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Sample records for benzofurans

  1. Benzofuran as a promising scaffold for the synthesis of antimicrobial and antibreast cancer agents: A review

    Directory of Open Access Journals (Sweden)

    Ghadamali Khodarahmi

    2015-01-01

    Full Text Available Benzofuran as an important heterocyclic compound is extensively found in natural products as well as synthetic materials. Since benzofuran drivatives display a diverse array of pharmacological activities, an interest in developing new biologically active agents from benzofuran is still under consideration. This review highlights recent findings on biological activities of benzofuran derivatives as antimicrobial and antibreast cancer agents and lays emphasis on the importance of benzofurans as a major source for drug design and development.

  2. 5-Iodo-2,7-dimethyl-3-phenylsulfinyl-1-benzofuran

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    Uk Lee

    2008-02-01

    Full Text Available The title compound, C16H13IO2S, was prepared by the oxidation of 5-iodo-2,7-dimethyl-3-phenylsulfanyl-1-benzofuran using 3-chloroperbenzoic acid. The O atom and the phenyl group of the phenylsulfinyl substituent lie on opposite sides of the plane of the benzofuran system. The phenyl ring is nearly perpendicular to the plane of the benzofuran fragment [89.15 (5°]. The crystal structure is stabilized by an I...O halogen bond [I...O = 3.177 (2 Å and C—I...O = 175.68 (6°] linking molecules into centrosymmetric dimers and by a weak C—H...π interaction between a phenyl H atom and the furan ring of the benzofuran system.

  3. Highly fluorescent benzofuran derivatives of the GFP chromophore

    DEFF Research Database (Denmark)

    Christensen, Mikkel Andreas; Jennum, Karsten Stein; Abrahamsen, Peter Bæch;

    2012-01-01

    Intramolecular cyclization reactions of Green Fluorescent Protein chromophores (GFPc) containing an arylethynyl ortho-substituent at the phenol ring provide new aryl-substituted benzofuran derivatives of the GFPc. Some of these heteroaromatic compounds exhibit significantly enhanced fluorescence ...

  4. Resolution of 2,3-dihydro-benzofuran-3-ols

    Indian Academy of Sciences (India)

    Cédric Charrier; Philippe Bertrand

    2011-07-01

    A new method for the preparation of enantiopure 2,2-disubstituted 2,3-dihydro-benzofuran-3-ols is described. A short synthesis is designed for obtaining various 2,2-disubstitued benzofuran-3-ols as racemic mixtures of the two possible syn and anti diastereoisomers, which can be separated after silylation. The major racemic anti isomers were transesterified using (R)-pentolactone, allowing separation of the pure enantiomers.

  5. Synthesis, Characterization, and Anticancer Activity of New Benzofuran Substituted Chalcones

    OpenAIRE

    COŞKUN, Demet; Tekin, Suat; SANDAL, Süleyman; Coşkun, Mehmet Fatih

    2016-01-01

    Benzofuran derivatives are of great interest in medicinal chemistry and have drawn considerable attention due to their diverse pharmacological profiles including anticancer activity. Similarly, chalcones, which are common substructures of numerous natural products belonging to the flavonoid class, feature strong anticancer properties. A novel series of chalcones, 3-aryl-1-(5-bromo-1-benzofuran-2-yl)-2-propanones propenones (3a–f), were designed, synthesized, and characterized. In vitro antitu...

  6. Expedited Synthesis of Benzofuran-2-Carboxylic Acids via Microwave-Assisted Perkin Rearrangement Reaction

    OpenAIRE

    Marriott, Karla-Sue C.; Bartee, Rena; Morrison, Andrew Z.; Stewart, Leonard; Wesby, Julian

    2012-01-01

    3-Halocoumarins are readily converted into benzofuran-2-carboxylic acids via a Perkin (coumarin-benzofuran ring contraction) rearrangement reaction. This rearrangement entails initial base catalyzed ring fission. The resulting phenoxide anion then attacks a vinyl halide to produce the final benzofuran moiety. We explored this reaction under microwave reaction conditions and were able to significantly reduce reaction times as well as obtain very high yields of a series of benzofuran-2-carboxyl...

  7. 5-Chloro-2-methyl-3-phenylsulfonyl-1-benzofuran

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    Hong Dae Choi

    2008-07-01

    Full Text Available The title compound, C15H11ClO3S, was prepared by the oxidation of 5-chloro-2-methyl-3-phenylsulfanyl-1-benzofuran with 3-chloroperoxybenzoic acid. There are two symmetry-independent molecules in the asymmetric unit. The dihedral angles formed by the phenyl ring and the plane of the benzofuran system are 77.80 (8 and 78.34 (8°. The crystal structure is stabilized by aromatic π–π stacking interactions between the furan ring and the benzene rings of neighbouring benzofuran fragments from two symmetry-independent molecules; the centroid–centroid distances within the stacks are 3.689 (4, 3.702 (4, 3.825 (4 and 3.826 (4 Å. Additionally, the stacked molecules exhibit inter- and intramolecular C—H...O interactions.

  8. 2-(4-Fluorophenyl-5-iodo-3-methylsulfinyl-1-benzofuran

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    Hong Dae Choi

    2010-01-01

    Full Text Available In the title compound, C15H10FIO2S, the O atom and the methyl group of the methylsulfinyl substituent are located on opposite sides of the plane through the benzofuran fragment. The 4-fluorophenyl ring is rotated out of the benzofuran plane by a dihedral angle of 28.33 (5°. The crystal structure is stabilized by a weak non-classical intermolecular C—H...O hydrogen bond and an I...O halogen interaction [3.211 (1 Å].

  9. Phytotoxic Activity of a Benzofuran Isolated from Trichocline reptans

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    C. Vaccarini

    2000-03-01

    Full Text Available Phytotoxic Activity of the 6-acetyl-5-hydroxy-2isopropenyl-2,3-dihydrobenzofurane (1 isolated from Trichocline reptans (Asteraceae was investigated in two weed species. Results indicate that the best growth inhibition effect ocurres on Chenopodium album weed. Phythotoxic effect of the T. reptans chloroformic extract and of the benzofurane are discussed and compared in the two weed species.

  10. Two new benzofuran lignan glycosides from Gelsemium elegans

    Institute of Scientific and Technical Information of China (English)

    Wei Hua; Qing Chun Zhao; Jia Yang; Guo Bing Shi; Li Jun Wu; Tao Guo

    2008-01-01

    Two new benzofuran lignan glycosides,gelsemiunoside A and B,were isolated from the whole plant of Gelsemium elegans Benth.Their structures were elucidated on the basis of spectroscopic evidence.Furthermore,gelsemiunoside A and B were shown a potent cytotoxic activity by suppressing the proliferation of A375-S2 cells.

  11. In Silico Antitubercular Activity Analysis of Benzofuran and Naphthofuran Derivatives

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    Prashantha Karunakar

    2014-01-01

    Full Text Available For the human health, Mycobacterium tuberculosis (MTB is the deadliest enemy since decades due to its multidrug resistant strains. During latent stage of tuberculosis infection, MTB consumes nitrate as the alternate mechanism of respiration in the absence of oxygen, thus increasing its survival and virulence. NarL is a nitrate/nitrite response transcriptional regulatory protein of two-component signal transduction system which regulates nitrate reductase and formate dehydrogenase for MTB adaptation to anaerobic condition. Phosphorylation by sensor kinase (NarX is the primary mechanism behind the activation of NarL although many response regulators get activated by small molecule phospho-donors in the absence of sensor kinase. Using in silico approach, the molecular docking of benzofuran and naphthofuran derivatives and dynamic study of benzofuran derivative were performed. It was observed that compound Ethyl 5-bromo-3-ethoxycarbonylamino-1-benzofuran-2-carboxylate could be stabilized at the active site for over 10 ns of simulation. Here we suggest that derivatives of benzofuran moiety can lead to developing novel antituberculosis drugs.

  12. Bioactive benzofuran derivatives: moracins A-Z in medicinal chemistry.

    Science.gov (United States)

    Naik, Ravi; Harmalkar, Dipesh S; Xu, Xuezhen; Jang, Kyusic; Lee, Kyeong

    2015-01-27

    Benzofuran heterocycles are fundamental structural units in a variety of biologically active natural products as well as synthetic materials. Over the time, benzofuran derivatives have attracted many researchers due to the broad scope of their biological activity, which include anticancer, antimicrobial, immunomodulatory, antioxidant and anti-inflammatory properties. Egonol, homoegonol and moracin families are biologically active natural products containing benzofuran heterocycle as basic structural units. This paper focuses on the moracin family (moracin A to Z). Morus, a genus of flowering plants in the family Moraceae, comprises 10-16 species of deciduous trees commonly known as mulberries. The root bark, stem bark and leaves of Morus alba, M. lhou, Morus macroura are the main sources for arylbenzofuran derivatives including the moracins. A large volume of research has been carried out on moracins and their derivatives, which has shown the pharmacological importance of this benzofuran heterocyclic nucleus. In this mini-review, we attempt to highlight the importance of moracins, as they have been a major source for drug development. Herein, we also summarize the current state of the art concerning the synthesis and medicinal use of moracins A-Z.

  13. 5-Ethyl-3-(2-fluorophenylsulfonyl-2-methyl-1-benzofuran

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    Hong Dae Choi

    2012-10-01

    Full Text Available In the title compound, C17H15FO3S, the 2-fluorophenyl ring makes a dihedral angle of 89.12 (8° with the mean plane of the benzofuran fragment. In the crystal, molecules are linked by weak C—H...O and C—H...π interactions.

  14. Synthesis of Benzofuran Derivatives via Rearrangement and Their Inhibitory Activity on Acetylcholinesterase

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    Ling-Yi Kong

    2010-11-01

    Full Text Available During a synthesis of coumarins to obtain new candidates for treating Alzheimer’s Disease (AD, an unusual rearrangement of a benzopyran group to a benzofuran group occurred, offering a novel synthesis pathway of these benzofuran derivatives. The possible mechanism of the novel rearrangement was also discussed. All of the benzofuran derivatives have weak anti-AChE activities compared with the reference compound, donepezil.

  15. 2-(4-Bromophenyl-5-fluoro-3-phenylsulfinyl-1-benzofuran

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    Hong Dae Choi

    2010-08-01

    Full Text Available In the title compound, C20H12BrFO2S, the O atom and the phenyl group of the phenylsulfinyl substituent lie on opposite sides of the plane through the benzofuran fragment; the phenyl ring is nearly perpendicular to this plane [dihedral angle = 86.98 (6°]. The 4-bromophenyl ring is rotated slightly out of the benzofuran plane, making a dihedral angle of 1.56 (8°. The crystal structure features aromatic π–π interactions between the furan and phenyl rings of neighbouring molecules [centroid–centroid distance = 3.506 (3 Å], and an intermolecular C—H...π interaction. The crystal structure also exhibits a short intermolecular S...S contact [3.2635 (8 Å].

  16. 3-(4-Fluorophenylsulfinyl-5-iodo-2-methyl-1-benzofuran

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    Hong Dae Choi

    2010-07-01

    Full Text Available In the title compound, C15H10FIO2S, the O atom and the 4-fluorophenyl group of the 4-fluorophenylsulfinyl substituent are located on opposite sides of the plane through the benzofuran fragment; the 4-fluorophenyl ring is nearly perpendicular to this plane, making a dihedral angle of 83.37 (7°. The crystal structure is stabilized by weak intermolecular C—H...O hydrogen bonds and an I...O interaction [I...O = 3.255 (2 Å]. The crystal structure also exhibits intermolecular C—F...π interactions [3.068 (2 Å], and aromatic π–π interactions between the furan and benzene rings of neighbouring benzofuran fragments [centroid–centroid distance = 3.636 (2 Å].

  17. 5-Bromo-2-(4-fluorophenyl-3-phenylsulfinyl-1-benzofuran

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    Pil Ja Seo

    2011-09-01

    Full Text Available In the title compound, C20H12BrFO2S, the 4-fluorophenyl ring makes a dihedral angle of 2.63 (6° with the mean plane of the benzofuran fragment. The dihedral angle between the phenyl ring and the mean plane of the benzofuran fragment is 84.60 (6°. In the crystal, molecules are linked by weak intermolecular C—H...O hydrogen bonds, and slipped π–π interactions between the benzene rings of neighbouring molecules [centroid–centroid distance = 3.719 (3 Å, interplanar distance = 3.000 (3 Å and slippage = 1.520 (3 Å].

  18. 5-Cyclopentyl-2-methyl-3-(4-methylphenylsulfonyl-1-benzofuran

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    Hong Dae Choi

    2014-05-01

    Full Text Available In the title compound, C21H22O3S, the cyclopentyl ring adopts a twist conformation. The dihedral angle between the mean planes of the benzofuran and 4-methylphenyl rings is 72.38 (6°. In the crystal, molecules are linked by C—H...O and C—H...π interactions, forming a three-dimensional supramolecular network.

  19. 2,5-Dimethyl-3-(4-methylphenylsulfinyl-1-benzofuran

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    Uk Lee

    2012-05-01

    Full Text Available In the title compound, C17H16O2S, the 4-methylphenyl ring makes a dihedral angle of 88.28 (5° with the mean plane [mean deviation = 0.009 (1 Å] of the benzofuran fragment. In the crystal, molecules are linked by weak C—H...O and C—H...π interactions.

  20. 5-Cyclohexyl-2-(3-fluorophenyl-3-methylsulfinyl-1-benzofuran

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    Hong Dae Choi

    2012-04-01

    Full Text Available In the title compound, C21H21FO2S, the cyclohexyl ring adopts a chair conformation. The 3-fluorophenyl ring makes a dihedral angle of 38.38 (6° with the mean plane [r.m.s. deviation = 0.010 (1 Å] of the benzofuran fragment. In the crystal, molecules are linked by weak C—H...O hydrogen bonds.

  1. 5-Bromo-3-(4-chlorophenylsulfinyl-2-methyl-1-benzofuran

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    Hong Dae Choi

    2010-11-01

    Full Text Available In the title compound, C15H10BrClO2S, the 4-chlorophenyl ring is oriented approximately perpendicular to the mean plane of the benzofuran ring [dihedral angle = 89.55 (9°]. In the crystal, molecules are linked through weak intermolecular C—H...O hydrogen bonds and and a Br...Br contact [3.783 (3 Å].

  2. Synthesis of substituted benzofurans via microwave-enhanced catch and release strategy.

    Science.gov (United States)

    Luca, Lidia De; Giacomelli, Giampaolo; Nieddu, Giammario

    2008-01-01

    A microwave-enhanced procedure for the synthesis of substituted benzofurans starting from 2-(1-hydroxyalkyl)-phenols and using triphenylphosphine polystirene resin is reported. The benzofurans are isolated in good to high yields and purities by simple workup. The procedure can be applied to chiral alpha-alkyl-2-benzofuranmethanamines too. PMID:18507476

  3. Synthesis of Benzofuran Analogue of Go6976, an Isoform Selective Protein Kinase C Inhibitor

    Institute of Scientific and Technical Information of China (English)

    MA, Da-Wei; ZHANG, Xin-Rong; WU, Shi-Hui; TAO, Feng-Gang

    2001-01-01

    Based on the structure of Go6976, a known isoform-selective protein kinase C inhibitor, a benzofuran analogue (1) was designed. This analogue was synthesized by coupling of benzofuran 3-acetic acid and 8-oxo-tryptamine and subsequent intramolecular Dieckmann condensation, alkylation, oxidative photocyclization and cyanation reaction of mesylate.

  4. 5-Cyclopentyl-2-(4-fluorophenyl-3-methylsulfinyl-1-benzofuran

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    Uk Lee

    2011-10-01

    Full Text Available In the title compound, C20H19FO2S, the cyclopentyl ring adopts an envelope conformation. The 4-fluorophenyl ring makes a dihedral angle of 27.10 (7° with the mean plane of the benzofuran fragment. In the crystal, molecules are linked by weak intermolecular C—H...O hydrogen bonds and C—H...π interactions. In the cyclopentyl ring, one C atom is disordered over two orientations with site-occupancy factors of 0.617 (7 and 0.383 (7.

  5. 3-Ethylsulfinyl-2-(4-iodophenyl-5-methyl-1-benzofuran

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    Hong Dae Choi

    2010-08-01

    Full Text Available In the title compound, C17H15IO2S, the 4-iodophenyl ring makes a dihedral angle of 35.39 (8° with the plane of the benzofuran fragment. In the crystal, molecules are linked by intermolecular C—H...O and C—H...π interactions, and an I...O contact [3.378 (2 Å]. The crystal structure also exhibits aromatic π–π interactions between the benzene rings of neighbouring molecules [centroid–centroid distance = 3.495 (3 Å].

  6. Synthesis, Characterization, and Anticancer Activity of New Benzofuran Substituted Chalcones

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    Demet Coşkun

    2016-01-01

    Full Text Available Benzofuran derivatives are of great interest in medicinal chemistry and have drawn considerable attention due to their diverse pharmacological profiles including anticancer activity. Similarly, chalcones, which are common substructures of numerous natural products belonging to the flavonoid class, feature strong anticancer properties. A novel series of chalcones, 3-aryl-1-(5-bromo-1-benzofuran-2-yl-2-propanones propenones (3a–f, were designed, synthesized, and characterized. In vitro antitumor activities of the newly synthesized (3a–f and previously synthesized (3g–j chalcone compounds were determined by using human breast (MCF-7 and prostate (PC-3 cancer cell lines. Antitumor properties of all compounds were determined by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay. Cell viability assay for the tested chalcone compounds was performed and the log⁡IC50 values of the compounds were calculated after 24-hour treatment. Our results indicate that the tested chalcone compounds show antitumor activity against MCF-7 and PC-3 cell lines (p<0.05.

  7. STRUCTURES OF TWO NEW BENZOFURAN DERIVATIVES FROM THE BARK OF MULBERRY TREE (MORUS MACROURA MIQ.)

    Institute of Scientific and Technical Information of China (English)

    SHENG-GUO SUN; RUO-YUN CHEN; DE-QUAN YU

    2001-01-01

    Two new benzofuran derivatives, macrourins A (1) and B (2), together with two known stilbene derivatives, were isolated from the barks of Morus macroura Miq. Their structures were elucidated by means of spectroscopic evidence.

  8. 2-(4-Fluorophenyl-5-iodo-3-phenylsulfinyl-1-benzofuran

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    Hong Dae Choi

    2012-04-01

    Full Text Available In the title compound, C20H12FIO2S, the dihedral angles between the mean plane [r.m.s. deviation = 0.014 (1 Å] of the benzofuran fragment and the pendant 4-fluorophenyl and phenyl rings are 8.0 (1 and 86.06 (6°, respectively. In the crystal, molecules are linked by weak C—H...O hydrogen bonds. The crystal structure also exhibits weak π–π interactions between the furan and benzene rings of neighbouring molecules [centroid–centroid distance = 3.547 (2 Å, interplanar distance = 3.397 (2 Å and slippage = 1.021 (2 Å].

  9. Spin transport in benzofurane bithiophene based organic spin valves

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    Mathieu Palosse

    2014-01-01

    Full Text Available In this paper we present spin transport in organic spin-valves using benzofurane bithiophene (BF3 as spacer layer between NiFe and Co ferromagnetic electrodes. The use of an AlOx buffer layer between the top electrode and the organic layer is discussed in terms of improvements of stacking topology, electrical transport and oxygen contamination of the BF3 layer. A study of magnetic hysteresis cycles evidences spin-valve behaviour. Transport properties are indicative of unshorted devices with non-linear I-V characteristics. Finally we report a magnetoresistance of 3% at 40 K and 10 mV in a sample with a 50 nm thick spacer layer, using an AlOx buffer layer.

  10. Spin transport in benzofurane bithiophene based organic spin valves

    Energy Technology Data Exchange (ETDEWEB)

    Palosse, Mathieu; Séguy, Isabelle; Bedel-Pereira, Élena [CNRS, LAAS, 7 avenue du Colonel Roche, F-31400 Toulouse (France); Université de Toulouse (France); UPS, INSA, INP, ISAE (France); LAAS (France); CEMES, F-31077 Toulouse (France); Villeneuve-Faure, Christina [Université de Toulouse (France); UPS, INSA, INP, ISAE (France); LAAS (France); CEMES, F-31077 Toulouse (France); LAPLACE, Université Paul Sabatier, 118, route de Narbonne 31062 Toulouse Cedex 9 (France); Mallet, Charlotte; Frère, Pierre [MOLTECH-Anjou, UMR CNRS 6200, Université d’Angers, 2 Bd Lavoisier 49045 ANGERS Cedex (France); Warot-Fonrose, Bénédicte; Biziere, Nicolas [Université de Toulouse (France); UPS, INSA, INP, ISAE (France); LAAS (France); CEMES, F-31077 Toulouse (France); CNRS, CEMES-CNRS UPR 8011, 29 rue Jeanne Marvig, BP 94347, FR-31055 Toulouse Cedex 4 (France); Bobo, Jean-François, E-mail: jfbobo@cemes.fr [Université de Toulouse (France); UPS, INSA, INP, ISAE (France); LAAS (France); CEMES, F-31077 Toulouse (France); CNRS, CEMES-ONERA, NMH, 2 avenue Edouard Belin, FR-31055 Toulouse Cedex 4 (France)

    2014-01-15

    In this paper we present spin transport in organic spin-valves using benzofurane bithiophene (BF3) as spacer layer between NiFe and Co ferromagnetic electrodes. The use of an AlO{sub x} buffer layer between the top electrode and the organic layer is discussed in terms of improvements of stacking topology, electrical transport and oxygen contamination of the BF3 layer. A study of magnetic hysteresis cycles evidences spin-valve behaviour. Transport properties are indicative of unshorted devices with non-linear I-V characteristics. Finally we report a magnetoresistance of 3% at 40 K and 10 mV in a sample with a 50 nm thick spacer layer, using an AlO{sub x} buffer layer.

  11. Novel psychoactive benzofurans strongly increase extracellular serotonin level in mouse corpus striatum.

    Science.gov (United States)

    Fuwa, Tatsu; Suzuki, Jin; Tanaka, Toyohito; Inomata, Akiko; Honda, Yoshiko; Kodama, Tohru

    2016-01-01

    We examined the effects of three benzofurans [1-(Benzofuran-5-yl)-N-methylpropan-2-amine (5-MAPB), 1-(Benzofuran-2-yl)-N-methylpropan-2-amine (2-MAPB), and 1-(Benzofuran-5-yl)-N-ethylpropan-2-amine (5-EAPB)] on the extracellular monoamine level in mouse corpus striatum by the microdialysis method and compared them with the effects of psychoactive 3,4-Methylenedioxymethamphetamine (MDMA). The effects of benzofurans on the extracellular monoamine level were qualitatively analogous to that of MDMA, with an increase in serotonin (5-HT) level exceeding dopamine (DA) level. The effects of 2-MAPB and 5-EAPB were almost the same as the effect of MDMA. However, 5-MAPB strongly increased extracellular monoamine level than MDMA. These differences in the potency appear to have a structure-activity relationship. The administration of 5-MAPB (1.6 × 10(-4) mol/kg B.W.) resulted in the death of two-thirds of the mice. The same dose of MDMA did not cause any deaths. The administration of 5-MAPB (1.6 × 10(-4) mol/kg B.W.) produced a 3.41°C ± 0.28°C rise in rectal temperature after 1 hr, whereas the administration of MDMA (1.6 × 10(-4) mol/kg B.W.) produced an approximate 1.85°C ± 0.26°C rise. These results suggest that benzofurans have 5-HT toxicity similar to MDMA, and 5-MAPB has a higher risk of lethal intoxication than MDMA. Furthermore, 5-APB, the metabolic product of 5-MAPB demethylation, may be involved in the acute 5-HT toxicity and may cause lethal intoxication in mice. PMID:27193726

  12. 2-(5-Fluoro-3-isopropylsulfanyl-7-methyl-1-benzofuran-2-ylacetic acid

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    Hong Dae Choi

    2012-04-01

    Full Text Available The title compound, C14H15FO3S, was prepared by alkaline hydrolysis of ethyl 2-(5-fluoro-3-isopropylsulfanyl-7-methyl-1-benzofuran-2-ylacetate. In the crystal, molecules are linked via pairs of O—H...O hydrogen bonds, forming inversion dimers. These dimers are connected by weak C—H...O hydrogen bonds.

  13. 2-(4-Fluorophenyl-5-iodo-7-methyl-3-methylsulfinyl-1-benzofuran

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    Hong Dae Choi

    2010-07-01

    Full Text Available In the title compound, C16H12FIO2S, the O atom and the methyl group of the methylsulfinyl substituent lie on opposite sides of the plane through the benzofuran fragment. The 4-fluorophenyl ring is rotated slightly out of the benzofuran plane, as indicated by the dihedral angle of 7.43 (6°. In the crystal structure, pairs of short I...O [3.074 (2 Å] contacts link the molecules into centrosymmetric dimers. These dimers are further linked via aromatic π–π interactions between the benzene and the 4-fluorophenyl rings of neighbouring molecules [centroid–centroid distance = 3.617 (3 Å].

  14. 3-(4-Fluorophenylsulfinyl-5-iodo-2,7-dimethyl-1-benzofuran

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    Hong Dae Choi

    2011-05-01

    Full Text Available In the title compound, C16H12FlO2S, the 4-fluorophenyl ring makes a dihedral angle of 80.21 (6° with the mean plane of the benzofuran fragment. In the crystal, molecules are linked through weak intermolecular C—H...O hydrogen bonds. The crystal structure also exhibits an intermolecular I...F contact [3.423 (2 Å].

  15. 5-Bromo-7-methyl-2-(4-methylphenyl-3-methylsulfinyl-1-benzofuran

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    Hong Dae Choi

    2012-12-01

    Full Text Available In the title compound, C17H15BrO2S, the 4-methylphenyl ring makes a dihedral angle of 14.46 (5° with the mean plane [r.m.s. deviation = 0.005 (1 Å] of the benzofuran fragment. In the crystal, molecules are linked by pairs of Br...O contacts [3.151 (2 Å] into centrosymmetric dimers.

  16. 3-(2-Fluorophenylsulfinyl-2,5,7-trimethyl-1-benzofuran

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    Hong Dae Choi

    2013-06-01

    Full Text Available In the title compound, C17H15FO2S, the benzofuran ring system, being essentially planar, with an r.m.s. deviation from the least-squares plane of 0.009 (2 Å, makes a dihedral angle of 79.02 (5° with the plane of the 2-fluorophenyl group. In the crystal, molecules are linked by pairs of weak C—H...O hydrogen bonds into centrosymmetric dimers.

  17. 2-(4-Fluorophenyl-5,6-methylenedioxy-3-phenylsulfinyl-1-benzofuran monohydrate

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    Pil Ja Seo

    2012-02-01

    Full Text Available In the title compound, C21H13FO4S·H2O, the dihedral angles between the mean plane of the benzofuran fragment (r.m.s. deviation = 0.005 Å and the pendant 4-fluorophenyl and phenyl rings are 6.24 (7 and 83.39 (6°, respectively. In the crystal, molecules are linked by O—H...O and C—H...O hydrogen bonds.

  18. Benzofurans as efficient dienophiles in normal electron demand [4 + 2] cycloadditions.

    Science.gov (United States)

    Chopin, Nathalie; Gérard, Hélène; Chataigner, Isabelle; Piettre, Serge R

    2009-02-01

    Dearomatization of electron-poor benzofurans is possible through involvement of the aromatic 2,3-carbon-carbon double bond as dienophile in normal electron demand [4 + 2] cycloadditions. The tricyclic heterocycles thereby produced bear a quaternary center at the cis ring junction, a feature of many alkaloids such as morphine, galanthamine, or lunaridine. The products arising from the reaction have been shown to depend on different factors among which the type of the electron-withdrawing substituent of the benzofuran, the nature of the reacting diene, and the method of activation. In the presence of all-carbon dienes, the reaction yields the expected Diels-Alder adducts. When thermal activation is insufficient, a biactivation associating zinc chloride catalysis and high pressure is required to generate the cycloadducts in good yields and high stereoselectivities, for instance, when cyclohexadiene is involved in the process. The use of more functionalized dienes, such as those bearing alkoxy or silyloxy substituents, also shows the limits of the thermal activation, and hyperbaric conditions are, in this case, well-suited. The involvement of Danishefsky's diene induces a competition in the site of reactivity. The aromatic 2,3-carbon-carbon double bond is unambiguously the most reactive dienophile, and the 3-carbonyl unit becomes a competitive site of reactivity with benzofurans bearing substituents prone to heterocyloaddition, in particular under Lewis acid activation. The sequential involvement of both the aromatic double bond and the carbonyl moiety as dienophiles is then possible by using an excess of diene under high-pressure activation. In line with the experimental results, DFT computations suggest that the Diels-Alder process involving the aromatic double bond is preferred over the hetero-Diels-Alder route through an asynchronous concerted transition state. However, Lewis acid catalysis appears to favor the heterocycloaddition pathway through a stepwise

  19. 5-Iodo-2,7-dimethyl-3-(4-methylphenylsulfonyl-1-benzofuran

    Directory of Open Access Journals (Sweden)

    Hong Dae Choi

    2012-10-01

    Full Text Available In the title compound, C17H15IO3S, the 4-methylphenyl ring makes a dihedral angle of 76.95 (5° with the mean plane [r.m.s. deviation = 0.019 (2 Å] of the benzofuran fragment. In the crystal, molecules are linked via pairs of C—H...O hydrogen bonds, forming inversion dimers. These dimers are connected by slipped π–π interactions between the benzene rings of neighbouring molecules [centroid–centroid distance = 3.671 (3 Å and slippage = 1.049 (3 Å].

  20. 2-(3-Fluorophenyl-5-iodo-7-methyl-3-methylsulfinyl-1-benzofuran

    Directory of Open Access Journals (Sweden)

    Hong Dae Choi

    2012-06-01

    Full Text Available In the title compound, C16H12FIO2S, the 3-fluorophenyl ring makes a dihedral angle of 34.93 (7° with the mean plane [r.m.s. deviation = 0.019 (1 Å] of the benzofuran fragment. In the crystal, molecules are linked via pairs of I...O contacts [3.088 (2 Å] into inversion dimers. These dimers are connected by weak C—H...O hydrogen bonds.

  1. 3-Ethylsulfinyl-2-(3-fluorophenyl-5-iodo-7-methyl-1-benzofuran

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    Hong Dae Choi

    2012-10-01

    Full Text Available In the title compound, C17H14FIO2S, the 3-fluorophenyl ring makes a dihedral angle of 14.56 (5° with the mean plane [r.m.s. deviation = 0.012 (1 Å] of the benzofuran fragment. In the crystal, molecules are linked via pairs of I...O contacts [3.038 (2 Å], forming inversion dimers. In the 3-fluorophenyl ring, the F atom is disordered over two positions, with site-occupancy factors of 0.747 (3 and 0.253 (3.

  2. 2-Chloroethyl 2-(5-bromo-3-methylsulfinyl-1-benzofuran-2-ylacetate

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    Uk Lee

    2009-05-01

    Full Text Available In the title compound, C13H12BrClO4S, the O atom and the methyl group of the methylsulfinyl substituent lie on opposite sides of the plane of the benzofuran fragment. There is a mean deviation of 0.016 (4 Å from the least-squares plane defined by the nine constituent benzofuran atoms. The crystal structure is stabilized by aromatic π–π interactions between the benzene rings of neighbouring molecules [centroid–centroid distance = 3.689 (7 Å]and by a weak C—H...π interaction between an H atom of the methylene group bonded to the carboxylate O atom and the benzene ring of an adjacent molecule. In addition, the crystal structure exhibits weak non-classical intermolecular C—H...O hydrogen bonds. The chloroethyl group is disordered over two positions, with refined site-occupancy factors of 0.767 (6 and 0.233 (6.

  3. Butyl 2-(5-iodo-3-methylsulfinyl-1-benzofuran-2-ylacetate

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    Uk Lee

    2009-02-01

    Full Text Available In the title compound, C15H17IO4S, the O atom and the methyl group of the methylsulfinyl substituent lie on opposite sides of the plane of the benzofuran fragment. The crystal structure is stabilized by weak intermolecular C—H...π interactions between a methyl H atom of the methylsulfinyl group and the benzene ring of the benzofuran system, and by an I...O halogen bond of 3.173 (3 Å and a nearly linear C—I...O angle of 171.7 (1°. In addition, the crystal structure exhibits weak intermolecular C—H...O hydrogen bonds. The O atom of the carbonyl group and the butyl chain are both disordered over two positions with site-occupancy factors from refinement of 0.55 (4 and 0.45 (4 (for the O atom, and 0.76 (2 and 0.24 (2 (for the butyl group.

  4. 5-(4-Bromophenyl-2-(3,4-methylenedioxyphenyl-3-methylsulfanyl-1-benzofuran

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    Hong Dae Choi

    2009-10-01

    Full Text Available The title compound, C22H15BrO3S, crystallizes with four molecules in the asymmetric unit. The 4-bromophenyl rings are rotated out of the benzofuran planes, with dihedral angles for the four molecules of 20.8 (2, 17.8 (2, 23.5 (4 and 23.9 (4°. The dihedral angles between the 3,4-methylenedioxyphenyl ring and the benzofuran plane are 13.5 (2, 7.1 (2, 18.6 (3 and 14.2 (3° in the four molecules. The crystal structure is stabilized by weak nonclassical intermolecular C—H...O hydrogen bonds. The crystal structure also exhibits intermolecular aromatic π–π interactions between the benzene and furan rings and between the 4-bromophenyl and 3,4-methylenedioxyphenyl rings from molecules of the same type; the centroid–centroid distances are 3.92 (1 and 3.79 (1, 3.91 (1, 3.77 (1 and 3.77 (1, and 3.79 (1 and 3.75 (1Å in the four molecules.

  5. Enantioselective synthesis of benzofurans and benzoxazines via an olefin cross-metathesis-intramolecular oxo-Michael reaction.

    Science.gov (United States)

    Zhang, Jun-Wei; Cai, Quan; Gu, Qing; Shi, Xiao-Xin; You, Shu-Li

    2013-09-11

    Chiral phosphoric acid and Hoveyda-Grubbs II were found to catalyze an olefin cross-metathesis-intramolecular oxo-Michael cascade reaction of the ortho-allylphenols and enones to provide a variety of benzofuran and benzoxazine derivatives in moderate to good yields and enantioselectivity.

  6. Anti-inflammatory and cytotoxic neoflavonoids and benzofurans from Pterocarpus santalinus.

    Science.gov (United States)

    Wu, Shou-Fang; Chang, Fang-Rong; Wang, Sheng-Yang; Hwang, Tsong-Long; Lee, Chia-Lin; Chen, Shu-Li; Wu, Chin-Chung; Wu, Yang-Chang

    2011-05-27

    Five new benzofurans, pterolinuses A-E (1-5), six new neoflavonoids, pterolinuses F-J (8-13), and five known compounds (6, 7, 14-16) were isolated from an extract of Pterocarpus santalinus heartwood. All new structures were elucidated by spectroscopic methods, and configurations were confirmed by CD spectral data and optical rotation values. The isolates were evaluated for anti-inflammatory and cytotoxic activities. Six compounds (1, 2, 4, 6, 7, and 15) showed significant inhibition in at least one anti-inflammatory assay. Compound 2 showed the best selective effect against superoxide anion generation in human neutrophils with, an IC50 value of 0.19 μg/mL, and was 6.2-fold more potent than the positive control LY294002. Compound 14 showed the highest cytotoxicity against Ca9-22 cancer cells, with an IC50 value of 0.46 μg/mL. PMID:21488654

  7. Fluorescent deep-blue and hybrid white emitting devices based on a naphthalene-benzofuran compound

    KAUST Repository

    Yang, Xiaohui

    2013-08-01

    We report the synthesis, photophysics and electrochemical properties of naphthalene-benzofuran compound 1 and its application in organic light emitting devices. Fluorescent deep-blue emitting devices employing 1 as the emitting dopant embedded in 4-4′-bis(9-carbazolyl)-2,2′-biphenyl (CBP) host show the peak external quantum efficiency of 4.5% and Commission Internationale d\\'Énclairage (CIE) coordinates of (0.15, 0.07). Hybrid white devices using fluorescent blue emitting layer with 1 and a phosphorescent orange emitting layer based on an iridium-complex show the peak external quantum efficiency above 10% and CIE coordinates of (0.31, 0.37). © 2013 Published by Elsevier B.V.

  8. Crystal structure of 1-(5-bromo-1-benzofuran-2-ylethanone oxime

    Directory of Open Access Journals (Sweden)

    G. Krishnaswamy

    2015-10-01

    Full Text Available The title compound, C10H8BrNO2, is almost planar (r.m.s. deviation for the non-H atoms = 0.031 Å and the conformation across the C=N bond is trans. Further, the O atom of the benzofuran ring is syn to the N atom of the oxime group. In the crystal, inversion dimers linked by pairs of O—H...N hydrogen bonds generate R22(6 loops. Very weak aromatic π–π stacking interactions [centroid–centroid separations = 3.9100 (12 and 3.9447 (12 Å] are also observed.

  9. 3-(4-Fluorophenylsulfonyl-5-iodo-2,7-dimethyl-1-benzofuran

    Directory of Open Access Journals (Sweden)

    Pil Ja Seo

    2012-01-01

    Full Text Available In the title compound, C16H12FIO3S, the 4-fluorophenyl ring makes a dihedral angle of 72.31 (6° with the mean plane of the benzofuran fragment. In the crystal, molecules are linked by weak C—H...O hydrogen bonds, and by an I...I contact [3.7764 (3 Å]. The crystal structure also exhibits a weak C—I...π [3.901 (3 Å] interaction and a slipped π–π interaction between the furan and benzene rings of neighbouring molecules [centroid–centroid distance = 3.845 (3, interplanar distance = 3.555 (3 and slippage = 1.465 (3 Å].

  10. 3-(3-Fluorophenylsulfinyl-5-iodo-2,7-dimethyl-1-benzofuran

    Directory of Open Access Journals (Sweden)

    Hong Dae Choi

    2012-10-01

    Full Text Available In the title compound, C16H12FIO2S, the 3-fluorophenyl ring makes a dihedral angle of 76.47 (6° with the mean plane [r.m.s. deviation = 0.013 (2 Å] of the benzofuran fragment. In the crystal, molecules are linked by weak C—H...O hydrogen bonds,forming chains along the b-axis direction, and an I...O contact [3.204 (2 Å]. The crystal structure also exhibits slipped π–π interactions between the 3-fluorophenyl rings of neighbouring molecules [centroid–centroid distance = 3.683 (3 Å and slippage = 1.708 (3 Å].

  11. A new benzofuran in Catalpa ovata%梓实中的新苯并呋喃

    Institute of Scientific and Technical Information of China (English)

    王奇志; 梁敬钰

    2005-01-01

    目的研究梓实的化学成分.方法采用各种色谱技术进行分离纯化,通过理化常数和光谱分析鉴定化合物的结构.结果通过UV、IR、ESI-MS、1H-NMR、13C-NMR、1H-1H COSY、HMQC、HMBC、NOESY和CD等光谱分析鉴定新化合物为2(S)-[3′-羟基-5′-甲氧基]苯基-3(S)-甲酸乙酯基-6-反丙烯酸乙酯基-8-甲氧基苯并呋喃[2(S)-(3'-hydroxy-5'-methoxy)-benz-3(S)-ethoxycarbonyl-6-trans-ethyl acrylate-8-methoxy-benzofuran].结论该化合物为新化合物,命名为梓呋新.

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

    Directory of Open Access Journals (Sweden)

    Shakya Ashok K.

    2016-09-01

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

  13. Rational design, synthesis and 2D-QSAR study of novel vasorelaxant active benzofuran-pyridine hybrids.

    Science.gov (United States)

    Srour, Aladdin M; Abd El-Karim, Somaia S; Saleh, Dalia O; El-Eraky, Wafaa I; Nofal, Zeinab M

    2016-05-15

    Reaction of 3-aryl-1-(benzofuran-2-yl)-2-propen-1-ones 3a-c with malononitrile in the presence of sufficient amount of sodium alkoxide in the corresponding alcohol proceeds in a regioselective manner to afford 2-alkoxy-4-aryl-6-(benzofuran-2-yl)-3-pyridinecarbonitriles 4-37, which also obtained by treating ylidenemalononitriles 6a-q with 2-acetylbenzofuran 1 in the presence of sufficient amount of sodium alkoxide in the corresponding alcohol. The new chemical entities showed significant vasodilation properties using isolated thoracic aortic rings of rats pre-contracted with norepinephrine hydrochloride standard technique. Compounds 11, 16, 21, 24 and 30 exhibited remarkable activity compared with amiodarone hydrochloride the reference standard used in the present study. CODESSA-Pro software was employing to obtain a statistically significant QSAR model describing the bioactivity of the newly synthesized analogs (N=31, n=5, R(2)=0.846, R(2)cvOO=0.765, R(2)cvMO=0.778, F=27.540. s(2)=0.002). PMID:27048942

  14. Rational design, synthesis and 2D-QSAR study of novel vasorelaxant active benzofuran-pyridine hybrids.

    Science.gov (United States)

    Srour, Aladdin M; Abd El-Karim, Somaia S; Saleh, Dalia O; El-Eraky, Wafaa I; Nofal, Zeinab M

    2016-05-15

    Reaction of 3-aryl-1-(benzofuran-2-yl)-2-propen-1-ones 3a-c with malononitrile in the presence of sufficient amount of sodium alkoxide in the corresponding alcohol proceeds in a regioselective manner to afford 2-alkoxy-4-aryl-6-(benzofuran-2-yl)-3-pyridinecarbonitriles 4-37, which also obtained by treating ylidenemalononitriles 6a-q with 2-acetylbenzofuran 1 in the presence of sufficient amount of sodium alkoxide in the corresponding alcohol. The new chemical entities showed significant vasodilation properties using isolated thoracic aortic rings of rats pre-contracted with norepinephrine hydrochloride standard technique. Compounds 11, 16, 21, 24 and 30 exhibited remarkable activity compared with amiodarone hydrochloride the reference standard used in the present study. CODESSA-Pro software was employing to obtain a statistically significant QSAR model describing the bioactivity of the newly synthesized analogs (N=31, n=5, R(2)=0.846, R(2)cvOO=0.765, R(2)cvMO=0.778, F=27.540. s(2)=0.002).

  15. Synthesis of 2-Substituted Benzofurans from o-Iodophenols and Terminal Alkynes with a Recyclable Palladium Catalyst Supported on Nano-sized Carbon Balls under Copper- and Ligand-Free Conditions

    Energy Technology Data Exchange (ETDEWEB)

    Yum, Eul Kgun; Yang, Okkyung; Kim, Jieun; Park, Hee Jank [Chungnam National Univ., Daejeon (Korea, Republic of)

    2013-09-15

    We have developed a one-step synthesis of benzofurans from o-iodophenol and various terminal alkynes, by using Pd catalyst supported on nano-sized carbon balls (NCB) under copper- and ligand free conditions. This recyclable catalyst could be reused more than 5 times in the same heteroannulation reaction. The results have demonstrated that diverse 2-substituted benzofurans with tolerant functional groups can be prepared simply and conveniently under these conditions.

  16. A Novel and Facile Synthesis of 2-(Benzofuran-2-yl)benzo[h]- quinoline-3-carboxylic Acid Derivatives

    Institute of Scientific and Technical Information of China (English)

    高文涛; 姜云; 李阳; 李凤; 闫岩

    2012-01-01

    A simple and concise approach for the synthesis of a series of new heterocyclic systems of 2-(benzofuran-2-yl)- benzo[h]quinoline-3-carboxylic acid derivatives (3a--3g) is described. The synthetic strategy features the one-pot reaction of ethyl 2-(chloromethyl)benzo[h]quinoline-3-carboxylate (2) with various substituted salicylaldehydes as well as 2-hydroxy-l-naphthaldehyde as a key step. The substrate 2 was prepared in good yield by a mild, efficient and direct reaction of 1-naphthylamine (1) with Vilsmeier-Haack reagent. The structures of all the new compounds were identified by spectral data and elemental analysis.

  17. Design, synthesis, biological evaluation and molecular docking studies of novel benzofuran-pyrazole derivatives as anticancer agents.

    Science.gov (United States)

    Abd El-Karim, Somaia S; Anwar, Manal M; Mohamed, Neama A; Nasr, Tamer; Elseginy, Samia A

    2015-12-01

    This study deals with design and synthesis of novel benzofuran-pyrazole hybrids as anticancer agents. Eight compounds were chosen by National Cancer Institute (NCI), USA to evaluate their in vitro antiproliferative activity at 10(-5)M in full NCI 60 cell panel. The preliminary screening of the tested compounds showed promising broad-spectrum anticancer activity. Compound 4c was further assayed for five dose molar ranges in full NCI 60 cell panel and exhibited remarkable growth inhibitory activity pattern against Leukemia CCRF-CEM, MOLT-4, Lung Cancer HOP-92, Colon Cancer HCC-2998, CNS Cancer SNB-75, Melanoma SK-MEL-2, Ovarian Cancer IGROV1, Renal Cancer 786-0, RXF 393, Breast Cancer HS 578T and T-47D (GI50: 1.00-2.71μM). Moreover, enzyme assays were carried out to investigate the possible antiproliferative mechanism of action of compound 4c. The results revealed that compound 4c has good c-Src inhibitory activity at 10μM. In addition, molecular docking studies showed that 4c could bind to the ATP Src pocket sites. Fulfilling the Lipinskiís rule of five in addition to its ADME profile and the biological results, all strongly suggest that 4c is a promising Src kinase inhibitor.

  18. Acute 5-(2-aminopropyl)benzofuran (5-APB) intoxication and fatality: a case report with postmortem concentrations.

    Science.gov (United States)

    McIntyre, Iain M; Gary, Ray D; Trochta, Amber; Stolberg, Susan; Stabley, Robert

    2015-03-01

    A 20-year-old man, a college student, became unresponsive in front of his girlfriend. He was known to consume alcohol and take an unknown drug at some point while in attendance at a local music festival earlier in the day/evening. Upon arrival of emergency personnel, he was noted to be asystolic and apneic. Despite aggressive medical intervention by emergency personnel and at a local hospital emergency room, he was pronounced deceased within 1.25 h of initial medical attention. Postmortem blood initially screened positive for methamphetamine by ELISA. An alkaline drug screen detected 5-(2-aminopropyl)benzofuran (5-APB) which was subsequently confirmed and quantified by a specific GC-MS SIM analysis following solid-phase extraction. Concentrations were determined in the peripheral blood (2.5 mg/L), central blood (2.9 mg/L), liver (16 mg/kg), vitreous (1.3 mg/L), urine (23 mg/L) and gastric contents (6 mg). No other common amphetamine-like compound was detected, although 5-(2-aminopropyl)-2,3-dihydrobenzofuran (5-APDB) was presumptively identified in both peripheral blood and urine. Alcohol, the only other drug identified, was confirmed at a concentration of 0.02% (w/v). PMID:25429871

  19. Synthesis, Characterization, and Antibacterial Activity of Co(II, Ni(II, Cu(II, Zn(II, Cd(II, and Hg(II Complexes of Schiff's Base Type Ligands Containing Benzofuran Moiety

    Directory of Open Access Journals (Sweden)

    N. Shashidhar Reddy

    2013-01-01

    Full Text Available Six new complexes of Co(II, Ni(II, Cu(II, Zn(II, Cd(II, and Hg(II with substituted benzofuran derivatives have been synthesized and characterized by elemental analysis, magnetic moments, conductance measurements, spectral characterization, and so forth. Elemental data coincide with the general formula MLC1n, where L = (E-7-Methoxy-N1-(2,4,5-trimethoxy benzylidene benzofuran-2-carbohydrazide (L1 or (E-N1-(2,6-dichloro benzylidene-7-methoxy benzofuran-2-carbohydrazide (L2, of the complexes. The ligands coordinate to the metal ions through the oxygen of the carbonyl group and the nitrogen of the hydrazine group. Electronic spectral data of the complexes suggests the probable geometry is octahedral in nature. All the complexes and ligands were screened for their antibacterial activity. Among them, Co, Ni, and Cu complexes of L2 showed good activity against all microbes.

  20. SYNTHESIS OF 1-({7-METHOXY-2-[4-(METHYLSULFANYL PHENYL]-1- BENZOFURAN-5-YL}-N-[(N-ETHYLPYRROLIDIN-2-YL METHYL]METHANAMINE BY REDUCTIVE AMINATION. Synthese von 1 - ({7-methoxy-2-[4 - (methylsulfanyl phenyl] -1 - BENZOFURAN-5-yl}-N-[(N-Ethylpyrrolidin-2-yl methyl] MethanaMine Durch reduktive LAMINATION.

    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. A solution of Mannich base in acetic anhydride was refluxed for 24 hrs to give crude diacetate which is purified and treated with HCl to give chloromethyl derivative. It is further treated with triphenylphosphine in dry benzene under reflux condition. The phosphonium salt undergoes condensation with 4-methylsulfanylbenzoyl chloride by refluxing in toluene in presence of triethylamine. The reaction was completed in 6 hrs. The crude product was purified by using column chromatography. The resulting 7-methoxy-2-[4- (methylsulfanylphenyl]-l-benzofuran-5-carboxaldehyde was subjected to reductive amination and the final product 1-({7-methoxy-2-[4-(methylsulfanylphenyl]-1-benzofuran-5-yl}-N-[(Nethylpyrrolidin- 2-ylmethyl]methan amine was purified by column chromatography and characterized by FT-IR, NMR and Mass spectroscopy.

  1. 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.

  2. Synthesis and Anti-TMV Activity of Dialkyl/dibenzyl 2-((6-Substituted-benzo[d]thiazol-2-ylamino(benzofuran-2-ylmethyl Malonates

    Directory of Open Access Journals (Sweden)

    Meichuan Li

    2013-11-01

    Full Text Available Starting from benzofuran-2-methanal, 6-substituted benzothiazole-2-amines and malonic esters, sixteen title compounds were designed and synthesized seeking to introduce anti-TMV activity. The structures of the newly synthesized compounds were confirmed by 1H-NMR, 13C-NMR, IR spectra, and MS (HREI analysis. The bioassays identified some of these new compounds as having moderate to good anti-TMV activity. The compounds 5i and 5m have good antiviral activity against TMV with a curative rate of 52.23% and 54.41%, respectively, at a concentration of 0.5 mg/mL.

  3. Synthesis of benzofuran derivatives as selective inhibitors of tissue-nonspecific alkaline phosphatase: effects on cell toxicity and osteoblast-induced mineralization.

    Science.gov (United States)

    Marquès, Stéphanie; Buchet, René; Popowycz, Florence; Lemaire, Marc; Mebarek, Saïda

    2016-03-01

    Tissue-nonspecific alkaline phosphatase (TNAP) by hydrolyzing pyrophosphate, an inhibitor of apatite formation, promotes extracellular matrix calcification during bone formation and growth, as well as during ectopic calcification under pathological conditions. TNAP is a target for the treatment of soft tissue pathological ossification. We synthesized a series of benzofuran derivatives. Among these, SMA14, displayed TNAP activity better than levamisole. SMA14 was found to be not toxic at doses of up to 40μM in osteoblast-like Saos-2 cells and primary osteoblasts. As probed by Alizarin Red staining, this compound inhibited mineral formation in murine primary osteoblast and in osteoblast-like Saos-2 cells.

  4. Synthesis of benzofuran based 1,3,5-substituted pyrazole derivatives: as a new class of potent antioxidants and antimicrobials--a novel accost to amend biocompatibility.

    Science.gov (United States)

    Rangaswamy, Javarappa; Kumar, Honnaiah Vijay; Harini, Salakatte Thammaiah; Naik, Nagaraja

    2012-07-15

    In search for a new antioxidant and antimicrobial agent with improved potency, we synthesized a series of benzofuran based 1,3,5-substituted pyrazole analogues (5a-l) in five step reaction. Initially, o-alkyl derivative of salicyaldehyde readily furnish corresponding 2-acetyl benzofuran 2 in good yield, on treatment with 1,8-diaza bicyclo[5.4.0]undec-7-ene (DBU) in the presence of molecular sieves. Further, aldol condensation with vanillin, Claisen-Schmidt condensation reaction with hydrazine hydrate followed by coupling of substituted anilines afforded target compounds. The structures of newly synthesized compounds were confirmed by IR, (1)H NMR, (13)C NMR, mass, elemental analysis and further screened for their antioxidant and antimicrobial activities. Among the tested compounds 5d and 5f exhibited good antioxidant property with 50% inhibitory concentration higher than that of reference while compounds 5h and 5l exhibited good antimicrobial activity at concentration 1.0 and 0.5 mg/mL compared with standard, streptomycin and fluconazole respectively.

  5. Synthesis of 2-(1-Benzofuran-2-yl-4-(1,3-benzoxazol-2-yl/ 1,3-benzothiazol-2-yl Quinolines as Blue Green Fluorescent Probes

    Directory of Open Access Journals (Sweden)

    Yadav D. Bodke

    2013-01-01

    Full Text Available A series of novel 2-(1-benzofuran-2-yl-4-(1,3 benzoxazol-2-yl/1,3-benzothiazol-2-yl quinoline derivatives 4(a–d were synthesized in one step by the reaction of 2-(1-benzofuran-2-yl quinoline-4-carboxylic acids 3(a-b with o-aminophenol and o-amino thiophenol, respectively, using polyphosphoric acid (PPA as a cyclizing agent. The fluorescent properties of newly synthesized compounds were investigated in three different organic solvents like chloroform (CHCl3, tetrahydrofuran (THF, and dimethyl sulfoxide (DMSO. The photophysical constants such as quantum yield and stokes shift were determined. From the results of fluorescence study, it is evident that all synthesized compounds are fluorescent in solution. Compound 4a emitted green light (490.4 nm, 518.2 nm, and 522.4 nm with high quantum yield in all the three solvents, while compounds 4b, 4c, and 4d emitted green light (512 nm, 499 nm, 510 nm only in polar solvent DMSO. All fluorescent probes exhibited a bathochromic shift on increase in polarity of the solvent.

  6. A study of anti-inflammatory activity of the benzofuran compound (3,4-dihydro 4-oxo-benzofuro [3,2-d] pyrimidine-2-propionic acid in chronic model of inflammation

    Directory of Open Access Journals (Sweden)

    Lakshminarayana K.

    2015-10-01

    Conclusion: Our experiment shows that the benzofuran compound under study has got significant anti-inflammatory activity and may, as well become an additional anti-inflammatory drug if further studies are conducted in this direction involving human beings. [Int J Basic Clin Pharmacol 2015; 4(5.000: 1021-1023

  7. Metabolic fate, mass spectral fragmentation, detectability, and differentiation in urine of the benzofuran designer drugs 6-APB and 6-MAPB in comparison to their 5-isomers using GC-MS and LC-(HR)-MS(n) techniques.

    Science.gov (United States)

    Welter, Jessica; Brandt, Simon D; Kavanagh, Pierce; Meyer, Markus R; Maurer, Hans H

    2015-05-01

    The number of so-called new psychoactive substances (NPS) is still increasing by modification of the chemical structure of known (scheduled) drugs. As analogues of amphetamines, 2-aminopropyl-benzofurans were sold. They were consumed because of their euphoric and empathogenic effects. After the 5-(2-aminopropyl)benzofurans, the 6-(2-aminopropyl)benzofuran isomers appeared. Thus, the question arose whether the metabolic fate, the mass spectral fragmentation, and the detectability in urine are comparable or different and how an intake can be differentiated. In the present study, 6-(2-aminopropyl)benzofuran (6-APB) and its N-methyl derivative 6-MAPB (N-methyl-6-(2-aminopropyl)benzofuran) were investigated to answer these questions. The metabolites of both drugs were identified in rat urine and human liver preparations using GC-MS and/or liquid chromatography-high resolution-mass spectrometry (LC-HR-MS(n)). Besides the parent drug, the main metabolite of 6-APB was 4-carboxymethyl-3-hydroxy amphetamine and the main metabolites of 6-MAPB were 6-APB (N-demethyl metabolite) and 4-carboxymethyl-3-hydroxy methamphetamine. The cytochrome P450 (CYP) isoenzymes involved in the 6-MAPB N-demethylation were CYP1A2, CYP2D6, and CYP3A4. An intake of a common users' dose of 6-APB or 6-MAPB could be confirmed in rat urine using the authors' GC-MS and the LC-MS(n) standard urine screening approaches with the corresponding parent drugs as major target allowing their differentiation. Furthermore, a differentiation of 6-APB and 6-MAPB in urine from their positional isomers 5-APB and 5-MAPB was successfully performed after solid phase extraction and heptafluorobutyrylation by GC-MS via their retention times. PMID:25711990

  8. Crystal structure of 5-(1-benzofuran-2-yl-3-(4-methylphenyl-4,5-dihydro-1,2-oxazol-5-ol

    Directory of Open Access Journals (Sweden)

    A. J. Ravi

    2015-07-01

    Full Text Available In the title compound, C18H15NO3, the isoxazole moiety adopts a shallow envelope conformation, with the C atom bearing the OH group displaced by 0.148 (1 Å from the mean plane through the other four atoms. The mean plane of this ring (all atoms subtends dihedral angles of 87.19 (6 and 15.51 (7° with the benzofuran ring system (r.m.s. deviation = 0.007 Å and the 4-methylphenyl ring, respectively. In the crystal, molecules are linked by O—H...N hydrogen bonds, generating [001] C(5 chains, with adjacent molecules in the chain related by c-glide symmetry. Weak C—H...O interactions link the chains into a three-dimensional network.

  9. Synthesis and preliminary characterization of radioiodinated benzofuran-3-yl-(indol-3-yl)maleimide derivatives as potential SPECT imaging probes for the detection of glycogen synthase kinase-3β (GSK-3β) in the brain.

    Science.gov (United States)

    Ono, Masahiro; Kitada, Ayane; Watanabe, Hiroyuki; Miyazaki, Anna; Kimura, Hiroyuki; Saji, Hideo

    2016-06-30

    We report on the synthesis and preliminary characterization of two radioiodinated benzofuran-3-yl-(indol-3-yl)maleimides, 3-(benzofuran-3-yl)-4-(5-[(125) I]iodo-1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione ([(125) I]5), and 3-(5-[(125) I]iodo-1-methyl-1H-indol-3-yl)-4-(6-methoxybenzofuran-3-yl)-1H-pyrrole-2,5-dione ([(125) I]6), as the first potential SPECT imaging probes targeting glycogen synthase kinase-3β (GSK-3β). In this study, we used (125) I as a surrogate of (123) I because of its ease of use. The radioiodinated ligands were prepared from the corresponding tributyltin precursors through an iododestannylation reaction using hydrogen peroxide as an oxidant with a radiochemical yield of 10-30%. In vitro binding experiments suggested that both compounds show high affinity for GSK-3β at a level similar to a known GSK-3β inhibitor. Biodistribution studies with normal mice revealed that the radioiodinated compounds display sufficient uptake into (1.8%ID/g at 10 min postinjection) and clearance from the brain (1.0%ID/g at 60 min postinjection). These preliminary results suggest that the further optimization of radioiodinated benzofuran-3-yl-(indol-3-yl)maleimide derivatives may facilitate the development of clinically useful SPECT imaging probes for the in vivo detection of GSK-3β. PMID:27126914

  10. Antiproliferative, DNA cleavage, and ADMET study of substituted 2-(1-benzofuran-2-yl quinoline-4-carboxylic acid and its esters

    Directory of Open Access Journals (Sweden)

    R. Anantacharya

    2016-12-01

    Full Text Available Synthesis, anti-proliferative, DNA cleavage, and in silico ADMET studies of 2-(1-benzofuran-2-yl quinoline-4-carboxylic acids and their resultant esters in acid catalyzed medium have been investigated. The synthesized compounds are characterized by UV, IR, 1H NMR, 13C NMR, and mass spectral analysis. The electrophoretic DNA cleavage studies on λ-DNA (Eco-RI/Hinda-III double digest using agarose gel method and the antiproliferative activity was carried out by MTT assay on five different human cancer cell lines (Chronic Myelogenous Leukemia (K562, Breast Cancer (MCF-7, Cervical Cancer (HeLa, Colorectal Adino carcinoma (Colo 205, and Hepato cellular carcinoma (HepG2. Doxorubicin is taken as standard for comparison. The cleavage study indicated that molecules (3b–6a and 7b–8c did cleave the DNA completely with no trace of fragments. The molecules (6b, 6c and 7a have appeared to cleave DNA partially and assessed by comparing the bands appeared in control and test compounds at 100 μg concentration. The MTT antiproliferative activity of the synthesized derivatives at a concentration of 10 mM screened that out of the five cancer cell lines tested, the compounds 8b (25.97%, MCF-7, 7a (25.36%, Colo 205, and 7b (24.22%, HePG showed considerable degree of activity at a very low concentration. The molecules were active against MCF-7, Colo 205, and HepG. The molecules exhibited acceptable range in in silico ADMET prediction, significant DNA cleavage, and antiproliferative properties. The study further provides identification of possible lead moiety as an antiproliferative agent.

  11. Benzofuran analogues of amphetamine and methamphetamine: studies on the metabolism and toxicological analysis of 5-APB and 5-MAPB in urine and plasma using GC-MS and LC-(HR)-MS(n) techniques.

    Science.gov (United States)

    Welter, Jessica; Kavanagh, Pierce; Meyer, Markus R; Maurer, Hans H

    2015-02-01

    5-APB (5-(2-aminopropyl)benzofuran) and its N-methyl derivative 5-MAPB (N-methyl-5-(2-aminopropyl)benzofuran) are analogues of amphetamine and methamphetamine, respectively, and belong to the so-called novel psychoactive substances (NPS). They were consumed as stimulants or entactogens with euphoric and empathogenic effects. Being controlled in some countries, both compounds should be covered by drug testing in clinical and forensic toxicology. Therefore, metabolism studies have been performed by working up rat urine samples after a high single dose of the corresponding NPS with solid-phase extraction without and after enzymatic conjugates cleavage. The phase I metabolites were separated and identified after acetylation by GC-MS and/or LC-HR-MS(n) and the phase II metabolites by LC-HR-MS(n). The main metabolite of 5-APB was 3-carboxymethyl-4-hydroxy amphetamine and the main metabolites of 5-MAPB were 5-APB (N-demethyl metabolite) and 3-carboxymethyl-4-hydroxy methamphetamine. The cytochrome P450 (CYP) isoenzymes involved in the 5-MAPB N-demethylation were CYP1A2, CYP2B6, CYP2C19, and CYP2D6, and according to the kinetic parameters, CYP2B6 was responsible for the main part of the total CYP-dependent clearance. An intake of a common users' dose of 5-APB or 5-MAPB could be confirmed in rat urine using the authors' GC-MS and the LC-MS(n) standard urine screening approaches with the corresponding parent drugs as major target. In authentic human urine samples after ingestion of unknown doses of 5-MAPB, both metabolites could also be detected besides the parent drug. The plasma concentrations determined in six clinical cases ranged from 5 to 124 μg/L for 5-MAPB and from 1 to 38 μg/L for its N-demethyl metabolite 5-APB. PMID:25471293

  12. An investigation on structural, vibrational and nonlinear optical behavior of 4b,9b-dihydroxy-7,8-dihydro-4bH-Indeno[1,2-b] Benzofuran-9,10(6H,9bH)-dione: A DFT study

    Indian Academy of Sciences (India)

    Tanveer Hasan; Sayed Hasan Mehdi; Raza Murad Ghalib; P K Singh; Neeraj Misra

    2015-12-01

    A detailed theoretical quantum chemical study on 4b,9b-dihydroxy-7,8-dihydro-4bH-indeno[1,2-b] benzofuran-9,10(6H,9bH)-dione (Dihydroxy-Dihydro-Indeno-Benzofuran-Dione) has been discussed. The structure of the title molecule has been optimized and the structural parameters have been calculated by DFT/B3LYP method with 6-311++G(d,p) basis set. The fundamental vibrational wavenumbers as well as their intensities were calculated and excellent agreement between observed and calculated wavenumbers has been achieved and was interpreted in terms of potential energy distribution analysis. The electronic properties such as HOMO and LUMO energies and associated frontier energy band gap were calculated. Thermodynamical parameters along with the nonlinear optical (NLO) behavior of the title molecule are also discussed. The lower value of frontier orbital energy gap and a higher value of dipole moment suggest that the title compound is highly reactive. The NLO behavior of the title compound has been achieved by dipole moment, polarizability and first static hyperpolarizability. The large value of hyperpolarizability total, indicates that the title molecule may serve as a good NLO material. The theoretical results were found to be in coherence with the measured experimental data.

  13. The amiodarone derivative 2-methyl-3-(3,5-diiodo-4-carboxymethoxybenzyl)benzofuran (KB130015) opens large-conductance Ca2+-activated K+ channels and relaxes vascular smooth muscle.

    Science.gov (United States)

    Gessner, Guido; Heller, Regine; Hoshi, Toshinori; Heinemann, Stefan H

    2007-01-26

    2-methyl-3-(3,5-diiodo-4-carboxymethoxybenzyl)benzofuran (KB130015) has been developed to retain the antiarrhythmic properties of the parent molecule amiodarone but to eliminate its undesired side effects. In patch-clamp experiments, KB130015 activated large-conductance, Ca2+-activated BK(Ca) channels formed by hSlo1 (alpha) subunits in HEK 293 cells. Channels were reversibly activated by shifting the open-probability/voltage (P(o)/V) relationship by about -60 mV in 3 muM intracellular free Ca2+ ([Ca2+]in). No effect on the single-channel conductance was observed. KB130015-mediated activation of BK(Ca) channels was half-maximal at 20 microM with a Hill coefficient of 2.8. BK(Ca) activation by KB130015 did not require the presence of Ca2+ and still occurred with saturating (100 microM) [Ca2+]in. Effects of the prototypic BK(Ca) activator NS1619 (1,3-dihydro-1-[2-hydroxy-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-2H-benzimidazol-2-one) and those of KB130015 were not additive suggesting that both activators may at least partially share a common mechanism of action. KB130015-mediated activation was observed also for BK(Ca) channels from insects and for human BK(Ca) channels with already profoundly left-shifted voltage-dependence. In contrast, human intermediate conductance Ca2+-activated channels were inhibited by KB130015. Using segments of porcine pulmonary arteries, KB130015 induced endothelium-independent vasorelaxation, half-maximal at 43 microM KB130015. Relaxation was inhibited by 1 mM tetraethylammonium, suggesting that KB130015 can activate vascular smooth muscle type BK(Ca) channels under physiological conditions. Interestingly, the shift in the P(o)/V relationship was considerably stronger (-90 mV in 3 microM [Ca2+]in) for BK(Ca) channels containing Slo-beta1 subunits. Thus, KB130015 belongs to a novel class of BK(Ca) channel openers that exert an effect depending on the subunit composition of the channel complex.

  14. 3-Cyclohexylsulfonyl-5-iodo-2,7-dimethyl-1-benzofuran

    Directory of Open Access Journals (Sweden)

    Pil Ja Seo

    2011-08-01

    Full Text Available In the title compound, C16H19IO3S, the cyclohexyl ring adopts a chair conformation. In the crystal, pairs of intermolecular I...O contacts [3.269 (2 Å] link the molecules into inversion dimers. These dimers are further stabilized by a slipped π–π interaction between the benzene and furan rings of adjacent molecules [centroid–centroid distance = 3.701 (3 Å, interplanar distance = 3.372 (3 Å and slippage = 1.525 (3 Å].

  15. Screening of benzofuran compound 3-acetamido-2-p-anisoyl benzofuran for anti-inflammatory activity in acute models of inflammation

    Directory of Open Access Journals (Sweden)

    Lakshminarayana K.

    2016-04-01

    Conclusions: Results from our study show that the compound under study has significant anti-inflammatory activity and further detailed works with this compound in different doses are needed. [Int J Basic Clin Pharmacol 2016; 5(2.000: 239-242

  16. New gas-phase cyclisation reactions leading to benzofurans and flavones

    OpenAIRE

    Chang, Da

    2013-01-01

    The main focus of the project was the synthesis of oxo-stabilised phosphonium ylides with an o-methoxy functionalised benzene ring, and flash vacuum pyrolysis (FVP) of the ylides leading to cyclisation forming a flavone or ring-fused benzopyranone. The first class examined were β,γ-dioxo ylides with two carbonyls on the same side. Two compounds of this type were prepared and in one case the structure was determined by X-ray diffraction. Upon FVP, the ylides underwent the desire...

  17. Benzofuran Small Molecules as Potential Inhibitors of Human Protein Kinases. A Review.

    Science.gov (United States)

    Kwiecień, Halina; Goszczyńska, Agata; Rokosz, Paulina

    2016-01-01

    Kinases are known to regulate the majority of human cellular processes such as communication, division, metabolism, survival and apoptosis therefore they can be promising targets in cancer diseases, viral infection and in other disorders. Small molecules acting as selective human protein kinase inhibitors are very attractive pharmacological targets. This review presents a number of examples of biologically active natural and synthetic benzo[b]furans and their derivatives, such as benzo[b]furan-2- and 3-ones, benzo[b]furan-2- and 3-carboxylic acids, as well as benzo[c]furans as potential inhibitors of various human protein kinases. The pathways of function and implication of the inhibitors in cancer and other diseases are discussed. PMID:26648467

  18. Crystal structure of 5-chloro-3-cyclohexylsulfinyl-2,4,6-trimethyl-1-benzofuran

    OpenAIRE

    Hong Dae Choi; Uk Lee

    2014-01-01

    In the title compound, C17H21ClO2S, the cyclohexyl ring adopts a chair conformation with the C—S bond in an equatorial orientation. In the crystal, molecules are linked by C—H...O and C—H...π hydrogen bonds and a Cl...π [3.594 (2) Å] contact into chains along the a-axis direction.

  19. Crystal structure of 5-chloro-3-cyclohexylsulfinyl-2,4,6-trimethyl-1-benzofuran

    Directory of Open Access Journals (Sweden)

    Hong Dae Choi

    2014-09-01

    Full Text Available In the title compound, C17H21ClO2S, the cyclohexyl ring adopts a chair conformation with the C—S bond in an equatorial orientation. In the crystal, molecules are linked by C—H...O and C—H...π hydrogen bonds and a Cl...π [3.594 (2 Å] contact into chains along the a-axis direction.

  20. Novel Antimicrobial Agents: Fluorinated 2-(3-(Benzofuran-2-yl pyrazol-1-ylthiazoles

    Directory of Open Access Journals (Sweden)

    Hanan A. Mohamed

    2013-01-01

    Full Text Available A new series of 2-pyrazolin-1-ylthiazoles 8a–d and 13–16 was synthesized by cyclization of N-thiocarboxamide-2-pyrazoline with different haloketones and 2,3-dichloroquinoxaline. The structures of the new compounds were confirmed by elemental analyses as well as NMR, IR, and mass spectral data. The newly synthesized compounds were evaluated for their antimicrobial activities, and also their minimum inhibitory concentration (MIC against most of test organisms was performed. Amongst the tested ones, compound 8c displayed excellent antimicrobial activity.

  1. Asetil Benzofuran Metakrilat Blendlerinin Termal, Elektriksel ve Biyolojik Özelliklerinin İncelenmesi

    OpenAIRE

     İlter, Zülfiye; Erol, Gülşen

    2016-01-01

    Bu çalışmada, asetilbenzofuran metakrilat (ABM) polimerinin Stiren (St) ve Akrilonitril (AN) polimerleri ile farklı yüzdelerde blendleri hazırlandı. Var olan kopolimer ve hazırlanan blendler FT‐IR ve 1H‐NMR ile karakterize edildi. Kopolimer ve blendlerin fiziksel ve biyolojik özellikleri araştırıldı ve birbirleri ile karşılaştırıldı. Blendlerin termal özellikleri DSC ve TGA teknikleri ile araştırılırken ortalama molekül ağırlıkları GPC tekniğiyle ile belirlendi. Sonuçlar incelendi...

  2. Bis(2,2-dimethyl-2,3-dihydro-1-benzofuran-7-yl carbonate

    Directory of Open Access Journals (Sweden)

    Lin-Tao Yang

    2011-02-01

    Full Text Available The title compound, C21H22O5, crystallizes with three molecules in the asymmetric unit. In one molecule, two methyl groups are disordered over two positions with a site occupation factor of 0.72 (2 for the major occupancy site. The benzene rings make dihedral angles of 35.3 (6, 29.7 (6 and 40.6 (7° in the three molecules.

  3. Enantiomeric Separation of 1-(Benzofuran-2-yl)alkylamines on Chiral Stationary Phases Based on Chiral Crown Ethers

    Energy Technology Data Exchange (ETDEWEB)

    Park, Soohyun; Kim, Sang Jun; Hyun, Myung Ho [Pusan National Univ., Busan (Korea, Republic of)

    2012-10-15

    Optically active chiral amines are important as building blocks for pharmaceuticals and as scaffolds for chiral ligands and, consequently, many efforts have been devoted to the development of efficient methods for their preparation. For example, reduction of amine precursors with chiral catalysts, enzymatic kinetic resolution or dynamic kinetic resolution of racemic amines and the direct amination of ketones with transaminases have been developed as the efficient methods for the preparation of optically active chiral amines. During the process of developing or utilizing optically active chiral amines, the methods for the determination of their enantiomeric composition are essential. Among various methods, liquid chromatographic resolution of enantiomers on chiral stationary phases (CSPs) have been known to be one of the most accurate and economic means for the determination of the enantiomeric composition of optically active chiral compounds. Especially, CSPs based on chiral crown ethers have been successfully used for the resolution of racemic primary amines. For example, CSPs based on (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid (CSP 1, Figure 1) or (3,3'-diphenyl-1,1'-binaphthyl)-20-crown-6 (CSP 2 and CSP 3, Figure 1) have been known to be quite effective for the resolution of cyclic and non-cyclic amines, various fluoroquinolone antibacterials containing a primary amino group, tocainide (antiarrhythmic agent) and its analogues, aryl-a-amino ketones and 3-amino-1,4-benzodiazepin-2-ones.

  4. Enantioselective Reduction by Crude Plant Parts: Reduction of Benzofuran-2-yl Methyl Ketone with Carrot ("Daucus carota") Bits

    Science.gov (United States)

    Ravia, Silvana; Gamenara, Daniela; Schapiro, Valeria; Bellomo, Ana; Adum, Jorge; Seoane, Gustavo; Gonzalez, David

    2006-01-01

    The use of biocatalysis and biotransformations are important tools in green chemistry. The enantioselective reduction of a ketone by crude plant parts, using carrot ("Daucus carota") as the reducing agent is presented. The experiment introduces an example of a green chemistry procedure that can be tailored to fit in a regular laboratory session.…

  5. Silver iodide nanoparticle as an efficient and reusable catalyst for the one-pot synthesis of benzofurans under aqueous conditions

    Indian Academy of Sciences (India)

    Javad Safaei-Ghomi; Mohammad Ali Ghasemzadeh

    2013-09-01

    Recyclable heterogeneous AgI nanoparticles were efficiently catalysed one-pot three-component reaction of aldehydes, secondary amines and alkyne in aqueous media. This method provides a novel and improved approach for the synthesis of 2,3-disubstituted benzo[b]furan derivatives to obtain excellent yields, short reaction times and low catalyst loading.

  6. Synthesis and characterization of benzofuran derivative%苯并呋喃衍生物的合成和结构表征

    Institute of Scientific and Technical Information of China (English)

    李洪森; 覃兆海; 付宾; 王明安; 李楠

    2008-01-01

    天然化合物常表现出各种独特的生物活性,使其成为寻找和筛选各种生物活性物质如医药、农药等的天然宝库。楝酰胺(rocaglamide)(结构式如图式1)是从楝属植物中分离出的具有良好杀虫活性的化合物[1],对疆叶蛾的LC50为0.91 μg/mL,与已知的天然杀虫剂苦楝素Azadirachtin(LC50为0.70 μg/mL)的活性相当旧[2-4],

  7. The Novel 7 Nicotinic Acetylcholine Receptor Agonist N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-7-[2-(methoxy)phenyl]-1-benzofuran-2-carboxamide Improves Working and Recognition Memory in Rodents

    NARCIS (Netherlands)

    Boess, F.G.; Vry, de J.; Erb, C.; Flessner, T.; Luithle, J.; Methfessel, C.; Schnizler, K.; Staay, van der F.J.; Kampen, van M.; Wiese, W.B.; Hendrix, M.; König, G.

    2007-01-01

    The relative contribution of alpha 4 beta 2, alpha 7 and other nicotinic acetylcholine receptor ( nAChR) subtypes to the memory enhancing versus the addictive effects of nicotine is the subject of ongoing debate. In the present study, we characterized the pharmacological and behavioral properties of

  8. (3aRS,7aSR-7a-Methoxy-2-oxo-2,3,3a,4,5,6,7,7a-octahydro-1-benzofuran-4,4-dicarbonitrile

    Directory of Open Access Journals (Sweden)

    María González

    2012-12-01

    Full Text Available The racemic title compound, C11H12N2O3, contains a [4.3.0]bicyclic unit in which the shared C—C bond adopts a cis configuration. The five- and six-membered rings are in twisted envelope (with the bridgehead C atom bearing the methoxy substituent as the flap and distorted chair conformations, respectively. In the crystal, the molecules are linked via weak C—H...O iteractions, forming ladder-like chains along [010].

  9. Biodegradation of Various Aromatic Compounds by Enriched Bacterial Cultures: Part B--Nitrogen-, Sulfur-, and Oxygen-Containing Heterocyclic Aromatic Compounds.

    Science.gov (United States)

    Oberoi, Akashdeep Singh; Philip, Ligy; Bhallamudi, S Murty

    2015-07-01

    Present study focused on the biodegradation of various heterocyclic nitrogen, sulfur, and oxygen (NSO) compounds using naphthalene-enriched culture. Target compounds in the study were pyridine, quinoline, benzothiophene, and benzofuran. Screening studies were carried out using different microbial consortia enriched with specific polycyclic aromatic hydrocarbon (PAH) and NSO compounds. Among different microbial consortia, naphthalene-enriched culture was the most efficient consortium based on high substrate degradation rate. Substrate degradation rate with naphthalene-enriched culture followed the order pyridine > quinoline > benzofuran > benzothiophene. Benzothiophene and benzofuran were found to be highly recalcitrant pollutants. Benzothiophene could not be biodegraded when concentration was above 50 mg/l. It was observed that 2-(1H)-quinolinone, benzothiophene-2-one, and benzofuran-2,3-dione were formed as metabolic intermediates during biodegradation of quinoline, benzothiophene, and benzofuran, respectively. Quinoline-N and pyridine-N were transformed into free ammonium ions during the biodegradation process. Biodegradation pathways for various NSO compounds are proposed. Monod inhibition model was able to simulate single substrate biodegradation kinetics satisfactorily. Benzothiophene and benzofuran biodegradation kinetics, in presence of acetone, was simulated using a generalized multi-substrate model.

  10. Neolignans and sesquiterpenes from leaves and embryogenic cultures of Ocotea Catharinensis (Lauraceae)

    Energy Technology Data Exchange (ETDEWEB)

    Funasaki, Mariko; Kato, Massuo J. [Universidade de Sao Paulo (USP), SP (Brazil). Inst. de Quimica; Lordello, Ana Luisa L. [Universidade Federal do Parana (UFPR), Curitiba, PR (Brazil). Dept. de Quimica; Viana, Ana Maria [Universidade Federal de Santa Catarina (UFSC), Florianopolis, SC (Brazil). Centro de Ciencias Biologicas. Dept. de Botanica; Santa-Catarina, Claudete; Floh, Eny I.S. [Universidade de Sao Paulo (USP), SP (Brazil). Inst. de Biociencias; Yoshida, Massayoshi [Centro de Biotecnologia da Amazonia, Manaus, AM (Brazil)

    2009-07-01

    The extracts from leaves of Ocotea catharinensis Mez (Lauraceae) were found to contain fourteen neolignans and two sesquiterpenes: nine benzofuran types (including three new compounds 1e, 2f and 4b), one new seco-benzofuran type (3b), two bicyclo[3.2.1]octane types (including the new compound 5c), two new dimers of bicyclo[3.2.1]octane type (7a and 7b) and two sesquiterpenes (including a new humulanol 9). In addition, seven neolignans were also showed to occur in somatic embryos of O. catharinensis including one new bicyclo[3.2.1]octane type (4a). (author)

  11. 1,3-Diphenylisobenzofuran

    Directory of Open Access Journals (Sweden)

    Kristapher E. Fischer

    2008-04-01

    Full Text Available The structure of the title compound, 1,3-diphenyl-2-benzofuran, C20H14O, exhibits a distinct alternation of short [mean 1.361 (3 Å] and long [mean 1.431 (3 Å] C—C bonds around the benzofuran ring system, indicating a predominantly polyene character. Over 60 Diels–Alder adducts of this commercially available furan have been structurally characterized, but this is the first report of the structure of the parent compound.

  12. Dye laser. Farbstofflaser

    Energy Technology Data Exchange (ETDEWEB)

    Telle, H.; Schieder, R.; Raue, R.; Eckstein, U.

    1987-02-12

    For a laser radiating in the range of wavelengths from 420 to 480 nm dye solutions are proposed. The dyes are produced by transformation of 4,4'-biphenylene-bis-(methylenoxy-2-benzaldehydes) or their bisaniles in bipolar aprotic solvents adding strongly basic alkali compounds to the benzofurans and subsequent sulfonation.

  13. Dye laser

    Energy Technology Data Exchange (ETDEWEB)

    Telle, H.; Schieder, R.; Raue, R.; Eckstein, U.

    1980-05-22

    For a laser radiating in the range of wavelengths from 420 to 480 nm dye solutions are proposed. The dyes are produced by transformation of 4,4'-biphenylene-bis-(methylenoxy-2-benzaldehydes) or their bisaniles in bipolar aprotic solvents adding strongly basic alkali compounds to the benzofurans and subsequent sulfonation.

  14. (+)-Geodin from Aspergillus terreus

    DEFF Research Database (Denmark)

    Rønnest, Mads Holger; Nielsen, Morten Thrane; Leber, Blanka;

    2011-01-01

    The fungal metabolite (+)-geodin [systematic name: (2R)-methyl 5,7-dichloro-4-hydroxy-6'-methoxy-6-methyl-3,4'-dioxospiro[benzofuran-2,1'-cyclohexa-2',5'-diene]-2'-carboxylate], C(17)H(12)Cl(2)O(7), was isolated from Aspergillus terreus. The crystal structure contains two independent molecules...

  15. Synthesis of a tricyclic mescaline analogue by catalytic C-H bond activation.

    Science.gov (United States)

    Ahrendt, Kateri A; Bergman, Robert G; Ellman, Jonathan A

    2003-04-17

    [reaction: see text] A tetrahydrobis(benzofuran) mescaline analogue has been prepared in six steps and 38% overall yield from (4'-O-methyl)methyl gallate. The key step in this synthesis is a tandem cyclization reaction via directed C[bond]H activation followed by olefin insertion.

  16. Modular construction of 2-substituted benzo[b]furans from 1,2-dichlorovinyl ethers.

    Science.gov (United States)

    Geary, Laina M; Hultin, Philip G

    2009-12-01

    (E)-1,2-Dichlorovinyl ethers and amides are easily accessible from trichloroethylene via nucleophilic addition across in situ synthesized dichloroacetylene. A one-pot, sequential Suzuki-Miyaura coupling/intramolecular direct arylation between dichlorovinyl ethers and organoboronic acids provides easy access to a variety of benzofurans in only two steps from inexpensive commercially available compounds. The method is extendable to the preparation of indoles from the analogous dichlorovinyl amides.

  17. Modulators of hepatic lipoprotein metabolism identified in a search for small-molecule inducers of tribbles pseudokinase 1 expression.

    Directory of Open Access Journals (Sweden)

    Marek M Nagiec

    Full Text Available Recent genome wide association studies have linked tribbles pseudokinase 1 (TRIB1 to the risk of coronary artery disease (CAD. Based on the observations that increased expression of TRIB1 reduces secretion of VLDL and is associated with lower plasma levels of LDL cholesterol and triglycerides, higher plasma levels of HDL cholesterol and reduced risk for myocardial infarction, we carried out a high throughput phenotypic screen based on quantitative RT-PCR assay to identify compounds that induce TRIB1 expression in human HepG2 hepatoma cells. In a screen of a collection of diversity-oriented synthesis (DOS-derived compounds, we identified a series of benzofuran-based compounds that upregulate TRIB1 expression and phenocopy the effects of TRIB1 cDNA overexpression, as they inhibit triglyceride synthesis and apoB secretion in cells. In addition, the compounds downregulate expression of MTTP and APOC3, key components of the lipoprotein assembly pathway. However, CRISPR-Cas9 induced chromosomal disruption of the TRIB1 locus in HepG2 cells, while confirming its regulatory role in lipoprotein metabolism, demonstrated that the effects of benzofurans persist in TRIB1-null cells indicating that TRIB1 is sufficient but not necessary to transmit the effects of the drug. Remarkably, active benzofurans, as well as natural products capable of TRIB1 upregulation, also modulate hepatic cell cholesterol metabolism by elevating the expression of LDLR transcript and LDL receptor protein, while reducing the levels of PCSK9 transcript and secreted PCSK9 protein and stimulating LDL uptake. The effects of benzofurans are not masked by cholesterol depletion and are independent of the SREBP-2 regulatory circuit, indicating that these compounds represent a novel class of chemically tractable small-molecule modulators that shift cellular lipoprotein metabolism in HepG2 cells from lipogenesis to scavenging.

  18. Synthesis of 2,3-Dimethoxy-7-methyl-7,12-dihydro-6H-[1]-benzofuro-[2,3-c]-[1]-benzazepin-6,12-dione

    Directory of Open Access Journals (Sweden)

    Karla-Sue C. Marriott

    2002-03-01

    Full Text Available Treatment of 5,6-dimethoxy-2-(methylphenylcarbamoyl-benzofuran-3-carboxylic acid with PPA yielded 2,3-dimethoxy-7-methyl-7,12-dihydro-6H-[1]-benzofuro-[2,3-c]-[1]-benzazepin-6,12-dione. The analogous 2-[(5,6-dimethoxybenzofuran-2-carbonylmethylamino]benzoic acid was resistant to cyclization, whereas 2-[(6-methoxybenzofuran-2-carbonyl-amino]benzoic acid underwent cyclization to the corresponding 3,1-benzoxazin-4-one.

  19. Dronedarone: evidence supporting its therapeutic use in the treatment of atrial fibrillation

    OpenAIRE

    Sullivan, Renee M; Brian Olshansky

    2010-01-01

    Renee M Sullivan, Brian OlshanskyDivision of Cardiovascular Medicine, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USAIntroduction: Dronedarone, a benzofuran derivative with a structure similar to amiodarone, has been developed as a potential therapy for patients with atrial fibrillation.Aim: To review the published evidence regarding the efficacy and safety of dronedarone use in patients with atrial fibrillation.Evidence review: Available evidence suggests that dronedarone 400 ...

  20. Structural Transformation of 8-5-Coupled Dehydrodiferulates by Human Intestinal Microbiota.

    Science.gov (United States)

    Schendel, Rachel R; Karrer, Cecile; Bunzel, Diana; Huch, Melanie; Hildebrand, Andreas A; Kulling, Sabine E; Bunzel, Mirko

    2015-09-16

    Ingested dehydrodiferulates (DFAs) are partially released from cereal dietary fiber by human colonic microbiota, but little research has explored the further microbial metabolism of 8-5-coupled DFAs. This study investigated the in vitro microbial metabolism and elucidated major metabolites of free 8-5-DFAs (benzofuran and open forms) and an esterified analogue, 8-5-DFA diethyl ester (benzofuran). Synthesized standard compounds were incubated with fresh human fecal suspensions. Metabolites were isolated and structurally elucidated using high-resolution-LC-time-of-flight-(ToF)-MS, GC-MS, and NMR. Nine metabolite structures were unambiguously characterized with NMR, and four additional metabolites were tentatively identified to reveal structural conversion motifs: propenyl side chain hydrogenation (all substrates), O-demethylation and reductive ring-opening (8-5-DFA diethyl ester and free 8-5-DFA [benzofuran]), and de-esterification (8-5-DFA diethyl ester). A pathway of microbial 8-5-DFA metabolism was proposed based on metabolite formation kinetics. Importantly, de-esterification of the 8-5-DFA diethyl ester occurred primarily after and/or concurrently with other metabolism steps. Cleavage to monomers was not observed. PMID:26287944

  1. 5-(2-amimo-4-styryl pyrimidine-4-yl-4-methoxybenzofuran-6-ol

    Directory of Open Access Journals (Sweden)

    Atteyat A Labib

    2013-05-01

    Full Text Available This study describes the organic synthesis of 5-(2-amimo-4-styryl pyrimidine-4-yl-4-methoxy benzofuran-6-ol (SPBF as an example of a benzofuran derivative used as a new series of amyloid imaging agents. These benzofuran derivatives may be useful amyloid imaging agents for detecting B-amyloid plagues in the brain of Alzheimer’s disease. The precursor is 1-[6-hydroxy-4-methoxybenzofuran-5-yl]-phenyl butadiene ketone, which react with guanidine hydrochloride. The purification process was done via crystallization using solvent ethanol. The overall yield was 75% and the structure of the synthesized compound was confirmed by correct analytical and spectral data. Also, The synthesized compound was labeled with radioactive iodine -125 via electrophilic substitution reaction, in the presence of iodogen as an oxidizing agent, the labeling process was carried out at 95oC for 20min. The radiochemical yield was determined by using a thin layer chromatography and the yield was equal to 80%. Preliminary an in-vivo study examined normal mice after intravenous injection through the tail vein and the data showed the labeling compound was quickly cleared from most body organs. The radioiodinated compound showed high brain uptake.The results of this study suggest that radioiodinated (SPBF may be useful as a brain imaging agents.

  2. Stereoselective synthesis of C-fused pyranoindoles, pyranobenzofurans and pyranobenzothiophene scaffolds using oxa-Pictet-Spengler type reaction of vinylogous carbonates.

    Science.gov (United States)

    Gharpure, Santosh J; Prasath, V

    2014-10-01

    C-fused pyranoheterocycles can be readily assembled using an intramolecular oxa-Pictet-Spengler type reaction of vinylogous carbonates in a highly stereoselective manner. Required indole and benzofuran rings tethered to vinylogous carbonates are prepared by a tandem Sonogashira coupling-nucleopalladation reaction. The entire process can also be carried out in a 'one-pot' manner starting from homopropargyl alcohol. The C-fused pyranoindoles could be converted to spirooxindoles as well as to ring expanded products under oxidative conditions. PMID:25137156

  3. Synthesis of benzofuranyl and indolyl methyl azides by tandem silver-catalyzed cyclization and azidation.

    Science.gov (United States)

    Ranjith Kumar, Gadi; Kiran Kumar, Yalla; Kant, Ruchir; Sridhar Reddy, Maddi

    2016-04-26

    Ag(i)-catalyzed synthesis of 2-azidomethyl benzofurans/indoles from linear and readily available hydroxyl/amino-phenyl propargyl alcohols is described via a highly regioselective C-O and C-N bond formation. Control experiments reveal that the reaction involves the sequential Ag(i)-catalyzed 5-exo-dig cyclization and a catalyst free γ-allylic azidation. The synthetic utility of this method has been demonstrated by using the azidomethyl unit of the above synthesized heterocycles as the base for a variety of other functionalizations, such as triazole-, tetrazole-, amide-, amine-, and pyrido-derivatives. PMID:27064507

  4. A novel series of 2,5-disubstituted 1,3,4-thiadiazoles as potential anticonvulsant agent

    Institute of Scientific and Technical Information of China (English)

    Harish Rajak; Chinmay K. Behera; Rajesh S. Pawar; Pradeep K. Singour; Murli Dhar Kharya

    2010-01-01

    In pursuit for better antiepileptic drug and the importance of semicarbazones and 2,5-disubstituted 1,3,4-thiadiazoles as anticonvulsant pharmacophore, a series of novel N-({5-[(6-methyl-1-benzofuran-3-yl)methyl]-1,3,4-thiadiazol-2-yl}carba-mothioyl)-2/3/4-substitutedbenzamide were designed, synthesized and evaluated for their anticonvulsant activity. The findings of the present studies confirmed that the pharmacophore model with four binding sites is crucial for anticonvuisant activity. Structure-activity relationships among synthesized compounds were also established.

  5. Trends in research of antitrypanosomal agents among synthetic heterocycles.

    Science.gov (United States)

    Kryshchyshyn, Anna; Kaminskyy, Danylo; Grellier, Philippe; Lesyk, Roman

    2014-10-01

    To date treatment of trypanosomiasis urgently requires new effective and non-toxic drugs. The article covers some of the achievements in the search for new antitrypanosomal agents; also the "validated" biological targets used in the antitrypanosomal agents design are outlined. The major part of the manuscript focuses on the synthetic small molecules, such as thiosemicarbazone and thiazole (as their cyclic analogues) derivatives, benzofuran derivatives, heterocycles bearing nitro group etc. Also, the attractiveness of metal complexes and well known drugs as sources for antitrypanosomal agent design is discussed. PMID:25072876

  6. Development of Several New Reactions and Their Application to the Total Synthesis of Biologically Active Natural Products :Synthesis of Linderol A and Determination of Its Absolute Configuration

    Institute of Scientific and Technical Information of China (English)

    Shunsaku Ohta

    2005-01-01

    @@ 1Introduction Linderol A (1), a monoterpene-polyketide, was isolated in 1995 from the fresh bark of Lindera umbellata (Lauraceae), and its absolute structure was not determined[1]. It was also reported potent inhibitory activity of 1 on the melanin biosynthesis of the cultured B-16 melanoma cells[1]. See Fig. 1. On the other hand,we reported in 1995 an interesting multi-tandem reaction of coumarin derivatives (2; W = electron withdrawing group) by treatment with CH2 = S(O)Me2 to yield stereoselectively a tricyclic 2-substituted cyclopenta [ b ] benzofuran-3-ol derivative (4) via a cyclopropane intermediate (3) (Scheme 1)[2].

  7. A review on dronedarone:Pharmacological, pharmacodynamic and pharmacokinetic profile

    Institute of Scientific and Technical Information of China (English)

    Farah Iram; Sadaf Ali; Aftab Ahmad; Shah Alam Khan; Asif Husain

    2016-01-01

    Dronedarone, a benzofuran containing chemical compound, is a derivative of amiodarone which is classified as a Class III antiarrhythmic agent. It is prescribed to the cardiovas-cular patients who have paroxysmal or persistent atrial fibrillation to lower the chances of hospitalization. Amiodarone, sotalol, procainamide dofetilide, quinidine, ibutilide, fle-cainide, and propafenone are the other useful medicinal products used to treat atrial fibrillation or cardiac arrhythmia. Dronedarone was approved for clinical use in atrial fibrillation by the Food and Drug Administration in 2009. The generic name for drone-darone is Multaq (Sanofi Aventis). This article briefly highlights the important pharma-cological, pharmacodynamic and pharmacokinetic properties of dronedarone.

  8. Molecular and morphological characterization of hydrochar produced by microwave-assisted hydrothermal carbonization of cellulose

    Directory of Open Access Journals (Sweden)

    Marcela Guiotoku

    2012-05-01

    Full Text Available The objective of this work was to characterize the morphology and molecular composition of the hydrochar produced by microwave-assisted hydrothermal carbonization of cellulose. The produced hydrochar consists mainly of aggregate microspheres with about 2.0 µm in diameter, with aliphatic and aromatic structures and the presence of carbonyl functional groups. The aromatic groups are formed mainly by benzofuran-like structures, being chemically different from common cellulose char. Microwave-assisted hydrothermal carbonization yields a functionalized carbon-rich material similar to that produced by the conventional hydrothermal process.

  9. Novel chlorinated dibenzofurans isolated from the cellular slime mold, Polysphondylium filamentosum, and their biological activities.

    Science.gov (United States)

    Kikuchi, Haruhisa; Kubohara, Yuzuru; Nguyen, Van Hai; Katou, Yasuhiro; Oshima, Yoshiteru

    2013-08-01

    Cellular slime molds are expected to have the huge potential for producing secondary metabolites including polyketides, and we have studied the diversity of secondary metabolites of cellular slime molds for their potential utilization as new biological resources for natural product chemistry. From the methanol extract of fruiting bodies of Polysphondylium filamentosum, we obtained new chlorinated benzofurans Pf-1 (4) and Pf-2 (5) which display multiple biological activities; these include stalk cell differentiation-inducing activity in the well-studied cellular slime mold, Dictyostelium discoideum, and inhibitory activities on cell proliferation in mammalian cells and gene expression in Drosophila melanogaster. PMID:23746784

  10. Phenolic compounds from the roots of Valeriana officinalis var. latifolia

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Peng-Cheng; Ran, Xin-Hui; Luo, Huai-Rong; Liu, Yu-Qing; Zhou Jun [State Key Laboratory of Phytochemistry and Plant Resources in West China. Kunming Institute of Botany, Chinese Academy of Sciences (China); Ma, Qing-Yun; Zhao, You-Xing, E-mail: zhoujun3264@yahoo.com.cn, E-mail: zhaoyouxing@itbb.org.cn [Key Laboratory of Biology and Genetic Resources of Tropical Crops. Ministry of Agriculture, Institute of Tropical Bioscience and Biotechnology. Chinese Academy of Tropical Agriculture Sciences (China)

    2013-09-15

    A new benzofuran neolignan, dihydrodehydrodiconiferyl alcohol 9-isovalerate, along with ten known phenolic compounds, olivil, pinoresinol, 8-hydroxypinoresinol, pinorespiol, 8-hydroxy- 7-epipinoresinol, trans-p-hydroxyphenyl- propenoic acid, cis-p-hydroxyphenyl-propenoic acid, ferulic acid, isoferulic acid and isovanillin were isolated from the roots of Valeriana officinalis var. latifolia. Their structures and configurations were elucidated on the basis of spectroscopic methods. The inhibitory activity for acetylcholinesterase (AChE) and enhancing activity on nerve growth factor (NGF)-mediated neurite outgrowth in PC12 cells of dihydrodehydrodiconiferyl alcohol 9-isovaterate and olivil were evaluated. (author)

  11. Synthesis, characterization and biological activities of novel chalcone derivatives, containing 4, 7-ethanoisoindole-1,3-dione units

    OpenAIRE

    Mustafa Ceylan; İsa Karaman; Meryem Keçeci Sarıkaya

    2013-01-01

    Novel chalcone derivatives, containing 4, 7-ethanoisoindole-1,3-dione units were synthesized starting from 1,3-cyclohexadine (4) and maleic anhydride (5). Addition of maleic anhydride (5) to 1,3-cyclehexadine (4) gave an endo-adduct, 3a,4,7,7a-tetrahydro-4,7-ethano-2-benzofuran-1,3-dione (6), in 90% yield. Heating the solution of the adduct dione (6) and 1-(4-aminophenyl)ethanone (7) in the presence of Et 3N in toluene at 110 oC for 24 hours afforded 2-(4-acetylphenyl)-3a,4,7,7a-tetrahydro-1H...

  12. Pd-NHC-Catalyzed Alkynylation of General Aryl Sulfides with Alkynyl Grignard Reagents.

    Science.gov (United States)

    Baralle, Alexandre; Yorimitsu, Hideki; Osuka, Atsuhiro

    2016-07-25

    Cross-coupling reactions of unactivated aryl sulfides with alkynylmagnesium chloride have been invented to afford 1-aryl-1-alkynes with the aid of a palladium/N-heterocyclic carbene complex. This reaction has by far the widest scope of all transformations utilizing aryl sulfides and alkynes, while known cross-coupling alkynylations of aryl-sulfur electrophiles require activated azaaryl sulfides, thiolactams, or arenesulfonyl chlorides. The alkynylation of aryl sulfides is compatible with typical protecting functional groups. The alkynylation is applied to the synthesis of benzofuran-based fluorescent molecules by taking advantage of characteristic organosulfur chemistry.

  13. Studies of initial stage in coal liquefaction. Effect of decomposition of oxygen-functional groups on coal liquefaction; Ekika hanno no shoki katei ni kansuru kenkyu. 3. Gansanso kannoki no bunkai kyodo to ekika hanno eno eikyo

    Energy Technology Data Exchange (ETDEWEB)

    Komeiji, A.; Kaneko, T.; Shimazaki, K. [Nippon Brown Coal Liquefaction Co. Ltd., Tokyo (Japan)

    1996-10-28

    Pretreatment of brown coal in oil was conducted using 1-methyl naphthalene or mixture of tetralin and 1-methyl naphthalene as solvent at temperatures ranging from 300 to 430{degree}C under nitrogen atmosphere. Effects of the solvent properties on the structural change of oxygen-functional groups (OFG) and coal liquefaction were investigated by means of quantitative analysis of OFG and solid state {sup 13}C-NMR measurement. When hydrogen transfer from solvent was insufficient, it was suggested that brown coal molecules loose their hydrogen to be aromatized. While, at lower temperatures ranging from 300 to 350{degree}C, hydrogen contained in brown coal molecules was consumed for the stabilization of pyrolytic radicals, and the deterioration of liquefaction was not observed. When hydrogen transfer from solvent was insufficient at higher temperatures above 400{degree}C in nitrogen atmosphere during pretreatment in oil, crosslinking like benzofuran type was formed by dehydration condensation of hydroxyl group in brown coal, to deteriorate the liquefaction, remarkably. The addition of donor solvent like tetralin decreased the formation of crosslinking like benzofuran type, which suppressed the deterioration of liquefaction. 8 refs., 5 figs.

  14. New Polyketides and New Benzoic Acid Derivatives from the Marine Sponge-Associated Fungus Neosartorya quadricincta KUFA 0081

    Science.gov (United States)

    Prompanya, Chadaporn; Dethoup, Tida; Gales, Luís; Lee, Michael; Pereira, José A. C.; Silva, Artur M. S.; Pinto, Madalena M. M.; Kijjoa, Anake

    2016-01-01

    Two new pentaketides, including a new benzofuran-1-one derivative (1) and a new isochromen-1-one (5), and seven new benzoic acid derivatives, including two new benzopyran derivatives (2a, b), a new benzoxepine derivative (3), two new chromen-4-one derivatives (4b, 7) and two new benzofuran derivatives (6a, b), were isolated, together with the previously reported 2,3-dihydro-6-hydroxy-2,2-dimethyl-4H-1-benzopyran-4-one (4a), from the culture of the marine sponge-associated fungus Neosartorya quadricincta KUFA 0081. The structures of the new compounds were established based on 1D and 2D NMR spectral analysis, and in the case of compounds 1, 2a, 4b, 5, 6a and 7, the absolute configurations of their stereogenic carbons were determined by an X-ray crystallographic analysis. None of the isolated compounds were active in the tests for antibacterial activity against Gram-positive and Gram-negative bacteria, as well as multidrug-resistant isolates from the environment (MIC > 256 μg/mL), antifungal activity against yeast (Candida albicans ATTC 10231), filamentous fungus (Aspergillus fumigatus ATTC 46645) and dermatophyte (Trichophyton rubrum FF5) (MIC > 512 µg/mL) and in vitro growth inhibitory activity against the MCF-7 (breast adenocarcinoma), NCI-H460 (non-small cell lung cancer) and A375-C5 (melanoma) cell lines (GI50 > 150 µM) by the protein binding dye SRB method. PMID:27438842

  15. Extraction, radiolabeling and in vivo biological evaluation of {sup 131}I labeled egonol glycosides extract

    Energy Technology Data Exchange (ETDEWEB)

    Akguel, Yurdanur; Pazar, Erdinc [Ege Univ., Izmir (Turkey). Chemistry Dept.; Yilmaz, Habibe; Sanlier, Senay Hamarat [Ege Univ., Izmir (Turkey). Biochemistry Dept.; Lambrecht, Fatma Yurt [Ege Univ., Izmir (Turkey). Dept. of Nuclear Applications; Yilmaz, Osman [Dokuz Eyluel Univ., Izmir (Turkey). Dept. of Lab. Animal Science

    2015-09-01

    Crude extract of S. officinalis L. was found to have suspending agent, hemolytic, antitumor, antioxidant and antimicrobial activities. Its major components benzofurans and benzofuran glycosides have antifungal, anticancer, antibacterial and anticomplement activities and display acetylcholinesterase-cyclooxygenase inhibitory and cytotoxic properties. Recently, it has been reported that egonolgentiobioside is a valuable target for structural modification and warrants further investigation for its potential as a novel pharmaceutical tool for the prevention of estrogen deficiency induced diseases. The aim of the current study is to perform in vivo biological evaluation of a glycosides extract, which was isolated from the fruits endocarp of Styrax officinalis L, identified as egonolgentiobioside and homoegonolgentiobioside and labeled with {sup 131}I. The radiolabeled glycosides extract was labeled with {sup 131}I with high yield. The labeled obtained radiolabeled compound was found to be quite stable and lipophilic. In order to determine its tissue distribution, an in vivo study was performed using healthy female Albino Wistar rats injected by {sup 131}I-glycosides. The biodistribution results showed that clearance of the radiolabeled compound is through the hepatobiliary pathway. The experimental study indicated that the radiolabeled glycosides extract accumulated in the large intestine. Therefore, the potential of {sup 131}I-glycosides might be evaluated in colon cancer cell lines and this might be a promising of tumor-imaging agent.

  16. New Psychoactive Substances: Chemistry, Pharmacology, Metabolism, and Detectability of Amphetamine Derivatives With Modified Ring Systems.

    Science.gov (United States)

    Welter-Luedeke, Jessica; Maurer, Hans H

    2016-02-01

    In recent years, new amphetamine derivatives with modified ring systems were sold and consumed as new drugs of abuse. They belong together with other new drugs of abuse classes to the so-called new psychoactive substances (NPS). The chemistry, pharmacology, toxicology, metabolism, and toxicokinetics are shortly discussed of camfetamine, 3 methylphenyl-amphetamines (2-MA, 3-MA, and 4-MA), 2-methiopropamine (2-MPA), and 5-(2-aminopropyl)benzofuran (5-APB), 6-(2-aminopropyl)benzofuran (6-APB, so-called "benzofury") and their N-methyl derivatives 5-MAPB and 6-MAPB. Only a rough assessment of the pharmacology and toxicology NPS can be performed in most cases using published data of analogs, trip reports, and described clinical cases. Accordingly, they all act more or less as central nervous stimulants mainly by increasing the concentration of the neurotransmitters noradrenaline, dopamine, and serotonin (5-HT) by inducing their release and reuptake inhibition. Thus, the acute toxicity is associated with the sympathomimetic effects, such as mydriasis, hyperthermia, hypertension, tachycardia, insomnia, and anxiety. With the exception of 5- and 6-APB, these NPS were extensively metabolized by N-demethylation and/or aromatic hydroxylation catalyzed by various cytochrome P450 isoenzymes followed by partial glucuronidation and/or sulfation. For urinalysis, the unchanged drugs and/or the nor-metabolites are the main targets. PMID:26327309

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

    Science.gov (United States)

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

    2015-07-27

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

  18. New Polyketides and New Benzoic Acid Derivatives from the Marine Sponge-Associated Fungus Neosartorya quadricincta KUFA 0081

    Directory of Open Access Journals (Sweden)

    Chadaporn Prompanya

    2016-07-01

    Full Text Available Two new pentaketides, including a new benzofuran-1-one derivative (1 and a new isochromen-1-one (5, and seven new benzoic acid derivatives, including two new benzopyran derivatives (2a, b, a new benzoxepine derivative (3, two new chromen-4-one derivatives (4b, 7 and two new benzofuran derivatives (6a, b, were isolated, together with the previously reported 2,3-dihydro-6-hydroxy-2,2-dimethyl-4H-1-benzopyran-4-one (4a, from the culture of the marine sponge-associated fungus Neosartorya quadricincta KUFA 0081. The structures of the new compounds were established based on 1D and 2D NMR spectral analysis, and in the case of compounds 1, 2a, 4b, 5, 6a and 7, the absolute configurations of their stereogenic carbons were determined by an X-ray crystallographic analysis. None of the isolated compounds were active in the tests for antibacterial activity against Gram-positive and Gram-negative bacteria, as well as multidrug-resistant isolates from the environment (MIC > 256 μg/mL, antifungal activity against yeast (Candida albicans ATTC 10231, filamentous fungus (Aspergillus fumigatus ATTC 46645 and dermatophyte (Trichophyton rubrum FF5 (MIC > 512 µg/mL and in vitro growth inhibitory activity against the MCF-7 (breast adenocarcinoma, NCI-H460 (non-small cell lung cancer and A375-C5 (melanoma cell lines (GI50 > 150 µM by the protein binding dye SRB method.

  19. Synthesis and classical pathway Complement inhibitory activity of C7-functionalized filifolinol derivatives, inspired in K-76 COOH.

    Science.gov (United States)

    Larghi, Enrique L; Operto, María A; Torres, Rene; Kaufman, Teodoro S

    2012-09-01

    A series of carboxylic acids carrying various functionalization on C-7 of their common 3H-spiro[benzofuran-2,1'-cyclohexane] skeleton were synthesized from filifolinol, as analogs of the natural Complement inhibitor K-76 COOH. In order to probe the relevance of the C-7 functionalization on their bioactivity, the ability of the analogs to inhibit Complement activation through the classical pathway was determined. The observed results suggest that functionalization of C-7 can modulate the inhibitory activity of the tested compounds. The 7-trifluoromethyl derivative was the compound with the lowest IC(50) value among the tested analogs (IC(50) = 100 μM), being more potent than K-76 COOH (IC(50) = 570 μM).

  20. New inhibitors of the complement system inspired in K76-COOH. A SAR study of filifolinol derivatives through modifications of the C3' position.

    Science.gov (United States)

    Larghi, Enrique L; Operto, María A; Torres, Rene; Kaufman, Teodoro S

    2009-11-01

    A new series of tricyclic carboxylic acids with a 3H-spiro[benzofuran-2,10-cyclohexane] skeleton were synthesized from filifolinol, as analogs of the natural complement inhibitor K76-COOH. Their complement inhibitory activity was determined aiming to probe the importance of structural characteristics of the alicyclic part of K76-COOH. The presence and stereochemistry of O- and N-functionalities on C3' of the filifolinol derivatives are relevant for biological activity. The IC50 values of the most potent compounds were comparable or surpassed the activity of K76-COOH. The results also suggest that the diol moiety of the natural product may be useful for improving compound solubility.

  1. Hepatoprotective activity of twelve novel 7'-hydroxy lignan glucosides from Arctii Fructus.

    Science.gov (United States)

    Yang, Ya-Nan; Huang, Xiao-Ying; Feng, Zi-Ming; Jiang, Jian-Shuang; Zhang, Pei-Cheng

    2014-09-17

    Twelve novel 7'-hydroxy lignan glucosides (1-12), including two benzofuran-type neolignans, two 8-O-4' neolignans, two dibenzylbutyrolactone lignans, and six tetrahydrofuranoid lignans, together with six known lignan glucosides (13-18), were isolated from the fruit of Arctium lappa L. (Asteraceae), commonly known as Arctii Fructus. Their structures were elucidated using spectroscopy (1D and 2D NMR, MS, IR, ORD, and UV) and on the basis of chemical evidence. The absolute configurations of compounds 1-12 were confirmed using rotating frame nuclear overhauser effect spectroscopy (ROESY), the circular dichroic (CD) exciton chirality method, and Rh2(OCOCF3)4-induced CD spectrum analysis. All of the isolated compounds were tested for hepatoprotective effects against D-galactosamine-induced cytotoxicity in HL-7702 hepatic cells. Compounds 1, 2, 7-12, and 17 showed significantly stronger hepatoprotective activity than the positive control bicyclol at a concentration of 1 × 10(-5) M.

  2. Synthesis of Oxygen Heterocycles via Aromatic C-O Bond Formation Using Arynes

    Directory of Open Access Journals (Sweden)

    Hideto Miyabe

    2015-07-01

    Full Text Available Most of the synthetic approaches to the benzo-fused heterocycles containing an oxygen atom have involved the use of phenol derivatives as a starting material. This review highlights the new synthetic approaches involving the aromatic C-O bond-forming process using arynes. The insertion of arynes into the C=O bond gives the unstable intermediates, [2 + 2] cycloaddition-type adducts, which can be easily converted into a variety of oxygen atom-containing heterocycles in a single operation. In this review, the syntheses of oxygen heterocycles, such as coumarin, chromene, xanthene, dihydrobenzofuran and benzofuran derivatives, via the insertion of arynes into the C=O bond of aldehydes or formamides are summarized.

  3. A comparison of several types of carbon in de novo dioxins formation: Effects of time, doping with copper, water vapour, and suppression by sulphur dioxide

    International Nuclear Information System (INIS)

    Activated carbon, three qualities of carbon black, and graphite are oxidised during 90 minutes at 300 degree Celsius in a flow air. Oxidation rates strikingly vary with time. Doping with CuCl2 strongly enhances the rate of carbon oxidation. Adding moisture to combustion air accelerates further; addition of sulphur dioxide suppresses carbon oxidation. Low temperature catalytic oxidation of carbon also generates Products of Incomplete Combustion (PICs), including polychlorinated di benzofurans (PCDF), dibenzo-p-dioxins (PCDD), biphenyls (PCB), benzenes (PCBz), i.e.dioxins and its surrogates in de novo formation of dioxins. Their formation is studied during the first thirty minutes of the oxidation test. An attempt is made to correlate the formation of dioxins and other chlorinated organics with test conditions and characteristics of the carbon samples. (author)

  4. Evaluation of analgesic activities of tremetone derivatives isolated from the Chilean altiplano medicine Parastrephia lepidophylla.

    Science.gov (United States)

    Benites, Julio; Gutierrez, Eunices; López, Jóse; Rojas, Mauricio; Rojo, Leonel; Costa, Maria do Céu; Vinardell, Maria Pilar; Calderon, Pedro Buc

    2012-05-01

    Parastrephia lepidophylla, family Asteraceae, has ancient use in traditional medicine in the region of Tarapacá, Chile. Bioguided fractionation of extracts of this plant was undertaken in the search for compounds with analgesic and antioxidant activity. Two benzofuran derivatives were isolated as the major components of this plant, identified as tremetone 1 and methoxytremetone 6. Remarkably, neither of these showed antioxidant activity, but tremetone 1 exhibited a morphine-like analgesic property. Reduction of this analgesic effect by naloxone suggests a direct effect on opiate receptors as a possible signaling pathway. However, both the low diffusion across lipid membranes (PAMPA assay) and the lipophilicity (Log P) shown by tremetone 1 make elusive the mechanism explaining its induced analgesia.

  5. Hepatoprotective activity of twelve novel 7'-hydroxy lignan glucosides from Arctii Fructus.

    Science.gov (United States)

    Yang, Ya-Nan; Huang, Xiao-Ying; Feng, Zi-Ming; Jiang, Jian-Shuang; Zhang, Pei-Cheng

    2014-09-17

    Twelve novel 7'-hydroxy lignan glucosides (1-12), including two benzofuran-type neolignans, two 8-O-4' neolignans, two dibenzylbutyrolactone lignans, and six tetrahydrofuranoid lignans, together with six known lignan glucosides (13-18), were isolated from the fruit of Arctium lappa L. (Asteraceae), commonly known as Arctii Fructus. Their structures were elucidated using spectroscopy (1D and 2D NMR, MS, IR, ORD, and UV) and on the basis of chemical evidence. The absolute configurations of compounds 1-12 were confirmed using rotating frame nuclear overhauser effect spectroscopy (ROESY), the circular dichroic (CD) exciton chirality method, and Rh2(OCOCF3)4-induced CD spectrum analysis. All of the isolated compounds were tested for hepatoprotective effects against D-galactosamine-induced cytotoxicity in HL-7702 hepatic cells. Compounds 1, 2, 7-12, and 17 showed significantly stronger hepatoprotective activity than the positive control bicyclol at a concentration of 1 × 10(-5) M. PMID:25180661

  6. Analysis of volatile chemical components of Radix Paeoniae Rubra by gas chromatography-mass spectrometry and chemometric resolution

    Institute of Scientific and Technical Information of China (English)

    LI Xiao-ru; LAN Zheng-gang; LIANG Yi-zeng

    2007-01-01

    The volatile chemical components of Radix Paeoniae Rubra (RPR) were analyzed by gas chromatography-mass spectrometry with the method of heuristic evolving latent projections and overall volume integration.The results show that 38 volatile chemical components of RPR are determined.accounting for 95.21% of total contents of volatile chemical components of RPR.The main volatile chemical components of RPR are(Z,Z)-9, 12-octadecadienoic acid, n-hexadecanoic acid, 2-hydroxy benzaldehyde, 1-(2-hydroxy-4-methoxyphenyl)-ethanone, 6,6-dimethyl-bicyclo[3.1.1]heptane-2-methanol, 4,7-dimethyl-benzofuran, 4-(1-methylethenyl)-1-cyclohexene-1-carboxaldehyde, and cyclohexadecane.

  7. Mechanistic study of electrochemical oxidation of catechols in the presence of 4-hydroxy-1-methyl-2(1H)-quinolone

    Energy Technology Data Exchange (ETDEWEB)

    Fakhari, Ali Reza [Department of Chemistry, Faculty of Science, University of Shahid Beheshti, Tehran 19835389 (Iran, Islamic Republic of)]. E-mail: a-zavareh@sbu.ac.ir; Nematollahi, Davood [Department of Chemistry, Faculty of Science, University of Bu-Ali-Sina, Hamadan (Iran, Islamic Republic of); Moghaddam, Abdolmajid Bayandori [Department of Chemistry, Faculty of Science, University of Shahid Beheshti, Tehran 19835389 (Iran, Islamic Republic of)

    2005-09-20

    Electrochemical oxidation of catechols (1a-1c) has been studied in the presence of 4-hydroxy-1-methyl-2(1H)-quinolone (3) as a nucleophile in aqueous solution using cyclic voltammetry and controlled-potential coulometry. The results indicate that the quinones derived from catechols (1a-1c) participate in Michael addition reactions with 3 to form the corresponding benzofuran (or isochromeno[4,3-c]quinoline) derivatives (6a-6c). The electrochemical synthesis of (6a-6c) has been successfully performed in an undivided cell in good yield and purity. The oxidation mechanism was deduced from voltammetric data and by coulometry at controlled-potential. The products have been characterized after purification by IR, {sup 1}H NMR, {sup 13}C NMR and MS.

  8. Novel Bioactivation Pathway of Benzbromarone Mediated by Cytochrome P450.

    Science.gov (United States)

    Kitagawara, Yumina; Ohe, Tomoyuki; Tachibana, Kumiko; Takahashi, Kyoko; Nakamura, Shigeo; Mashino, Tadahiko

    2015-09-01

    Benzbromarone (BBR) is a hepatotoxic drug, but the detailed mechanism of its toxicity remains unknown. We identified 2,6-dibromohydroquinone (DBH) and mono-debrominated catechol (2-ethyl-3-(3-bromo-4,5-dihydroxybenzoyl)benzofuran; CAT) as novel metabolites of BBR in rat and human liver microsomal systems by comparison with chemically synthesized authentic compounds, and we also elucidated that DBH is formed by cytochrome P450 2C9 and that CAT is formed mainly by CYP1A1, 2D6, 2E1, and 3A4. Furthermore, CAT, DBH, and the oxidized form of DBH are highly cytotoxic in HepG2 compared with BBR. Taken together, our data demonstrate that DBH, a novel reactive metabolite, may be relevant to BBR-induced hepatotoxicity. PMID:26106235

  9. Analytical characterization of four new ortho-methoxybenzylated amphetamine-type designer drugs.

    Science.gov (United States)

    Westphal, Folker; Girreser, Ulrich; Waldmüller, Delia

    2016-09-01

    In a seizure of German custom authorities four N-(ortho-methoxybenzyl)amines with amphetamine partial structure were obtained as pure compounds: N-(ortho-methoxybenzyl)-3,4-dimethoxyamphetamine (3,4-DMA-NBOMe (1)), N-(ortho-methoxybenzyl)-4-ethylamphetamine (4-EA-NBOMe (2)), N-(ortho-methoxybenzyl)-4-methylmethamphetamine (4-MMA-NBOMe (3)), and N-(ortho-methoxybenzyl)-5-(2-aminopropyl)benzofuran (5-APB-NBOMe (4)). The compounds have been detected in Germany for the first time and no analytical data had been previously published. Mass spectrometric (MS), infrared (IR) spectroscopic, and nuclear magnetic resonance (NMR) spectroscopic data are presented. Copyright © 2015 John Wiley & Sons, Ltd.

  10. Isolation, Stereochemical Study, and Antioxidant Activity of Benzofuranone Derivatives from a Mangrove-derived Fungus Eurotium rubrum MA-150.

    Science.gov (United States)

    Meng, Ling-Hong; Mándi, Attila; Li, Xiao-Ming; Liu, Yang; Kurtán, Tibor; Wang, Bin-Gui

    2016-08-01

    Enantiomers of a 2-benzofuran-1(3H)-one derivative [(-)- and (+)-] and four known analogs () were isolated and identified from the culture extract of Eurotium rubrum MA-150, a fungus obtained from the mangrove-derived rizospheric soil. Their structures were established by detailed interpretation of nuclear magnetic resonance (NMR) data and the structure of (±)- was confirmed by single-crystal X-ray diffraction analysis. The absolute configuration of the enantiomers (-)- and (+)- was determined by means of online high-performance liquid chromatography - electronic circular dichroism (HPLC-ECD) measurements and time-dependent Density Functional Theory - electronic circular dichroism (TDDFT-ECD) calculations. Compounds (±)- as well as and exhibited potent DPPH radical scavenging activities with IC50 values of 1.23, 2.26, and 3.99 μg/mL, respectively. Chirality 28:581-584, 2016. © 2016 Wiley Periodicals, Inc. PMID:27376714

  11. New neolignans from Krameria tomentosa A. St.-Hil

    Energy Technology Data Exchange (ETDEWEB)

    Madeiro, Sara A.L.; Lucena, Hellane F.S. de; Siqueira, Caroline D.; Duarte, Marcelo C.; Barbosa Filho, Jose M.; Silva, Marcelo S. da; Tavares, Josean F., E-mail: josean@ltf.ufpb.br [Universidade Federal da Paraiba (UFPB), Joao Pessoa, PB (Brazil). Departamento de Ciencias Farmaceuticas; Braz-Filho, Raimundo [Universidade Estadual do Norte Fluminense (UENF), Campos dos Goytacazes, RJ (Brazil). Laboratorio de Ciencias Quimicas

    2012-11-15

    A phytochemical investigation of the roots of Krameria tomentosa A. St.-Hil. led to the isolation of five neolignans, two of them with novel structures [1,1'-(E)-propenyl-4-methoxy- 3,4'-oxyneolignan (ottomentosa) and 2-(2'-hydroxy-4',6'-dimethoxyphenyl)benzofuran- 5-carboxylic acid (sobraline)] and three known compounds [eupomatenoid 6, dihydrocarinatidin and 2-(2',4'-dihydroxyphenyl)-5-(E)-propenylbenzofuran]. The structural characterization of the compounds isolated was established based on infrared spectroscopy, mass spectrometry, one- and two-dimensional nuclear magnetic resonance, along with comparison with spectral data described in the literature. (author)

  12. Catalysis induced by radiations; Catalisis inducida por radiaciones

    Energy Technology Data Exchange (ETDEWEB)

    Jimenez B, J.; Gonzalez J, J. C., E-mail: jaime.jimenez@inin.gob.m [ININ, Departamento de Quimica, Carretera Mexico-Toluca s/n, 52750 Ocoyoacac, Estado de Mexico (Mexico)

    2010-07-01

    In Mexico is generated a great quantity of residuals considered as dangerous, for its capacity of corrosion, reactivity, toxicity to the environment, inflammability and biological-infectious potential. It is important to mention that the toxic compounds cannot be discharged to the sewerage systems and much less to the receiving bodies of water. The usual treatment that receives the dangerous residuals is the incineration and the bordering. The incineration is an efficient form of treating the residuals, but it can be dioxins source and benzofurans, being the phenol and chloro phenol the precursors of these compounds. At the present time the radiolytic degradation of organic compounds has been broadly studied, especially the 4-chloro phenol and of same form the photo catalysis of organic compounds. However the combination of both processes, called radio catalysis is barely reported. In this work the results of the experiments realized for to degrade the 4-chloro phenol by means of radio catalysis are reported. (Author)

  13. Synthesis, biological evaluation and molecular docking of N-phenyl thiosemicarbazones as urease inhibitors.

    Science.gov (United States)

    Hameed, Abdul; Khan, Khalid Mohammed; Zehra, Syeda Tazeen; Ahmed, Ramasa; Shafiq, Zahid; Bakht, Syeda Mahwish; Yaqub, Muhammad; Hussain, Mazhar; de la Vega de León, Antonio; Furtmann, Norbert; Bajorath, Jürgen; Shad, Hazoor Ahmad; Tahir, Muhammad Nawaz; Iqbal, Jamshed

    2015-08-01

    Urease is an important enzyme which breaks urea into ammonia and carbon dioxide during metabolic processes. However, an elevated activity of urease causes various complications of clinical importance. The inhibition of urease activity with small molecules as inhibitors is an effective strategy for therapeutic intervention. Herein, we have synthesized a series of 19 benzofurane linked N-phenyl semithiocarbazones (3a-3s). All the compounds were screened for enzyme inhibitor activity against Jack bean urease. The synthesized N-phenyl thiosemicarbazones had varying activity levels with IC50 values between 0.077 ± 0.001 and 24.04 ± 0.14 μM compared to standard inhibitor, thiourea (IC50 = 21 ± 0.11 μM). The activities of these compounds may be due to their close resemblance of thiourea. A docking study with Jack bean urease (PDB ID: 4H9M) revealed possible binding modes of N-phenyl thiosemicarbazones. PMID:26119990

  14. Responses of the L5178Y tk/sup +//tk/sup -/ mouse lymphoma cell forward mutation assay. II. 18 coded chemicals

    Energy Technology Data Exchange (ETDEWEB)

    McGregor, D.B.; Brown, A.; Cattanach, P.; Edwards, I.; McBride, D.; Caspary, W.J.

    1988-01-01

    Eighteen chemicals were tested for their mutagenic potential in the L5178Y tk/sup +///sup -/ mouse lymphoma cell forward mutation assay by the use of procedures based upon those described previously. Cultures were exposed to the chemicals for 4 hr, then cultured for 2 days before plating in soft agar with or without trifluorothymidine (TFT), 3 ..mu..g/ml. The chemicals were tested at least twice. Significant responses were obtained with benzofuran, benzyl chloride, bromodichloromethane, butylated hydroxytoluene, chlorendic acid, o-chlorobenzalmalonitrile, 1,2,3,4-diepoxybutane, dimethyl formamide, dimethyl hydrogen phosphite, furfural, glutaraldehyde, hydroquinone, 8-hydroxyquinoline, and resorcinol. Apart from bromodichloromethane, butylated hydroxytoluene and dimethyl hydrogen phosphite, rat liver S9 mix was not a requirement for the activity of any of these compounds. Chemicals not identified as mutagens were water, tert-butyl alcohol, pyridine, and witch hazel.

  15. Amiodarone Pulmonary, Neuromuscular and Ophthalmologic Toxicity

    Directory of Open Access Journals (Sweden)

    Karen EA Burns

    2000-01-01

    Full Text Available Amiodarone is an iodinated benzofuran derivative class III antiarrhythmic that is highly effective in suppressing ventricular and supraventricular arrhythmias. It is also associated with an imposing side effect profile, which often limits its use. Numerous adverse effects have been documented including skin discolouration, photosensitivity, hepatitis, thyroid dysfunction, corneal deposits, pulmonary fibrosis, bone marrow suppression and drug interactions. These side effects are thought to be correlated with the total cumulative dose of amiodarone, but idiopathic reactions have been reported. The majority of adverse reactions resolve with discontinuation of the drug; however, rapid progression may occur, which may be fatal. The present report documents a patient who had a combination of serious amiodarone toxicities that, once recognized, were treated and eventually resulted in a good outcome.

  16. 1,3-Benzoxazole-4-carbonitrile as a novel antifungal scaffold of β-1,6-glucan synthesis inhibitors.

    Science.gov (United States)

    Kuroyanagi, Jun-ichi; Kanai, Kazuo; Sugimoto, Yuuichi; Horiuchi, Takao; Achiwa, Issei; Takeshita, Hiroshi; Kawakami, Katsuhiro

    2010-11-01

    Synthesis and in vitro antifungal evaluations of 1,3-benzoxazole-7-carbonitrile 3, 1,3-benzoxazole-4-carbonitrile 4, benzofuran 5, benzoxazine 7, and benzimidazole 8 were reported. Among them, 1,3-benzoxazole-4-carbonitrile was found to be a superior scaffold structure with moderate growth inhibition against Candida species. 1,3-Benzoxazole-4-carbonitrile 6 showed potent activity against Candida species compared to 5-desmethyl compound 4 and triazolopyridine 2. Compound 6 was efficiently prepared from versatile intermediate 24, which possessed six different substituents on the benzene ring. Conversion of benzene 24 into various 1,3-benzoxazole derivatives such as 2-aliphatic 34, 2-amino 35, and lactone 38 was demonstrated.

  17. Antioxidant effects of phenolic rye (Secale cereale L.) extracts, monomeric hydroxycinnamates, and ferulic acid dehydrodimers on human low-density lipoproteins

    DEFF Research Database (Denmark)

    Andreasen, M.F.; Landbo, Anne-Katrine Regel; Christensen, L.P.;

    2001-01-01

    Dietary antioxidants that protect low-density lipoprotein (LDL) from oxidation may help to prevent atherosclerosis and coronary heart disease. The antioxidant activities of purified monomeric and dimeric hydroxycinnamates and of phenolic extracts from rye (whole grain, bran, and flour) were...... neither 5-5-diFA nor 8- 5-benzofuran-diFA inhibited LDL oxidation when added at 10-40 muM. The antioxidant activity of the monomeric hydroxycinnamates decreased in the following order: caffeic acid > sinapic acid > ferulic acid > p-coumaric acid. The antioxidant activity of rye extracts was significantly...... correlated with their total content of monomeric and dimeric hydroxycinnamates, and the rye bran extract was the most potent. The data suggest that especially rye bran provides a source of dietary phenolic antioxidants that may have potential health effects....

  18. Antioxidant effects of phenolic rye (Secale cereale L.) extracts, monomeric hydroxycinnamates, and ferulic acid dehydrodimers on human low-density lipoproteins

    DEFF Research Database (Denmark)

    Andreasen, Mette Findal; Landbo, A K; Christensen, L P;

    2001-01-01

    Dietary antioxidants that protect low-density lipoprotein (LDL) from oxidation may help to prevent atherosclerosis and coronary heart disease. The antioxidant activities of purified monomeric and dimeric hydroxycinnamates and of phenolic extracts from rye (whole grain, bran, and flour) were...... neither 5-5-diFA nor 8-5-benzofuran-diFA inhibited LDL oxidation when added at 10-40 microM. The antioxidant activity of the monomeric hydroxycinnamates decreased in the following order: caffeic acid > sinapic acid > ferulic acid > p-coumaric acid. The antioxidant activity of rye extracts was...... significantly correlated with their total content of monomeric and dimeric hydroxycinnamates, and the rye bran extract was the most potent. The data suggest that especially rye bran provides a source of dietary phenolic antioxidants that may have potential health effects. Udgivelsesdato: 2001-Aug...

  19. Synthesis, in Vivo Anti-inflammatory, and in Vitro Antimicrobial Activity of New 5-Benzofuranyl Fused Pyrimidines.

    Science.gov (United States)

    Nassar, Ekhlass; El-Badry, Yaser Abdel-Moemen; El Kazaz, Hagar

    2016-01-01

    Chalcone (3) has been synthesized as a new chalcone derivative bearing benzofuran moiety at 1 position. Such chalcone was used as a model dielectrophile applied to react with some nucleophiles such as 5-amino pyrazoles, 5-amino-1,2,4-triazole, 2-aminobenzimidazole, and 6-uraciles under Michael reaction conditions and resulted in a new series of fused pyrimidines such as pyrazolo[1,5-a]pyrimidines 7a-e, [1,2,4]-triazolo[1,5-a]pyrimidine 9, pyrimido[1,2-a]benzimidazole 11, and synthesis of pyrido[2,3-d]pyrimidinones 13a and b. The structures of the synthesized target heterocyclic compounds were confirmed by microanalytical and spectral data such as Fourier transform (FT)-IR, (1)H-NMR, and MS spectra. The newly synthesized compounds were evaluated for their anti-inflammatory and antimicrobial activities; most showed significant activities. PMID:27250790

  20. Combined etiology of anaphylactic cardiogenic shock: Amiodarone, epinephrine, cardioverter defibrillator, left ventricular assist devices and the Kounis syndrome

    Directory of Open Access Journals (Sweden)

    Nicholas G Kounis

    2015-01-01

    Full Text Available Anaphylactic shock is a life-threatening condition which needs detailed and mediculous clinical assessment and thoughtful treatment. Several causes can join forces in order to degranulate mast cells. Amiodarone which is an iodine-containing highly lipophilic benzofuran can induce allergic reactions and anaphylactic shock in sensitized patients. Epinephrine is a life saving drug, but in sulfite allergic patients it should be given with caution due its metabisulfite preservative. Metals covering cardiac defibrillators and pacemakers can act as antigens attached to serum proteins and induce allergic reactions. In anaphylactic shock, myocardial involvement due to vasospasm-induced coronary blood flow reduction manifesting as Kounis syndrome should be always considered. Clinically, combined treatment targeting the primary cause of anaphylaxis together with protection of cardiac tissue seems to be of paramount importance.

  1. Biological activities of lignoids from Amazon Myristicaceae species: Virota michelii, V. mollissima, V. pavonis and Iryanthera juruensis

    Energy Technology Data Exchange (ETDEWEB)

    Morais, Sabrina K.R.; Yoshida, Massayoshi [Universidade de Sao Paulo (USP), SP (Brazil). Inst. de Quimica; Centro de Biotecnologia da Amazonia, Manaus, AM (Brazil)], e-mail: myoshida@iq.usp.br; Teixeira, Ana F. [Universidade do Estado do Amazonas, Manaus, AM (Brazil). Escola Normal Superior; Torres, Zelina E. dos S. [Universidade do Estado do Amazonas, Manaus, AM (Brazil). Escola Superior de Ciencias da Saude; Numomura, Sergio M. [Instituto Nacional de Pesquisas da Amazonia (INPA), Manaus, AM (Brazil). Coordenacao de Pesquisa de Produtos Naturais; Yamashiro-Kanashiro, Edite H.; Lindoso, Jose Angelo I. [Universidade de Sao Paulo, SP (Brazil). Hospital das Clinicas. Lab. de Epidemiologia e Imunobiologia

    2009-07-01

    This work revisits the fruits of Iryanthera juruensis and Virola pavonis and the leaves from V. michelii, as well as describing a study of the fruits of V. mollissima. In I. juruensis aryltetraline neolignan (1) and tetrahydrofuran neolignan (2), were found while from V. pavonis neolignans of benzofuran type (6-9), the tetrahydrofuran type (2, 11-13, 17) and the biphenyl type (10), in addition to diastereoisomers of the 8.O.4'-oxyneolignan type (14 and 15) and others were isolated. The V. mollissima accumulates the aryltetralone neolignan 4 and its seco derivative (5). The lignoids 1 and 2 obtained from I. juruensis arils possess antileishmanial activity against the promastigote form of Leishmania amazonensis. (author)

  2. 基于MCM-41微反应器的微波辅助合成新方法研究%Investigation on Novel Microwave-Assisted Synthesis Method Based on MCM-41 Microreactor

    Institute of Scientific and Technical Information of China (English)

    肖尚友; 杨昊书; 李倩倩; 邱静; 夏之宁

    2011-01-01

    MCM-41 mesoporous molecular sieve was synthesized under microwave irradiation and used as microreactor.2-Hydroxyphenylacetic acid was assembled into MCM-41 microreactor in toluene solution, and benzofuran-2(3H)-one was obtained by the intramolecular esterification of 2-hydroxyphenylacetic acid with high selectivity.The reaction conditions including temperature, reaction time, microwave irradiation and so on were investigated.The yield of benzofuran-2(3H)-one was improved by 2~12 and 2~33 times in MCM-41 microreactor than that in solution under conventional heating and microwave irradiation respectively.In addition, the yield of the reaction in MCM-41 reactor under microwave irradiation could be improved by 20%~ 100%.%采用微波辐射合成法合成了纳米介孔分子筛MCM-41作为微反应器.以苯并呋喃-2(3H)-酮的合成为实例,在甲苯介质中将邻羟基苯乙酸组装到MCM-41微反应器中,研究了溶液体系及微反应器中反应温度、反应时间及微波辐射时间对反应的影响.结果显示,在施加微波与不施加微波情况下,MCM-41微反应器中进行的反应较溶液体系中进行的反应产率提高了2~33与2~12倍.对于MCM-41微反应器中的反应,施加微波辐射后反应产率可进一步提高20%~100%.

  3. Genetic and metabolic analysis of the carbofuran catabolic pathway in Novosphingobium sp. KN65.2.

    Science.gov (United States)

    Nguyen, Thi Phi Oanh; Helbling, Damian E; Bers, Karolien; Fida, Tekle Tafese; Wattiez, Ruddy; Kohler, Hans-Peter E; Springael, Dirk; De Mot, René

    2014-10-01

    The widespread agricultural application of carbofuran and concomitant contamination of surface and ground waters has raised health concerns due to the reported toxic effects of this insecticide and its degradation products. Most bacteria that degrade carbofuran only perform partial degradation involving carbamate hydrolysis without breakdown of the resulting phenolic metabolite. The capacity to mineralize carbofuran beyond the benzofuran ring has been reported for some bacterial strains, especially sphingomonads, and some common metabolites, including carbofuran phenol, were identified. In the current study, the catabolism of carbofuran by Novosphingobium sp. KN65.2 (LMG 28221), a strain isolated from a carbofuran-exposed Vietnamese soil and utilizing the compound as a sole carbon and nitrogen source, was studied. Several KN65.2 plasposon mutants with diminished or abolished capacity to degrade and mineralize carbofuran were generated and characterized. Metabolic profiling of representative mutants revealed new metabolic intermediates, in addition to the initial hydrolysis product carbofuran phenol. The promiscuous carbofuran-hydrolyzing enzyme Mcd, which is present in several bacteria lacking carbofuran ring mineralization capacity, is not encoded by the Novosphingobium sp. KN65.2 genome. An alternative hydrolase gene required for this step was not identified, but the constitutively expressed genes of the unique cfd operon, including the oxygenase genes cfdC and cfdE, could be linked to further degradation of the phenolic metabolite. A third involved oxygenase gene, cfdI, and the transporter gene cftA, encoding a TonB-dependent outer membrane receptor with potential regulatory function, are located outside the cfd cluster. This study has revealed the first dedicated carbofuran catabolic genes and provides insight in the early steps of benzofuran ring degradation.

  4. New phenethylamines in Europe.

    Science.gov (United States)

    King, L A

    2014-01-01

    Sixteen phenethylamines are now included in Schedules I and II of the United Nations 1971 Convention on Psychotropic Substances. Most of the ring-substituted compounds are in Schedule I, whereas 2C-B, amphetamine, and methamphetamine are listed in Schedule II. Substances in Schedule IV (e.g. benzphetamine) are now regarded as obsolete pharmaceutical products. They all represent the 'old phenethylamines'. By 2013, nearly 100 illicit phenethylamines had been found in the European Union (EU). Of these, nine (MBDB, 4-MTA, PMMA, 2C-I, 2C-T-2, 2C-T-7, TMA-2, 5-IT and 4-MA) were submitted for risk assessment by the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). All except MBDB were recommended for EU-wide control. Of the 'new phenethylamines', 2C-B was the most commonly reported, but other 2C compounds were widespread. Many of the ring-substituted phenethylamines are described in the 1991 book PIHKAL. Many fused ring phenethylamines have appeared in the past few years; they include further benzofurans (e.g. 5-and 6-APB), indanylalkylamines (e.g. 5-IAP), dibenzofurans (e.g. 2C-B-FLY) and 2-aminopropylindoles (e.g.5-IT). The recent and rapid rise of phenethylamines with bulky N-substituents (e.g. 25I-NBOMe) has been particularly significant. Although not phenethylamines, it is notable that the thiophene bioisosteres of amphetamine and methamphetamine as well as certain conformationally-restricted variants (e.g. aminoindanes) have been found in recent drug seizures. In the United Kingdom Misuse of Drugs Act, most ring-substituted phenethylamines are either listed by name or are covered by generic definitions dating from 1977. In 2013, temporary generic legislation included a number of benzofurans, indanylalkylamines and certain 'NBOMe' compounds.

  5. Dioxin-ähnliche Wirkungen durch Grundwasser am Industriestandort Zeitz

    Science.gov (United States)

    Schirmer, Kristin; Bopp, Stephanie; Russold, Sandra; Popp, Peter

    Kurzfassung Im Rahmen der Etablierung des Standortes Zeitz (Sachsen-Anhalt) als Referenztestfeld zur Implementierung des Natural-Attenuation-Ansatzes, haben wir Grundwasser auf seine Fähigkeit untersucht, eine Dioxin-ähnliche Wirkung hervorzurufen. Die Dioxin-ähnliche Wirkung ist die Arylhydrocarbon Rezeptor-vermittelte Induktion des Proteinkomplexes Cytochrom CYP1A, welches als 7-Ethoxyresorufin-O-Deethylase (EROD) Enzymaktivität in einer Fischleberzelllinie gemessen wurde. Von 32 Probennahmestellen wiesen sieben eine signifikante EROD-Induktion auf, welche zu einem geringen Teil auf Polyzyklische Aromatische Kohlenwasserstoffe zurückzuführen war. Ein weiterer Teil der EROD-Induktion konnte den Substanzen Benzofuran, Indan und Inden zugesprochen werden, welche hier erstmalig als EROD-Induktoren identifiziert wurden. Alle Probennahmestellen mit signifikanter EROD-Induktion lagen im Anstrom bzw. westlich des früheren Standortes der Benzolanlage in Zeitz, was einen signifikanten Einfluss von Benzol vor allem auf den Transport und das Lösungsverhalten EROD-induzierender Grundwasserkontaminanten vermuten lässt. Insgesamt zeigen diese Untersuchungen, wie eine Kombination von chemischer und biologischer Analytik zu einer deutlich verbesserten Aussagekraft führt und somit zu einer nachhaltigen Überwachung der Qualität von Grundwasser beitragen kann. As part of setting up the test field Zeitz (Saxony-Anhalt, Germany) as a reference site for the implementation of Natural Attenuation as a remediation option, we have investigated groundwater for its ability to cause a dioxin-like response. The dioxin-like response is the aryl hydrocarbon receptor-mediated induction of the protein complex cytochrome CYP1A, which was measured as 7-Ethoxyresorufin-O-deethylase (EROD) enzyme activity in a fish liver cell line. Out of 32 sampling locations, seven showed significant EROD induction, which could be explained, to a minor extent, by the presence of polycyclic aromatic

  6. Metabolites in safety testing assessment in early clinical development: a case study with a glucokinase activator.

    Science.gov (United States)

    Sharma, Raman; Litchfield, John; Atkinson, Karen; Eng, Heather; Amin, Neeta B; Denney, William S; Pettersen, John C; Goosen, Theunis C; Di, Li; Lee, Esther; Pfefferkorn, Jeffrey A; Dalvie, Deepak K; Kalgutkar, Amit S

    2014-11-01

    The present article summarizes Metabolites in Safety Testing (MIST) studies on a glucokinase activator, N,N-dimethyl-5-((2-methyl-6-((5-methylpyrazin-2-yl)carbamoyl)benzofuran-4-yl)oxy)pyrimidine-2-carboxamide (PF-04937319), which is under development for the treatment of type 2 diametes mellitus. Metabolic profiling in rat, dog, and human hepatocytes revealed that PF-04937319 is metabolized via oxidative (major) and hydrolytic pathways (minor). N-Demethylation to metabolite M1 [N-methyl-5-((2-methyl-6-((5-methylpyrazin-2-yl)carbamoyl)benzofuran-4-yl)oxy)pyrimidine-2-carboxamide] was the major metabolic fate of PF-04937319 in human (but not rat or dog) hepatocytes, and was catalyzed by CYP3A and CYP2C isoforms. Qualitative examination of circulating metabolites in humans at the 100- and 300-mg doses from a 14-day multiple dose study revealed unchanged parent drug and M1 as principal components. Because M1 accounted for 65% of the drug-related material at steady state, an authentic standard was synthesized and used for comparison of steady-state exposures in humans and the 3-month safety studies in rats and dogs at the no-observed-adverse-effect level. Although circulating levels of M1 were very low in beagle dogs and female rats, adequate coverage was obtained in terms of total maximal plasma concentration (∼7.7× and 1.8×) and area under the plasma concentration-time curve (AUC; 3.6× and 0.8× AUC) relative to the 100- and 300-mg doses, respectively, in male rats. Examination of primary pharmacology revealed M1 was less potent as a glucokinase activator than the parent drug (compound PF-04937319: EC50 = 0.17 μM; M1: EC50 = 4.69 μM). Furthermore, M1 did not inhibit major human P450 enzymes (IC50 > 30 μM), and was negative in the Salmonella Ames assay, with minimal off-target pharmacology, based on CEREP broad ligand profiling. Insights gained from this analysis should lead to a more efficient and focused development plan for fulfilling MIST requirements with

  7. Coumestan inhibits radical-induced oxidation of DNA: is hydroxyl a necessary functional group?

    Science.gov (United States)

    Xi, Gao-Lei; Liu, Zai-Qun

    2014-06-18

    Coumestan is a natural tetracycle with a C═C bond shared by a coumarin moiety and a benzofuran moiety. In addition to the function of the hydroxyl group on the antioxidant activity of coumestan, it is worth exploring the influence of the oxygen-abundant scaffold on the antioxidant activity as well. In this work, seven coumestans containing electron-withdrawing and electron-donating groups were synthesized to evaluate the abilities to trap 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS(•+)), 2,2'-diphenyl-1-picrylhydrazyl radical (DPPH), and galvinoxyl radical, respectively, and to inhibit the oxidations of DNA mediated by (•)OH, Cu(2+)/glutathione (GSH), and 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH), respectively. It was found that all of the coumestans used herein can quench the aforementioned radicals and can inhibit (•)OH-, Cu(2+)/GSH-, and AAPH-induced oxidations of DNA. In particular, substituent-free coumestan exhibits higher ability to quench DPPH and to inhibit AAPH-induced oxidation of DNA than Trolox. In addition, nonsubstituted coumestan shows a similar ability to inhibit (•)OH- and Cu(2+)/GSH-induced oxidations of DNA relative to that of Trolox. The antioxidant effectiveness of the coumestan can be attributed to the lactone in the coumarin moiety and, therefore, a hydroxyl group may not be a necessary functional group for coumestan to be an antioxidant.

  8. Dronedarone.

    Science.gov (United States)

    Tamargo, J; López-Farré, A; Caballero, R; Delpón, E

    2011-02-01

    Atrial fibrillation (AF), the most common cardiac arrhythmia, is associated with substantial morbidity and mortality. Dronedarone is an amiodarone-like benzofuran which lacks the iodine moiety and presents a methane sulfonyl group that decreases its lipophilicity, thus shortening the half-life and decreasing tissue accumulation. Like amiodarone, dronedarone blocks multiple cardiac ion channels and β-adrenoceptors, presenting electrophysiological characteristics of all four Vaughan Williams classes of antiarrhythmic drugs. In clinical trials, dronedarone has been found effective for both rhythm and rate control. Dronedarone was more effective than placebo in maintaining sinus rhythm in patients with paroxysmal and/or persistent AF and was also effective for ventricular rate control during AF recurrences, providing incremental rate control on top of standard drugs in permanent AF. Furthermore, in the ATHENA trial, dronedarone reduced the incidence of hospitalization due to cardiovascular events or death in patients with nonpermanent AF. Even when dronedarone was less effective than amiodarone in decreasing AF recurrence, it had a better safety profile, being devoid of thyroid, pulmonary and neurological toxicity. This review analyzes the electrophysiological and pharmacological properties, as well as the efficacy and safety of dronedarone in patients with atrial fibrillation.

  9. A Lean Methane Prelixed Laminar Flame Doped witg Components of Diesel Fuel. Part I: n)Butylbenzene

    CERN Document Server

    Pousse, Emir; Fournet, René; Battin-Leclerc, Frédérique; 10.1016/j.combustflame.2008.09.012

    2009-01-01

    To better understand the chemistry involved during the combustion of components of diesel fuel, the structure of a laminar lean premixed methane flame doped with n-butylbenzene has been investigated. The inlet gases contained 7.1% (molar) of methane, 36.8% of oxygen and 0.96% of n-butylbenzene corresponding to an equivalence ratio of 0.74 and a ratio C10H14 / CH4 of 13.5%. The flame has been stabilized on a burner at a pressure of 6.7 kPa using argon as diluent, with a gas velocity at the burner of 49.2 cm/s at 333 K. Quantified species included the usual methane C0-C2 combustion products, but also 16 C3-C5 hydrocarbons, 7 C1-C3 oxygenated compounds, as well as 20 aromatic products, namely benzene, toluene, phenylacetylene, styrene, ethylbenzene, xylenes, allylbenzene, propylbenzene, cumene, methylstyrenes, butenylbenzenes, indene, indane, naphthalene, phenol, benzaldehyde, anisole, benzylalcohol, benzofuran, and isomers of C10H10 (1-methylindene, dihydronaphtalene, butadienylbenzene). A new mechanism for the...

  10. Effects of ultrasonic processing on degradation of salvianolic acid B in aqueous solution.

    Science.gov (United States)

    Guo, Y X; Zhang, L; Lu, L; Liu, E H; Shi, C Z

    2016-09-10

    To evaluate the stability of salvianolic acid B (Sal B) under ultrasound-assisted extraction in the pharmaceutical industry, degradation of Sal B under ultrasonic irradiation was investigated as the function of buffer concentration, pH, and temperature. With regard to Sal-B concentration, a first-order degradation process was determined, with 10% change in assay from its initial concentration as t90=4.81h, under maximum stability acidic conditions (pH 2.0) and at 25°C. The logkpH-pH profile described by specific acid-base catalysis and water molecules supported the experimental results. Liquid chromatography-mass spectrometry (LC-MS) analyses revealed 7 major degradation products whose structures were characterized by electrospray ionization/mass spectrometry. A primary degradation pathway involved cleavage of the ester bond and ring-opening of benzofuran in Sal B was proposed. The complete degradation pathway of Sal B was also proposed. Results showed that ultrasonic irradiation leads to degradation of Sal B in aqueous solution. PMID:27442887

  11. Synthesis of New Schiff Base from Natural Products for Remediation of Water Pollution with Heavy Metals in Industrial Areas

    Directory of Open Access Journals (Sweden)

    Reham Hassan

    2013-01-01

    Full Text Available A resin of [5-((E-1-(ethylimino ethyl-4, 7-dimethoxy benzofuran-6-ol] Schiff base (EEDB was prepared, characterized, and successfully applied in the removal of Cu (II ions from aqueous real samples. While the metal cation was detected using ICP-OES, the prepared Schiff base resin was characterized by means of FTIR, 1HNMR, mass spectral data, and elemental analysis. Various factors affecting the uptake behavior such as pH (2–12, contact time, effect of initial metal concentration (10–250 ppm, and effect of Schiff base weight (0.1–1.5 gm were studied. The adsorption process was relatively fast and equilibrium was established after about 60 min. The optimum initial pH was 8.0 at a metal ion concentration (100 ppm. Under the optimized conditions, the removal of Cu (II from real samples of tap water was applied and the removal efficiency reached nearly 85%. The biological activity for Schiff base was also investigated. The results showed that there is no significant difference between the effects of Schiff base on serum (alanine amino transferase ALT and creatinine concentration activities in treated mice and control, at confidence limits 95%.

  12. Identification of print-related contaminants in food packaging.

    Science.gov (United States)

    Lago, Miguel A; Ackerman, Luke K

    2016-01-01

    Since the UV ink photoinitiator (PI) isopropylthioxanthone (ITX) was discovered in packaged milk, studies of print contamination have focused primarily on PIs but have also included amine synergists. Many other substances are used or formed during the print process, yet their identity and set-off properties have yet to be catalogued in food packaging. Three different techniques: direct analysis in real-time high-resolution mass spectrometry (DART-HRMS), gas chromatography-mass spectrometry (GC-MS) and ultra-high-pressure liquid chromatography electrospray ionisation/HRMS (UHPLC/ESI-HRMS) were used to detect and identify print-related molecules from the food-contact and print surfaces of three different packages with under-cured prints. This approach tentatively identified or confirmed 110 compounds, including 35 print-related molecules. The majority of compounds identified on food-contact surfaces were packaging monomers/byproducts, solvents/plasticisers, antioxidants/degradants or slip agents/lubricants. Of these, 28 showed evidence of set-off. The identities of 16 PIs, seven known scission products and five probable PI degradants were confirmed, most showing signs of set-off. Of the print-related molecules, at least five are novel print contaminants such as 4-morpholin-4-yl-benzaldehyde or 3-phenyl-2-benzofuran-1(3H)-one. PMID:26789986

  13. Chemical compositions of the volatile extracts from seeds of Dendranthema nankingense and Borago officinalis

    Directory of Open Access Journals (Sweden)

    Shimin Wu

    2015-06-01

    Full Text Available Volatile extracts from the seeds of Dendranthema nankingense Hand.-Mazz. and Borago officinalis L. were prepared using simultaneous distillation and extraction, and analyzed with gas chromatography–mass spectrometry on two capillary gas chromatography columns of different polarity. Ninety-five volatile compounds were identified in D. nankingense seeds, with hexanal, benzeneacetaldehyde, borneol, (−-camphor, and 3-methyl-1-butanol being the predominant species. Sixty-five volatile compounds were identified in B. officinalis seeds, with 2-pentanone, 2,3-dihydro-benzofuran, 3-methyl butanal, and hexanal being the most abundant species. Thirty-three compounds, including short-chain aliphatic aldehydes, alcohols, and ketones, were common to both seeds. The volatile composition of both seeds varied significantly depending on their respective origins. The volatile terpenoids borneol and (−-camphor could be key bioactive contributors to the characteristic flavor and cooling effects of D. nankingense. For the first time, coumaran was identified as an abundant species in plant seeds.

  14. Degradation of carbofuran-contaminated water by the Fenton process.

    Science.gov (United States)

    Ma, Ying-Shih; Kumar, Mathava; Lin, Jih-Gaw

    2009-07-15

    In this study, the Fenton process was applied for the degradation of carbofuran from aqueous system. Batch experiments were conducted at two different carbofuran concentrations i.e., 10 and 50 mg/L, and at pH 3. Batch experiments at each carbofuran concentration were designed by central composite design (CCD) with two independent variables i.e. Fe2+ and H2O2. Experimental results indicate that more than 90% of carbofuran removal was observed within 5 mins of Fenton reaction at 5 mg/L of Fe2+ concentration and 100 mg/L of H202 concentration. Increases in Fe2+ and/or H2O2 concentrations beyond 5 and 100 mg/L, respectively produced 100% carbofuran removal. Based on the experimental observations, the optimal Fe2+ and H2O2 dosages required for 10 mg/L of aqueous carbofuran removal were estimated as 7.4 and 143 mg/L, respectively. During this study, three carbofuran intermediates such as 7-benzofuranol,2,3,-dihydro-2,2-dimethyl, 7-hydroxy-2,2-dimethyl-benzofuran-3-one and 1,4-Benzene-di-carboxaldehyde were identified using GC/MS analyses.

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

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    Pritipadma Panda

    2015-01-01

    Full Text Available Background: Clerodendrum viscosum is commonly found in India and Bangladesh. Previously, various parts of this plant were reported for treatment of different types of diseases and there was no report on GC-Ms analysis. Objective: To analyze and characterize the phytochemical compounds of methanol extract of Clerodendrum viscosum using GC-MS. Materials and Methods: The preliminary phytochemical screening of methanol extract was carried out according to standard procedures described in WHO guidelines. Various bioactive compounds of the extract were determined by GC-MS technique. Results: The presence of steroids, triterpenoids, alkaloids, saponins, flavonoids, tannins and carbohydrate was found on phytochemical screening of methanol extract of the leaves. The GC-MS analysis showed 16 peaks of different phytoconstituents namely acetamide,N,N-carbonylbis-, 4-Pyranone,2,3-dihydro-, alpha-D-Galactofuranoside, methyl 2,3,5,6-tetra-O-methyl-, Glycerin, Xylitol, N,N-Dimethylglycine, 4H-Pyran-4-one,2,3-dihydro-3, 5-dihydroxy-6-methyl-, Benzofuran,2,3-dihydro-, 5-Hydroxymethylfurfural, 2(1HPyrimidinone,1-methyl-, 2,4-Dihydroxy-5,6-dimethylpyrimidine, 3-Deoxy-d-mannoic lactone, 1,3-Methylene-d-arabitol, Orcinol, n-Hexadecanoic acid and Phenol,4,4′-(1-methyl ethylidene bis etc. Conclusion: The bioactive compounds present in the methanol extract of Clerodendrum viscosum suggest the application of this extract for the treatment of various diseases by the aborigine tribes.

  16. High-throughput screening for new psychoactive substances (NPS) in whole blood by DLLME extraction and UHPLC-MS/MS analysis.

    Science.gov (United States)

    Odoardi, Sara; Fisichella, Marco; Romolo, Francesco Saverio; Strano-Rossi, Sabina

    2015-09-01

    The increasing number of new psychoactive substances (NPS) present in the illicit market render their identification in biological fluids/tissues of great concern for clinical and forensic toxicology. Analytical methods able to detect the huge number of substances that can be used are sought, considering also that many NPS are not detected by the standard immunoassays generally used for routine drug screening. The aim of this work was to develop a method for the screening of different classes of NPS (a total of 78 analytes including cathinones, synthetic cannabinoids, phenethylamines, piperazines, ketamine and analogues, benzofurans, tryptamines) from blood samples. The simultaneous extraction of analytes was performed by Dispersive Liquid/Liquid Microextraction DLLME, a very rapid, cheap and efficient extraction technique that employs microliters amounts of organic solvents. Analyses were performed by a target Ultrahigh Performance Liquid Chromatography tandem Mass Spectrometry (UHPLC-MS/MS) method in multiple reaction monitoring (MRM). The method allowed the detection of the studied analytes with limits of detection (LODs) ranging from 0.2 to 2ng/mL. The proposed DLLME method can be used as an alternative to classical liquid/liquid or solid-phase extraction techniques due to its rapidity, necessity to use only microliters amounts of organic solvents, cheapness, and to its ability to extract simultaneously a huge number of analytes also from different chemical classes. The method was then applied to 60 authentic real samples from forensic cases, demonstrating its suitability for the screening of a wide number of NPS. PMID:26209771

  17. Experimental study of the structure of a lean premixed indane/CH4/O2/Ar flame

    CERN Document Server

    Pousse, Emir; Fournet, René; Battin-Leclerc, Frédérique

    2009-01-01

    In order to better understand the chemistry involved during the combustion of components of diesel fuel, the structure of a laminar lean premixed methane flame doped with indane has been investigated. The gases of this flame contains 7.1% (molar) of methane, 36.8% of oxygen and 0.90% of indane corresponding to an equivalence ratio of 0.74 and a ratio C9H10/CH4 of 12.75%. The flame has been stabilized on a burner at a pressure of 6.7 kPa using argon as dilutant, with a gas velocity at the burner of 49.2 cm/s at 333 K. Quantified species included usual methane C0-C2 combustion products, but also 11 C3-C5 hydrocarbons and 3 C1-C3 oxygenated compounds, as well as 17 aromatic products, namely benzene, toluene, phenylacetylene, styrene, ethylbenzene, xylenes, trimethylbenzenes, ethyltoluenes, indene methylindane, methylindene, naphthalene, phenol, benzaldehyde, benzofuran. The temperature was measured thanks to a thermocouple in PtRh (6%)-PtRh (30%) settled inside the enclosure and ranged from 800 K close to the bu...

  18. Managing atrial fibrillation in the elderly: critical appraisal of dronedarone

    Directory of Open Access Journals (Sweden)

    Trigo P

    2011-12-01

    Full Text Available Paula Trigo, Gregory W FischerDepartment of Anesthesiology, Mount Sinai School of Medicine, New York, NY, USAAbstract: Atrial fibrillation is the most commonly seen arrhythmia in the geriatric population and is associated with increased cardiovascular morbidity and mortality. Treatment of the elderly with atrial fibrillation remains challenging for physicians, because this unique subpopulation is characterized by multiple comorbidities requiring chronic use of numerous medications, which can potentially lead to severe drug interactions. Furthermore, age-related changes in the cardiovascular system as well as other physiological changes result in altered drug pharmacokinetics. Dronedarone is a new drug recently approved for the treatment of arrhythmias, such as atrial fibrillation and/or atrial flutter. Dronedarone is a benzofuran amiodarone analog which lacks the iodine moiety and contains a methane sulfonyl group that decreases its lipophilicity. These differences in chemical structure are responsible for making dronedarone less toxic than amiodarone which, in turn, results in fewer side effects. Adverse events for dronedarone include gastrointestinal side effects and rash. No dosage adjustments are required for patients with renal impairment. However, the use of dronedarone is contraindicated in the presence of severe hepatic dysfunction.Keywords: atrial fibrillation, elderly, antiarrhythmic agents, amiodarone, dronedarone

  19. Study of the cytotoxic activity of Styrax camporum extract and its chemical markers, egonol and homoegonol.

    Science.gov (United States)

    de Oliveira, Pollyanna Francielli; Damasceno, Jaqueline Lopes; Bertanha, Camila Spereta; Araújo, Alba Regina Barbosa; Pauletti, Patrícia Mendonça; Tavares, Denise Crispim

    2016-08-01

    The benzofuran lignans egonol and homoegonol are found in all species of the genus Styrax. Since natural products are important sources of new anticancer drugs, this study evaluated the cytotoxic activity of a hydroalcoholic extract of the stems of S. camporum (SCHE) and their chemical markers, egonol (EG) and homoegonol (HE), against different tumor cell lines (B16F10, MCF-7, HeLa, HepG2, and MO59J). A normal human cell line (GM07492A) was included. Cytotoxic activity was evaluated at different treatment times (24, 48 and 72 h) using the XTT assay. More effective results were observed after 72 h of treatment. The lowest IC50 values were found for the HepG2 cell line, ranging from 11.2 to 55.0 µg/mL. The combination of EG and HE exerted higher cytotoxic activity than SCHE or treatment with either lignan alone, with the lowest IC50 (13.31 µg/mL) being observed for the MCF-7 line. Furthermore, treatment with these lignans was significantly more cytotoxic for some tumor cell lines compared to the normal cell line, GM07492A, indicating selectivity. These results suggest that these lignans may be used to treat cancer without affecting normal cells.

  20. Hyperacute drug-induced hepatitis with intravenous amiodarone: case report and review of the literature

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    Nasser M

    2013-09-01

    Full Text Available Mohammad Nasser, Timothy R Larsen, Barryton Waanbah, Ibrahim Sidiqi, Peter A McCullough Providence Hospitals and Medical Centers, Department of Medicine, Division of Cardiology, Southfield and Novi, MI, USA Abstract: Amiodarone is a benzofuran class III antiarrhythmic drug used to treat a wide spectrum of ventricular tachyarrhythmias. The parenteral formulation is prepared in polysorbate 80 diluent. We report an unusual case of acute elevation of aminotransaminase concentrations after the initiation of intravenous amiodarone. An 88-year-old Caucasian female developed acute hepatitis and renal failure after initiating intravenous amiodarone for atrial fibrillation with a rapid ventricular response in the setting of acutely decompensated heart failure and hepatic congestion. Liver transaminases returned to baseline within 7 days after discontinuing the drug. Researchers hypothesized that this type of injury is related to liver ischemia with possible superimposed direct drug toxicity. The CIOMS/RUCAM scale identifies our patient’s acute hepatitis as a highly probable adverse drug reaction. Future research is needed to understand the mechanisms by which hyperacute drug toxicity occurs in the setting of impaired hepatic perfusion and venous congestion. Keywords: intravenous amiodarone, acute hepatotoxicity, liver transaminases, drug-induced liver toxicity

  1. Antimicrobial activities of the methanol extract and compounds from Artocarpus communis (Moraceae

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    Ngadjui Bonaventure T

    2011-05-01

    Full Text Available Abstract Background Artocarpus communis is used traditionally in Cameroon to treat several ailments, including infectious and associated diseases. This work was therefore designed to investigate the antimicrobial activities of the methanol extract (ACB and compounds isolated from the bark of this plant, namely peruvianursenyl acetate C (1, α-amyrenol or viminalol (2, artonin E (4 and 2-[(3,5-dihydroxy-(Z-4-(3-methylbut-1-enylphenyl]benzofuran-6-ol (5. Methods The liquid microdilution assay was used in the determination of the minimal inhibitory concentration (MIC and the minimal microbicidal concentration (MMC, against seven bacterial and one fungal species. Results The MIC results indicated that ACB as well as compounds 4 and 5 were able to prevent the growth of all tested microbial species. All other compounds showed selective activities. The lowest MIC value of 64 μg/ml for the crude extract was recorded on Staphylococcus aureus ATCC 25922 and Escherichia coli ATCC 8739. The corresponding value of 32 μg/ml was recorded with compounds 4 and 5 on Pseudomonas aeruginosa PA01 and compound 5 on E. coli ATCC 8739, their inhibition effect on P. aeruginosa PA01 being more than that of chloramphenicol used as reference antibiotic. Conclusion The overall results of this study provided supportive data for the use of A. communis as well as some of its constituents for the treatment of infections associated with the studied microorganisms.

  2. Characterization of Melanogenesis Inhibitory Constituents of Morus alba Leaves and Optimization of Extraction Conditions Using Response Surface Methodology

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    Ji Yeon Jeong

    2015-05-01

    Full Text Available Melanin is a natural pigment that plays an important role in the protection of skin, however, hyperpigmentation cause by excessive levels of melatonin is associated with several problems. Therefore, melanogenesis inhibitory natural products have been developed by the cosmetic industry as skin medications. The leaves of Morus alba (Moraceae have been reported to inhibit melanogenesis, therefore, characterization of the melanogenesis inhibitory constituents of M. alba leaves was attempted in this study. Twenty compounds including eight benzofurans, 10 flavonoids, one stilbenoid and one chalcone were isolated from M. alba leaves and these phenolic constituents were shown to significantly inhibit tyrosinase activity and melanin content in B6F10 melanoma cells. To maximize the melanogenesis inhibitory activity and active phenolic contents, optimized M. alba leave extraction conditions were predicted using response surface methodology as a methanol concentration of 85.2%; an extraction temperature of 53.2 °C and an extraction time of 2 h. The tyrosinase inhibition and total phenolic content under optimal conditions were found to be 74.8% inhibition and 24.8 μg GAE/mg extract, which were well-matched with the predicted values of 75.0% inhibition and 23.8 μg GAE/mg extract. These results shall provide useful information about melanogenesis inhibitory constituents and optimized extracts from M. alba leaves as cosmetic therapeutics to reduce skin hyperpigmentation.

  3. Synthesis, characterization and biological activities of novel chalcone derivatives, containing 4, 7-ethanoisoindole-1,3-dione units

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    Mustafa Ceylan

    2013-09-01

    Full Text Available Novel chalcone derivatives, containing 4, 7-ethanoisoindole-1,3-dione units were synthesized starting from 1,3-cyclohexadine (4 and maleic anhydride (5. Addition of maleic anhydride (5 to 1,3-cyclehexadine (4 gave an endo-adduct, 3a,4,7,7a-tetrahydro-4,7-ethano-2-benzofuran-1,3-dione (6, in 90% yield. Heating the solution of the adduct dione (6 and 1-(4-aminophenylethanone (7 in the presence of Et 3N in toluene at 110 oC for 24 hours afforded 2-(4-acetylphenyl-3a,4,7,7a-tetrahydro-1H-4,7-ethanoisoindole-1,3-dione (8 in high yield. Piperidine-catalyzed addition of benzaldehyde derivatives (9a-i to the compound 8 in CH 2Cl 2 at 55 oC gave the expected chalcone derivatives (10-i in the range of 42% - 96% yields. The antibacterial activities of the chalcone derivatives (10a-i were evaluated against human pathogenic microorganism and the compounds showed low activity compared to the standard, name of the standard.

  4. Iodine-123 iodobenzofuran (I-123 IBF) SPECT in patients with parkinsonism

    Energy Technology Data Exchange (ETDEWEB)

    Nakabeppu, Yoshiaki; Nakajo, Masayuki; Mitsuda, Mitsuru; Tsuchimochi, Shinsaku; Tani, Atsushi; Osame, Mitsuhiro [Kagoshima Univ. (Japan). Faculty of Medicine

    1999-12-01

    Iodine-123 benzofuran (I-123 IBF) is a dopaminergic antagonist which is suitable for SPECT imaging of D2 receptors. The purpose of this study is to evaluate the potential usefulness of semi-quantitative parameters obtained from brain SPECT data of I-123 IBF for differential diagnosis in patients with parkinsonism (PN). Subjects were 10 patients with PN: 2 patients with striato-nigral degeneration (SND), 5 patients with Parkinson's disease (PD), 2 patients with progressive supranuclear palsy (PSP) and one patient with olivo-ponto-cerebellar atrophy (OPCA). The data were acquired with a triple-head gamma camera at 2 hours after intravenous injection of 167 MBq of I-123 IBF. Transverse images were reconstructed by means of filtered backprojection, and attenuation correction was performed by Chang's method ({mu}=0.08). The basal ganglia-to-frontal cortex ratio (GFR) and the basal ganglia-to-occipital cortex ratio (GOR) on slices of 5 different thicknesses were calculated. The GFR and GOR were lower in the SND group than in the other disease groups in all slices with different thicknesses (7.2 mm, 14.4 mm, 21.6 mm, 28.8 mm and 43.2 mm). The semiquantitative parameters (GFR and GOR) obtained from brain SPECT data at 2 hours after intravenous injection of I-123 IBF may be useful for differential diagnosis in patients with PN. (author)

  5. Insecticidal activities and active components of the alcohol extract from green peel of Juglans mandshurica

    Institute of Scientific and Technical Information of China (English)

    SUN Mo-long; WANG Yan-mei; SONG Zhan-qian; FANG Gui-zhen

    2007-01-01

    The extract of green peel of Juglans mandshurica Maxim was extracted by common method for studying its insecticidal activities and analyzing the active components. Results showed that the alcohol extract and the chloroform part of extract (separated with chloroform from alcohol extract) form green peel of J. mandshurica have insecticidal activities in contact toxicity and stomach toxicity against larvae of Lymantria dispar L.. After application of the extracts for five days, the corrected mortality of larvae of Lymantria dispar for both extracts was more than 50% in contact toxicity and stomach toxicity at the concentration of > 5 g·L1. The insecticidal activity for both alcohol extract and chloroform part of extract is more effect in contact toxicity than in stomach toxicity, but no significant difference in the insecticidal activities was found between alcohol extract and chloroform part of extract. The active components in the chloroform part of extract from green peel of J. mandshurica were analyzed by GC-MS. The analyzed results showed that the active components in the chloroform part of extract are: (1)juglone (5-hydroxy-1,4- naphthaoquinone), the relative content 27.11%, (2) 1,5-Naphthalenediol, the relative content 9.52%, (3) 7-Methoxy-l-tetralone, the relative content 6.81%, (4) Benzofuran, 2,3-dihydro-, the relative content 6.76%, (5)4-Hydroxy-2-methoxycinnamaldehyde, the relative content 3.99%, (6) 2-Methoxy-4-vinylphenol, the relative content 3.05%.

  6. Cryptogenic organizing pneumonia due to amiodarone: long-term follow-up after corticosteroid treatment.

    Science.gov (United States)

    Schindler, Katja; Schima, Wolfgang; Kaliman, Josef F

    2010-08-01

    Cryptogenic organizing pneumonia (formerly known as bronchiolitis obliterans organizing pneumonia) is a clinicopathological entity with characteristical radiographic findings such as bilateral, asymmetrical, sometimes migrating, patchy infiltrates in chest radiograph and ground-glass opacities in computed tomography. The disease has been observed in the context of gastrointestinal disorders, certain lung infections, autoimmune-mediated diseases (such as Wegener granulomatosis), inhalation of toxic fumes, bone marrow transplantation and administration of drugs. The benzofuran amiodarone, a commonly used antiarrythmic drug for atrial fibrillation, can exhibit several pulmonary adverse effects, amongst them cryptogenic organizing pneumonia as a rarely diagnosed and published one. We report a case of cryptogenic organizing pneumonia secondary to amiodarone treatment, its clinical course with significant improvement of clinical symptoms within a few days after discontinuation of amiodarone treatment and administration of corticosteroids. Also the infiltrations found in chest X-ray and computed tomography responded well and showed remarkable resolution tendency quickly. During 5 months of corticoid therapy pulmonary abnormalities gradually resolved almost completely and remained equal during the 8 months follow-up after corticoid termination. PMID:20668958

  7. Biomolecular Force Field Parameterization via Atoms-in-Molecule Electron Density Partitioning.

    Science.gov (United States)

    Cole, Daniel J; Vilseck, Jonah Z; Tirado-Rives, Julian; Payne, Mike C; Jorgensen, William L

    2016-05-10

    Molecular mechanics force fields, which are commonly used in biomolecular modeling and computer-aided drug design, typically treat nonbonded interactions using a limited library of empirical parameters that are developed for small molecules. This approach does not account for polarization in larger molecules or proteins, and the parametrization process is labor-intensive. Using linear-scaling density functional theory and atoms-in-molecule electron density partitioning, environment-specific charges and Lennard-Jones parameters are derived directly from quantum mechanical calculations for use in biomolecular modeling of organic and biomolecular systems. The proposed methods significantly reduce the number of empirical parameters needed to construct molecular mechanics force fields, naturally include polarization effects in charge and Lennard-Jones parameters, and scale well to systems comprised of thousands of atoms, including proteins. The feasibility and benefits of this approach are demonstrated by computing free energies of hydration, properties of pure liquids, and the relative binding free energies of indole and benzofuran to the L99A mutant of T4 lysozyme. PMID:27057643

  8. {beta} - amyloid imaging probes

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Jae Min [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2007-04-15

    Imaging distribution of {beta} - amyloid plaques in Alzheimer's disease is very important for early and accurate diagnosis. Early trial of the {beta} -amyloid plaques includes using radiolabeled peptides which can be only applied for peripheral {beta} - amyloid plaques due to limited penetration through the blood brain barrier (BBB). Congo red or Chrysamine G derivatives were labeled with Tc-99m for imaging {beta} - amyloid plaques of Alzheimer patient's brain without success due to problem with BBB penetration. Thioflavin T derivatives gave breakthrough for {beta} - amyloid imaging in vivo, and a benzothiazole derivative [C-11]6-OH-BTA-1 brought a great success. Many other benzothiazole, benzoxazole, benzofuran, imidazopyridine, and styrylbenzene derivatives have been labeled with F-18 and I-123 to improve the imaging quality. However, [C-11]6-OH-BTA-1 still remains as the best. However, short half-life of C-11 is a limitation of wide distribution of this agent. So, it is still required to develop an Tc-99m, F-18 or I-123 labeled agent for {beta} - amyloid imaging agent.

  9. Synthesis and Antimycobacterial and Photosynthesis-Inhibiting Evaluation of 2-[(E-2-Substituted-ethenyl]-1,3-benzoxazoles

    Directory of Open Access Journals (Sweden)

    Ales Imramovsky

    2014-01-01

    Full Text Available A series of twelve 2-[(E-2-substituted-ethenyl]-1,3-benzoxazoles was designed. All the synthesized compounds were tested against three mycobacterial strains. The compounds were also evaluated for their ability to inhibit photosynthetic electron transport (PET in spinach (Spinacia oleracea L. chloroplasts. 2-[(E-2-(4-Methoxyphenylethenyl]-1,3-benzoxazole, 2-[(E-2-(2,3-dihydro-1-benzofuran-5-ylethenyl]-1,3-benzoxazole and 2-{(E-2-[4-(methylsulfanylphenyl]ethenyl}-1,3-benzoxazole showed the highest activity against M. tuberculosis, M. kansasii, and M. avium, and they demonstrated significantly higher activity against M. avium and M. kansasii than isoniazid. The PET-inhibiting activity of the most active ortho-substituted compound 2-[(E-2-(2-methoxyphenylethenyl]-1,3-benzoxazole was IC50 = 76.3 μmol/L, while the PET-inhibiting activity of para-substituted compounds was significantly lower. The site of inhibitory action of tested compounds is situated on the donor side of photosystem II. The structure-activity relationships are discussed.

  10. Synthesis and Antimycobacterial and Photosynthesis-Inhibiting Evaluation of 2-[(E)-2-Substituted-ethenyl]-1,3-benzoxazoles

    Science.gov (United States)

    Imramovsky, Ales; Kozic, Jan; Stolarikova, Jirina; Vinsova, Jarmila

    2014-01-01

    A series of twelve 2-[(E)-2-substituted-ethenyl]-1,3-benzoxazoles was designed. All the synthesized compounds were tested against three mycobacterial strains. The compounds were also evaluated for their ability to inhibit photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. 2-[(E)-2-(4-Methoxyphenyl)ethenyl]-1,3-benzoxazole, 2-[(E)-2-(2,3-dihydro-1-benzofuran-5-yl)ethenyl]-1,3-benzoxazole and 2-{(E)-2-[4-(methylsulfanyl)phenyl]ethenyl}-1,3-benzoxazole showed the highest activity against M. tuberculosis, M. kansasii, and M. avium, and they demonstrated significantly higher activity against M. avium and M. kansasii than isoniazid. The PET-inhibiting activity of the most active ortho-substituted compound 2-[(E)-2-(2-methoxyphenyl)ethenyl]-1,3-benzoxazole was IC50 = 76.3 μmol/L, while the PET-inhibiting activity of para-substituted compounds was significantly lower. The site of inhibitory action of tested compounds is situated on the donor side of photosystem II. The structure-activity relationships are discussed. PMID:25197708

  11. Formation of Bound Residues of 14C-Carbofuran in Carrot Roots and Their Bioavailability to Rats

    International Nuclear Information System (INIS)

    Carrot roots were allowed to absorb radiolabelled carbofuran (2,3-dihydro-[ring-3-14C]2,2-dimethyl benzofuran-7-gamma l methyl carbamate) for 7 days. After Soxhlet extraction with methanol, the amounts of residues bound to plant tissues were determined. The data indicate the rate of binding increased with time reaching 7% of the applied dose (about 25% of the total amount taken up in one week. When rats were fed the extracted tissues, the bound residues were found to be considerably bioavailable. From the 14C-activity in the feed, 10.7% 14C-carbon dioxide and 29.03% urinary 14C-metabolites could be recovered. In feces, 30.16% of the given dose was methanol-extractable while 18.43% was determined as non-extractable. Various tissues including fat, liver, kidney, muscle, blood, heart, spleen and lungs contained 2.08%. Thin layer chromatographic analysis of rat urine indicated the presence of two main metabolites identified as carbofuran phenol and 3-hydroxy carbofuran

  12. Amiodarone Induced Morphological Changes in Rabbit Pneumocytes

    Directory of Open Access Journals (Sweden)

    Fereshteh Mehraein

    2009-01-01

    Full Text Available Objective: Amiodarone as an iodinated benzofuran derivative is a potent antiarrhythmicagent currently used for the treatment of ventricular arrhythmias. Pulmonary toxicityis one of the complications of Amiodarone therapy. The aim of this study was todetermine the toxicity of Amiodarone for pneumocytes.Materials and Methods: 14 male white New Zealand rabbits were divided in a controlgroup and an experimental group. The experimental group was subjected to intraperitoneal injection with a single daily dose of 80 mg/kg Amiodarone for two weeks.The control group received only normal saline. At the end of the injection period, thetwo groups were anesthetized and perfused with Karnovsky fixative. The lung tissuewas removed and fixed, then prepared for light and electron microscope studies.Morphometric studies were made on sections to find nucleus profile dimensions.Results: Light microscope observation showed acute changes in the alveolus includingcongestion of alveolar capillaries and infiltration of red blood cells (RBCs intothe lumen of the alveoli. Electron microscope study of lung tissue revealed abnormalinclusion bodies within type ΙΙ & Ι pneumocytes. The micrographs also showedthe presence of vacuoles in 5% of the type ΙΙ pneumocytes. Morphometric studiesshowed that the nucleus of the cells in the experimental group were smaller than inthe control group (p<0.01.Conclusion: These results indicate that Amiodarone administration can cause damageto pnuemocytes and the alveolus of rabbit lung, so the effectiveness of Amiodaronein long term treatment of heart failure patients is limited because of the developmentof lung toxicity.

  13. Biochemical characterization of an inhibitor of Escherichia coli UDP-N-acetylmuramyl-l-alanine ligase.

    Science.gov (United States)

    Ehmann, David E; Demeritt, Julie E; Hull, Kenneth G; Fisher, Stewart L

    2004-05-01

    UDP-N-acetylmuramyl-l-alanine ligase (MurC) is an essential bacterial enzyme involved in peptidoglycan biosynthesis and a target for the discovery of novel antibacterial agents. As a result of a high-throughput screen (HTS) against a chemical library for inhibitors of MurC, a series of benzofuran acyl-sulfonamides was identified as potential leads. One of these compounds, Compound A, inhibited Escherichia coli MurC with an IC(50) of 2.3 microM. Compound A exhibited time-dependent, partially reversible inhibition of E. coli MurC. Kinetic studies revealed a mode of inhibition consistent with the compound acting competitively with the MurC substrates ATP and UDP-N-acetyl-muramic acid (UNAM) with a K(i) of 4.5 microM against ATP and 6.3 microM against UNAM. Fluorescence binding experiments yielded a K(d) of 3.1 microM for the compound binding to MurC. Compound A also exhibited high-affinity binding to bovine serum albumin (BSA) as evidenced by a severe reduction in MurC inhibition upon addition of BSA. This finding is consistent with the high lipophilicity of the compound. Advancement of this compound series for further drug development will require reduction of albumin binding. PMID:15134649

  14. Darifenacin hydrobromide

    Directory of Open Access Journals (Sweden)

    S. Selvanayagam

    2009-06-01

    Full Text Available In the title compound {systematic name: (S-3-[(aminocarbonyldiphenylmethyl]-1-[2-(2,3-dihydrobenzofuran-5-ylethyl]pyrrolidinium bromide}, C28H31N2O2+·Br−, the pyrrolidine rings adopts an envelope conformation. The two phenyl rings make a dihedral angle of 72.5 (1°. The four coplanar atoms of the pyrrolidine ring makes dihedral angles of 33.1 (2 and 82.8 (2° with the two phenyl rings. The molecular conformation is influenced by a C—H...O interaction. In the crystal packing, there are two N—H...Br hydrogen bonds running in opposite directions. They appear to form C(10 and C(9 chain motifs in the unit cell. In addition, the molecular packing is further stabilized by C—H...Br and C—H...O hydrogen bonds. The C atom bonded to the benzofuran ring system is disordered in a 0.66:0.34 ratio.

  15. Exploiting the repertoire of CK2 inhibitors to target DYRK and PIM kinases.

    Science.gov (United States)

    Cozza, Giorgio; Sarno, Stefania; Ruzzene, Maria; Girardi, Cristina; Orzeszko, Andrzej; Kazimierczuk, Zygmunt; Zagotto, Giuseppe; Bonaiuto, Emanuela; Di Paolo, Maria Luisa; Pinna, Lorenzo A

    2013-07-01

    Advantage has been taken of the relative promiscuity of commonly used inhibitors of protein kinase CK2 to develop compounds that can be exploited for the selective inhibition of druggable kinases other than CK2 itself. Here we summarize data obtained by altering the scaffold of CK2 inhibitors to give rise to novel selective inhibitors of DYRK1A and to a powerful cell permeable dual inhibitor of PIM1 and CK2. In the former case one of the new compounds, C624 (naphto [1,2-b]benzofuran-5,9-diol) displays a potency comparable to that of the first-in-class DYRK1A inhibitor, harmine, lacking however the drawback of drastically inhibiting monoamine oxidase-A (MAO-A) as harmine does. On the other hand the promiscuous CK2 inhibitor 4,5,6,7-tetrabromo-1H-benzimidazole (TBI,TBBz) has been derivatized with a sugar moiety to generate a 1-(β-D-2'-deoxyribofuranosyl)-4,5,6,7-tetrabromo-1H-benzimidazole (TDB) compound which inhibits PIM1 and CK2 with comparably high efficacy (IC50 values<100nM) and remarkable selectivity. TDB, unlike other dual PIM1/CK2 inhibitors described in the literature is readily cell permeable and displays a cytotoxic effect on cancer cells consistent with concomitant inhibition of both its onco-kinase targets. This article is part of a Special Issue entitled: Inhibitors of Protein Kinases (2012). PMID:23360763

  16. Detection and chemical profiling of Ling-Gui-Zhu-Gan decoction by ultra performance liquid chromatography-hybrid linear ion trap-Orbitrap mass spectrometry.

    Science.gov (United States)

    Wang, Pei; Wang, Bo; Xu, Jingyao; Sun, Jianbo; Yan, Qin; Ji, Bin; Zhao, Yunli; Yu, Zhiguo

    2015-02-01

    Ling-Gui-Zhu-Gan decoction (LGZGD), a well-known traditional Chinese medicine (TCM) formula, has been extensively used for the treatment of cardiovascular disease in clinic. However, the chemical constituents in LGZGD had not been investigated so far. In this study, an ultra performance liquid chromatography-hybrid electrospray ionization linear ion trap-Orbitrap mass spectrometry (UPLC-LTQ-Oribitrap-MS/MS) method was established for rapid separation and structural identification of the constituents in LGZGD. Separation was performed on an ACQUITY(TM) UPLC BEH C18 column (50 × 2.1 mm, 1.7 μm) by gradient elution mode, using acetonitrile-water containing 0.1% formic acid as mobile phase at the flow rate of 0.2 mL/min. Accurate mass measurement for molecular ions and characteristic fragment ions could represent identification criteria for these compounds. As a result, 95 compounds including triterpene acids, triterpene saponins, flavonoids, coumarins, coumestans, benzofurans, phenylpropanoids and sesquiterpenoid lactones were detected, and 90 of them were tentatively identified. All compounds were further assigned in the individual raw material. In conclusion, the UPLC-LTQ-Orbitrap-MS/MS is a highly efficient technique to separate and identify constituents in complex matrices of TCMs. These results obtained in this research will provide a basis for quality control and further in vivo study of LGZGD. PMID:24920655

  17. Synthesis and Thermal Decomposition Mechanism of Rare Earth (RE=La, Y, Gd) Salicylates

    Institute of Scientific and Technical Information of China (English)

    LI, Liang-Chao(李良超); ZHOU, Xiang-Chun(周享春); ZHENG, Ren-Wei(郑人卫)

    2004-01-01

    The rare earth (RE=La, Y, Gd) salicylates were synthesized by the rheological phase reaction method. The complexes were characterized by elemental analysis, infrared spectra (IR), X-ray powder diffraction (XRD) and thermal gravity analysis (TG). They can be represented by general formula RE(HSal)3 (RE=La, Y, Gd; HSal=C6H4(OH)COO). The crystals of them are monoclinic and have layered structure. The mechanism of thermal decomposition of rare earth salicylates was studied by using TG, DTA, IR and gas chromatography-mass spectrometry (GC-MS). The thermal decomposition of the rare earth salicylates in nitrogen gas proceeded in three stages: firstly, they were decomposed to form RE2(Sal)3 (Sal=C6H4OCOO) and salicylic acid; then, RE2(Sal)3 were decomposed further to form RE2O(CO3)2 and some organic compounds; finally, RE2O(CO3)2 were decomposed to form rare earth metal oxides (RE2O3) and carbon dioxide. The organic compounds obtained from the second step of the reaction are mainly dibenzofuran, xanthenone, 6H-benzo[c]chromen-6-one, 6-phenyl-6H-benzo[c]chromene, and 1,3-diphenyl-1, 3-dihydro-2-benzofuran.

  18. Hierarchical self-assembly of switchable nucleolipid supramolecular gels based on environmentally-sensitive fluorescent nucleoside analogs

    Science.gov (United States)

    Nuthanakanti, Ashok; Srivatsan, Seergazhi G.

    2016-02-01

    Exquisite recognition and folding properties have rendered nucleic acids as useful supramolecular synthons for the construction of programmable architectures. Despite their proven applications in nanotechnology, scalability and fabrication of nucleic acid nanostructures still remain a challenge. Here, we describe a novel design strategy to construct new supramolecular nucleolipid synthons by using environmentally-sensitive fluorescent nucleoside analogs, based on 5-(benzofuran-2-yl)uracil and 5-(benzo[b]thiophen-2-yl)uracil cores, as the head group and fatty acids, attached to the ribose sugar, as the lipophilic group. These modified nucleoside-lipid hybrids formed organogels driven by hierarchical structures such as fibers, twisted ribbons, helical ribbons and nanotubes, which depended on the nature of fatty acid chain and nucleobase modification. NMR, single crystal X-ray and powder X-ray diffraction studies revealed the coordinated interplay of various non-covalent interactions invoked by modified nucleobase, sugar and fatty acid chains in setting up the pathway for the gelation process. Importantly, these nucleolipid gels retained or displayed aggregation-induced enhanced emission and their gelation behavior and photophysical properties could be reversibly switched by external stimuli such as temperature, ultrasound and chemicals. Furthermore, the switchable nature of nucleolipid gels to chemical stimuli enabled the selective two channel recognition of fluoride and Hg2+ ions through visual phase transition and fluorescence change. Fluorescent organogels exhibiting such a combination of useful features is rare, and hence, we expect that this innovative design of fluorescent nucleolipid supramolecular synthons could lead to the emergence of a new family of smart optical materials and probes.Exquisite recognition and folding properties have rendered nucleic acids as useful supramolecular synthons for the construction of programmable architectures. Despite their

  19. Identification of a Glycogen Synthase Kinase-3[beta] Inhibitor that Attenuates Hyperactivity in CLOCK Mutant Mice

    Energy Technology Data Exchange (ETDEWEB)

    Kozikowski, Alan P.; Gunosewoyo, Hendra; Guo, Songpo; Gaisina, Irina N.; Walter, Richard L.; Ketcherside, Ariel; McClung, Colleen A.; Mesecar, Andrew D.; Caldarone, Barbara (Psychogenics); (Purdue); (UIC); (UTSMC)

    2012-05-02

    Bipolar disorder is characterized by a cycle of mania and depression, which affects approximately 5 million people in the United States. Current treatment regimes include the so-called 'mood-stabilizing drugs', such as lithium and valproate that are relatively dated drugs with various known side effects. Glycogen synthase kinase-3{beta} (GSK-3{beta}) plays a central role in regulating circadian rhythms, and lithium is known to be a direct inhibitor of GSK-3{beta}. We designed a series of second generation benzofuran-3-yl-(indol-3-yl)maleimides containing a piperidine ring that possess IC{sub 50} values in the range of 4 to 680 nM against human GSK-3{beta}. One of these compounds exhibits reasonable kinase selectivity and promising preliminary absorption, distribution, metabolism, and excretion (ADME) data. The administration of this compound at doses of 10 to 25 mg kg{sup -1} resulted in the attenuation of hyperactivity in amphetamine/chlordiazepoxide-induced manic-like mice together with enhancement of prepulse inhibition, similar to the effects found for valproate (400 mg kg{sup -1}) and the antipsychotic haloperidol (1 mg kg{sup -1}). We also tested this compound in mice carrying a mutation in the central transcriptional activator of molecular rhythms, the CLOCK gene, and found that the same compound attenuates locomotor hyperactivity in response to novelty. This study further demonstrates the use of inhibitors of GSK-3{beta} in the treatment of manic episodes of bipolar/mood disorders, thus further validating GSK-3{beta} as a relevant therapeutic target in the identification of new therapies for bipolar patients.

  20. Determination of cathinones and other stimulant, psychedelic, and dissociative designer drugs in real hair samples.

    Science.gov (United States)

    Salomone, Alberto; Gazzilli, Giulia; Di Corcia, Daniele; Gerace, Enrico; Vincenti, Marco

    2016-03-01

    The detection of new psychoactive substances (NPS) in hair proved to provide insight into their current diffusion among the population and the social characteristics of these synthetic drugs' users. Therefore, a UHPLC-MS/MS method was developed in order to determine 31 stimulant and psychedelic substituted phenethylamines, and dissociative drugs in hair samples. The method proved to be simple, fast, specific, and sensitive. The absence of matrix interferents, together with excellent repeatability of both retention times and relative abundances of diagnostic transitions, allowed the correct identification of all analytes tested. The method showed optimal linearity in the interval 10-1000 pg/mg, with correlation coefficient values varying between 0.9981 and 0.9997. Quantitation limits ranged from 1.8 pg/mg for 4-methoxyphencyclidine (4-MeO-PCP) up to 35 pg/mg for 6-(2-aminopropyl)benzofuran (6-APB). The method was applied to (i) 23 real samples taken from proven MDMA and ketamine abusers and (ii) 54 real hair samples which had been previously tested negative during regular drug screening in driver's license recovery. Six samples tested positive for at least one target analyte. Methoxetamine (MXE) was found in three cases (range of concentration 7.7-27 pg/mg); mephedrone (4-MMC) was found in two cases (50-59 pg/mg) while one sample tested positive for methylone at 28 pg/mg. Other positive findings included 4-methylethcathinone (4-MEC), alpha-pyrrolidinovalerophenone (α-PVP), 4-fluoroamphetamine (4-FA), 3,4-methylenedioxypyrovalerone (MDPV), and diphenidine. The present study confirms the increasing diffusion of new designer drugs with enhanced stimulant activity among the target population of poly-abuse consumers. PMID:26680593

  1. Identification of Modulators of the Nuclear Receptor Peroxisome Proliferator-Activated Receptor α (PPARα in a Mouse Liver Gene Expression Compendium.

    Directory of Open Access Journals (Sweden)

    Keiyu Oshida

    Full Text Available The nuclear receptor family member peroxisome proliferator-activated receptor α (PPARα is activated by therapeutic hypolipidemic drugs and environmentally-relevant chemicals to regulate genes involved in lipid transport and catabolism. Chronic activation of PPARα in rodents increases liver cancer incidence, whereas suppression of PPARα activity leads to hepatocellular steatosis. Analytical approaches were developed to identify biosets (i.e., gene expression differences between two conditions in a genomic database in which PPARα activity was altered. A gene expression signature of 131 PPARα-dependent genes was built using microarray profiles from the livers of wild-type and PPARα-null mice after exposure to three structurally diverse PPARα activators (WY-14,643, fenofibrate and perfluorohexane sulfonate. A fold-change rank-based test (Running Fisher’s test (p-value ≤ 10-4 was used to evaluate the similarity between the PPARα signature and a test set of 48 and 31 biosets positive or negative, respectively for PPARα activation; the test resulted in a balanced accuracy of 98%. The signature was then used to identify factors that activate or suppress PPARα in an annotated mouse liver/primary hepatocyte gene expression compendium of ~1850 biosets. In addition to the expected activation of PPARα by fibrate drugs, di(2-ethylhexyl phthalate, and perfluorinated compounds, PPARα was activated by benzofuran, galactosamine, and TCDD and suppressed by hepatotoxins acetaminophen, lipopolysaccharide, silicon dioxide nanoparticles, and trovafloxacin. Additional factors that activate (fasting, caloric restriction or suppress (infections PPARα were also identified. This study 1 developed methods useful for future screening of environmental chemicals, 2 identified chemicals that activate or suppress PPARα, and 3 identified factors including diets and infections that modulate PPARα activity and would be hypothesized to affect chemical

  2. Potent inhibition of human neutrophil activations by bractelactone, a novel chalcone from Fissistigma bracteolatum

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Yang-Chang [Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 807, Taiwan (China); Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung 404, Taiwan (China); Sureshbabu, Munisamy; Fang, Yao-Ching; Wu, Yi-Hsiu [Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan (China); Lan, Yu-Hsuan [School of Pharmacy, China Medical University, Taichung 404, Taiwan (China); Chang, Fang-Rong [Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 807, Taiwan (China); Chang, Ya-Wen [Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan (China); Hwang, Tsong-Long, E-mail: htl@mail.cgu.edu.tw [Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan (China); Chinese Herbal Medicine Research Team, Healthy Aging Research Center, Chang Gung University, Kweishan, Taoyuan 333, Taiwan (China)

    2013-02-01

    Fissistigma bracteolatum is widely used in traditional medicine to treat inflammatory diseases. However, its active components and mechanisms of action remain unclear. In this study, (3Z)-6,7-dihydroxy-4-methoxy-3-(phenylmethylidene)-5-(3-phenylpropanoyl) -1-benzofuran-2(3H) (bractelactone), a novel chalcone from F. bracteolatum, showed potent inhibitory effects against superoxide anion (O{sub 2}{sup ·−}) production, elastase release, and CD11b expression in formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP)-induced human neutrophils. However, bractelactone showed only weak inhibition of phorbol myristate acetate-caused O{sub 2}{sup ·−} production. The peak cytosolic calcium concentration ([Ca{sup 2+}]{sub i}) was unaltered by bractelactone in FMLP-induced neutrophils, but the decay time of [Ca{sup 2+}]{sub i} was significantly shortened. In a calcium-free solution, changes in [Ca{sup 2+}]{sub i} caused by the addition of extracellular Ca{sup 2+} were inhibited by bractelactone in FMLP-activated cells. In addition, bractelactone did not alter the phosphorylation of p38 MAPK, ERK, JNK, or AKT or the concentration of cAMP. These results suggest that bractelactone selectively inhibits store-operated calcium entry (SOCE). In agreement with this concept, bractelactone suppressed sustained [Ca{sup 2+}]{sub i} changes in thapsigargin-activated neutrophils. Furthermore, bractelactone did not alter FMLP-induced formation of inositol 1,4,5-triphosphate. Taken together, our results demonstrate that the anti-inflammatory effects of bractelactone, an active ingredient of F. bracteolatum, in human neutrophils are through the selective inhibition of SOCE. Highlights: ► Bractelactone isolated from Fissistigma bracteolatum. ► Bractelactone inhibited FMLP-induced human neutrophil activations. ► Bractelactone had no effect on IP3 formation. ► Bractelactone did not alter MAPKs, AKT, and cAMP pathways. ► Bractelactone inhibited store-operated calcium entry.

  3. In Situ and ex Situ Catalytic Pyrolysis of Pine in a Bench-Scale Fluidized Bed Reactor System

    Energy Technology Data Exchange (ETDEWEB)

    Iisa, Kristiina; French, Richard J.; Orton, Kellene A.; Yung, Matthew M.; Johnson, David K.; ten Dam, Jeroen; Watson, Michael J.; Nimlos, Mark R.

    2016-03-17

    In situ and ex situ catalytic pyrolysis were compared in a system with two 2-in. bubbling fluidized bed reactors. Pine was pyrolyzed in the system with a catalyst, HZSM-5 with a silica-to-alumina ratio of 30, placed either in the first (pyrolysis) reactor or the second (upgrading) reactor. Both the pyrolysis and upgrading temperatures were 500 degrees C, and the weight hourly space velocity was 1.1 h-1. Five catalytic cycles were completed in each experiment. The catalytic cycles were continued until oxygenates in the vapors became dominant. The catalyst was then oxidized, after which a new catalytic cycle was begun. The in situ configuration gave slightly higher oil yield but also higher oxygen content than the ex situ configuration, which indicates that the catalyst deactivated faster in the in situ configuration than the ex situ configuration. Analysis of the spent catalysts confirmed higher accumulation of metals in the in situ experiment. In all experiments, the organic oil mass yields varied between 14 and 17% and the carbon efficiencies between 20 and 25%. The organic oxygen concentrations in the oils were 16-18%, which represented a 45% reduction compared to corresponding noncatalytic pyrolysis oils prepared in the same fluidized bed reactor system. GC/MS analysis showed the oils to contain one- to four-ring aromatic hydrocarbons and a variety of oxygenates (phenols, furans, benzofurans, methoxyphenols, naphthalenols, indenols). High fractions of oxygen were rejected as water, CO, and CO2, which indicates the importance of dehydration, decarbonylation, and decarboxylation reactions. Light gases were the major sources of carbon losses, followed by char and coke.

  4. New acyclic bis phenylpropanoid and neolignans, from Myristica fragrans Houtt., exhibiting PARP-1 and NF-κB inhibitory effects.

    Science.gov (United States)

    Muñoz Acuña, Ulyana; Carcache, Peter J Blanco; Matthew, Susan; Carcache de Blanco, Esperanza J

    2016-07-01

    The bioassay-guided fractionation of the aril of Myristica fragrans (mace spice) yielded five phenolic compounds, one new acyclic bis phenylpropanoid (1) and four previously known phenolic compounds: compounds (1) (S) 1-(3,4,5-trimethoxyphenyl)-2-(3-methoxy-5-(prop-1-yl) phenyl)-propan-1-ol, (2) benzenemethanol; α-[1-[2,6-dimethoxy-4-(2-propen-1-yl)phenoxy]ethyl]-3,4-dimethoxy-1-acetate, (3) odoratisol A, phenol, 4-[(2S,3S)-2,3-dihydro-7-methoxy-3-methyl-5-(1E)-1-propenyl-2-benzofuranyl]-2,6-dimethoxy, (4) 1,3-benzodioxate-5-methanol,α-[1-[2,6-dimethoxy-4-(2-propenyl)phenoxy]ethyl]-acetate, (5) licarin C; benzofuran,2,3-dihydro-7-methoxy-3-methyl-5-(1E)-1-yl-2-(3,4,5-trimethoxyphenyl). An NMR tube Mosher ester reaction was used in an approach to characterize and determine the assignment of the absolute configuration of the new isolated chiral alcohol (1). The PARP-1 inhibitory activity was evaluated for compound (1) (IC50=3.04μM), compound (2) (IC50=0.001μM), compound (4) (IC50=22.07μM) and compound (5) (IC50=3.11μM). Furthermore, the isolated secondary metabolites were tested for NF-κB and K-Ras inhibitory activities. When tested in the p65 assay, compounds (2) and (4) displayed potent NF-κB inhibition (IC50=1.5 nM and 3.4nM, respectively). PMID:26920294

  5. Dronedarone: an emerging therapy for atrial fibrillation.

    Science.gov (United States)

    Rosei, Enrico Agabiti; Salvetti, Massimo

    2010-06-01

    Atrial fibrillation (AF) is a common arrhythmia, with a prevalence ranging from 0.1% to 9.0% at different ages, and is associated with increased cardiovascular events and mortality. A significant increase in the prevalence of the disease is expected to occur in the coming years as a consequence of the aging of the population and advances in the management of coronary artery disease and heart failure. Effective rhythm control may be difficult to obtain in a significant proportion of patients with AF. The limited efficacy and the possible adverse effects of antiarrhythmic drugs has led researchers to focus their attention on new molecules, in a search of compounds with antiarrhythmic efficacy and a more favourable safety profile. Among several new drugs developed for the management of AF, dronedarone, a benzofuran derivative that shares many of the antiarrhythmic properties of amiodarone, but with a more favourable safety profile, seems particularly promising. The drug is noniodinated, has less lipophilicity, reaches therapeutic concentrations over a shorter period of time and has lower tissue accumulation. Dronedarone, similarly to amiodarone, exhibits electrophysiologic characteristics of all 4 Vaughan Williams classes. Clinical studies have shown that dronedarone effectively reduces ventricular rate, may prevent or delay the recurrence of AF, and may reduce cardiovascular morbidity and mortality in patients with AF or atrial flutter. The drug has an overall good safety profile, in particular with low pulmonary and thyroid toxicity. An important exception is represented by patients with unstable haemodynamic conditions, in which the use of dronedarone has been found to be associated with an increase in mortality. Dronedarone has been recently approved for clinical use by the Food and Drug Administration and by the European Medicines Agency. Further results from trials and clinical use will better define the efficacy and safety profile of dronedarone in AF compared

  6. Bioavailability and influence of ¹⁴C-carbofuran on Eisenia andrei avoidance, growth and reproduction in treated natural tropical soils.

    Science.gov (United States)

    Ferreira, Regina C B; Papini, Solange; de Andréa, Mara M

    2015-01-01

    The bioavailability of carbofuran to the compost worms Eisenia andrei and the influence of its residual amounts on the avoidance, reproduction and growth of this species were studied in two natural tropical soils: a Typic Humaquept (GM) and a Typic Hapludox (LVD), as indicated by the Brazilian environmental authorities for ecotoxicological tests. The worms avoided the soil LVD treated with different doses of carbofuran. The pesticide also affected the production of juvenile specimens in both soils, but cocoon production was reduced only in the GM soil. The earthworms' growth and weight loss were affected by carbofuran (2,2-dimethyl-2,3-dihydro-1-1-benzofuran-7-yl methylcarbamate. CAS number 1563-66-2) only in the LVD and the mortality detected at 56 days of contact with the treated soils was not statistically significant in both of them. Fourteen days after the soil treatment with(14) c-carbofuran, most residues detected in the soils were bound residues (approximately 36% and 30% in the GM and LVD, respectively) and neither mortality nor bioaccumulation was detected in the earthworms, even with absorptions of 13% and 43%, respectively. The LVD soil has lower organic matter content, and the effects of carbofuran on different aspects of the earthworms' life were more pronounced in this soil, most likely due to the higher bioavailability of the pesticide in the soil solution. The results for carbofuran clearly demonstrate that even small quantities of residues do not assure lack of toxicity. They also make evident the necessity of studying the effects of pesticides in natural agricultural soils. Furthermore, as the bound residues and the earthworm contamination are not detected by conventional techniques, they are not taken into account and may be underestimated on environmental risk assessments. PMID:25714458

  7. Degradation of carbofuran derivatives in restricted water environments: basic hydrolysis in AOT-based microemulsions.

    Science.gov (United States)

    Morales, Jorge; Manso, José A; Cid, Antonio; Lodeiro, Carlos; Mejuto, Juan Carlos

    2012-04-15

    The effect of sodium bis(2-ethylhexyl)sulfosuccinate/isooctane/water microemulsions on the stability of 2,2-dimethyl-2,3-dihydro-1-benzofuran-7-yl methylcarbamate (carbofuran, CF), 3-hydroxy-2,3-dihydro-2,2-dimethylbenzofuran-7-yl methylcarbamate (3-hydroxycarbofuran, HCF) and 3-keto-2,3-dihydro-2,2-dimethylbenzofuran-7-yl methylcarbamate (3-ketocarbofuran, KCF) in basic media has been studied. The presence of these microheterogeneous media implies a large basic hydrolysis of CF and HCF on increasing surfactant concentration and, also, on increasing water content in the microemulsion. The hydrolysis rate constants are approximately 2- and 10-fold higher than those in pure water for HCF and CF, respectively. In contrast, a steep descent in the rate of decomposition for KCF was observed. These behaviours can be ascribed to the presence of CF derivatives both in the hydrophilic phase and in the lipophilic phase, while the hydroxyl ions are only restricted to the water pool of the microemulsion (hydrophilic phase). The kinetic rate constants for the basic hydrolysis in AOT-based microemulsions have been obtained on the basis of a pseudophase model. Taking into account that an important part of soils are colloids, the possibility of the presence of restricted water environments implies that soil composition and its structure will play an important role in the stability of these carbamates. In fact, we observed that the presence of these restricted aqueous media in the environment, in particular in watersheds and in wastewaters, could reduce significantly the half-life of these pesticides (33% and 91% for HCF and CF, respectively).

  8. Bioavailability and influence of ¹⁴C-carbofuran on Eisenia andrei avoidance, growth and reproduction in treated natural tropical soils.

    Science.gov (United States)

    Ferreira, Regina C B; Papini, Solange; de Andréa, Mara M

    2015-01-01

    The bioavailability of carbofuran to the compost worms Eisenia andrei and the influence of its residual amounts on the avoidance, reproduction and growth of this species were studied in two natural tropical soils: a Typic Humaquept (GM) and a Typic Hapludox (LVD), as indicated by the Brazilian environmental authorities for ecotoxicological tests. The worms avoided the soil LVD treated with different doses of carbofuran. The pesticide also affected the production of juvenile specimens in both soils, but cocoon production was reduced only in the GM soil. The earthworms' growth and weight loss were affected by carbofuran (2,2-dimethyl-2,3-dihydro-1-1-benzofuran-7-yl methylcarbamate. CAS number 1563-66-2) only in the LVD and the mortality detected at 56 days of contact with the treated soils was not statistically significant in both of them. Fourteen days after the soil treatment with(14) c-carbofuran, most residues detected in the soils were bound residues (approximately 36% and 30% in the GM and LVD, respectively) and neither mortality nor bioaccumulation was detected in the earthworms, even with absorptions of 13% and 43%, respectively. The LVD soil has lower organic matter content, and the effects of carbofuran on different aspects of the earthworms' life were more pronounced in this soil, most likely due to the higher bioavailability of the pesticide in the soil solution. The results for carbofuran clearly demonstrate that even small quantities of residues do not assure lack of toxicity. They also make evident the necessity of studying the effects of pesticides in natural agricultural soils. Furthermore, as the bound residues and the earthworm contamination are not detected by conventional techniques, they are not taken into account and may be underestimated on environmental risk assessments.

  9. PBCDD/F formation from radical/radical cross-condensation of 2-Chlorophenoxy with 2-Bromophenoxy, 2,4-Dichlorophenoxy with 2,4-Dibromophenoxy, and 2,4,6-Trichlorophenoxy with 2,4,6-Tribromophenoxy

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Xiangli [Environment Research Institute, Shandong University, Jinan 250100 (China); Yu, Wanni [Environment Research Institute, Shandong University, Jinan 250100 (China); College of Resources and Environment, Linyi University, Linyi 276000 (China); Xu, Fei [Environment Research Institute, Shandong University, Jinan 250100 (China); Zhang, Qingzhu, E-mail: zqz@sdu.edu.cn [Environment Research Institute, Shandong University, Jinan 250100 (China); Hu, Jingtian; Wang, Wenxing [Environment Research Institute, Shandong University, Jinan 250100 (China)

    2015-09-15

    Highlights: • We studied the formation of PBCDD/Fs from the reaction of three CPRs with BPRs. • The substitution pattern of halogenated phenols determines those of PBCDD/Fs. • The substitution of halogenated phenols influence the coupling of phenoxy radicals. • The rate constants of the crucial elementary steps were evaluated. - Abstract: Quantum chemical calculations were carried out to investigate the homogeneous gas-phase formation of mixed polybrominated/chlorinated dibenzo-p-dioxins/benzofurans (PBCDD/Fs) from the cross-condensation of 2-chlorophenoxy radical (2-CPR) with 2-bromophenoxy radical (2-BPR), 2,4-dichlorophenoxy radical (2,4-DCPR) with 2,4-dibromophenoxy radical (2,4-DBPR), and 2,4,6-trichlorophenoxy radical (2,4,6-TCPR) with 2,4,6-tribromophenoxy radical (2,4,6-TBPR). The geometrical parameters and vibrational frequencies were calculated at the MPWB1K/6-31+G(d,p) level, and single-point energy calculations were performed at the MPWB1K/6-311+G(3df,2p) level of theory. The rate constants of the crucial elementary reactions were evaluated by the canonical variational transition-state (CVT) theory with the small curvature tunneling (SCT) correction over a wide temperature range of 600–1200 K. Studies show that the substitution pattern of halogenated phenols not only determines the substitution pattern of the resulting PBCDD/Fs, but also has a significant influence on the formation mechanism of PBCDD/Fs, especially on the coupling of the halogenated phenoxy radicals.

  10. Activity-guided isolation and identification of anti-staphylococcal components from Senecio tenuifolius Burm. F. leaf extracts

    Institute of Scientific and Technical Information of China (English)

    Manjunath Manubolu; Lavanya Goodla; Sivajyothi Ravilla; Vijayasarathi Reddy Obulum

    2013-01-01

    Objective: To investigate activity-guided isolation and identification of anti-Staphylococcus aures components from Senecio tenuifolius Burm. F. (S. tenuifolius). Methods: Hexane, chloroform, ethyl acetate, methanol and aqueous extracts of S. tenuifolius were prepared by soxilation for antimicrobial activity against one registered Staphylococcus aureus (S. aureus) (ATCC No: 25923) and two clinical isolates, methicillin resistant and methicillin sensitive S. aureus. NCCL standard methods were followed for antibacterial activity. GC-MS was performed to identify the chemical composition of bio active fraction. Results:Among all solvent extracts, methanol extract significantly reduced the growth of S. aureus (ATCC No: 25923), methicillin resistant and methicillin sensitive S. aureus with the best zone of inhibition at 16.23, 14.06 and 15.23 mm and minimum inhibition concentration (MIC) values at 426.16, 683.22 and 512.12 µg/mL, respectively. In order to detect the active component in methanol extract, it was further purified by column chromatography, which yielded four fractions (St1, St2, St3, and St4). Among these four fractions, St3 was effective against the tested strains of S. aures, with the best zone of inhibition at 15.09, 13.25 and 14.12 mm and with best MIC values at 88.16, 128.11 and 116.12 µg/mL, respectively. Effective fraction partially purified from S. tenuifolius (St3) yielded MIC’s that were at least 20 fold less when compared to crude extract. GC-MS analysis of St3 revealed the presence of 3-[methyl-6,7-dihydro benzofuran-4 (5H)-one], 1,2-benzenedicarboxylic acid, hydroquinone, methyl ester and 3 unknown compounds. Conclusions:The study provides scientific evidence for traditional and folklore medicinal use of S. tenuifolius in skin infections treatment.

  11. The prevalence of new psychoactive substances in biological material - a three-year review of casework in Poland.

    Science.gov (United States)

    Adamowicz, Piotr; Gieroń, Joanna; Gil, Dominika; Lechowicz, Wojciech; Skulska, Agnieszka; Tokarczyk, Bogdan

    2016-01-01

    New psychoactive substances (NPS) pose a challenge for forensic and clinical toxicologists, as well as for legislators. We present our findings from cases where NPS have been detected in biological material. During the three-year period 2012-2014 we found NPS in 112 cases (out of 1058 analyzed), with 75 cases in 2014 alone. The prevalence of all NPS (15.1-17.6%) was similar to amphetamine alone that was detected in 15.1-16.5% of cases. The new drugs found belonged to the following classes: cathinones (88%), synthetic cannabinoids (5%), phenethylamines (3%), piperazines and piperidines (3%), arylalkylamines (1%) and other (1%). The drugs detected were (in the order of decreased frequency): 3-MMC (50), α-pyrrolidinopentiophenone (α-PVP) (23), pentedrone (16), 3',4'-methylenedioxy-α-pyrrolidinobutyrophenone (MDPBP) (12), synthetic cannabinoid UR-144 (7), ethcathinone (5), mephedrone (5), methylenedioxypyrovalerone (MDPV) (4), 4-methylethcathinone (4-MEC) (3), buphedrone (3), desoxypipradrol (2-DPMP) (3), methylone (2) and 2C-B (2). In single cases, 2-methylmethcathinone (2-MMC), 2C-P, eutylone, 25I-NBOMe, meta-chlorophenylpiperazine (mCPP), ephedrone, methiopropamine (MPA), and 5-(2-aminopropyl)benzofuran (5-APB) were found. One NPS was the sole agent in 35% of all cases, and two or more NPS were present in 19% of cases. NPS (one or more) with other conventional drugs (like amphetamines, cannabinoids, cocaine, and benzodiazepines) were detected in most (65%) of the cases. NPS were very often detected in the blood of drivers which was a challenge for toxicologists due to a lack of data on their influence on psychomotor performance. A review of concentrations showed a wide range of values in different types of cases, especially driving under the influence of drugs (DUID) and intoxication.

  12. Genotoxicity of heterocyclic PAHs in the micronucleus assay with the fish liver cell line RTL-W1.

    Directory of Open Access Journals (Sweden)

    Markus Brinkmann

    Full Text Available Heterocyclic aromatic hydrocarbons are, together with their un-substituted analogues, widely distributed throughout all environmental compartments. While fate and effects of homocyclic PAHs are well-understood, there are still data gaps concerning the ecotoxicology of heterocyclic PAHs: Only few publications are available investigating these substances using in vitro bioassays. Here, we present a study focusing on the identification and quantification of clastogenic and aneugenic effects in the micronucleus assay with the fish liver cell line RTL-W1 that was originally derived from rainbow trout (Oncorhynchus mykiss. Real concentrations of the test items after incubation without cells were determined to assess chemical losses due to, e.g., sorption or volatilization, by means of gas chromatography-mass spectrometry. We were able to show genotoxic effects for six compounds that have not been reported in vertebrate systems before. Out of the tested substances, 2,3-dimethylbenzofuran, benzothiophene, quinoline and 6-methylquinoline did not cause substantial induction of micronuclei in the cell line. Acridine caused the highest absolute induction. Carbazole, acridine and dibenzothiophene were the most potent substances compared with 4-nitroquinoline oxide, a well characterized genotoxicant with high potency used as standard. Dibenzofuran was positive in our investigation and tested negative before in a mammalian system. Chemical losses during incubation ranged from 29.3% (acridine to 91.7% (benzofuran and may be a confounding factor in studies without chemical analyses, leading to an underestimation of the real potency. The relative potency of the investigated substances was high compared with their un-substituted PAH analogues, only the latter being typically monitored as priority or indicator pollutants. Hetero-PAHs are widely distributed in the environment and even more mobile, e.g. in ground water, than homocyclic PAHs due to the higher water

  13. Photophysical properties of heteroaromatic ring-fused (di)benzosiloles

    Institute of Scientific and Technical Information of China (English)

    SHIMIZU Masaki; MOCHIDA Kenji; KATOH Masaki; HIYAMA Tamejiro

    2012-01-01

    Benzosiloles fused to heterocycles such as thiophene,benzothiophene,and benzofuran,and indole- and benzosilole-fused dibenzosiloles were prepared by palladium-catalyzed intramolecular coupling of the corresponding 2-(arylsilyl)aryl triflates in good to high yields.Molecular and crystal structures of 5,7-dihydro-5,5,7,7-tetrakis(1- methylethyl)bis[1]benzosilolo-[2,3-b:3',2'-d]thiophene,6-methyl- 12,12-diisopropyl- 12H-indololo[3,2-b][ 1 ]silafluorene,and 5,5,11,11-tetraisopropyl-5,11H-benzosi lolo[3,2-c]silafluorene were determined by X-ray diffraction analysis.The UV absorption spectra of the (di)benzosilole derivatives in cyclohexane red-shifted when compared to 1,1-diisopropyldibenzosilole,indicating that replacing a benzene ring of dibenzosilole by the heterocycles as well as fusion of indole and benzosilole moieties onto dibenzosilole narrowed the HOMO-LUMO gaps of the π-conjugation system.The thiophene-fused benzosiloles were faintly fluorescent in solution and in the solid state,whereas the dibenzosiloles exhibited luminescence with moderate and high quantum yields in cyclohexane and in microcrystals,respectively.In other words,aggregation-induced emission was observed for the dibenzosiloles.Notably,5,5,11,11- tetraisopropyl-5,11 H-benzosilolo[3,2-c]silafluorene in microcrystals exhibited violet fluorescence (λmax =396 nm) with a quantum yield of 0.70.Density functional theory (DFT) calculations of the prepared (di)benzosiloles were also performed.

  14. Polycyclic aromatic hydrocarbon concentrations in gas and particle phases and source determination in atmospheric samples from a semiurban area of Dourados, Brazil.

    Science.gov (United States)

    Ré, Nilva; Kataoka, Vanessa Mayumi Fukuy; Cardoso, Claudia Andrea Lima; Alcantara, Glaucia Braz; de Souza, João Batista Gomes

    2015-07-01

    A headspace solid-phase microextraction (HS-SPME) procedure that employs a PDMS/DVB fiber was developed for the analysis of gas-phase polycyclic aromatic hydrocarbons (PAHs) collected in polyurethane foam (PUF) by gas chromatography (GC) mass spectrometry. The method exhibited good linearity (R (2) > 0.99) and repeatability (4.9-25 %) as well as an impressive detection limit that ranged from 1.1 to 3.3 ng. Twenty-two air samples were collected by high-volume samplers from January to November 2007 in a semiurban area of Dourados (Brazil) and were analyzed for their content of total suspended particulates and PAHs. The PAHs were extracted from the PUF samples using the developed procedure (HS-SPME), and PAHs adsorbed on particulate matter were extracted with dichloromethane/methanol (4:1 [v/v]) in an ultrasonic bath. The values of the total daily concentrations of 16 PAHs determined in the samples ranged from 0.375 to 8.407 ng m(-3). In addition, diagnostic ratios were calculated, showing that the PAHs in the atmosphere at the sampling site originated predominantly from vehicle emissions and the combustion of grass and wood. Hierarchical cluster analysis and principal component analysis were performed as well, the results of which indicated (1) the same sources of PAH identified by the diagnostic ratios and (2) that the sampling days could be categorized into three groups depending on the atmospheric conditions. GC retention indices were also used to identify PAHs, biphenyl (phenylbenzene), and heterocyclic organic compounds (benzofurans) in some of the samples. PMID:25851064

  15. Infrared and Raman spectra of bicyclic molecules using scaled noncorrelated and correlated {ital ab initio} force fields

    Energy Technology Data Exchange (ETDEWEB)

    Collier, W.B. [Department of Chemistry, Oral Roberts University, Tulsa, Oklahoma 74171 (United States); Magdo, I. [Gedeon Richter Ltd., Molecular Design Unit, P.O. Box 27, H-1475, Budapest (Hungary); Klots, T.D. [Bartlesville Thermodynamic Group, BDM Petroleum Technologies, P.O. Box 2543, Bartlesville, Oklahoma 74005 (United States)

    1999-03-01

    This paper reports the application of a scaled {ital ab initio} calculated harmonic force field to predict the frequencies, infrared intensities, Raman intensities, and depolarization ratios of benzofuran, benzothiophene, indole, benzothiazole, and benzoxazole. The theoretical calculations were made using the Hartree{endash}Fock HF/3-21G{sup {asterisk}} and HF/6-31G{sup {asterisk}} basis sets and density-functional theory (DFT)B3-LYP/6-31G{sup {asterisk}} levels. The equilibrium calculated force constants are scaled according to the method of Pulay and compared with the experimentally determined frequencies, intensities, and depolarization ratios to assess the accuracy and fit of the theoretical calculation. Methods for quantitative comparison of intensities were developed. The double numerical differentiation algorithm of Komornicki and McIver was analyzed and used to calculate the Raman intensities for the (DFT)B3-LYP/6-31G{sup {asterisk}} model. The (DFT)B3-LYP/6-31G{sup {asterisk}} model is approaching the harmonic limit in the planar and nonplanar refinement of these bicyclics with wave number fits of 5 and 4 cm{sup {minus}1}, respectively. It reduces the need for scale factors and increases their transfer accuracy, largely because the scale factors values cluster near unity. The Komornicki and McIver algorithm is still a viable method for calculating Raman intensity information for methods that do not have analytic routines programmed. The main shortcoming to this method may lie in the tighter self-consistent field (SCF) convergence criterion possibly needed to calculate Raman intensities for the totally symmetric modes of large molecules. The (DFT)B3-LYP/6-31G{sup {asterisk}} model was superior for calculating the planar intensities, but equal to the HF methods for predicting the nonplanar intensities. {copyright} {ital 1999 American Institute of Physics.}

  16. C-H and N-H bond dissociation energies of small aromatic hydrocarbons

    Energy Technology Data Exchange (ETDEWEB)

    Barckholtz, C.; Barckholtz, T.A.; Hadad, C.M.

    1999-01-27

    A survey of computational methods was undertaken to calculate the homolytic bond dissociation energies (BDEs) of the C-H and N-H bonds in monocyclic aromatic molecules that are representative of the functionalities present in coal. These include six-membered rings (benzene, pyridine, pyridazine, pyrimidine, pyrazine) and five-membered rings (furan, thiophene, pyrrole, oxazole). By comparison of the calculated C-H BDEs with the available experimental values for these aromatic molecules, the B3LYP/6-31G(d) level of theory was selected to calculate the BDEs of polycyclic aromatic hydrocarbons (PAHs), including carbonaceous PAHs (naphthalene, anthracene, pyrene, coronene) and heteroatomic PAHs (benzofuran, benzothiophene, indole, benzoxazole, quinoline, isoquinoline, dibenzofuran, carbazole). The cleavage of a C-H or a N-H bond generates a {sigma} radical that is, in general, localized at the site from which the hydrogen atom was removed. However, delocalization of the unpaired electron results in {approximately} 7 kcal {center{underscore}dot} mol{sup {minus}1} stabilization of the radical with respect to the formation of phenyl when the C-H bond is adjacent to a nitrogen atom in the azabenzenes. Radicals from five-membered rings are {approximately} 6 kcal {center{underscore}dot} mol{sup {minus}1} less stable than those formed from six-membered rings due to both localization of the spin density and geometric factors. The location of the heteroatoms in the aromatic ring affects the C-H bond strengths more significantly than does the size of the aromatic network. Therefore, in general, the monocyclic aromatic molecules can be used to predict the C-H BDE of the large PAHs within 1 kcal {center{underscore}dot} mol{sup {minus}1}.

  17. Discovery and Evaluation of Thiazinoquinones as Anti-Protozoal Agents

    Directory of Open Access Journals (Sweden)

    Marcel Kaiser

    2013-09-01

    Full Text Available Pure compound screening has identified the dioxothiazino-quinoline-quinone ascidian metabolite ascidiathiazone A (2 to be a moderate growth inhibitor of Trypanosoma brucei rhodesiense (IC50 3.1 μM and Plasmodium falciparum (K1 dual drug resistant strain (IC50 3.3 μM while exhibiting low levels of cytotoxicity (L6, IC50 167 μM. A series of C-7 amide and Δ2(3 analogues were prepared that explored the influence of lipophilicity and oxidation state on observed anti-protozoal activity and selectivity. Little variation in anti-malarial potency was observed (IC50 0.62–6.5 μM, and no correlation was apparent between anti-malarial and anti-T. brucei activity. Phenethylamide 7e and Δ2(3-glycine analogue 8k exhibited similar anti-Pf activity to 2 but with slightly enhanced selectivity (SI 72 and 93, respectively, while Δ2(3-phenethylamide 8e (IC50 0.67 μM, SI 78 exhibited improved potency and selectivity towards T. brucei rhodesiense compared to the natural product hit. A second series of analogues were prepared that replaced the quinoline ring of 2 with benzofuran or benzothiophene moieties. While esters 10a/10b and 15 were once again found to exhibit cytotoxicity, carboxylic acid analogues exhibited potent anti-Pf activity (IC50 0.34–0.035 μM combined with excellent selectivity (SI 560–4000. In vivo evaluation of a furan carboxylic acid analogue against P. berghei was undertaken, demonstrating 85.7% and 47% reductions in parasitaemia with ip or oral dosing respectively.

  18. Analyzing a potential drug target N-myristoyltransferase of Plasmodium falciparum through in silico approaches

    Directory of Open Access Journals (Sweden)

    Amit Kumar Banerjee

    2012-01-01

    Full Text Available Background: Despite concerted global efforts to combat malaria, malaria elimination is still a remote dream. Fast evolution rate of malarial parasite along with its ability to respond quickly to any drug resulting in partial or complete resistance has been a cause of concern among researcher communities. Materials and Methods: Molecular modeling approach was adopted to gain insight about the structure and various analyses were performed. Modeller 9v3, Protparam, Protscale, MEME, NAMD and other tools were employed for this study. PROCHECK and other tools were used for stereo-chemical quality evaluation. Results and Conclusion: It was observed during the course of study that this protein contains 32.2% of aliphatic amino acids among which Leucine (9.5% is predominant. Theoretical pI of 8.39 identified the protein as basic in nature and most of the amino acids present in N-Myristoyltransferase are hydrophobic (46.1%. Secondary structure analysis shows predominance of alpha helices and random coils. Motif analyses revealed that this target protein contains 2 signature motifs, i.e., EVNFLCVHK and KFGEGDG. Apart from motif search, three-dimensional model was generated and validated and the stereo-chemical quality check confirmed that 97.7% amino acid residues fall in the core region of Ramachandran plot. Molecular dynamics simulation resulted in maximum 1.3 Å Root Mean Square Deviation (RMSD between the initial structure and the trajectories obtained later on. The template and the target molecule has shown 1.5 Å RMSD for the C alpha trace. A docking study was also conducted with various ligand molecules among which specific benzofuran compounds turned out to be effective. This derived information will help in designing new inhibitor molecules for this target protein as well in better understanding the parasite protein.

  19. 地胆草的化学成分研究%Chemical Constituents of Elephantopus scaber L.

    Institute of Scientific and Technical Information of China (English)

    郭妍; 陈晨; 高纯; 袁丹; 付宏征

    2016-01-01

    对地胆草全草的化学成分进行研究.采用硅胶柱色谱、Sephadex LH-20以及半制备型高效液相色谱技术进行分离纯化,通过1D、2D NMR,MS等方法鉴定化合物的结构.结果从地胆草95%乙醇提取物中分离并鉴定了9个化合物,分别为1-[(2R*,3S*)-3-ethoxy-2,3-dihydro-6-hydroxy-2-(1-methylethenyl)-1-benzofuran-5-yl]ethanone(1)、7-hydroxy-6-acetyl-2-methylchromone (2)、matriisobenzofuran (3)、桦木酸(betulinic acid,4)、木犀草素(luteolin,5)、木犀草素-7-O-β-D-葡萄糖苷(luteolin-7-O-β-D-glucoside,6)、对香豆酸(p-coumaric acid,7)、3,4-二羟基苯甲醛(3,4-dihydroxy benzaldehyde,8)、豆甾醇-3-O-β-D-葡萄糖苷(stigmasterol-3-O-β-D-glucoside,9).其中化合物1~3均为首次从该属植物中分离得到,化合物3在国内未见从其它植物中分离报道.

  20. 汉防己叶挥发油成分GC-MS分析%Analysis of Volatile Oil of Leaves from Stephania tetrandra S. Moore by GC.MS

    Institute of Scientific and Technical Information of China (English)

    巩江; 倪士峰; 骆蓉芳; 路锋; 侯晓艺; 曹梦晔; 李娜; 陈烨丹; 袁东亚

    2011-01-01

    [ Objective ] To analyze the chemical constituents of the essential oil from leaves of Stephania tetrandra S. Moore. [ Method ] Extracted by steam distillation, the chemical components of essential oil were analyzed and identified by CC-MS combined with computer retrieval. The relative content of each component was determined by area normalization. [ Result] Forty-eight volatile compounds were obtained, representing 85.87% of the total off, the main constituents of which were 2,2 -dihydroxy -benzofuran (3.96%), 3,7,11 -trimethyl-1,6,10 - cyclododecatriene-3-ol ( 10. O1% ), cyclohexanone( 13.07% ) and 2-methoxy-4-ethyl-phenol ( 19.58% ). [ Conclusion] This case will provide basis for the development and application of essential oll from leaves of Stephan ia tetrandra S. Moore.%[目的]分析汉防己叶挥发油的化学成分.[方法]将汉防已叶经水蒸气蒸馏得到挥发油,运用GC-MS技术,结合计算机检索对其成分进行分析和鏊定,并用峰面积归一法计算各个组分相对含量.[结果]共鉴定出48种化合物,占挥发油总量的85.87%,主要成分为:2,2-二羟基-苯并呋喃(3.96%)、3,7,11-三甲基-1,6,10-十二碳三烯-3-醇(10.01%)、环己酮(13.07%)和2-甲氧基-4-乙基-苯酚(19.58%).[结论]该研究为汉防已叶挥发油成分的开发利用奠定了基础.

  1. Biomass burning emissions and potential air quality impacts of volatile organic compounds and other trace gases from temperate fuels common in the United States

    Directory of Open Access Journals (Sweden)

    J. B. Gilman

    2015-08-01

    Fourmile Canyon Fire that affected Boulder, Colorado in September 2010 allowed us to investigate biomass burning (BB emissions in the presence of other VOC sources (i.e., urban and biogenic emissions and identify several promising BB markers including benzofuran, 2-furaldehyde, 2-methylfuran, furan, and benzonitrile.

  2. Triphenyltin impairs a protein kinase A (PKA)-dependent increase of cytosolic Na+ and Ca2+ and PKA-independent increase of cytosolic Ca2+ associated with insulin secretion in hamster pancreatic β-cells

    International Nuclear Information System (INIS)

    Oral administration of triphenyltin chloride (TPT) (60 mg/kg body weight) inhibits the insulin secretion by decreasing the cytoplasmic Ca2+ concentration ([Ca2+] i) induced by glucose-dependent insulinotropic polypeptide (GIP) in pancreatic β-cells of the hamster. To test the possibility that the abnormal level of [Ca2+] i induced by TPT administration could be due to a defect in the cAMP-dependent cytoplasmic Na+ concentration ([Na+] i) in the β-cells, we investigated the effects of TPT administration on the changes of [Na+] i induced by GIP, glucagon-like peptide-1 (GLP-1), or forskolin, an activator of adenylyl cyclase, and on the changes of [Na+] i or [Ca2+] i induced by 6-Bnz-cAMP, an activator of protein kinase A (PKA), and 8-pCPT-2'-O-Me-cAMP, an activator of Epac. The [Na+] i and [Ca2+] i were measured in islet cells loaded with sodium-binding benzofuran isophthalate (SBFI) and fura-2, respectively. In the presence of 135 mM Na+, TPT administration significantly reduced the rise in [Na+] i by 10 nM GLP-1, 10 μM forskolin, and 50 μM 6-Bnz-cAMP, but had not effect in a Na+-free medium. In the presence of 135 mM Na+, TPT administration also reduced the rise in [Ca2+] i by 8-pCPT-2'-O-Me-cAMP plus10 μM H-89, a inhibitor of PKA, and 6-Bnz-cAMP. Moreover, TPT administration significantly reduced the insulin secretion by 2 mM db-cAMP, GLP-1, GIP, and 8-pCPT-2'-O-Me-cAMP with and without H-89, and that by 6-Bnz-cAMP and forskolin. Our study suggested that TPT has inhibitory effects on the cellular Ca2+ response due to a reduced Na+ permeability through PKA-dependent mechanisms in hamster islet cells. Also TPT has the reduction of [Ca2+] i related to Na+-dependent insulin secretion after an activation of Epac

  3. Identification of novel compounds inhibiting chikungunya virus-induced cell death by high throughput screening of a kinase inhibitor library.

    Directory of Open Access Journals (Sweden)

    Deu John M Cruz

    Full Text Available Chikungunya virus (CHIKV is a mosquito-borne arthrogenic alphavirus that causes acute febrile illness in humans accompanied by joint pains and in many cases, persistent arthralgia lasting weeks to years. The re-emergence of CHIKV has resulted in numerous outbreaks in the eastern hemisphere, and threatens to expand in the foreseeable future. Unfortunately, no effective treatment is currently available. The present study reports the use of resazurin in a cell-based high-throughput assay, and an image-based high-content assay to identify and characterize inhibitors of CHIKV-infection in vitro. CHIKV is a highly cytopathic virus that rapidly kills infected cells. Thus, cell viability of HuH-7 cells infected with CHIKV in the presence of compounds was determined by measuring metabolic reduction of resazurin to identify inhibitors of CHIKV-associated cell death. A kinase inhibitor library of 4,000 compounds was screened against CHIKV infection of HuH-7 cells using the resazurin reduction assay, and the cell toxicity was also measured in non-infected cells. Seventy-two compounds showing ≥50% inhibition property against CHIKV at 10 µM were selected as primary hits. Four compounds having a benzofuran core scaffold (CND0335, CND0364, CND0366 and CND0415, one pyrrolopyridine (CND0545 and one thiazol-carboxamide (CND3514 inhibited CHIKV-associated cell death in a dose-dependent manner, with EC50 values between 2.2 µM and 7.1 µM. Based on image analysis, these 6 hit compounds did not inhibit CHIKV replication in the host cell. However, CHIKV-infected cells manifested less prominent apoptotic blebs typical of CHIKV cytopathic effect compared with the control infection. Moreover, treatment with these compounds reduced viral titers in the medium of CHIKV-infected cells by up to 100-fold. In conclusion, this cell-based high-throughput screening assay using resazurin, combined with the image-based high content assay approach identified compounds against

  4. Amiodarone: review of pulmonary effects and toxicity.

    Science.gov (United States)

    Papiris, Spyros A; Triantafillidou, Christina; Kolilekas, Likurgos; Markoulaki, Despoina; Manali, Effrosyni D

    2010-07-01

    Amiodarone, a bi-iodinated benzofuran derivative, is, because of its high effectiveness, one of the most widely used antiarrhythmic agents. However, adverse effects, especially potentially fatal and non-reversible acute and chronic pulmonary toxicity, continue to be observed. This review provides an update of the epidemiology, pathophysiology, clinical presentation, treatment and outcome of amiodarone pulmonary effects and toxicity. Lung adverse effects occur in approximately 5% of treated patients. The development of lung complications appears to be associated with older age, duration of treatment and cumulative dosage, high levels of its desethyl metabolite, history of cardiothoracic surgery and/or use of high oxygen mixtures, use of iodinated contrast media, and probably pre-existing lung disease as well as co-existing respiratory infections. Amiodarone-related adverse pulmonary effects may develop as early as from the first few days of treatment to several years later. The onset of pulmonary toxicity may be either insidious or rapidly progressive. Cough, new chest infiltrates in imaging studies and reduced lung diffusing capacity in the appropriate clinical setting of amiodarone use, after the meticulous exclusion of infection, malignancy and pulmonary oedema, are the cardinal clinical and laboratory elements for diagnosis. Pulmonary involvement falls into two categories of different grades of clinical significance: (i) the ubiquitous 'lipoid pneumonia', the so-called 'amiodarone effect', which is usually asymptomatic; and (ii) the more appropriately named 'amiodarone toxicity', which includes several distinct clinical entities related to the differing patterns of lung inflammatory reaction, such as eosinophilic pneumonia, chronic organizing pneumonia, acute fibrinous organizing pneumonia, nodules or mass-like lesions, nonspecific interstitial pneumonia-like and idiopathic pulmonary fibrosis-like interstitial pneumonia, desquamative interstitial pneumonia

  5. Molecular pharmacology of kidney and inner ear CLC-K chloride channels

    Directory of Open Access Journals (Sweden)

    Antonella eGradogna

    2010-10-01

    Full Text Available CLC-K channels belong to the CLC gene family, which comprises both Cl- channels and Cl-/H+ antiporters. They form homodimers which additionally co-assemble with the small protein barttin. In the kidney, they are involved in NaCl reabsorption ; in the inner ear they are important for endolymph production. Mutations in CLC-Kb lead to renal salt loss (Bartter’s syndrome; mutations in barttin lead additionally to deafness. CLC-K channels are interesting potential drug targets. CLC-K channel blockers have potential as alternative diuretics, whereas CLC-K activators could be used for the treatment of patients with Bartter’s syndrome. Several small organic acids inhibit CLC-K channels from the outside by binding to a site in the external vestibule of the ion conducting pore. Benzofuran derivatives with affinities better than 10 µM have been discovered. Niflumic acid (NFA exhibits a complex interaction with CLC-K channels. Below ~ 1 mM, NFA activates CLC-Ka, whereas at higher concentrations NFA inhibits channel activity. The co-planarity of the rings of the NFA molecule is essential for its activating action. Mutagenesis has led to the identification of potential regions of the channel that interact with NFA. CLC-K channels are also modulated by pH and [Ca2+]ext. The inhibition at low pH has been shown to be mediated by a His-residue at the beginning of helix Q, the penultimate transmembrane helix. Two acidic residues from opposite subunits form two symmetrically related intersubunit Ca2+ binding sites, whose occupation increases channel activity.The relatively high affinity CLC-K blockers may already serve as leads for the development of useful drugs. On the other hand, the CLC-K potentiator NFA has a quite low affinity, and, being a non-steroidal anti-inflammatory drug, can be expected to exert significant side effects. More specific and more potent activators will be needed and it will be important to understand the molecular mechanisms that

  6. National implementation plan on reduction and elimination of persistent organic pollutants in the Republic of Macedonia

    International Nuclear Information System (INIS)

    The aim of the Stockholm Convention' is to protect human health and the environment from Persistent Organic Pollutants (POPs). Currently the Convention lists twelve POPs. They have similar physical, chemical, and biological characteristics. They possess toxic properties, resist degradation, bio accumulate and are transported, through air, water and migratory species, across international boundaries and deposited far from their place of release, where they accumulate in terrestrial and aquatic ecosystems. To reach its objectives, the Convention groups POPs into three categories. Annex A lists those intentionally produced chemicals, whose production, use, import and export have to be eliminated. They are, on the one hand, organo chlorine pesticides (Aldrin, Chlordane, Dieldrin, Endrin, Hexachlorobenze, Heptachlor, Mirex, Toxaphene) and industrial chemicals (PCBs) on the other. Annex B of the Convention lists those chemicals, whose production, import, export and use are allowed but restricted. Currently only DDT is listed in Annex B. Annex C to the Convention details those chemicals which are formed and released unintentionally from anthropogenic sources. They are Polychlorinated dibenzo-p-dioxins and di benzofurans (PCDD/PCDF), Hexachlorobenzene (HCB) and Polychlorinated biphenyls (PCB). Their releases should continuously be reduced, and where feasible, with the goal of their ultimate elimination. The Convention also aims to increase public awareness on POPs and on the activities related to POPs. It also requests parties to develop a National Implementation Plan, which describes what measures the party will take, how much time and financial support would be required to meet the obligations of this treaty. Macedonia signed the Stockholm Convention on 23rd May 2001, and ratified it on March 19th 2004. With the fund from the Global Environment Facility (GEF) and with the assistance of the United Nations Industrial Development Organization, the Ministry of Environment

  7. Synthetic Transformations through Alkynoxy-Palladium Interactions and C-H Activation.

    Science.gov (United States)

    Minami, Yasunori; Hiyama, Tamejiro

    2016-01-19

    internal alkynes and the alkynoxy group to produce 2-methylidene-2H-1-benzopyrans. Mechanistic studies have shown that the presence of both oxygen and alkynyl moieties is essential for selective ortho-C-H bond activation and subsequent annulation. In addition to internal alkynes, norbornene, allenes, isocyanates, and ketenes produce the corresponding oxacycles. It is worthy of note that benzoxadinones formed by the reaction with isocyanates exhibit solid-state luminescence. In addition, 2-methylphenyl alkynyl ethers and 2-alkynoxybiaryls undergo intramolecular annulation at the benzylic γ-position and aryl δ-position via C-H bond activation to give benzofurans and dibenzopyrans, respectively. The disclosed methods allow us to construct useful π-conjugated systems in a straightforward manner. PMID:26651014

  8. Chemical Composition as Analyzed by GC-MC and Antibacterial Activity of Volatile Oil from Stems and Leaves of Seseli seseloides Hiroe%邪蒿挥发油化学成分的GC-MS分析及抑菌作用

    Institute of Scientific and Technical Information of China (English)

    潘素娟; 王长青; 李晓东; 汪之波; 朱元成

    2011-01-01

    The volatile oil in the stems and leaves of Seseli seseloides Hiroe.was extracted by steam distillation method with an extraction rate of 1.33%.GC-MS was used to analyze the chemical composition of the oil and the antibacterial activity was also measured.Under the optimal analytical conditions,37 peaks were separated and 31 of them were identified,accounting for 93.7% of the total volatile oil.The major compounds were nutmeg ether(64.05%),celery brain(8.98%),dimethoxy butane(2.09%),benzofuran,2,3-dihydro-(1.87%),hong tree ene(1.35%),guaiacyl-ene(1.37%),etc.The results of antibacterial experiments showed that the oil had strong inhibitory effect on the growth of Staphylococcus aureus,Escheichia coli and Shigella dysenteriae.%采用气相色谱-质谱联用(gas chromatography-mass spectrometry,GC-MS)对邪蒿挥发油成分进行分析,并对其抑菌作用进行研究。结果表明:采用水蒸气蒸馏法从邪蒿中提取挥发油的提取率为1.33%;在最佳分析条件下,共分离出37个峰,并对其化学成分进行分析,鉴定出31个化学成分,占总挥发油量的93.7%,其主要成分为肉豆蔻醚(64.05%)、芹菜脑(8.98%)、2-甲氧基丁烷(2.02%)、香豆酮(1.87%)、香树烯(1.35%)、α-愈创木烯(1.3 7%)等;邪蒿挥发油对金黄色葡萄球菌、大肠杆菌和痢疾杆菌生长有强抑制作用。

  9. Histopathological and Biochemical Toxic Effect of Amiodarone on Thyroid Gland in Albino Rat

    Directory of Open Access Journals (Sweden)

    Ola A. El Sayed*, Safaa E. Gawish

    2007-12-01

    Full Text Available Backgrounds: Amiodarone AMD (Cordarone was a benzofuran derivative, used in management of angina and refractory ventricular arrhythmia. Its effect on the thyroid gland structure and function was investigated in this study. Material and Methods: Fifty adult male albino rats were used and divided into three groups. The first group was consisted of 10 rats which served as control, received distilled water orally (1ml. The second group was consisted of 20 rats used as therapeutic dose treated group, received 40 mg/Kg b. w. of amiodarone while the third group was consisted of 20 rats used as a toxic dose treated group which received 60 mg/Kg b. w. of amiodarone orally daily for three months. Body weight of animals was determined. Serum concentration of tri-iodothyonine (T3, thyroxine (T4, thyrotrophin (TSH, interleukin 6 (IL6, tumour marker P53 and tissue residue for amiodarone in plasma, fat, liver, lung, thyroid gland and heart was determined. Results: Specimens from thyroid gland were taken and prepared for light and electron microscope examination. Highly significant decrease in body weight (P<0.001 were observed in both therapeutic and toxic doses treated groups in comparison to the control one. A very highly significant increase (P<0.001 of serum (T4 & T3 with Concomitant suppression of (TSH (P<0.001. Serum levels of IL6 and P53 showed also a very highly significant increase (P<0.001. Amiodarone concentration in plasma, fat, liver, lung, thyroid gland and heart showed significant increase in therapeutic dose treated group and highly significant increase in toxic dose treated group. Histopathological examination of thyroid gland of therapeutic dose treated group by light microscope showed marked evidence of thyotoxicosis in the form of microcystic follicular changes and peripheral scalloping, cellular degeneration with scanty cytoplasm and vesicular nuclei appeared. These changes became more severe in toxic dose treated group in the form of

  10. Biomass burning emissions and potential air quality impacts of volatile organic compounds and other trace gases from fuels common in the US

    Science.gov (United States)

    Gilman, J. B.; Lerner, B. M.; Kuster, W. C.; Goldan, P. D.; Warneke, C.; Veres, P. R.; Roberts, J. M.; de Gouw, J. A.; Burling, I. R.; Yokelson, R. J.

    2015-12-01

    were the dominant potential SOA precursors. In addition, ambient air measurements of emissions from the Fourmile Canyon Fire that affected Boulder, Colorado in September 2010 allowed us to investigate biomass burning (BB) emissions in the presence of other VOC sources (i.e., urban and biogenic emissions) and identify several promising BB markers including benzofuran, 2-furaldehyde, 2-methylfuran, furan, and benzonitrile.

  11. 固相微萃取-气质联用技术测定5种食用植物油挥发性成分%Detection of volatile components in 5 edible vegetable oils by solid phase micro-extraction-gas chromatography-mass spectrometry

    Institute of Scientific and Technical Information of China (English)

    高蓓; 章晴; 杨悠悠; 杨永坛

    2015-01-01

    Objective To identify and classify the volatile components in 5 kinds of edible vegetable oils (soybean oil, sesame oil, peanut oil, olive oil, and grape seed oil) by gas chromatography-mass spectrometry (GC-MS) technology.MethodsThe solid phase micro-extraction (SPME) technology had been used to extract volatile components in those edible vegetable oils, and the volatile components in 5 kinds of edible vegetable oils were determined by gas chromatography-mass spectrometry (GC-MS).ResultsThe total of 101 volatile compounds were detected in 5 edible vegetable oils, with soybean oil 11, peanut oil 28, sesame oil 65, olive oil 25, and grape seed oil 5, respectively. The volatile compounds were mainly aldehydes, ester, alcohols, heterocyclic, phenols and acids. The major components were pentanal, hexanal and hexanoic acid in soybean oil, hexanal, 2,5-dimethyl pyrazine and benzofuran, 2,3-dihydro- in peanut oil,2-furancarboxaldehyde, 5-methyl-, 2-formylpyrrole,2-furanmethanol, phenol, 2-methoxy-, pyrazine, methyl-,and pyrazine, 2-ethyl-6-methyl- in sesame oil,3-hexen-1-ol, (Z)- and 4-hexen-1-ol, acetate in olive oil, and hexanal in grape seed oil. ConclusionThe volatile composition and content are greatly different in 5 edible vegetable oils, which can provide reference to the adulteration of edible vegetable oil.%目的:采用气相色谱-质谱(GC-MS)对大豆油、芝麻油、花生油、橄榄油、葡萄籽油5种食用植物油中挥发性成分进行分析。方法采用顶空固相微萃取(HS-SPME)技术对5种食用植物油中的挥发性成分进行萃取,并结合气相色谱-质谱(GC-MS)技术对挥发性成分进行测定。结果5种食用植物油中共检测出101种挥发性化合物,其中大豆油11种、花生油28种、芝麻油65种、橄榄油25种、葡萄籽油5种。主要包括醛类、酯类、醇类、杂环类、酚类、酸类等10类物质。大豆油中主要的挥发性成分有戊醛、已醛和己酸,花生油中主要

  12. A snapshot on NPS in Italy: Distribution of drugs in seized materials analysed in an Italian forensic laboratory in the period 2013-2015.

    Science.gov (United States)

    Odoardi, Sara; Romolo, Francesco Saverio; Strano-Rossi, Sabina

    2016-08-01

    The diffusion of New Psychoactive Substances (NPS) in the illicit drug market is a worldwide problem. The aim of the study is to describe the qualitative distribution of drugs of abuse in seized materials confiscated in the Italian territory over the last two years. Between 2013 and 2015 162 seizures of substances purchased through the Internet and confiscated by police authorities were analyzed: 35 seizures (22%) were crystals of 3-methylmethcathinone (3-MMC). Although 3-MMC is subject to the relevant legislation in Italy, it is not controlled in other countries such as the Netherlands, from which the shipments originated. 33 seizures (20%) were crystals of 4-methylethcathinone (4-MEC), 19 seizures (12%) were powders containing methylenedioxypyrovalerone (MDPV). N,N-diallyl-5-methoxytryptamine (5-MeO-DALT) was identified in 5 powders, whereas ethylphenidate in six and pyrrolidinophenones in fourteen seized powders: 6 α-PVP (alpha-pyrrolidinovalerophenone), 6 α-PHP (alpha-pyrrolidinohexiophenone) and 1 α-PVT (alpha-pyrrolidinopentiothiophenone). Other substances identified were cathinones such as pentedrone, methylone, buthylone, ethylone, methedrone, 3-CMC (3-chloromethcathinone), 3,4-dimethylmethcathinone (3,4-DMMC), flephedrone (4-fluoromethcathinone or 4-FMC), 2-FMC and 3-FMC (2- and 3-fluoromethcathinone), MPPP (4-methyl-alpha-pyrrolidinopropiophenone), bk-2C-B (2-amino-1-(4-bromo-2,5-dimethoxyphenyl)ethan-1-one). Other compounds were NM2AI (N-methyl-2-aminoindane), MPA (1-(thiophen-2-yl)-2-methylaminopropane), MTTA (mephtetramine), 4-APB and 6-APB (4- and 6- (2-aminopropyl)benzofuran), 2-fluoromethamphetamine, 1mCPP (1-meta-chlorophenylpiperazine) and diphenidine, detected for the first time in Europe. Only three seizures contained synthetic cannabinoids, consisting of herbal blends soaked in N-(1-adamantyl)-1-pentyl-1H-indazole-3-carboxamide (AKB48), or a mixture of 5-F-AKB48 and BB-22 (1-(cyclohexylmethyl)-8-quinolinyl ester-1H-indole-3-carboxylic acid

  13. Synthesis and molecular docking towards HIV-1 integrase of the new dihydrobenzofuran%苯并二氢呋喃新化合物的合成与 HIV-1整合酶分子对接研究

    Institute of Scientific and Technical Information of China (English)

    罗杨; 范晔; 杨旭超; 马成

    2016-01-01

    Objective With the HIV-1 integrase enzyme molecular docking analysis synthetic dihydrobenzo-furan compounds (3)and the integrase binding mode and inhibition.Methods From vanillin and malonic acid as raw material,the Knoevenagel condensation,esterification,oxidation coupling reaction,synthesis of dihydro-benzofuran new compounds (3)2-(4-hydroxy-3-methoxy)phenyl-7-methoxy-5-[3-(2-methoxy-2-oxoethoxy)-3-oxopropenyl ]-2,3-dihydrobenzofuran-3-carboxylic acid methoxycarbonyl methyl ester. Using the computer software of Autodock compound (3)by molecular docking,prediction and analysis of the compounds have inhibition of HIV-1 integrase.Results The yield of the synthetic target compound (3)was 21.4%,which was determined by the structural identification data (3),Molecular docking showed that the compounds by docking analysis to HIV integrase (PDB:1QS4)indicates that the amino acids resi-due of asparagine,glutamine and histidine interact with the enzyme through hydrogen bond,π-π coinci-dence and hydrophobic force.Conclusion The synthesis route of the oxidative coupling reaction is short, the reaction condition is mild,the operation is simple and easy to control,the target compound is obtained by column chromatography,docking displayed that compounds inhibited the HIV-1 integration enzyme.%目的:通过与 HIV-1整合酶的分子对接,分析合成的苯并二氢呋喃类化合物(3)与整合酶的结合方式和抑制作用。方法以香草醛和丙二酸为原料,经 Knoevenagel 缩合、酯化、氧化偶联反应,合成苯并二氢呋喃新化合物(3)2-(4-羟基-3-甲氧基)苯基-7-甲氧基-5-[3-(2-甲氧基-2-氧代乙氧基)-3-氧代丙烯基]-2,3-二氢苯并呋喃-3-羧酸甲氧羰基甲酯,采用计算机 Autodock 软件对化合物(3)进行分子对接,预测分析该化合物是否有抑制 HIV-1整合酶的作用。结果合成目标化合物(3)的产率为21.4%,经结构鉴定数据确定为化合物(3),

  14. Molecular imaging of {sigma} receptors: synthesis and evaluation of the potent {sigma}{sub 1} selective radioligand [{sup 18}F]fluspidine

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, Steffen; Hiller, Achim; Deuther-Conrad, Winnie; Scheunemann, Matthias; Steinbach, Joerg; Brust, Peter [Institute of Radiopharmacy, Forschungszentrum Dresden-Rossendorf, Research Site Leipzig, Interdisciplinary Isotope Research, Leipzig (Germany); Wiese, Christian; Grosse Maestrup, Eva; Schepmann, Dirk; Wuensch, Bernhard [Institut fuer Pharmazeutische und Medizinische Chemie der Westfaelischen Wilhelms-Universitaet Muenster, Muenster (Germany)

    2011-03-15

    Neuroimaging of {sigma}{sub 1} receptors in the human brain has been proposed for the investigation of the pathophysiology of neurodegenerative and psychiatric diseases. However, there is a lack of suitable {sup 18}F-labelled PET radioligands for that purpose. The selective {sigma}{sub 1} receptor ligand [{sup 18}F]fluspidine (1'-benzyl-3-(2-[{sup 18}F]fluoroethyl)-3H-spiro[[2]benzofuran-1,4'-piperidine]) was synthesized by nucleophilic {sup 18}F{sup -} substitution of the tosyl precursor. In vitro receptor binding affinity and selectivity were assessed by radioligand competition in tissue homogenate and autoradiographic approaches. In female CD-1 mice, in vivo properties of [{sup 18}F]fluspidine were evaluated by ex vivo brain section imaging and organ distribution of intravenously administered radiotracer. Target specificity was validated by organ distribution of [{sup 18}F]fluspidine after treatment with 1 mg/kg i.p. of the {sigma} receptor antagonist haloperidol or the emopamil binding protein (EBP) inhibitor tamoxifen. In vitro metabolic stability and in vivo metabolism were investigated by LC-MS{sup n} and radio-HPLC analysis. [{sup 18}F]Fluspidine was obtained with a radiochemical yield of 35-45%, a radiochemical purity of {>=} 99.6% and a specific activity of 150-350 GBq/{mu}mol (n = 6) within a total synthesis time of 90-120 min. In vitro, fluspidine bound specifically and with high affinity to {sigma}{sub 1} receptors (K{sub i} = 0.59 nM). In mice, [{sup 18}F]fluspidine rapidly accumulated in brain with uptake values of 3.9 and 4.7%ID/g and brain to blood ratios of 7 and 13 at 5 and 30 min after intravenous application of the radiotracer, respectively. By ex vivo autoradiography of brain slices, resemblance between binding site occupancy of [{sup 18}F]fluspidine and the expression of {sigma}{sub 1} receptors was shown. The radiotracer uptake in the brain as well as in peripheral {sigma}{sub 1} receptor expressing organs was significantly

  15. Employing Arynes in Diels-Alder Reactions and Transition-Metal-Free Multicomponent Coupling and Arylation Reactions.

    Science.gov (United States)

    Bhojgude, Sachin Suresh; Bhunia, Anup; Biju, Akkattu T

    2016-09-20

    Arynes are highly reactive intermediates having several applications in organic synthesis for the construction of various ortho-disubstituted arenes. Traditionally, arynes are generated in solution from haloarenes under strongly basic conditions. However, the scopes of many of the aryne reactions are limited because of the harsh conditions used for their generation. The renaissance of interest in aryne chemistry is mainly due to the mild conditions for their generation by the fluoride-induced 1,2-elimination of 2-(trimethylsilyl)aryl triflates. This Account is focused on the Diels-Alder reaction of arynes and their transition-metal-free application in multicomponent couplings as well as arylation reactions. The Diels-Alder reaction of arynes is a powerful tool for constructing benzo-fused carbocycles and heterocycles. In 2012, we developed an efficient, broad-scope, and scalable Diels-Alder reaction of pentafulvenes with arynes affording benzonorbornadiene derivatives. Subsequently, we accomplished the Diels-Alder reaction of arynes with dienes such as 1,2-benzoquinones and tropones. Moreover, we uncovered a transition-metal-free protocol for the synthesis of 9,10-dihydrophenanthrenes by the reaction of arynes with styrenes that proceeds via a Diels-Alder/ene-reaction cascade. In addition, we demonstrated the reaction of arynes with indene/benzofurans, which proceeds via a tandem [4 + 2]/[2 + 2] sequence. Multicomponent coupling (MCC) involving arynes mainly comprises the initial addition of a nucleophile to the aryne followed by interception of the aryl anion intermediate with an electrophile (provided the nucleophilic and electrophilic moieties do not belong to the same molecule). We have disclosed aryne MCCs initiated by N-heterocycles such as (iso)quinoline, pyridine, and aziridines. When (iso)quinoline is used as the nucleophilic trigger and N-substituted isatin as the third component, the reaction affords spirooxazino(iso)quinolines via 1,4-dipolar

  16. 直火和蒸汽加热方式制备豆乳对豆腐风味的影响%Effect of Direct-fire and Steam-heating in Soymilk Preparation on Flavor of Tofu

    Institute of Scientific and Technical Information of China (English)

    李景妍; 任建华; 郭顺堂

    2012-01-01

    -butanal, hexanoic acid, methylbenzoate and benzofuran were detected only in tofu processed in direct-fire heating method, and azeti dine,diethyl malonate,dimethylamine and paeonol were specific compounds in steam-heating tofu.

  17. Using BPCA and pyrolysis-GC/MS patterns as a measure of charring intensity

    Science.gov (United States)

    Kaal, Joeri; Schneider, Maximilian P. W.; Schmidt, Michael W. I.

    2010-05-01

    Many questions remain on the molecular properties of Black C (organic fire residues such as charcoal and soot). Here we compare parameters from two methods that have recently shown to be related to the degree of thermal modification ("charring intensity") of charcoal-Black C: i) the proportion of mellitic acid (B6CA) among benzenepolycarboxylic acids in the BPCA method [1,2,3] and ii) the relative proportions and degree of alkylation of pyrolysis products from Black C in pyrolysis-GC/MS [4]. For that purpose we used laboratory chars from rice straw (grass) and chestnut wood (wood) produced at 200-1000 °C under N2 flow. The chars obtained at 450 °C are reference materials of the Black Carbon Ring Trial [5]. Positive correlations between the charring temperature and BPCA and pyrolysis patterns confirm that these methods can be used to study the degree of thermal impact of charred remains. Pyrolysis-GC/MS allowed us to track the thermal degradation of the major biocomponents lignin, polysaccharides, tannin, aliphatic chain lipids, triterpenoids, chlorophyll and proteins, mostly between 250 and 450 °C. The proportions of the pyrolysis products of Black C (benzene, toluene, benzonitrile, PAHs, etc.) and also the ratios that reflect the abundance of aliphatic cross-linkages between aromatic moieties (benzene/toluene, naphthalene/alkylnaphthalenes, benzofuran/alkylbenzofurans), increase with charring intensity. Nonetheless, chars obtained at T > 600 °C (especially for wood) gave low quality pyrograms and poor reproducibility because of high thermal stability. The relative contributions of B6CA, one of the molecular markers used for the BPCA method, are indicative for the degree of condensation of the chars. The BPCA approach showed a clear increase in the relative contribution of B6CA from ca. 5 % at 200 °C to ca. 95 % at 1000 °C, confirming the ability of this parameter to assess charring intensity. The relative contribution of B6CA remains almost constant at ca

  18. Changes in Volatile Composition during Fruit Development and Ripening of ‘Friar' Plum%‘黑宝石'李果实发育期间香气成分的组成及变化

    Institute of Scientific and Technical Information of China (English)

    王华瑞; 马燕红; 王伟; 李建华; 张生万

    2012-01-01

    This study analyzed changes in volatile composition in ‘Friar' plum during fruit development and ripening. Dichloromethane extracts from ‘Friar' plum fruits harvested at different stages of maturity, mature-green, coloring, commercial maturity and full maturity were determined by GC-MS. A total of 49 compounds were identified from all investigated samples, mainly alcohols, aldehydes, esters, lactones, ketones, acids and phenols along with small amounts of alkanes and amines. Considerable differences in volatile composition were found for ‘Friar' plum fruits harvested at different stages of maturity. The dominant alcohols in ‘Friar' plum were fatty alcohols (mainly C6 alcohols), sterols and aromatic alcohols. The maximum C6 alcohol content was found at the mature-green stage and progressively declined with maturity. The most abundant sterol was 22,23-dihydro-stigmasterol, which became more abundant with maturity. Aldehydes were the most dominant volatile compounds in ‘Friar' plum (29.16%), mainly C6 aldehydes and aromatic aldehydes. The former showed a trend similar to C6 alcohols with maturity, whereas the latter revealed a gradual upward trend until commercial maturity and declined to 0.29% at full maturity. The major ester ethyl acetate and the major lactone gamma-dodecalactone were detected until commercial maturity or full maturity with a level less than 1%. Seven ketones except 2,3-dihydro-benzofuran and 3 acids except n-hexadecanoic acid were only found in fully mature fruits. The major phenols were 2-methoxy-4-vinylphenol and butylated hydroxytoluene, which showed maximum levels in mature-green fruits and minimum levels in fuUy mature fruits. The contents of other compounds such as 3-hydroxy-2- butanone, benzaldehyde, n-hexadecanoic acid, trans-cinnamic acid, acetic acid, butyl ester, hexyl ester, gamma-dodecalactone, 22,23-dihydro-stigmasterol gradually increased with maturity. They were considered as major aroma compounds.%研究‘黑宝石’