gene polymorphism in normal and cancer human tissues affecting pre-mRNA splicing in the AhR gene-coding transactivation domain region (exon 10, intron 10, exon 11 region), previously shown to be associated with AhR dysfunction. We tested 126 pairs of normal and cancer tissue samples from liver, lung, stomach, kidney, mucous, breast, and pancreas of 49 males and 77 females (45-70 years of age). We used in vitro splicing assay, RT-PCR and sequencing methods. Our results showed that in an in vitro system it is possible to reconstitute cellular pre-mRNA splicing events. Tested cancer tissues did not contain mutations in the AhR transactivation domain region when the DNA sequences were compared with those from normal tissues. There were also no differences in AhR mRNA splice variants between normal and malignant breast tissues and no polymorphisms in the studied regions or cDNA.

  16. Enzymatic aryl-O-methyl-14C labeling of model lignin monomers

    International Nuclear Information System (INIS)

    Aryl-O-methyl ethers are abundant in aerobic and anaerobic environments. In particular, lignin is composed of units of this type. Lignin monomers specifically radiolabeled in methoxy, side chain, and ring carbons have been synthesized by chemical procedures and are important in studies of lignin synthesis and degradation, humus formation, and microbial O-demethylation. In this paper attention is drawn to an enzymatic procedure for preparing O-methyl-14C-labeled aromatic lignin monomers which has not previously been exploited in microbial ecology and physiology studies and which has several advantages compared with chemical synthesis procedures. O-[methyl-14C]vanillic and O-[methyl-14C]ferulic acids were prepared with S-[methyl-14C]adenosyl-L-methionine as the methyl donor, using commercially obtained porcine liver catechol-O-methyltransferase (EC 2.1.1.6). The specific activity of the methylated products was the same as that of the methyl donor, a maximum of about 58 ?Ci/?mol, and the yields were 42% (vanillate) and 35% (ferulate). Thus lignin monomers are readily prepared as O-methylated products of the catechol-O-methyltransferase reaction and, with this enzyme method of preparation, would be more widely available than labeled compounds which require chemical synthesis

  17. Synthesis, Characterization and Antibacterial Activity of New 1,2- and 1,4-Bis(N' -Substituted Thioureido)benzene Derivatives

    Scientific Electronic Library Online (English)

    Aamer, Saeed; Naeem, Abbas; Zaman, Ashraf; Michael, Bolte.

    2013-08-01

    Full Text Available Synthesis of two series of 1,2- and 1,4-bis(thioureido)benzene derivatives was accomplished by the treatment of corresponding alkanoyl/aroyl chlorides with potassium thiocyanate in dry acetone to afford the respective isothiocyanates as intermediates. The latter were treated in situ with 1,2- and 1, [...] 4-diaminobenzene, respectively, to afford the title compounds in high yields. A total of sixteen new compounds are reported herein. The structures of the products were confirmed by spectroscopic techniques (IR, ¹H and 13C NMR, mass spectrometry), elemental analysis and in case of 1d, by X-ray diffraction technique. All the synthesized compounds were also subjected to antibacterial bioevaluation against ten different Gram-positive and Gram-negative bacterial strains using levofloxacin as the standard drug and were shown to possess promising activities.

  18. Reactivity of Aryl Halides for Reductive Dehalogenation in (Seawater Using Polymer-Supported Terpyridine Palladium Catalyst

    Directory of Open Access Journals (Sweden)

    Toshimasa Suzuka

    2015-05-01

    Full Text Available A polymer-supported terpyridine palladium complex was prepared. The complex was found to promote hydrodechlorination of aryl chlorides with potassium formate in seawater. Generally, reductive cleavage of aryl chlorides using transition metal catalysts is more difficult than that of aryl bromides and iodides (reactivity: I > Br > Cl; however, the results obtained did not follow the general trend. Therefore, we investigated the reaction inhibition agents and found a method to remove these inhibitors. The polymeric catalysts showed high catalytic activity and high reusability for transfer reduction in seawater.

  19. Portuguese compounds

    OpenAIRE

    Rio-torto, Grac?a; Ribeiro, Si?lvia

    2012-01-01

    This article presents an overview of compounding in Portuguese. Conceived as a plurilexematic unit used as a holistic denomination, a compound is characterized by lexical atomicity. The compound classes’ continuum we propose is based on the morpho-lexical nature of the internal units (root, word) and on the (non) conformity of compound constructions with Portuguese syntactic templates. Since Portuguese compounds constitute a heterogeneous and bordering class, this analysis al...

  20. Oxidative Aromatization, Cytotoxic Activity Evaluation and Conformational Study of Novel 7-aryl-10, 11-dihydro-7H-chromeno [4, 3-b]quinoline-6, 8(9H, 12H)-dione Derivatives.

    Science.gov (United States)

    Motamedi, Radineh; Shafiee, Abbas; Rezai, Mohammad Reza; Firuzi, Omidreza; Edraki, Najmeh; Miri, Ramin

    2014-01-01

    In the present work, novel 7-aryl-10, 11-dihydro-7H-chromeno [4, 3-b]quinoline-6, 8(9H, 12H)-dione derivatives were synthesized by oxidation of 7-aryl-8, 9, 10, 12-tetrahydro-7H-chromeno[4, 3-b]quinoline-6, 8-diones in the presence of silica sulfuric acid/NaNO2 with yields of 64-74%. Cytotoxic activity of synthesized compounds was assessed on three different human cancer cell lines (K562, LS180, and MCF-7). Synthesized compounds showed moderate cytotoxic activities. The most active one apeared to be 2e, containing a methoxy group on the meta position of phenyl ring (IC50 range in different cell lines: 11.1-55.7 µM). Furthermore; comparison of the cytotoxic activity of these novel oxidized derivatives with non-oxidized counterparts revealed that oxidation of dihydropyridine ring to pyridine, improves the activity especially in LS180 cell line. Conformational analysis revealed that some conformational aspects of oxidized derivatives such as orientation of C7-aryl substitute were clearly different from non-oxidized ones. PMID:24734061

  1. Novel aryl ?-aminocarbonyl derivatives as inhibitors of Trypanosoma cruzi trypanothione reductase: binding mode revised by docking and GRIND2-based 3D-QSAR procedures.

    Science.gov (United States)

    de Paula da Silva, Carlos Henrique Tomich; Bernardes, Lílian Sibelle Campos; da Silva, Vinícius Barreto; Zani, Carlos Leomar; Carvalho, Ivone

    2012-01-01

    Trypanothione reductase has long been investigated as a promising target for chemotherapeutic intervention in Chagas disease, since it is an enzyme of a unique metabolic pathway that is exclusively present in the pathogen but not in the human host, which has the analog Glutathione reductase. In spite of the present data-set includes a small number of compounds, a combined use of flexible docking, pharmacophore perception, ligand binding site prediction, and Grid-Independent Descriptors GRIND2-based 3D-Quantitative Structure-Activity Relationships (QSAR) procedures allowed us to rationalize the different biological activities of a series of 11 aryl ?-aminocarbonyl derivatives, which are inhibitors of Trypanosoma cruzi trypanothione reductase (TcTR). Three QSAR models were built and validated using different alignments, which are based on docking with the TcTR crystal structure, pharmacophore, and molecular interaction fields. The high statistical significance of the models thus obtained assures the robustness of this second generation of GRIND descriptors here used, which were able to detect the most important residues of such enzyme for binding the aryl ?-aminocarbonyl derivatives, besides to rationalize distances among them. Finally, a revised binding mode has been proposed for our inhibitors and independently supported by the different methodologies here used, allowing further optimization of the lead compounds with such combined structure- and ligand-based approaches in the fight against the Chagas disease. PMID:22546000

  2. An LFER study of the protolytic equilibria of 4-aryl-2,4-dioxobutanoic acids in aqueous solutions

    Directory of Open Access Journals (Sweden)

    TATJANA Z. VERBIC

    2007-12-01

    Full Text Available The protolytic equilibria of 13 4-aryl-2,4-dioxobutanoic acids (ADKs were spectrophotometrically studied in aqueous solutions in the pH range 1–9 at 25±1 °C and an ionic strength of 0.1 mol l-1 (NaCl, with the exception of the 4-OH- derivative which was also potentiometrically studied in the pH range 7–10 at 25±1 °C and an ionic strength of 0.1 mol l-1 (NaCl. In solution, the compounds simultaneously exist in one diketo and two enolic forms; therefore, the determined acidity constants (pKa1 1.87–2.29, pKa2 6.63–8.13 and pKa3(4-OH- 9.52 represent system macro constants. The 1H-NMR spectrum of the basic compound (4-phenyl-2,4-dioxobutanoic acid (25 °C, pD 5.0 proved the existence of all tautomeric forms. Using the extended Hammett relation, the determined pKa values were correlated with literature ? values. The predicted pKa values were in fair accordance with the experimentally observed ones. Molecular, monoanionic and dianionic forms of the basic compound were optimized by the semi-empirical molecular orbital PM6 method using the implicit water solvation model (COSMO. The obtained geometries were used to explain the quality of the LFER models.

  3. Selective C-arylation of 2,5-dibromo-3-hexylthiophene via Suzuki cross coupling reaction and their pharmacological aspects.

    Science.gov (United States)

    Ikram, Hafiz Mansoor; Rasool, Nasir; Ahmad, Gulraiz; Chotana, Ghayoor Abbas; Musharraf, Syed Ghulam; Zubair, Muhammad; Rana, Usman Ali; Zia-Ul-Haq, Muhammad; Jaafar, Hawa Ze

    2015-01-01

    The present study reports the synthesis of various new derivatives based on 5-aryl-2-bromo-3-hexylthiophene with moderate-to-good yields via a palladium-catalyzed Suzuki cross-coupling reaction. This coupling method involved the reaction of 2,5-dibromo-3-hexylthiophene with several arylboronic acids in order to synthesize corresponding thiophene derivatives under controlled and optimal reaction conditions. The different substituents (CH3, OCH3, Cl, F etc.) present on arylboronic acids are found to have significant electronic effects on the overall properties of new products. The synthesized thiophene molecules were studied for their haemolytic, biofilm inhibition and anti-thrombolytic activities, and almost all products showed potentially good properties. The compound 2-bromo-5-(3-chloro-4-fluorophenyl)-3-hexylthiophenein particular exhibited the highest values for haemolytic and bio-film inhibition activities among all newly synthesized derivatives. In addition, the compound 2-bromo-3-hexyl-5-(4-iodophenyl)thiophene also showed high anti-thrombolytic activity, suggesting the potential medicinal applications of these newly synthesized compounds. PMID:25806546

  4. Selective C-Arylation of 2,5-Dibromo-3-hexylthiophene via Suzuki Cross Coupling Reaction and Their Pharmacological Aspects

    Directory of Open Access Journals (Sweden)

    Hafiz Mansoor Ikram

    2015-03-01

    Full Text Available The present study reports the synthesis of various new derivatives based on 5-aryl-2-bromo-3-hexylthiophene with moderate-to-good yields via a palladium-catalyzed Suzuki cross-coupling reaction. This coupling method involved the reaction of 2,5-dibromo-3-hexylthiophene with several arylboronic acids in order to synthesize corresponding thiophene derivatives under controlled and optimal reaction conditions. The different substituents (CH3, OCH3, Cl, F etc. present on arylboronic acids are found to have significant electronic effects on the overall properties of new products. The synthesized thiophene molecules were studied for their haemolytic, biofilm inhibition and anti-thrombolytic activities, and almost all products showed potentially good properties. The compound 2-bromo-5-(3-chloro-4-fluorophenyl-3-hexylthiophenein particular exhibited the highest values for haemolytic and bio-film inhibition activities among all newly synthesized derivatives. In addition, the compound 2-bromo-3-hexyl-5-(4-iodophenylthiophene also showed high anti-thrombolytic activity, suggesting the potential medicinal applications of these newly synthesized compounds.

  5. Influence of substituents on the strength of aryl C-H...anion hydrogen bonds.

    Science.gov (United States)

    Bryantsev, Vyacheslav S; Hay, Benjamin P

    2005-10-27

    [structure: see text]When electron-withdrawing substituents are present, aryl C-H groups become powerful hydrogen bond donors, forming stronger complexes than obtained with conventional O-H and N-H groups. PMID:16235950

  6. Site-selective modification of peptides using rhodium and palladium catalysis: complementary electrophilic and nucleophilic arylation.

    OpenAIRE

    Chapman, CJ; Matsuno, A; Frost, CG; Willis, MC

    2007-01-01

    The site-selective modification of peptides containing dehydroalanine, tyrosine and tryptophan residues has been achieved using rhodium catalysed conjugate additions or palladium catalysed aryl-amination and -etherification reactions.

  7. Pd-catalyzed arylation of silyl enol ethers of substituted alpha-fluoroketones.

    Science.gov (United States)

    Guo, Yong; Twamley, Brendan; Shreeve, Jean'ne M

    2009-04-21

    Alpha-fluoro-alpha-aryl-ketones were synthesized by the Pd-catalyzed cross-coupling of aryl bromides with either alpha-fluoroketones or their corresponding silyl enol ethers. The direct arylation with an alpha-fluoroketone requires a strong base, such as potassium tert-butoxide, and under these conditions the presence of a base-sensitive functional group is not compatible. However, good functional tolerance was achieved when the anionic coupling moieties were generated from the silyl enol ethers obtained by reacting alpha-fluoroketones with tetrabutylammonium (tripheny1silyl)difluorosilicate (TBAT) as the fluoride source under nearly neutral conditions. The aryl halides with a carbmethoxy, nitro, cyano or carbonyl group were used. The reaction with nonfluorinated silyl enol ether 1h gave a cross-coupling product in low yield. PMID:19343262

  8. Catalytic asymmetric dearomatizing redox cross coupling of ketones with aryl hydrazines giving 1,4-diketones.

    Science.gov (United States)

    Huang, Shenlin; Kötzner, Lisa; De, Chandra Kanta; List, Benjamin

    2015-03-18

    An asymmetric Brønsted acid catalyzed dearomatizing redox cross coupling reaction has been realized, in which aryl hydrazines react with ketones to deliver 1,4-diketones, bearing an all-carbon quarternary stereocenter in high enantiopurity. PMID:25715060

  9. The Aryl Hydrocarbon Receptor: A Target for Breast Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Joann B. Powell

    2013-08-01

    Full Text Available The aryl hydrocarbon receptor (AhR is a ligand-activated transcription factor that regulates a battery of genes in response to exposure to a broad class of environmental poly aromatic hydrocarbons (PAH. AhR is historically characterized for its role in mediating the toxicity and adaptive responses to these chemicals, however mounting evidence has established a role for it in ligand-independent physiological processes and pathological conditions, including cancer. The AhR is overexpressed and constitutively activated in advanced breast cancer cases and was shown to drive the progression of breast cancer. In this article we will review the current state of knowledge on the possible role of AhR in breast cancer and how it will be exploited in targeting AhR for breast cancer therapy.

  10. Aryl hydrocarbon receptor ligands in cancer: friend and foe.

    Science.gov (United States)

    Murray, Iain A; Patterson, Andrew D; Perdew, Gary H

    2014-12-01

    The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that is best known for mediating the toxicity and tumour-promoting properties of the carcinogen 2,3,7,8-tetrachlorodibenzo-p-dioxin, commonly referred to as ‘dioxin’. AHR influences the major stages of tumorigenesis — initiation, promotion, progression and metastasis — and physiologically relevant AHR ligands are often formed during disease states or during heightened innate and adaptive immune responses. Interestingly, ligand specificity and affinity vary between rodents and humans. Studies of aggressive tumours and tumour cell lines show increased levels of AHR and constitutive localization of this receptor in the nucleus. This suggests that the AHR is chronically activated in tumours, thus facilitating tumour progression. This Review discusses the role of AHR in tumorigenesis and the potential for therapeutic modulation of its activity in tumours. PMID:25568920

  11. HPLC analysis of commercial alkyl and aryl quaternary ammonium compounds used in organoclay type rheological additives.

    Science.gov (United States)

    Spagnolo, F; Hatcher, M T; Faulseit, B K

    1987-09-01

    Mixtures of aliphatic and aromatic "quats" can be qualitatively identified in a one step chromatographic run. After separation on a strong cation exchange column, the eluted components are detected using a UV and RI detector system in series. The quaternaries present in organoclays (e.g., BENTONE type products) can also be identified by prior destruction of the silicate with hydrofluoric acid followed by chromatography of the residual quat fluorides. PMID:3667837

  12. Synthesis of Aza-Aromatic Compounds by Photocyclodehydrogenation Reaction of N-Aryl Imines.

    Czech Academy of Sciences Publication Activity Database

    Kos, Martin

    Prague : Institute of Chemical Process Fundamental of the CAS, v. v. i, 2015 - (Bendová, M.; Wagner, Z.), s. 32 ISBN 978-80-86186-70-2. [Bažant Postgraduate Conference 2015. Prague (CZ)] Institutional support: RVO:67985858 Keywords : photocyclodehydrogenation reaction * acid * polxyaromatic molecules Subject RIV: CI - Industrial Chemistry, Chemical Engineering

  13. Characterization and Thermodynamic Stability of Polymorphs of Di(arylamino) Aryl Compound ASP3026.

    Science.gov (United States)

    Takeguchi, Kazuhiro; Hirakura, Yutaka; Yamazaki, Kouji; Shimada, Itsuro; Ieda, Shigeru; Okada, Minoru; Takiyama, Hiroshi

    2015-01-01

    ASP3026 (N-{2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}-N'-[2-(propane-2-sulfonyl)phenyl]-1,3,5-triazine-2,4-diamine) was developed in Astellas Pharma Inc. as a novel and selective inhibitor of the fusion protein EML4-ALK. We investigated the thermodynamic stability of five polymorphs of ASP3026 (A01, A02, A03, A04, and A05) in detail. To determine the most stable form at ambient temperature, powder X-ray diffraction, differential scanning calorimetry, and solubility measurements were conducted. Of the five polymorphs, A04 was the most stable and A05 was the least stable. The relationship between A04 and A03 and A04 and A01 were mutually monotropic, while that between A01 and A02 was enantiotropic. The transition temperature from A02 to A01 was estimated as 325?K. A02 was more thermodynamically stable at ambient temperature than A01. Furthermore, the method to estimate polymorphic transition temperatures using solution calorimetry was found to be effective. The systematic characterization of ASP3026 polymorphs presented in this study enables the selective crystallization of the most stable form and design of solid formulations. PMID:26027465

  14. PEGylated Polyamidoamine Dendrimers with Bis-Aryl Hydrazone Linkages for Enhanced Gene Delivery

    OpenAIRE

    Yuan, Quan; Yeudall, W. Andrew; Yang, Hu

    2010-01-01

    Surface modification of polyamidoamine (PAMAM) dendrimers with polyethylene glycol (PEG) often results in the decrease in their buffering capacity, which is essential for gene transfer. In this work, bis-aryl hydrazone bond, which possesses protonatable pyridine and amines, was explored as a new linkage for PEGylation of PAMAM dendrimers. PEGylated polyamidoamine (PAMAM) dendrimer G4.0 conjugates with bis-aryl hydrazone (BAH) linkages were synthesized following a two-step procedure: activatio...

  15. Synthesis and preliminary evaluation of antinociceptive activity of novel isoxazolyl-aryl-hydrazones

    International Nuclear Information System (INIS)

    New 2-isoxazoline aldehydes were synthesized, in good yields, from cycloadduct of the 1,3-dipolar cycloaddition reaction between endocyclic enecarbamate and carboethoxyformonitrile oxide (CEFNO). Condensation of these 2-isoxazoline aldehydes with several phenyl-hydrazines produced new isoxazolyl-aryl-hydrazones, which showed low toxicity and excellent antinociceptive activity, when compared to dipyrone. The antinociceptive activity of isoxazolyl-aryl-hydrazones was performed using the acetic acid-induced mice abdominal constrictions test. (author)

  16. Aryl(hydro)boranes: versatile building blocks for boron-doped ?-electron materials.

    Science.gov (United States)

    Lorbach, Andreas; Hübner, Alexander; Wagner, Matthias

    2012-05-28

    Boron-containing ?-conjugated molecules offer a substantial application potential in the field of organic electronics. During the last decade, aryl(hydro)boranes have established themselves as versatile novel building blocks for sophisticated boron-doped materials. This perspective article comprehensively discusses key structural motifs and reactivity patterns of recently developed aryl(hydro)boranes and shows how these have been used for the synthesis of macromolecular organoboranes through hydroboration polymerisation, ring-opening polymerisation and condensation polymerisation protocols. PMID:22546926

  17. Palladium-Catalyzed Carbonylative alpha-Arylation of 2-Oxindoles with (Hetero)aryl Bromides : Efficient and Complementary Approach to 3-Acyl-2-oxindoles

    DEFF Research Database (Denmark)

    Lian, Zhong; Friis, Stig D.

    2014-01-01

    An efficient Pd-catalyzed carbonylative alpha-arylation of 2-oxindoles with aryl and heteroaryl bromides for the one-step synthesis of 3-acyl-2-oxindoles has been developed. This reaction proceeds efficiently under mild conditions and is complementary to the more common oxindole forming reactions. The transformation only requires a mild base and provides good to excellent yields even with heteroaromatic substrates. Employing a near stoichiometric amount of (13)COgen, the methodology was easily extended to [C-13] acyl labeling. The general applicability of the reaction conditions was demonstrated in the synthesis of a structure related to the pharmaceutically active 3-acyl-2-oxindoles, tenidap.

  18. 5-( [aryl or aryloxy (or thio)]methyl)-3-(1H-imidazol-1-ylmethyl)-3- (2-thienyl)-2-methylisoxazolidine derivatives as novel antifungal agents.

    Science.gov (United States)

    Mullen, G B; Mitchell, J T; Allen, S D; St Georgiev, V

    1988-12-01

    The in vitro antifungal activity of a novel series of cis- and trans-5-([aryl or aryloxy (or thio)]methyl)-3-(1H-imidazol-1-ylmethyl)-3- (2-thienyl)-2-methylisoxazolidines (13-24) was evaluated and compared with ketoconazole. The title series of compounds was prepared via a 1,3-dipolar cycloaddition reaction of 1-(2-thienyl)-2-(1H-imidazol-1-yl)-N-methylethanimine N-oxides with appropriate styrenes, allyl phenyl ethers, or allyl phenyl thioether precursors. The resulting products were mixtures of the corresponding cis- and trans-diastereomers which were readily separated by flash chromatography on neutral silica gel. The majority of compounds 13-24, when tested in solid agar cultures, exhibited moderate to potent activity against Trichophyton rubrum, Aspergillus fumigatus, and Candida albicans at concentrations ranging between less than or equal to 2.0 and 70.0 micrograms/mL. PMID:3244110

  19. Redox-active tetrathiafulvalene and dithiolene compounds derived from allylic 1,4-diol rearrangement products of disubstituted 1,3-dithiole derivatives

    Directory of Open Access Journals (Sweden)

    Filipe Vilela

    2010-10-01

    Full Text Available We present a series of compounds by exploiting the unusual 1,4-aryl shift observed for electron-rich 1,3-dithiole-2-thione and tetrathiafulvalene (TTF derivatives in the presence of perchloric acid. The mechanistic features of this rearrangement are discussed since this synthetic strategy provides an alternative route for the synthesis and functionalisation of sulfur rich compounds including redox active compounds of TTFs, and a Ni dithiolene.

  20. New air-stable planar chiral ferrocenyl monophosphine ligands: Suzuki cross-coupling of aryl chlorides and bromides

    DEFF Research Database (Denmark)

    Jensen, Jakob Feldthusen; Johannsen, Mogens

    2003-01-01

    GraphicA novel class of planar chiral electron-rich monophosphine ligands has been developed. The modular design allows a short and efficient synthesis of an array of aryl-ferrocenyl derivatives carrying the donating bis(dicyclohexyl)phosphino moiety. These new ligands have successfully been applied in the palladium-catalyzed Suzuki cross-coupling of activated as well as nonactivated aryl chlorides at room temperature. The asymmetric coupling of an aryl bromide and an aryl boronic acid was also tested, giving ees up to 54%.

  1. New class of 2-aryl-6-chloro-3,4-dihydroisoquinolinium salts as potential antifungal agents for plant protection: synthesis, bioactivity and structure-activity relationships.

    Science.gov (United States)

    Yang, Rui; Gao, Zhao-Feng; Zhao, Jie-Yu; Li, Wei-Bo; Zhou, Le; Miao, Fang

    2015-02-25

    Thirty-four new 2-aryl-6-chloro-3,4-dihydroisoquinolin-2-ium bromides were synthesized, and their structures were elucidated by spectroscopic analysis. Antifungal activities against Alternaria alternate, Curvularia lunata and Valsa mali were evaluated by the mycelium linear growth rate method. SAR was discussed also. All compounds showed some activity against each of the fungi at 25 ?g/mL. Compared to azoxystrobin, a commercial fungicide, 31 out of 34 test compounds showed higher inhibition rates against C. lunata and 10 were more effective against A. alternate and V. mali. Compounds 5-4, 5-2 and 5-34 showed the highest activity against A. alternate (EC50 = 10.3 ?g/mL), C. lunata (EC50 = 4.6 ?g/mL) and V. mali (EC50 = 3.9 ?g/mL), respectively, superior to azoxystrobin (EC50 = 12.8, 71.9, 37.2 ?g/mL). Compound 5-4 displayed good activities against each of the fungi with EC50 of 10.3, 4.7, and 18.0 ?g/mL while 5-34 displayed excellent activities against V. mali (EC50 = 3.9 ?g/mL) and C. lunata (EC50 = 5.8 ?g/mL). The SAR showed that the type and position of substituents on the C-ring had significant effects on the activity. Generally, the presence of 2'-F, 4'-F or 2'-CH3 could significantly improve the activities, whereas OH, OMe, NO2 or CF3 groups decreased the activities. Thus, it was concluded that the present research provided a new series of 2-aryl-6-chloro-3,4-dihydroisoquinolin-2-iums with excellent antifungal potency, and the results were of importance for the structure optimization design, synthesis and development of more potent isoquinoline antifungal agents. PMID:25645055

  2. Microwave-mediated and customery synthesis of N-benzoyl- or N-substituted benzoyl-N,N'-dialkylureas from arylcarboxylic acids and N,N'-disubstituted carbodiimides under solvent-free conditions

    Scientific Electronic Library Online (English)

    Ricardo A. W., Neves Filho; Ronaldo N. de, Oliveira; Rajendra M., Srivastava.

    1410-14-01

    Full Text Available Uma síntese fácil, eficiente e rápida de N-benzoil-(e benzoil N-substituída)-N,N'-dialquiluréias foi realizada com bons rendimentos em condições livre de solvente. Primeiramente, a reação entre um ácido carboxílico e uma carbodiimida dissubstituída foi feita empregando radiação de microondas, e depo [...] is a mesma reação foi realizada sob aquecimento convencional. Os rendimentos são comparáveis em ambos os casos. Abstract in english An easy, efficient and quick synthesis of N-benzoyl-(and N-substituted benzoyl)-N,N'dialkylureas, in good yields, under solvent-free conditions is described. First, the reaction between a carboxylic acid and a disubstituted carbodiimide was carried out employing microwave radiation, and later on the [...] same reaction was performed separately under dry heating without any radiation. The yields are comparable in both cases.

  3. In vitro cytotoxicity and apoptotic inducing activity of the synthesized 4-aryl-4H-chromenes derivatives against human cancer cell lines

    Directory of Open Access Journals (Sweden)

    Mohagheghi MA

    2009-09-01

    Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: 4-Aryl-4H-chromenes are novel anticancer agents which induce apoptosis in cancer cells. These compounds were found to induce apoptosis by targeting the tubulin/microtubule system in cell proliferation process. The aim of this study was to report cyototoxic and apoptosis inducing activities of a new series of synthesized 4-aryl-4H-chromenes compounds."n"n Methods: The in vitro cytotoxic activity of the synthesized 4-aryl-4H-chromenes was investigated against a paned of human cancer cell lines including MCF-7 (breast carcinoma, A549 (lung carcinoma, HEPG-2 (liver carcinoma, SW-480 (colon adenocarcinoma, U87-MG (glioblastoma, 1321N1 (astrocytoma, and DAOY (medulloblastoma. The percentage of growth inhibitory activity was evaluated using MTT colorimetric assay versus controls not treated with test derivatives. The data for etoposide, a well known anticancer drug, was included for comparison. For each compound, the 50% inhibitory concentration (IC50 were determined. Apoptosis inducing activity were assessed by DAPI staining."n"n Results: Preliminary screening showed that those chromenes analogs bearing phenyl-isoxazole-3-yl substitution or the derivatives containing methoxyphenyl in chromene ring exhibited cytotoxic and apoptotic inducing activity comparable with or even superior than the reference drug, etoposide. The compounds without this type of substitution have lower activity. "n"nConclusions: Replacement of 3, 4, 5-trimethoxyphenyl group with thiazol ring in the synthesized derivatives reduced the cytotoxic activity. However, the derivatives with phenyl-isoxazole analogue showed potent cytotoxic and apoptotic inducing activity.

  4. Harman induces CYP1A1 enzyme through an aryl hydrocarbon receptor mechanism

    International Nuclear Information System (INIS)

    Harman is a common compound in several foods, plants and beverages. Numerous studies have demonstrated its mutagenic, co-mutagenic and carcinogenic effects; however, the exact mechanism has not been fully identified. Aryl hydrocarbon receptor (AhR) is a transcription factor regulating the expression of the carcinogen-activating enzyme; cytochrome P450 1A1 (CYP1A1). In the present study, we examined the ability of harman to induce AhR-mediated signal transduction in human and rat hepatoma cells; HepG2 and H4IIE cells. Our results showed that harman significantly induced CYP1A1 mRNA in a time- and concentration-dependent manner. Similarly, harman significantly induced CYP1A1 at protein and activity levels in a concentration-dependent manner. Moreover, the AhR antagonist, resveratrol, inhibited the increase in CYP1A1 activity by harman. The RNA polymerase inhibitor, actinomycin D, completely abolished the CYP1A1 mRNA induction by harman, indicating a transcriptional activation. The role of AhR in CYP1A1 induction by harman was confirmed by using siRNA specific for human AhR. The ability of harman to induce CYP1A1 was strongly correlated with its ability to stimulate AhR-dependent luciferase activity and electrophoretic mobility shift assay. At post-transcriptional and post-translational levels, harman did not affect the stability of CYP1A1 at the mRNA and the protein levels, excluding other mechanisms participating in the obtained effects. We concluded that harman can did effects. We concluded that harman can directly induce CYP1A1 gene expression in an AhR-dependent manner and may represent a novel mechanism by which harman promotes mutagenicity, co-mutagenicity and carcinogenicity.

  5. Evidence for an aryl hydrocarbon receptor-mediated cytochrome p450 autoregulatory pathway.

    Science.gov (United States)

    Chiaro, Christopher R; Patel, Rushang D; Marcus, Craig B; Perdew, Gary H

    2007-11-01

    The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor responsible for mediating the cellular response to the toxic compound 2,3,7,8,-tetrachlorodibenzo-p-dioxin. An essential role for the AhR in cellular biology has been established previously, but no high-affinity endogenous ligand has yet been identified. We have confirmed the presence of a putative endogenous ligand(s) in CV-1 cells through transient transfection with various cytochrome P450 isoforms. Expression of cytochromes P450 1A1, 1A2, or 1B1 reduced AhR-mediated luciferase reporter activity, whereas cytochrome P450 2E1 exhibited no significant effect. Studies with 2,4,3',5'-tetramethoxystilbene, a potent and specific inhibitor of cytochrome P450 1B1, was able to partially block cytochrome P450 1B1-mediated reduction in reporter gene activity. These results provide evidence of the existence of a possible feedback mechanism in which AhR-regulated cytochromes P450 from the CYP1A and CYP1B families are able to metabolically alter putative endogenous ligand(s). Several experiments were performed to provide initial characterization of these putative endogenous ligands, including electrophoretic mobility shift assay analyses, which demonstrated that these ligands directly activate the AhR. Soluble extracts from various C57BL/6J and Ahr-null mouse tissues were also analyzed for the presence of AhR activators. Studies revealed that Ahr-null mouse lung tissue had a 4-fold increase in AhR-mediated reporter activity in cells. Quantitative polymerase chain reaction analysis revealed that lung tissue exhibits relatively high constitutive CYP1A1 mRNA levels. These results suggest that there is an autoregulatory feedback loop between the AhR and cytochrome P450 1A1 in mouse lung. PMID:17720764

  6. Association between polymorphisms in the aryl hydrocarbon receptor repressor gene and disseminated testicular germ cell cancer

    DEFF Research Database (Denmark)

    Brokken, Leon J S; Lundberg-Giwercman, Yvonne

    2013-01-01

    In the Western world, testicular germ cell cancer (TGCC) is the most common malignancy of young men. The malignant transformation of germ cells is thought to be caused by developmental and hormonal disturbances, probably related to environmental and lifestyle factors because of rapidly increasing incidence of TGCC in some countries. Additionally, there is a strong genetic component that affects susceptibility. However, genetic polymorphisms that have been identified so far only partially explain the risk of TGCC. Many of the persistent environmental pollutants act through the aryl hydrocarbon receptor (AHR). AHR signaling pathway is known to interfere with reproductive hormone signaling, which is supposed to play a role in the pathogenesis and invasive progression of TGCC. The aim of the present study was to identify whether AHR-related polymorphisms were associated with risk as well as histological and clinical features of TGCC in 367 patients and 537 controls. Haplotype-tagging single-nucleotide polymorphisms (SNPs) were genotyped in genes encoding AHR and AHR repressor (AHRR). Binary logistic regression was used to calculate the risk of TGCC, non-seminoma versus seminoma, and metastasis versus localized disease. Four SNPs in AHRR demonstrated a significant allele association with risk to develop metastases (rs2466287: OR = 0.43, 95% CI 0.21-0.90; rs2672725: OR = 0.49, 95% CI: 0.25-0.94; rs6879758: OR = 0.27, 95% CI: 0.08-0.92; rs6896163: OR = 0.34, 95% CI: 0.12-0.98). This finding supports the hypothesis that compounds acting through AHR may play a role in the invasive progression of TGCC, either directly or through modification of reproductive hormone action.

  7. Toxicological implications of polymorphisms in receptors for xenobiotic chemicals: The case of the aryl hydrocarbon receptor

    International Nuclear Information System (INIS)

    Mechanistic toxicology has predominantly been focused on adverse effects that are caused by reactive metabolites or by reactive oxygen species. However, many important xenobiotics exert their toxicity, not by generating reactive products, but rather by altering expression of specific genes. In particular, some environmental contaminants target nuclear receptors that function as regulators of transcription. For example, binding of xenobiotic chemicals to steroid receptors is a principle mechanism of endocrine disruption. The aryl hydrocarbon receptor (AHR) mediates toxicity of dioxin-like compounds. In mice, a polymorphism in the AHR ligand-binding domain reduces binding affinity by about 10-fold in the DBA/2 strain compared with the C57BL/6 strain; consequently, dose-response curves for numerous biochemical and toxic effects are shifted about one log to the right in DBA/2 mice. In the Han/Wistar (Kuopio) (H/W) rat strain, a polymorphism causes a deletion of 38 or 43 amino acids from the AHR transactivation domain. This deletion is associated with a greater than 1000-fold resistance to lethality from 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Genes in the conventional AH gene battery (e.g. CYP1A1, CYP1A2, CYP1B1, ALDH3A1, NQO1 and UGT1A1) remain responsive to TCDD in H/W rats despite the large deletion. However, the deletion may selectively alter the receptor's ability to dysregulate specific genes that are key to dioxin toxicity. We are identifying these genes using ity. We are identifying these genes using an expression array approach in dioxin-sensitive vs. dioxin-resistant rat strains and lines. Polymorphisms exist in the human AH receptor, but thus far they have not been shown to have any substantial effect on human responses to AHR-ligands

  8. The levels of PAHs and aryl hydrocarbon receptor effects in sediments of Taihu Lake, China.

    Science.gov (United States)

    Lei, Bingli; Kang, Jia; Wang, Xuetong; Yu, Yingxin; Zhang, Xiaolan; Wen, Yu; Wang, Yipei

    2014-05-01

    A total of 16 priority polycyclic aromatic hydrocarbons (PAHs) in sediment samples from Taihu Lake were analyzed by instruments, and sediment extracts were assayed for aryl hydrocarbon receptor (AhR)-mediated ethoxyresorufin-o-deethylase (EROD) induction using a rat hepatoma cell line (H4IIE). The cause-effect relationship between the observed EROD activity and chemical concentrations of PAHs was examined. Our results showed that sediment extracts could induce significant AhR effects, and the bioassay-derived 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents of raw extracts (TEQ(bio)s) ranged from 2.7 to 39.8 pg g(-1) dw. Chemical analysis showed that 16 PAHs were all detected in all samples, and their total concentrations (?16PAHs) ranged from 179.8 to 1,669.4 ng g(-1) dw. The abundance of sedimentary PAHs in the three regions (Meiliang Bay, Gonghu Bay, and Xukou Bay) showed a decreasing trend from the inflow region to the outflow region. Chemical analysis-derived TEQs (TEQ(cal)s) contributed by PAHs ranged from 1.6 to 20.7 pg g(-1) dw. The mean contribution rates (CRs) of PAHs to TEQ(bio)s were 48.9%. In Meiliang Bay, EROD effects of 60% samples were caused by PAHs whose CRs were more than 60%, while in most sampling sites of Gonghu Bay and Xukou Bay, the CRs of PAHs to TEQ(bio)s were basically below 40%. In addition, preliminary ecological risk assessment found that PAHs in sediments have very low ecological impact based on the chemical data of PAHs, while the sediments might pose an unacceptable risk to aquatic organisms and their predators based on the data of TEQ(bio). These findings showed that EROD effects of sediment extracts from Taihu Lake were also caused by other compounds, such as dioxins, polychlorinated biphenyls, etc., together. PMID:24497304

  9. Aryl sulfate formation in sea urchins (Strongylocentrotus droebachiensis) ingesting marine algae (Fucus distichus) containing 2,6-dimethylnapthalene

    International Nuclear Information System (INIS)

    The metabolism of tritiated 2,6-dimethylnapthalene (2,6-DMN) was studied in sea urchins (Strongylocentrotus droebachiensis) feeding on marine algae (Fucus distichus). The Fucus accumulated this hydrocarbon from sea water without converting it to metabolites. Most of the tritium accumulated by the sea urchins (e.g., 70.8% after 3 days) from feeding on 2,6-DMN-exposed Fucus was present in the exoskeleton (shell and spines). Moreover, after 3 days feeding, about 90% of the tritium in the total metabolite fraction of the gonads and digestive tract of the sea urchin was present as sulfate derivatives. These metabolites were identified through hydrolysis with aryl sulfatase, followed by thin-layer chromatography of the products. After 14 days of feeding, the tritium associated with the sulfate derivatives decreased in the gonads and digestive tract to 61 and 65%, respectively, of the total metabolite fraction. Hydroxy compounds from sulfatase hydrolysis were chromatographed using multiple elutions with toluene. The hydroxy isomers were separated and the R/sub f/ values were compared to those of pure reference compounds. The data indicated that 80% of the 2,6-dimethylnaphtyl sulfate contained the sulfate on the 1 and/or 3 position of the aromatic ring. Moreover, 6-methyl-2-naphthalenemethanol was not detected, which implies that sea urchins, unlike fish, metabolize alkyl-substituted aromatic hydrocarbons primarily through aromatic ring oxidationsng oxidations

  10. Regioselective Multi-component Synthesis of 7-Aryl-benzo[h][1,2,4]-triazolo[5,1-b]quinazoline-5,6-diones Catalyzed by n-Propylsulfonated ?-Al{sub 2}O{sub 3}

    Energy Technology Data Exchange (ETDEWEB)

    Li, Weilin; Tian, Shuanbao; Wu, Liqiang [Xinxiang Medical Univ., Xinxiang (China)

    2013-09-15

    We have developed a straightforward method for the synthesis of 7-aryl-benzo[h][1,2,4]-triazolo[5,1-b] quinazoline-5,6-dione derivatives by nano n-propylsulfonated ?-Al{sub 2}O{sub 3} catalyzed three-component reaction of aldehyde, 2-hydroxy-1,4-naphthoquinone and 3-amino-1,2,4-triazole. A series of 7-aryl-benzo[h][1,2,4]-triazolo[5,1-b]quinazoline-5,6-dione derivatives have been synthesized in excellent yield (85-96%). The catalyst can be recycled up to six cycles without much decrease in catalytic activity. Environment friendly catalyst, high regioselectivity and good yield are the advantages of the method. To the best of our knowledge this is the first report on synthesis of 7-aryl-benzo[h][1,2,4]-triazolo[5,1-b]quinazoline-5,6-dione derivatives. We are evaluating anticancer activity of 4, which will be published elsewhere. Naphthoquinones constitute a major class of naturally occurring compounds, and interests in their chemistry continues unabated because of their wide range of biological and therapeutic properties such as antioxidant, antifungal, anti-inflammatory, antiallergic, antiviral, and anticancer activity.

  11. Regioselective Multi-component Synthesis of 7-Aryl-benzo[h][1,2,4]-triazolo[5,1-b]quinazoline-5,6-diones Catalyzed by n-Propylsulfonated ?-Al2O3

    International Nuclear Information System (INIS)

    We have developed a straightforward method for the synthesis of 7-aryl-benzo[h][1,2,4]-triazolo[5,1-b] quinazoline-5,6-dione derivatives by nano n-propylsulfonated ?-Al2O3 catalyzed three-component reaction of aldehyde, 2-hydroxy-1,4-naphthoquinone and 3-amino-1,2,4-triazole. A series of 7-aryl-benzo[h][1,2,4]-triazolo[5,1-b]quinazoline-5,6-dione derivatives have been synthesized in excellent yield (85-96%). The catalyst can be recycled up to six cycles without much decrease in catalytic activity. Environment friendly catalyst, high regioselectivity and good yield are the advantages of the method. To the best of our knowledge this is the first report on synthesis of 7-aryl-benzo[h][1,2,4]-triazolo[5,1-b]quinazoline-5,6-dione derivatives. We are evaluating anticancer activity of 4, which will be published elsewhere. Naphthoquinones constitute a major class of naturally occurring compounds, and interests in their chemistry continues unabated because of their wide range of biological and therapeutic properties such as antioxidant, antifungal, anti-inflammatory, antiallergic, antiviral, and anticancer activity

  12. Aryl hydrocarbon receptor (AHR)-active pharmaceuticals are selective AHR modulators in MDA-MB-468 and BT474 breast cancer cells.

    Science.gov (United States)

    Jin, Un-Ho; Lee, Syng-ook; Safe, Stephen

    2012-11-01

    Leflunomide, flutamide, nimodipine, mexiletine, sulindac, tranilast, 4-hydroxytamoxifen, and omeprazole are pharmaceuticals previously characterized as aryl hydrocarbon receptor (AHR) agonists in various cell lines and animal models. In this study, the eight AHR-active pharmaceuticals were investigated in highly aggressive aryl hydrocarbon (Ah)-responsive BT474 and MDA-MB-468 breast cancer cell lines, and their effects on AHR protein, CYP1A1 (protein and mRNA), CYP1B1 (mRNA), and cell migration were determined. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) was used as a positive control. The AHR agonist activities of the pharmaceuticals depended on structure, response, and cell context. Most compounds induced one or more AHR-mediated responses in BT474 cells, whereas in Ah-responsive MDA-MB-468 cells effects of the AHR-active pharmaceuticals were highly variable. 4-Hydroxytamoxifen, mexiletine, and tranilast did not induce CYP1A1 in MDA-MB-468 cells; moreover, in combination with TCDD, mexiletine was a potent AHR antagonist, tranilast was a partial antagonist, and 4-hydroxytamoxifen also exhibited some AHR antagonist activity. Omeprazole and, to a lesser extent, sulindac and leflunomide were full and partial AHR agonists, respectively, in both breast cancer cell lines. These data indicate that the AHR-active pharmaceuticals are selective AHR modulators, and applications of these drugs for targeting the AHR must be confirmed by studies using the most relevant cell context. PMID:22879383

  13. Expedient synthesis of C-aryl carbohydrates by consecutive biocatalytic benzoin and aldol reactions.

    Science.gov (United States)

    Hernández, Karel; Parella, Teodor; Joglar, Jesús; Bujons, Jordi; Pohl, Martina; Clapés, Pere

    2015-02-16

    The introduction of aromatic residues connected by a C-C bond into the non-reducing end of carbohydrates is highly significant for the development of innovative structures with improved binding affinity and selectivity (e.g., C-aril-sLex). In this work, an expedient asymmetric "de novo" synthetic route to new aryl carbohydrate derivatives based on two sequential stereoselectively biocatalytic carboligation reactions is presented. First, the benzoin reaction of aromatic aldehydes to dimethoxyacetaldehyde is conducted, catalyzed by benzaldehyde lyase from Pseudomonas fluorescens biovar I. Then, the ?-hydroxyketones formed are reduced by using NaBH4 yielding the anti diol. After acetal hydrolysis, the aldol addition of dihydroxyacetone, hydroxyacetone, or glycolaldehyde catalyzed by the stereocomplementary D-fructose-6-phosphate aldolase and L-rhamnulose-1-phosphate aldolase is performed. Both aldolases accept unphosphorylated donor substrates, avoiding the need of handling the phosphate group that the dihydroxyacetone phosphate-dependent aldolases require. In this way, 6-C-aryl-L-sorbose, 6-C-aryl-L-fructose, 6-C-aryl-L-tagatose, and 5-C-aryl-L-xylose derivatives are prepared by using this methodology. PMID:25640727

  14. On the search for potential antimycobacterial drugs: synthesis of naphthoquinoidal, phenazinic and 1,2,3-triazolic compounds and evaluation against mycobacterium tuberculosis

    Scientific Electronic Library Online (English)

    Guilherme A. M., Jardim; Eduardo H. G., Cruz; Wagner O., Valença; Jarbas M., Resende; Bernardo L., Rodrigues; Daniela F., Ramos; Ronaldo N., Oliveira; Pedro E. A., Silva; Eufrânio N. da, Silva Júnior.

    2015-05-01

    Full Text Available Fifteen naphthoquinones, sixteen phenazines and fifteen aryl triazoles were synthesized and evaluated against Mycobacterium tuberculosis. Twenty five substances are reported here for the first time and, among all of the compounds evaluated, six presented MIC (minimal inhibitory concentration) values [...

  15. Probing the Reactivity of Dimethylsulfoxonium Methylide with Conjugated and Nonconjugated Carbonyl Compounds: An Undergraduate Experiment Combining Synthesis, Spectral Analysis, and Mechanistic Discovery

    Science.gov (United States)

    Ciaccio, James A.; Guevara, Elena L.; Alam, Rabeka; D'agrosa, Christina D.

    2010-01-01

    We introduce students to dimethylsulfoxonium methylide (DMSY) epoxidation of aryl and nonconjugated aliphatic aldehydes and ketones without revealing that DMSY cyclopropanates enones by Michael-initiated ring closure (MIRC). Each student performs the reaction of DMSY with one of nine carbonyl compounds, including four enones, and then analyzes the…

  16. Preparation and assessment of [99mTc]technetium aquacarbonyl complexes with 1,2-diaminoethane-N-substituted ligands for tumor detection

    International Nuclear Information System (INIS)

    Over least 15 years the complex [[99mTc](H20)3(CO)3]+ has been used as an intermediary to obtain technetium radiopharmaceuticals for applications in cardiology, neurology and oncology. Two important characteristics of this molecule are: the facility for obtaining that compound from aqueous solutions and the easiness of substituting H2O molecules by atoms of other ligand molecules. In this project we prepared new complexes [[99mTc](CMNS001-3)(H2O)(CO)3]+, where (CMNS001) = N-[(4-methoxy) benzyl]-1,2-diaminoethane, (CMNS003) = N,N'-bis-[(4-methoxy)benzyl]-1,2-diaminoethane, and assessed the uptake of these complexes in murine melanoma cancer cell B16F10 and breast cells MCF-7 and MDA-MD-231, and compared with [[99m](MIBI)6]+ uptake. In vitro uptake for both new technetium complex reached values close to 5%, for all cell lines, whereas the [[99mTc](MIBI)6]+ uptake was close to 1 %. The assessment of subcellular distribution showed high accumulation of the new complex in the membrane fraction, for MDAMB-231, while for B16F10 accumulation occurred both in membrane and cytoplasm; the concentration of [[99mTc](MIBI)6]+ was mainly in the cytoplasm portion. Biodistribution study in mice allowed to observe the capture of up to 1.6% of the administered dose per gram of tumor tissue for the complex [[99mTc](CMNS001)(H2O)(CO)3]+, whereas other organs such as heart, lung and muscle, showed uptake of about 5.6%, 6.4% and 2%, respectively. The complexes in this work showed a high rate of uptake in vitro, but was not reproduced in vivo model, which can be related to low concentration of the complexes inside the cells and reduced vascularity of tumor tissue, with lower intake of complex through the blood system. (author)

  17. Homocoupling of aryl halides in flow: Space integration of lithiation and FeCl3 promoted homocoupling

    Directory of Open Access Journals (Sweden)

    Aiichiro Nagaki

    2011-08-01

    Full Text Available The use of FeCl3 resulted in a fast homocoupling of aryllithiums, and this enabled its integration with the halogen–lithium exchange reaction of aryl halides in a flow microreactor. This system allows the homocoupling of two aryl halides bearing electrophilic functional groups, such as CN and NO2, in under a minute.

  18. Copper-Catalyzed N-Arylation of Amides Using (S-N-Methylpyrrolidine-2-carboxylate as the Ligand

    Directory of Open Access Journals (Sweden)

    Dong-Sheng Ma

    2010-03-01

    Full Text Available (S-N-methylpyrrolidine-2-carboxylate, a derivative of natural L-proline, was found to be an efficient ligand for the copper-catalyzed Goldberg-type N-arylation of amides with aryl halides under mild conditions. A variety of N-arylamides were synthesized in good to high yields.

  19. Effect of dioxins on regulation of tyrosine hydroxylase gene expression by aryl hydrocarbon receptor: a neurotoxicology study

    Directory of Open Access Journals (Sweden)

    Akahoshi Eiichi

    2009-06-01

    Full Text Available Abstract Background Dioxins and related compounds are suspected of causing neurological disruption. Epidemiological studies indicated that exposure to these compounds caused neurodevelopmental disturbances such as learning disability and attention deficit hyperactivity disorder, which are thought to be closely related to dopaminergic dysfunction. Although the molecular mechanism of their actions has not been fully investigated, a major participant in the process is aryl hydrocarbon receptor (AhR. This study focused on the effect of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD exposure on the regulation of TH, a rate-limiting enzyme of dopamine synthesis, gene expression by AhR. Methods N2a-R? cells were established by transfecting murine neuroblastoma Neuro2a with the rat AhR cDNA. TH expression induced by TCDD was assessed by RT-PCR and Western blotting. Participation of AhR in TCDD-induced TH gene expression was confirmed by suppressing AhR expression using the siRNA method. Catecholamines including dopamine were measured by high-performance liquid chromatography. A reporter gene assay was used to identify regulatory motifs in the promoter region of TH gene. Binding of AhR with the regulatory motif was confirmed by an electrophoretic mobility shift assay (EMSA. Results Induction of TH by TCDD through AhR activation was detected at mRNA and protein levels. Induced TH protein was functional and its expression increased dopamine synthesis. The reporter gene assay and EMSA indicated that AhR directly regulated TH gene expression. Regulatory sequence called aryl hydrocarbon receptor responsive element III (AHRE-III was identified upstream of the TH gene from -285 bp to -167 bp. Under TCDD exposure, an AhR complex was bound to AHRE-III as well as the xenobiotic response element (XRE, though AHRE-III was not identical to XRE, the conventional AhR-binding motif. Conclusion Our results suggest TCDD directly regulate the dopamine system by TH gene transactivation via an AhR-AHRE-III-mediated pathway. The AhR- mediated pathway could have a particular AhR-mediated genomic control pathway transmitting the effects of TCDD action to target cells in the development of dopaminergic disabilities.

  20. Brønsted Acidic Ionic Liquid Accelerated Halogenation of Organic Compounds with N-Halosuccinimides (NXS)

    OpenAIRE

    Stojan Stavber; Kenneth K. Laali; Dejan Vraži?; Marjan Jereb

    2012-01-01

    The Brønsted-acidic ionic liquid 1-methyl-3-(4-sulfobutyl)imidazolium triflate [BMIM(SO3H)][OTf] was demonstrated to act efficiently as solvent and catalyst for the halogenation of activated organic compounds with N-halosuccinimides (NXS) under mild conditions with short reaction times. Methyl aryl ketones were converted into ?-halo and ?,?-dihaloketones, depending on the quantity of NXS used. Ketones with activated aromatic rings were selectively halogenat...

  1. Transition metal imido compounds as Ziegler-Natta olefin polymerisation catalysts

    OpenAIRE

    Bolton, PD; Mountford, P

    2005-01-01

    Transition metal imido compounds having the general formula [(L) nM(NR)] [where (L) n is a supporting ligand or ligand set, and R typically is alkyl or aryl] have been known for nearly 50 years, and during the last two decades have been the focus of considerable attention. Relatively recently their potential application in the Ziegler-Natta polymerisation of olefins has been realised. In this contribution we review the Ziegler-Natta poly...

  2. Catalytic enantioselective arylations: boron to zinc exchange as a powerful tool for the generation of transferable aryl groups

    Scientific Electronic Library Online (English)

    Márcio W., Paixão; Antonio L., Braga; Diogo S., Lüdtke.

    Full Text Available A transmetalação entre boro e zinco apresenta uma grande importância para diversas aplicações em síntese orgânica, uma vez que permite a formação de novas ligações carbono-carbono entre reagentes organometálicos e espécies eletrofílicas. A arilação direta de aldeídos e, mais raramente de cetonas, de [...] maneira catalítica e enantiosseletiva, empregando catalisadores quirais, têm sido descrita recentemente. Os diaril metanóis opticamente enriquecidos, obtidos nessas reações são precursores valiosos para a síntese de moléculas bioativas. O presente trabalho apresenta uma revisão sobre essa crescente área de atuação e destaca alguns dos desafios que ainda permanecem. Abstract in english The transmetalation between boron and zinc is of great importance for application in organic synthesis, since it allows the formation of new carbon-carbon bonds between organometallic units and electrophiles. The direct arylation of aldehydes or more scarcely ketones, in a catalytic, enantioselectiv [...] e manner using chiral catalysts has been described recently. The enantiomerically enriched diarylmethanols obtained in these reactions are valuable precursors for important bioactive molecules. This review provides a synopsis of this ever-growing field and highlights some of the challenges that still remain.

  3. Short and efficient syntheses of protoberberine alkaloids using palladium-catalyzed enolate arylation.

    Science.gov (United States)

    Gatland, Alice E; Pilgrim, Ben S; Procopiou, Panayiotis A; Donohoe, Timothy J

    2014-12-22

    A concise synthesis of the biologically active alkaloid berberine is reported, and a versatile palladium-catalyzed enolate arylation is used to form the isoquinoline core. The overall yield of 50?% is a large improvement over the single, previous synthesis. By design, this modular route allows the rapid synthesis of other members of the protoberberine family (e.g., pseudocoptisine and palmatine) by substitution of the readily available aryl bromide and ketone coupling partners. Moreover, by combining enolate arylation with in?situ functionalization, substituents can be rapidly and regioselectively introduced at the alkaloid C13 position, as demonstrated by the total synthesis of dehydrocorydaline. The avoidance of electrophilic aromatic substitution reactions to make the isoquinoline allows direct access to analogues possessing more varied electronic properties, such as the fluorine-containing derivative synthesized here. PMID:25348493

  4. Eco-friendly solvents for palladium-catalyzed desulfitative c?h bond arylation of heteroarenes.

    Science.gov (United States)

    Hfaiedh, Anoir; Yuan, Kedong; Ben Ammar, Hamed; Ben Hassine, Bechir; Soulé, Jean-François; Doucet, Henri

    2015-05-22

    Herein, we report the Pd-catalyzed regioselective direct arylation of heteroarenes in which benzenesulfonyl chlorides are used as coupling partners through a desulfitative cross-coupling that can be performed in diethyl carbonate (DEC) or cyclopentyl methyl ether (CPME) as green and renewable solvents or even in neat conditions instead of dioxane or dimethylacetamide (DMA). Under these solvent conditions, the reaction proceeds with a wide range of heteroarenes. C2- or C5-arylated products were obtained with furan and pyrrole derivatives. Benzofuran was also arylated regioselectively at the C2-position, whereas the reaction proceeds selectively at the C3- or C4-positions if thiophenes and benzothiophenes are used. Moreover, in some cases, especially with 1-methylindole, solvent-free conditions afforded better regioselectivities and/or yields than the reaction performed in the presence of solvents. PMID:25881692

  5. 197Au-Moessbauer spectroscopic studies of organogold compounds

    International Nuclear Information System (INIS)

    197Au-Moessbauer spectroscopic data are presented for some organogold compounds of the type of RAuPPh3 and their binuclear cation complexes: [R(AuPPh3)2]BF4 (R=aryl groups). Both the 197Au- and 57Fe-Moessbauer parameters of ferrocenyl complex [(C5H5)Fe(C5H4)(AuPPh3)2]BF4 manifest a typical Au(I) state and ferrocene like Fe(II) state, respectively. (author)

  6. KEGG COMPOUND / Water [KEGG COMPOUND

    Lifescience Database Archive (English)

    Full Text Available COMPOUND: C00001 Entry C00001Compound Name H2O; Water ... Formula H2O Exact mass 18.0106 Mol weight ... oid hormone synthesismap04962Vasopressin-regulated water ... reabsorptionmap04964Proximal tubule bicarbonate re ... se 71Dispensing medicines 713Solvents 7131Purified water ... D00001Water ... (JP16/USP); Purified water ... (JP16); Pur ...

  7. Podophyllum hexandrum Offers Radioprotection by Modulating Free Radical Flux: Role of Aryl-Tetralin Lignans

    OpenAIRE

    Shawl, A. S.; Sultan, P.; Khan, H. A.; Puri, C.; Sharma, A.; Tripathi, R. P.; Kumar, R.; Rakesh Kumar Sharma; Sagar, R. K.; Shikha Singh; Rajesh Arora; Raman Chawla; Tej Krishan; Qazi, G. N.

    2006-01-01

    We have evaluated the effect of variation in aryl-tetralin lignans on the radioprotective properties of Podophyllum hexandrum. Two fractionated fractions of P. hexandrum [methanolic (S1) and chloroform fractions (S2)], with varying aryl-tetralin lignan content were utilized for the present study. The peroxyl ion scavenging potentials of S1 and S2 were found to be comparable [i.e. 45.88% (S1) and 41% (S2)] after a 48 h interval in a time-dependent study, whereas in a 2 h study, S2 exhibited si...

  8. Cross-coupling of aryl-bromide and porphyrin-bromide on an Au(111) surface.

    Science.gov (United States)

    Kuang, Guowen; Zhang, Qiushi; Li, Deng Yuan; Shang, Xue Song; Lin, Tao; Liu, Pei Nian; Lin, Nian

    2015-05-26

    Cross-coupling is of great importance in organic synthesis. Here it is demonstrated that cross-coupling of aryl-bromide and porphyrin-bromide takes place on a Au(111) surface in vacuo. The products are oligomers consisting of porphyrin moieties linked by p-phenylene at porphyrin's meso-positions. The ratio of the cross-coupled versus homocoupled bonds can be regulated by the reactant concentrations. Kinetic Monte Carlo simulations were applied to determine the activation barrier. It is expected that this reaction can be employed in other aryl-bromide precursors for designing alternating co-polymers incorporating porphyrin and other functional moieties. PMID:25882898

  9. Kinetic and chemical characterization of aldehyde oxidation by fungal aryl-alcohol oxidase

    OpenAIRE

    Ferreira, Patricia; Hernández-Ortega, Aitor; Herguedas, Beatriz; Rencoret, Jorge; Gutiérrez, Ana; Martínez, Maria Jesús; Jiménez-Barbero, Jesús; Medina, Milagros; Martínez, Ángel T.

    2010-01-01

    Abstract Fungal aryl-alcohol oxidase (AAO) provides H2O2 for lignin biodegradation. AAO is active on benzyl alcohols that are oxidized to aldehydes. However, the H2O2 formed from some of them was more than stoichiometric with respect to the aldehyde detected. This was due to a double reaction that involves aryl-aldehyde oxidase activity. The latter was investigated using different benzylic aldehydes, whose oxidation to acids was demonstrated by GC-MS. The steady and pre-steady stat...

  10. Ralfuranone Is Produced by an Alternative Aryl-Substituted ?-Lactone Biosynthetic Route in Ralstonia solanacearum.

    Science.gov (United States)

    Pauly, Julia; Nett, Markus; Hoffmeister, Dirk

    2014-07-17

    The aryl-substituted ?-lactones ralfuranones A and B were isolated after feeding l-[1-(13)C]-phenylalanine to a liquid culture of the plant pathogenic bacterium Ralstonia solanacearum. (13)C NMR analysis demonstrated specific enrichment of the label at position 2 of the ?-lactone. This labeling pattern is consistent with a biosynthetic mechanism that includes direct cyclization of two monomeric phenylpyruvate precursors into an ?,?-substituted lactone, but incompatible with a terphenylquinone intermediate. As the latter was shown as an intermediate in allantofuranone biosynthesis, we conclude that aryl-substituted ?-lactones can be assembled via divergent biosynthetic routes. PMID:25033087

  11. Reduction of aryl halides by consecutive visible light-induced electron transfer processes.

    Science.gov (United States)

    Ghosh, Indrajit; Ghosh, Tamal; Bardagi, Javier I; König, Burkhard

    2014-11-01

    Biological photosynthesis uses the energy of several visible light photons for the challenging oxidation of water, whereas chemical photocatalysis typically involves only single-photon excitation. Perylene bisimide is reduced by visible light photoinduced electron transfer (PET) to its stable and colored radical anion. We report here that subsequent excitation of the radical anion accumulates sufficient energy for the reduction of stable aryl chlorides giving aryl radicals, which were trapped by hydrogen atom donors or used in carbon-carbon bond formation. This consecutive PET (conPET) overcomes the current energetic limitation of visible light photoredox catalysis and allows the photocatalytic conversion of less reactive chemical bonds in organic synthesis. PMID:25378618

  12. Polybenzimidazole compounds

    Science.gov (United States)

    Klaehn, John R. (Idaho Falls, ID); Peterson, Eric S. (Idaho Falls, ID); Orme, Christopher J. (Shelley, ID); Jones, Michael G. (Chubbuck, ID); Wertsching, Alan K. (Idaho Falls, ID); Luther, Thomas A. (Idaho Falls, ID); Trowbridge, Tammy L. (Idaho Falls, ID)

    2011-11-22

    A PBI compound includes imidazole nitrogens at least a portion of which are substituted with a moiety containing a carbonyl group, the substituted imidazole nitrogens being bonded to carbon of the carbonyl group. At least 85% of the nitrogens may be substituted. The carbonyl-containing moiety may include RCO--, where R is alkoxy or haloalkyl. The PBI compound may exhibit a first temperature marking an onset of weight loss corresponding to reversion of the substituted PBI that is less than a second temperature marking an onset of decomposition of an otherwise identical PBI compound without the substituted moiety. The PBI compound may be included in separatory media. A substituted PBI synthesis method may include providing a parent PBI in a less than 5 wt % solvent solution. Substituting may use more than 5 equivalents in relation to the imidazole nitrogens to be substituted.

  13. Muscarinic receptor 1 agonist activity of novel N-aryl carboxamide substituted 3-morpholino arecoline derivatives in Alzheimer's presenile dementia models.

    Science.gov (United States)

    Malviya, Manish; Kumar, Y C Sunil; Mythri, R B; Venkateshappa, C; Subhash, M N; Rangappa, K S

    2009-08-01

    Earlier we have reported the effect of arecoline thiazolidinone and morpholino arecoline derivatives as muscarinic receptor 1 agonists in Alzheimer's presenile dementia models. To elucidate further our Structure-Activity Relationship (SAR) studies on the chemistry and muscarinic receptor 1 binding efficacy, a series of novel carboxamide derivatives of 2-(1-methyl-1,2,5,6-tetrahydropyridin-3-yl)morpholine molecule have been designed and synthesized as a new class of M1 receptor agonists with a low toxicity effect profile that enhances memory function in animal models of Alzheimer's presenile dementia and also modulates the APP secretion from rat brain cerebrocortical slices by activating M1 receptor in vitro. Results suggest that compound 9b having methyl group at the para position of the aryl group attached to the carboxamide of morpholino arecoline could emerge as a potent molecule having antidementia activity. PMID:19595599

  14. Synthesis and serotonin transporter activity of 1,3-bis(aryl)-2-nitro-1-propenes as a new class of anticancer agents

    DEFF Research Database (Denmark)

    McNamara, Yvonne M.; Cloonan, Suzanne M.

    2011-01-01

    Structural derivatives of 4-MTA, an illegal amphetamine analogue have been previously shown to have anticancer effects in vitro. In this study we report the synthesis of a series of novel 1,3-bis(aryl)-2-nitro-1-propene derivatives related in structure to 4-MTA. A number of these compounds containing a classic nitrostyrene structure are shown to have antiproliferative activities in vitro in a range of malignant cell lines, particularly against Burkitt’s lymphoma derived cell lines, whilst having no effect on ‘normal’ peripheral blood mononuclear cells. Such effects appear to be independent of the serotonin transporter, a high affinity target for amphetamines and independent of protein tyrosine phosphatases and tubulin dynamics both of which have been previously associated with nitrostyrene-induced cell death. We demonstrate that a number of these compounds induce caspase activation, PARP cleavage, chromatin condensation and membrane blebbing in a Burkitt’s lymphoma derived cell line, consistent with these compounds inducing apoptosis in vitro. Although no specific target has yet been identified for the action of these compounds, the cell death elicited is potent, selective and worthy of further investigation.

  15. X-ray crystal structure investigation of an N-substituted ciprofloxacin:1-cyclopropyl-6-fluoro-1,4-dihydro-7-[4-(1-isovaleramido- 1-trifluoromethyl-2,2,2-trifluoroethyl)-1-piperazinyl]-4-oxoquinoline- 3-carboxylic acid

    International Nuclear Information System (INIS)

    The x-ray crystal and molecular structure of an N-substituted ciprofloxacinC25H27F7N4O4(I) was determined: sp. gr. P21/c; a=9.870(1); b=28.443(3), and c=9.534(1) A; ?=99.09(1) deg., Z=4; and R=0.046 [automated CAD-4 diffractometer,?CuK?; 2687 unique reflections with I?2?]. Molecule I contains a flattened bicyclic 1,4-dihydro-4-oxoquinoline skeleton and a COOH group coplanar to it, which forms a strong intramolecular hydrogen bond with the 4-oxo group. The piperazine ring in I has a chair conformation, and the plane through its four C atoms forms an angle of 37 deg. with the plane through the adjacent benzene ring. Two unusual intramolecular hydrogen bonds are observed in the structure: C(sp3)-H···F-C(ar) and N(sp2)-H···F-C(sp3). In the crystal, molecules I are connected by the intermolecular hydrogen bonds ···O=C-N-H···O=C-N-H···etc., into infinite chains running along the z-axis

  16. Labeling of alprenolol with fluorescent aryl iodide as a reagent based on Mizoroki-Heck coupling reaction.

    Science.gov (United States)

    Kishikawa, Naoya; Ohkuma, Mizuho; Wada, Mitsuhiro; Ohyama, Kaname; Ikeda, Rie; Nakashima, Kenichiro; Kuroda, Naotaka

    2011-05-20

    A novel fluorescent labeling method for alprenolol was developed based on Mizoroki-Heck coupling reaction. We designed and synthesized fluorescent aryl iodide, 4-(4,5-diphenyl-1H-imidazol-2-yl)iodobenzene (DIBI) as a labeling reagent. DIBI has a lophine skeleton carrying an iodide atom acting as fluorophore and reactive center, respectively. In order to evaluate the usefulness of DIBI, a high-performance liquid chromatography (HPLC) with fluorescence detection method was developed for the determination of alprenolol as a model compound of terminal double bond. The fluorescent labeling of alprenolol with DIBI was achieved in the presence of palladium acetate as a catalyst, and the labeled alprenolol was detected fluorometrically. In addition, it was found that the fluorescence of DIBI derivative increased and red shifted when compared with that of DIBI. Furthermore, the proposed method could be applied to determine the alprenolol concentration in rat plasma after administration of alprenolol without interferences from biological components. The detection limit (S/N=3) for alprenolol in rat plasma was 0.74 ng/mL (30 fmol on column). PMID:21489541

  17. Aryl hydrocarbon receptor activation and developmental toxicity in zebrafish in response to soil extracts containing unsubstituted and oxygenated PAHs.

    Science.gov (United States)

    Wincent, Emma; Jönsson, Maria E; Bottai, Matteo; Lundstedt, Staffan; Dreij, Kristian

    2015-03-17

    Many industrial sites are polluted by complex mixtures of polycyclic aromatic compounds (PACs). Besides polycyclic aromatic hydrocarbons (PAHs), these mixtures often contain significant amounts of more polar PACs including oxygenated PAHs (oxy-PAHs). The effects of oxy-PAHs are, however, poorly known. Here we used zebrafish embryos to examine toxicities and transcriptional changes induced by PAC containing soil extracts from three different industrial sites: a gasworks (GAS), a former wood preservation site (WOOD), and a coke oven (COKE), and to PAH and oxy-PAH containing fractions of these. All extracts induced aryl hydrocarbon receptor (Ahr)-regulated mRNAs, malformations, and mortality. The WOOD extract was most toxic and the GAS extract least toxic. The extracts induced glutathione transferases and heat shock protein 70, suggesting that the toxicity also involved oxidative stress. With all extracts, Ahr2-knock-down reduced the toxicity, indicating a significant Ahr2-dependence on the effects. Ahr2-knock-down was most effective with the PAH fraction of the WOOD extract and with the oxy-PAH fraction of the COKE extract. Our results indicate that oxy-PAH containing mixtures can be as potent Ahr activators and developmental toxicants as PAHs. In addition to Ahr activating potency, the profile of cytochrome P4501 inhibitors may also determine the toxic potency of the extracts. PMID:25715055

  18. Decarboxylative C-H arylation of benzoic acids under radical conditions.

    Science.gov (United States)

    Seo, Sangwon; Slater, Mark; Greaney, Michael F

    2012-05-18

    A decarboxylative radical cyclization reaction has been developed for the synthesis of fluorenones. The reaction uses Ag(I)/K2S2O8 to oxidatively decarboxylate an aroylbenzoic acid to an aryl radical, which undergoes cyclization to afford fluorenone products in good yield. PMID:22571756

  19. Magnetic silica supported palladium catalyst: synthesis of allyl aryl ethers in water

    Science.gov (United States)

    A simple and benign procedure for the synthesis of aryl allyl ethers has been developed using phenols, allyl acetates and magnetically recyclable silica supported palladium catalyst in water; performance of reaction in air and easy separation of the catalyst using an external mag...

  20. Palladium-catalyzed carbonylative Sonogashira coupling between aryl triazenes and alkynes.

    Science.gov (United States)

    Li, Wanfang; Wu, Xiao-Feng

    2015-04-29

    We developed a palladium-catalyzed carbonylative Sonogashira reaction with aryl triazenes and alkynes as substrates and methanesulfonic acid as the additive. A series of ?,?-ynones were synthesized by this alternative procedure. Notably, bromides, iodides and hydroxyl groups could be well-tolerated under these reaction conditions. PMID:25849661

  1. Palladium-catalyzed carbonylative sonogashira coupling of aryl bromides using near stoichiometric carbon monoxide

    DEFF Research Database (Denmark)

    Neumann, Karoline T.; Laursen, Simon R.

    2014-01-01

    A general procedure for the palladium-catalyzed carbonylative Sonogashira coupling of aryl bromides is reported, using near stoichiometric amounts of carbon monoxide. The method allows a broad substrate scope in moderate to excellent yields. The formed alkynone motive serves as a platform for synthesis of various heterocyclic structures, including pyrimidines. Furthermore, the presented strategy allows effective 13C labeling.

  2. Tandem copper-catalysed aryl and alkenyl amination reactions: the synthesis of N-functionalised indoles.

    OpenAIRE

    Hodgkinson, Rc; Schulz, J.; Willis, Mc

    2009-01-01

    A Cu-diamine complex effectively catalyses tandem C-N bond formation on 2-(2-haloalkenyl)-aryl halide substrates, to deliver a series of N-functionalised indoles. Anilines, amides and carbamates are all effective coupling partners under the developed conditions.

  3. Kinetics and Mechanism of the Aminolysis of Aryl N-Allyl Thiocarbamates in Acetonitrile

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Han Na; Oh, Hyuck Keun [Chonbuk National Univ., Jeonju (Korea, Republic of)

    2010-02-15

    We propose a concerted mechanism with a hydrogen bonded cyclic transition state for the aminolysis of aryl N-allyl thiocarbamates with benzylamines in acetonitrile based on the negative cross-interaction constant, failure of RSP, the kinetic isotope effects greater than unity and relatively low ?H{sup ?}. with large negative ?S{sup ?}. values. The aminolysis mechanism of aryl carbamates, 1, is quite similar to that of aryl carbonates, 2, and aryl esters, 3. A change in the mechanism of the aminolysis with benzylamines in acetonitrile has been observed from stepwise through a tetrahedral intermediate, T{sup ±}, to concerted for the carbamates (1 with R = Ph) as well as for the carbonates (2 with R = Et) when leaving group is changed from phenoxides (a : {sup -}OAr) to thiophenoxides (b : {sup -}SAr). This suggests that the strength of push provided to expel the leaving group from T{sup ±} by PhNH is similar to that by EtO, and the destabilization of T{sup ±} due to this push is strong enough for {sup -}SAr but is too weak for {sup -}OAr to lead the aminolysis to a concerted process.

  4. Kinetics and Mechanism of the Aminolysis of Aryl N-Allyl Thiocarbamates in Acetonitrile

    International Nuclear Information System (INIS)

    We propose a concerted mechanism with a hydrogen bonded cyclic transition state for the aminolysis of aryl N-allyl thiocarbamates with benzylamines in acetonitrile based on the negative cross-interaction constant, failure of RSP, the kinetic isotope effects greater than unity and relatively low ?H?. with large negative ?S?. values. The aminolysis mechanism of aryl carbamates, 1, is quite similar to that of aryl carbonates, 2, and aryl esters, 3. A change in the mechanism of the aminolysis with benzylamines in acetonitrile has been observed from stepwise through a tetrahedral intermediate, T±, to concerted for the carbamates (1 with R = Ph) as well as for the carbonates (2 with R = Et) when leaving group is changed from phenoxides (a : -OAr) to thiophenoxides (b : -SAr). This suggests that the strength of push provided to expel the leaving group from T± by PhNH is similar to that by EtO, and the destabilization of T± due to this push is strong enough for -SAr but is too weak for -OAr to lead the aminolysis to a concerted process

  5. Efficient and Simple Synthesis of 6-Aryl-1,4-dimethyl-9H-carbazoles

    Directory of Open Access Journals (Sweden)

    Sylvain Rault

    2008-06-01

    Full Text Available A synthetic method for the preparation of 6-aryl-1,4-dimethyl-9H-carbazoles involving a palladium catalyzed coupling reaction of 1,4-dimethyl-9H-carbazole-6-boronic acids and (heteroaryl halides is described.

  6. Novel synthesis of primary arylamides from aryl methyl ketone oxidations using iodine in aqueous ammonia

    Scientific Electronic Library Online (English)

    Norma A., Angeles; Felipe, Villavicencio; Carlos, Guadarrama; David, Corona; Erick, Cuevas-Yañez.

    Full Text Available Arilamidas primárias foram obtidas em bons rendimentos quando diversas arilmetilcetonas foram tratadas com iodo em amônia aquosa a temperatura ambiente. [...] Abstract in english Primary arylamides were obtained when several aryl methyl ketones were treated with iodine in aqueous ammonia at room temperature in goods yields. [...

  7. Continuous flow photolysis of aryl azides: Preparation of 3H-azepinones

    Directory of Open Access Journals (Sweden)

    Farhan R. Bou-Hamdan

    2011-08-01

    Full Text Available Photolysis of aryl azides to give nitrenes, and their subsequent rearrangement in the presence of water to give 3H-azepinones, is performed in continuous flow in a photoreactor constructed of fluorinated ethylene polymer (FEP tubing. Fine tuning of the reaction conditions using the flow reactor allowed minimization of secondary photochemical reactions.

  8. Continuous flow photolysis of aryl azides: Preparation of 3H-azepinones

    OpenAIRE

    Bou-hamdan, Farhan R.; Le?vesque, Franc?ois; O Brien, Alexander G.; Seeberger, Peter H.

    2011-01-01

    Photolysis of aryl azides to give nitrenes, and their subsequent rearrangement in the presence of water to give 3H-azepinones, is performed in continuous flow in a photoreactor constructed of fluorinated ethylene polymer (FEP) tubing. Fine tuning of the reaction conditions using the flow reactor allowed minimization of secondary photochemical reactions.

  9. Continuous flow photolysis of aryl azides: Preparation of 3H-azepinones

    OpenAIRE

    Bou-hamdan, Farhan R.; Vesque, Fran Ois L.; Brien, Alexander G. O.; Seeberger, Peter H.

    2011-01-01

    Photolysis of aryl azides to give nitrenes, and their subsequent rearrangement in the presence of water to give 3H-azepinones, is performed in continuous flow in a photoreactor constructed of fluorinated ethylene polymer (FEP) tubing. Fine tuning of the reaction conditions using the flow reactor allowed minimization of secondary photochemical reactions.

  10. Brønsted acid-surfactant (BAS catalysed cyclotrimerization of aryl methyl ketone

    Directory of Open Access Journals (Sweden)

    Kiran Phatangare

    2012-07-01

    Full Text Available A brønsted acid-surfactant catalysed and simple, mild, metal catalyst free and chemo-selective method has been developed for synthesis of 1, 3, 5-triaryl benzenes from aryl methyl ketones. The advantages of this protocol subsume green and sustainable reaction medium, mild reaction conditions, easy product recovery and its good yields.

  11. Efficient synthesis of new 1-[Alkyl(aryl)]-5-(3,3,3-trihalo-2-oxopropylidene)pyrrolidin-2-ones

    Scientific Electronic Library Online (English)

    Alex F. C., Flores; Darlene C., Flores; Graciela, Oliveira; Lucas, Pizzuti; Rubia M. S. da, Silva; Marcos A. P., Martins; Helio G., Bonacorso.

    Full Text Available Este trabalho mostra a síntese, em bons rendimentos (57-95%), de duas séries de 1-alquil(aril)amino-2-oxo-5-(2-oxo-3,3,3-trialopropiliden)-pirrolidinas 5 e 6, a partir dos intermediários 4-[alquil(aril)amino]-6-oxo-7,7,7-trialo-4-hepteno-atos de metila 3 e 4 obtidos por substituição da metoxila-beta [...] nos precursores 4-metoxi-6-oxo-7,7,7-trialo-4-heptenoatos de metila 1 e 2, pela série de aminas primárias RNH2, onde R = PhCH2, PhCH2CH2, Ph, 4-MeC6H4, 4-MeOC6H4, 4-ClC6H4, 4-BrC6H4, 2-piridnil, 5-metil-3-isoxazolil, 4-NH2C6H4. A estrutura molecular dos produtos inéditos foi atribuída a partir dos dados de RMN ¹H, 13C e espectrometria de massas. A configuração geométrica dos compostos 3d e 5b foi confirmada pelos dados de difração de raios-X em monocristal. Abstract in english Reactions of methyl 4-methoxy-6-oxo-7,7,7-trihalo-4-heptenoates 1 and 2 with primary amines RNH2, where R = PhCH2, PhCH2CH2, Ph, 4-MeC6H4, 4-MeOC6H4, 4-ClC6H4, 4-BrC6H4, 2-pyridyl, 5-methyl-3-isoxazolyl, 4-NH2C6H4 affording methyl 4-[alkyl(aryl)amino]-6-oxo-7,7,7-trihalo-4-heptenoates 3, 4, in good [...] yields (57-95%), which suffer quantitative intramolecular cyclocondensation to produce 1-alkyl(aryl)-5-(2-oxo-3,3,3-trihalopropylidene)pyrrolidin-2-ones 5, 6, are reported. The structures of the isolated new products were assigned by means of ¹H,13C NMR measurements and mass spectrometry. The Z and E configuration of compounds 3d and 5b respectively were established from X-ray crystallography.

  12. Synthesis of acyl carbamates via four component Pd-catalyzed carbonylative coupling of aryl halides, potassium cyanate, and alcohols.

    Science.gov (United States)

    Yin, Hongfei; de Almeida, Angelina M; de Almeida, Mauro V; Lindhardt, Anders T; Skrydstrup, Troels

    2015-03-01

    A simple and mild method is demonstrated for assembling acyl carbamates through a base-free four-component Pd-catalyzed carbonylation of aryl halides in the presence of potassium cyanate and alcohols in a two-chamber system. This approach produces a wide range of aryl acyl carbamates in good to excellent yields from the corresponding aryl bromides or iodides with near-stoichiometric carbon monoxide. In addition, the method can be extended to the synthesis of primary amides thereby expanding the usefulness of cyanate as an ammonia equivalent. PMID:25679260

  13. Polymer compound

    OpenAIRE

    Lange, RFM (Ronald); Meijer, EW (Bert)

    1995-01-01

    A Polymer compound comprising a polymer (a) that contains cyclic imidesgroups and a polymer (b) that contains monomer groups with a 2,4-diamino-1,3,5-triazine side group. According to the formula (see formula) whereby themole percentage ratio of the cyclic imides groups in the polymer compoundwith respect to the mole percentage of the monomer units with 2,4-diamino-1,3,5-triazine side group in the polymer compound is 0.1-10.0. Preferablypolymer (a) and/or polymer (b) contain styrene and/or al...

  14. DFT Study on Amine-Mediated Ring-Opening Mechanism of ?-Amino Acid N-Carboxyanhydride and N-Substituted Glycine N-Carboxyanhydride: Secondary Amine versus Primary Amine.

    Science.gov (United States)

    Liu, Junhua; Ling, Jun

    2015-07-01

    Is decarboxylation the rate-determining step of amine-mediated ring-opening polymerizations (ROPs) of ?-amino acid N-carboxyanhydride (NCA) and N-substituted glycine N-carboxyanhydride (NNCA)? Can a secondary amine initiate living a ROP of NCA to produce primary amine as an active chain end? We investigate the normal amine mechanism (NAM) of polymerizations of l-alanine-NCA (Ala-NCA) and sarcosine-NCA (Sar-NCA) principally by means of density functional theory (DFT) computation. Detailed Gibbs free energy profiles of elemental reactions in NAM of Ala-NCA and Sar-NCA ROPs have been successfully obtained. In addition, the reaction pathways are checked by DFT, Møller-Plesset perturbation theory, and coupled cluster theory. The rate-determining steps in all ROPs of NCA and NNCA initiated by either secondary or primary amine are amine addition on a 5-carbonyl group rather than decarboxylation. The energy barrier in the case of a secondary amine is lower than that of a primary amine with quite a small difference, which confirms that the secondary amine can initiate the ROPs of NCA and NNCA as fast as, if not faster than, a primary amine does, which supports the experimental results. All the results obtained from various calculation methods show that the reactivity ratios (r) of Ala-NCA and Sar-NCA as well as the product of r1 × r2 are close to 1, indicating a random copolymerization of the two different kinds of NCAs. PMID:26086174

  15. N-aryl-6-methoxy-1,2,3,4-tetrahydroquinolines: a novel class of antitumor agents targeting the colchicine site on tubulin.

    Science.gov (United States)

    Wang, Xiao-Feng; Wang, Sheng-Biao; Ohkoshi, Emika; Wang, Li-Ting; Hamel, Ernest; Qian, Keduo; Morris-Natschke, Susan L; Lee, Kuo-Hsiung; Xie, Lan

    2013-09-01

    Structural optimizations of the prior lead 1a led to the discovery of a series of N-aryl-6-methoxy-1,2,3,4-tetrahydroquinoline derivatives as a novel class of tubulin polymerization inhibitors targeted at the colchicine binding site. The most active compound 6d showed extremely high cytotoxicity against a human tumor cell line panel (A549, KB, KBvin, and DU145) with GI50 values ranging from 1.5 to 1.7 nM, significantly more potent than paclitaxel, especially against the drug-resistant KBvin cell line, in the same assays. Analogs 5f, 6b, 6c, and 6e were also quite potent, with a GI50 range of 0.011-0.19 ?M. In further studies, active compounds 6b-e and 5f significantly inhibited tubulin assembly, with IC50 values of 0.92-1.0 ?M and strongly inhibited colchicine binding to tubulin, with inhibition rates of 75-99% (at 5 ?M), comparable with or more potent than combretastatin A-4 (IC50 0.96 ?M). Current studies included design, synthesis, and biological evaluations of 24 new compounds (series 3-6). Related SAR analysis, molecular modeling, and evaluation of essential drug-like properties, i.e. water solubility, log P, and in vitro metabolic stability, were also performed. PMID:23867604

  16. Orally Active Metabotropic Glutamate Subtype 2 Receptor Positive Allosteric Modulators: Structure-Activity Relationships and Assessment in a Rat Model of Nicotine Dependence

    OpenAIRE

    Sidique, Shyama; Dhanya, Raveendra-Panickar; Sheffler, Douglas J.; Nickols, Hilary Highfield; YANG, Li; Dahl, Russell; Mangravita-Novo, Arianna; Smith, Layton H.; D’Souza, Manoranjan S.; Semenova, Svetlana; Conn, P. Jeffrey; Markou, Athina; Cosford, Nicholas D P

    2012-01-01

    Compounds that modulate metabotropic glutamate subtype 2 (mGlu2) receptors have the potential to treat several disorders of the central nervous system (CNS) including drug dependence. Herein we describe the synthesis and structure-activity relationship (SAR) studies around a series of mGlu2 receptor positive allosteric modulators (PAMs). The effects of N-substitution (R1) and substitutions on the aryl ring (R2) were identified as key areas for SAR exploration (Figure 3). Investigation of the ...

  17. Asymmetric synthesis of planar chiral ferrocenes by enantioselective intramolecular C-H arylation of N-(2-haloaryl)ferrocenecarboxamides.

    Science.gov (United States)

    Liu, Lantao; Zhang, An-An; Zhao, Rui-Juan; Li, Feng; Meng, Tuan-Jie; Ishida, Naoki; Murakami, Masahiro; Zhao, Wen-Xian

    2014-10-17

    The palladium-catalyzed intramolecular C-H arylation reaction of N-(2-bromoaryl)ferrocenecarboxamides furnishes planar chiral ferrocene derivatives. TADDOL-derived phosphoramide ligands induce enantioselectivities ranging from 91:9 to 98:2 er. PMID:25264929

  18. Synthesis of 4-Aryl Substituted 3,4-Dihydropyrimidinones Using Silica-chloride Under Solvent Free Conditions

    OpenAIRE

    M P Kaushik; Manisha Sathe; Hitendra N Karade

    2007-01-01

    This paper describes an improved procedure for the efficient and facile synthesis of 4-aryl substituted 3, 4-dihydropyrimidinones under mild reaction conditions with excellent yields using inexpensive silica chloride under solvent free conditions.

  19. Synthesis of 4-Aryl Substituted 3,4-Dihydropyrimidinones Using Silica-chloride Under Solvent Free Conditions

    Directory of Open Access Journals (Sweden)

    M P Kaushik

    2007-07-01

    Full Text Available This paper describes an improved procedure for the efficient and facile synthesis of 4-aryl substituted 3, 4-dihydropyrimidinones under mild reaction conditions with excellent yields using inexpensive silica chloride under solvent free conditions.

  20. Radioisotope incorporation via aryl and alkenyl trialkyltin intermediates

    International Nuclear Information System (INIS)

    Organometallic chemistry has long played an important role in the synthesis of structurally unique and complex bioorganic compounds; however, it has been only within the last decade that the principles developed for synthetic organic chemistry have been applied to radiopharmaceutical chemistry. Since 1978 one can observe, in addition to the organotin reagents, the use of organolithium and Grignard reagents, organoboranes, organomercurials, and organosilanes in the preparation of radio- chemicals. Although each of these reagents possesses certain methodological advantages, none can be applied to synthesis of all classes of compounds nor to the incorporation of all radionuclides. Organostannanes, organoboranes and organosilanes share many similar features with respect to the types of radionuclides that can be introduced and the classes of compounds which are accessible to radioisotope incorporation. However, it is the special features associated with the organostannanes that have made them of particular interest to us in our radiopharmaceutical chemistry program. It is the purpose of this review to describe the specific application of organotin chemistry to preparation of radiohalogenated bioorganic compounds as radiotracers

  1. C-C or C-O bond cleavage in a phenolic lignin model compound: selectivity depends on vanadium catalyst.

    Science.gov (United States)

    Hanson, Susan K; Wu, Ruilian; Silks, Louis A Pete

    2012-04-01

    The aerobic oxidation of a phenolic lignin model compound with a vanadium catalyst results in the oxidative cleavage of the C-C bond between the aryl ring and the adjacent hydroxy-substituted carbon atom. Labeling experiments indicate key mechanistic differences to a previously reported related C-O bond cleavage reaction. The selectivity in C-C versus C-O bond cleavage depends on the choice of the vanadium catalyst. PMID:22266711

  2. Radical 1,4-aryl transfer in arylcarboxamides leading to phthalimides, biaryls and enantiomerically enriched beta-arylethylamines

    OpenAIRE

    Robertson, J.; Palframan, Mj; Shea, Sa; Tchabanenko, K.; Unsworth, Wr; Winters, C.

    2008-01-01

    5-exo Cyclisation of vinyl-, aryl- and alkyl-radicals onto the aryl group of arylcarboxamides is followed by ?-scission of the resulting spirocyclohexadienyl radicals with ejection of a carbamoyl radical. The fate of this radical depends on the substrate but, in the cases studied, either 5-endo cyclisation or direct reduction follows to give phthalimides, biaryls or ?-arylethylamines. © 2008 Elsevier Ltd. All rights reserved.

  3. Stereoselective Synthesis of Arylglycine Derivatives via Palladium-Catalyzed ?-Arylation of a Chiral Nickel(II) Glycinate.

    Science.gov (United States)

    Zhang, Fan; Sun, Hengzhi; Song, Zhuang; Zhou, Shuxi; Wen, Xiaoan; Xu, Qing-Long; Sun, Hongbin

    2015-05-01

    A practical and efficient stereoselective synthesis of arylglycine derivatives was realized via palladium-catalyzed ?-arylation of a chiral nickel(II) glycinate complex with aryl bromides. The structurally diverse arylglycine products were obtained in excellent isolated yields and with good diastereoselectivity. A simple acidic hydrolysis furnished optically pure arylglycines in high yield, and the chiral ligand (S)-BPB could be efficiently recovered and reused. PMID:25818727

  4. Palladium catalysed 3-component cascade synthesis of bis(2-arylallyl) tertiary amines from aryl iodides, allene and primary amines.

    Science.gov (United States)

    Gai, X; Grigg, R; Collard, S; Muir, J E

    2001-09-21

    A 3-component cascade synthesis of bis(2-arylallyl) tertiary amines from aryl iodide, allene and primary aliphatic amines is described; chiral amines give analogous products with no detectable racemisation; mixtures of two different aryl iodides can be utilised to give the mixed tertiary amines as the sole, or major, product; the reaction is sensitive to stereoelectronic effects which lead to mono(2-arylallyl) secondary amines. PMID:12240278

  5. N-Heterocyclic carbene–palladium(II-1-methylimidazole complex catalyzed Mizoroki–Heck reaction of aryl chlorides with styrenes

    Directory of Open Access Journals (Sweden)

    Ting-Ting Gao

    2012-11-01

    Full Text Available A well-defined N-heterocyclic carbene–palladium(II-1-methylimidazole [NHC-Pd(II-Im] complex 1 was found to be an effective catalyst for the Mizoroki–Heck reaction of a variety of aryl chlorides with styrenes. Both activated and deactivated aryl chlorides work well to give the corresponding coupling products in good to excellent yields by using tetrabutylammonium bromide (TBAB as the ionic liquid.

  6. Magnesium compounds

    Science.gov (United States)

    Kramer, D.A.

    2006-01-01

    In 2005, seawater and natural brines accounted for 51% of US magnesium compounds production. World magnesia production was estimated to be 14.5 Mt. Most of the production came from China, North Korea, Russia and Turkey. Although no specific production figures are available, Japan and the United States are estimated to account for almost one-half of the world's capacity from seawater and brines.

  7. Aryl hydrocarbon receptor and aryl hydrocarbon nuclear translocator expression in human and rat placentas and transcription activity in human trophoblast cultures.

    Science.gov (United States)

    Stejskalova, Lucie; Vecerova, Lenka; Peréz, Laura Mesa; Vrzal, Radim; Dvorak, Zdenek; Nachtigal, Petr; Pavek, Petr

    2011-09-01

    Aryl hydrocarbon receptor (AHR) and its heterodimer aryl hydrocarbon nuclear translocator (ARNT) form a ligand-activated transcription complex that regulates expression of the AHR battery of target genes that includes the most important placental biotransformation enzyme cytochrome CYP1A1. Expression, placental localization, and ontogeny of AHR/Ahr and ARNT/Arnt have not been systematically studied in either human or rat placentas. Moreover, induction of such AHR target genes as CYP1A1, CYP1A2, CYP1B1, UGT1A1, and breast cancer resistance protein (BCRP), as well as of AHR, ARNT, and aryl hydrocarbon receptor repressor (AHRR) genes, after exposure to AHR ligands have not been studied in human placental trophoblast cultures. In this article, we show that only CYP1A1 messenger RNA (mRNA), but not CYP1A2, CYP1B1, UGT1A1, BCRP, AHR, ARNT, and AHRR mRNAs, is significantly induced in human term placental trophoblast cultures after exposure to prototype AHR ligands/activators 2,3,7,8-tetrachlorodibenzo-p-dioxin, 3-methylcholanthrene, omeprazole, and ?-naphthoflavone. We localized AHR/Ahr and ARNT/Arnt in rat placental trophoblasts throughout gestation and in first trimester and term human placental trophoblast, which comprise the crucial component of the maternal-fetal barrier. We demonstrate that rat Ahr and Cyp1a1 reached highest expression during gestation days 15 and 18, which might indicate different response to Ahr ligands in placental Cyp1a1 induction during rat gestation. We also propose the JEG3 choriocarcinoma cell line as a cellular model for human trophoblast induction studies through AHR. In conclusion, we describe expression and ontogeny of AHR/Ahr and ARNT/Arnt and systematically characterize induction of major AHR target genes in human placental trophoblast forming the placental maternal-fetal morphological and metabolic barrier. PMID:21666223

  8. Altered Subcellular Localization of Heat Shock Protein 90 Is Associated with Impaired Expression of the Aryl Hydrocarbon Receptor Pathway in Dogs

    OpenAIRE

    Steenbeek, Frank G.; Spee, Bart; Penning, Louis C.; Kummeling, Anne; Gils, Ingrid H. M.; Grinwis, Guy C. M.; Leenen, Dik; Holstege, Frank C. P.; Vos-loohuis, Manon; Rothuizen, Jan; Leegwater, Peter A. J.

    2013-01-01

    The aryl hydrocarbon receptor (AHR) mediates biological responses to toxic chemicals. An unexpected role for AHR in vascularization was suggested when mice lacking AHR displayed impaired closure of the ductus venosus after birth, as did knockout mice for aryl hydrocarbon receptor interacting protein (AIP) and aryl hydrocarbon receptor nuclear translocator (ARNT). The resulting intrahepatic portosystemic shunts (IHPSS) are frequently diagnosed in specific dog breeds, such as the Irish wolfhoun...

  9. Utilization of Acidic ?-Amino Acids as Acyl Donors: An Effective Stereo-Controllable Synthesis of Aryl-Keto ?-Amino Acids and Their Derivatives

    OpenAIRE

    Lei Wang; Yuta Murai; Takuma Yoshida; Masashi Okamoto; Zetryana Puteri Tachrim; Yasuyuki Hashidoko; Makoto Hashimoto

    2014-01-01

    Aryl-keto-containing ?-amino acids are of great importance in organic chemistry and biochemistry. They are valuable intermediates for the construction of hydroxyl ?-amino acids, nonproteinogenic ?-amino acids, as well as other biofunctional components. Friedel-Crafts acylation is an effective method to prepare aryl-keto derivatives. In this review, we summarize the preparation of aryl-keto containing ?-amino acids by Friedel-Crafts acylation using acidic ?-amino acids as acyl-donors a...

  10. Silver-mediated palladium-catalyzed direct C-H arylation of 3-bromoisothiazole-4-carbonitrile.

    Science.gov (United States)

    Ioannidou, Heraklidia A; Koutentis, Panayiotis A

    2011-03-18

    Silver(I) fluoride-mediated Pd-catalyzed C-H direct arylation/heteroarylation of 3-bromoisothiazole-4-carbonitrile (1a) gives twenty-four 5-aryl/heteroaryl-3-bromoisothiazole-4-carbonitriles. The reaction was partially optimized with respect to catalyst, ligand, and base. During this study 3,3'-dibromo-5,5'-biisothiazole-4,4'-dicarbonitrile (3a) was isolated as a byproduct and subsequently prepared via the silver-mediated Pd-catalyzed oxidative dimerization of 3-bromoisothiazole-4-carbonitrile in 67% yield. The analogous phenylation and oxidative dimerization of 3-chloroisothiazole-4-carbonitrile (1b) gave 3-chloro-5-phenylisothiazole-4-carbonitrile (4) and 3,3'-dichloro-5,5'-biisothiazole-4,4'-dicarbonitrile (3b) in 96% and 69% yields, respectively. PMID:21314108

  11. A novel poly(aryl ether) containing azobenzene chromophore and pendant oligoaniline: Synthesis and electrochromic properties

    International Nuclear Information System (INIS)

    Graphical abstract: This work describes a novel poly(aryl ether) functionalized with azobenzene chromophore and pendant oligoaniline, that exhibits a satisfied electrochromic properties with high contrast value, good coloration efficiency, moderate switching times and acceptable stability. - Abstract: A novel poly(aryl ether), containing pendant oligoaniline and azobenzene moieties (Azo-PAE-p-OA), was synthesized by nucleophilic polycondensation. The structures were confirmed spectroscopically via nuclear magnetic resonance (NMR) and Fourier-transform infrared spectra (FTIR), morphological data was ascertained via X-ray diffraction (XRD), and the thermal stability was probed via thermogravimetric analysis (TGA). Due to the coexistence of oligoaniline and azobenzene groups, Azo-PAE-p-OA shows reversible electroactivity and expectable photoresponse to light irradiation, chemical redox and electrochemical modulation. The electrochromic performance of a Azo-PAE-p-OA film on indium tin oxide (ITO) was investigated by spectrochronoamperometry, and exhibited electrochromic properties with high contrast value, good coloration efficiency, moderate switching times, and acceptable stability.

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

    Directory of Open Access Journals (Sweden)

    José A. Henao

    2009-12-01

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

  13. Aryl-derivatized, water-soluble functionalized carbon nanotubes for biomedical applications

    International Nuclear Information System (INIS)

    The functionalization of very-thin multi-walled carbon nanotubes (VT-MWNTs) with an aniline derivative, via the protocol of in situ generated aryl diazonium salts results, upon acidic deprotection of the terminal BOC group, on the formation of the water-soluble positively charged ammonium functionalized VT-MWNTs-NH3+ material. The new materials have been structurally and morphologically characterized by infra-red (ATR-IR) spectroscopy and transmission electron microscopy (TEM). The quantitative calculation of the grafted aryl units onto the skeleton of VT-MWNTs has been estimated by thermogravimetric analysis (TGA), while the quantitative Kaiser test showed the amine group loaded onto VT-MWNTs-NH3+ material. The aqueous solubility of this material has allowed the performance of some initial toxicological in vitro investigations

  14. Flavonoids as aryl hydrocarbon receptor agonists/antagonists: effects of structure and cell context.

    OpenAIRE

    Zhang, Shu; Qin, Chunhua; Safe, Stephen H.

    2003-01-01

    Chemoprotective phytochemicals exhibit multiple activities and interact with several cellular receptors, including the aryl hydrocarbon (Ah) receptor (AhR). In this study we investigated the AhR agonist/antagonist activities of the following flavonoids: chrysin, phloretin, kaempferol, galangin, naringenin, genistein, quercetin, myricetin, luteolin, baicalein, daidzein, apigenin, and diosmin. We also investigated the AhR-dependent activities of cantharidin and emodin (in herbal extracts) in Ah...

  15. Palladium(II) Aryl-amido Complexes of Diphosphinoazines in Unsymmetrical PNP' Pincer-type Configuration.

    Czech Academy of Sciences Publication Activity Database

    Storch, Jan; ?ermák, Jan; Pošta, Martin; Sýkora, Jan; Císa?ová, I.

    2008-01-01

    Ro?. 693, ?. 18 (2008), s. 3029-3034. ISSN 0022-328X R&D Projects: GA ?R GA203/01/0554; GA ?R GA203/06/0738; GA MŠk(CZ) LC06070 Institutional research plan: CEZ:AV0Z40720504 Keywords : diphosphinoazines * pincer complexes * aryl- amido complexes Subject RIV: CC - Organic Chemistry Impact factor: 1.866, year: 2008

  16. Carbonylative Suzuki Couplings of Aryl Bromides with Boronic Acid Derivatives under Base-Free Conditions

    DEFF Research Database (Denmark)

    Bjerglund, Klaus Meier; Skrydstrup, Troels

    2014-01-01

    The carbonylative Suzuki-Miyaura reaction between aryl bromides and arylboronic acid equivalents is herein reported, using base-free conditions and a limited excess of carbon monoxide generated ex situ from stable CO. precursors. Under these conditions, unsymmetrical biaryl ketones were obtained in modest to excellent yields. This method was adapted to the synthesis of the triglyceride and cholesterol regulator drug, fenofibrate, and its C-13-labeled derivative in good yields from the appropriate CO-precursor.

  17. Anaerobic Aryl Reductive Dehalogenation of Halobenzoates by Cell Extracts of “Desulfomonile tiedjei”

    OpenAIRE

    DeWeerd, Kim A.; Suflita, Joseph M.

    1990-01-01

    We studied the transformation of halogenated benzoates by cell extracts of a dehalogenating anaerobe, “Desulfomonile tiedjei.” We found that cell extracts possessed aryl reductive dehalogenation activity. The activity was heat labile and dependent on the addition of reduced methyl viologen, but not on that of reduced NAD, NADP, flavin mononucleotide, flavin adenine dinucleotide, desulfoviridin, cytochrome c3, or benzyl viologen. Dehalogenation activity in extracts was stimulated by format...

  18. The Role of the Aryl Hydrocarbon Receptor in the Female Reproductive System

    OpenAIRE

    Hernández-Ochoa, Isabel; Karman, Bethany N.; Flaws, Jodi A

    2008-01-01

    In recent years, many studies have emphasized how changes in aryl hydrocarbon receptor (AHR)-mediated gene expression result in biological effects, raising interest in this receptor as a regulator of normal biological function. This review focuses on what is known about the role of the AHR in the female reproductive system, which includes the ovaries, fallopian tubes or oviduct, uterus and vagina. This review also focuses on the role of the AHR in reproductive outcomes such as cyclicity, sene...

  19. Microwave-Assisted Synthesis of Some 3,5-Arylated 2-Pyrazolines

    Directory of Open Access Journals (Sweden)

    Hassan Ghasemnejad

    2003-07-01

    Full Text Available Condensation of 2-acetylnaphthalene with benzaldehydes under microwave irradiation affords chalcones which undergo facile and clean cyclizations with hydrazines RNHNH2 (R= H, Ph, Ac to afford 3,5-arylated 2-pyrazolines in quantitative yields, also under microwave irradiation and in the presence of dry AcOH as cyclizing agent. The results obtained indicate that, unlike classical heating, microwave irradiation results in higher yields, shorter reaction times (2-12 min. and cleaner reactions.

  20. CuO hollow nanosphere-catalyzed cross-coupling of aryl iodides with thiols

    OpenAIRE

    Woo, Hyunje; Mohan, Balaji; Heo, Eunjung; Park, Ji Chan; Song, Hyunjoon; Park, Kang Hyun

    2013-01-01

    New functionalized CuO hollow nanospheres on acetylene black (CuO/AB) and on charcoal (CuO/C) have been found to be effective catalysts for C-S bond formation under microwave irradiation. CuO catalysts showed high catalytic activity with a wide variety of substituents which include electron-rich and electron-poor aryl iodides with thiophenols by the addition of two equivalents of K2CO3 as base in the absence of ligands.

  1. Acid Chloride Synthesis by the Palladium-Catalyzed Chlorocarbonylation of Aryl Bromides.

    Science.gov (United States)

    Quesnel, Jeffrey S; Kayser, Laure V; Fabrikant, Alexander; Arndtsen, Bruce A

    2015-06-22

    We report a palladium-catalyzed method to synthesize acid chlorides by the chlorocarbonylation of aryl bromides. Mechanistic studies suggest the combination of sterically encumbered PtBu3 and CO coordination to palladium can rapidly equilibrate the oxidative addition/reductive elimination of carbon-halogen bonds. This provides a useful method to assemble highly reactive acid chlorides from stable and available reagents, and can be coupled with subsequent nucleophilic reactions to generate new classes of carbonylated products. PMID:25982536

  2. Suzuki–Miyaura Cross-Coupling of Aryl Carbamates and Sulfamates: Experimental and Computational Studies

    OpenAIRE

    Quasdorf, Kyle W.; Antoft-finch, Aurora; Liu, Peng; Silberstein, Amanda L.; Komaromi, Anna; Blackburn, Tom; Ramgren, Stephen D.; Houk, K. N.; Snieckus, Victor; Garg, Neil K.

    2011-01-01

    The first Suzuki–Miyaura cross-coupling reactions of the synthetically versatile O-aryl carbamate and O-sulfamate groups is described. The transformations utilize the inexpensive, bench-stable catalyst NiCl2(PCy3)2 to furnish biaryls in good to excellent yields. A broad scope for this methodology has been demonstrated. Substrates with electron-donating and electron-withdrawing groups (EDGs, EWGs) are tolerated, in addition to those that possess ortho substitutents. Furthermore, heteroaryl s...

  3. Fluoroalkylative aryl migration of conjugated N-arylsulfonylated amides using easily accessible sodium di- and monofluoroalkanesulfinates.

    Science.gov (United States)

    He, Zhengbiao; Tan, Ping; Ni, Chuanfa; Hu, Jinbo

    2015-04-17

    Fluorinated sulfinate salts RfSO2Na (Rf = CF2H, CF2Ph, and CH2F) have been prepared via NaBH4-mediated reduction of the corresponding benzo[d]thiazol-2-yl sulfones, and their synthetic application as di- and monofluoroalkyl radical precursors is demonstrated in the silver-catalyzed cascade fluoroalkylation/aryl migration/SO2 extrusion of conjugated N-arylsulfonylated amides. PMID:25839912

  4. Spectral and catalytic properties of aryl-alcohol oxidase, a fungal flavoenzyme acting on polyunsaturated alcohols

    OpenAIRE

    P Ferreira; Medina, M.; Guillén, F.; Martínez, M. J.; Berkel, W.J.H., van; Martínez, A.T.

    2005-01-01

    Spectral and catalytic properties of the flavoenzyme AAO (aryl-alcohol oxidase) from Pleurotus eryngii were investigated using recombinant enzyme. Unlike most flavoprotein oxidases, AAO does not thermodynamically stabilize a flavin semiquinone radical and forms no sulphite adduct. AAO catalyses the oxidative dehydrogenation of a wide range of unsaturated primary alcohols with hydrogen peroxide production. This differentiates the enzyme from VAO (vanillyl-alcohol oxidase), which is specific fo...

  5. Design and Synthesis of Some Novel 4-(4-substituted aryl) Semicarbazones as Anticonvulsant Agents

    OpenAIRE

    Singh Anita; Pande C; Gahtori P; Pandeya S; Stables J

    2010-01-01

    In the present study, a series of 4-(4-substituted aryl) semicarbazones were synthesized from substituted anilines and subsequently evaluated for their anticonvulsant activities. The anticonvulsant activities were established by the anticonvulsant drug development (ADD) programme NIH, USA using experimental animal, adult male FCM mice (20-25 g) and adult Sprague-Dawley rats (100-150 g) and screened against electroshock seizure, subcutaneous metrazole and minimal neurotoxicity tests in mice. C...

  6. Corrigendum to Solvent-dependent oxidative coupling of 1-aryl-1,3-dicarbonyls and styrene

    OpenAIRE

    Casey, Brian M.; Eakin, Cynthia A.; Jiao, Jingliang; Sadasivam, Dhandapani V.; Flowers, Robert A.

    2010-01-01

    This report describes the scope and mechanism of the solvent-dependent, chemoselective oxidative coupling of 1-aryl-1,3-dicarbonyls with styrene using Ce(IV) reagents. Dihydrofuran derivatives are obtained when reactions are performed in methanol whereas nitrate esters can be selectively synthesized in acetonitrile and methylene chloride. Mechanistic studies are consistent with the rate of solvent-assisted deprotonation of a radical cation intermediate playing an integral role in the selectiv...

  7. Solvent-dependent oxidative coupling of 1-aryl-1,3-dicarbonyls and styrene

    OpenAIRE

    Casey, Brian M.; Eakin, Cynthia A.; Jiao, Jingliang; Sadasivam, Dhandapani V.; Flowers, Robert A.

    2009-01-01

    This report describes the scope and mechanism of the solvent-dependent, chemoselective oxidative coupling of 1-aryl-1,3-dicarbonyls with styrene using Ce(IV) reagents. Dihydrofuran derivatives are obtained when reactions are performed in methanol whereas ?-tetralones can be selectively synthesized in acetonitrile and methylene chloride. Mechanistic studies are consistent with the rate of solvent-assisted deprotonation of a radical cation intermediate playing an integral role in the selective...

  8. The role of the aryl hydrocarbon receptor in normal and malignant B cell development

    OpenAIRE

    Sherr, David H.; Monti, Stefano

    2013-01-01

    The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor historically studied for its role in environmental chemical-mediated toxicity and carcinogenicity. In the last 5 years, however, it has become clear that the AhR, presumably activated by endogenous ligand(s), plays an important role in immune system development and function. Other articles in this edition summarize AhR function during T cell and antigen-presenting cell development and function, including the effec...

  9. Synthesis, central nervous system activity and structure-activity relationships of novel 1-(1-Alkyl-4-aryl-4,5-dihydro-1H-imidazo)-3-substituted urea derivatives.

    Science.gov (United States)

    Szaco?, El?bieta; Rz?dkowska, Marzena; Kaczor, Agnieszka A; K?dzierska, Ewa; Fidecka, Sylwia; Matosiuk, Dariusz

    2015-01-01

    A series of 10 novel urea derivatives has been synthesized and evaluated for their central nervous system activity. Compounds 3a-3h were prepared in the reaction between the respective 1-alkyl-4-aryl-4,5-dihydro-1H-imidazol-2-amines 1a and 1b and appropriate benzyl-, phenethyl-isocyanate or ethyl 4-isocyanatobenzoate and ethyl isocyanatoacetate 2 in dichloromethane. Derivatives 4c and 4g resulted from the conversion of 3c and 3g into the respective amides due to action of an aqueous ammonia solution. The results obtained in this study, based on literature data suggest a possible involvement of serotonin system and/or the opioid system in the effects of tested compounds, and especially in the effect of compound 3h. The best activity of compound 3h may be primarily attributed to its favourable ADMET properties, i.e., higher lipophilicity (related to lower polar surface area and greater molecular surface, volume and mass than for other compounds) and good blood-brain permeation. This compound has also the greatest polarizability and ovality. The HOMO and LUMO energies do not seem to be directly related to activity. PMID:25730390

  10. Synthesis, Central Nervous System Activity and Structure-Activity Relationships of Novel 1-(1-Alkyl-4-aryl-4,5-dihydro-1H-imidazo-3-substituted Urea Derivatives

    Directory of Open Access Journals (Sweden)

    El?bieta Szaco?

    2015-02-01

    Full Text Available A series of 10 novel urea derivatives has been synthesized and evaluated for their central nervous system activity. Compounds 3a–3h were prepared in the reaction between the respective 1-alkyl-4-aryl-4,5-dihydro-1H-imidazol-2-amines 1a and 1b and appropriate benzyl-, phenethyl-isocyanate or ethyl 4-isocyanatobenzoate and ethyl isocyanatoacetate 2 in dichloromethane. Derivatives 4c and 4g resulted from the conversion of 3c and 3g into the respective amides due to action of an aqueous ammonia solution. The results obtained in this study, based on literature data suggest a possible involvement of serotonin system and/or the opioid system in the effects of tested compounds, and especially in the effect of compound 3h. The best activity of compound 3h may be primarily attributed to its favourable ADMET properties, i.e., higher lipophilicity (related to lower polar surface area and greater molecular surface, volume and mass than for other compounds and good blood-brain permeation. This compound has also the greatest polarizability and ovality. The HOMO and LUMO energies do not seem to be directly related to activity.

  11. Intermetallic Compounds

    Science.gov (United States)

    Takagiwa, Y.; Matsuura, Y.; Kimura, K.

    2014-06-01

    We have focused on the binary narrow-bandgap intermetallic compounds FeGa3 and RuGa3 as thermoelectric materials. Their crystal structure is FeGa3-type (tetragonal, P42/ mnm) with 16 atoms per unit cell. Despite their simple crystal structure, their room temperature thermal conductivity is in the range 4-5-W-m-1-K-1. Both compounds have narrow-bandgaps of approximately 0.3-eV near the Fermi level. Because their Seebeck coefficients are quite large negative values in the range 350-thermoelectric materials both by adjusting the carrier concentration and by reducing the thermal conductivity. Here, we report the effects of doping on the thermoelectric properties of FeGa3 and RuGa3 as n and p-type materials. The dimensionless figure of merit, ZT, was significantly improved by substitution of Sn for Ga in FeGa3 (electron-doping) and by substitution of Zn for Ga in RuGa3 (hole-doping), mainly as a result of optimization of the electronic part, S 2 ?.

  12. 4-Aryl-3,5-bis(arylethynyl)aryl-4H-1,2,4-triazoles: multitasking skeleton as a self-assembling unit.

    Science.gov (United States)

    Pastor, M Jesús; Torres, Iván; Cebrián, Cristina; Carrillo, José Ramón; Díaz-Ortiz, Ángel; Matesanz, Emilio; Buendía, Julia; García, Fátima; Barberá, Joaquín; Prieto, Pilar; Sánchez, Luis

    2015-01-19

    The synthesis of a series of 4-aryl-3,5-bis(arylethynyl)aryl-4H-1,2,4-triazoles derivatives is reported and the influence exerted by peripheral substitution on the morphology of the aggregates generated from these 1,2,4-triazoles is investigated by SEM imaging. The presence of paraffinic side chains results in long fibrillar supramolecular structures, but unsubstituted triazoles self-assemble into thinner ribbons and needle-like aggregates. The crystals obtained from methoxy-substituted triazoles have been utilised to elaborate a model that helps to justify aggregation of the investigated 1,2,4-triazoles, in which the operation of arrays of C-H???? non-covalent interactions plays a significant role. The results presented herein demonstrate the ability of simple molecules to behave as multitasking scaffolds with different properties, depending on peripheral substitution. Thus, although 1,2,4-triazoles without long paraffinic side chains exhibit optical waveguiding behaviour, triazoles endowed with peripheral paraffinic side chains exhibit hexagonal columnar mesomorphism. PMID:25413614

  13. Inhibitors of Alzheimer's BACE-1 with 3,5-bis-N-(aryl/heteroaryl) carbamoyl-4-aryl-1,4-dihydropyridine structure.

    Science.gov (United States)

    Miri, Ramin; Firuzi, Omidreza; Razzaghi-Asl, Nima; Javidnia, Katayoun; Edraki, Najmeh

    2015-04-01

    ?-site amyloid precursor protein cleaving enzyme (BACE-1) is a validated target for Alzheimer therapy due to its distinctive role in pathogenesis of AD. In the present contribution, a series of new 3,5-bis-N-(aryl/heteroaryl) carbamoyl-4-aryl-1,4-dihydropyridine structures were synthesized as BACE-1 inhibitors (6a-6n). In vitro BACE-1 inhibitory activities were determined by enzymatic fluorescence resonance energy transfer assay. Synthesized dihydropyridine (DHP) analogues exhibited weak to good inhibitory activities while 6i, 6n and 6a were found to be the most potent molecules with 83.76, 79.45 and 72.47 % BACE-1 inhibition at 10 ?M, respectively. Structure binding/activity relationship elucidations revealed that superior BACE-1 inhibitory activities were observed for DHP derivatives bearing fused/non-fused thiazole groups and particularly 3,5-bis-N-(6-ethoxy-2-benzothiazolyl) moiety. Binding maps showed that enhanced activity may be attributed to the additional H-bond and hydrophobic interactions with S2-S3 subpockets of BACE-1. PMID:24771353

  14. Synthesis of ladder-type pi-conjugated heteroacenes via palladium-catalyzed double N-arylation and intramolecular O-arylation.

    Science.gov (United States)

    Kawaguchi, Keiko; Nakano, Koji; Nozaki, Kyoko

    2007-07-01

    Ladder-type heteroacenes containing pyrrole or furan rings, indolo[3,2-b]carbazoles and dibenzo[d,d']benzo[1,2-b:4,5-b']difurans, were effectively synthesized from the common intermediates, 2,5-bis(o-chloroaryl)hydroquinones. The key reactions are palladium-catalyzed double N-arylation of aniline and intramolecular O-arylation, which enable regioselective ring closure. In addition to the parent indolo[3,2-b]carbazole and dibenzo[d,d']benzo[1,2-b:4,5-b']difuran, their derivatives with an alkyl or cyano group were first synthesized. Photophysical and electrochemical studies showed that the obtained heteroacenes have lower HOMO energy levels and larger band gaps than the corresponding hydrocarbon acene, pentacene. An X-ray analysis of dibenzo[d,d']benzo[1,2-b:4,5-b']difuran revealed that it was packed in herringbone fashion. PMID:17552565

  15. Analysis of aryl hydrocarbon receptor ligands in kraft mill effluents by a combination of yeast bioassays and CG-MS chemical determinations.

    Science.gov (United States)

    Chamorro, Soledad; Monsalvez, Elizabeth; Piña, Benjamín; Olivares, Alba; Hernández, Víctor; Becerra, José; Vidal, Gladys

    2013-01-01

    Aryl Hydrocarbon Receptor (AhR) ligands also known as dioxin-like compounds, constitute a substantial part of the total toxicity from many pollution sources, including pulp mill effluents. The aim of this article was to evaluate dioxin-like activity in different kraft mill effluents by a combination of yeast bioassays and gas chromatography-mass spectrometry (GC-MS) chemical analysis. The study includes kraft mill effluents from three sources of raw material: Pinus radiata, Eucalyptus globulus and a combination of both (50% each). The Recombinant Yeast Assay (RYA) showed an effective concentration of AhR ligands more than 30-fold higher in Eucalyptus globulus than in Pinus radiata effluents. Our results suggest that specific ligands, rather than the total amount of extractive material, determined the observed activity. Analysis of extract composition by GC-MS indicated that moderately hydrophobic aromatic compounds were likely responsible for the observed dioxin-like activity. In particular, benzaldehyde derivatives appeared as candidates for eliciting the observed dioxin-like activity in pulp mill effluents, giving their structural properties and their high concentration in AhR ligand-rich samples. PMID:23043335

  16. Bismaleimide compounds

    Energy Technology Data Exchange (ETDEWEB)

    Adams, J.E.; Jamieson, D.R.

    1986-01-14

    Bismaleimides of the formula shown in the diagram wherein R[sub 1] and R[sub 2] each independently is H, C[sub 1-4]-alkyl, C[sub 1-4]-alkoxy, Cl or Br, or R[sub 1] and R[sub 2] together form a fused 6-membered hydrocarbon aromatic ring, with the proviso that R[sub 1] and R[sub 2] are not t-butyl or t-butoxy; X is O, S or Se; n is 1--3; and the alkylene bridging group, optionally, is substituted by 1--3 methyl groups or by fluorine, form polybismaleimide resins which have valuable physical properties. Uniquely, these compounds permit extended cure times, i.e., they remain fluid for a time sufficient to permit the formation of a homogeneous melt prior to curing.

  17. Bulk Compounds

    Science.gov (United States)

    Beaumale, M.; Barbier, T.; Bréard, Y.; Raveau, B.; Kinemuchi, Y.; Funahashi, R.; Guilmeau, E.

    2014-06-01

    The thermoelectric properties of Nb-substituted TiS2 compounds have been investigated in the temperature range of 300 K to 700 K. Polycrystalline samples in the series Ti1- x Nb x S2 with x varying from 0 to 0.05 were prepared using solid-liquid-vapor reaction and spark plasma sintering. Rietveld refinements of x-ray diffraction data are consistent with the existence of full solid solution for x ? 0.05. Transport measurements reveal that niobium can be considered as an electron donor when substituted at Ti sites. Consequently, the electrical resistivity and the absolute value of the Seebeck coefficient decrease as the Nb content increases, due to an increase in the carrier concentration. Moreover, due to mass fluctuation, the lattice thermal conductivity is reduced, leading to a slight increase of ZT values as compared with TiS2.

  18. Bismaleimide compounds

    Science.gov (United States)

    Adams, Johnnie E. (Grandview, MO); Jamieson, Donald R. (Merriam, KS)

    1986-01-14

    Bismaleimides of the formula ##STR1## wherein R.sub.1 and R.sub.2 each independently is H, C.sub.1-4 -alkyl, C.sub.1-4 -alkoxy, C1 or Br, or R.sub.1 and R.sub.2 together form a fused 6-membered hydrocarbon aromatic ring, with the proviso that R.sub.1 and R.sub.2 are not t-butyl or t-butoxy; X is O, S or Se; n is 1-3; and the alkylene bridging group, optionally, is substituted by 1-3 methyl groups or by fluorine, form polybismaleimide resins which have valuable physical properties. Uniquely, these compounds permit extended cure times, i.e., they remain fluid for a time sufficient to permit the formation of a homogeneous melt prior to curing.

  19. Synthesis, urease inhibition, antioxidant and antibacterial studies of some 4-amino-5-aryl-3H-1,2,4-triazole-3-thiones and their 3,6-disubstituted 1,2,4-triazolo[3,4-b]1,3,4-thiadiazole derivatives

    International Nuclear Information System (INIS)

    A new series of 4-amino-5-aryl-3H-1,2,4-triazole-3-thiones, bearing various methoxybenzyl- and methoxyphenethyl groups, was synthesized by refluxing potassium hydrazinecarbodithioate salts in dilute aqueous solution of hydrazine hydrate. These salts were formed by the reaction of acid hydrazides and carbon disulfide in methanolic potassium hydroxide solution at 0-5 deg C. 4-Amino- 5-aryl-3H-1,2,4-triazole-3-thiones were condensed with different substituted aromatic acids to yield 3,6-disubstituted-1,2,4-triazolo[3,4-b]1,3,4-thiadiazoles. The structures of the synthesized compounds were characterized by infrared (IR), 1H and 13C nuclear magnetic resonance (NMR), elemental analysis and mass spectrometric (MS) studies. All the synthesized compounds were screened for their urease inhibition, antioxidant and antibacterial activities. Some compounds showed excellent urease inhibition activity, more than the standard drug. Others exhibited potent antioxidant activity. All the compounds showed significant antibacterial activities as compared to the standard drug. (author)

  20. Synthesis, urease inhibition, antioxidant and antibacterial studies of some 4-amino-5-aryl-3H-1,2,4-triazole-3-thiones and their 3,6-disubstituted 1,2,4-triazolo[3,4-b]1,3,4-thiadiazole derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Hanif, Muhammad; Saleem, Muhammad; Rama, Nasim Hasan, E-mail: nhrama@qau.edu.pk, E-mail: drjamshed@ciit.net.pk [Department of Chemistry, Quaid-i-Azam University, Islamabad (Pakistan); Hussain, Muhammad Tahir [Department of Applied Sciences, National Textile University, Faisalabad (Pakistan); Zaib, Sumera; Aslam, Muhammad Adil M.; Iqbal, Jamshed [Department of Pharmaceutical Sciences, COMSATS Institute of Information Technology, Abbottabad (Pakistan); Jones, Peter G. [Institute for Inorganic and Analytical Chemistry, Technical University of Braunschweig, Braunschweig (Germany)

    2012-05-15

    A new series of 4-amino-5-aryl-3H-1,2,4-triazole-3-thiones, bearing various methoxybenzyl- and methoxyphenethyl groups, was synthesized by refluxing potassium hydrazinecarbodithioate salts in dilute aqueous solution of hydrazine hydrate. These salts were formed by the reaction of acid hydrazides and carbon disulfide in methanolic potassium hydroxide solution at 0-5 deg C. 4-Amino- 5-aryl-3H-1,2,4-triazole-3-thiones were condensed with different substituted aromatic acids to yield 3,6-disubstituted-1,2,4-triazolo[3,4-b]1,3,4-thiadiazoles. The structures of the synthesized compounds were characterized by infrared (IR), {sup 1}H and {sup 13}C nuclear magnetic resonance (NMR), elemental analysis and mass spectrometric (MS) studies. All the synthesized compounds were screened for their urease inhibition, antioxidant and antibacterial activities. Some compounds showed excellent urease inhibition activity, more than the standard drug. Others exhibited potent antioxidant activity. All the compounds showed significant antibacterial activities as compared to the standard drug. (author)

  1. The suggested physiologic aryl hydrocarbon receptor activator and cytochrome P4501 substrate 6-formylindolo[3,2-b]carbazole is present in humans.

    Science.gov (United States)

    Wincent, Emma; Amini, Nahid; Luecke, Sandra; Glatt, Hansruedi; Bergman, Jan; Crescenzi, Carlo; Rannug, Agneta; Rannug, Ulf

    2009-01-30

    Dioxins and other polycyclic aromatic compounds formed during the combustion of waste and fossil fuels represent a risk to human health, as well as to the well being of our environment. Compounds of this nature exert carcinogenic and endocrine-disrupting effects in experimental animals by binding to the orphan aryl hydrocarbon receptor (AhR). Understanding the mechanism of action of these pollutants, as well as the physiological role(s) of the AhR, requires identification of the endogenous ligand(s) of this receptor. We reported earlier that activation of AhR by ultraviolet radiation is mediated by the chromophoric amino acid tryptophan (Trp), and we suggested that a new class of compounds derived from Trp, in particular 6-formylindolo[3,2-b]carbazole (FICZ), acts as natural high affinity ligands for this receptor. Here we describe seven new FICZ-derived indolo[3,2-b]carbazole-6-carboxylic acid metabolites and two sulfoconjugates, and we demonstrate the following. (i) FICZ is formed efficiently by photolysis of Trp upon exposure to visible light. (ii) FICZ is an exceptionally good substrate for cytochromes P450 (CYP) 1A1, 1A2, and 1B1, and its hydroxylated metabolites are remarkably good substrates for the sulfotransferases (SULTs) 1A1, 1A2, 1B1, and 1E1. Finally, (iii) sulfoconjugates of phenolic metabolites of FICZ are present in human urine. Our findings indicate that formylindolo[3,2-b]carbazols are the most potent naturally occurring activators of the AhR signaling pathway and may be the key substrates of the CYP1 and SULT1 families of enzymes. These conclusions contradict the widespread view that xenobiotic compounds are the major AhR ligands and CYP1 substrates. PMID:19054769

  2. Synthesis of novel 7-substituted pyrido[2',3':4,5]furo[3,2-d]pyrimidin-4-amines and their N-aryl analogues and evaluation of their inhibitory activity against Ser/Thr kinases.

    Science.gov (United States)

    Deau, Emmanuel; Loidreau, Yvonnick; Marchand, Pascal; Nourrisson, Marie-Renée; Loaëc, Nadège; Meijer, Laurent; Levacher, Vincent; Besson, Thierry

    2013-12-15

    The efficient synthesis of 7-substituted pyrido[2',3':4,5]furo[3,2-d]pyrimidin-4-amines and their N-aryl analogues is described. 3,5-Dibromopyridine was converted into 3-amino-6-bromofuro[3,2-b]pyridine-2-carbonitrile intermediate which was formylated with DMFDMA. Functionalization at position 7 of the tricyclic scaffold was accomplished, before or after cyclisation step, by palladium-catalyzed Suzuki-Miyaura cross-coupling while the pyrimidin-4-amines and N-aryl counterparts were synthesized by microwave-assisted formamide degradation and Dimroth rearrangement, respectively. The final products were evaluated for their potent inhibition of a series of five Ser/Thr kinases (CDK5/p25, CK1?/?, CLK1, DYRK1A, GSK3?/?). Compound 35 showed the best inhibitory activity with an IC50 value of 49 nM and proved to be specific to CLK1 among the panel of tested kinases. PMID:24176400

  3. Isotopically modified compounds

    International Nuclear Information System (INIS)

    In this chapter the nomenclature of isotopically modified compounds in Slovak language is described. This chapter consists of following parts: (1) Isotopically substituted compounds; (2) Specifically isotopically labelled compounds; (3) Selectively isotopically labelled compounds; (4) Non-selectively isotopically labelled compounds; (5) Isotopically deficient compounds.

  4. One-pot four-component synthesis of 2-aryl-3,3-dihaloacrylonitriles using potassium hexacyanoferrate(II) as environmentally benign cyanide source

    International Nuclear Information System (INIS)

    An efficient route to one-pot four-component reactions of aroyl chlorides, potassium hexacyanoferrate(II), triphenylphosphine and carbon tetrahalides to synthesize 2-aryl-3,3-dichloroacrylonitriles and 2-aryl-3,3-dibromoacrylonitriles was described. This protocol has advantages of use of non-toxic cyanide source, high yield and simple work-up procedure. (author)

  5. Synthesis of 2,3-epoxy-1-phenyl-3-aryl-1-propanone by combination of phase transfer catalyst and ultrasound irradiation

    Directory of Open Access Journals (Sweden)

    Ji-Tai Li

    2009-03-01

    Full Text Available Seven 2,3-epoxy-1-phenyl-3-aryl-1-propanones were synthesized via epoxidation of thecorresponding 1-phenyl-3-aryl-2-propen-1-ones with 30% aqueous hydrogen peroxide in 74-99% yields usingbenzyldimethyltetradecylammonium chloride as phase transfer catalyst under ultrasound irradiation.

  6. Metal-free C(3)-H arylation of coumarins promoted by catalytic amounts of 5,10,15,20-tetrakis(4-diethylaminophenyl)porphyrin.

    Science.gov (United States)

    Kojima, Masahiro; Oisaki, Kounosuke; Kanai, Motomu

    2015-05-28

    The metal-free C-H arylation of coumarins was achieved in the presence of catalytic amounts of 5,10,15,20-tetrakis(4-diethylaminophenyl)porphyrin. This mild and environmentally friendly Meerwein arylation provided facile access to a broad variety of 3-arylcoumarins in synthetically useful yields. PMID:25982924

  7. Synthesis of a carbon-14 analogue of aryl N-alkoxycarbamates and its application for synthesis of unsymmetrical N,N'-urea derivatives

    International Nuclear Information System (INIS)

    Aryl N-alkoxycarbamates labeled with carbon- 14 have been synthesized from aryl nitrile-[cyano-14C] as part of a 2-step sequence. The resulted carbamates were treated with amines, generating [carbonyl-14C]-Ureas in high yield and purity. (author)

  8. 3-Arylisoxazolyl-5-carboxylic acid and 5-(Hydroxymethyl)-3-aryl-2-isoxazoline as molecular platforms for liquid-crystalline materials

    Scientific Electronic Library Online (English)

    Aline, Tavares; Paolo R., Livotto; Paulo F. B., Gonçalves; Aloir A., Merlo.

    Full Text Available A síntese de uma plataforma molecular para materiais líquido-cristalinos derivados do ácido 3-arilisoxazolil-5-carboxílico (1) e do 5-(hidroximetil)-3-aril-2-isoxazolina (2) é descrita. Os intermediários 1 e 2 são obtidos através da reação de cicloadição [3+2] 1,3-dipolar entre arilóxidos de nitrila [...] s e os dipolarófilos ácido acrílico e álcool alílico, respectivamente. Os compostos cristais líquidos são sintetizados através de uma estratégia de alongamento molecular do núcleo primitivo isoxazolínico pela conexão de subunidades arilacetilênicas, as quais foram obtidas da reação de Sonogashira. Sob essas condições, séries de cristais líquidos 5a-c, 6, 7a-g e 8a-d têm sido sintetizadas com rendimentos de médios para bons. Os compostos finais apresentam propriedades líquido-cristalinas nematogênica e esmectogênica. Um cálculo DFT no nível B3LYP/6-31G(d,p) é também apresentado e alguns parâmetros estruturais obtidos são analisados. Abstract in english The synthesis of the molecular platform for liquid-crystalline materials based on 3-arylisoxazolyl-5-carboxylic acid (1) and 5-(hydroxymethyl)-3-aryl-2-isoxazoline (2) is described. The key intermediates 1 and 2 are obtained by [3+2] 1,3-dipolar cycloaddition reaction between an arylnitrile oxide an [...] d an acrylic acid and allylic alcohol as the dipolarophile. The liquid crystals (LC) compounds are synthesized through a "molecular elongation strategy" from the initial isoxazolinic core by connecting the arylacetylene moiety obtained from the Sonogashira reaction. Under these conditions, the series of liquid crystals 5a-c, 6, 7a-g and 8a-d have been successfully synthesized in fair to good yields. The final compounds display nematic and smectic liquid-crystalline properties. The structural properties of the series of the liquid crystals has been studied using DFT methods at level B3LYP/6-31G(d,p). The equilibrium geometries in the gas phase are presented and analyzed.

  9. A novel role of the aryl hydrocarbon receptor (AhR in centrosome amplification - implications for chemoprevention

    Directory of Open Access Journals (Sweden)

    Chatterjee Payel

    2010-06-01

    Full Text Available Abstract Background Centrosome aberrations can cause genomic instability and correlate with malignant progression in common human malignancies such as breast and prostate cancer. Deregulation of cyclin/cyclin-dependent kinase 2 (CDK2 activity has previously been shown to be critically involved in centrosome overduplication. We therefore test here whether small molecule CDK inhibitors derived from the bis-indole indirubin can be used to suppress centrosome aberrations as a novel approach to chemoprevention of malignant progression. Results As expected, we found that the CDK inhibitor indirubin-3'-oxime (IO suppresses centrosome amplification in breast cancer cells. However, we made the unexpected discovery that indirubin-derived compounds that have been chemically modified to be inactive as kinase inhibitors such as 1-methyl-indirubin-3'-oxime (MeIO still significantly reduced centrosome amplification. All indirubins used in the present study are potent agonists of the aryl hydrocarbon receptor (AhR, which is known for its important role in the cellular metabolism of xenobiotics. To corroborate our results, we first show that the coincidence of nuclear AhR overexpression, reflecting a constitutive activation, and numerical centrosome aberrations correlates significantly with malignancy in mammary tissue specimens. Remarkably, a considerable proportion (72.7% of benign mammary tissue samples scored also positive for nuclear AhR overexpression. We furthermore provide evidence that continued expression of endogenous AhR is critical to promote centriole overduplication induced by cyclin E and that AhR and cyclin E may function in the same pathway. Overexpression of the AhR in the absence of exogenous ligands was found to rapidly disrupt centriole duplication control. Nonetheless, the AhR agonists IO and MeIO were still found to significantly reduce centriole overduplication stimulated by ectopic AhR expression. Conclusions Our results indicate that continued expression of endogenous AhR promotes centrosome amplification in breast cancer cells in a pathway that involves cyclin E. AhR agonists such as indirubins inhibit centrosome amplification even when stimulated by ectopic expression of the AhR suggesting that these compounds are potentially useful for the chemoprevention of centrosome-mediated cell division errors and malignant progression in neoplasms in which the AhR is overexpressed. Future studies are warranted to determine whether individuals in which nuclear AhR overexpression is detected in benign mammary tissue are at a higher risk for developing pre-cancerous or cancerous breast lesions.

  10. Synthesis of new trimeric lignin model compounds containing 5-5' and b-O-4' substructures, and their characterization by 1D and 2D NMR Techniques

    Directory of Open Access Journals (Sweden)

    Alves Vera L.

    2000-01-01

    Full Text Available Trimeric lignin model compounds containing biphenyl (5-5' and beta-aryl ether (beta-O-4' were synthesized from dehydrodivanillin derivatives and alpha-bromo acetovanillone derivatives via Williamson's reaction. The ¹H and 13C NMR characteristics of the resulting trimers were studied using corresponding ¹H and 13C NMR spectra as well as homo- and heteronuclear 2D NMR techniques. The results are discussed in terms of signal assignment and conformation of the molecules.

  11. Synthesis of new trimeric lignin model compounds containing 5-5' and b-O-4' substructures, and their characterization by 1D and 2D NMR Techniques

    OpenAIRE

    Alves Vera L.; Drumond Mariza G.; Stefani Guglielmo M.; Chen Chen-Loung; Piló-Veloso Dorila

    2000-01-01

    Trimeric lignin model compounds containing biphenyl (5-5') and beta-aryl ether (beta-O-4') were synthesized from dehydrodivanillin derivatives and alpha-bromo acetovanillone derivatives via Williamson's reaction. The ¹H and 13C NMR characteristics of the resulting trimers were studied using corresponding ¹H and 13C NMR spectra as well as homo- and heteronuclear 2D NMR techniques. The results are discussed in terms of signal assignment and conformation of the molecules.

  12. Electrosynthesis and structural characterization of a novel aryl ether trimer

    Energy Technology Data Exchange (ETDEWEB)

    Besbes-Hentati, Salma [Laboratoire de Thermodynamique et d' Electrochimie, Departement de Chimie, Faculte des Sciences de Bizerte, Zarzouna 7021, Bizerte (Tunisia)]. E-mail: salma.hentati@fsb.rnu.tn; Said, Hechmi [Laboratoire de Thermodynamique et d' Electrochimie, Departement de Chimie, Faculte des Sciences de Bizerte, Zarzouna 7021, Bizerte (Tunisia); Bouvet, Marcel [Laboratoire de Chimie Inorganique et Materiaux Moleculaires, CNRS-UMR 7071, Universite Pierre et Marie Curie-Paris 6, 4 Place Jussieu, 75252 Paris Cedex 05 (France)

    2007-04-01

    The structure of a novel trimer formed by three p-tert-butyl anisole moieties via the controlled potential electrolysis of p-tert-butyl anisole was determined by X-ray diffraction method. By cyclic voltammetry, we report a multistep electron transfer, each followed by a chemical reaction, resulting in an ECECEC mechanism. Preparative scale oxidation of p-tert-butyl anisole in dry acetonitrile leads to its two first oligomers. The symmetrical dimer, 2,2'-dimethoxy-5,5'-di-tert-butylbiphenyl, shows that the favored coupling sites are those in the ortho position of the methoxy group. The title compound, namely the 1-methoxy-bis-2,3-(2'-methoxy-5'-tert-butylphenyl)-4-tert-butylbenzene crystallizes in triclinic space group P-1 with a = 10.571(3) A, b = 11.739(1) A, c = 12.733(2) A, {alpha} = 74.64(1){sup o}, {beta} = 88.71(2){sup o}, {gamma} 76.58(2){sup o}, V = 1480.8(5) A{sup 3}, and Z = 2. The structural analysis reveals that two p-tert-butyl anisole moieties are linked in ortho position on a third p-tert-butyl anisole fragment.

  13. Synthesis of N-functionalized/NH-multisubstituted indoles, thienopyrroles, pyrroloindoles, and pyrazolopyrroles via sequential one-pot base-mediated and copper-catalyzed inter- and intramolecular amination of 2-[2-bromo(het)aryl]-3-(het)aryl-3-(methylthio)acrylonitriles.

    Science.gov (United States)

    Vijay Kumar, S; Saraiah, B; Parameshwarappa, G; Ila, H; Verma, Girijesh K

    2014-09-01

    A novel, efficient route to substituted 1-N-(het)aryl/NH-2-(het)aryl-3-cyanoindoles and related pyrrolo-fused heterocycles such as thienopyrroles, pyrroloindoles, and pyrazolopyrroles has been reported. The overall protocol involves sequential cycloamination of readily available 2-[2-bromo(het)aryl]-3-(het)aryl-3-(methylthio)acrylonitrile precursors with primary amines or amides via two key C-N bond-forming processes, one base-mediated intermolecular and the other Cu-catalyzed intramolecular arylamination leading to N(1)-C(2) and N(1)-C(7a) bond formation, respectively, in a two-step one-pot procedure. PMID:25072886

  14. Design and stereoselective synthesis of a C-aryl furanoside as a conformationally constrained CHIR-090 analogue

    DEFF Research Database (Denmark)

    Oddo, Alberto; Holl, Ralph

    2012-01-01

    The UDP-3-O-[(R)-3-hydroxymyristoyl]-N-acetylglucosamine deacetylase (LpxC) is a promising target for the development of novel antibiotic substances against multidrug-resistant Gram-negative bacteria. The C-aryl glycoside 3 was designed as conformationally constrained analogue of the potent LpxC-inhibitor CHIR-090. The chiral pool synthesis of 3 started with D-mannose. The C-aryl glycoside 8 was synthesized stereoselectively by nucleophilic attack of 4-iodine-substituted phenyllithium and subsequent reduction with Et(3)SiH. The ester 10 was obtained in a one-pot diol cleavage, CrO(3) oxidation, and esterification. A Sonogashira reaction of the aryl iodide 11 led to the alkyne 17 which was transformed with H(2)NOH into the hydroxamic acid 3.

  15. Determination of arylglycerol-beta-aryl ethers and other linkages in lignins using DFRC/(31)P NMR.

    Science.gov (United States)

    Tohmura, S; Argyropoulos, D S

    2001-02-01

    An analytical method for lignins has been developed that involves derivatization followed by reductive cleavage (DFRC), depolymerization, and quantitative (31)P NMR spectroscopy. This technique detects and quantifies the various ether linkages present in softwood residual kraft lignins (RKL) and milled wood lignins (MWL). In addition, the technique supplies new quantitative information about beta-aryl ethers linked to condensed and noncondensed aromatic moieties, including dibenzodioxocins. Within RKL, beta-aryl ether bonds connected to condensed phenolic moieties predominated over those connected to noncondensed phenolic moieties. In addition, the amount of DFRC monomers determined by gas chromatography was minute in the RKL but large in the MWL. This indicates that almost all noncondensed beta-aryl ether linkages were cleaved during kraft pulping. The method offers new avenues for the detailed investigation of the bonding patterns of native and technical lignins. PMID:11261988

  16. Synthesis of New Bioactive Sulfur Compounds Bearing Heterocyclic Moiety and Their Analytical Applications

    Directory of Open Access Journals (Sweden)

    Mohammad. S. T. Makki

    2011-01-01

    Full Text Available Some new bioactive sulfur compounds bearing heterocyclic nitrogen moieties such as 3- imino–2-thioxo-4,5-dihydro- thiazolidin – 4-one (3, 3-imino – 2-thioxo -3,4,5,6-tetrahydro-1, 3-thiazine-4, 6- (2 Hdione(4, N- substituted – pyrazol -3,5-dione (10 , 1,3 –disubstituted -2-thioxo-pyrimidin-4,6 –dione (11 and di –(3,5-diaminopyrazolin-1-ylthioketone (13 derived from dithioc formic acid hydrazide (1 and thiocarbohydrazide (7were prepared via condensation of compound 1 or 7 with acyclic and cyclic oxo compounds (e.g. aldehydes andketones in 1:1 and 1:2 molar ratios, and addition of iso thiocyanate or treatment with active methylene compoundsfollowed by ring closing reactions in different media (Schemes I & II. The biocidal effect of some compoundstowards some bacteria and fungi was evaluated. Compound 4 was used as selective chelating agent forspectrophotometric determination of mercury (II ions. The limit of detection (LOD and quantification (LOQ ofthe developed spectrophotometric method were found to be equal to 0.16 and 0.52 ?g mL-1 mercury (II,respectively. Compound 4 was also physically immobilized onto polyurethane foam (PUFs and was successfullyused as solid sorbent in packed column for removal of mercury (II ions from wastewater.

  17. PEGylated polyamidoamine dendrimers with bis-aryl hydrazone linkages for enhanced gene delivery.

    Science.gov (United States)

    Yuan, Quan; Yeudall, W Andrew; Yang, Hu

    2010-08-01

    Surface modification of polyamidoamine (PAMAM) dendrimers with polyethylene glycol (PEG) often results in the decrease in their buffering capacity, which is essential for gene transfer. In this work, bis-aryl hydrazone bond, which possesses protonatable pyridine and amines, was explored as a new linkage for PEGylation of PAMAM dendrimers. PEGylated polyamidoamine (PAMAM) dendrimer G4.0 conjugates with bis-aryl hydrazone (BAH) linkages were synthesized following a two-step procedure: activation of PAMAM dendrimer G4.0 and monofunctional methoxypolyethylene glycol amine (MW=5000 Da) with succinimidyl 4-hydrazinonicotinate acetone hydrazone (SANH) and succinimidyl 4-formylbenzoate (SFB), respectively, and coupling of SFB-activated PEG to SANH-activated G4.0 to generate PEGylated G4.0 with bis-aryl hydrazone linkages (G4.0-BAH-PEG). It was found that the incorporation of BAH linkages into the vector significantly enhanced the buffering capacity of the vector even with a high degree of PEGylation (42 PEG chains per dendrimer). G4.0-BAH-PEG conjugates could complex with DNA plasmid tightly at low weight ratios and display dramatically improved cytocompatibility. According to gene transfection studies in 293T and HN12 cells, this new vector has been shown to be capable of both transfecting more cells and inducing higher gene expression than the parent dendrimer. This work demonstrates that the use of the BAH linkage in coupling of PEG to the dendrimer helps maintain or increase the buffering capacity of the functionalized dendrimer and results in enhanced transfection. PMID:20593893

  18. Photochemistry of 3-alkoxychromones: photocyclisation of 2-aryl-6-chloro-3-{(thiophen-2-yl)methoxy}chromones

    Scientific Electronic Library Online (English)

    Ramesh C., Kamboj; Urmila, Berar; Surinder, Berar; Zeba N., Siddiqui; Satish C., Gupta.

    Full Text Available 1,4-Biradicais gerados da fotoirradiação de cromonos 2-aril-3-[(tiofen-2-il)metóxi] produziram compostos tetraciclicos angulares contendo grupos tienil. A dehidrogenação e contração do anel dos produtos foram também observadas dependendo da densidade elétrica no anel 2-aril. [...] Abstract in english 1,4-Biradicals generated upon photo-irradiation of 2-aryl-3-{(thiophen-2-yl)methoxy}chromones produced angular tetracyclic products bearing the thienyl group. The dehydrogenation and ring contraction products were also observed depending upon the electron density on the 2-aryl ring. [...

  19. Synthesis and investigation of mass spectra of some heterocyclic compounds containing sulphur atom

    International Nuclear Information System (INIS)

    3-Aryl-l,4,5-trihydro-l,2,4-triazol-5-thiones (2), 2-substituted-1,2,3-trihydro-l,3,4-thiadia-zine (3) and 3-substituted 2-thioxoimida-zolidin-4-ones (4) were prepared via the reaction of 4-substituted benzaldehyde thiosemicarbazones (1) with bromine in Ac OH, thioglycolic acid and ethyl chloroacetate in the presence of different bases. Acetylation of 4 with Ac2O gave the corresponding monoacetyl derivative (5), while the acetylation of 4 with Ac2O in presence of AcONa gave the corresponding diacetyl derivative (6). 5-Arylidene-thiazolidine-2,4-diones (8) were synthesized by the reaction of compound 4 with aromatic aldehydes to give 3-substituted 5-arylidene-2-thioxoimid-azolidin-4-ones (7), followed by bromination of 7 in presence of AcONa in acetic acid. The mass spectral fragmentation patterns of some prepared compounds are investigated in order to elucidate the structure of the synthesized compounds

  20. Effect of exposure duration on the aryl hydrocarbon receptor-mediated activity of polycyclic aromatic hydrocarbons measured by in vitro reporter gene assay

    Energy Technology Data Exchange (ETDEWEB)

    Masunaga, S.; Sakashita, R.; Furuichi, T.; Shirai, J. [Yokohama National Univ. (Japan). Graduate School of Environment and Information Sciences; Kannan, K. [New York State Dept. of Health, Albany, NY (United States). Dept. of Health]|[State Univ. of New York, Albany, NY (United States). Environmental Toxicology and Health; Giesy, J. [Michigan State Univ., East Lansing, MI (United States). Dept. of Zoology, National Food Safety and Toxicology Center, Inst. for Environmental Toxicology

    2004-09-15

    Due to the time and cost required for the measurement of dioxins using highresolution gas chromatograph coupled with high-resolution mass spectrometer (HRGC-HRMS), the application of in vitro bioassays to monitor aryl hydrocarbon receptor (AhR) mediated activity is receiving much attention recently. Values obtained by the in vitro bioassays, however, reflect not only the AhR activity caused by dioxins but also by other compounds that interact with the AhR. In other words, this is a valuable feature of the assay; it can serve as a conservative measure of AhR mediated activity in samples and as a measure to detect and identify unknown AhR active components. Thus, when using bioassays in place of HRGC-HRMS to estimate the amount of dioxins or dioxin-like toxicity, pretreatment to remove compounds other than dioxins and related AhR agonists have been sought and applied. Polycyclic aromatic hydrocarbons (PAHs) are among those compounds that elicit AhR mediated activity and exist at much larger concentrations than dioxins in the environment and foods, but are not regarded as potent as dioxins in terms of dioxin-like toxicity because they are more easily metabolised in animals. However, exposure of humans and wildlife to PAHs is certain. Thus, information on the potencies of PAHs relative to 2,3,7,8- tetrachlorodibenzo-p-dioxin (2378-TCDD) is necessary to characterize the dioxinlike activities obtained in the bioassays. In this study, AhR mediated activities of nineteen PAHs were examined by chemically-activated luciferase gene expression (CALUX) assay using H4IIEluciferase cells at various exposure durations.

  1. Pharmacological interactions between phenylbenzothiazoles and aryl hydrocarbon receptor (AhR)

    OpenAIRE

    Bazzi, Rana

    2008-01-01

    The aryl hydrocarbon receptor is a ligand-dependent transcription factor that induces expression of a number of genes encoding drug metabolizing enzymes, such as CYP1A1, CYP1A2 and CYP1B1. Recently, it was suggested that the AhR signaling pathway may be involved in mediating the anticancer activity of novel 2-(4-aminophenyl) benzothiazole drugs in MCF-7 breast cancer cells. There is no direct proof of direct binding between these drugs and AhR, and it is also unclear how AhR signaling per se ...

  2. 3-Methylcholanthrene Induces Differential Recruitment of Aryl Hydrocarbon Receptor to Human Promoters

    OpenAIRE

    Pansoy A; Ahmed S; Valen E; Sandelin A*.; Matthews J.

    2010-01-01

    The paper by Pansoy and coworkers investigates the effects of the aryl hydrocarbon receptor (AHR) ligand 3-methylcholanthrene (3MC) on recruitment of the AHR complex to human promoters in T47D breast cancer cells. The results are particularly important because they can be compared with a prior study using the potent AHR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the same cell line. The chromatin immunoprecipitation and promoter-focused microarrays (ChIP-chip) demonstrated that after...

  3. One-pot, four-component synthesis of novel cytotoxic agents 1-(5-aryl-1,3,4-oxadiazol-2-yl)-1-(1H-pyrrol-2-yl)methanamines.

    Science.gov (United States)

    Ramazani, Ali; Khoobi, Mehdi; Torkaman, Azar; Nasrabadi, Fatemeh Zeinali; Forootanfar, Hamid; Shakibaie, Mojtaba; Jafari, Mandana; Ameri, Alieh; Emami, Saeed; Faramarzi, Mohammad Ali; Foroumadi, Alireza; Shafiee, Abbas

    2014-05-01

    A series of N-benzyl-1-(5-aryl-1,3,4-oxadiazol-2-yl)-1-(1H-pyrrol-2-yl)methanamines were synthesized via one-pot reaction of appropriate benzylamine, pyrrole-2-carbaldehyde, (N-isocyanimino)triphenylphosphorane, and a carboxylic acid. The anti-tumor potential of title compounds was tested against several cancer cell lines by using MTT assay. Some tested compounds including 5e, 5p and 5q exhibited comparable or better cytotoxic activity against A549, HT29 or HT1080 cells in comparison to the reference drug doxorubicin. Also, the cytotoxic activity of compounds 5d and 5n against MCF-7 was better than that of doxorubicin. Compound 5n with IC50 value of 4.3 ?M was 4-fold more potent than doxorubicin. The structure-activity relationship study revealed that the introduction of halogen atoms on both 5-phenyl ring and N-benzyl part improved the cytotoxic activity against all tested cell lines. PMID:24681979

  4. Anti-cancer agents based on 4-(hetero)Ary1-1,2,5-oxadiazol-3-yl Amino derivatives and a method of making

    Science.gov (United States)

    Gakh, Andrei A.; Krasavin, Mikhail; Karapetian, Ruben; Rufanov, Konstantin A.; Konstantinov, Igor; Godovykh, Elena; Soldatkina, Olga; Sosnov, Andrey V.

    2013-01-29

    The present disclosure relates to novel compounds that can be used as anti-cancer agents in the prostate cancer therapy. ##STR00001## In particular, the invention relates N-substituted derivatives of 4-(hetero)aryl-1,2,5-oxadiazol-3-yl amines having the structural Formula (I) and (II), stereoisomers, tautomers, racemics, prodrugs, metabolites thereof, or pharmaceutically acceptable salt and/or solvate thereof. Meaning of R1 and R2 in the Formula (I) and (II) are defined in claim 1. The invention also relates to methods for preparing said compounds, and to pharmaceutical compositions comprising said compounds.

  5. Aromatic hydrocarbons upregulate glyceraldehyde-3-phosphate dehydrogenase and induce changes in actin cytoskeleton. Role of the aryl hydrocarbon receptor (AhR)

    International Nuclear Information System (INIS)

    Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a multifunctional enzyme involved in several cellular functions including glycolysis, membrane transport, microtubule assembly, DNA replication and repair, nuclear RNA export, apoptosis, and the detection of nitric oxide stress. Therefore, modifications in the regulatory ability and function of GAPDH may alter cellular homeostasis. We report here that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and ?-naphthoflavone, which are well-known ligands for the aryl hydrocarbon receptor (AhR), increase GAPDH mRNA levels in vivo and in vitro, respectively. These compounds fail to induce GAPDH transcription in an AhR-null mouse model, suggesting that the increase in GAPDH level is dependent upon AhR activation. To analyse the consequences of AhR ligands on GAPDH function, mice were treated with TCDD and the level of liver activity of GAPDH was determined. The results showed that TCDD treatment increased GAPDH activity. On the other hand, treatment of Hepa-1 cells with ?-naphthoflavone leads to an increase in microfilament density when compared to untreated cultures. Collectively, these results suggest that AhR ligands, such as polycyclic hydrocarbons, can modify GAPDH expression and, therefore, have the potential to alter the multiple functions of this enzyme.

  6. Inhibition of aryl hydrocarbon receptor-dependent transcription by resveratrol or kaempferol is independent of estrogen receptor ? expression in human breast cancer cells.

    Science.gov (United States)

    Macpherson, Laura; Matthews, Jason

    2010-12-28

    Resveratrol and kaempferol are natural chemopreventative agents that are also aryl hydrocarbon receptor (AHR) antagonists and estrogen receptor (ER) agonists. In this study we evaluated the role of ER? in resveratrol- and kaempferol-mediated inhibition of AHR-dependent transcription. Kaempferol or resveratrol inhibited dioxin-induced cytochrome P450 1A1 (CYP1A1) and CYP1B1 expression levels and recruitment of AHR, ER? and co-activators to CYP1A1 and CYP1B1. Both phytochemicals induced the expression and recruitment of ER? to gene amplified in breast cancer 1 (GREB1). RNAi-mediated knockdown of ER? in T-47D cells did not affect the inhibitory action of either phytochemical on AHR activity. Both compounds also inhibited AHR-dependent transcription in ER?-negative MDA-MB-231 and BT-549 breast cancer cells. These data show that ER? does not contribute to the AHR-inhibitory activities of resveratrol and kaempferol. PMID:20846786

  7. Thermodynamic properties of donor–acceptor complexes of tertiary amine with aryl ketones in hexane medium

    International Nuclear Information System (INIS)

    Highlights: ? Ultrasonic scan is carried out on ternary systems of aromatic tertiary amine and three aryl ketones. ? Formation of CT complexes is found between tertiary amine with aryl ketones. ? Stability constant values are computed by ultrasonic and spectral methods are compared. ? The trend in the ‘K’ suggests that substituents in ketones influence the stabilities of these complexes. ? The thermodynamic parameters suggest CT interaction is exothermic and the complexes are thermodynamically stable. - The thermodynamic stability of complexes formed between N,N-dimethylaniline (DMANI) and three ketones, namely, acetophenone (ACP), 4-chloroactophenone (ClACP) and 4-methylacetophenone (MACP) in n-hexane is extensively investigated by spectral and ultrasonic methods. The ultrasound scan was carried out in the temperature range 208.15–313.15 K and at atmospheric pressure on solutions containing equimolar concentrations of components ranging from 0.025 to 0.2 M. The existence of solute–solute interactions has also been confirmed through electronic absorption spectra analyzed with Benesi-Hildebrand theory at 303.15 K. The stability constants of the donor–acceptor complexes determined both by spectroscopic and ultrasonic methods are comparable and follow similar trends. The trend in the formation constants is discussed with structures of the components. The thermodynamic behavior of the systems was explained through the computed values of the free energyues of the free energy (?G), enthalpy (?H) and entropy (?S) changes for complex formation are computed and discussed.

  8. The aryl hydrocarbon receptor and glucocorticoid receptor interact to activate human metallothionein 2A

    International Nuclear Information System (INIS)

    Although the aryl hydrocarbon receptor (AHR) and glucocorticoid receptor (GR) play essential roles in mammalian development, stress responses, and other physiological events, crosstalk between these receptors has been the subject of much debate. Metallothioneins are classic glucocorticoid-inducible genes that were reported to increase upon treatment with AHR agonists in rodent tissues and cultured human cells. In this study, the mechanism of human metallothionein 2A (MT2A) gene transcription activation by AHR was investigated. Cotreatment with 3-methylcholanthrene and dexamethasone, agonists of AHR and GR respectively, synergistically increased MT2A mRNA levels in HepG2 cells. MT2A induction was suppressed by RNA interference against AHR or GR. Coimmunoprecipitation experiments revealed a physical interaction between AHR and GR proteins. Moreover, chromatin immunoprecipitation assays indicated that AHR was recruited to the glucocorticoid response element in the MT2A promoter. Thus, we provide a novel mechanism whereby AHR modulates expression of human MT2A via the glucocorticoid response element and protein–protein interactions with GR. - Highlights: • Aryl hydrocarbon receptor forms a complex with glucocorticoid receptor in cells. • Human metallothionein gene is regulated by the AHR and GR interaction. • AHR–GR complex binds to glucocorticoid response element in metallothionein gene. • We demonstrated a novel transcriptional mechanism via AHR and GR inter

  9. The aryl hydrocarbon receptor and glucocorticoid receptor interact to activate human metallothionein 2A

    Energy Technology Data Exchange (ETDEWEB)

    Sato, Shoko, E-mail: satosho@rs.tus.ac.jp [Laboratory of Nutrition, Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555 (Japan); Shirakawa, Hitoshi, E-mail: shirakah@m.tohoku.ac.jp [Laboratory of Nutrition, Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555 (Japan); Tomita, Shuhei, E-mail: tomita@med.tottori-u.ac.jp [Division of Molecular Pharmacology, Department of Pathophysiological and Therapeutic Science, Yonago 683-8503 (Japan); Tohkin, Masahiro, E-mail: tohkin@phar.nagoya-cu.ac.jp [Department of Medical Safety Science, Graduate School of Pharmaceutical Science, Nagoya City University, Nagoya 267-8603 (Japan); Gonzalez, Frank J., E-mail: gonzalef@mail.nih.gov [Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Komai, Michio, E-mail: mkomai@m.tohoku.ac.jp [Laboratory of Nutrition, Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555 (Japan)

    2013-11-15

    Although the aryl hydrocarbon receptor (AHR) and glucocorticoid receptor (GR) play essential roles in mammalian development, stress responses, and other physiological events, crosstalk between these receptors has been the subject of much debate. Metallothioneins are classic glucocorticoid-inducible genes that were reported to increase upon treatment with AHR agonists in rodent tissues and cultured human cells. In this study, the mechanism of human metallothionein 2A (MT2A) gene transcription activation by AHR was investigated. Cotreatment with 3-methylcholanthrene and dexamethasone, agonists of AHR and GR respectively, synergistically increased MT2A mRNA levels in HepG2 cells. MT2A induction was suppressed by RNA interference against AHR or GR. Coimmunoprecipitation experiments revealed a physical interaction between AHR and GR proteins. Moreover, chromatin immunoprecipitation assays indicated that AHR was recruited to the glucocorticoid response element in the MT2A promoter. Thus, we provide a novel mechanism whereby AHR modulates expression of human MT2A via the glucocorticoid response element and protein–protein interactions with GR. - Highlights: • Aryl hydrocarbon receptor forms a complex with glucocorticoid receptor in cells. • Human metallothionein gene is regulated by the AHR and GR interaction. • AHR–GR complex binds to glucocorticoid response element in metallothionein gene. • We demonstrated a novel transcriptional mechanism via AHR and GR interaction.

  10. MÉTODO DE SÍNTESE DE AZIDAS AROMÁTICAS USANDO VINAGRE / METHOD FOR THE SYNTHESIS OF ARYL AZIDES USING VINEGAR

    Scientific Electronic Library Online (English)

    Kauanna Naguissa, Hino; Álvaro Takeo, Omori.

    2015-01-01

    Full Text Available [...] Abstract in english The present paper describes a simple and low-cost procedure for preparation of aryl azides from anilines using vinegar as an unusual solvent/reagent. We observed the sequence of diazotation followed by diazo displacement with sodium azide can be carried out in aqueous solution of acetic acid [...

  11. Mild Pd-catalyzed N-arylation of methanesulfonamide and related nucleophiles: avoiding potentially genotoxic reagents and byproducts.

    Science.gov (United States)

    Rosen, Brandon R; Ruble, J Craig; Beauchamp, Thomas J; Navarro, Antonio

    2011-05-20

    A convenient, general, and high yielding Pd-catalyzed cross-coupling of methanesulfonamide with aryl bromides and chlorides is reported. The use of this method eliminates concern over genotoxic impurities that can arise when an aniline is reacted with methanesulfonyl chloride. The application of this method to the synthesis of dofetilide is also reported. PMID:21510692

  12. Direct asymmetric aldol addition-isomerization of ?,?-unsaturated ?-butyrolactam with aryl ?-ketoesters: synthesis of MBH-type products.

    Science.gov (United States)

    Zhang, Jinlong; Liu, Xihong; Ma, Xiaojuan; Wang, Rui

    2013-04-25

    A highly efficient direct asymmetric aldol addition-isomerization reaction at the ?-position of ?,?-unsaturated ?-butyrolactam and aryl ?-ketoesters by using a bifunctional thiourea catalyst was achieved. Morita-Baylis-Hillman type adducts containing a quaternary stereocenter can be obtained in high yields and with excellent enantioselectivities (up to 99% ee). PMID:23503364

  13. Microwave-Assisted Heck Arylations of Non-Activated N-Acyl-3-pyrrolines with Arenediazonium Tetrafluoroborates

    Scientific Electronic Library Online (English)

    Fernanda G., Finelli; Marla N., Godoi; Carlos R. D., Correia.

    2015-05-01

    Full Text Available Successful Heck-Matsuda arylations of non-activated olefins applying microwave irradiation as an alternative heating mode are presented. Cleaner reactions were performed with arenediazonium tetrafluoroborates bearing electron-donating and electron-withdrawing groups in good to excellent yields with [...] reaction times reduced from 3.5-18 h to 12-30 min.

  14. Semisynthetic derivatives of sesquiterpene lactones by palladium-catalyzed arylation of the alpha-methylene-gamma-lactone substructure.

    Science.gov (United States)

    Han, Changho; Barrios, Francis J; Riofski, Mark V; Colby, David A

    2009-09-18

    The palladium-catalyzed arylation of different alpha-methylene-gamma-lactone-containing sesquiterpene lactones was shown to produce E-olefin coupling products selectively in moderate to excellent yields. Biological evaluation of these semisynthetic sesquiterpene lactone derivatives in HeLa cells showed interesting antiproliferative profiles and provided initial structure-activity data. PMID:19697954

  15. Kinetic of the [2 +3] cycloaddition of Z-C-aryl-N-phenylonitrones with 1-bromo-1-nitroethene

    OpenAIRE

    Mikulska, Maria; Bara??ski, Andrzej

    2011-01-01

    Kinetic measurements of the [2+3] cycloaddition reaction between 1-bromo-1-nitroethene and Z-C-aryl-N-phenylnitrones were carried out. Kinetic studies proved that despite the high p-deficiency of the nitroalkene, the reactions proceed according to the concerted mechanism. This is evidenced in particular by the character of the Dimroth-Hammet correlation.

  16. Induction of aryl hydrocarbon receptor-mediated and estrogen receptor-mediated activities, and modulation of cell proliferation by dinaphthofurans.

    Czech Academy of Sciences Publication Activity Database

    Vondrá?ek, Jan; Chramostová, Kate?ina; Plíšková, M.; Bláha, L.; Brack, W.; Kozubík, Alois; Machala, M.

    2004-01-01

    Ro?. 23, ?. 9 (2004), s. 2214-2220. ISSN 0730-7268 R&D Projects: GA ?R GA525/03/1527 Institutional research plan: CEZ:AV0Z5004920 Keywords : aryl hydrocarbon receptor-mediated activity * estrogenicity * intercellular communication inhibition Subject RIV: BO - Biophysics Impact factor: 2.121, year: 2004

  17. A general catalyst for Suzuki-Miyaura and Sonogashira reactions of aryl and heteroaryl chlorides in water.

    Science.gov (United States)

    Peng, Hui; Chen, Ya-Qin; Mao, Shu-Lan; Pi, Yun-Xiao; Chen, You; Lian, Ze-Yu; Meng, Tong; Liu, Sheng-Hua; Yu, Guang-Ao

    2014-09-21

    We report the synthesis of 2-(3-sulfonatomesityl)-5-sulfonatoindenyl)dicyclohexylphosphine hydrate sodium salt and its use in palladium-catalyzed Suzuki-Miyaura and Sonogashira coupling reactions in water (and biphasic water-organic solvent mixtures) to prepare a variety of functionalized biaryls and aryl alkynes in excellent yield. PMID:25070296

  18. IODIDE-ION QUENCHING OF THE PHOTOLYSIS OF 1-IODOANTHRAQUINONE ANION RADICAL - EVIDENCE FOR AN ARYL RADICAL NUCLEOPHILE REACTION

    OpenAIRE

    Bethell, D; Compton, R; R Wellington

    1992-01-01

    The photolysis of 1-iodoanthraquinone anion radical in acetonitrile containing tetrabutylammonium iodide(TBA+l-) is unaffected by changes in [TBA+|-] up to 0.2 mol dm-3, confirming that the previously observed iodide ion quenching results from capture of photogenerated aryl radicals by the nucleophilic iodide, a process analogous to that in nucleophilic aromatic substitution by the SRN1 mechanism.

  19. Over-expression of AhR (aryl hydrocarbon receptor induces neural differentiation of Neuro2a cells: neurotoxicology study

    Directory of Open Access Journals (Sweden)

    Ishihara-Sugano Mitsuko

    2006-09-01

    Full Text Available Abstract Background Dioxins and related compounds are suspected of causing neurological disruption in human and experimental animal offspring following perinatal exposure during development and growth. The molecular mechanism(s of the actions in the brain, however, have not been fully investigated. A major participant in the process of the dioxin-toxicity is the dioxin receptor, namely the aryl hydrocarbon receptor (AhR. AhR regulates the transcription of diverse genes through binding to the xenobiotic-responsive element (XRE. Since the AhR has also been detected in various regions of the brain, the AhR may play a key role in the developmental neurotoxicity of dioxins. This study focused on the effect of AhR activation in the developing neuron. Methods The influence of the AhR on the developing neuron was assessed using the Neuro2a-AhR transfectant. The undifferentiated murine neuroblastoma Neuro2a cell line (ATCC was stably transfected with AhR cDNA and the established cell line was named N2a-R?. The activation of exogenous AhR in N2a-R? cells was confirmed using RNAi, with si-AhR suppressing the expression of exogenous AhR. The neurological properties of N2a-R? based on AhR activation were evaluated by immunohistochemical analysis of cytoskeletal molecules and by RT-PCR analysis of mRNA expression of neurotransmitter-production related molecules, such as tyrosine hydroxylase (TH. Results N2a-R? cells exhibited constant activation of the exogenous AhR. CYP1A1, a typical XRE-regulated gene, mRNA was induced without the application of ligand to the culture medium. N2a-R? cells exhibited two significant functional features. Morphologically, N2a-R? cells bore spontaneous neurites exhibiting axon-like properties with the localization of NF-H. In addition, cdc42 expression was increased in comparison to the control cell line. The other is the catecholaminergic neuron-like property. N2a-R? cells expressed tyrosine hydroxylase (TH mRNA as a functional marker of catecholaminergic neurotransmitter production. Thus, exogenous AhR induced catecholaminergic differentiation in N2a-R? cells. Conclusion The excessive activation of AhR resulted in neural differentiation of Neuro2a cells. This result revealed that dioxins may affect the nervous system through the AhR-signaling pathway. Activated AhR may disrupt the strictly regulated brain formation with irregular differentiation occurring rather than cell death.

  20. Palladium-catalyzed arylic/allylic aminations: permutable domino sequences for the synthesis of dihydroquinolines from Morita-Baylis-Hillman adducts.

    Science.gov (United States)

    Lorion, Mélanie M; Gasperini, Danila; Oble, Julie; Poli, Giovanni

    2013-06-21

    An efficient palladium-catalyzed synthesis of 1,2-dihydroquinolines has been developed via the reaction between anilines and Morita-Baylis-Hillman adducts derived from o-bromobenzaldehyde. This new Pd(0)-catalyzed pseudo-domino type I sequence involves a Buchwald-Hartwig arylic amination and an allylic amination. When starting from an o-bromo allylic alcohol, the chronology is arylic amination/allylic arylation. However, the sequence reverses when the reaction is performed on the corresponding o-bromo allylic acetate. PMID:23734985

  1. ZnO-supported Pd nanoparticle-catalyzed ligand- and additive-free cyanation of unactivated aryl halides using K4[Fe(CN)6].

    Science.gov (United States)

    Chatterjee, Tanmay; Dey, Raju; Ranu, Brindaban C

    2014-06-20

    The use of a new ZnO-supported palladium(0) nanoparticle catalyst for the cyanation of aryl halides using a relatively benign cyanide source, K4[Fe(CN)6], is described. This catalyst has been applied for the efficient cyanation of a variety of functionalized aryl bromides and activated aryl chlorides. This process circumvents the need for an additive and a ligand for the reaction and offers the advantages of high product yields, low catalyst loading (0.2 mol % Pd), and recyclability of the catalyst. PMID:24856411

  2. Radiosynthesis and in vitro stability evaluation of various radioiodine-labelled ?-iodoalkylether prosthetic groups linked to model compounds

    International Nuclear Information System (INIS)

    A systematic comparative investigation into the in vitro radiochemical stabilities of model compounds containing radioiodinated ?-iodoethoxyl units and derivatives thereof, as well as those of similar compounds lacking a ?-oxygen to serve as control references, was undertaken. The radioiodinations were carried out in fair to modest yields by means of substitution of a tosyl group by iodide. Stability evaluations were carried out by incubating the labeled compounds in human blood serum at 37 deg. C and measuring free radioiodide by means of radio-HPLC and radio-TLC. The compounds containing ?-iodoethoxyl units displayed much superior stabilities than those without, while the presence of small alkyl or aryl groups in such a unit rendered an additional degree of stability to the carbon-iodine bond, especially over a long period

  3. Cardiac toxicity of 5-ring polycyclic aromatic hydrocarbons is differentially dependent on the aryl hydrocarbon receptor 2 isoform during zebrafish development

    International Nuclear Information System (INIS)

    Petroleum-derived compounds, including polycyclic aromatic hydrocarbons (PAHs), commonly occur as complex mixtures in the environment. Recent studies using the zebrafish experimental model have shown that PAHs are toxic to the embryonic cardiovascular system, and that the severity and nature of this developmental cardiotoxicity varies by individual PAH. In the present study we characterize the toxicity of the relatively higher molecular weight 5-ring PAHs benzo[a]pyrene (BaP), benzo[e]pyrene (BeP), and benzo[k]fluoranthene (BkF). While all three compounds target the cardiovascular system, the underlying role of the ligand-activated aryl hydrocarbon receptor (AHR2) and the tissue-specific induction of the cytochrome p450 metabolic pathway (CYP1A) were distinct for each. BaP exposure (40 ?M) produced AHR2-dependent bradycardia, pericardial edema, and myocardial CYP1A immunofluorescence. By contrast, BkF exposure (4–40 ?M) caused more severe pericardial edema, looping defects, and erythrocyte regurgitation through the atrioventricular valve that were AHR2-independent (i.e., absent myocardial or endocardial CYP1A induction). Lastly, exposure to BeP (40 ?M) yielded a low level of CYP1A+ signal in the vascular endothelium of the head and trunk, without evident toxic effects on cardiac function or morphogenesis. Combined with earlier work on 3- and 4-ring PAHs, our findings provide a more complete picture of how individual PAHs may drive the cardiotoxicity of mixtures in which they predominate. This will improve toxic injury assessments and risk assessments for wild fish populations that spawn in habitats altered by overlapping petroleum-related human impacts such as oil spills, urban stormwater runoff, or sediments contaminated by legacy industrial activities. -- Highlights: ? PAH compounds with 5 rings in different arrangements caused differential tissue-specific patterns of CYP1A induction in zebrafish embryos. ? These compounds produced differential cardiac developmental toxicity that did not strictly correlate with associated CYP1A induction. ? Cardiotoxicity of benzo(a)pyrene was partially dependent on the AHR2 isoform, while benzo(k)fluoranthene cardiotoxicity was not. ? Individual PAH compounds have distinct toxicokinetic pathways in fish embryos, and act through different toxic mechanisms.

  4. Differential ligand-dependent activation and a role for Y322 in aryl hydrocarbon receptor-mediated regulation of gene expression.

    Science.gov (United States)

    Powis, Melanie; Celius, Trine; Matthews, Jason

    2011-07-15

    The aryl hydrocarbon receptor (AHR) mediates the toxic effects of halogenated aromatic hydrocarbons (HAHs), such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD), 2,3,4,7,8-pentachlorodibenzofuran (2,3,4,7,8-PeCDF) and 2,3,7,8-tetrachlorodibenzofuran (2,3,7,8-TCDF). Non-traditional activators, including omeprazole (Omp), are thought to regulate AHR action through phosphorylation rather than binding to the receptor. In this study, we examined the ability of these compounds to induce AHR-dependent regulation of cytochrome P450 1A1 (CYP1A1) and CYP1B1 in T-47D human breast cancer cells. The role of Y322, a residue implicated in Omp-dependent activation of AHR was also investigated. All four compounds induced CYP1A1 and CYP1B1 mRNA expression, with Omp differing from the HAHs. Chromatin immunoprecipitation assays revealed ligand- and gene-selectivity in the recruitment patterns of AHR coactivators. We also found that residue Y322 of human AHR was important for maximum activation of AHR by 2,3,7,8-TCDD and 2,3,4,7,8-PeCDF, but required for 2,3,7,8-TCDF and Omp in an AHR-deficient MCF-7 human breast cancer cell line. In summary, this study provides evidence for context- and ligand-selective differences in coactivator recruitment in AHR-regulated gene expression and reveal an important role of Y322 in AHR activation. PMID:21703235

  5. Modulation of aryl hydrocarbon receptor target genes in circulating lymphocytes from dairy cows bred in a dioxin-like PCB contaminated area.

    Science.gov (United States)

    Girolami, Flavia; Spalenza, Veronica; Carletti, Monica; Sacchi, Paola; Rasero, Roberto; Nebbia, Carlo

    2013-04-15

    Animal productions (i.e. fish, eggs, milk and dairy products) represent the major source of exposure to dioxins, furans, and dioxin-like (DL) polychlorobiphenyls for humans. The negative effects of these highly toxic and persistent pollutants are mediated by the activation of the aryl hydrocarbon receptor (AHR) that elicits the transcriptional induction of several genes, including those involved in xenobiotic metabolism. Previously we demonstrated the presence and functioning of the AHR signaling pathway in primary cultures of bovine blood lymphocytes. The aim of the present study was to investigate by real time PCR the expression and the inducibility of selected target genes (i.e. AHR, AHR nuclear translocator (ARNT), AHR repressor, CYP1A1 and CYP1B1) in uncultured cells from dairy cows naturally exposed to DL-compounds. The study was carried out on two groups of animals bred in a highly polluted area and characterized by a different degree of contamination, as assessed by bulk milk TEQ values, and a control group reared in an industry free area. Bovine lymphocytes expressed only AHR, ARNT and CYP1B1 genes to a detectable level; moreover, only CYP1B1 expression appeared to be correlated to TEQ values, being higher in the most contaminated group, and decreasing along with animal decontamination. Finally, lymphocytes from exposed cows displayed a lower inducibility of both CYP1A1 and CYP1B1 after the in vitro treatment with a specific AHR ligand. In conclusion, our results indicate that DL-compound contaminated cows may display significant changes in AHR-target gene expression of circulating lymphocytes. PMID:23454571

  6. Modulation of aryl hydrocarbon receptor target genes in circulating lymphocytes from dairy cows bred in a dioxin-like PCB contaminated area

    International Nuclear Information System (INIS)

    Animal productions (i.e. fish, eggs, milk and dairy products) represent the major source of exposure to dioxins, furans, and dioxin-like (DL) polychlorobiphenyls for humans. The negative effects of these highly toxic and persistent pollutants are mediated by the activation of the aryl hydrocarbon receptor (AHR) that elicits the transcriptional induction of several genes, including those involved in xenobiotic metabolism. Previously we demonstrated the presence and functioning of the AHR signaling pathway in primary cultures of bovine blood lymphocytes. The aim of the present study was to investigate by real time PCR the expression and the inducibility of selected target genes (i.e. AHR, AHR nuclear translocator (ARNT), AHR repressor, CYP1A1 and CYP1B1) in uncultured cells from dairy cows naturally exposed to DL-compounds. The study was carried out on two groups of animals bred in a highly polluted area and characterized by a different degree of contamination, as assessed by bulk milk TEQ values, and a control group reared in an industry free area. Bovine lymphocytes expressed only AHR, ARNT and CYP1B1 genes to a detectable level; moreover, only CYP1B1 expression appeared to be correlated to TEQ values, being higher in the most contaminated group, and decreasing along with animal decontamination. Finally, lymphocytes from exposed cows displayed a lower inducibility of both CYP1A1 and CYP1B1 after the in vitro treatment with a specific AHR ligand. In conclusion, our results indicate that DL-compound contaminated cows may display significant changes in AHR-target gene expression of circulating lymphocytes. - Highlights: ? The expression of AHR-target genes in blood bovine lymphocytes was evaluated. ? The lymphocyte CYP1B1 expression appears to be related to bulk milk TEQ values. ? Blood lymphocytes from dairy cows might represent a matrix for dioxin biomonitoring

  7. Modulation of aryl hydrocarbon receptor target genes in circulating lymphocytes from dairy cows bred in a dioxin-like PCB contaminated area

    Energy Technology Data Exchange (ETDEWEB)

    Girolami, Flavia, E-mail: flavia.girolami@unito.it [Department of Animal Pathology, University of Turin, Via Leonardo da Vinci 44, 10095 Grugliasco (Italy); Spalenza, Veronica, E-mail: veronica.spalenza@unito.it [Department of Animal Production, Epidemiology and Ecology, University of Turin, Via Leonardo da Vinci 44, 10095 Grugliasco (Italy); Carletti, Monica, E-mail: monica.carletti@unito.it [Department of Animal Pathology, University of Turin, Via Leonardo da Vinci 44, 10095 Grugliasco (Italy); Sacchi, Paola, E-mail: paola.sacchi@unito.it [Department of Animal Production, Epidemiology and Ecology, University of Turin, Via Leonardo da Vinci 44, 10095 Grugliasco (Italy); Rasero, Roberto, E-mail: roberto.rasero@unito.it [Department of Animal Production, Epidemiology and Ecology, University of Turin, Via Leonardo da Vinci 44, 10095 Grugliasco (Italy); Nebbia, Carlo, E-mail: carlo.nebbia@unito.it [Department of Animal Pathology, University of Turin, Via Leonardo da Vinci 44, 10095 Grugliasco (Italy)

    2013-04-15

    Animal productions (i.e. fish, eggs, milk and dairy products) represent the major source of exposure to dioxins, furans, and dioxin-like (DL) polychlorobiphenyls for humans. The negative effects of these highly toxic and persistent pollutants are mediated by the activation of the aryl hydrocarbon receptor (AHR) that elicits the transcriptional induction of several genes, including those involved in xenobiotic metabolism. Previously we demonstrated the presence and functioning of the AHR signaling pathway in primary cultures of bovine blood lymphocytes. The aim of the present study was to investigate by real time PCR the expression and the inducibility of selected target genes (i.e. AHR, AHR nuclear translocator (ARNT), AHR repressor, CYP1A1 and CYP1B1) in uncultured cells from dairy cows naturally exposed to DL-compounds. The study was carried out on two groups of animals bred in a highly polluted area and characterized by a different degree of contamination, as assessed by bulk milk TEQ values, and a control group reared in an industry free area. Bovine lymphocytes expressed only AHR, ARNT and CYP1B1 genes to a detectable level; moreover, only CYP1B1 expression appeared to be correlated to TEQ values, being higher in the most contaminated group, and decreasing along with animal decontamination. Finally, lymphocytes from exposed cows displayed a lower inducibility of both CYP1A1 and CYP1B1 after the in vitro treatment with a specific AHR ligand. In conclusion, our results indicate that DL-compound contaminated cows may display significant changes in AHR-target gene expression of circulating lymphocytes. - Highlights: ? The expression of AHR-target genes in blood bovine lymphocytes was evaluated. ? The lymphocyte CYP1B1 expression appears to be related to bulk milk TEQ values. ? Blood lymphocytes from dairy cows might represent a matrix for dioxin biomonitoring.

  8. Characterization of in vitro metabolites of the aryl hydrocarbon receptor ligand 6-formylindolo[3,2-b]carbazole by liquid chromatography-mass spectrometry and NMR.

    Science.gov (United States)

    Bergander, Linda; Wahlström, Niklas; Alsberg, Tomas; Bergman, Jan; Rannug, Agneta; Rannug, Ulf

    2003-02-01

    The tryptophan photoproduct 6-formylindolo[3,2-b]carbazole (FICZ) exhibits the highest aryl hydrocarbon receptor (AhR) binding affinity reported so far. In different cells, in vitro, both extracts of UV-irradiated tryptophan and the synthesized pure compound FICZ induce a rapid and transient expression of AhR-regulated genes. The transient induction suggests that the biotransformation gene battery induced by AhR activation takes part in a metabolic degradation of the ligand, whereby a low steady-state level is regained. The down-regulation of AhR-regulated gene expression was previously shown to be dependent on cytochrome P450 1A1 (CYP1A1). Metabolism of FICZ generates five major metabolites, which appeared as three peaks (M1-M3) in the high performance liquid chromatography. The aim of the present study was to use rat liver S9 from Aroclor-pretreated rats to produce large enough quantities of FICZ metabolites for structure characterization and to determine their product precursor relationship. NMR analysis of large combined fractions of the metabolites indicated that M3 and M2 contained 2 isomers, respectively. By means of liquid chromatography-mass spectrometry (negative ion electrospray mode) and NMR spectroscopy (by (1)H-NMR, correlation spectroscopy, and nuclear Overhauser effect spectroscopy techniques) five metabolites of FICZ were identified, and their structures were elucidated. The molecular weights of the two M3 isomers were 300 and both M2 and M1 compounds demonstrated molecular weights of 316, corresponding to addition of one (M3) and of two oxygen (M2 and M1), respectively. The structures were assigned as 2- and 8-hydroxy (M3), 2,10- and 4,8-dihydroxy (M2) and 2,8-dihydroxy derivatives of indolo[3,2-b]carbazole-6-carboxaldehyde (6-formylindolo[3,2-b]carbazole). PMID:12527705

  9. Synthesis, topoisomerase I and II inhibitory activity, cytotoxicity, and structure-activity relationship study of 2-phenyl- or hydroxylated 2-phenyl-4-aryl-5H-indeno[1,2-b]pyridines.

    Science.gov (United States)

    Kadayat, Tara Man; Song, Chanju; Shin, Somin; Magar, Til Bahadur Thapa; Bist, Ganesh; Shrestha, Aarajana; Thapa, Pritam; Na, Younghwa; Kwon, Youngjoo; Lee, Eung-Seok

    2015-07-01

    A series of novel twenty-eight rigid 2-phenyl- or hydroxylated 2-phenyl-4-aryl-5H-indeno[1,2-b]pyridines were synthesized and evaluated for their topoisomerase inhibitory activity as well as their cytotoxicity against several human cancer cell lines. Generally, hydroxylated compounds (16-18, 22-25, and 29-31) containing furyl or thienyl moiety at 4-position of central pyridine exhibited strong topoisomerase I and II inhibitory activity compared to positive control, camptothecin and etoposide, respectively, in low micromolar range. Structure-activity relationship study revealed that indenopyridine compounds with hydroxyl group at 2-phenyl ring in combination with furyl or thienyl moiety at 4-position are important for topoisomerase inhibition. Compounds (22-25) which contain hydroxyl group at meta position of the 2-phenyl ring at 2-position and furanyl or thienyl substitution at 4-position of indenopyridine, showed concrete correlations between topo I and II inhibitory activity, and cytotoxicity against evaluated human cancer cell lines. PMID:26022080

  10. Walking a supramolecular tightrope: a self-assembled dodecamer from an 8-aryl-2'-deoxyguanosine derivative.

    Science.gov (United States)

    Rivera-Sánchez, María del C; Andújar-de-Sanctis, Ivonne; García-Arriaga, Marilyn; Gubala, Vladimir; Hobley, Gerard; Rivera, José M

    2009-08-01

    Controlling the properties of self-assembled supramolecules via intrinsic parameters (i.e., structural information in the subunits) enables the reliable construction of assemblies of well-defined size and composition. Here we show that an optimum balance between repulsive (e.g., steric) and attractive (e.g., pi-pi, dipole-dipole) noncovalent interactions between subunits of a lipophilic 8-(3-pyridyl)-2'-deoxyguanosine derivative enables the high fidelity formation of a stable and discrete self-assembled dodecamer. In contrast, the isosteric 8-phenyl-2'-deoxyguanosine derivative assembles into an octamer because it cannot engage in additional dipole-dipole interactions. Adding dodecamers to a supramolecular construction toolbox, already containing octamers and hexadecamers made from other 8-aryl-2'-deoxyguanosine derivatives, should enable the preparation of a wide variety of self-assembled nanostructures where the size and the number of functional elements can be precisely fine-tuned for specific applications. PMID:19722619

  11. The Use of Aryl Hydrazide Linkers for the Solid Phase Synthesis of Chemically Modified Peptides

    Energy Technology Data Exchange (ETDEWEB)

    Woo, Y; Mitchell, A R; Camarero, J A

    2006-11-03

    Since Merrifield introduced the concept of solid phase synthesis in 1963 for the rapid preparation of peptides, a large variety of different supports and resin-linkers have been developed that improve the efficiency of peptide assembly and expand the myriad of synthetically feasible peptides. The aryl hydrazide is one of the most useful resin-linkers for the synthesis of chemically modified peptides. This linker is completely stable during Boc- and Fmoc-based solid phase synthesis and yet it can be cleaved under very mild oxidative conditions. The present article reviews the use of this valuable linker for the rapid and efficient synthesis of C-terminal modified peptides, head-to-tail cyclic peptides and lipidated peptides.

  12. Preparation of MIP grafts for quercetin by tandem aryl diazonium surface chemistry and photopolymerization

    International Nuclear Information System (INIS)

    The food antioxidant quercetin was used as a template in an ultrathin molecularly imprinted polymer (MIP) film prepared by photopolymerization. Indium tin oxide (ITO) plates were electrografted with aryl layers via a diazonium salt precursor bearing two terminal hydroxyethyl groups. The latter act as hydrogen donors for the photosensitizer isopropylthioxanthone and enabled the preparation of MIP grafts through radical photopolymerization of methacrylic acid (the functional monomer) and ethylene glycol dimethacrylate (the crosslinker) in the presence of quercetin (the template) on the ITO. The template was extracted, and the remaining ITO electrode used for the amperometric determination of quercetin at a working potential of 0.26 V (vs. SCE). The analytical range is from 5.10?8 to 10?4 mol L?1, and the detection limit is 5.10?8 mol L?1. (author)

  13. Dendritic ionic liquids based on imidazolium-modified poly(aryl ether) dendrimers.

    Science.gov (United States)

    Qin, Tianyi; Li, Xuying; Chen, Jinping; Zeng, Yi; Yu, Tianjun; Yang, Guoqiang; Li, Yi

    2014-12-01

    A series of dendritic ionic liquids (DILs) based on imidazolium-modified poly(aryl ether) dendrimers IL-Br-Gn (n=0-3) were synthesized by a modified convergent approach and "click" chemistry. The resulting DILs exhibited high thermal resistance with decomposition temperatures up to 270 °C and low glass transition temperatures in the range of approximately -5-0 °C. All IL-Br-Gn were found to be miscible with water at any ratio and could encapsulate hydrophobic molecules. The reversible phase transfer of the DILs between the aqueous and organic phases was accomplished by simple anion exchange between the hydrophilic Br(-) anion and the hydrophobic bis(trifluoromethylsulfonyl)amide anion (NTf2(-)). IL-Br-Gn could be used as transporters to shuttle hydrophobic molecules between the organic and aqueous phases efficiently. The present work provides a new kind of transporting materials with potential applications in substance separation, drug delivery, and biomolecule transport. PMID:25318861

  14. Novel routes in flame retardancy of bisphenol A polycarbonate/impact modifier/aryl phosphate blends

    Energy Technology Data Exchange (ETDEWEB)

    Wawrzyn, Eliza

    2013-07-01

    The massive use of electronic engineering products accompanied by high demands on fire safety has led to increasing interest in environmentally friendly flame retardancy of bisphenol A polycarbonate (PC) based materials. In this work, novel routes for enhancing the flame retardancy of PC/Impact Modifier/Aryl phosphate were studied with respect to pyrolysis (TG, TG-FTIR, ATR-FTIR, NMR), flammability (LOI and UL 94) and fire behavior (cone calorimeter at different irradiations). To improve charring of PC/ABS{sub PTFE}+Aryl phosphate, the exchange of bisphenol A bis(diphenyl phosphate) (BDP) with novel aryl phosphates was proposed. Two novel flame retardants were synthesized: 3,3,5-trimethylcyclohexylbisphenol-bis(diphenyl phosphate) (TMC-BDP) and bisphenol A-bis(diethylphosphate) (BEP). TMC-BDP was more stable than BDP, thus gave a potential to increase the chemical reactions between the components of the PC/ABS{sub PTFE}+Aryl phosphate, whereas more reactive BEP was expected to increase the cross linking activity with the polymer matrix. Nevertheless, the corresponding blends did not enhance the flame retardancy compared to PC/ABS{sub PTFE}+BDP. BEP in PC/ABS{sub PTFE} preferred to cross-link with itself instead of with PC, thus it showed poor fire protection performance. TMC-BDP gave as good results as BDP in PC/ABS PTFE material. The results delivered evidence that BDP possesses a high degree of optimization in PC/ABS{sub PTFE} system. To provide a novel impact modifier improving not only mechanical properties but also the fire retardancy of PC/BDP material, the replacement of highly flammable acrylonitrile-butadiene-styrene (ABS) with silicon acrylate rubber (SiR) with high content of polydimethylsiloxane (PDMS) was studied. In PC/SiR{sub PTFE}/BDP the replacement of ABS is beneficial, but PDMS worsened the BDP gas phase and condensed phase action. PDMS reacted also with PC during combustion. PDMS-PC and PDMS-BDP interactions led to silicon dioxide. In fact, the inorganic residue of PC/SiR{sub PTFE}/BDP contributed to fire residue and greatly improved the LOI of about 10 % in comparison to PC/ABS{sub PTFE}+BDP system. Thus, the use of SiR with high PDMS content is proposed as replacement of ABS in PC/Impact Modifier/BDP blend. To enhance the fire protection, the PC/SiR{sub PTFE}/BDP was combined with several adjuvants: (i) layered fillers: talc and organically modified layered silicate (LS), (ii) metal hydroxides: magnesium hydroxide (Mg(OH){sub 2}) and boehmite (AlO(OH)), (iii) metal oxides and carbonate: magnesium oxide (MgO) and silicium dioxide (SiO{sub 2}) and calcium carbonate (CaCO{sub 3}) as well as (iiii) hydrated metal borates: zinc borate (ZnB), calcium borate (CaB) and magnesium borate (MgB). It was demonstrated that the blend PC/SiR{sub PTFE}/BDP+filler is very sensitive to chemical (e.g. hydrolysis) and physical (e.g. viscosity) effects. Additionally, the large deformations of PC/SiR{sub PTFE}/BDP materials make difficult to optimize the char. Overall, the ZnB, MgB and CaB are proposed for enhancing the flame retardancy of PC/SiR/BDP with respect to flammability results, reduction of fire hazard and maximum of heat release rate. The results of this work enable the under standing of various mechanisms controlling the fire behavior and thus effective selection of the most appropriate flame retardant, impact modifier and inorganic fillers for producing fire resistant PC based polymers.

  15. Palladium Catalyzed Heck Arylation of 2,3-Dihydrofuran—Effect of the Palladium Precursor

    Directory of Open Access Journals (Sweden)

    Adam Morel

    2014-06-01

    Full Text Available Heck arylation of 2,3-dihydrofuran with iodobenzene was carried out in systems consisting of different palladium precursors (Pd2(dba3, Pd(acac2, PdCl2(cod, [PdCl(allyl]2, PdCl2(PhCN2, PdCl2(PPh32 and ionic liquids (CILs with L-prolinate or L-lactate anions. All the tested CILs caused remarkable increases of the conversion values and in all of the reactions 2-phenyl-2,3-dihydrofuran (3 was obtained as the main product with a yield of up to 59.2%. The highest conversions of iodobenzene were achieved for the [PdCl(allyl]2 precursor. Formation of Pd(0 nanoparticles, representing the resting state of the catalyst, was evidenced by TEM.

  16. A mechanistic investigation of the ruthenium porphyrin catalysed aziridination of olefins by aryl azides.

    Science.gov (United States)

    Zardi, P; Pozzoli, A; Ferretti, F; Manca, G; Mealli, C; Gallo, E

    2015-05-27

    A mechanism for the aziridination of olefins by aryl azides (ArN3), promoted by ruthenium(ii) porphyrin complexes, is proposed on the basis of kinetic and theoretical studies. All the recorded data support the involvement of a mono-imido ruthenium complex as the active intermediate in the transfer of the nitrene moiety "ArN" to the olefin. The selectivity of the aziridination vs. the uncatalysed triazoline formation can be enhanced by fine-tuning the electronic features of the porphyrin ligand and the olefin/azide catalytic ratio. The DFT study highlights the importance of an accessible triplet ground state of the intermediate ruthenium mono-imido complex to allow the evolution of the aziridination process. PMID:25978346

  17. KEGG COMPOUND / Ammonium hydroxide [KEGG COMPOUND

    Lifescience Database Archive (English)

    Full Text Available COMPOUND: C01358 Entry C01358Compound Name NH4OH; Ammonium hydroxide Formula NH4. OH Exact mass ... s 223Expectorants 2232Ammonium salts D04594Ammonia water ... (JP16) 26Epidermides 264Analgesics, anti-itchings, ... lammatory agents 2643Ammonium agents D04594Ammonia water ... (JP16) Classification of Japanese OTC drugs [BR:br ...

  18. Aryl Hydrocarbon Receptor (AHR)-Active Pharmaceuticals Are Selective AHR Modulators in MDA-MB-468 and BT474 Breast Cancer Cells

    OpenAIRE

    Jin, Un-ho; Lee, Syng-ook; Safe, Stephen

    2012-01-01

    Leflunomide, flutamide, nimodipine, mexiletine, sulindac, tranilast, 4-hydroxytamoxifen, and omeprazole are pharmaceuticals previously characterized as aryl hydrocarbon receptor (AHR) agonists in various cell lines and animal models. In this study, the eight AHR-active pharmaceuticals were investigated in highly aggressive aryl hydrocarbon (Ah)-responsive BT474 and MDA-MB-468 breast cancer cell lines, and their effects on AHR protein, CYP1A1 (protein and mRNA), CYP1B1 (mRNA), and cell migrati...

  19. Synthesis of 2-(2-R1-Hydrazino-5-(R2-benzyl-2-thiazolines on the Basis of Meerweins Arylation Products of Allyl Isothiocyanate

    Directory of Open Access Journals (Sweden)

    Mykola I. Ganushchak

    2003-02-01

    Full Text Available 3-Aryl-2-chloropropylisothiocyanates (1 are formed by interaction of arenediazonium chlorides with allyl isothiocyanate. Adducts 1 react with monoacylhydrazines to form 1-acyl-4-(3-aryl-2-chloropropylthiosemicarbazides (2a–d. Thiosemicarbazides 2a–d in the presence of bases selectively transform into 2-(2-R1-hydrazino-5-(R2-benzyl-2-thiazolines (3a–d.

  20. Synthesis of 2-(2-R1-Hydrazino)-5-(R2-benzyl)-2-thiazolines on the Basis of Meerweins Arylation Products of Allyl Isothiocyanate

    OpenAIRE

    Ganushchak, Mykola I.; Obushak, Mykola D.; Karpyak, Volodymyr V.

    2003-01-01

    3-Aryl-2-chloropropylisothiocyanates (1) are formed by interaction of arenediazonium chlorides with allyl isothiocyanate. Adducts 1 react with monoacylhydrazines to form 1-acyl-4-(3-aryl-2-chloropropyl)thiosemicarbazides (2a–d). Thiosemicarbazides 2a–d in the presence of bases selectively transform into 2-(2-R1-hydrazino)-5-(R2-benzyl)-2-thiazolines (3a–d).

  1. Síntese e avaliação preliminar da atividade antinociceptiva de novas isoxazolil-aril-hidrazonas Synthesis and preliminary evaluation of antinociceptive activity of novel isoxazolyl-aryl-hydrazones

    Directory of Open Access Journals (Sweden)

    Sílvio Leandro Gonçalves Bomfim Reis

    2011-01-01

    Full Text Available New 2-isoxazoline aldehydes were synthesized, in good yields, from cycloadduct of the 1,3-dipolar cycloaddition reaction between endocyclic enecarbamate and carboethoxyformonitrile oxide (CEFNO. Condensation of these 2-isoxazoline aldehydes with several phenyl-hydrazines produced new isoxazolyl-aryl-hydrazones, which showed low toxicity and excellent antinociceptive activity, when compared to dipyrone. The antinociceptive activity of isoxazolyl-aryl-hydrazones was performed using the acetic acid-induced mice abdominal constrictions test.

  2. Síntese e avaliação preliminar da atividade antinociceptiva de novas isoxazolil-aril-hidrazonas Synthesis and preliminary evaluation of antinociceptive activity of novel isoxazolyl-aryl-hydrazones

    OpenAIRE

    Sílvio Leandro Gonçalves Bomfim Reis; Valderes Moraes de Almeida; Gleybson Correia de Almeida; Karinna Moura Boaviagem; Charles Christophe Du Barriere Mendes; Antônio Rodolfo de Faria; Alexandre José da Silva Góes; Laudelina Rodrigues Magalhães; Teresinha Gonçalves da Silva

    2011-01-01

    New 2-isoxazoline aldehydes were synthesized, in good yields, from cycloadduct of the 1,3-dipolar cycloaddition reaction between endocyclic enecarbamate and carboethoxyformonitrile oxide (CEFNO). Condensation of these 2-isoxazoline aldehydes with several phenyl-hydrazines produced new isoxazolyl-aryl-hydrazones, which showed low toxicity and excellent antinociceptive activity, when compared to dipyrone. The antinociceptive activity of isoxazolyl-aryl-hydrazones was performed using the acetic ...

  3. Natrolite zeolite supported copper nanoparticles as an efficient heterogeneous catalyst for the 1,3-diploar cycloaddition and cyanation of aryl iodides under ligand-free conditions.

    Science.gov (United States)

    Nasrollahzadeh, Mahmoud; Sajadi, S Mohammad; Rostami-Vartooni, Akbar; Khalaj, Mehdi

    2015-09-01

    In this paper, we report the preparation of Natrolite zeolite supported copper nanoparticles as a heterogeneous catalyst for 1,3-diploar cycloaddition and synthesis aryl nitriles from aryl iodides under ligand-free conditions. The catalyst was characterized using XRD, SEM, TEM, EDS and TG-DTA. The experimental procedure is simple, the products are formed in high yields and the catalyst can be recycled and reused several times without any significant loss of catalytic activity. PMID:25988488

  4. Synthesis and preliminary evaluation of antinociceptive activity of novel isoxazolyl-aryl-hydrazones; Sintese e avaliacao preliminar de atividade antinociceptiva de novas isoxazolil-aril-hidrazonas

    Energy Technology Data Exchange (ETDEWEB)

    Reis, Silvio Leandro Goncalves Bomfim; Almeida, Valderes Moraes de; Almeida, Gleybson Correia de; Boaviagem, Karinna Moura; Mendes, Charles Christophe du Barriere; Faria, Antonio Rodolfo de, E-mail: rodolfo@ufpe.b [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil). Dept. de Ciencias Farmaceuticas; Goes, Alexandre Jose da Silva; Magalhaes, Laudelina Rodrigues; Silva, Teresinha Goncalves da [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil). Dept. de Antibioticos

    2011-07-01

    New 2-isoxazoline aldehydes were synthesized, in good yields, from cycloadduct of the 1,3-dipolar cycloaddition reaction between endocyclic enecarbamate and carboethoxyformonitrile oxide (CEFNO). Condensation of these 2-isoxazoline aldehydes with several phenyl-hydrazines produced new isoxazolyl-aryl-hydrazones, which showed low toxicity and excellent antinociceptive activity, when compared to dipyrone. The antinociceptive activity of isoxazolyl-aryl-hydrazones was performed using the acetic acid-induced mice abdominal constrictions test. (author)

  5. Regioselective iodination of aryl amines using 1,4-dibenzyl-1,4-diazoniabicyclo [2.2.2] octane dichloroiodate in solution and under solvent-free conditions

    Directory of Open Access Journals (Sweden)

    M. Alikarami

    2015-01-01

    Full Text Available 1,4-Dibenzyl-1,4-diazoniabicyclo[2.2.2]octane dichloroiodate is an efficient and regioselective reagent for iodination of aryl amines. A wide variety of aryl amines in reaction with this reagent afforded regioselectively iodinated products. The iodination reaction can be carried out in solution or under solvent-free condition at room temperature. DOI: http://dx.doi.org/10.4314/bcse.v29i1.15

  6. Enantiodiscrimination of racemic electrophiles by diketopiperazine enolates: asymmetric synthesis of methyl 2-amino-3-aryl-butanoates and 3-methyl-aspartates

    OpenAIRE

    Bull, Sd; Davies, Sg; Epstein, Sw; Garner, Ac; Mujtaba, N.; Roberts, Pm; Savory, Ed; Smith, Ad; Tamayo, Ja; Watkin, Dj

    2006-01-01

    Enolates of (S)-N,N?-bis-(p-methoxybenzyl)-3-iso-propylpiperazine-2,5-dione exhibit high levels of enantiodiscrimination in alkylations with (RS)-1-aryl-1-bromoethanes and (RS)-2-bromoesters, affording substituted diketopiperazines containing two new stereogenic centres in high de. Deprotection and hydrolysis of the resultant substituted diketopiperazines provides a route to the asymmetric synthesis of homochiral methyl 2-amino-3-aryl-butanoates and 3-methyl-aspartates in high de and ee. ©...

  7. Site-directed mutagenesis of selected residues at the active site of aryl-alcohol oxidase, an H2O2-producing ligninolytic enzyme.

    OpenAIRE

    Ferreira, P.; Ruiz-duenas, F. J.; Martinez, M. J.; Berkel, W. J. H.; Martinez, A. T.

    2006-01-01

    Aryl-alcohol oxidase provides H2O2 for lignin biodegradation, a key process for carbon recycling in land ecosystems that is also of great biotechnological interest. However, little is known of the structural determinants of the catalytic activity of this fungal flavoenzyme, which oxidizes a variety of polyunsaturated alcohols. Different alcohol substrates were docked on the aryl-alcohol oxidase molecular structure, and six amino acid residues surrounding the putative substrate-binding site we...

  8. Purification and Characterization of an NAD+-Dependent XylB-Like Aryl Alcohol Dehydrogenase Identified in Acinetobacter baylyi ADP1

    OpenAIRE

    Uthoff, Stefan; Steinbu?chel, Alexander

    2012-01-01

    The gene xylBADP1 from Acinetobacter baylyi ADP1 (gene annotation number ACIAD1578), coding for a putative aryl alcohol dehydrogenase, was heterologously expressed in Escherichia coli BL21(DE3). The respective aryl alcohol dehydrogenase was purified by fast protein liquid chromatography to apparent electrophoretic homogeneity. The predicted molecular weight of 39,500 per subunit was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. According to the native Mw as determine...

  9. Palladium-catalyzed allylation of aryl halides with homoallyl alcohols bearing a trisubstituted double bond: application to chirality transfer from hydroxylated carbon to benzylic one.

    Science.gov (United States)

    Wakabayashi, Ryota; Fujino, Daishi; Hayashi, Sayuri; Yorimitsu, Hideki; Oshima, Koichiro

    2010-07-01

    A facile route to homoallyl alcohols bearing a trisubstituted double bond has been devised. The palladium-catalyzed reactions of aryl halides with the alcohols thus synthesized result in regiospecific allyl transfer from the alcohols to aryl halides via retro-allylation, providing allylarenes having two substituents at the 1 and 2 positions of the allyl moiety. Optically active homoallyl alcohols transfer their chirality at the hydroxylated carbon to the benzylic carbon of the product. PMID:20545371

  10. Kinetic and chemical characterization of aldehyde oxidation by fungal aryl-alcohol oxidase.

    Science.gov (United States)

    Ferreira, Patricia; Hernández-Ortega, Aitor; Herguedas, Beatriz; Rencoret, Jorge; Gutiérrez, Ana; Martínez, María Jesús; Jiménez-Barbero, Jesús; Medina, Milagros; Martínez, Angel T

    2010-02-01

    Fungal AAO (aryl-alcohol oxidase) provides H2O2 for lignin biodegradation. AAO is active on benzyl alcohols that are oxidized to aldehydes. However, during oxidation of some alcohols, AAO forms more than a stoichiometric number of H2O2 molecules with respect to the amount of aldehyde detected due to a double reaction that involves aryl-aldehyde oxidase activity. The latter reaction was investigated using different benzylic aldehydes, whose oxidation to acids was demonstrated by GC-MS. The steady- and presteady state kinetic constants, together with the chromatographic results, revealed that the presence of substrate electron-withdrawing or electron-donating substituents had a strong influence on activity; the highest activity was with p-nitrobenzaldehyde and halogenated aldehydes and the lowest with methoxylated aldehydes. Moreover, activity was correlated to the aldehyde hydration rates estimated by 1H-NMR. These findings, together with the absence in the AAO active site of a residue able to drive oxidation via an aldehyde thiohemiacetal, suggested that oxidation mainly proceeds via the gem-diol species. The reaction mechanism (with a solvent isotope effect, 2H2Okred, of approx. 1.5) would be analogous to that described for alcohols, the reductive half-reaction involving concerted hydride transfer from the alpha-carbon and proton abstraction from one of the gem-diol hydroxy groups by a base. The existence of two steps of opposite polar requirements (hydration and hydride transfer) explains some aspects of aldehyde oxidation by AAO. Site-directed mutagenesis identified two histidine residues strongly involved in gem-diol oxidation and, unexpectedly, suggested that an active-site tyrosine residue could facilitate the oxidation of some aldehydes that show no detectable hydration. Double alcohol and aldehyde oxidase activities of AAO would contribute to H2O2 supply by the enzyme. PMID:19891608

  11. A selective aryl hydrocarbon receptor modulator 3,3'-Diindolylmethane inhibits gastric cancer cell growth

    Directory of Open Access Journals (Sweden)

    Yin Xiao-Fei

    2012-05-01

    Full Text Available Abstract Background Aryl hydrocarbon receptor (AhR is a ligand-activated transcription factor associated with gastric carcinogenesis. 3,3'-Diindolylmethane (DIM is a relatively non-toxic selective AhR modulator. This study was to detect the effects of DIM on gastric cancer cell growth. Methods Gastric cancer cell SGC7901 was treated with DIM at different concentrations (0,10,20,30,40,50??mol/L with or without an AhR antagonist, resveratrol. The expression of AhR and Cytochrome P4501A1 (CYP1A1, a classic target gene of AhR pathway, were detected by RT-PCR and Western blot; cell viability was measured by MTT assay, and the changes in cell cycle and apoptosis were analyzed by flow cytometry. Results RT-PCR and western-blot showed that with the increase of the concentration of DIM, AhR protein gradually decreased and CYP1A1 expression increased, suggesting that DIM activated the AhR pathway and caused the translocation of AhR from cytoplasm to nucleus. MTT assay indicated that the viability of SGC7901 cells was significantly decreased in a concentration- and time-dependent manner after DIM treatment and this could be partially reversed by resveratrol. Flow cytometry analysis showed that DIM arrested cell cycle in G1 phase and induced cell apoptosis. Conclusion Selective aryl hydrocarbon receptor modulator 3,3'-Diindolylmethane inhibits SGC7901 cell proliferation by inducing apoptosis and delaying cell cycle progression. AhR may be a potential therapeutic target for gastric cancer treatment.

  12. Efficacious N-protection of O-aryl sulfamates with 2,4-dimethoxybenzyl groups.

    Science.gov (United States)

    Reuillon, Tristan; Bertoli, Annalisa; Griffin, Roger J; Miller, Duncan C; Golding, Bernard T

    2012-10-01

    Sulfamates are important functional groups in certain areas of current medicinal chemistry and drug development. Alcohols and phenols are generally converted into the corresponding primary sulfamates (ROSO(2)NH(2) and ArOSO(2)NH(2), respectively) by reaction with sulfamoyl chloride (H(2)NSO(2)Cl). The lability of the O-sulfamate group, especially to basic conditions, usually restricts this method to a later stage of a synthesis. To enable a more flexible approach to the synthesis of phenolic O-sulfamates, a protecting group strategy for sulfamates has been developed. Both sulfamate NH protons were replaced with either 4-methoxybenzyl or 2,4-dimethoxybenzyl. These N-protected sulfamates were stable to oxidising and reducing agents, as well as bases and nucleophiles, thus rendering such masked sulfamates suitable for multi-step synthesis. The protected sulfamates were synthesised by microwave heating of 1,1'-sulfonylbis(2-methyl-1H-imidazole) with a substituted phenol to give an aryl 2-methyl-1H-imidazole-1-sulfonate. This imidazole-sulfonate was N-methylated by reaction with trimethyloxonium tetrafluoroborate, which enabled subsequent displacement of 1,2-dimethylimidazole by a dibenzylamine (e.g. bis-2,4-dimethoxybenzylamine). The resulting N-diprotected, ring-substituted phenol O-sulfamates were further manipulated through reactions at the aryl substituent and finally deprotected with trifluoroacetic acid to afford a phenol O-sulfamate. The use of 2,4-dimethoxybenzyl was particularly attractive because deprotection occurred quantitatively within 2 h at room temperature with 10% trifluoroacetic acid in dichloromethane. The four key steps in the protocol described [reaction of 1,1'-sulfonylbis(2-methyl-1H-imidazole) with a phenol, methylation, displacement with a dibenzylamine and deprotection] all proceeded in very high yields. PMID:22893112

  13. A highly versatile catalyst system for the cross-coupling of aryl chlorides and amines.

    Science.gov (United States)

    Lundgren, Rylan J; Sappong-Kumankumah, Antonia; Stradiotto, Mark

    2010-02-01

    The syntheses of 2-(di-tert-butylphosphino)-N,N-dimethylaniline (L1, 71%) and 2-(di-1-adamantylphosphino)-N,N-dimethylaniline (L2, 74 %), and their application in Buchwald-Hartwig amination, are reported. In combination with [Pd(allyl)Cl](2) or [Pd(cinnamyl)Cl](2), these structurally simple and air-stable P,N ligands enable the cross-coupling of aryl and heteroaryl chlorides, including those bearing as substituents enolizable ketones, ethers, esters, carboxylic acids, phenols, alcohols, olefins, amides, and halogens, to a diverse range of amine and related substrates that includes primary alkyl- and arylamines, cyclic and acyclic secondary amines, N-H imines, hydrazones, lithium amide, and ammonia. In many cases, the reactions can be performed at low catalyst loadings (0.5-0.02 mol % Pd) with excellent functional group tolerance and chemoselectivity. Examples of cross-coupling reactions involving 1,4-bromochlorobenzene and iodobenzene are also reported. Under similar conditions, inferior catalytic performance was achieved when using Pd(OAc)(2), PdCl(2), [PdCl(2)(cod)] (cod = 1,5-cyclooctadiene), [PdCl(2)(MeCN)(2)], or [Pd(2)(dba)(3)] (dba = dibenzylideneacetone) in combination with L1 or L2, or by use of [Pd(allyl)Cl](2) or [Pd(cinnamyl)Cl](2) with variants of L1 and L2 bearing less basic or less sterically demanding substituents on phosphorus or lacking an ortho-dimethylamino fragment. Given current limitations associated with established ligand classes with regard to maintaining high activity across the diverse possible range of C-N coupling applications, L1 and L2 represent unusually versatile ligand systems for the cross-coupling of aryl chlorides and amines. PMID:20024992

  14. Probing Complex Free-Radical Reaction Pathways of Fuel Model Compounds

    Energy Technology Data Exchange (ETDEWEB)

    Buchanan III, A C [ORNL; Kidder, Michelle [ORNL; Beste, Ariana [ORNL; Britt, Phillip F [ORNL

    2012-01-01

    Fossil (e.g. coal) and renewable (e.g. woody biomass) organic energy resources have received considerable attention as possible sources of liquid transportation fuels and commodity chemicals. Knowledge of the reactivity of these complex materials has been advanced through fundamental studies of organic compounds that model constituent substructures. In particular, an improved understanding of thermochemical reaction pathways involving free-radical intermediates has arisen from detailed experimental kinetic studies and, more recently, advanced computational investigations. In this presentation, we will discuss our recent investigations of the fundamental pyrolysis pathways of model compounds that represent key substructures in the lignin component of woody biomass with a focus on molecules representative of the dominant beta-O-4 aryl ether linkages. Additional mechanistic insights gleaned from DFT calculations on the kinetics of key elementary reaction steps will also be presented, as well as a few thoughts on the significant contributions of Jim Franz to this area of free radical chemistry.

  15. Copper-catalyzed formal C - H carboxylation of aromatic compounds with carbon dioxide through arylaluminum intermediates.

    Science.gov (United States)

    Ueno, Atsushi; Takimoto, Masanori; O, Wylie W N; Nishiura, Masayoshi; Ikariya, Takao; Hou, Zhaomin

    2015-04-01

    The C - H bond carboxylation of various aromatic compounds with CO2 was achieved by the deprotonative alumination with a mixed alkyl amido lithium aluminate compound iBu3 Al(TMP)Li followed by the NHC-copper-catalyzed carboxylation of the resulting arylaluminum species, which afforded the corresponding carboxylation products in high yield and high selectivity. In addition to benzene derivatives, heteroarenes such as benzofuran, benzothiophene, and indole derivatives are also suitable substrates. Functional groups such as Cl, Br, I, vinyl, amide, and CN could survive the reaction conditions. Some key reaction intermediates such as the copper aryl and isobutyl complexes and their carboxylation products were isolated and structurally characterized by X-ray crystallographic analyses, thus offering important information on the reaction mechanism. PMID:25491488

  16. Synthesis and Reactions of Some New Heterocyclic Carbohydrazides and Related Compounds as Potential Anticancer Agents

    Directory of Open Access Journals (Sweden)

    Nasser S. A. M. Khalil

    2003-10-01

    Full Text Available Acylation of 3-hydrazino-5,6-diphenyl-1,2,4-triazine (2 and hydrazine hydrate (7 with 4-aryl-1,3,7-triphenyl-8-oxa-1,2,6-triazaspiro[4.4]nona-2,6-dien-9-ones 5a,b gave the corresponding heterocyclic carbohydrazides 6a,b and 8a,b respectively. Conversion of compounds 8a,b into the versatile carbohydrazide derivatives 9a-g, 10, 13 and the related oxadiazoles 11, 12a,b was undertaken. A primary in vitro test of compound 8a (concentration 10-4 M showed activity against leukemia cell lines (CCRFCEM, K-256, MOLT-4, PRMI-8226, SR.

  17. Synthesis of a novel C2-aryl pyrrolo[2,1-c][1,4]benzodiazepine-5,11-dione library: effect of C2-aryl substitution on cytotoxicity and non-covalent DNA binding.

    Science.gov (United States)

    Antonow, Dyeison; Jenkins, Terence C; Howard, Philip W; Thurston, David E

    2007-04-15

    A 23-member C2-aryl pyrrolo[2,1-c][1,4]benzodiazepine-5,11-dione (PBD dilactam) library has been synthesized using Suzuki coupling, and the effect of base upon racemisation at the C11a-position during the cross-coupling reaction studied. Three library members (21, 30 and 33) were sufficiently cytotoxic in the NCI's preliminary screen to warrant further evaluation, and one (30, R=p-Br) was found to be cytotoxic at the sub-micromolar level in the A498 renal cancer cell line. DNA thermal denaturation studies suggested that this activity may be associated with non-covalent DNA interaction, and also demonstrated that introduction of C2-C3 unsaturation and addition of C2-aryl functionalities to the PBD dilactam skeleton significantly enhanced helix stabilisation compared to the unsubstituted PBD dilactam (6). PMID:17317191

  18. Volatile Organic Compounds (VOCs)

    Science.gov (United States)

    ... Air Introduction to IAQ Volatile Organic Compounds An Introduction to Indoor Air Quality (IAQ) Volatile Organic Compounds ( ... cause, cancer in humans. Search EPA's Integrated Risk Information System (IRIS) (a compilation of electronic reports on specific ...

  19. WITTIG REACTION APPROACH FOR THE SYNTHESIS OF 7-METHOXY-2-[4- ALKYL/ARYL]-L-BENZOFURAN-5-CARBOXALDEHYDE Wittig-Reaktion Ansatz für die Synthese von 7-Methoxy-2-[4 - ALKYL / ARYL]-L-BENZOFURAN-5-CARBOXALDEHYDE

    Directory of Open Access Journals (Sweden)

    Bapu R Thorata, Dyneshwar Shelke, Ramdas Atram and Ramesh Yamgar

    2013-07-01

    Full Text Available Vanillin undergoes sequence of reaction forming phosphonium salt through dimethyaminomethyl derivative (Mannich reaction. The synthesis of phosphonium salt can be achieved by sequence of three steps which was condense with series of aliphatic/aromatic acid chlorides by refluxing in toluene in presence of triethylamine (Wittig reaction as key step resulting 7-methoxy-2-alkyl/aryl-l-benzofuran-5-carboxaldehyde. The crude product was purified by using column chromatography and characterized by FTIR, NMR and Mass spectroscopy.

  20. Aryl Hydrocarbon Receptor Repressor and TiPARP (ARTD14 Use Similar, but also Distinct Mechanisms to Repress Aryl Hydrocarbon Receptor Signaling

    Directory of Open Access Journals (Sweden)

    Laura MacPherson

    2014-05-01

    Full Text Available The aryl hydrocarbon receptor (AHR regulates the toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD. The AHR repressor (AHRR is an AHR target gene and functions as a ligand-induced repressor of AHR; however, its mechanism of inhibition is controversial. Recently, we reported that TCDD-inducible poly (ADP-ribose polymerase (TiPARP; ARTD14 also acts as a repressor of AHR, representing a new player in the mechanism of AHR action. Here we compared the ability of AHRR- and TiPARP-mediated inhibition of AHR activity. TCDD increased AHRR mRNA levels and recruitment of AHRR to cytochrome P450 1A1 (CYP1A1 in MCF7 cells. Knockdown of TiPARP, but not AHRR, increased TCDD-induced CYP1A1 mRNA and AHR protein levels. Similarly, immortalized TiPARP?/? mouse embryonic fibroblasts (MEFs and AHRR?/? MEFs exhibited enhanced AHR transactivation. However, unlike TiPARP?/? MEFs, AHRR?/? MEFs did not exhibit increased AHR protein levels. Overexpression of TiPARP in AHRR?/? MEFs or AHRR?8, the active isoform of AHRR, in TiPARP?/? MEFs reduced TCDD-induced CYP1A1 mRNA levels, suggesting that they independently repress AHR. GFP-AHRR?8 and GFP-TiPARP expressed as small diffuse nuclear foci in MCF7 and HuH7 cells. GFP-AHRR?8_?1-49, which lacks its putative nuclear localization signal, localized to both the nucleus and the cytoplasm, while the GFP-AHRR?8_?1-100 mutant localized predominantly in large cytoplasmic foci. Neither GFP-AHRR?8_?1-49 nor GFP-AHRR?8_?1-100 repressed AHR. Taken together, AHRR and TiPARP repress AHR transactivation by similar, but also different mechanisms.

  1. Synthesis, Spectroscopy and Electrochemistry of New 3-(5-Aryl-4,5-Dihydro-1H-Pyrazol-3-yl-4-Hydroxy-2H-Chromene-2-One 4, 5 as a Novel Class of Potential Antibacterial and Antioxidant Derivatives

    Directory of Open Access Journals (Sweden)

    Abdullah Sulaiman Al-Ayed

    2011-09-01

    Full Text Available 3-((2E-3(arylprop-2-enoyl-2H-chromen-2-one 3 was synthesized from 4-hydroxy coumarin by refluxing 3-acetyl-4-hydroxy coumarin with aromatic aldehydes in chloroform in the presence of a catalytic amount of piperidine. 3 was converted to pyrazoles 4, 5 by treatment with hydrazine and phenylhydrazine in toluene, respectively. The structures of the new compounds were confirmed by elemental analysis, IR, and multinuclear/multidimensional NMR spectroscopy (1H, 13C-NMR, NOESY, HMBC which allowed us to assign the complete network of proton and carbon atoms. All the compounds exhibited one quasireversible redox process. All the newly synthesized compounds were screened for their antibacterial and antioxidant activities. Antimicrobial studies revealed that 3-(5-(2,5-dimethylphenyl-1-phenyl-4,5-dihydro-1H-pyrazol-3-yl-4- hydroxy-2H-chromene-2-one 5c showed significant antibacterial activity against Escherichia coli and Pseudomonas Aeruginosa 27853. Furthermore, 3-(5-(aryl-4,5-dihydro-1H-pyrazol-3-yl-4-hydroxy-2H-chromene- 2-ones 4, 5 showed antioxidant activities of different extents with respect to individual compounds as well as to the antioxidant methods. The 3-(5-(phenyl-4,5-dihydro-1H-pyrazol-3-yl-4-hydroxy-2H-chromene-2-ones 4a was found to be the most active antioxidant in the series and more active than trolox which makes the investigated complexes a new promising class of antibacterial compounds.

  2. Isotopically labelled compounds

    International Nuclear Information System (INIS)

    A comprehensive account of the title topic, divided into chapters as follows: Introduction (history, definition and nomenclature), Synthesis (hydrogen isotope compounds, carbon isotope compounds, compounds of isotopes of halogens, isotopes of other light elements (oxygen, nitrogen, phosphorus, sulfur), compounds of isotopes of heavier elements, particularly metals), Analysis (purity, chromatography, NMR spectroscopy, mass spectrometry, vibrational spectroscopy), and Applications (chemical reaction mechanisms, tracing methods, kinetic isotopic effects). (P.A.)

  3. Aryl hydrocarbon receptor-interacting protein gene mutations in familial isolated pituitary adenomas: analysis in 73 families.

    OpenAIRE

    Daly, Adrian; Vanbellinghen, Jean-franc?ois; Khoo, Sok Kean; Jaffrain-rea, Marie-lise; Naves, Luciana A.; Guitelman, Mirtha A.; Murat, Arnaud; Emy, Philippe; Gimenez-roqueplo, Anne-paule; Tamburrano, Guido; Raverot, Gerald; Barlier, Anne; Herder, Wouter; Penfornis, Alfred; Ciccarelli, Enrica

    2007-01-01

    CONTEXT: An association between germline aryl hydrocarbon receptor-interacting protein (AIP) gene mutations and pituitary adenomas was recently shown. OBJECTIVE: The objective of the study was to assess the frequency of AIP gene mutations in a large cohort of patients with familial isolated pituitary adenoma (FIPA). DESIGN: This was a multicenter, international, collaborative study. SETTING: The study was conducted in 34 university endocrinology and genetics departments in nine countries. PAT...

  4. Activation of the Aryl Hydrocarbon Receptor Sensitizes Mice to Nonalcoholic Steatohepatitis by Deactivating Mitochondrial Sirtuin Deacetylase Sirt3

    OpenAIRE

    He, Jinhan; Hu, Bingfang; Shi, Xiongjie; Weidert, Eric R.; Lu, Peipei; Xu, Meishu; Huang, Min; Kelley, Eric E.; Xie, Wen

    2013-01-01

    Nonalcoholic steatohepatitis (NASH) is a liver disorder that still demands improved treatment. Understanding the pathogenesis of NASH will help to develop novel approaches to prevent or treat this disease. In this study, we revealed a novel function of the aryl hydrocarbon receptor (AhR) in NASH. Transgenic or pharmacological activation of AhR heightened animal sensitivity to NASH induced by the methionine- and choline-deficient (MCD) diet, which was reasoned to be due to increased hepatic st...

  5. Aryl radical involvement in amiodarone-induced pulmonary toxicity: Investigation of protection by spin-trapping nitrones

    International Nuclear Information System (INIS)

    Amiodarone (AM), an antidysrrhythmic drug, can produce serious adverse effects, including potentially fatal AM-induced pulmonary toxicity (AIPT). AM-induced cytotoxicity and pulmonary fibrosis are well recognized, but poorly understood mechanistically. The hypothesis of aryl radical involvement in AM toxicity was tested in non-biological and biological systems. Photolysis of anaerobic aqueous solutions of AM, or N-desethylamiodarone (DEA) resulted in the formation of an aryl radical, as determined by spin-trapping and electron paramagnetic resonance (EPR) spectroscopy experiments. The non-iodinated AM analogue, didesiodoamiodarone (DDIA), did not form aryl radicals under identical conditions. The toxic susceptibility of human lung epithelioid HPL1A cells to AM, DEA, and DDIA showed time- and concentration-dependence. DEA had a more rapid and potent toxic effect (LC50 = 8 ?M) than AM (LC50 = 146 ?M), whereas DDIA cytotoxicity was intermediate (LC50 = 26 ?M) suggesting a minor contribution of the iodine atoms. Incubation of human lung epithelial cells with the spin-trapping nitrones ?-phenyl-N-t-butylnitrone (PBN, 10 mM) or ?-(4-pyridyl N-oxide)-N-t-butylnitrone (POBN, 5.0 mM) did not significantly protect against AM, DEA, or DDIA cytotoxicity. Intratracheal administration of AM to hamsters produced pulmonary fibrosis at day 21, which was not prevented by 4 days of treatment with 150 mg/kg/day PBN or 164 mg/kg/day POBN. However, theN or 164 mg/kg/day POBN. However, the body weight loss in AM-treated animals was counteracted by PBN. These results suggest that, although AM can generate an aryl radical photochemically, its in vivo formation may not be a major contributor to AM toxicity, and that spin-trapping reagents do not halt the onset of AM toxicity

  6. Tin-free three-component coupling reaction of aryl halides, norbornadiene (or norbornene), and alkynols using a palladium catalyst

    International Nuclear Information System (INIS)

    Good-to-excellent yields of 2,3-Disubstituted norbornenes (or norbornanes) were obtained using a Pd/Cu catalyzed three-component ternary coupling reaction of aryl halides, norbornadiene (or norbornene), and alkynols in toluene at 100 .deg. C in the presence of 5.5 M NaOH as a base and benzyltriethylammonium chloride as a phase transfer catalyst. The results of experiments using various aromatic halides suggest that the ternary coupling reaction is promoted by bromide

  7. Palladium-Catalyzed Heck Coupling Reaction of Aryl Bromides in Aqueous Media Using Tetrahydropyrimidinium Salts as Carbene Ligands

    Directory of Open Access Journals (Sweden)

    ?smail Özdemir

    2010-01-01

    Full Text Available An efficient and stereoselective catalytic system for the Heck cross coupling reaction using novel 1,3-dialkyl-3,4,5,6-tetrahydropyrimidinium salts (1, LHX and Pd(OAc2 loading has been reported. The palladium complexes derived from the salts 1a-f prepared in situ exhibit good catalytic activity in the Heck coupling reaction of aryl bromides under mild conditions.

  8. Aryl Hydrocarbon Receptor-Mediated Impairment of Chondrogenesis and Fracture Healing by Cigarette Smoke and Benzo(?)pyrene

    OpenAIRE

    Kung, Ming H.; Yukata, Kiminori; O’keefe, Regis J.; Zuscik, Michael J.

    2012-01-01

    The clinical literature strongly suggests that bone healing in cigarette smokers is impaired. Since cigarette smoke (CS) contains numerous polycyclic aromatic hydrocarbons (PAHs), and since dioxins impair bone formation in vivo via the Aryl Hydrocarbon Receptor (AHR), we investigated the impact of PAH/AHR signaling on chondrogenesis and on healing in a mouse tibial fracture model. We established that CS activates AHR signaling in fractures by up-regulating the AHR target gene cytochrome p4501...

  9. Activation of the Aryl Hydrocarbon Receptor by TCDD Inhibits Mammary Tumor Metastasis in a Syngeneic Mouse Model of Breast Cancer

    OpenAIRE

    Wang, Tao; Wyrick, Katie L.; Meadows, Gary G.; Wills, Tamara B.; Vorderstrasse, Beth A.

    2011-01-01

    Treatment with aryl hydrocarbon receptor (AhR) agonists can slow or reverse the growth of primary mammary tumors in rodents, which has fostered interest in developing selective AhR modulators for treatment of breast cancer. However, the major goal of breast cancer therapy is to inhibit metastasis, the primary cause of mortality in women with this disease. Studies conducted using breast cancer cell lines have demonstrated that AhR agonists suppress proliferation, invasiveness, and colony forma...

  10. Electron and Fluorescence Microscopy of Extracellular Glucan and Aryl-Alcohol Oxidase during Wheat-Straw Degradation by Pleurotus eryngii

    OpenAIRE

    Barrasa, J. M.; Gutiérrez, A.; Escaso, V.; Guillén, F.; Martínez, M. J.; Martínez, A.T.

    1998-01-01

    The ligninolytic fungus Pleurotus eryngii grown in liquid medium secreted extracellular polysaccharide (87% glucose) and the H2O2-producing enzyme aryl-alcohol oxidase (AAO). The production of both was stimulated by wheat-straw. Polyclonal antibodies against purified AAO were obtained, and a complex of glucanase and colloidal gold was prepared. With these tools, the localization of AAO and extracellular glucan in mycelium from liquid medium and straw degraded under solid-state fermentation co...

  11. Substrate diffusion and oxidation in GMC oxidoreductases: an experimental and computational study on fungal aryl-alcohol oxidase

    OpenAIRE

    Hernández-Ortega, Aitor; Borrelli, Kenneth; Ferreira, Patricia; Medina, Milagros; Martínez, Ángel T.; Guallar, Victor

    2011-01-01

    AAO (aryl-alcohol oxidase) provides H2O2 in fungal degradation of lignin, a process of high biotechnological interest. The crystal structure of AAO does not show open access to the active site, where different aromatic alcohols are oxidized. In the present study we investigated substrate diffusion and oxidation in AAO compared with the structurally related CHO (choline oxidase). Cavity finder and ligand diffusion simulations indicate the substrate-entrance channel, requiring side-chain displa...

  12. Endothelial cell-specific aryl hydrocarbon receptor knockout mice exhibit hypotension mediated, in part, by an attenuated angiotensin II responsiveness

    OpenAIRE

    Agbor, Larry N.; Elased, Khalid M.; Walker, Mary K.

    2011-01-01

    Hypotension in aryl hydrocarbon receptor knockout mice (ahr?/?) is mediated, in part, by a reduced contribution of angiotensin (Ang) II to basal blood pressure (BP). Since AHR is highly expressed in endothelial cells (EC), we hypothesized that EC-specific ahr?/? (ECahr?/?) mice would exhibit a similar phenotype. We generated ECahr?/? mice by crossing AHR floxed mice (ahrfx/fx) to mice expressing Cre recombinase driven by an EC-specific promoter. BP was assessed by radiotelemet...

  13. SYNTHESIS AND SPECTRAL ANALYSIS OF AN ARRAY OF NOVEL 4-(4-MORPHOLINOPHENYL)-6-ARYL-PYRIMIDIN-2-AMINES

    Scientific Electronic Library Online (English)

    J, THANUSU; V, KANAGARAJAN; M, GOPALAKRISHNAN.

    2010-12-01

    Full Text Available An array of newly synthesized novel 4-(4-morpholinophenyl)-6-arylpyrimidin-2-amines (20-28) are synthesized from the respective (E)-1-4-morpholinophenyl)-3-aryl-prop-2-en-1-ones (11-19) by the treatment of guanidine nitrate in refluxing ethanol catalyzed by lithium hydroxide and characterized by mel [...] ting point, elemental analysis, MS, FT-IR, one-dimensional NMR (¹H & 13C) spectroscopic data.

  14. Differences in the Interaction between Aryl Propionic Acid Derivatives and Poly(Vinylpyrrolidone) K30: A Multi-Methodological Approach

    OpenAIRE

    Gobetto, Roberto; Masic, Admir

    2009-01-01

    The present work aims at the application of several methods to explain differences in the physical interaction of some aryl propionic acid derivatives (ibuprofen [IBP], ketoprofen [KET], flurbiprofen [FLU], naproxen [NAP], fenbufen [FEN]) with poly(vinylpyrrolidone) (PVP) K30, stored together at 298 +/- 0.5 K and 22% RH. X-ray powder diffractometry and C-13-solid state NMR demonstrated that IBP was able to strongly interact with the polymer, while weak interaction was observed for KET, FLU, N...

  15. Oxidation of N-alkyl and N-aryl azaheterocycles by free and immobilized rabbit liver aldehyde oxidase

    OpenAIRE

    Angelino, S.A.G.F.

    1984-01-01

    Aldehyde oxidase isolated from rabbit liver is studied in this thesis with regard to its application in organic synthesis. The enzyme has a broad substrate specificity towards azaheterocycles and therefore offers great potential for profitable use.The oxidation of 1-alkyl(aryl)-3-aminocarbonylpyridiniwn chlorides by aldehyde oxidase shows that reaction can occur in principle at two different positions in the pyridinium ring. Only the 1-alkyl-1,6-dihydro-6-oxo-3-pyridinecarboxamides are obtain...

  16. Efficient access to novel androsteno-17-(1',3',4')-oxadiazoles and 17?-(1',3',4')-thiadiazoles via N-substituted hydrazone and N,N'-disubstituted hydrazine intermediates, and their pharmacological evaluation in vitro.

    Science.gov (United States)

    Kovács, Dóra; Wölfling, János; Szabó, Nikoletta; Szécsi, Mihály; Minorics, Renáta; Zupkó, István; Frank, Éva

    2015-06-15

    A series of novel 17-exo-oxadiazoles and -thiadiazoles in the ?(5) androstene series were efficiently synthesized from pregnenolone acetate and pregnadienolone acetate via multistep pathways. 17?-(1',3',4')-Oxadiazoles were obtained in high yields by the phenyliodonium diacetate-induced oxidative ring closure of semicarbazone and N-acylhydrazones derived from 3?-acetoxy- and 3?-hydroxyandrost-5-ene-17?-carbaldehydes. For the synthesis of analogous ?(16)-17-oxadiazolyl derivatives, N,N'-disubstituted hydrazine intermediates were prepared from 3?-acetoxyandrosta-5,16-diene-17-carboxylic acid, which then underwent cyclodehydration in the presence of POCl3. The cyclization of steroidal N,N'-diacylhydrazines containing a saturated ring D with the Lawesson reagent afforded 17?-(1',3',4')-thiadiazoles in good yields. Most of the products were subjected to deacetylation in basic media in order to enlarge the compound library available for pharmacological studies. All of these derivatives were screened in vitro for their antiproliferative effects against four malignant human adherent cell lines (HeLa, A2780, MCF7 and A431) by means of the MTT assay. The 3?-hydroxy derivatives of the newly-synthesized 17-exo-heterocycles were tested in vitro to investigate their inhibitory effects on rat testicular C17,20-lyase. One of the 1,3,4-oxadiazolyl derivatives proved to exert noteworthy enzyme-inhibitory action, with an IC50 (0.065 ?M) of the same order of magnitude as that of abiraterone. PMID:25993309

  17. Identifying toxic mechanisms using DNA microarrays: evidence that an experimental inhibitor of cell adhesion molecule expression signals through the aryl hydrocarbon nuclear receptor

    International Nuclear Information System (INIS)

    Microarray analysis of gene expression has become a powerful approach for exploring the biological effects of drugs and other chemicals. In toxicology research, gene expression profiling may help identify hazards by comparing results for an experimental compound with a database, and establish mechanistic hypotheses through examination of discrete gene changes. Here we examine the hepatic effects of a thienopyridine inhibitor of NF-?B-mediated expression of cellular adhesion proteins. In a 3-day toxicity study in Sprague-Dawley rats, A-277249 induced hypertrophy of the liver and elevated serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP). To investigate mechanism, microarray analysis was done on RNA from livers of A-277249-treated rats. Gene expression profiles from A-277249 were compared with a database of profiles from fifteen known hepatotoxins. Agglomerative hierarchical cluster analysis showed A-277249 to have a profile most similar to the aromatic hydrocarbons Aroclor 1254 and 3-methylcholanthrene (3MC), two known activators of the aryl hydrocarbon nuclear receptor (AhR). Several genes regulated by the AhR, including cytochrome P450 1A1, were upregulated by A-277249. In addition, several genes involved in apoptosis and cell cycle were differentially expressed consistent with cell turnover, hypertrophy and hyperplasia observed by histology. Results from this study indicate that A-277249 hepatic toxicityy indicate that A-277249 hepatic toxicity is mediated by the AhR either directly or through effects on NF-?B, and demonstrate the utility of microarray analysis for the rapid identification of toxic hazards for new chemical entities

  18. Effects of currently used pesticides and their mixtures on the function of thyroid hormone and aryl hydrocarbon receptor in cell culture.

    Science.gov (United States)

    Ghisari, Mandana; Long, Manhai; Tabbo, Agnese; Bonefeld-Jørgensen, Eva Cecilie

    2015-05-01

    Evidence suggest that exposure to pesticides can interfere with the endocrine system by multiple mechanisms. The endocrine disrupting potential of currently used pesticides in Denmark was analyzed as single compounds and in an equimolar mixture of 5 selected pesticides. The pesticides were previously analyzed for effects on the function of estrogen and androgen receptors, the aromatase enzyme and steroidogenesis in vitro. In this study, the effect on thyroid hormone (TH) function and aryl hydrocarbon receptor (AhR) transactivity was assessed using GH3 cell proliferation assay (T-screen) and AhR responsive luciferase reporter gene bioassay, respectively. Thirteen pesticides were analyzed as follows: 2-methyl-4-chlorophenoxyacetic acid, terbuthylazine, iodosulfuron-methyl-sodium, mesosulfuron-methyl, metsulfuron-methyl, chlormequat chloride, bitertanol, propiconazole, prothioconazole, mancozeb and its metabolite ethylene thiourea, cypermethrin, tau-fluvalinate, and malathion (currently banned in DK). In the T-screen, prothioconazole, malathion, tau-fluvalinate, cypermethrin, terbuthylazine and mancozeb significantly stimulated and bitertanol and propiconazole slightly reduced the GH3 cell proliferation. In the presence of triiodothyronine (T3), prothioconazole, tau-fluvalinate, propiconazole, cypermethrin and bitertanol significantly antagonized the T3-induced GH3 cell proliferation. Eleven of the tested pesticides agonized the AhR function, and bitertanol and prothioconazole inhibited the basal AhR activity. Bitertanol, propiconazole, prothioconazole and cypermethrin antagonized the TCDD-induced AhR transactivation at the highest tested concentration. The 5-component mixture had inducing effect but the combined effect could not be predicted due to the presence of bitertanol eliciting inhibitory effect. Upon removal of bitertanol from the mixture, the remaining four pesticides acted additively. In conclusion, our data suggest that pesticides currently used in Denmark can interfere with TH signaling and AhR function in vitro and might have the potential to cause endocrine disruption. PMID:25684042

  19. Activation of the c-Jun N-terminal kinase/activating transcription factor 3 (ATF3) pathway characterizes effective arylated diazeniumdiolate-based nitric oxide-releasing anticancer prodrugs.

    Science.gov (United States)

    Maciag, Anna E; Nandurdikar, Rahul S; Hong, Sam Y; Chakrapani, Harinath; Diwan, Bhalchandra; Morris, Nicole L; Shami, Paul J; Shiao, Yih-Horng; Anderson, Lucy M; Keefer, Larry K; Saavedra, Joseph E

    2011-11-24

    Improved therapies are needed for nonsmall cell lung cancer. Diazeniumdiolate-based nitric oxide (NO)-releasing prodrugs are a growing class of promising NO-based therapeutics. Recently, we have shown that O(2)-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate (JS-K, 1) is effective against nonsmall cell lung cancer (NSCLC) cells in culture and in vivo. Here we report mechanistic studies with compound 1 and its homopiperazine analogue and structural modification of these into more stable prodrugs. Compound 1 and its homopiperazine analogue were potent cytotoxic agents against NSCLC cells in vitro and in vivo, concomitant with activation of the SAPK/JNK stress pathway and upregulation of its downstream effector ATF3. Apoptosis followed these events. An aryl-substituted analogue, despite extended half-life in the presence of glutathione, did not activate JNK or have antitumor activity. The data suggest that rate of reactivity with glutathione and activation of JNK/ATF3 are determinants of cancer cell killing by these prodrugs. PMID:22003962

  20. QSAR analysis of a series of 2-aryl(heteroaryl)-2,5-dihydropyrazolo[4,3-c]quinolin-3-(3H)-ones using piecewise hyper-sphere modeling by particle swarm optimization

    International Nuclear Information System (INIS)

    In the present work, we employed piecewise hyper-sphere modeling by particle swarm optimization (PHMPSO) which splits the dataset into subsets with desired linearity in each model for QSAR studies of a series of 2-aryl(heteroaryl)-2,5-dihydropyrazolo[4,3-c]quinolin-3-(3H)-ones (PQs) for their affinity to benzodiazepine receptor (BzR). The results were compared to those obtained by MLR modeling in a single model with the whole data set as well as in submodels based on K-means clustering analysis. It has been clearly shown that electronic descriptors and spatial descriptors play the important roles in the compounds' affinity to BzR. In addition, the molecular density, the Y component of the principal moment of inertia, the magnitude and the Y component of the dipole moment of the molecules can detrimentally affect PQ analogue BzR affinity, while the X component of the dipole moment of the molecules can favorably affect compounds' affinity

  1. Targeting conserved water molecules: design of 4-aryl-5-cyanopyrrolo[2,3-d]pyrimidine Hsp90 inhibitors using fragment-based screening and structure-based optimization.

    Science.gov (United States)

    Davies, Nicholas G M; Browne, Helen; Davis, Ben; Drysdale, Martin J; Foloppe, Nicolas; Geoffrey, Stephanie; Gibbons, Ben; Hart, Terance; Hubbard, Roderick; Jensen, Michael Rugaard; Mansell, Howard; Massey, Andrew; Matassova, Natalia; Moore, Jonathan D; Murray, James; Pratt, Robert; Ray, Stuart; Robertson, Alan; Roughley, Stephen D; Schoepfer, Joseph; Scriven, Kirsten; Simmonite, Heather; Stokes, Stephen; Surgenor, Allan; Webb, Paul; Wood, Mike; Wright, Lisa; Brough, Paul

    2012-11-15

    Inhibitors of the Hsp90 molecular chaperone are showing promise as anti-cancer agents. Here we describe a series of 4-aryl-5-cyanopyrrolo[2,3-d]pyrimidine ATP competitive Hsp90 inhibitors that were identified following structure-driven optimization of purine hits revealed by NMR based screening of a proprietary fragment library. Ligand-Hsp90 X-ray structures combined with molecular modeling led to the rational displacement of a conserved water molecule leading to enhanced affinity for Hsp90 as measured by fluorescence polarization, isothermal titration calorimetry and surface plasmon resonance assays. This displacement was achieved with a nitrile group, presenting an example of efficient gain in binding affinity with minimal increase in molecular weight. Some compounds in this chemical series inhibit the proliferation of human cancer cell lines in vitro and cause depletion of oncogenic Hsp90 client proteins and concomitant elevation of the co-chaperone Hsp70. In addition, one compound was demonstrated to be orally bioavailable in the mouse. This work demonstrates the power of structure-based design for the rapid evolution of potent Hsp90 inhibitors and the importance of considering conserved water molecules in drug design. PMID:23018093

  2. Electroactive carbon nanoforms: a comparative study via sequential arylation and click chemistry reactions

    Science.gov (United States)

    Mateos-Gil, Jaime; Rodríguez-Pérez, Laura; Moreno Oliva, María; Katsukis, Georgios; Romero-Nieto, Carlos; Herranz, M. Ángeles; Guldi, Dirk M.; Martín, Nazario

    2014-12-01

    The reactivity of several carbon nanoforms (CNFs), single-walled carbon nanotubes (SWCNTs), multi-walled carbon nanotubes (MWCNTs) and graphene, has been investigated through a combination of arylation and click chemistry CuI-mediated azide-alkyne cycloaddition (CuAAC) reactions. The approach is based on the incorporation of electroactive ?-extended tetrathiafulvalene (exTTF) units into the triazole linkers to modulate the electronic properties of the obtained conjugates. The introduction of strain, by bending the planar graphene sheet into a 3D carbon framework, is responsible for the singular reactivity observed in carbon nanotubes. The formed nanoconjugates were fully characterized by analytical, spectroscopic, and microscopic techniques (TGA, FTIR, Raman, UV-Vis-NIR, cyclic voltammetry, TEM and XPS). In the case of SWCNT conjugates, where the functionalization degree is higher, a series of steady-state and time resolved spectroscopy experiments revealed a photoinduced electron transfer from the exTTF unit to the electron-accepting SWCNT.The reactivity of several carbon nanoforms (CNFs), single-walled carbon nanotubes (SWCNTs), multi-walled carbon nanotubes (MWCNTs) and graphene, has been investigated through a combination of arylation and click chemistry CuI-mediated azide-alkyne cycloaddition (CuAAC) reactions. The approach is based on the incorporation of electroactive ?-extended tetrathiafulvalene (exTTF) units into the triazole linkers to modulate the electronic properties of the obtained conjugates. The introduction of strain, by bending the planar graphene sheet into a 3D carbon framework, is responsible for the singular reactivity observed in carbon nanotubes. The formed nanoconjugates were fully characterized by analytical, spectroscopic, and microscopic techniques (TGA, FTIR, Raman, UV-Vis-NIR, cyclic voltammetry, TEM and XPS). In the case of SWCNT conjugates, where the functionalization degree is higher, a series of steady-state and time resolved spectroscopy experiments revealed a photoinduced electron transfer from the exTTF unit to the electron-accepting SWCNT. Electronic supplementary information (ESI) available: Experimental section, synthetic procedures, characterization data and selected supplementary figures. See DOI: 10.1039/c4nr04365k

  3. 4-[18F]Fluorophenylpiperazines by Improved Hartwig-Buchwald N-Arylation of 4-[18F]fluoroiodobenzene, Formed via Hypervalent ?3-Iodane Precursors: Application to Build-Up of the Dopamine D4 Ligand [18F]FAUC 316

    Directory of Open Access Journals (Sweden)

    Fabian Kügler

    2014-12-01

    Full Text Available Substituted phenylpiperazines are often neuropharmacologically active compounds and in many cases are essential pharmacophores of neuroligands for different receptors such as D2-like dopaminergic, serotoninergic and other receptors. Nucleophilic, no-carrier-added (n.c.a. 18F-labelling of these ligands in an aromatic position is desirable for studying receptors with in vivo molecular imaging. 1-(4-[18F]Fluorophenylpiperazine was synthesized in two reaction steps starting by 18F-labelling of a iodobenzene-iodonium precursor, followed by Pd-catalyzed N-arylation of the intermediate 4-[18F]fluoro-iodobenzene. Different palladium catalysts and solvents were tested with particular attention to the polar solvents dimethylformamide (DMF and dimethylsulfoxide (DMSO. Weak inorganic bases like potassium phosphate or cesium carbonate seem to be essential for the arylation step and lead to conversation rates above 70% in DMF which is comparable to those in typically used toluene. In DMSO even quantitative conversation was observed. Overall radiochemical yields of up to 40% and 60% in DMF and DMSO, respectively, were reached depending on the labelling yield of the first step. The fluorophenylpiperazine obtained was coupled in a third reaction step with 2-formyl-1H-indole-5-carbonitrile to yield the highly selective dopamine D4 ligand [18F]FAUC 316.

  4. On labelled compounds nomenclature

    International Nuclear Information System (INIS)

    Different approaches of major labelled compounds producers to their nomenclature in technical and commercial documentation are discussed. Some draft options of a standard technical guide document for labelled compounds nomenclature rules are suggested. Such a document after due discussion by the experts will serve to unification of the labelled compounds nomenclature within the frame of the CMEA member-countries co-operation in this field. The suggested options are based on the general recommendations by the International Union of Pure and Applied Chemistry and incorporate some more accurate definitions originating from the labelled compounds production and application experience

  5. Synthesis of novel room temperature chiral ionic liquids: application as reaction media for the heck arylation of aza-endocyclic acrylates

    International Nuclear Information System (INIS)

    New achiral and chiral RTILs were prepared using novel and/or optimized synthetic routes. These new series of imidazolinium, imidazolium, pyridinium and nicotine-derived ionic liquids were fully characterized including differential scanning calorimetry (DSC) analysis. The performance of these achiral and chiral room temperature ionic liquids (RTILs) was demonstrated by means of the Heck arylation of endocyclic acrylates employing arenediazonium salts and aryl iodides. The Heck arylations performed in the presence of these ionic entities, either as a solvent or as an additive, were effective leading to complete conversion of the substrate and good to excellent yield of the Heck adduct. In spite of the good performances, no asymmetric induction was observed in any of the cases studied. Two new diastereoisomeric NHC-palladium complexes were prepared in good yields from a chiral imidazolium salt and their structure characterized by X-ray diffraction. Overall, the Heck arylations employing arenediazonium tetrafluoroborates in RTILs were more effective than the traditional protocols employing aryl iodides in terms of reactivity and yields. (author)

  6. Synthesis of novel room temperature chiral ionic liquids: application as reaction media for the heck arylation of aza-endocyclic acrylates

    Energy Technology Data Exchange (ETDEWEB)

    Pastre, Julio C.; Correia, Carlos R.D., E-mail: genisson@chimie.ups-tlse.f, E-mail: roque@iqm.unicamp.b [Universidade Estadual de Campinas (UNICAMP), SP (Brazil). Inst. de Quimica; Genisson, Yves [Universite Paul Sabatier, Toulouse (France). Lab. de Synthese et Physicochimie des Molecules d' Interet Biologique; Saffon, Nathalie [Universite Paul Sabatier, Toulouse (France). Structure federative toulousaine en chimie moleculaire (SFTCM); Dandurand, Jany [Universite Paul Sabatier, Toulouse (France). Lab. de Physique des Polymeres

    2010-07-01

    New achiral and chiral RTILs were prepared using novel and/or optimized synthetic routes. These new series of imidazolinium, imidazolium, pyridinium and nicotine-derived ionic liquids were fully characterized including differential scanning calorimetry (DSC) analysis. The performance of these achiral and chiral room temperature ionic liquids (RTILs) was demonstrated by means of the Heck arylation of endocyclic acrylates employing arenediazonium salts and aryl iodides. The Heck arylations performed in the presence of these ionic entities, either as a solvent or as an additive, were effective leading to complete conversion of the substrate and good to excellent yield of the Heck adduct. In spite of the good performances, no asymmetric induction was observed in any of the cases studied. Two new diastereoisomeric NHC-palladium complexes were prepared in good yields from a chiral imidazolium salt and their structure characterized by X-ray diffraction. Overall, the Heck arylations employing arenediazonium tetrafluoroborates in RTILs were more effective than the traditional protocols employing aryl iodides in terms of reactivity and yields. (author)

  7. Aryl hydrocarbon receptor-induced adrenomedullin mediates cigarette smoke carcinogenicity in humans and mice.

    Science.gov (United States)

    Portal-Nuñez, Sergio; Shankavaram, Uma T; Rao, Mahadev; Datrice, Nicole; Atay, Scott; Aparicio, Marta; Camphausen, Kevin A; Fernández-Salguero, Pedro M; Chang, Han; Lin, Pinpin; Schrump, David S; Garantziotis, Stavros; Cuttitta, Frank; Zudaire, Enrique

    2012-11-15

    Cigarette smoking (CS) is a leading cause of death worldwide. The aryl hydrocarbon receptor (AHR) is partially responsible for tobacco-induced carcinogenesis although the underlying mechanisms involving early effector genes have yet to be determined. Here, we report that adrenomedullin (ADM) significantly contributes to the carcinogenicity of tobacco-activated AHR. CS and AHR activating ligands induced ADM in vitro and in vivo but not in AHR-deficient fibroblasts and mice. Ectopic transfection of AHR rescued ADM expression in AHR(-/-) fibroblasts whereas AHR blockage with siRNA in wild type cells significantly decreased ADM expression. AHR regulates ADM expression through two intronic xenobiotic response elements located close to the start codon in the ADM gene. Using tissue microarrays we showed that ADM and AHR were coupregulated in lung tumor biopsies from smoker patients. Microarray meta-analysis of 304 independent microarray experiments showed that ADM is elevated in smokers and smokers with cancer. In addition, ADM coassociated with a subset of AHR responsive genes and efficiently differentiated patients with lung cancer from nonsmokers. In a novel preclinical model of CS-induced tumor progression, host exposure to CS extracts significantly elevated tumor ADM although systemic treatment with the ADM antagonist NSC16311 efficiently blocked tobacco-induced tumor growth. In conclusion, ADM significantly contributes the carcinogenic effect of AHR and tobacco combustion products. We suggest that therapeutics targeting the AHR/ADM axis may be of clinical relevance in the treatment of tobacco-induced pulmonary malignancies. PMID:22993405

  8. No evidence of somatic aryl hydrocarbon receptor interacting protein mutations in sporadic endocrine neoplasia

    DEFF Research Database (Denmark)

    Raitila, A; Georgitsi, M

    2007-01-01

    Germline mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene were recently observed in patients with pituitary adenoma predisposition (PAP). Though AIP mutation-positive individuals with prolactin-, mixed growth hormone/prolactin-, and ACTH-producing pituitary adenomas as well as non-secreting pituitary adenomas have been reported, most mutation-positive patients have had growth hormone-producing adenomas diagnosed at relatively young age. Pituitary adenomas are also component tumors of some familial endocrine neoplasia syndromes such as multiple endocrine neoplasia type 1 (MEN1) and Carney complex (CNC). Genes underlying MEN1 and CNC are rarely mutated in sporadic pituitary adenomas, but more often in other lesions contributing to these two syndromes. Thus far, the occurrence of somatic AIP mutations has not been studied in endocrine tumors other than pituitary adenomas. Here, we have analyzed 32 pituitary adenomas and 79 other tumors of the endocrine system for somatic AIP mutations bydirect sequencing. No somatic mutations were identified. However, two out of nine patients with prolactin-producing adenoma were shown to harbor a Finnish founder mutation (Q14X) with a complete loss of the wild-type allele in the tumors. These results are in agreement with previous studies in that prolactin-producing adenomas are component tumors in PAP. The data also support the previous finding that somatic AIP mutations are not common in pituitary adenomas and suggest that such mutations are rare in other endocrine tumors as well.

  9. Aryl hydrocarbon receptor agonists in European herring gull (Larus argentatus) eggs from Norway.

    Science.gov (United States)

    Muusse, Martine; Christensen, Guttorm; Langford, Katherine; Tollefsen, Knut-Erik; Thomas, Kevin V

    2014-01-01

    Herring gull eggs from two locations in Norway, an island situated in the north (Musvær, 69.88° N, 18.55° E) and an island in the southeast (Reiaren, 59.15° N, 10.46° E) of the country, were analyzed for the presence of aryl hydrocarbon receptor (AhR) agonists. AhR agonist activity was determined using the dioxin-responsive chemically activated luciferase expression (DR-CALUX) assay to calculate the toxic equivalent quotient (TEQ)CALUX. TEQCALUX ranged from 16 to 401 pg TEQ/g lipid in the samples from the north (n = 11) and between 6 and 360 pg TEQ/g lipid (n = 12) in the southeastern samples. The large variance between the individual samples is postulated to be due to different feeding habits of individual birds. The levels of AhR agonists detected might lead to adverse effects for the developing embryo or to a significant increase of contaminant load for human consumers of eggs. PMID:24754391

  10. Zinc finger transcription factor Slug is a novel target gene of aryl hydrocarbon receptor

    International Nuclear Information System (INIS)

    The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor. We previously showed that AhR localizes predominantly in the cytoplasm under high cell densities of a keratinocytes cell line, HaCaT, but accumulates in the nucleus at low cell densities. In the current report, we show that the Slug, which is a member of the snail/slug family of zinc finger transcriptional repressors critical for induction of epithelial-mesenchymal transitions (EMT), is activated transcriptionally in accordance with nuclear accumulation of AhR. By reporter assay of the promoter of the Slug gene, gel shift and chromatin immunoprecipitation analyses showed AhR directly binds to xenobiotic responsive element 5 at - 0.7 kb of the gene. AhR-targeted gene silencing by small interfering RNA duplexes led to the abolishment of not only CYP1A1 but also Slug induction by 3-methycholanthrene. The Slug was co-localized to the AhR at the wound margins of HaCaT cells, where apparent nuclear distribution of AhR and Slug was observed. The induced Slug was associated with reduction of an epithelial marker of cytokeratin-18 and with an increase in the mesenchymal marker, fibronectin. Taken together, these findings suggest that AhR participated in Slug induction, which, in turn, regulates cellular physiology including cell adhesion and migration

  11. Suppression of adipocyte differentiation by Cordyceps militaris through activation of the aryl hydrocarbon receptor.

    Science.gov (United States)

    Shimada, Tsuyoshi; Hiramatsu, Nobuhiko; Kasai, Ayumi; Mukai, Mai; Okamura, Maro; Yao, Jian; Huang, Tao; Tamai, Minori; Takahashi, Shuhei; Nakamura, Tomoyuki; Kitamura, Masanori

    2008-10-01

    Mycelial extracts have a wide range of biological activities that modulate functions of mammalian cells. In this report, we sought to identify antiadipogenic mycelia with the use of 3T3-L1 cells and found that the extract of Cordyceps militaris exclusively suppressed differentiation of 3T3-L1 preadipocytes into mature adipocytes without affecting cell viability. This inhibitory effect was dose dependent, reversible, and associated with 1) a decrease in lipid accumulation, 2) blunted induction of adipocyte markers including adiponectin, peroxisome proliferator-activated receptor-gamma, and CCAAT/enhancer binding protein-alpha, and 3) sustained expression of a preadipocyte marker, monocyte chemoattractant protein-1. C. militaris also significantly decreased accumulation of lipid and hypertrophy in mature adipocytes and preserved their response to insulin (phosphorylation of Akt) during prolonged culture. Subsequent experiments revealed that C. militaris has the potential to activate the aryl hydrocarbon receptor (AhR). In 3T3-L1 cells, treatment with AhR agonists including benzo[a]pyrene and 3-methylcholanthrene reproduced the antiadipogenic effect of C. militaris. Furthermore, dominant-negative inhibition of AhR abrogated the suppressive effect of C. militaris on adipocyte differentiation. These results suggest that C. militaris has the potential to interfere with adipocyte differentiation through activation of AhR. PMID:18664595

  12. Chelation in metal intoxication XXX: ?-mercapto-?-aryl acrylic acids as antidotes to cadmium toxicity

    International Nuclear Information System (INIS)

    ?-Mercapto-?-(2-furyl) acrylic acid (MFA), ?-mercapto-?-(2-hydroxyphenyl) acrylic acid (MHA), ?-1,2-phenylene di-?-mercaptoacrylic acid (1,2-PDMA) and ?-l,4-phenylene di-?-mercapto acrylic acid (1,4-PDMA) were compared to sodium N-benzyl-D-glucamine dithiocarbamate (NBG-DTC) an effective cadmium chelator, for their ability to mobilize Cd and influence the Cd induced tissue metallothionein (MT) in rats administered 109CdCl2, 72 hr earlier. MFA was almost as effective as NBG-DTC but more effective than MHA in enhancing urinary and faecal excretion of Cd, reducing tissue and blood levels of Cd and in lowering Cd induced increase in hepatic and renal MT contents. 1,2-PDMA and l,4-PDMA were effective only in reducing the hepatic burden of Cd. The results do not indicate any direct relationship between the efficacy of ?-mercapto-?-aryl acrylic acids to decorporate body Cd and their lipophilic-hydrophilic character or number-arrangement of their sulfhydryl groups. (author)

  13. Potential therapeutic significance of increased expression of aryl hydrocarbon receptor in human gastric cancer

    Directory of Open Access Journals (Sweden)

    Tie-Li Peng, Jie Chen, Wei Mao, Xin Liu, Yu Tao, Lian-Zhou Chen, Min-Hu Chen

    2009-04-01

    Full Text Available AIM: To determine the functional significance of aryl hydrocarbon receptor (AhR in gastric carcinogenesis, and to explore the possible role of AhR in gastric cancer (GC treatment.METHODS: RT-PCR, real-time PCR, and Western blotting were performed to detect AhR expression in 39 GC tissues and five GC cell lines. AhR protein was detected by immunohistochemistry (IHC in 190 samples: 30 chronic superficial gastritis (CSG, 30 chronic atrophic gastritis (CAG, 30 intestinal metaplasia (IM, 30 atypical hyperplasia (AH, and 70 GC. The AhR agonist tetrachlorodibenzo-para-dioxin (TCDD was used to treat AGS cells. MTT assay and flow cytometric analysis were performed to measure the viability, cell cycle and apoptosis of AGS cells.RESULTS: AhR expression was significantly increased in GC tissues and GC cell lines. IHC results indicated that the levels of AhR expression gradually increased, with the lowest levels in CSG, followed by CAG, IM, AH and GC. AhR expression and nuclear translocation were significantly higher in GC than in precancerous tissues. TCDD inhibited proliferation of AGS cells via induction of growth arrest at the G1-S phase.CONCLUSION: AhR plays an important role in gastric carcinogenesis. AhR may be a potential therapeutic target for GC treatment.

  14. The Unexpected Role for the Aryl Hydrocarbon Receptor on Susceptibility to Experimental Toxoplasmosis

    Directory of Open Access Journals (Sweden)

    Yuriko Sanchez

    2010-01-01

    Full Text Available The aryl hydrocarbon receptor (AhR is part of a signaling system that is mainly triggered by xenobiotic agents. Increasing evidence suggests that AhR may regulate immunity to infections. To determine the role of AhR in the outcome of toxoplasmosis, we used AhR-/- and wild-type (WT mice. Following an intraperitoneal infection with Toxoplasma gondii (T. gondii, AhR-/- mice succumbed significantly faster than WT mice and displayed greater liver damage as well as higher serum levels of tumor necrosis factor (TNF-?, nitric oxide (NO, and IgE but lower IL-10 secretion. Interestingly, lower numbers of cysts were found in their brains. Increased mortality was associated with reduced expression of GATA-3, IL-10, and 5-LOX mRNA in spleen cells but higher expression of IFN-? mRNA. Additionally, peritoneal exudate cells from AhR-/- mice produced higher levels of IL-12 and IFN-? but lower TLR2 expression than WT mice. These findings suggest a role for AhR in limiting the inflammatory response during toxoplasmosis.

  15. Deletion of the Aryl Hydrocarbon Receptor Enhances the Inflammatory Response to Leishmania major Infection

    Directory of Open Access Journals (Sweden)

    Guillermo Elizondo, Miriam Rodríguez-Sosa, Elizabet Estrada-Muñiz, Frank J. Gonzalez, Libia Vega

    2011-01-01

    Full Text Available The aryl hydrocarbon receptor (AhR is a ligand-activated receptor that mediates the toxicity of environmental pollutants, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD. Recently, it has been shown that the AhR plays a role in immune and inflammatory regulation. However, most of these studies are based on the activation of AhR by exogenous ligands. Therefore, in the present study, we addressed the role of this transcription factor, in the absent of exogenous ligand, on the immune response to Leishmania major infection. Our results indicate that inactivation of the AhR results in an alteration of the levels of several cytokines. Lymph node cells from infected Ahr-null animals displayed an increase in IFN? and IL-12 levels, together with a decrease in IL-4 and IL-10 levels compared to wild-type (wt mice. Ahr-null mice also presented higher serum levels of the pro-inflammatory cytokine TNF-? prior to parasite inoculation and during infection compared to wt mice. Moreover, a 30% decrease in the population of Treg cells was observed in Ahr-null mice. This decrease was associated with a reduction in Foxp3 mRNA levels. Finally, the alteration in the cytokine profile results in a better resolution of the L. major infection.

  16. The Aryl Hydrocarbon Receptor Pathway: A Key Component of the microRNA-Mediated AML Signalisome

    Directory of Open Access Journals (Sweden)

    Julia E. Rager

    2012-05-01

    Full Text Available Recent research has spotlighted the role of microRNAs (miRNAs as critical epigenetic regulators of hematopoietic stem cell differentiation and leukemia development. Despite the recent advances in knowledge surrounding epigenetics and leukemia, the mechanisms underlying miRNAs’ influence on leukemia development have yet to be clearly elucidated. Our aim was to identify high ranking biological pathways altered at the gene expression level and under epigenetic control. Specifically, we set out to test the hypothesis that miRNAs dysregulated in acute myeloid leukemia (AML converge on a common pathway that can influence signaling related to hematopoiesis and leukemia development. We identified genes altered in AML patients that are under common regulation of seven key miRNAs. By mapping these genes to a global interaction network, we identified the “AML Signalisome”. The AML Signalisome comprises 53 AML-associated molecules, and is enriched for proteins that play a role in the aryl hydrocarbon receptor (AhR pathway, a major regulator of hematopoiesis. Furthermore, we show biological enrichment for hematopoiesis-related proteins within the AML Signalisome. These findings provide important insight into miRNA-regulated pathways in leukemia, and may help to prioritize targets for disease prevention and treatment.

  17. The aryl hydrocarbon receptor in barrier organ physiology, immunology, and toxicology.

    Science.gov (United States)

    Esser, Charlotte; Rannug, Agneta

    2015-04-01

    The aryl hydrocarbon receptor (AhR) is an evolutionarily old transcription factor belonging to the Per-ARNT-Sim-basic helix-loop-helix protein family. AhR translocates into the nucleus upon binding of various small molecules into the pocket of its single-ligand binding domain. AhR binding to both xenobiotic and endogenous ligands results in highly cell-specific transcriptome changes and in changes in cellular functions. We discuss here the role of AhR for immune cells of the barrier organs: skin, gut, and lung. Both adaptive and innate immune cells require AhR signaling at critical checkpoints. We also discuss the current two prevailing views-namely, 1) AhR as a promiscuous sensor for small chemicals and 2) a role for AhR as a balancing factor for cell differentiation and function, which is controlled by levels of endogenous high-affinity ligands. AhR signaling is considered a promising drug and preventive target, particularly for cancer, inflammatory, and autoimmune diseases. Therefore, understanding its biology is of great importance. PMID:25657351

  18. Interaction Networks in Yeast Define and Enumerate the Signaling Steps of the Vertebrate Aryl Hydrocarbon Receptor

    Directory of Open Access Journals (Sweden)

    Yao Guang

    2004-01-01

    Full Text Available The aryl hydrocarbon receptor (AHR is a vertebrate protein that mediates the toxic and adaptive responses to dioxins and related environmental pollutants. In an effort to better understand the details of this signal transduction pathway, we employed the yeast S. cerevisiae as a model system. Through the use of arrayed yeast strains harboring ordered deletions of open reading frames, we determined that 54 out of the 4,507 yeast genes examined significantly influence AHR signal transduction. In an effort to describe the relationship between these modifying genes, we constructed a network map based upon their known protein and genetic interactions. Monte Carlo simulations demonstrated that this network represented a description of AHR signaling that was distinct from those generated by random chance. The network map was then explored with a number of computational and experimental annotations. These analyses revealed that the AHR signaling pathway is defined by at least five distinct signaling steps that are regulated by functional modules of interacting modifiers. These modules can be described as mediating receptor folding, nuclear translocation, transcriptional activation, receptor level, and a previously undescribed nuclear step related to the receptor's Per-Arnt-Sim domain.

  19. Polycyclic aromatic hydrocarbon components contribute to the mitochondria-antiapoptotic effect of fine particulate matter on human bronchial epithelial cells via the aryl hydrocarbon receptor

    Science.gov (United States)

    2010-01-01

    Background Nowadays, effects of fine particulate matter (PM2.5) are well-documented and related to oxidative stress and pro-inflammatory response. Nevertheless, epidemiological studies show that PM2.5 exposure is correlated with an increase of pulmonary cancers and the remodeling of the airway epithelium involving the regulation of cell death processes. Here, we investigated the components of Parisian PM2.5 involved in either the induction or the inhibition of cell death quantified by different parameters of apoptosis and delineated the mechanism underlying this effect. Results In this study, we showed that low levels of Parisian PM2.5 are not cytotoxic for three different cell lines and primary cultures of human bronchial epithelial cells. Conversely, a 4 hour-pretreatment with PM2.5 prevent mitochondria-driven apoptosis triggered by broad spectrum inducers (A23187, staurosporine and oligomycin) by reducing the mitochondrial transmembrane potential loss, the subsequent ROS production, phosphatidylserine externalization, plasma membrane permeabilization and typical morphological outcomes (cell size decrease, massive chromatin and nuclear condensation, formation of apoptotic bodies). The use of recombinant EGF and specific inhibitor led us to rule out the involvement of the classical EGFR signaling pathway as well as the proinflammatory cytokines secretion. Experiments performed with different compounds of PM2.5 suggest that endotoxins as well as carbon black do not participate to the antiapoptotic effect of PM2.5. Instead, the water-soluble fraction, washed particles and organic compounds such as polycyclic aromatic hydrocarbons (PAH) could mimic this antiapoptotic activity. Finally, the activation or silencing of the aryl hydrocarbon receptor (AhR) showed that it is involved into the molecular mechanism of the antiapoptotic effect of PM2.5 at the mitochondrial checkpoint of apoptosis. Conclusions The PM2.5-antiapoptotic effect in addition to the well-documented inflammatory response might explain the maintenance of a prolonged inflammation state induced after pollution exposure and might delay repair processes of injured tissues. PMID:20663163

  20. Polycyclic aromatic hydrocarbon components contribute to the mitochondria-antiapoptotic effect of fine particulate matter on human bronchial epithelial cells via the aryl hydrocarbon receptor

    Directory of Open Access Journals (Sweden)

    Baeza-Squiban Armelle

    2010-07-01

    Full Text Available Abstract Background Nowadays, effects of fine particulate matter (PM2.5 are well-documented and related to oxidative stress and pro-inflammatory response. Nevertheless, epidemiological studies show that PM2.5 exposure is correlated with an increase of pulmonary cancers and the remodeling of the airway epithelium involving the regulation of cell death processes. Here, we investigated the components of Parisian PM2.5 involved in either the induction or the inhibition of cell death quantified by different parameters of apoptosis and delineated the mechanism underlying this effect. Results In this study, we showed that low levels of Parisian PM2.5 are not cytotoxic for three different cell lines and primary cultures of human bronchial epithelial cells. Conversely, a 4 hour-pretreatment with PM2.5 prevent mitochondria-driven apoptosis triggered by broad spectrum inducers (A23187, staurosporine and oligomycin by reducing the mitochondrial transmembrane potential loss, the subsequent ROS production, phosphatidylserine externalization, plasma membrane permeabilization and typical morphological outcomes (cell size decrease, massive chromatin and nuclear condensation, formation of apoptotic bodies. The use of recombinant EGF and specific inhibitor led us to rule out the involvement of the classical EGFR signaling pathway as well as the proinflammatory cytokines secretion. Experiments performed with different compounds of PM2.5 suggest that endotoxins as well as carbon black do not participate to the antiapoptotic effect of PM2.5. Instead, the water-soluble fraction, washed particles and organic compounds such as polycyclic aromatic hydrocarbons (PAH could mimic this antiapoptotic activity. Finally, the activation or silencing of the aryl hydrocarbon receptor (AhR showed that it is involved into the molecular mechanism of the antiapoptotic effect of PM2.5 at the mitochondrial checkpoint of apoptosis. Conclusions The PM2.5-antiapoptotic effect in addition to the well-documented inflammatory response might explain the maintenance of a prolonged inflammation state induced after pollution exposure and might delay repair processes of injured tissues.

  1. Stable isotopes labelled compounds

    International Nuclear Information System (INIS)

    The catalogue on stable isotopes labelled compounds offers deuterium, nitrogen-15, and multiply labelled compounds. It includes: (1) conditions of sale and delivery, (2) the application of stable isotopes, (3) technical information, (4) product specifications, and (5) the complete delivery programme

  2. Proof of principle for the synthesis of hydroxy-aryl esters of glycosidic polyols and non-reducing oligosaccharides with subsequent enzymatic coupling to a tyrosine-containing tripeptide.

    Science.gov (United States)

    ter Haar, Ruud; Wildschut, Jelle; Sugih, Asaf K; Bart Möller, W; de Waard, Pieter; Boeriu, Carmen G; Heeres, Hero J; Schols, Henk A; Gruppen, Harry

    2011-06-01

    To enable enzymatic coupling of saccharides to proteins, several di- and trisaccharides were hydroxy-arylated using anhydrous transesterification with methyl 3-(4-hydroxyphenyl)propionate, catalyzed by potassium carbonate. This transesterification resulted in the attachment of up to 3 hydroxy-aryl units per oligosaccharide molecule, with the monosubstituted product being by far the most abundant. The alkaline reaction conditions, however, resulted in a partial breakdown of reducing sugars. This breakdown could easily be bypassed by a preceding sugar reduction step converting them to polyols. Hydroxy-arylated products were purified by using solid phase extraction, based on the number of hydroxy-aryl moieties attached. Monohydroxy-arylated saccharose was subsequently linked to a tyrosine-containing tripeptide using horseradish peroxidase, as monitored by LC-MS(n). This proof of principle for peptide and protein glycation with a range of possible saccharides and glycosidic polyols can lead to products with unique new properties. PMID:21486666

  3. Nomenclature for labelled compounds

    International Nuclear Information System (INIS)

    This paper report on isotopically labelled compounds. The first indexing system for isotopically labelled organic compounds is generally credited to Boughton and named after him. An extension of his principles for designating compounds containing hydrogen isotopes has been part of the Chemical Abstracts Service index nomenclature system for many years. After close on five years labor the IUPAC sponsored Commission on Nomenclature of Organic Chemistry presented in 1979 their findings on Isotopically Modified Compounds. The system codified in their rules provides for recognition of various types of isotopic modification and is therefore of more general applicability. Concurrently the rules for the nomenclature of isotopically modified inorganic compounds are developed. These are to be seen as supplementing and extending the guidelines laid down in the IUPAC Inorganic Nomenclature Rules already published

  4. Diagnostic radiopharmaceutical compounds

    International Nuclear Information System (INIS)

    Compounds comprising Technetium-99m have a lipo-philicity sufficiently high at a pH of 7.6 to permit passage of the compounds from the blood of a mammal into a target organ or tissue and sufficiently low at a pH of 6.6 to prevent rapid return of the compounds from the target organ or tissue to the blood. A method and kit for selectively depositing a radiopharmaceutical compound in at least one target tissue or organ of a mammal which tissue or organ has a significantly different intracellular pH than the blood of the mammal, by introducing one or more compounds of the invention into the bloodstream of the mammal

  5. 3-Phenyl/Pyridinyl Derivatives of Trans-2-(aryl/heterylvinyl-3H-quinazolin-4-ones: Synthesis and Fluorescent Properties

    Directory of Open Access Journals (Sweden)

    Emiliya V. Nosova

    2012-03-01

    Full Text Available Novel 3-phenyl/pyridinyl-trans-2-(aryl/heterylvinyl-3H-quinazolin-4-ones 3a,b, 4a, 5a, 7a and their 6,7-difluoro de- rivatives 3c,d, 4b, 5b, 7b have been obtained by condensation of the correspondent 2-methylquinazolin-4-ones 1, 6 with aromatic (heterocyclic aldehydes in the presence of ZnCl2 (AcONa or by the reaction of 2-methyl-3,1-benzoxazin-4- ones 2 with the Shiff bases. Effects of aryl(heteryl substituents on photophysical properties of (aryl/heteryl quinazolinylethenes have been studied.

  6. Acidic brønsted ionic liquids catalyzed the preparation of 1-((benzo[d]thiazol-2-ylamino)(aryl)-methyl)naphthalen-2-ol derivatives 1-[(1,3-benzothiazol-2-ylamino)(aryl)methyl]-2-naphthol

    Scientific Electronic Library Online (English)

    H.R., Shaterian; M., Mohammadnia.

    2013-08-01

    Full Text Available The acidic ionic liquids, triethylammonium hydrogen sulfate ([Et3NH]HSO4), 2-pyrrolidonium hydrogen sulfate ([Hnhp]HSO4), 3-methyl-1-sulfonic acid imidazolium chloride ([Msim]Cl), and 1-methylimidazolium hydrogen sulfate ([Hmim]HSO4) catalyzed three-component condensation reaction of aromatic aldehy [...] des, 2-aminobenzothiazole, and ?-naphthol to afford corresponding 1-((benzo[d]thiazol-2-ylamino)(aryl)-methyl)naphthalen-2-ol derivatives. The inexpensive and non-toxic ionic liquids can be reused several times without noticeable loss of their activities.

  7. Construction and screening of 2-aryl benzimidazole library identifies a new antifouling and antifungal agent.

    Digital Repository Service at National Institute of Oceanography (India)

    Majik, M.S.; Tilvi, S.; Mascarenhas, S.; Kumar, Vikash.; Chatterjee, Amrita; Banerjee, Mainak.

    2014-01-01

    performance against 10 strains of marine biofilm forming bacteria developed on copper panels exposed for 14 days at Dona Paula, Arabian Sea, India. These compounds were also evaluated for their antibacterial and antifungal activities. Two compounds, i.e. 4j...

  8. Palladium catalyzed Suzuki cross-coupling of 3-iodo-2-(methylthio)-benzo[b]furan derivatives: synthesis of 3-aryl-2-(methylthio)benzo[b]furans

    Scientific Electronic Library Online (English)

    Rafaela M, Gay; Flávia, Manarin; Ricardo, Brandão; Gilson, Zeni.

    1635-16-01

    Full Text Available Neste trabalho desenvolvemos um método seletivo e eficiente para a síntese de derivados de 3-aril-2-(tiometil)-benzo[b]furanos, via reação de acoplamento com ácidos borônicos, catalisada por paládio. As condições reacionais usadas foram brandas e compatíveis com ácidos borônicos contendo substituint [...] es retiradores, doadores de elétrons ou neutros. Abstract in english A selective and efficient method for the synthesis of 3-aryl-2-(methylthio)benzo[b]furans derivatives by palladium catalyzed cross-coupling reaction with boronic acids has been developed. The reaction proceeded cleanly under mild conditions and was performed with aryl boronic acids bearing electron- [...] withdrawing, electron donating and neutral substituents.

  9. Comparison of arylboron-based nucleophiles in Ni-catalyzed Suzuki-Miyaura cross-coupling with aryl mesylates and sulfamates.

    Science.gov (United States)

    Zhang, Na; Hoffman, David J; Gutsche, Nicholas; Gupta, Jayesh; Percec, Virgil

    2012-07-20

    The efficiency of arylboron-based nucleophiles, boronic acid, potassium trifluoroborate, neopentylglycolboronate, and pinacol boronate in nickel-catalyzed Suzuki-Miyaura cross-coupling reactions with the two C-O electrophiles, mesylates, and sulfamates was compared. Arylboronic acid is the most reactive and most atom-economic of the four boron species studied. Arylpotassium trifluoroborate cross-couples efficiently only in the presence of water. In the absence of water, aryl neopentylglycolboronate is more efficient, less expensive, and more atom-economic than aryl pinacolboronate. PMID:22712768

  10. Practical Iron- and Cobalt-Catalyzed Cross-Coupling Reactions between N-Heterocyclic Halides and Aryl or Heteroaryl Magnesium Reagents.

    Science.gov (United States)

    Kuzmina, Olesya M; Steib, Andreas K; Fernandez, Sarah; Boudot, Willy; Markiewicz, John T; Knochel, Paul

    2015-05-26

    The reaction scope of iron- and cobalt-catalyzed cross-coupling reactions in the presence of isoquinoline (quinoline) in the solvent mixture tBuOMe/THF has been further investigated. Various 2-halogenated pyridine, pyrimidine, and triazine derivatives were arylated under these mild conditions in excellent yields. The presence of isoquinoline allows us to perform Fe-catalyzed cross-coupling reactions between 6-chloroquinoline and aryl magnesium reagents. Furthermore, it was found that the use of 10?% N,N-dimethylquinoline-8-amine increases the yields of some Co-catalyzed cross-coupling reactions with chloropyridines bearing electron-withdrawing substituents. PMID:25899175

  11. One pot synthesis of diarylfurans from aryl esters and PhI(OAc)2via palladium-associated iodonium ylides.

    Science.gov (United States)

    Bao, Yong-Sheng; Agula, Bao; Zhaorigetu, Bao; Jia, Meilin; Baiyin, Menghe

    2015-04-14

    The example of palladium-catalyzed intermolecular cyclization for the synthesis of various diarylfurans in which one of the aromatic rings originates from the phenolic part of the starting ester and the other one from PhI(OAc)2 has been reported. The reaction is carried out through two steps: the rearrangement of palladium-associated iodonium ylides to form o-iodo diaryl ether and then palladium catalyzed intramolecular direct arylation. This reaction can tolerate a variety of functional groups and is alternative or complementary to the previous methods for the synthesis of diarylfurans. PMID:25758755

  12. Cancer immunoediting and dioxin-activating aryl hydrocarbon receptor: a missing link in the shift toward tumor immunoescape?

    OpenAIRE

    Laura Ridolfi; Massimo Guidoboni; Ruggero Ridolfi

    2010-01-01

    The aryl hydrocarbon receptor (AhR), a member of the PAS protein family, is found in organisms as diverse as Drosophila melano­gaster, nematodes, and mammals. While several reviews have reported that AhR, once activated by agonist ligands, causes long-term effects such as modification of cell growth through cell cycle control, there is also recent evidence of its decisive role in immunosuppression. The most widely studied AhR agonist is 2,3,7,8-tetrachlorodibenzo-p-dioxin, which binds AhR wi...

  13. No-carrier-added (NCA) aryl (18E) fluorides via the nucleophilic aromatic substitution of electron rich aromatic rings

    Science.gov (United States)

    Ding, Yu-Shin (Central Islip, NY); Fowler, Joanna S. (Bellport, NY); Wolf, Alfred P. (Setauket, NY)

    1993-01-01

    A method for synthesizing no-carrier-added (NCA) aryl [.sup.18 F] fluoride substituted aromatic aldehyde compositions bearing an electron donating group is described. The method of the present invention includes the step of reacting aromatic nitro aldehydes having a suitably protected hydroxyl substitutent on an electron rich ring. The reaction is The U.S. Government has rights in this invention pursuant to Contract Number DE-AC02-76CH00016, between the U.S. Department of Energy and Associated Universities Inc.

  14. Structural Basis for Inhibition of Mycobacterial and Human Adenosine Kinase by 7-Substituted 7-(Het)aryl-7-deazaadenine Ribonucleosides.

    Czech Academy of Sciences Publication Activity Database

    Snášel, Jan; Nauš, Petr; Dostál, Ji?í; Hnízda, Aleš; Fanfrlík, Jind?ich; Brynda, Ji?í; Bourderioux, Aurelie; Dušek, Michal; Dvo?áková, H.; Stola?íková, J.; Zábranská, Helena; Pohl, Radek; Kone?ný, P.; Džubák, P.; Votruba, Ivan; Hajdúch, M.; ?ezá?ová, Pavlína; Veverka, Václav; Hocek, Michal; Pichová, Iva

    2014-01-01

    Ro?. 57, ?. 20 (2014), s. 8268-8279. ISSN 0022-2623 R&D Projects: GA ?R GAP207/11/0344; GA MŠk LO1302; GA MŠk(CZ) LK11205 Grant ostatní: GA MŠk(CZ) LM2011020; European Commission(XE) FP7-241587 SysteMTb Institutional support: RVO:61388963 ; RVO:68378271 Keywords : 7-(het)aryl-7-deazaadenine ribonucleosides * enzyme inhibition * adenosine kinase * cytostatic activity Subject RIV: CC - Organic Chemistry Impact factor: 5.480, year: 2013

  15. Influence of aryl hydrocarbon- (Ah) receptor and genotoxins on DNA repair gene expression and cell survival of mouse hepatoma cells.

    OpenAIRE

    Schreck, Ilona; Chudziak, Doreen; Schneider, Sandra; Seidel, Albrecht; Platt, Karl L.; Oesch, Franz; Weiss, Carsten

    2009-01-01

    The aryl hydrocarbon receptor (AhR) mediates toxicity of a variety of environmental pollutants such as polycyclic aromatic hydrocarbons (PAHs) and dioxins. However, the underlying mechanisms and genetic programmes regulated by AhR to cause adverse effects but also to counteract poisoning are still poorly understood. Here we analysed the effects of two AhR ligands, benzo[a]pyrene (B[a]P), a DNA damaging tumour initiator and promotor and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a pure tumour...

  16. Modulating O2 reactivity in a fungal flavoenzyme: Involvement of aryl-alcohol oxidase Phe-501 contiguous to catalytic histidine

    OpenAIRE

    Hernández-Ortega, Aitor; Lucas, Fátima; Ferreira, Patricia; Medina, Milagros; Guallar, Victor; Martínez, Ángel T.

    2011-01-01

    Aryl-alcohol oxidase (AAO) is a flavoenzyme responsible for activation of O2 to H2O2 in fungal degradation of lignin. The AAO crystal structure shows a buried active site connected to the solvent by a hydrophobic funnel-shaped channel, with Phe-501 and two other aromatic residues forming a narrow bottleneck that prevents the direct access of alcohol substrates. However, ligand diffusion simulations show O2 access to the active site following this channel. Site-directed mutagenesis of Phe-501 ...

  17. OVEREXPRESSION OF ANTIOXIDANT ENZYMES UPREGULATES ARYL HYDROCARBON RECEPTOR EXPRESSION VIA INCREASED SP1 DNA-BINDING ACTIVITY

    OpenAIRE

    Tang, Tian; Lin, Xinghua; Yang, Hong; Zhou, Lichun; Wang, Zefen; Shan, Guang; Guo, Zhongmao

    2010-01-01

    We previously reported up-regulation of aryl hydrocarbon receptor (AhR) expression as a mechanism by which overexpression of Cu/Zn-superoxide dismutase (SOD) and/or catalase accelerates benzo(a)pyrene (BaP) detoxification in mouse aorta endothelial cells (MAECs). The objective of this study was to investigate the regulatory role of specificity protein-1 (Sp1) in AhR expression in MAECs that overexpress Cu/Zn-SOD and/or catalase. Our data demonstrated comparable levels of nuclear Sp1 protein i...

  18. No-carrier-added (NCA) aryl ([sup 18]F) fluorides via the nucleophilic aromatic substitution of electron rich aromatic rings

    Science.gov (United States)

    Yushin Ding; Fowler, J.S.; Wolf, A.P.

    1993-10-19

    A method for synthesizing no-carrier-added (NCA) aryl [.sup.18 F] fluoride substituted aromatic aldehyde compositions bearing an electron donating group is described. The method of the present invention includes the step of reacting aromatic nitro aldehydes having a suitably protected hydroxyl substitutent on an electron rich ring. The reaction is The U.S. Government has rights in this invention pursuant to Contract Number DE-AC02-76CH00016, between the U.S. Department of Energy and Associated Universities Inc.

  19. Diverse Chemicals Including Aryl Hydrocarbon Receptor Ligands Modulate Transcriptional Activity of the 3?Immunoglobulin Heavy Chain Regulatory Region

    OpenAIRE

    Henseler, Rebecca A.; Romer, Eric J.; Sulentic, Courtney E.W.

    2009-01-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a known disruptor of B-cell differentiation and a ligand for the aryl hydrocarbon receptor (AhR), induces binding of the AhR to dioxin responsive elements (DRE) in sensitive genes. The Ig heavy chain (IgH) gene is a sensitive target of TCDD and may be transcriptionally inhibited by TCDD through inhibition of the 3?IgH transcriptional regulatory region (3?IgHRR). While the 3?IgHRR contains binding sites for several transcription factors, two DRE moti...

  20. Synthesis of pyrazole containing ?-amino acids via a highly regioselective condensation/aza-Michael reaction of ?-aryl ?,?-unsaturated ketones.

    Science.gov (United States)

    Gilfillan, Lynne; Artschwager, Raik; Harkiss, Alexander H; Liskamp, Rob M J; Sutherland, Andrew

    2015-03-31

    A synthetic approach for the preparation of a new class of highly conjugated unnatural ?-amino acids bearing a 5-arylpyrazole side-chain has been developed. Horner-Wadsworth-Emmons reaction of an aspartic acid derived ?-keto phosphonate ester with a range of aromatic aldehydes gave ?-aryl ?,?-unsaturated ketones. Treatment of these with phenyl hydrazine followed by oxidation allowed the regioselective synthesis of pyrazole derived ?-amino acids. As well as evaluating the fluorescent properties of the ?-amino acids, their synthetic utility was also explored with the preparation of a sulfonyl fluoride derivative, a potential probe for serine proteases. PMID:25774874

  1. Insulin like growth factor 2 regulation of aryl hydrocarbon receptor in MCF-7 breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Tomblin, Justin K.; Salisbury, Travis B., E-mail: salisburyt@marshall.edu

    2014-01-17

    Highlights: •IGF-2 stimulates concurrent increases in AHR and CCND1 expression. •IGF-2 promotes the binding of AHR to the endogenous cyclin D1 promoter. •AHR knockdown inhibits IGF-2 stimulated increases in CCND1 mRNA and protein. •AHR knockdown inhibits IGF-2 stimulated increases in MCF-7 proliferation. -- Abstract: Insulin like growth factor (IGF)-1 and IGF-2 stimulate normal growth, development and breast cancer cell proliferation. Cyclin D1 (CCND1) promotes cell cycle by inhibiting retinoblastoma protein (RB1). The aryl hydrocarbon receptor (AHR) is a major xenobiotic receptor that also regulates cell cycle. The purpose of this study was to investigate whether IGF-2 promotes MCF-7 breast cancer proliferation by inducing AHR. Western blot and quantitative real time PCR (Q-PCR) analysis revealed that IGF-2 induced an approximately 2-fold increase (P < .001) in the expression of AHR and CCND1. Chromatin immunoprecipitation (ChIP), followed by Q-PCR indicated that IGF-2 promoted (P < .001) a 7-fold increase in AHR binding on the CCND1 promoter. AHR knockdown significantly (P < .001) inhibited IGF-2 stimulated increases in CCND1 mRNA and protein. AHR knockdown cells were less (P < .001) responsive to the proliferative effects of IGF-2 than control cells. Collectively, our findings have revealed a new regulatory mechanism by which IGF-2 induction of AHR promotes the expression of CCND1 and the proliferation of MCF-7 cells. This previously uncharacterized pathway could be important for the proliferation of IGF responsive cancer cells that also express AHR.

  2. Correlating gene expression with deformities caused by aryl hydrocarbon receptor agonists in zebrafish (Danio rerio)

    International Nuclear Information System (INIS)

    Exposure to aryl hydrocarbon receptor (AhR) agonists in fish causes lethal disturbances in fish development, but the effects of acute AhR agonist exposure on the cardiovascular system and deformities remain unclear. This study addressed this issue by performing a series of experiments on zebrafish (Danio rerio). The authors hypothesized that genes needed for cardiovascular regulation (PTGS) would exhibit a stronger link to deformities than detoxification enzymes (CYPs). Zebrafish eggs were exposed aqueously until 4 days post-fertilization (dpf) to the AhR agonists benzo(a)pyrene (BaP) or 2,3,7,8-tetrachlorodibenzop-dioxin (TCDD) alone and in combination with the putative AhR antagonists resveratrol or alpha-naphthoflavone (ANF). Gene expression was measured using real-time, reverse transcriptase PCR in zebrafish at 5 and 10 dpf. Although the mortalities did not differ considerably among groups at 10 dpf, the deformities increased significantly after BaP-ANF at 5 dpf and after BaP at 10 dpf, but not after TCDD treatment. CYP and PTGS isozymes exhibited small, but statistically significant changes at 5 dpf. By 10 dpf, the expression returned to control values. In general, CYP1A and PTGS-1 expression at 5 dpf were positively correlated with deformities, while all other genes were negatively correlated with deformities. It was concluded that changes in CYP1A, CYP1C2, and PTGS-1 gene expression at 5 dpf are associated with developmental deformities, but additional work is ental deformities, but additional work is needed to determine which has the most important mechanistic link.

  3. A possible role of aryl hydrocarbon receptor in spontaneous preterm birth.

    Science.gov (United States)

    Li, Yan; Wang, Kai; Zou, Qing-Yun; Zhou, Chi; Magness, Ronald R; Zheng, Jing

    2015-05-01

    Preterm birth (PTB) is defined as birth before 37 weeks of gestation and is a leading cause of neonatal mortality and morbidity. To date, the etiology of spontaneous PTB (sPTB) remains unclear; however, intrauterine bacterial infection-induced inflammation is considered to be one of the major triggers. Aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor. Upon activation, AhR signaling mediates many biological processes. AhR is abundantly expressed in human placentas, primarily in trophoblasts, and several fetal organs and tissues. The activation of AhR signaling can modulate inflammatory responses via promoting production of pro-inflammatory cytokines by the placenta and fetal membranes. These cytokines could enhance expression and/or activity of cyclooxygenase-2 (COX2) in human trophoblasts and amniotic epithelia, which in turn stimulate synthesis and release of prostaglandins (PGs; e.g., PGE2 and PGF2?). Given the discovery of a number of natural and endogenous AhR ligands in human, we hypothesize that in a subset of patients with high AhR expression in placentas and fetal membranes, repeated exposure to these AhR ligands hyperactivates AhR, inducing hyperactivation of the cytokines/COX2/PGs pathway, resulting in myometrial contractions, ultimately leading to sPTB. We further hypothesize that hyperactivation of this AhR pathway can induce sPTB either directly or in synergy with the bacterial infection. Proof of this hypothesis may provide a novel mechanism underlying sPTB. PMID:25697115

  4. Aryl hydrocarbon receptors in osteoclast lineage cells are a negative regulator of bone mass.

    Science.gov (United States)

    Yu, Tai-yong; Pang, Wei-jun; Yang, Gong-she

    2015-01-01

    Aryl hydrocarbon receptors (AhRs) play a critical role in various pathological and physiological processes. Although recent research has identified AhRs as a key contributor to bone metabolism following studies in systemic AhR knockout (KO) or transgenic mice, the cellular and molecular mechanism(s) in this process remain unclear. In this study, we explored the function of AhR in bone metabolism using AhR(RANK?Oc/?Oc) (RANK(Cre/+);AhR(flox/flox)) mice. We observed enhanced bone mass together with decreased resorption in both male and female 12 and 24-week-old AhR(RANK?Oc/?Oc) mice. Control mice treated with 3-methylcholanthrene (3MC), an AhR agonist, exhibited decreased bone mass and increased bone resorption, whereas AhR(Ctsk?Oc/?Oc) (Ctsk(Cre/+);AhR(flox/flox)) mice injected with 3MC appeared to have a normal bone phenotype. In vitro, bone marrow-derived macrophages (BMDMs) from AhR(RANK?Oc/?Oc) mice exhibited impaired osteoclastogenesis and repressed differentiation with downregulated expression of B lymphocyte-induced maturation protein 1 (Blimp1), and cytochrome P450 genes Cyp1b1 and Cyp1a2. Collectively, our results not only demonstrated that AhR in osteoclast lineage cells is a physiologically relevant regulator of bone resorption, but also highlighted the need for further studies on the skeletal actions of AhR inhibitors in osteoclast lineage cells commonly associated with bone diseases, especially diseases linked to environmental pollutants known to induce bone loss. PMID:25615839

  5. Aryl?hydrocarbon receptor activity modulates prolactin expression in the pituitary

    International Nuclear Information System (INIS)

    Pituitary tumors account for 15% of intracranial neoplasms, however the extent to which environmental toxicants contribute to the proliferation and hormone expression of pituitary cells is unknown. Aryl-hydrocarbon receptor (AhR) interacting protein (AIP) loss of function mutations cause somatotrope and lactotrope adenomas in humans. AIP sequesters AhR and inhibits its transcriptional function. Because of the link between AIP and pituitary tumors, we hypothesize that exposure to dioxins, potent exogenous ligands for AhR that are persistent in the environment, may predispose to pituitary dysfunction through activation of AhR. In the present study, we examined the effect of AhR activation on proliferation and endogenous pituitary hormone expression in the GH3 rat somatolactotrope tumor cell line and the effect of loss of AhR action in knockout mice. GH3 cells respond to nM doses of the reversible AhR agonist ?-naphthoflavone with a robust induction of Cyp1a1. Although mRNA levels of the anti-proliferative signaling cytokine TGFbeta1 are suppressed upon ?-naphthoflavone treatment, we did not observe an alteration in cell proliferation. AhR activation with ?-naphthoflavone suppresses Ahr expression and impairs expression of prolactin (PRL), but not growth hormone (GH) mRNA in GH3 cells. In mice, loss of Ahr similarly leads to a reduction in Prl mRNA at P3, while Gh is unaffected. Additionally, there is a significant reduction in pituitary hormones Lhb and Fshb in the absence of Ahr. Overall, these results demonstrate that AhR is important for pituitary hormone expression and suggest that environmental dioxins can exert endocrine disrupting effects at the pituitary. -- Highlights: ? AhR signaling suppresses Prl mRNA expression. ? AhR signaling does not influence pituitary proliferation in culture. ? AhR is necessary for Prl, Lhb and Fshb expression at postnatal day 3.

  6. Cobaltous chloride and hypoxia inhibit aryl hydrocarbon receptor-mediated responses in breast cancer cells

    International Nuclear Information System (INIS)

    The aryl hydrocarbon receptor (AhR) is expressed in estrogen receptor (ER)-positive ZR-75 breast cancer cells. Treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces CYP1A1 protein and mRNA levels and also activates inhibitory AhR-ER? crosstalk associated with hormone-induced reporter gene expression. In ZR-75 cells grown under hypoxia, induction of these AhR-mediated responses by TCDD was significantly inhibited. This was not accompanied by decreased nuclear AhR levels or decreased interaction of the AhR complex with the CYP1A1 gene promoter as determined in a chromatin immunoprecipitation assay. Hypoxia-induced loss of Ah-responsiveness was not associated with induction of hypoxia-inducible factor-1? or other factors that sequester the AhR nuclear translocation (Arnt) protein, and overexpression of Arnt under hypoxia did not restore Ah-responsiveness. The p65 subunit of NF?B which inhibits AhR-mediated transactivation was not induced by hypoxia and was primarily cytosolic in ZR-75 cells grown under hypoxic and normoxic conditions. In ZR-75 cells maintained under hypoxic conditions for 24 h, BRCA1 (an enhancer of AhR-mediated transactivation in breast cancer cells) was significantly decreased and this contributed to loss of Ah-responsiveness. In cells grown under hypoxia for 6 h, BRCA1 was not decreased, but induction of CYP1A1 by TCDD was significantly decreased. Cotreatment of ZR-75 cells with TCDD plus the protein synthesis inhibitor cycloheximide foin synthesis inhibitor cycloheximide for 6 h enhanced CYP1A1 expression in cells grown under hypoxia and normoxia. These results suggest that hypoxia rapidly induces protein(s) that inhibit Ah-responsiveness and these may be similar to constitutively expressed inhibitors of Ah-responsiveness (under normoxia) that are also inhibited by cycloheximide

  7. Correlating gene expression with deformities caused by aryl hydrocarbon receptor agonists in zebrafish (Danio rerio)

    Energy Technology Data Exchange (ETDEWEB)

    Bugiak, B.; Weber, L. [Saskatchewan Univ., Saskatoon, SK (Canada)

    2009-07-01

    Exposure to aryl hydrocarbon receptor (AhR) agonists in fish causes lethal disturbances in fish development, but the effects of acute AhR agonist exposure on the cardiovascular system and deformities remain unclear. This study addressed this issue by performing a series of experiments on zebrafish (Danio rerio). The authors hypothesized that genes needed for cardiovascular regulation (PTGS) would exhibit a stronger link to deformities than detoxification enzymes (CYPs). Zebrafish eggs were exposed aqueously until 4 days post-fertilization (dpf) to the AhR agonists benzo(a)pyrene (BaP) or 2,3,7,8-tetrachlorodibenzop-dioxin (TCDD) alone and in combination with the putative AhR antagonists resveratrol or alpha-naphthoflavone (ANF). Gene expression was measured using real-time, reverse transcriptase PCR in zebrafish at 5 and 10 dpf. Although the mortalities did not differ considerably among groups at 10 dpf, the deformities increased significantly after BaP-ANF at 5 dpf and after BaP at 10 dpf, but not after TCDD treatment. CYP and PTGS isozymes exhibited small, but statistically significant changes at 5 dpf. By 10 dpf, the expression returned to control values. In general, CYP1A and PTGS-1 expression at 5 dpf were positively correlated with deformities, while all other genes were negatively correlated with deformities. It was concluded that changes in CYP1A, CYP1C2, and PTGS-1 gene expression at 5 dpf are associated with developmental deformities, but additional work is needed to determine which has the most important mechanistic link.

  8. Insulin like growth factor 2 regulation of aryl hydrocarbon receptor in MCF-7 breast cancer cells

    International Nuclear Information System (INIS)

    Highlights: •IGF-2 stimulates concurrent increases in AHR and CCND1 expression. •IGF-2 promotes the binding of AHR to the endogenous cyclin D1 promoter. •AHR knockdown inhibits IGF-2 stimulated increases in CCND1 mRNA and protein. •AHR knockdown inhibits IGF-2 stimulated increases in MCF-7 proliferation. -- Abstract: Insulin like growth factor (IGF)-1 and IGF-2 stimulate normal growth, development and breast cancer cell proliferation. Cyclin D1 (CCND1) promotes cell cycle by inhibiting retinoblastoma protein (RB1). The aryl hydrocarbon receptor (AHR) is a major xenobiotic receptor that also regulates cell cycle. The purpose of this study was to investigate whether IGF-2 promotes MCF-7 breast cancer proliferation by inducing AHR. Western blot and quantitative real time PCR (Q-PCR) analysis revealed that IGF-2 induced an approximately 2-fold increase (P < .001) in the expression of AHR and CCND1. Chromatin immunoprecipitation (ChIP), followed by Q-PCR indicated that IGF-2 promoted (P < .001) a 7-fold increase in AHR binding on the CCND1 promoter. AHR knockdown significantly (P < .001) inhibited IGF-2 stimulated increases in CCND1 mRNA and protein. AHR knockdown cells were less (P < .001) responsive to the proliferative effects of IGF-2 than control cells. Collectively, our findings have revealed a new regulatory mechanism by which IGF-2 induction of AHR promotes the expression of CCND1 and the proliferation of MCF-7 cells. This previously uncharacterized pathway could be important for the proliferation of IGF responsive cancer cells that also express AHR

  9. Aryl hydrocarbon hydroxylase inducibility among primary relatives of children with leukemia or solid tumors.

    Science.gov (United States)

    Levine, A S; McKinney, C E; Echelberger, C K; Kouri, R E; Edwards, B K; Nebert, D W

    1984-01-01

    In mice, there is a correlation between genetically regulated levels of inducible aryl hydrocarbon hydroxylase (AHH) activity and the risk of polycyclic hydrocarbon-induced leukemia or solid tumors. Recent clinical studies suggest a relationship between high AHH activity and lung cancer associated with cigarette smoking (Kouri, R.E., McKinney, C.E., Slomiany, D.J., Snodgrass, D.R., Wray, N.P., and McLemore, T.L. Cancer Res. 42: 5030-5037, 1982). To determine whether there is a similar genetic relationship in humans between inducible AHH and the occurrence of pediatric cancers, we examined AHH activity in mitogen-stimulated benzo(a)anthracene-treated lymphocyte cultures from primary relatives of children with leukemia or solid tumors. Control families (parents and siblings with no history of cancer) comprised friends or neighbors of the proband families. By comparing variance among family members with variance among nonrelated individuals, we conclude that a small, but real, genetic component is detectable. Adjusting for age, smoking history, and the length of time during which the lymphocytes had been cryopreserved, however, we find no difference among 77 leukemia, 71 solid tumor, and 100 control family members with regard to median units (+/- median S.E.) of maximally induced AHH activity per unit of reduced nicotinamide adenine dinucleotide-cytochrome c reductase activity: 0.31 +/- 0.03; 0.28 +/- 0.03; and 0.28 +/- 0.03, respectively. Thus, benzo(a)anthracene-induced AHH activity in cultured mitogen-activated lymphocytes in our study population does not appear to be associated with the risk of occurrence of childhood leukemia or solid tumors. PMID:6690048

  10. Aryl?hydrocarbon receptor activity modulates prolactin expression in the pituitary

    Energy Technology Data Exchange (ETDEWEB)

    Moran, Tyler B.; Brannick, Katherine E.; Raetzman, Lori T., E-mail: raetzman@life.illinois.edu

    2012-11-15

    Pituitary tumors account for 15% of intracranial neoplasms, however the extent to which environmental toxicants contribute to the proliferation and hormone expression of pituitary cells is unknown. Aryl-hydrocarbon receptor (AhR) interacting protein (AIP) loss of function mutations cause somatotrope and lactotrope adenomas in humans. AIP sequesters AhR and inhibits its transcriptional function. Because of the link between AIP and pituitary tumors, we hypothesize that exposure to dioxins, potent exogenous ligands for AhR that are persistent in the environment, may predispose to pituitary dysfunction through activation of AhR. In the present study, we examined the effect of AhR activation on proliferation and endogenous pituitary hormone expression in the GH3 rat somatolactotrope tumor cell line and the effect of loss of AhR action in knockout mice. GH3 cells respond to nM doses of the reversible AhR agonist ?-naphthoflavone with a robust induction of Cyp1a1. Although mRNA levels of the anti-proliferative signaling cytokine TGFbeta1 are suppressed upon ?-naphthoflavone treatment, we did not observe an alteration in cell proliferation. AhR activation with ?-naphthoflavone suppresses Ahr expression and impairs expression of prolactin (PRL), but not growth hormone (GH) mRNA in GH3 cells. In mice, loss of Ahr similarly leads to a reduction in Prl mRNA at P3, while Gh is unaffected. Additionally, there is a significant reduction in pituitary hormones Lhb and Fshb in the absence of Ahr. Overall, these results demonstrate that AhR is important for pituitary hormone expression and suggest that environmental dioxins can exert endocrine disrupting effects at the pituitary. -- Highlights: ? AhR signaling suppresses Prl mRNA expression. ? AhR signaling does not influence pituitary proliferation in culture. ? AhR is necessary for Prl, Lhb and Fshb expression at postnatal day 3.

  11. Analysis of photoaffinity-labeled aryl hydrocarbon receptor heterogeneity by two-dimensional gel electrophoresis

    International Nuclear Information System (INIS)

    The level of charge heterogeneity in the aryl hydrocarbon receptor (AhR) was examined by high-resolution denaturing two-dimensional (2D) gel electrophoresis. Hepa 1c1c7 cell cytosolic fraction was photoaffinity-labeled with 2-azido-3-[125I]-iodo-7,8-dibromodibenzo-p-dioxin and applied to isoelectric focusing (IEF) tube gels. After optimization of focusing conditions a broad peak of radioactivity was detected in the apparent pI range of 5.2-5.7. IEF tube gels were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by visualization of the radiolabeled AhR by autoradiography; three distinct isoforms were detected. The same 2D electrophoretic isoform pattern was obtained when the AhR from Hepa 1c1c7 was photoaffinity-labeled in cell culture. BPrCl cells, a mutant line derived from Hepa 1c1c7 cells, contain an AhR that is unable to bind to DNA. Photoaffinity-labeled BPrCl cytosolic fractions were subjected to 2D gel electrophoretic analysis resulting in essentially the same molecular weight and isoform pattern as seen in Hepa 1c1c7 cytosol. This result would suggest that if a mutation is present in the BPrCl AhR it has not caused a significant change in its IEF pattern, although a small shift in the pI values was observed. Two-dimensional gel electrophoresis of photoaffinity-labeled cytosolic fractions from HeLa cells, the rat liver tumor cell line McA-RH777, and buffalo rat thymus revealed three isofand buffalo rat thymus revealed three isoforms, essentially the same isoform pattern as in Hepa 1c1c7 cells. This would indicate that despite the considerable molecular weight polymorphism between species the level of charge heterogeneity is high conserved

  12. Aryl hydrocarbon receptor ligand effects in RBL2H3 cells

    DEFF Research Database (Denmark)

    Maaetoft-Udsen, Kristina; Shimoda, Lori M. N.

    2012-01-01

    The aryl hydrocarbon receptor (AHR) mediates toxic effects of dioxin and xenobiotic metabolism. AHR has an emerging role in the immune system, but its physiological ligands and functional role in immunocytes remain poorly understood. Mast cells are immunocytes that are central to inflammatory responses and release a spectrum of pro-inflammatory mediators including histamine, mast cell proteases, and pro-inflammatory cytokines such as IL-6 upon stimulation. The aim was to investigate the AHR in model mast cells and examine how both putative and known AHR ligands, e.g., kynurenine, kynurenic acid (KA), Resveratrol, indolmycin, and violacein, affect mast cell activation and signaling. These ligands were tested on calcium signaling, degranulation, and gene expression. The data show that AHR is present in three model mast cell lines, and that various known and putative AHR ligands regulate gene expression of Cyp1a1, a gene down-stream of AHR. Furthermore, it was found that calcium influxes and mast cell secretory responses were enhanced or suppressed after chronic treatment with AHR agonists or antagonists, and that AHR ligands modified RBL2H3 cell degranulation. AHR ligands can chronically change cytokine gene expression in activated mast cells, as exemplified by IL-6. The antagonist Resveratrol repressed expression of induced IL-6 gene expression. Although KA and kynurenine are both AHR agonists, these ligands behaved differently in regards to degranulation and IL-6 expression, indicating that they may function outside of AHR pathways. These data suggest considerable complexity in RBL2H3 responses to AHR ligands, with implications for understanding of both dioxin pathology and the immunological effects of endogenous AHR ligands.

  13. Synthetic approach of norbadione A: new preparation of alcohols from sulfones and boron compounds

    International Nuclear Information System (INIS)

    The synthetic approach of norbadione A, a pigment from mushrooms related to pulvinic acids, was studied. This compound has the property to complex caesium and has shown an antioxidant activity. The first strategy, based on a double Suzuki-Miyaura coupling between a naphtho-lactone with two boron functions and two pulvinic moieties with a triflate was unsuccessful and has shown a deactivating effect of the lactone. Modifications aimed to inhibit the electro-attracting character of the lactone permitted to obtain a bis(coupled) product with a poor yield. A second approach based on a the cyclization of enol aryl-acetates was studied in order to build the pulvinic moiety in several steps. The important reaction of introduction of an alkyl-acetate from a triflate was realised by a palladium-mediated coupling. The cyclization attempts carried out using a naphthalenic compound allowed us to isolate a monocyclised product. A parallel study was to first build a tetronic moiety and then to construct the exocyclic double bond by a method developed in the laboratory for the preparation of an iodated pulvinic compound. Finally, a new preparation of alcohols from sulfones and boron compounds was developed. Two known reactions in the chemistry of boron were combined. The first one is the reaction between anions of sulfones and tri-alkyl-boranes, the second one is a thermal isomerization which places the boron atom in a terminal position. A new preparation of primary alcohols was thus carried out. (author)

  14. Aplicação de análise de componentes principais para verificação de atribuições de sinais nos espetros de RMN ¹H: o caso dos 3-aril (1,2,4)-oxadiazol-5-carboidrazida benzilidenos / Principal component analysis for verifying ¹H NMR spectral assignments: the case of 3-aryl (1,2,4)-oxadiazol-5-carbohydrazide benzylidenes

    Scientific Electronic Library Online (English)

    João Bosco P. da, Silva; Ivani, Malvestiti; Fernando, Hallwass; Mozart N., Ramos; Lúcia F. C. da Costa, Leite; Eliezer J., Barreiro.

    2005-06-01

    Full Text Available [...] Abstract in english The ¹H NMR data set of a series of 3-aryl (1,2,4)-oxadiazol-5-carbohydrazide benzylidene derivatives synthesized in our group was analyzed using the chemometric technique of principal component analysis (PCA). Using the original ¹H NMR data PCA allowed identifying some misassignments of the proton a [...] romatic chemical shifts. As a consequence of this multivariate analysis, nuclear Overhauser difference experiments were performed to investigate the ambiguity of other assignments of the ortho and meta aromatic hydrogens for the compound with the bromine substituent. The effect of the 1,2,4-oxadiazol group as an electron acceptor, mainly for the hydrogens 12,13, has been highlighted.

  15. Compound Semiconductor Radiation Detectors

    CERN Document Server

    Owens, Alan

    2012-01-01

    Although elemental semiconductors such as silicon and germanium are standard for energy dispersive spectroscopy in the laboratory, their use for an increasing range of applications is becoming marginalized by their physical limitations, namely the need for ancillary cooling, their modest stopping powers, and radiation intolerance. Compound semiconductors, on the other hand, encompass such a wide range of physical and electronic properties that they have become viable competitors in a number of applications. Compound Semiconductor Radiation Detectors is a consolidated source of information on all aspects of the use of compound semiconductors for radiation detection and measurement. Serious Competitors to Germanium and Silicon Radiation Detectors Wide-gap compound semiconductors offer the ability to operate in a range of hostile thermal and radiation environments while still maintaining sub-keV spectral resolution at X-ray wavelengths. Narrow-gap materials offer the potential of exceeding the spectral resolutio...

  16. Nomenclature on organic compound

    International Nuclear Information System (INIS)

    This book records the specific nomenclature on compounds it consists of three parts, which deal with hydrocarbon like acyclic hydrocarbon, a single cyclic hydrocarbon, a spiro hydrocarbon and terpene hydrocarbon. The second chapter has basic hetero cyclic on special nomenclature, spiro compound for hetero cyclic. Hetero cyclic assembly and bridged hetero cyclic. The last chapter includes carbon, hydrogen, oxygen, nitrogen, halogen, sulfur, selenium and characteristic of tellurium.

  17. Phenolic Molding Compounds

    Science.gov (United States)

    Koizumi, Koji; Charles, Ted; de Keyser, Hendrik

    Phenolic Molding Compounds continue to exhibit well balanced properties such as heat resistance, chemical resistance, dimensional stability, and creep resistance. They are widely applied in electrical, appliance, small engine, commutator, and automotive applications. As the focus of the automotive industry is weight reduction for greater fuel efficiency, phenolic molding compounds become appealing alternatives to metals. Current market volumes and trends, formulation components and its impact on properties, and a review of common manufacturing methods are presented. Molding processes as well as unique advanced techniques such as high temperature molding, live sprue, and injection/compression technique provide additional benefits in improving the performance characterisitics of phenolic molding compounds. Of special interest are descriptions of some of the latest innovations in automotive components, such as the phenolic intake manifold and valve block for dual clutch transmissions. The chapter also characterizes the most recent developments in new materials, including long glass phenolic molding compounds and carbon fiber reinforced phenolic molding compounds exhibiting a 10-20-fold increase in Charpy impact strength when compared to short fiber filled materials. The role of fatigue testing and fatigue fracture behavior presents some insight into long-term reliability and durability of glass-filled phenolic molding compounds. A section on new technology outlines the important factors to consider in modeling phenolic parts by finite element analysis and flow simulation.

  18. Endocrine disrupting effects of compounds in Danish streams

    DEFF Research Database (Denmark)

    Long, Manhai; Strand, Jakob

    2014-01-01

    Effluents from municipal wastewater-treatment plants and scattered dwellings, as well as runoff from agricultural fields, are sources of endocrine-disrupting compounds (EDCs) in the aquatic environment. The present study investigated the correlation between the occurrence of EDCs in nine Danish streams using passive samplers (polar organic integrative samplers and silicone membranes) and determined their possible biological effects as assessed by mammal cell cultures and the mussel (Unio tumidus). The passive samplers and mussels were exposed simultaneously at the study sites. The extracts from the passive samplers were used to measure the concentrations of EDCs and the biological effects on the estrogen (ER), androgen (AR), and aryl hydrocarbon (AhR)-receptor transactivation. Male mussels were investigated for biomarkers of endocrine effects, such as the levels of vitellogenin-like proteins measured as alkali-labile phosphate (ALP). EDC concentrations, hormone-receptor transactivation (ER, AR, AhR), and level of ALP were greater downstream of wastewater-treatment plants compared with upstream sites and sites supposed to be relatively nonimpacted by wastewater. Furthermore, there was a significant positive correlation between in vitro AhR transactivation and frequency of ALP of male mussels. We conclude that wastewater effluent is an important source of endocrine-disrupting effects in the aquatic environment and that the combination of biological effect measurements and chemical analyses based on passive sampling is useful in the assessment of the ecological state of the aquatic environment.

  19. Endocrine-disrupting effects of compounds in Danish streams

    DEFF Research Database (Denmark)

    Long, Manhai; Strand, Jakob

    2014-01-01

    Effluents from municipal wastewater-treatment plants and scattered dwellings, as well as runoff from agricultural fields, are sources of endocrine-disrupting compounds (EDCs) in the aquatic environment. The present study investigated the correlation between the occurrence of EDCs in nine Danish streams using passive samplers (polar organic integrative samplers and silicone membranes) and determined their possible biological effects as assessed by mammal cell cultures and the mussel (Unio tumidus). The passive samplers and mussels were exposed simultaneously at the study sites. The extracts from the passive samplers were used to measure the concentrations of EDCs and the biological effects on the estrogen (ER), androgen (AR), and aryl hydrocarbon (AhR)-receptor transactivation. Male mussels were investigated for biomarkers of endocrine effects, such as the levels of vitellogenin-like proteins measured as alkali-labile phosphate (ALP). EDC concentrations, hormone-receptor transactivation (ER, AR, AhR), and level of ALP were greater downstream of wastewater-treatment plants compared with upstream sites and sites supposed to be relatively nonimpacted by wastewater. Furthermore, there was a significant positive correlation between in vitro AhR transactivation and frequency of ALP of male mussels. We conclude that wastewater effluent is an important source of endocrine-disrupting effects in the aquatic environment and that the combination of biological effect measurements and chemical analyses based on passive sampling is useful in the assessment of the ecological state of the aquatic environment.

  20. The compound ethers of glycerin

    International Nuclear Information System (INIS)

    In this chapter of book authors describe several methods of receiving of compound ethers of glycerin. The important technic significance have compound glycerin ether and nitric acid. This compound receive by reaction of glycerin with fuming nitric acid