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Sample records for benzofurans

  1. Synthesis of benzofurans from oxygenated phenoxyamines

    Energy Technology Data Exchange (ETDEWEB)

    Castellino, A.J.; Rapoport, H.

    1984-11-16

    O-Aryloximes having various oxygenated substitution patterns have been converted to benzofurans, with implications toward natural product synthesis, through an extension of the Fischer indole type of synthesis. The effect of the substituent pattern in the benzene ring and the nature of the carbonyl derived portion of the oxime on benzofuranization were explored. 11 references, 4 tables.

  2. A New Benzofuran Derivative from the Bark of Mulberry Tree

    Institute of Scientific and Technical Information of China (English)

    Sheng Jun DAI; Zhi Bo MA; Shuai LI; Ruo Yun CHEN; De Quan YU

    2004-01-01

    From the EtOH extract of the barks of Morus macroura Miq, a new benzofuran derivative, macrourin D 1, together with four known benzofuran derivatives, macrourin B 2, 2-(3, 5-dihydroxyphenyl)-5, 6-dihydroxybenzofuran 3, moracin M 4, and mulberroside C 5 were isolated, and their structures were determined on the basis of spectroscopic evidence and chemical correlation with known compounds.

  3. 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.

  4. 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.

  5. 2-(4-Bromophenyl-5-fluoro-3-methylsulfinyl-1-benzofuran

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    Hong Dae Choi

    2009-09-01

    Full Text Available In the title compound, C15H10BrFO2S, the O atom and the methyl group of the methylsulfinyl substituent lie on opposite sides of the plane through the benzofuran fragment. The 4-bromophenyl ring is rotated out of the benzofuran plane [dihedral angle = 38.98 (8°], while the structure is stabilized by an intermolecular C—H...O hydrogen bond and a Br...O halogen bond [3.036 (2 Å] and has an intermolecular C–H...π interaction between the 4-bromophenyl H atom and the benzene ring of an adjacent benzofuran molecule, as well as aromatic π–π interactions between the benzene rings of the benzofuran systems [centroid–centroid distance = 3.482 (3 Å].

  6. 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 ...

  7. 5-Bromo-2-phenyl-3-phenylsulfinyl-1-benzofuran

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    Hong Dae Choi

    2009-11-01

    Full Text Available In the title compound, C20H13BrO2S, the O atom and the phenyl group of the phenylsulfinyl substituent are located on opposite sides of the plane of the benzofuran system. The S-bound phenyl ring is almost perpendicular to this plane [80.35 (8°]. The phenyl ring in the 2-position is twisted with respect to the benzofuran plane, making a dihedral angle of 16.0 (1°.

  8. 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.

  9. 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.

  10. 2,5-Dimethyl-3-phenylsulfonyl-1-benzofuran

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    Uk Lee

    2008-05-01

    Full Text Available The title compound, C16H14O3S, was prepared by the oxidation of 2,5-dimethyl-3-phenylsulfanyl-1-benzofuran with 3-chloroperoxybenzoic acid. The phenyl ring makes a dihedral angle of 76.98 (9° with the plane of the benzofuran fragment. The crystal structure is stabilized by π–π interactions between furan and benzene rings of neighbouring molecules [centroid–centroid distance = 3.775 (4 Å]. In addition, the crystal structure exhibits intra- and intermolecular C—H...O interactions.

  11. 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].

  12. 5-Chloro-2-(4-fluorophenyl-3-methylsulfinyl-1-benzofuran

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    Hong Dae Choi

    2009-11-01

    Full Text Available In the title compound, C15H10ClFO2S, 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, making a dihedral angle of 25.99 (4°. The crystal structure is stabilized by a non-classical intermolecular C—H...O hydrogen bond and a Cl...O halogen bond [3.244 (1 Å].

  13. 2-(4-Chlorophenyl-3-ethylsulfinyl-5-fluoro-1-benzofuran

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    Hong Dae Choi

    2010-04-01

    Full Text Available In the title compound, C16H12ClFO2S, the 4-chlorophenyl ring is rotated out of the benzofuran plane, as indicated by the dihedral angle of 19.79 (8°. The crystal structure exhibits weak intermolecular C—H...O hydrogen bonds and C—H...π interactions.

  14. 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.

  15. 5-Cyclohexyl-2-(4-fluorophenyl-3-isopropylsulfonyl-1-benzofuran

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    Hong Dae Choi

    2011-04-01

    Full Text Available In the title compound, C23H25FO2S, the cyclohexyl ring adopts a chair conformation. The 4-fluorophenyl ring makes a dihedral angle of 50.74 (4° with the mean plane of the benzofuran fragment. In the crystal, molecules are linked by intermolecular C—H...π interactions.

  16. 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.

  17. 5-Ethyl-3-(3-fluorophenylsulfonyl-2-methyl-1-benzofuran

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    Hong Dae Choi

    2011-05-01

    Full Text Available In the title compound, C17H15FO3S, the fluorophenyl ring makes a dihedral angle of 76.11 (5° 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.

  18. 5-Chloro-3-ethylsulfinyl-2-(4-iodophenyl-1-benzofuran

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    Hong Dae Choi

    2010-09-01

    Full Text Available In the title compound, C16H12ClIO2S, the 4-iodophenyl ring is rotated out of the benzofuran plane by 9.4 (1°. In the crystal structure, intermolecular C—H...π interactions and short intermolecular I...O contacts [3.142 (2 Å] are observed.

  19. 3-(3-Chlorophenylsulfonyl-2,5-dimethyl-1-benzofuran

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    Uk Lee

    2011-10-01

    Full Text Available In the title molecule, C16H13ClO3S, the 3-chlorophenyl ring makes a dihedral angle of 76.30 (5° with the mean plane of the benzofuran fragment. In the crystal, pairs of intermolecular C—H...π interactions link the molecules into inversion dimers.

  20. 3-(4-Chlorophenylsulfonyl-5-isopropyl-2-methyl-1-benzofuran

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    Hong Dae Choi

    2011-05-01

    Full Text Available In the title molecule, C18H17ClO3S, the 4-chlorophenyl ring makes a dihedral angle of 77.03 (5° with the mean plane of the benzofuran fragment. In the crystal structure, the molecules are linked by weak intermolecular C—H...O hydrogen bonds and C—H...π interactions

  1. 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.

  2. 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.

  3. 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.

  4. 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].

  5. 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].

  6. 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].

  7. 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.

  8. 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.

  9. 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.

  10. 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].

  11. 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.

  12. 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].

  13. 5-Bromo-3-cyclohexylsulfinyl-2,7-dimethyl-1-benzofuran

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    Hong Dae Choi

    2011-05-01

    Full Text Available In the title compound, C16H19BrO2S, the cyclohexyl ring adopts a chair conformation. In the crystal, molecules are linked by a Br...Br [3.5994 (5 Å] contact and a C—H...π interaction involving the phenyl ring of the benzofuran. The crystal structure also exhibits a slipped π–π interaction between the furan rings of neighbouring molecules [centroid–centroid distance = 3.767 (1 Å and interplanar distance of 3.452 (1 Å with a slippage of 1.508 Å].

  14. 5-Fluoro-2-methyl-3-(4-methylphenylsulfonyl-1-benzofuran

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    Hong Dae Choi

    2012-02-01

    Full Text Available In the title compound, C16H13FO3S, the 4-methylphenyl ring makes a dihedral angle of 76.04 (4° with the mean plane of the benzofuran fragment. In the crystal, molecules are linked by weak C—H...O hydrogen bonds, and by a slipped π–π interaction between the furan and benzene rings of adjacent molecules [centroid–centroid distance = 3.780 (2 Å, interplanar distance = 3.475 (2 Å and slippage = 1.488 (2 Å].

  15. 5-Cyclohexyl-3-(4-fluorophenylsulfinyl-2-methyl-1-benzofuran

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    Hong Dae Choi

    2011-04-01

    Full Text Available In the title compound, C21H21FO2S, the cyclohexyl ring adopts a chair conformation. The 4-fluorophenyl ring makes a dihedral angle of 83.55 (4° with the mean plane of the benzofuran fragment. In the crystal, molecules are linked through weak intermolecular C—H...O and C—H...π interactions. The crystal structure also exhibits aromatic π–π interactions between the furan rings of neighbouring molecules [centroid–centroid distance = 3.541 (2 Å].

  16. 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.

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

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    Hong Dae Choi

    2013-09-01

    Full Text Available The asymmetric unit of the title compound, C26H23FO2S, contains two independent molecules (A and B, in both of which the cyclohexyl ring adopts a chair conformation. The benzofuran ring systems, the 4-fluorophenyl and phenyl rings are essentially planar, with r.m.s. deviations of 0.008 (1, 0.002 (1 and 0.003 (1 Å, respectively, for molecule A, and 0.016 (1, 0.004 (1 and 0.002 (1 Å, respectively, for molecule B. The dihedral angles between the benzofuran ring system and the pendant 4-fluorophenyl and phenyl rings are 12.3 (7 and 85.42 (4°, respectively, for molecule A, and 39.67 (6 and 72.17 (4°, respectively, for molecule B. In the crystal, molecules are linked by weak C—H...O and C—H...π interactions, resulting in a three-dimensional network.

  18. 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.

  19. Isopropyl 2-[5-(4-hydroxyphenyl-3-methylsulfanyl-1-benzofuran-2-yl]acetate

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    Hong Dae Choi

    2009-09-01

    Full Text Available In the title compound, C20H20O4S, the 4-hydroxyphenyl ring is rotated out of the plane of the benzofuran unit by 32.87 (8°. The S—Cmethyl bond is almost perpendicular to the plane of the benzofuran fragment [77.8 (1°] and is slightly tilted towards it. The crystal structure is stabilized by intermolecular O—H...O and C—H...O hydrogen bonds.

  20. Synthesis and antiprotozoal properties of pentamidine congeners bearing the benzofuran motif.

    Science.gov (United States)

    Bakunov, Stanislav A; Bakunova, Svetlana M; Bridges, Arlene S; Wenzler, Tanja; Barszcz, Todd; Werbovetz, Karl A; Brun, Reto; Tidwell, Richard R

    2009-09-24

    Forty-eight cationically substituted pentamidine congeners possessing benzofuran rings were synthesized by a copper mediated heteroannulation of substituted o-iodophenols with phenyl acetylenes. Activities of compounds 1-48 against Trypanosoma brucei rhodesiense, Plasmodium falciparum, and Leishmania donovani and cytotoxicities for mammalian cells were influenced by the nature of cationic substituents, placement of the benzofuran fragment, and the length of the carbon linker between aromatic moieties. Several dications exhibited superior antiplasmodial and antileishmanial potencies compared to pentamidine.

  1. Zinc–gold cooperative catalysis for the direct alkynylation of benzofurans

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    Yifan Li

    2013-08-01

    Full Text Available The direct alkynylation of benzofurans was achieved for the first time using the hypervalent iodine reagent 1-[(triisopropylsilylethynyl]-1,2-benziodoxol-3(1H-one (TIPS-EBX based on the cooperative effect between a gold catalyst and a zinc Lewis acid. High selectivity was observed for C2-alkynylation of benzofurans substituted with alkyl, aryl, halogen and ether groups. The reaction was also successful in the case of the more complex drug 8-methoxypsoralen (8-MOP.

  2. 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].

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

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    Hong Dae Choi

    2013-06-01

    Full Text Available In the title compound, C21H21FO2S, the cyclohexyl ring adopts a chair conformation. The 2-fluorobenzene ring makes a dihedral angle of 38.68 (6° with the mean plane [r.m.s. deviation = 0.018 (2 Å] of the benzofuran fragment. In the crystal, molecules are linked by pairs of C—H...O hydrogen bonds into dimers, which are further packed into stacks along the c axis by C—H...O hydrogen bonds. In addition, the stacked molecules exhibit S...O contacts [3.1733 (13 Å] involving the sulfinyl groups. The F atom is disordered over two positions, with site-occupancy factors of 0.961 (3 and 0.039 (3.

  4. 3-Cyclopentylsulfonyl-5-fluoro-2-methyl-1-benzofuran

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    Pil Ja Seo

    2011-07-01

    Full Text Available There are two independent molecules, A and B, in the asymmetric unit of the title compound, C14H15FO3S, in each of which the cyclopentyl ring adopts an envelope conformation. The benzofuran units in each molecule are essentially planar, with mean deviations from the least-squares plane defined by the nine constituent ring atoms of 0.009 (2 Å for molecule A and 0.013 (2 Å for molecule B. In the crystal, molecules are linked by weak C—H...O hydrogen bonds. In the cyclopentyl ring of molecule B, one C atom is disordered over two positions with site-occupancy factors of 0.60 (2 and 0.40 (2.

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

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    Hong Dae Choi

    2012-05-01

    Full Text Available In the title compound, C16H13BrO2S, the 4-methylphenyl ring makes a dihedral angle of 87.83 (6° with the mean plane [mean deviation = 0.007 (1 Å] of the benzofuran fragment. In the crystal, molecules are linked by weak C—H...O hydrogen bonds and Br...O contacts [3.099 (2 Å]. The crystal structure also exhibits π–π interactions between the furan and benzene rings of neighbouring molecules [centroid–centroid distance = 3.637 (2 Å, interplanar distance = 3.317 (2 Å and slippage = 1.492 (2 Å].

  6. Spin transport in benzofurane bithiophene based organic spin valves

    Directory of Open Access Journals (Sweden)

    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.

  7. 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.

  8. Identification of benzofuran central cores for the inhibition of leukotriene A(4) hydrolase.

    Science.gov (United States)

    Eccles, Wendy; Blevitt, Jonathan M; Booker, Jamila N; Chrovian, Christa C; Crawford, Shelby; de Leon, Aimee Rose; Deng, Xiaohu; Fourie, Anne M; Grice, Cheryl A; Herman, Krystal; Karlsson, Lars; Kearney, Aaron M; Lee-Dutra, Alice; Liang, Jimmy; Luna, Rosa; Pippel, Dan; Rao, Navin; Riley, Jason P; Santillán, Alejandro; Savall, Brad; Tanis, Virginia M; Xue, Xiaohua; Young, Arlene L

    2013-02-01

    Leukotrienes (LT's) are known to play a physiological role in inflammatory immune response. Leukotriene A(4) hydrolase (LTA(4)H) is a cystolic enzyme that stereospecifically catalyzes the transformation of LTA(4) to LTB(4). LTB(4) is a known pro-inflammatory mediator. This paper describes the identification and synthesis of substituted benzofurans as LTH(4)H inhibitors. The benzofuran series demonstrated reduced mouse and human whole blood LTB(4) levels in vitro and led to the identification one analog for advanced profiling. Benzofuran 28 showed dose responsive target engagement and provides a useful tool to explore a LTA(4)H inhibitor for the treatment of inflammatory diseases, such as asthma and inflammatory bowel disease (IBD).

  9. Isopropyl 2-(4,6-dimethyl-3-methylsulfinyl-1-benzofuran-2-ylacetate

    Directory of Open Access Journals (Sweden)

    Hong Dae Choi

    2008-11-01

    Full Text Available Molecules of title compound, C16H20O4S, which was synthesized by the oxidation of isopropyl 2-(4,6-dimethyl-3-methylsulfanyl-1-benzofuran-2-ylacetate, interact through C—H...π interactions between a methylene H atom and the aromatic carbon ring of the benzofuran ring system, and by C—H...O hydrogen bonds. Adjacent stacked molecules exhibit a carbonyl–carbonyl interaction [3.295 (2 Å]. The O atom of the methylsulfinyl group is disordered over two positions with site-occupancy factors of 0.9 and 0.1.

  10. Methyl 2-(5-bromo-3-methylsulfinyl-1-benzofuran-2-ylacetate

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    Uk Lee

    2008-12-01

    Full Text Available The title compound, C12H11BrO4S, was synthesized by the oxidation of methyl 2-(5-bromo-3-methylsulfanyl-1-benzofuran-2-ylacetate with 3-chloroperoxybenzoic acid. The O atom and the methyl group of the methylsulfinyl substituent lie on opposite sides of the plane of the benzofuran ring system. The crystal structure is stabilized by C—H...π interactions, involving a methyl H atom and the benzene ring of a neighbouring molecule, and by weak intermolecular C—H...O hydrogen bonds.

  11. (Z-3-(1-Benzofuran-2-yl-2-(3,4,5-trimethoxyphenylacrylonitrile

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    Sean Parkin

    2012-03-01

    Full Text Available In the title compound, C20H17NO4, the double bond of the acrylonitrile group separating the 1-benzofuran moiety from the 3,4,5-trimethoxyphenyl ring has Z geometry. The 1-benzofuran groups are π–π stacked with inversion-related counterparts such that the furan ring centroid–centroid distance is 3.804 (5 Å. The dihedral angle between the planes of the trimethoxyphenyl ring and the acrylonitrile group is 24.2 (2°.

  12. 2,5,7-Trimethyl-3-(4-methylphenylsulfonyl-1-benzofuran

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    Hong Dae Choi

    2012-06-01

    Full Text Available In the title compound, C18H18O3S, the 4-methylphenyl ring makes a dihedral angle of 86.35 (3° with the mean plane [mean deviation = 0.006 (1 Å] of the benzofuran fragment. In the crystal, molecules are linked by weak C—H...O and C—H...π interactions. The crystal structure also exhibits weak π–π interactions between the furan and benzene rings of neighbouring benzofuran systems [centroid–centroid distance = 3.685 (2, interplanar distance = 3.572 (2 and slippage = 0.906 (2 Å].

  13. Expeditious Synthesis of Natural Benzofuran, Eupomatenoid-6 by Umpolung of α-Aminophosphonates

    Energy Technology Data Exchange (ETDEWEB)

    Damodar, Kongara; Jun, Jong Gab [Hallym University, Chuncheon (Korea, Republic of)

    2014-09-15

    Simple and practical synthesis of natural benzofuran derivative eupomatenoid-6 via Horner-Emmons type condensation as the key step is described. The umpolung property of aldehyde derivative, α-aminophosphonate was efficiently employed in this reaction. α-Aminophosphonate of anisaldehyde subjected to Horner-Emmons type condensation with 5-bromo-2-methoxybenzaldehyde to yield the deoxybenzoin, which was further methylated and then underwent tandem demethylation-cyclodehydration to afford the benzofuran scaffold in excellent yield. Finally Suzuki coupling with propenyl boronic acid afforded eupomatenoid-6 with an overall yield of 56.8%.

  14. 1-(1-Benzofuran-2-yl-3-(4-chlorophenylprop-2-en-1-one

    Directory of Open Access Journals (Sweden)

    S. Jeyaseelan

    2010-02-01

    Full Text Available In the title compound, C17H11ClO2, the benzofuran ring system is almost planar (r.m.s. deviation = 0.011 Å and forms a dihedral angle of 10.53 (6° with the chlorophenyl ring. No significant intermolecular interactions are observed.

  15. 2-(5-Fluoro-3-isopropylsulfanyl-7-methyl-1-benzofuran-2-ylacetic acid

    Directory of Open Access Journals (Sweden)

    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.

  16. Controllable Rh(III)-Catalyzed Annulation between Salicylaldehydes and Diazo Compounds: Divergent Synthesis of Chromones and Benzofurans.

    Science.gov (United States)

    Sun, Peng; Gao, Shang; Yang, Chi; Guo, Songjin; Lin, Aijun; Yao, Hequan

    2016-12-16

    A Rh(III)-catalyzed annulation between salicylaldehydes and diazo compounds with controllable chemoselectivity is described. AgNTf2 favored benzofurans via a tandem C-H activation/decarbonylation/annulation process, while AcOH led to chromones through a C-H activation/annulation pathway. The reaction exhibited good functional group tolerance and scalability. Moreover, only a single regioisomer of benzofuran was obtained due to the in situ decarbonylation orientation effect.

  17. 2-(4-Fluorophenyl-5-iodo-7-methyl-3-methylsulfinyl-1-benzofuran

    Directory of Open Access Journals (Sweden)

    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].

  18. 3-(4-Fluorophenylsulfinyl-2,4,5,6-tetramethyl-1-benzofuran

    Directory of Open Access Journals (Sweden)

    Hong Dae Choi

    2014-07-01

    Full Text Available In the title compound, C18H17FO2S, the dihedral angle between the plane of the benzofuran ring system (r.m.s. deviation = 0.013 Å and that of the 4-fluorophenyl ring is 74.30 (5°. In the crystal, weak C—H...O and C—H...F hydrogen bonds link the molecules into columns extending in direction [100].

  19. Isopropyl 2-(5-bromo-3-methylsulfinyl-1-benzofuran-2-ylacetate

    Directory of Open Access Journals (Sweden)

    Uk Lee

    2008-12-01

    Full Text Available In the title compound, C14H15BrO4S, 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 C—H...π interactions between a methyl H atom and the benzene ring of a neighbouring molecule, and by weak intermolecular C—H...O hydrogen bonds.

  20. 5-Bromo-7-methyl-2-(4-methylphenyl-3-methylsulfinyl-1-benzofuran

    Directory of Open Access Journals (Sweden)

    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.

  1. 3-(4-Bromophenylsulfinyl-2,5,6-trimethyl-1-benzofuran

    Directory of Open Access Journals (Sweden)

    Uk Lee

    2013-08-01

    Full Text Available In the title compound, C17H15BrO2S, the dihedral angle between the mean plane [r.m.s. deviation = 0.003 (2 Å] of the benzofuran ring system and the mean plane [r.m.s. deviation = 0.006 (2 Å] of the 4-bromophenyl ring is 83.09 (7°. In the crystal, weak C—H...π interactions are observed.

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

    Directory of Open Access Journals (Sweden)

    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].

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

    Directory of Open Access Journals (Sweden)

    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.

  4. 3-(2-Fluorophenylsulfinyl-2,4,6-trimethyl-1-benzofuran

    Directory of Open Access Journals (Sweden)

    Hong Dae Choi

    2013-06-01

    Full Text Available In the title compound, C17H15FO2S, the 2-fluorophenyl ring makes a dihedral angle of 87.53 (5° with the mean plane [r.m.s. deviation = 0.013 (1 Å] of the benzofuran fragment. In the crystal, molecules are linked by weak C—H...F, C—H...O and C—H...π interactions, forming a three-dimensional network.

  5. 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.

  6. A new 1,2-ethanedione benzofurane derivative from Tephrosia purpurea.

    Science.gov (United States)

    Peng, Yan; Chen, Yinning; Gao, Chenghai; Yan, Tao; Cao, Wenhao; Huang, Riming

    2014-01-01

    A new 1,2-ethanedione benzofurane derivative, purpdione (1), was isolated from Tephrosia purpurea, together with seven known flavonoids, purpurenone (2), pongamol (3), ovalitenin A (4), karanjin (5), lanceolatin B (6), tachrosin (7) and villosinol (8). The new structure was elucidated based on the analysis of its spectroscopic data. The structures of the known compounds were identified by comparing their spectroscopic data with those reported in the literature. The isolates exhibited marginal ability to inhibit the settlement of barnacle (Balanus reticulatus).

  7. Synthesis and cytotoxic properties of halogen and aryl-/heteroarylpiperazinyl derivatives of benzofurans.

    Science.gov (United States)

    Krawiecka, Mariola; Kuran, Bozena; Kossakowski, Jerzy; Cieslak, Marcin; Kazmierczak-Baranska, Julia; Krolewska, Karolina; Nawrot, Barbara

    2015-01-01

    A series of seven derivatives of 1,1'-(5,6-dimethoxy-3-methyl-1-benzofuran-2,7-diyl)diethanone was synthesized and characterized by (1)HNMR and ESI MS spectra and elemental analyses. The obtained new compounds and three halogen derivatives of benzofuran, reported in our earlier work, were tested for their cytotoxic properties in human chronic (K562) and acute (HL60) leukemia cells, human cervical cancer (HeLa), and normal endothelial cells (HUVEC). Four compounds (2, 3, 4, 5), which contain halogens in their structure showed significant anticancer activity. The most promising was 1,1'-[3- (bromomethyl)-5,6-dimethoxy-1-benzofuran-2,7-diyl]diethanone (2), which was highly and selectively toxic for K562 cells (IC50 of 5µM) and HL60 cells (IC50 of 0.1µM), which showed no cytotoxicity toward HeLa and HUVEC cells. Moreover, the observed remarkable cytotoxicity of this compound toward K562 cells resulted from cells apoptosis.

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

    Science.gov (United States)

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

    2009-02-06

    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

  9. 3-(2-Oxo-2,3,4,5-tetrahydrofuran-3-yl-1-benzofuran-2-carbonitrile

    Directory of Open Access Journals (Sweden)

    Kensuke Okuda

    2012-09-01

    Full Text Available The asymmetric unit of the title compound, C13H9NO3, consists of two crystallographically independent molecules. In each molecule, the tetrahydrofuran (THF ring adopts an envelope conformation with one of the methylene C atoms positioned at the flap. The dihedral angles between the mean plane of the THF and the benzofuran ring system are 70.85 (5 and 89.59 (6°. In the crystal, molecules are stacked in a column along the a-axis direction through C—H...O hydrogen bonds, with columns further linked by C—H...N and C—H...O interactions.

  10. A New Benzofuran Derivative from Flemingia philippinensis Merr. et Rolfe

    Directory of Open Access Journals (Sweden)

    Hua Li

    2012-06-01

    Full Text Available A new prenylated benzofuran derivative, named flemiphilippinone A, was isolated together with ten known flavonoids from the roots of Flemingia philippinensis. Flemiphilippinone A was identified as (2S,3aS-5-(1-hydroxy-3-(4-methoxyphenyl- propylidene-2-(2-hydroxypropan-2-yl-3a,7-bis(3-methylbut-2-en-1-yltetrahydrobenzo- furan-4,6(2H,5H-dione, and its structure was established by a combination of HR EIMS, 1H-NMR, 13C-NMR, HMQC, HMBC and NOESY spectra data.

  11. 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].

  12. 5-Bromo-2,7-dimethyl-3-(3-methylphenylsulfonyl-1-benzofuran

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    Hong Dae Choi

    2014-05-01

    Full Text Available In the title compound, C17H15BrO3S, the dihedral angle between the mean planes of the benzofuran and 3-methylphenyl rings is 77.37 (5°. In the crystal, molecules are linked via pairs of Br...O [Br...O = 3.335 (2 Å] contacts into inversion dimers. These dimers are further linked by C—H...O hydrogen bonds and π–π interactions between the benzene and furan rings of neighbouring molecules [centroid–centroid separation = 3.884 (3 Å] into supramolecular chains running along the a-axis direction.

  13. 3-(4-Fluorophenylsulfinyl-2,4,6-trimethyl-1-benzofuran

    Directory of Open Access Journals (Sweden)

    Uk Lee

    2010-03-01

    Full Text Available In the title compound, C17H15FO2S, the O atom and the 4-fluorophenyl group of the 4-fluorophenylsulfinyl substituent lie on opposite sides of the plane of the benzofuran; the 4-fluorophenyl ring is almost perpendicular to this plane, making a dihedral angle of 88.99 (4°. The crystal structure exhibits intermolecular C—H...O hydrogen bonds and C—H...π interactions between the methyl H atom and the 4-fluorophenyl ring.

  14. 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.

  15. 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.

  16. 3-(3-Fluorophenylsulfinyl-2,4,6-trimethyl-1-benzofuran

    Directory of Open Access Journals (Sweden)

    Pil Ja Seo

    2011-11-01

    Full Text Available In the title compound, C17H15FO2S, the 3-fluorophenyl ring makes a dihedral angle of 78.38 (4° with the mean plane of the benzofuran fragment. In the crystal, molecules are linked by weak C—H...O and C—H...π interactions. The crystal structure also exhibits a slipped π–π interaction between the furan and benzene rings of neighbouring molecules [centroid–centroid distances = 3.628 (2 Å, interplanar distance = 3.417 (2 Å and slippage = 1.219 (2 Å].

  17. Propyl 2-(5-chloro-3-methylsulfinyl-1-benzofuran-2-ylacetate

    Directory of Open Access Journals (Sweden)

    2009-03-01

    Full Text Available In the title compound, C14H15ClO4S, 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 aromatic π–π interactions between the benzene rings of neighbouring molecules [centroid-to-centroid distance = 3.635 (3 Å], and by C—H...π interactions between a propyl methylene H atom and the furan ring of an adjacent molecule. In addition, the crystal structure exhibits weak intermolecular C—H...O hydrogen bonds.

  18. 5-Chloro-3-(4-fluorophenylsulfonyl-2,7-dimethyl-1-benzofuran

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    Hong Dae Choi

    2014-09-01

    Full Text Available In the title compound, C16H12ClFO3S, the dihedral angle between the plane of the benzofuran ring system [r.m.s. deviation = 0.007 (1 Å] and that of the 4-fluorophenyl ring is 76.11 (5°. In the crystal, molecules are linked into [010] chains via two different inversion-generated pairs of C—H...O hydrogen bonds. The crystal structure also exhibits weak π–π interactions between the benzene and furan rings of neighbouring molecules [centroid–centroid distance = 3.820 (2 Å].

  19. Ethyl 2-(5-fluoro-3-methylsulfinyl-1-benzofuran-2-ylacetate

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    Hong Dae Choi

    2009-08-01

    Full Text Available In the title compound, C13H13FO4S, the O atom and the methyl group of the methylsulfinyl substituent lie on opposite sides of the plane through the benzofuran fragment. The crystal structure exhibits four intermolecular non-classical C—H...O hydrogen bonds. In addition, the crystal structure contains aromatic π–π interactions between the furan and benzene rings of adjacent molecules [centroid–centroid distance = 3.743 (2 Å], and two intermolecular C—H...π interactions.

  20. The discovery of novel benzofuran-2-carboxylic acids as potent Pim-1 inhibitors.

    Science.gov (United States)

    Xiang, Yibin; Hirth, Bradford; Asmussen, Gary; Biemann, Hans-Peter; Bishop, Kimberly A; Good, Andrew; Fitzgerald, Maria; Gladysheva, Tatiana; Jain, Annuradha; Jancsics, Katherine; Liu, Jinyu; Metz, Markus; Papoulis, Andrew; Skerlj, Renato; Stepp, J David; Wei, Ronnie R

    2011-05-15

    Novel benzofuran-2-carboxylic acids, exemplified by 29, 38 and 39, have been discovered as potent Pim-1 inhibitors using fragment based screening followed by X-ray structure guided medicinal chemistry optimization. The compounds demonstrate potent inhibition against Pim-1 and Pim-2 in enzyme assays. Compound 29 has been tested in the Ambit 442 kinase panel and demonstrates good selectivity for the Pim kinase family. X-ray structures of the inhibitor/Pim-1 binding complex reveal important salt-bridge and hydrogen bond interactions mediated by the compound's carboxylic acid and amino groups.

  1. 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.

  2. Bioactive Benzofuran Derivatives from Cortex Mori Radicis, and Their Neuroprotective and Analgesic Activities Mediated by mGluR1

    Directory of Open Access Journals (Sweden)

    Ya-Nan Wang

    2017-02-01

    Full Text Available Four new benzofuran-type stilbene glycosides and 14 known compounds including 8 benzofuran-type stilbenes and 6 flavonoids were isolated from the traditional Chinese medicine, Cortex Mori Radicis. The new compounds were identified as (9R-moracin P 3′-O-α-l-arabinopyranoside (1, (9R-moracin P 9-O-β-d-glucopyranoside (2, (9R-moracin P 3′-O-β-d-glucopyranoside (3, and (9R-moracin O 10-O-β-d-glucopyranoside (4 based on the spectroscopic interpretation and chemical analysis. Three benzofuran-type stilbenes, moracin O (5, R (7, and P (8 showed significant neuroprotective activity against glutamate-induced cell death in SK-N-SH cells. In addition, moracin O (5 and P (8 also demonstrated a remarkable inhibition of the acetic acid-induced pain. The molecular docking with metabotropic glutamate receptor 1 (mGluR1 results indicated that these neuroprotective benzofuran-type stilbenes might be the active analgesic components of the genus Morus, and acted by mediating the mGluR1 pathway.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

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

    Directory of Open Access Journals (Sweden)

    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.

  6. Synthesis and photophysical properties of metallophthalocyanines substituted with a benzofuran based fluoroprobe.

    Science.gov (United States)

    Yarasir, Meryem N; Kandaz, Mehmet; Güney, Orhan; Salih, Bekir

    2012-07-01

    The synthesis, characterization and photophysical properties of the tetra- {6-(-benzofuran-2-carboxylate)-hexylthio} substituted copper(II), cobalt(II), manganese(III) and zinc (II) phthalocyanines, {M[Pc(β-S(CH(2))(6)OCOBz-Furan)(4)], which were derived from 6-(3,4-dicyanophenylthio)-hexyl-2-benzofuranate (BzF) (1-4) are reported for the first time. The new compounds have been synthesized and fully characterized by elemental analysis, FTIR, UV-vis, (1)H- and (13)C NMR, MS (Maldi-TOF). In this work, we also report the effects of peripherally bound BzF substituent on the photophysical properties of metallo phthalocyanine derivatives. The effects of changing the central metal ions on quantum yield are discussed. It was found that the substitution of BzF groups on the framework of phthalocyanines diminished the fluorescence quantum yield of these complexes depending on paramagnetic behavior of central metal atoms. In addition, central metal atoms like Co and Cu also caused to decrease in quantum yield of phthalocyanine backbone.

  7. Synthesis and Antimicrobial Activity of Furochromone, Benzofuran and Furocoumarin Derivatives Bearing Sulfonyl Moiety

    Directory of Open Access Journals (Sweden)

    Sadia A. Hessein

    2016-06-01

    Full Text Available New visnagin-9-sulfonamide derivatives 3 and 4a−c were synthesized through the reaction of visnagin-9-sulfonyl chloride 2 with amino compounds. Acetylation of compounds 4b and 4c gave the monoacetyl and diacetyl derivatives 5 and 6, respectively. Diazotization reaction of compound 4b afforded the corresponding benzotriazole derivative 8. Pyrazole and thiopyrimidine derivatives 9 and 10 were obtained via the opening of pyrone ring upon reaction of compound 3 with hydrazine hydrate and thiourea, respectively. In addition, hydrolysis of compound 3 with potassium hydroxide furnished the visnaginone derivative 11 which used as starting material for synthesize benzofuran derivatives 12−14 and bergaptene derivatives 15−17. The synthesized compounds were tested for antimicrobial activity. Furochromone derivatives 3, 4a−c, 5, 6 and 8 (visnagin-9-sulfonamide derivatives demonstrate moderate antibacterial and antifungal activities compared with the antibacterial and antifungal activites of the standard drugs. Benzofuran derivatives 11−14 (visnaginone derivatives showed the lowest antimicrobial activity among all the compounds investigated in this study. Furocoumarin derivatives 15a,b, 16 and 17 (furobenzopyransulfonamide [bergaptensulfonamides] are moderately active against all the tested strains. This work is licensed under a Creative Commons Attribution 4.0 International License.

  8. The cobalt-mediated [2+2+2]cycloaddition of thiophenes and benzofurans to alkynes

    Energy Technology Data Exchange (ETDEWEB)

    Malaska, M.J.

    1991-01-01

    The cobalt-mediated [2+2+2]cycloaddition of thiophenes and benzofurans to alkynes was investigated. The cocyclization of 2-propynyloxymethylthiophenes provided two types of cyclohexadiene complexes. It was found that one of these complexes could be converted to the other by a thermal rearrangement. This novel transformation was investigated by deuterium-labelling and kinetic studies, and a mechanism was proposed. The complexes could be oxidatively demetallated to provide the liberated organic framework. Further reorganization of these dienes were observed during the decomplexation process and in the presence of CpCo(C[sub 2]H[sub 4])[sub 2]. In this manner several new heterocyclic ring systems could be constructed from 2-substituted thiophenes. Following the success of the thiophene cyclizations, the cocyclization of the benzofuran nucleus was examined. Reagents and conditions were developed that provide an efficient synthesis of alkynols from carboxylic acids; other functional group interconversions of the alkynols were briefly studied. The synthesis and cyclization of 1-[7-methoxy-4-benzofuranyl]-3-butyn-2-ol produced a cobalt complex containing the A,B,C, and D rings of the morphine skeleton. A synthetic advantage of this methodology would be the ease of substitution at pharmaco-logically relevant C-6 and C-7 positions of the morphine framework. Synthetic routes using a cobalt cyclization strategy were proposed.

  9. Synthesis and photophysical properties of metallophthalocyanines substituted with a benzofuran based fluoroprobe

    Science.gov (United States)

    Yarasir, Meryem N.; Kandaz, Mehmet; Güney, Orhan; Salih, Bekir

    The synthesis, characterization and photophysical properties of the tetra- {6-(-benzofuran-2-carboxylate)-hexylthio} substituted copper(II), cobalt(II), manganese(III) and zinc (II) phthalocyanines, {M[Pc(β-S(CH2)6OCOBz-Furan)4], which were derived from 6-(3,4-dicyanophenylthio)-hexyl-2-benzofuranate (BzF) (1-4) are reported for the first time. The new compounds have been synthesized and fully characterized by elemental analysis, FTIR, UV-vis, 1H- and 13C NMR, MS (Maldi-TOF). In this work, we also report the effects of peripherally bound BzF substituent on the photophysical properties of metallo phthalocyanine derivatives. The effects of changing the central metal ions on quantum yield are discussed. It was found that the substitution of BzF groups on the framework of phthalocyanines diminished the fluorescence quantum yield of these complexes depending on paramagnetic behavior of central metal atoms. In addition, central metal atoms like Co and Cu also caused to decrease in quantum yield of phthalocyanine backbone.

  10. Crystal structure of 5-chloro-2,7-dimethyl-3-[(4-methylphenylsulfonyl]-1-benzofuran

    Directory of Open Access Journals (Sweden)

    Hong Dae Choi

    2014-09-01

    Full Text Available In the title compound, C17H15ClO3S, the dihedral angle between the planes of the benzofuran ring system [r.m.s. deviation = 0.008 Å] and the 4-methylphenyl ring is 77.29 (4°. In the crystal, molecules are linked by π–π interactions between the benzene rings of neighbouring molecules [centroid–centroid distance = 3.847 (2 Å] and between the benzene and furan rings of neighbouring molecules [centroid–centroid distance = 3.743 (2 Å]. The molecules are stacked along the a-axis direction. In addition, pairs of C—H...O hydrogen bonds are observed between inversion-related dimers: these generate R22(12 loops.

  11. 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].

  12. 2-(5-Bromo-3-isopropylsulfanyl-1-benzofuran-2-ylacetic acid

    Directory of Open Access Journals (Sweden)

    Pil Ja Seo

    2012-01-01

    Full Text Available The title compound, C13H13BrO3S, was prepared by alkaline hydrolysis of ethyl 2-(5-bromo-3-isopropylsulfanyl-1-benzofuran-2-ylacetate. In the crystal, the carboxyl groups are involved in intermolecular O—H...O hydrogen bonds, which link the molecules into dimers. These dimers are further packed into stacks along the c axis by intermolecular C—H...π interactions, and by slipped π–π interactions between the furan rings of adjacent molecules [centroid–centroid distance = 3.472 (2 Å, interplanar distance = 3.398 (2 Å and slippage = 0.713 (2 Å].

  13. 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].

  14. Ethyl 2-(5-bromo-3-ethylsulfinyl-1-benzofuran-2-ylacetate

    Directory of Open Access Journals (Sweden)

    Hong Dae Choi

    2009-04-01

    Full Text Available The title compound, C14H15BrO4S, was prepared by the oxidation of ethyl 2-(5-bromo-3-ethylsulfanyl-1-benzofuran-2-ylacetate with 3-chloroperoxybenzoic acid. The crystal structure is stabilized by aromatic π–π interactions between the benzene rings of neighbouring molecules [centroid–centroid distance = 3.814 (9 Å], and possibly by weak C—H...π interactions. In addition, the crystal structure exhibits three intermolecular C—H...O non-classical hydrogen bonds. The ethyl group bonded to carboxylate O atom is disordered over two positions, with refined site-occupancy factors of 0.686 (18 and 0.314 (18.

  15. Crystal structure of 2-ethyl-3-(4-fluorophenylsulfonyl-5,7-dimethyl-1-benzofuran

    Directory of Open Access Journals (Sweden)

    Hong Dae Choi

    2014-10-01

    Full Text Available In the title compound, C18H17FO3S, the dihedral angle between the plane of the benzofuran ring [r.m.s. deviation = 0.006 (1 Å] and that of the 4-fluorophenyl ring [r.m.s. deviation = 0.004 (1 Å] is 82.45 (4°. In the crystal, molecules are linked via three different pairs of C—H...O hydrogen bonds, forming chains along [001] and enclosing two R22(10 and one R22(12 ring motifs. The chains are further linked by π–π interactions [inter-centroid distance = 3.566 (1 Å] between the furan rings of inversion-related molecules, forming a two-dimensional network lying parallel to (100.

  16. 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.

  17. Synthesis and characterization of selected methyl 5-methoxy-2-methyl-1-benzofuran-3-carboxylate derivatives with potential antimicrobial activity.

    Science.gov (United States)

    Krawiecka, Mariola; Kuran, Bozena; Kossakowski, Jerzy; Wolska, Irena; Kierzkowska, Marta; Młynarczyk, Grazyna

    2012-01-01

    Halogen and aminoalkyl derivatives of methyl 5-methoxy-2-methyl-1-benzofuran-3-carboxylate were prepared using 5-hydroxy-2-methyl-3-benzofuranocarboxylic acid as starting material. (1)H-NMR spectra were obtained for all of the synthesized structures, and for compounds 1 and 2 X-ray crystal structures were obtained too. All derivatives were tested for antimicrobial activity against a selection of Gram-positive cocci, Gram-negative rods and yeasts.

  18. Synthesis of indoles, benzofurans, and related heterocycles via an acetylene-activated SNAr/intramolecular cyclization cascade sequence in water or DMSO.

    Science.gov (United States)

    Hudson, R; Bizier, N P; Esdale, K N; Katz, J L

    2015-02-28

    The synthesis of 2-substituted indoles and benzofurans was achieved by nucleophilic aromatic substitution, followed by subsequent 5-endo-dig cyclization between the nucleophile and an ortho acetylene. The acetylene serves the dual role of the electron withdrawing group to activate the substrate for SNAr, and the C1-C2 carbon scaffold for the newly formed 5-membered heteroaromatic ring. This method allows for the bond forming sequence of Ar-X-N/O-C1 to proceed in a single synthetic step, furnishing indoles and benzofurans in moderate to high yields. Since the method is not transition metal mediated, brominated and chlorinated substrates are tolerated, and benzofuran formation can be conducted using water or water-DMSO mixtures as solvent.

  19. A (68)Ga complex based on benzofuran scaffold for the detection of β-amyloid plaques.

    Science.gov (United States)

    Watanabe, Hiroyuki; Ono, Masahiro; Iikuni, Shimpei; Yoshimura, Masashi; Matsumura, Kenji; Kimura, Hiroyuki; Saji, Hideo

    2014-10-15

    Since the imaging of β-amyloid (Aβ) plaques in the brain is believed to be a useful tool for the early diagnosis of Alzheimer's disease (AD), a number of imaging probes to detect Aβ plaques have been developed. Because the radionuclide (68)Ga (t1/2=68 min) for PET imaging could become an attractive alternative to (11)C and (18)F, we designed and synthesized a benzofuran derivative conjugated with a (68)Ga complex ((68)Ga-DOTA-C3-BF) as a novel Aβ imaging probe. In an in vitro binding assay, Ga-DOTA-C3-BF showed high affinity for Aβ(1-42) aggregates (Ki=10.8 nM). The Ga-DOTA-C3-BF clearly stained Aβ plaques in a section of Tg2576 mouse, reflecting the affinity for Aβ(1-42) aggregates in vitro. In a biodistribution study in normal mice, (68)Ga-DOTA-C3-BF displayed low initial uptake (0.45% ID/g) in the brain at 2 min post-injection. While improvement of the brain uptake of (68)Ga complexes appears to be essential, these results suggest that novel PET imaging probes that include (68)Ga as the radionuclide for PET may be feasible.

  20. 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.

  1. Activation of a Carbon-Oxygen Bond of Benzofuran by Precoordination of Manganese to the Carbocyclic Ring: A Model for Hydrodeoxygenation.

    Science.gov (United States)

    Zhang; Watson; Dullaghan; Gorun; Sweigart

    1999-08-01

    Stable unsaturated heterocycles such as benzofuran are difficult to remove from petroleum by conventional catalytic hydrotreating. However, in a model system, coordination of Mn(CO)(3)(+) to the aromatic ring of benzofuran activates the C-O bond towards insertion of [Pt(PPh(3))(2)] [Eq. (1)]. The insertion is preceded by precoordination to the furan C=C bond; thus, the 2,3-dihydro analogue of 1, which lacks this double bond, does not undergo insertion of the Pt moiety.

  2. Isolation and structure determination of a benzofuran and a bis-nor-isoprenoid from Aspergillus niger grown on the water soluble fraction of Morinda citrifolia Linn. leaves.

    Science.gov (United States)

    Siddiqui, Bina S; Ismail, Fouzia A Sattar; Gulzar, Tahsin; Begum, Sabira

    2003-10-01

    The leaves of Morinda citrifolia, Linn. afforded a new benzofuran and a bis-nor-isoprenoid, blumenol C, hitherto unreported from this source. The structures of these have been elucidated as 5-benzofuran carboxylic acid-6-formyl methyl ester (1) and 4-(3'(R)-hydroxybutyl)-3,5,5, trimethyl-cyclohex-2-en-1-one (2) respectively through spectroscopic studies. The NMR data (including 1D, 2D techniques) and stereochemistry at C-3' of Compound 2 is also being reported for the first time.

  3. 2-(2-Hydroxypropan-2-yl-6-(prop-2-ynyloxy-1-benzofuran-3(2H-one

    Directory of Open Access Journals (Sweden)

    Henok H. Kinfe

    2012-12-01

    Full Text Available In the title compound, C14H14O4, the prop-2-ynyloxy O—C—C[triple-bond]C plane [maximum deviation = 0.0116 (12 Å] forms a dihedral angle of 78.44 (9° with the benzofuran-3(2H-one ring system. In the crystal, molecules are linked by O—H...O hydrogen bonds, forming a tape along the a-axis direction. C—H...O interactions are observed between the tapes.

  4. 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.

  5. A Quantitative Method for the Measurement of Three Benzofuran Ketones in Rayless Goldenrod (Isocoma pluriflora) and White Snakeroot (Ageratine altissima) by HPLC

    Science.gov (United States)

    White snakeroot (Ageratina altissima) and rayless goldenrod (Isocoma pluriflora) can cause “trembles” and “milk sickness” in livestock and humans, respectively. Tremetol, a complex mixture of sterols and derivatives of methyl ketone benzofuran has been extracted from white snakeroot and rayless gol...

  6. 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).

  7. Benzofuran-chalcone hybrids as potential multifunctional agents against Alzheimer's disease: synthesis and in vivo studies with transgenic Caenorhabditis elegans.

    Science.gov (United States)

    Sashidhara, Koneni V; Modukuri, Ram K; Jadiya, Pooja; Dodda, Ranga Prasad; Kumar, Manoj; Sridhar, Balasubramaniam; Kumar, Vikash; Haque, Rizwanul; Siddiqi, Mohammad Imran; Nazir, Aamir

    2014-12-01

    In the search for effective multifunctional agents for the treatment of Alzheimer's disease (AD), a series of novel hybrids incorporating benzofuran and chalcone fragments were designed and synthesized. These hybrids were screened by using a transgenic Caenorhabditis elegans model that expresses the human β-amyloid (Aβ) peptide. Among the hybrids investigated, (E)-3-(7-methyl-2-(4-methylbenzoyl)benzofuran-5-yl)-1-phenylprop-2-en-1-one (4 f), (E)-3-(2-benzoyl-7-methylbenzofuran-5-yl)-1-phenylprop-2-en-1-one (4 i), and (E)-3-(2-benzoyl-7-methylbenzofuran-5-yl)-1-(thiophen-2-yl)prop-2-en-1-one (4 m) significantly decreased Aβ aggregation and increased acetylcholine (ACh) levels along with the overall availability of ACh at the synaptic junction. These compounds were also found to decrease acetylcholinesterase (AChE) levels, reduce oxidative stress in the worms, lower lipid content, and to provide protection against chemically induced cholinergic neurodegeneration. Overall, the multifunctional effects of these hybrids qualify them as potential drug leads for further development in AD therapy.

  8. Discovery of benzofuran propanoic acid GPR120 agonists: From uHTS hit to mechanism-based pharmacodynamic effects.

    Science.gov (United States)

    Lombardo, Matthew; Bender, Kate; London, Clare; Kirkland, Melissa; Mane, Joel; Pachanski, Michele; Geissler, Wayne; Cummings, John; Habulihaz, Bahanu; Akiyama, Taro E; Di Salvo, Jerry; Madeira, Maria; Pols, Joanna; Powles, Mary Ann; Finley, Michael F; Johnson, Eric; Roussel, Thomas; Uebele, Victor N; Crespo, Alejandro; Leung, Dennis; Alleyne, Candice; Trusca, Dorina; Lei, Ying; Howard, Andrew D; Ujjainwalla, Feroze; Tata, James R; Sinz, Christopher J

    2016-12-01

    The transformation of an aryloxybutanoic acid ultra high-throughput screening (uHTS) hit into a potent and selective series of G-protein coupled receptor 120 (GPR120) agonists is reported. uHTS hit 1 demonstrated an excellent rodent pharmacokinetic profile and selectivity over the related fatty acid receptor GPR40, but only modest GPR120 potency. Optimization of the "left-hand" aryl group led to compound 6, which demonstrated a GPR120 mechanism-based pharmacodynamic effect in a mouse oral glucose tolerance test (oGTT). Further optimization gave rise to the benzofuran propanoic acid series (exemplified by compound 37), which demonstrated acute mechanism-based pharmacodynamic effects. The combination of in vivo efficacy and attractive rodent pharmacodynamic profiles suggests compounds generated from this series may afford attractive candidates for the treatment of Type 2 diabetes.

  9. The isolation and synthesis of a novel benzofuran compound from Tephrosia purpurea, and the synthesis of several related derivatives, which suppress histamine H1 receptor gene expression.

    Science.gov (United States)

    Shill, Manik Chandra; Das, Asish Kumar; Itou, Tomohiro; Karmakar, Sanmoy; Mukherjee, Pulok K; Mizuguchi, Hiroyuki; Kashiwada, Yoshiki; Fukui, Hiroyuki; Nemoto, Hisao

    2015-11-01

    A novel naturally occurring compound with a benzofuran skeleton was isolated from a plant, Tephrosia purpurea collected in Bangladesh. The chemical synthesis of this compound confirmed its structure, and preliminary biological results showed its suppressive activity towards histamine H1 gene expression. One isomer and four derivatives were also synthesized, and their suppression activity was investigated. Although only small quantities of this compound can be isolated from its natural source, a 10 g scale synthesis was demonstrated by the newly developed method.

  10. 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.

  11. Development of (99m)Tc-Labeled Pyridyl Benzofuran Derivatives To Detect Pancreatic Amylin in Islet Amyloid Model Mice.

    Science.gov (United States)

    Yoshimura, Masashi; Ono, Masahiro; Watanabe, Hiroyuki; Kimura, Hiroyuki; Saji, Hideo

    2016-06-15

    While islet amyloid deposition comprising amylin is one of pathological hallmarks of type 2 diabetes mellitus (T2DM), no useful amylin-imaging probe has been reported. In this study, we evaluated two (99m)Tc-labeled pyridyl benzofuran derivatives as novel amylin-imaging probes using the newly established islet amyloid model mouse. Binding experiments in vitro demonstrated that [(99m)Tc]1 displayed a higher affinity for amylin aggregates than [(99m)Tc]2. Autoradiographic studies using human pancreas sections with T2DM revealed that [(99m)Tc]1 clearly labeled islet amyloid in T2DM pancreatic sections, while [(99m)Tc]2 did not. Although the initial uptake of [(99m)Tc]1 by the normal mouse pancreas was low (0.74%ID/g at 2 min post-injection), [(99m)Tc]1 showed higher retention in the model mouse pancreas than that of the normal mouse, and exhibited strong binding to amylin aggregates in the living pancreas of the model mice. These results suggest that [(99m)Tc]1 is a potential imaging probe targeting islet amyloids in the T2DM pancreas.

  12. 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.

  13. 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.

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

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    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.

  15. 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.

  16. 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

  17. 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.

  18. 2,3-Dihydro-1-benzofuran-5-ols as analogues of alpha-tocopherol that inhibit in vitro and ex vivo lipid autoxidation and protect mice against central nervous system trauma.

    Science.gov (United States)

    Grisar, J M; Bolkenius, F N; Petty, M A; Verne, J

    1995-02-03

    A series of alpha-tocopherol analogues was synthesized with potential therapeutic value for such pathological conditions as stroke and trauma. A set of criteria such as the inhibition of in vitro lipid peroxidation, superoxyl radical scavenging, and brain penetration, as measured by ex vivo inhibition of lipid peroxidation, was applied to select the most effective compound. 2,3-Dihydro-2,2,4,6,7-pentamethyl-3-[(4-methylpiperazino)methyl]-1 - benzofuran-5-ol dihydrochloride (22) was selected because of its superior antioxidant properties and better brain penetration. This compound also protected mice against the effects of head injury. The criteria thus turned out to be useful for the characterization of a neuroprotective analogue of alpha-tocopherol.

  19. Discovery of a benzofuran derivative (MBPTA) as a novel ROCK inhibitor that protects against MPP⁺-induced oxidative stress and cell death in SH-SY5Y cells.

    Science.gov (United States)

    Chong, Cheong-Meng; Shen, Mingyun; Zhou, Zhong-Yan; Pan, Peichen; Hoi, Pui-Man; Li, Shang; Liang, Wang; Ai, Nana; Zhang, Lun-Qing; Li, Cheuk-Wing; Yu, Huidong; Hou, Tingjun; Lee, Simon Ming-Yuen

    2014-09-01

    Parkinson disease (PD) is a neurodegenerative disease with multifactorial etiopathogenesis. The discovery of drug candidates that act on new targets of PD is required to address the varied pathological aspects and modify the disease process. In this study, a small compound, 2-(5-methyl-1-benzofuran-3-yl)-N-(5-propylsulfanyl-1,3,4-thiadiazol-2-yl) acetamide (MBPTA) was identified as a novel Rho-associated protein kinase inhibitor with significant protective effects against 1-methyl-4-phenylpyridinium ion (MPP(+))-induced damage in SH-SY5Y neuroblastoma cells. Further investigation showed that pretreatment of SH-SY5Y cells with MBPTA significantly suppressed MPP(+)-induced cell death by restoring abnormal changes in nuclear morphology, mitochondrial membrane potential, and numerous apoptotic regulators. MBPTA was able to inhibit MPP(+)-induced reactive oxygen species (ROS)/NO generation, overexpression of inducible NO synthase, and activation of NF-κB, indicating the critical role of MBPTA in regulating ROS/NO-mediated cell death. Furthermore, MBPTA was shown to activate PI3K/Akt survival signaling, and its cytoprotective effect was abolished by PI3K and Akt inhibitors. The structural comparison of a series of MBPTA analogs revealed that the benzofuran moiety probably plays a crucial role in the anti-oxidative stress action. Taken together, these results suggest that MBPTA protects against MPP(+)-induced apoptosis in a neuronal cell line through inhibition of ROS/NO generation and activation of PI3K/Akt signaling.

  20. 4-(2-[2-(2(R)-methylpyrrolidin-1-yl)ethyl]benzofuran-5-yl)benzonitrile and related 2-aminoethylbenzofuran H3 receptor antagonists potently enhance cognition and attention.

    Science.gov (United States)

    Cowart, Marlon; Faghih, Ramin; Curtis, Michael P; Gfesser, Gregory A; Bennani, Youssef L; Black, Lawrence A; Pan, Liping; Marsh, Kennan C; Sullivan, James P; Esbenshade, Timothy A; Fox, Gerard B; Hancock, Arthur A

    2005-01-13

    H(3) receptor antagonists based on a 2-aminoethylbenzofuran skeleton have been discovered, which are potent in vitro at human and rat H(3) receptors, with K(i) values of 0.1-5.8 nM. Analogues were discovered with potent (0.01-1 mg/kg) cognition and attention enhancing properties in animal models. One compound in particular, 4-(2-[2-(2(R)-methylpyrrolidin-1-yl)ethyl]benzofuran-5-yl)benzonitrile (ABT-239), combined potent and selective H(3) receptor antagonism and excellent pharmacokinetic and metabolic properties across species, with full efficacy in two behavioral models: a five-trial inhibitory avoidance acquisition model in rat pups at 0.1 mg/kg and a social recognition memory model in adult rats at 0.01 mg/kg. Furthermore, this compound did not stimulate locomotor activity and showed high selectivity for the induction of behavioral efficacy versus central nervous system based side effects. The potency and selectivity of this compound and of analogues from this class support the potential of H(3) receptor antagonists for the treatment of cognitive dysfunction.

  1. Study of New Analytical Methodologies for the Analysis of Polychlorinated Dibenzo-P-Dioxins (PCDDs) and Polychlorinated Di benzofurans (PCDFs) by Quadrupole Ion Storage Tandem-in-time Mass Spectrometry. Application to Environmental Samples; Estudio de nuevas metodologias analiticas en la determinacion de policlorodibenzo-P-dioxinas (PCDDs) y policlosrodibenzofuranos (PCDFs) por espectrometria de masas con trampa ionica. Aplicacion a muestras medioambientales

    Energy Technology Data Exchange (ETDEWEB)

    Sanz Chichon, M. P.

    2008-07-01

    Two alternative analytical methodologies have been developed for the analysis of polychlorinated dibenzo-p-dioxins (PCDDs) and di benzofurans (PCDFs) in environmental samples. The techniques studied have been: Pressurized Fluid Extraction (PFE) and Microwave-Assisted Extraction (MAE) versus Soxhlet extraction; the automated system Power-PrepTM versus the conventional cleanup using open chromatographic columns with different adsorbents and the application of tandem mass spectrometry (HRGC-MS/MS) versus high resolution mass spectrometry (HRGC-HRMS) for PCDD/Fs detection and quantification. (Author) 233 refs.

  2. 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.

  3. 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.

  4. Synthesis of a novel 5a,10a-dihydroxy-5aH-[1,3]dioxolo[4,5-f] indeno[1,2-b]benzofuran-10(10aH)-one their XRD, FTIR, NMR and DFT studies

    Science.gov (United States)

    Aggarwal, Komal; Khurana, Jitender M.

    2017-02-01

    A novel compound 5a,10a-dihydroxy-5aH-[1,3]dioxolo[4,5-f]indeno[1,2-b]benzofuran-10 (10aH)-one (1) was synthesized and its structure has been characterized by X-ray crystallography, FTIR and NMR studies. X-ray studies revealed the presence of π-π stacking and intermolecular hydrogen bonding interactions which stabilises the molecular lattice. A detailed interpretation of vibrational spectra has been carried out on the basis of peak positions and relative intensities. The optimized molecular geometry, vibrational frequencies and NMR analysis of the compound in the ground state have also been calculated by the density function theory method (DFT) with 6-311G (d,p) basis set. All the theoretically obtained data has been compared with experimental data and it shows good agreement. TDDFT calculations were used to compare the experimental and theoretical absorption spectra. The calculated HOMO and LUMO energies show that charge transfer occurs within the molecule. In addition, the molecular electrostatic potential (MEP) analysis of the title molecule has been investigated using theoretical calculations.

  5. Thermochemical Properties, ΔfH°(298.15 K), S°(298.15 K), and Cp°(T), of 1,4-Dioxin, 2,3-Benzodioxin, Furan, 2,3-Benzofuran, and Twelve Monochloro and Dichloro Dibenzo-p-dioxins and Dibenzofurans

    Science.gov (United States)

    Zhu, Li; Bozzelli, Joeseph W.

    2003-12-01

    Values for ΔfH°(298.15 K), S°(298.15 K), and Cp°(T) (5⩽T/K⩽6000) are computed by density functional B3LYP/6-31G(d,p) and B3LYP/6-311+G(3df,2p) calculation methods for 12 monochloro and dichloro dibenzo-p-dioxins and dibenzofurans: 1-chloro dibenzo-p-dioxin, 2-chloro dibenzo-p-dioxin, 1,6-dichloro dibenzo-p-dioxin, 1,8-dichloro dibenzo-p-dioxin, 1,9-dichloro dibenzo-p-dioxin, 2,8-dichloro dibenzo-p-dioxin, 3-chloro dibenzofuran, 4-chloro dibenzofuran, 1,6-dichloro dibenzofuran, 3,6-dichloro dibenzofuran, 3,7-dichloro dibenzofuran, and 4,6-dichloro dibenzofuran. Molecular structures and vibration frequencies are determined at the B3LYP/6-31G(d,p) level of theory. Isodesmic reactions are utilized at each calculation level to determine the enthalpy of formation of each species. Contributions to the entropy and the heat capacity from translation, vibration, and external rotations are calculated using the rigid-rotor-harmonic-oscillator approximation based on the B3LYP/6-31G(d,p) structures. The enthalpies of formation for 1,4-dioxin, furan, 2,3-benzodioxin, 2,3-benzofuran, dibenzo-p-dioxin, and dibenzofuran are also calculated. Thermochemical properties of two composite central atom groups and four interaction groups are derived for use in a group additivity scheme to calculate these thermochemical properties of polychlorinated dibenzo-p-dioxins and dibenzofurans.

  6. 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].

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

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    Hong Dae Choi

    2011-04-01

    Full Text Available There are two independent molecules in the asymmetric unit of the title compound, C15H17ClO2S, in each of which the cyclohexyl rings adopt chair conformations. In the crystal, molecules are linked by weak intermolecular C—H...O hydrogen bonds.

  8. 5-Cyclohexyl-2-(4-methylphenyl-3-methylsulfinyl-1-benzofuran

    Directory of Open Access Journals (Sweden)

    Hong Dae Choi

    2012-10-01

    Full Text Available In the title compound, C22H24O2S, the cyclohexyl ring adopts a chair conformation. In the crystal, molecules are linked by weak C—H...O and C—H...π interactions. In the methylsulfinyl group, the methyl group and S atom are disordered over two sets of sites, with site-occupancy factors of 0.58 (3 and 0.42 (3. In the ring of the 4-methylphenyl group, the four C atoms are disordered over two sets of sites, with site-occupancy factors of 0.858 (5 and 0.142 (5.

  9. 5-Bromo-3-cyclohexylsulfonyl-2-methyl-1-benzofuran

    Directory of Open Access Journals (Sweden)

    Hong Dae Choi

    2011-03-01

    Full Text Available In the title compound, C15H17BrO3S, the cyclohexyl ring adopts a practically undistorted chair conformation [endocyclic torsion angles are within a 54.5–56.4 (3° range] and the arylsulfonyl unit is positioned equatorial relative to the cyclohexyl group. In the crystal, molecules are linked through C—H...O hydrogen bonds and donor–acceptor Br...O contacts [3.250 (2 Å]. The crystal structure also exhibits aromatic π–π overlap between the benzene and furan rings of neighbouring molecules [centroid–centroid distance = 3.635 (2 Å].

  10. 1-(5-Bromo-1-benzofuran-2-ylethanone

    Directory of Open Access Journals (Sweden)

    Hoong-Kun Fun

    2012-06-01

    Full Text Available The title compound, C10H7BrO2, is approximately planar (r.m.s. deviation = 0.057 Å for the 13 non-H atoms. In the crystal, molecules are linked via C—H...O hydrogen bonds into C(5 chains propagating in [100].

  11. 5-Bromo-3-cyclopentylsulfinyl-2,7-dimethyl-1-benzofuran

    Directory of Open Access Journals (Sweden)

    Hong Dae Choi

    2012-02-01

    Full Text Available In the title compound, C15H17BrO2S, the cyclopentyl ring adopts an envelope conformation. In the crystal, molecules are linked by weak C—H...O hydrogen bonds. A slipped π–π interaction occurs between the furan and benzene rings of adjacent molecules [centroid–centroid distance = 3.892 (3 Å and slippage = 1.786 (3 Å]. The crystal structure also exhibits a weak C—Br...π [2.919 (3 Å] interaction.

  12. 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

  13. 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.

  14. 2-(2,2-Dimethyl-2,3-dihydro-1-benzofuran-7-yloxyacetic acid monohydrate

    Directory of Open Access Journals (Sweden)

    Lin-Tao Yang

    2010-06-01

    Full Text Available In the title compound, C12H14O4·H2O, the dihydrobenzofuran ring adopts an envelope conformation with the substituted C atom 0.142 (1 Å out of the least-squares plane. In the crystal, the components are linked via intermolecular Owater—H...O and O—H...Owater hydrogen-bonding interactions, forming a three-dimensional network.

  15. Ethyl 2-(5-cyclohexyl-3-methylsulfinyl-1-benzofuran-2-ylacetate

    Directory of Open Access Journals (Sweden)

    Pil Ja Seo

    2011-08-01

    Full Text Available In the title compound, C19H24O4S, the cyclohexyl ring adopts a chair conformation. In the crystal, molecules are linked by weak intermolecular C—H...O hydrogen bonds. The O atom of the sulfinyl group is disordered over two orientations with site-occupancy factors of 0.875 (4 and 0.125 (4.

  16. 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.

  17. 2,2-Dimethyl-2,3-dihydro-1-benzofuran-7-yl N-ethylcarbamate

    OpenAIRE

    2009-01-01

    The title compound, C13H17NO3, crystallizes with two independent molecules in the asymmetric unit. In the crystal, N—H...O hydrogen bonds link the molecules, forming chains propagaiting in [100]. A weak C—H...O interaction also occurs.

  18. Synthesis of a Functionalized Benzofuran as a Synthon for Salvianolic Acid C Analogues as Potential LDL Antioxidants

    Directory of Open Access Journals (Sweden)

    Gabriela López-Frías

    2015-05-01

    Full Text Available A palladium mediated synthesis of a common synthon for the syntheses of antioxidant analogues of naturally occurring salvianolic acids is presented. The synthetic route may be used to obtain analogues with a balanced lipophilicity/hydrophilicity which may result in potentially interesting LDL antioxidants for the prevention of cardiovascular diseases.

  19. 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.

  20. Molecular mechanism of hepatitis C virus replicon variants with reduced susceptibility to a benzofuran inhibitor, HCV-796.

    Science.gov (United States)

    Howe, Anita Y M; Cheng, Huiming; Johann, Stephen; Mullen, Stanley; Chunduru, Srinivas K; Young, Dorothy C; Bard, Joel; Chopra, Rajiv; Krishnamurthy, Girija; Mansour, Tarek; O'Connell, John

    2008-09-01

    HCV-796 selectively inhibits hepatitis C virus (HCV) NS5B RNA-dependent RNA polymerase. In hepatoma cells containing a genotype 1b HCV replicon, HCV-796 reduced HCV RNA levels by 3 to 4 log(10) HCV copies/mug total RNA (the concentration of the compound that inhibited 50% of the HCV RNA level was 9 nM). Cells bearing replicon variants with reduced susceptibility to HCV-796 were generated in the presence of HCV-796, followed by G418 selection. Sequence analysis of the NS5B gene derived from the replicon variants revealed several amino acid changes within 5 A of the drug-binding pocket. Specifically, mutations were observed at Leu314, Cys316, Ile363, Ser365, and Met414 of NS5B, which directly interact with HCV-796. The impacts of the amino acid substitutions on viral fitness and drug susceptibility were examined in recombinant replicons and NS5B enzymes with the single-amino-acid mutations. The replicon variants were 10- to 1,000-fold less efficient in forming colonies in cells than the wild-type replicon; the S365L variant failed to establish a stable cell line. Other variants (L314F, I363V, and M414V) had four- to ninefold-lower steady-state HCV RNA levels. Reduced binding affinity with HCV-796 was demonstrated in an enzyme harboring the C316Y mutation. The effects of these resistance mutations were structurally rationalized using X-ray crystallography data. While different levels of resistance to HCV-796 were observed in the replicon and enzyme variants, these variants retained their susceptibilities to pegylated interferon, ribavirin, and other HCV-specific inhibitors. The combined virological, biochemical, biophysical, and structural approaches revealed the mechanism of resistance in the variants selected by the potent polymerase inhibitor HCV-796.

  1. Synthesis and in vivo evaluation of a new fluorine-19 labeled dopamine D2 radioligand with benzofuran benzamide skeleton

    Energy Technology Data Exchange (ETDEWEB)

    Takao, Futoshi; Sasaki, Shigeki; Maeda, Minoru (Kyushu Univ., Fukuoka (Japan). Faculty of Pharmaceutical Sciences); Fukumura, Toshimitsu; Tahara, Takashi; Masuda, Kouji; Ichiya, Yuichi (Kyushu Univ., Fukuoka (Japan). Faculty of Medicine)

    1993-12-01

    N-[(1-Ethyl-2-pyrrolidinyl)methyl]-5-(2-[[sup 18]F]fluorethyl)-2,3 -dihydrobenzofuran-7-carboxamide ([[sup 18]F]5) was synthesized via nucleophilic substitution with K[sup 18]F/Kryptofix222 complex in 5.4[approx]6.8% radiochemical yields with a specific activity of larger than 5.6 TBq/mmol (150 Ci/mmol) at the end of the 110 minutes synthetic period. Its in vivo affinity toward CNS dopamine D2 receptors was investigated using rats in order to evaluate as a radiotracer for the PET (positron emission tomography) study of the dopamine D2 receptors. (Author).

  2. Synthesis of a Functionalized Benzofuran as a Synthon for Salvianolic Acid C Analogues as Potential LDL Antioxidants.

    Science.gov (United States)

    López-Frías, Gabriela; Camacho-Dávila, Alejandro A; Chávez-Flores, David; Zaragoza-Galán, Gerardo; Ramos-Sánchez, Víctor H

    2015-05-14

    A palladium mediated synthesis of a common synthon for the syntheses of antioxidant analogues of naturally occurring salvianolic acids is presented. The synthetic route may be used to obtain analogues with a balanced lipophilicity/hydrophilicity which may result in potentially interesting LDL antioxidants for the prevention of cardiovascular diseases.

  3. (5-Benzoyl-2-methyl-4-{[1-(pyridin-4-yl-1H-1,2,3-triazol-4-yl]methoxy}-1-benzofuran-7-yl(phenylmethanone

    Directory of Open Access Journals (Sweden)

    Xiao-qin Zhang

    2012-06-01

    Full Text Available The crystal structure of the title compound, C31H22N4O4, features weak C—H...O interactions. The dihedral angle between the fused benzene and furan rings is 2.49 (15°, while that between the triazole and pyridine rings is 10.23(18°.

  4. Evaluation of DNA cleavage, antimicrobial and anti-tubercular activities of potentially active transition metal complexes derived from 2,6-di(benzofuran-2-carbohydrazono)-4-methylphenol

    Science.gov (United States)

    Kokare, Dhoolesh Gangaram; Kamat, Vinayak; Naik, Krishna; Nevrekar, Anupama; Kotian, Avinash; Revankar, Vidyanand K.

    2017-01-01

    A 2,6-diformyl-4-methyl phenol based multidentate novel symmetric ligand and it is late first-row transition metal complexes have been prepared. The ligand and metal complexes were characterized by different spectroscopic techniques. The ligand shows a symmetric polydentate coordination mode through the phenoxide bimetallic bridge, two azomethine nitrogen atoms and two carbonyl oxygen atoms. All the complexes appear to be binuclear with octahedral geometry and nonelectrolytic nature. Complexes have shown significant growth inhibitory activity against tested bacterial and fungal strains as compared to that of ligand. The cobalt complex exhibited better antifungal potency than the standard used. Copper complex exhibits good antifungal activity whereas cobalt and zinc complexes are found to be good antibacterial agents. Ligand and complexes have shown excellent anti-tubercular activity and Calf Thymus-DNA cleavage property.

  5. [Cu]-catalyzed domino Sonogashira coupling followed by intramolecular 5-exo-dig cyclization: synthesis of 1,3-dihydro-2-benzofurans.

    Science.gov (United States)

    Mahendar, Lodi; Reddy, Alavala Gopi Krishna; Krishna, Jonnada; Satyanarayana, Gedu

    2014-09-19

    An efficient [Cu]-catalyzed domino Sonogashira coupling of o-bromobenzyl tertiary alcohols with terminal aryl acetylenes followed by an intramolecular anti-5-exo-dig cyclization is presented. The terminal aryl acetylenes were identified as ideal coupling partners that permit in situ intramolecular oxacyclization by the hydroxyl group as a pre-existing nucleophile of the alcohol. Notably, the intramolecular nucleophilic attack of the hydroxyl group took place on the alkyne moiety in a highly regio- and stereoselective manner. Interestingly, this method was amenable to a wide variety of o-bromobenzyl tertiary alcohols and furnished the corresponding cyclic ethers. On the other hand, when terminal alkyl acetylenes were used as the coupling partners, the reaction was impeded after the Sonogashira coupling.

  6. Synthesis and antimicrobial evaluation of 2-(2-butyl- 4-chloro-1H-imidazol-5-yl-methylene-substituted-benzofuran-3-ones

    Directory of Open Access Journals (Sweden)

    Bhaskar S. Dawane

    2010-05-01

    Full Text Available In the present study, the oxidation of 3-(4-chloro-1H-imidazol-5-yl-1-(2-hydroxyphenylprop-2-en-1-ones with mercuric(II acetate in in polyethylene glycol (PEG-400 gave the corresponding 2-((4-chloro-1H-imidazol-5-ylmethylenebenzofuran-3(2H-ones. Newly synthesized compounds were tested for their in vitro antimicrobial activity.

  7. A novel benzofuran, 4-methoxybenzofuran-5-carboxamide, from Tephrosia purpurea suppressed histamine H1 receptor gene expression through a protein kinase C-δ-dependent signaling pathway.

    Science.gov (United States)

    Shill, Manik Chandra; Mizuguchi, Hiroyuki; Karmakar, Sanmoy; Kadota, Takuya; Mukherjee, Pulok K; Kitamura, Yoshiaki; Kashiwada, Yoshiki; Nemoto, Hisao; Takeda, Noriaki; Fukui, Hiroyuki

    2016-01-01

    Histamine H1 receptor (H1R) gene is upregulated in patients with allergic rhinitis (AR), and its expression level is strongly correlated with the severity of allergic symptoms. We previously reported isolation of the putative anti-allergic compound, 4-methoxybenzofuran-5-carboxamide (MBCA) from Tephrosia purpurea and its chemical synthesis (Shill et al., Bioorg Med Chem 2015;23:6869-6874). However, the mechanism underlying its anti-allergic activity remains to be elucidated. Here, we report the mechanism of MBCA on phorbol 12-myristate-13-acetate (PMA)- or histamine-induced upregulation of H1R gene expression in HeLa cells, and in vivo effects of MBCA were also determined in toluene-2,4-diisocyanate (TDI)-sensitized rats. MBCA suppressed PMA- and histamine-induced upregulation of H1R expression at both mRNA and protein levels and inhibited PMA-induced phosphorylation of PKCδ at Tyr(311) and subsequent translocation to the Golgi. Furthermore, MBCA ameliorated allergic symptoms and suppressed the elevation of H1R and helper T cell type 2 (Th2) cytokine mRNAs in TDI-sensitized rats. Data suggest that MBCA alleviates nasal symptoms in TDI-sensitized rats through the inhibition of H1R and Th2 cytokine gene expression. The mechanism of its H1R gene suppression underlies the inhibition of PKCδ activation.

  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. Ethyl 2-[1-(4-chlorophenyl-2,5-dioxo-1,2,3,5-tetrahydroimidazo[1′,2′:1,2]pyrimidino[5,4-b][1]benzofuran-3-yl]acetate

    Directory of Open Access Journals (Sweden)

    Yang-Gen Hu

    2008-01-01

    Full Text Available The asymmetric unit of the title compound, C22H16ClN3O5, consists of two crystallographically independent molecules. The fused rings of the imidazo[1,2-a]benzo[4,5]furo[3,2-d]pyrimidine system are nearly coplanar and the chlorophenyl rings are twisted with respect to the two pyrimidinone ring systems by 71.00 (2 and 62.59 (2°. The C atoms of the ethyl side chain are disordered and were refined using a split model. In the crystal structure, the molecules are connected via weak intra- and intermolecular C—H...O interactions are present. The ethyl group in one molecule is disordered over two positions, with site occupancy factors 0.55 and 0.45; in the other molecule only the methyl group is disordered over two positions, with site occupancy factors 0.6 and 0.4.

  10. 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

  11. Phytotoxic activities of (2R)-6-hydroxytremetone.

    Science.gov (United States)

    Romano, Elida; Raschi, Ana B; González, Ana M; Jaime, Gloria; Fortuna, Mario A; Hernández, Luis R; Bach, Horacio; Benavente, Alba M

    2011-06-01

    Benzofurans are bioactive compounds isolated from the Asteraceae family. Benzofuran derivatives have been extensively studied because of their toxic effects on humans and animals. The phytotoxic activity of the benzofuran derivative (2R)-6-hydroxytremetone was studied on germination, seedling development, and cytotoxic and genotoxic effects on monocotyledoneous (onion and wheat) and dicotyledoneous (lettuce and tomato) species. Results of these assays demonstrated that (2R)-6-hydroxytremetone is a potent germination inhibitor of onion, lettuce, and tomato seeds. Germination reductions of approximately 80% were measured when seeds were exposed to 100 mg l(-1) of the compound, and showed considerably effects on the posterior development of the sprouts, including rootlets and hypocotyl elongations. Moreover, this benzofuran derivative also significantly reduced the root length and mitotic division of Allium cepa bulbs, although DNA damages were not observed. Our findings suggest that a mechanism of mitosis inhibition may play a role in the phytotoxic effects of plants producing these compounds.

  12. Experimental rayless goldenrod (Isocoma pluriflora) toxicosis in horses

    Science.gov (United States)

    Rayless goldenrod (Isocoma pluriflora) sporadically poisons horses and other livestock in the southwestern United States. Similar to livestock poisoning by white snakeroot (Ageratina altissima) in the midwestern United States, previous research suggests that benzofuran ketones (BFK: tremetone, dehy...

  13. 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.

  14. Synthesis of resorcinolic lipids bearing structural similarities to cytosporone A

    Directory of Open Access Journals (Sweden)

    Edson dos Anjos dos Santos

    2009-01-01

    Full Text Available Inspired by the structure and biological activities of resorcinolic lipids and, particularly cytosporone A- a potent inhibitor of plantule germination and growth, we have performed the synthesis of the analogs 3-heptyl-3-hydroxy-5,7-dimethoxy-2-benzofuran-1(3H-one (1 and 3-heptyl-3-hydroxy-4,6-dimethoxy-2-benzofuran-1(3H-one (2. The intermediates and products were submitted to allelopathic test using Lactuca sativa L. seeds. Target compound 1 showed an inhibitory effect on germination and growth of hypocotyl and radicle in milimolar range.

  15. Synthesis of resorcinolic lipids bearing structural similarities to cytosporone A

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Edson dos Anjos dos; Beatriz, Adilson; Lima, Denis Pires de [Universidade Federal Mato Grosso do Sul (UFMS), Campo Grande, MS (Brazil). Centro de Ciencias Exatas e Tecnologia. Dept. de Quimica], e-mail: dlima@nin.ufms.br; Marques, Maria Rita; Leite, Carla Braga [Universidade Federal Mato Grosso do Sul (UFMS), Campo Grande, MS (Brazil). Centro de Ciencias Biologicas. Dept. de Morfofisiologia

    2009-07-01

    Inspired by the structure and biological activities of resorcinolic lipids and, particularly cytosporone A- a potent inhibitor of plantule germination and growth, we have performed the synthesis of the analogs 3-heptyl-3-hydroxy-5,7-dimethoxy-2-benzofuran-1(3H)-one (1) and 3-heptyl-3-hydroxy-4,6-dimethoxy-2-benzofuran-1(3H)-one (2). The intermediates and products were submitted to allelopathic test using Lactuca sativa L. seeds. Target compound 1 showed an inhibitory effect on germination and growth of hypocotyl and radicle in millimolar range. (author)

  16. 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)

  17. 7H-1-Benzofuro[2,3-b]carbazole

    Directory of Open Access Journals (Sweden)

    V. Manivannan

    2011-10-01

    Full Text Available In the title compound, C18H11NO, the carbazole and benzofuran rings are almost co-planar, making a dihedral angle of 3.31 (3°. The crystal structure is stabilized by weak C—H...π interactions.

  18. 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.

  19. 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.

  20. 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.

  1. Rhodium(I)-Catalyzed Benzannulation of Heteroaryl Propargylic Esters: Synthesis of Indoles and Related Heterocycles.

    Science.gov (United States)

    Li, Xiaoxun; Xie, Haibo; Fu, Xiaoning; Liu, Ji-Tian; Wang, Hao-Yuan; Xi, Bao-Min; Liu, Peng; Xu, Xiufang; Tang, Weiping

    2016-07-18

    A de novo synthesis of a benzene ring allows for the preparation of a diverse range of heterocycles including indoles, benzofurans, benzothiophenes, carbazoles, and dibenzofurans from simple heteroaryl propargylic esters using a unified carbonylative benzannulation strategy. Multiple substituents can be easily introduced to the C4-C7 positions of indoles and related heterocycles.

  2. Construction of Nine-Membered Heterocycles through Palladium-Catalyzed Formal [5+4] Cycloaddition.

    Science.gov (United States)

    Yang, Li-Cheng; Rong, Zi-Qiang; Wang, Ya-Nong; Tan, Zher Yin; Wang, Min; Zhao, Yu

    2017-03-06

    The first catalytic formal [5+4] cycloaddition to prepare nine-membered heterocycles is presented. Under palladium catalysis, the reaction of N-tosyl azadienes and substituted vinylethylene carbonates (VECs) proceeds smoothly to produce benzofuran-fused heterocycles in uniformly high efficiency. Highly diastereoselective functionalization of the nine-membered heterocycles through peripheral attack is also demonstrated.

  3. Two New Secondary Metabolites from Tephrosia purpurea.

    Science.gov (United States)

    Chen, Yin-Ning; Peng, Yan; Gao, Cheng-Hai; Yan, Tao; Xu, Zhi-Fang; Qius, Samuel X; Cao, Wen-Hao; Deng, Ligao; Huang, Ri-Ming

    2015-06-01

    Further investigation of Tephrosia purpurea led to the isolation of a new prenylated flavone, isoglabratephrin B (1) and a new 1,2-ethanedione benzofuran derivative, purpdione B (2). The structures of the new isolates were elucidated on the basis of extensive spectroscopic analysis.

  4. (+)-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...

  5. 3-(Substituted Aryl-1-benzofuranyl-2-propenones: Antimicrobial Properties of Some Chalcones-Type Compounds and their 2-Pyrazoline Derivatives

    Directory of Open Access Journals (Sweden)

    Demet Coskun

    2011-01-01

    Full Text Available 2-Acetylbenzofuran on condensation with furan-2-carboxaldehyde and pyrrole-2-carboxaldehyde in methanolic KOH solution yielded the corresponding benzofuran chalcones. These two compounds and nine benzofuran chalcones were synthesized before, were further reacted with hydrazine hydrate in ethanol which led to the formation of 2-pyrazoline derivatives. All the synthesized compounds were characterized by elemental analysis, melting point determination, infrared spectroscopy and nuclear magnetic resonance spectroscopy. Nine chalcone-type compounds and eleven 2-pyrazolines were evaluated for their biological activities against the six bacteria and the three yeast and it was seen that thirteen compounds showed activity. Four of them are chalcone-type compounds showed more or less activity.

  6. COX, LOX and platelet aggregation inhibitory properties of Lauraceae neolignans.

    Science.gov (United States)

    Coy, Ericsson David; Cuca, Luis Enrique; Sefkow, Michael

    2009-12-15

    The anti-inflammatory potential of 26 neolignans (14 of the bicyclooctane-type and 12 of the benzofuran-type), isolated from three Lauraceae species (Pleurothyrium cinereum, Ocotea macrophylla and Nectandra amazonum), was evaluated in vitro through inhibition of COX-1, COX-2, 5-LOX and agonist-induced aggregation of rabbit platelets. Benzofuran neolignans were found to be selective COX-2 inhibitors, whereas bicyclooctane neolignans inhibit selectively the PAF-action as well as COX-1 and 5-LOX. The neolignan 9-nor-7,8-dehydro-isolicarin B 15 and cinerin C 7 were found to be the most potent COX-2 inhibitor and PAF-antagonist, respectively. Nectamazin C 10 exhibited dual 5-LOX/COX-2 inhibition.

  7. Neural Network Analysis of Chemical Compounds in Nonrebreathing Fisher-344 Rat Breath

    Science.gov (United States)

    1995-12-01

    Midterm Exam for EENG 617, Math Modeling of the Central Nervous System, February 1995. 5. Frankel, Donald S., et al. "Use of a Neural Net Computer... Central Nervous System." School of Engineering, Air Force Institute of Technology, Wright-Patterson AFB OH, Winter Quarter 1995. 19. Ruck, Dennis W., et al...Octanone/ Benzofuran 2octbenz 2-Pentanone 2pent n-Pentanal npent o-Dichlorobenzene odi p-Chlorotoluene pchloro Table 22. Chemical Compound Key 53 Appendix E

  8. 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.

  9. 9-Methoxy-6a,11a-dimethyl-6a,11a-dihydro-6H-1-benzofuro[3,2-c]chromen-3-ol from Dalbergia oliveri

    Directory of Open Access Journals (Sweden)

    Sujittra Deesamer

    2009-10-01

    Full Text Available The title compound, commonly known as (+-(6aS,11aS-medicarpin, C16H14O4, was isolated from Dalbergia oliveri and displays a rigid molecule consisting of four fused rings. The benzofuran system is inclined at an angle of 76.49 (2° with respect to the chroman unit. The compound exists as a polymeric chain arising from intermolecular O—H...O bonding.

  10. Evidence for a transition state model compound of in-plane vinylic SN2 reaction.

    Science.gov (United States)

    Yamaguchi, Torahiko; Yamamoto, Yohsuke; Fujiwara, Yoshihisa; Tanimoto, Yoshifumi

    2005-06-23

    [reaction: see text] To isolate a transition state model compound of an in-plane vinylic S(N)2 reaction, vinyl bromide 6 bearing a newly synthesized tridentate ligand derived from 1,8-dimethoxythioxanthen-9-one (5) was prepared as a precursor. Although irradiation of 6 gave demethylated benzofuran 12, a transient broad peak which indicates formation of the desired transition state model compound was observed in the laser flash photolytic study.

  11. 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.

  12. Phytochemicals and biological studies of plants in genus Hedysarum

    OpenAIRE

    Dong, Yinmao; Tang, Dongyan; Zhang, Na; Li, Yue; Zhang, Chunhong; Li, Li; Li, Minhui

    2013-01-01

    In China, several species (Hedysarum polybotrys Hand.-Mazz., Hedysarum limprichtii Hlbr., Hedysarum vicioider Turcz. var. Taipeicum Hand.-Mazz. Liu, Hedysarum smithianum, et al.) of genus Hedysarum have a long history of use in traditional Chinese medicine (TCM). In TCM, these plants are used to increase the energy of the body. To date, 155 compounds, including flavonoids, triterpenes, coumarins, lignanoids, nitrogen compounds, sterols, carbohydrates, fatty compounds, and benzofuran, have bee...

  13. New Neolignans and a Phenylpropanoid Glycoside from Twigs of Miliusa mollis

    Directory of Open Access Journals (Sweden)

    Kittisak Likhitwitayawuid

    2010-01-01

    Full Text Available From the twigs of Miliusa mollis Pierre, three new compounds including (2S,3S-2,3-dihydro-2-(4-methoxyphenyl-3-methyl-5-[1(E-propenyl]benzofuran, (7S,8S- threo-Δ8'-4-methoxyneolignan and tyrosol-1-O-β-xylopyranosyl-(1→6-O-β-gluco-pyranoside were isolated, along with seven known compounds. Their structures were elucidated through analysis of their spectroscopic data.

  14. 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.

  15. 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.

  16. A microenvironment-sensitive fluorescent pyrimidine ribonucleoside analogue: synthesis, enzymatic incorporation, and fluorescence detection of a DNA abasic site.

    Science.gov (United States)

    Tanpure, Arun A; Srivatsan, Seergazhi G

    2011-11-04

    Base-modified fluorescent ribonucleoside-analogue probes are valuable tools in monitoring RNA structure and function because they closely resemble the structure of natural nucleobases. Especially, 2-aminopurine, a highly environment-sensitive adenosine analogue, is the most extensively utilized fluorescent nucleoside analogue. However, only a few isosteric pyrimidine ribonucleoside analogues that are suitable for probing the structure and recognition properties of RNA molecules are available. Herein, we describe the synthesis and photophysical characterization of a small series of base-modified pyrimidine ribonucleoside analogues derived from tagging indole, N-methylindole, and benzofuran onto the 5-position of uracil. One of the analogues, based on a 5-(benzofuran-2-yl)pyrimidine core, shows emission in the visible region with a reasonable quantum yield and, importantly, displays excellent solvatochromism. The corresponding triphosphate substrate is effectively incorporated into oligoribonucleotides by T7 RNA polymerase to produce fluorescent oligoribonucleotide constructs. Steady-state and time-resolved spectroscopic studies with fluorescent oligoribonucleotide constructs demonstrate that the fluorescent ribonucleoside photophysically responds to subtle changes in its environment brought about by the interaction of the chromophore with neighboring bases. In particular, the emissive ribonucleoside, if incorporated into an oligoribonucleotide, positively reports the presence of a DNA abasic site with an appreciable enhancement in fluorescence intensity. The straightforward synthesis, amicability to enzymatic incorporation, and sensitivity to changes in the microenvironment highlight the potential of the benzofuran-conjugated pyrimidine ribonucleoside as an efficient fluorescent probe to investigate nucleic acid structure, dynamics, and recognition events.

  17. Design, synthesis, and structure-affinity relationships of regioisomeric N-benzyl alkyl ether piperazine derivatives as sigma-1 receptor ligands.

    Science.gov (United States)

    Moussa, Iman A; Banister, Samuel D; Beinat, Corinne; Giboureau, Nicolas; Reynolds, Aaron J; Kassiou, Michael

    2010-08-26

    A series of N-(benzofuran-2-ylmethyl)-N'-benzylpiperazines bearing alkyl or fluoroalkyl aryl ethers were synthesized and evaluated at various central nervous system receptors. Examination of in vitro sigma1 {[3H]+-pentazocine} and sigma2 ([3H]DTG) receptor binding profiles of piperazines 11-13 and 25-36 revealed several highly potent and sigma1 selective ligands, notably, N-(benzofuran-2-ylmethyl)-N'-(4'-methoxybenzyl)piperazine (13, Ki=2.7 nM, sigma2/sigma1=38) and N-(benzofuran-2-ylmethyl)-N'-(4'-(2''-fluoroethoxy)benzyl)piperazine (30, Ki=2.6 nM, sigma2/sigma1=187). Structural features for optimal sigma1 receptor affinity and selectivity over the sigma2 receptor were identified. On the basis of its favorable log D value, 13 was selected as a candidate for the development of a sigma1 receptor positron emission tomography radiotracer. [11C]13 showed high uptake in the brain and other sigma receptor-rich organs of a Papio hamadryas baboon. The in vivo evaluation of [11C]13 indicates that this radiotracer is a suitable candidate for imaging the sigma1 receptor in neurodegenerative processes.

  18. Synthesis and antifungal activity of derivatives of 2- and 3-benzofurancarboxylic acids.

    Science.gov (United States)

    Hejchman, Elzbieta; Ostrowska, Kinga; Maciejewska, Dorota; Kossakowski, Jerzy; Courchesne, William E

    2012-11-01

    We found that amiodarone has potent antifungal activity against a broad range of fungi, potentially defining a new class of antimycotics. Investigations into its molecular mechanisms showed amiodarone mobilized intracellular Ca2+, which is thought to be an important antifungal characteristic of its fungicidal activity. Amiodarone is a synthetic drug based on the benzofuran ring system, which is contained in numerous compounds that are both synthetic and isolated from natural sources with antifungal activity. To define the structural components responsible for antifungal activity, we synthesized a series of benzofuran derivatives and tested them for the inhibition of growth of two pathogenic fungi, Cryptococcus neoformans and Aspergillus fumigatus, to find new compounds with antifungal activity. We found several derivatives that inhibited fungal growth, two of which had significant antifungal activity. We were surprised to find that calcium fluxes in cells treated with these derivatives did not correlate directly with their antifungal effects; however, the derivatives did augment the amiodarone-elicited calcium flux into the cytoplasm. We conclude that antifungal activity of these new compounds includes changes in cytoplasmic calcium concentration. Analyses of these benzofuran derivatives suggest that certain structural features are important for antifungal activity. Antifungal activity drastically increased on converting methyl 7-acetyl-6-hydroxy-3-methyl-2-benzofurancarboxylate (2b) into its dibromo derivative, methyl 7-acetyl-5-bromo-6-hydroxy-3-bromomethyl-2-benzofurancarboxylate (4).

  19. Absolute configuration of anti-HIV-1 agent (-)-concentricolide: total synthesis of (+)-(R)-concentricolide.

    Science.gov (United States)

    Chang, Chih-Wei; Chein, Rong-Jie

    2011-05-20

    The first enantioselective total synthesis of (+)-(R)-concentricolide, the enantiomer of an anti-HIV-1 agent isolated from Daldinia concentrica, from 2-iodophenol in 7 steps reveals the (S)-configuration for the natural form of the furanophthalide. The key features include an anionic ortho-Fries rearrangement to furnish 3-iodosalicylamide, facile construction of the benzofuran system employing the tandem Sonogashira coupling annulation reaction, directed ortho metalation to introduce a propanoyl group, as well as CBS reduction, establishing the stereocenter enantioselectively.

  20. 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.

  1. Practical synthesis of new functionalized tetraphenylenes

    Institute of Scientific and Technical Information of China (English)

    DU, Da-Ming(杜大明); ZHOU, Ling-Ping(周灵萍); WANG, Jian- Wu(王建武); WANG, Shao-Kun(王少坤)

    2000-01-01

    The practical synthesis procedure of substituted tetraphenylene derivatives involving the synthesis of a precursor for 4, 7-benzofuran and Diels-Alder addition of 4, 7-obenzofuran generated in situ to 5,6, 11,12-te-tradehydrodibenzo[ a, e] cyclooctene, followed by a low valent titanium mediated deoxygenation to give 1, 4, 11, 14-tetra-methoxy-dibenzo[b,n]tetraphenylene, which can be further demethylated to the corresponding phenolic compound, which was acetylated to afford 1,4,11,14-tetraacetoxy-dibenzo-[b,n]tetraphenylene.

  2. 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.

  3. Double Intramolecular Transacetalization of Polyhydroxy Acetals: Synthesis of Conformationally-Restricted 1,3-Dioxanes with Axially-Oriented Phenyl Moiety

    OpenAIRE

    Samuel Asare-Nkansah; Bernhard Wünsch

    2016-01-01

    The synthesis of conformationally-restricted 1,3-dioxanes with a phenyl moiety fixed in an axial orientation at the acetalic center is described. Starting with diethyl 3-hydroxyglutarate (15), benzaldehyde acetal 12a and acetophenone ketal 12b bearing a protected 1,3,5-trihydroxypentyl side chain in the o-position were prepared. The first acid-catalyzed intramolecular transacetalization gave a mixture of diastereomeric 2-benzofurans 18 (ratio of diastereomers 2:2:1:1). After OH group deprotec...

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

    OpenAIRE

    Reham Hassan; Hassan Arida; Manal Montasser; Nehad Abdel Latif

    2013-01-01

    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...

  5. Features of the reaction of heterocyclic analogs of chalcone with lanthanide shift reagents

    Energy Technology Data Exchange (ETDEWEB)

    Turov, A.V.; Khilya, V.P. [Taras Shevchenko Kiev Univ. (Russian Federation)

    1994-10-01

    The PMR spectra of heterocyclic analogs of 2-hydroxychalcone containing thiazole, benzofuran, triazole, imidazole, benzodioxane, or pyridine rings in the presence of lanthanide shift reagents are studied. It is found that the most effective reagent for modifying the spectra of these compounds is Yb(fod)3. The broadening of the spectra of 2-hydroxy chalcones in the presence of lanthanide shift reagents is explained by the dynamic effects of complex formation. An example is given of the determination of the conformation of molecules of 2-hydroxychalcone by the simultaneous use of lanthanide shift reagents and the homonuclear Overhauser effect. 9 refs., 1 fig., 1 tab.

  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. Antithrombotic effects of bromophenol,an alga-derived thrombin inhibitor

    Institute of Scientific and Technical Information of China (English)

    史大永; 李晓红; 李敬; 郭书举; 苏华; 范晓

    2010-01-01

    Thrombin,the ultimate proteinase of the coagulation cascade,is an attractive target for the treatment of a variety of cardiovascular diseases.A bromophenol derivative named (+)-3-(2,3-dibromo-4,5-dihydroxy-phenyl)-4-bromo-5,6-dihydroxy-1,3-dihydroiso-benzofuran 1,isolated from the brown alga Leathesia nana exhibited significant thrombin inhibitory activity.In this study,we investigated the inhibition of human thrombin in vitro with this bromophenol derivative,and its antithrombotic efficacy in vivo using th...

  8. Synthesis of some new Thieno[2,3-b]pyridines, Pyrimidino[4',5':4,5]thieno[2,3-b]pyridine and Pyridines Incorporating 5-Bromobenzofuran-2-yl Moiety.

    Science.gov (United States)

    Abdelriheem, Nadia Abdelhamed; Ahmad, Sayed Abdel-Kader; Abdelhamid, Abdou Osman

    2015-01-07

    2-Sulfanyl-6-(2-thienyl)pyridine-3-carbonitrile, 1-Amino-6-(5-bromo-benzofuran-2-yl)-2-oxo-1,2-dihydro-pyridine-3-carbonitrile, thieno[2,3-b]pyridins, pyrimidino[4',5':4,5] thieno[2,3-b]pyridine, quinazoline and carbamate derivatives were synthesized from sodium 3-(5-bromobenzofuran-2-yl)-3-oxoprop-1-en-1-olate with. The newly synthesized compounds were elucidated by elemental analysis, spectral data, and alternative synthesis whenever possible and chemical transportation.

  9. 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.

  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. 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.

  12. Variation in toxicity during the biodegradation of various heterocyclic and homocyclic aromatic hydrocarbons in single and multi-substrate systems.

    Science.gov (United States)

    Oberoi, Akashdeep Singh; Philip, Ligy

    2017-01-01

    In the present study, an attempt was made to understand the variation in the toxicity during the biodegradation of aromatic hydrocarbons in single and multi-substrate system. The bacterial bioassay based on the inhibition of dehydrogenase enzyme activity of two different bacterial sp. E.coli and Pseudomonas fluorescens was used for toxicity assessment. Amongst the chosen pollutants, the highest acute toxicity was observed for benzothiophene followed by benzofuran having EC50 value of 16.60mg/L and 19.30mg/L respectively. Maximum residual toxicity of 30.8% was observed at the end during the degradation of benzothiophene. Due to the accumulation of transitory metabolites in both single and multisubstrate systems, reduction in toxicity was not proportional to the decrease in pollutant concentration. In multi-substrate system involving mixture of heterocyclic hydrocarbons, maximum residual toxicity of 39.5% was observed at the end of biodegradation. Enhanced degradation of benzofuran, benzothiophene and their metabolic intermediates were observed in the presence of naphthalene resulting in significant reduction in residual toxicity. 2 (1H) - quinolinone, an intermediate metabolite of quinoline was observed having significant eco-toxicity amongst all other intermediates investigated.

  13. Conformation-sensitive nucleoside analogues as topology-specific fluorescence turn-on probes for DNA and RNA G-quadruplexes

    Science.gov (United States)

    Tanpure, Arun A.; Srivatsan, Seergazhi G.

    2015-01-01

    Development of probes that can discriminate G-quadruplex (GQ) structures and indentify efficient GQ binders on the basis of topology and nucleic acid type is highly desired to advance GQ-directed therapeutic strategies. In this context, we describe the development of minimally perturbing and environment-sensitive pyrimidine nucleoside analogues, based on a 5-(benzofuran-2-yl)uracil core, as topology-specific fluorescence turn-on probes for human telomeric DNA and RNA GQs. The pyrimidine residues of one of the loop regions (TTA) of telomeric DNA and RNA GQ oligonucleotide (ON) sequences were replaced with 5-benzofuran-modified 2′-deoxyuridine and uridine analogues. Depending on the position of modification the fluorescent nucleoside analogues distinguish antiparallel, mixed parallel-antiparallel and parallel stranded DNA and RNA GQ topologies from corresponding duplexes with significant enhancement in fluorescence intensity and quantum yield. Further, these GQ sensors enabled the development of a simple fluorescence binding assay to quantify topology- and nucleic acid-specific binding of small molecule ligands to GQ structures. Together, our results demonstrate that these nucleoside analogues are useful GQ probes, which are anticipated to provide new opportunities to study and discover efficient G-quadruplex binders of therapeutic potential. PMID:26202965

  14. 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.

  15. 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.

  16. 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

  17. Utilization of an intramolecular hydrogen bond to increase the CNS penetration of an NK(1) receptor antagonist.

    Science.gov (United States)

    Ashwood, V A; Field, M J; Horwell, D C; Julien-Larose, C; Lewthwaite, R A; McCleary, S; Pritchard, M C; Raphy, J; Singh, L

    2001-07-05

    This paper describes the synthesis and physical and biological effects of introducing different substituents at the alpha-position of the tryptophan containing neurokinin-1 receptor antagonist [(R)-2-(1H-indol-3-yl)-1-methyl-1-((S)-1-phenyl-ethylcarbamoyl)-ethyl]-carbamic acid benzofuran-2-ylmethyl ester (CI 1021). The described compounds all exhibit less than 5 nM binding affinities for the human neurokinin-1 receptor and selectivity over the tachykinin NK(2) and NK(3) receptor subtypes. Application of variable temperature nuclear magnetic resonance spectroscopy studies of the amide and urethane protons was utilized to determine the existence of an intramolecular hydrogen bond. This intramolecular hydrogen bond increases the apparent lipophilicity to allow increased central nervous system penetration and pharmacological activity (gerbil foot tap test) in the case of the highest affinity compound [(S)-1-dimethylaminomethyl-2-(1H-indol-3-yl)-1-((S)-1-phenyl-ethylcarbamoyl)-ethyl]-carbamic acid benzofuran-2-ylmethyl ester (PD 174424) over those analogues that could not form an intramolecular hydrogen bond.

  18. 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.

  19. Synthesis of iboga-like isoquinuclidines: Dual opioid receptors agonists having antinociceptive properties.

    Science.gov (United States)

    Banerjee, Tuhin Suvro; Paul, Sibasish; Sinha, Surajit; Das, Sumantra

    2014-11-01

    Some novel iboga-analogues consisting of benzofuran moiety and dehydroisoquinuclidine ring connected by -CH2-, (CH2)2 and (CH2)3 linkers have been synthesized with the view to develop potential antinociceptive drugs. The compounds 14 and 21 showed binding at the μ-opioid receptor (MOR), while the compound 11a exhibited dual affinities at both MOR and κ-opioid receptor (KOR). MAP kinase activation indicated all three compounds have opioid agonistic properties. The presence of a double bond and endo-methylcarboxylate group in the dehydroisoquinuclidine ring and the benzofuran and methylene spacer appeared to be essential for opioid receptor binding. Further studies demonstrated 11a caused significant antinociception in mice in the hot-plate test which was comparable to that produced by morphine. The compound 11a was also found to be nontremorigenic unlike various iboga congeners. This study identifies a new pharmacophore which may lead to the development of suitable substitute of morphine in the treatment of pain.

  20. 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.

  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, 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.

  3. Schiff Bases of Indoline-2,3-dione: Potential Novel Inhibitors of Mycobacterium Tuberculosis (Mtb DNA Gyrase

    Directory of Open Access Journals (Sweden)

    Jane Thanassi

    2011-09-01

    Full Text Available In the present study a series of Schiff bases of indoline-2,3-dione were synthesized and investigated for their Mtb gyrase inhibitory activity. Promising inhibitory activity was demonstrated with some of these derivatives, which exhibited IC50 values ranging from 50–157 mM. The orientation and the ligand-receptor interactions of such molecules within the Mtb DNA gyrase A subunit active site were investigated applying a multi-step docking protocol using Molecular Operating Environment (MOE and Autodock4 docking software. The results revealed the importance of the isatin moiety and the connecting side chain for strong interactions with the enzyme active site. Among the tested compounds the terminal aromatic ring benzofuran showed the best activity. Promising new leads for developing a novel class of Mtb gyrase inhibitors were obtained from Schiff bases of indoline-2,3-dione.

  4. 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)

  5. 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)

  6. Synthesis and photophysical characterisation of a fluorescent nucleoside analogue that signals the presence of an abasic site in RNA.

    Science.gov (United States)

    Tanpure, Arun A; Srivatsan, Seergazhi G

    2012-11-05

    The synthesis and site-specific incorporation of an environment-sensitive fluorescent nucleoside analogue (2), based on a 5-(benzofuran-2-yl)pyrimidine core, into DNA oligonucleotides (ONs), and its photophysical properties within these ONs are described. Interestingly and unlike 2-aminopurine (a widely used nucleoside analogue probe), when incorporated into an ON and hybridised with a complementary ON, the emissive nucleoside 2 displays significantly higher emission intensity than the free nucleoside. Furthermore, photophysical characterisation shows that the fluorescence properties of the nucleoside analogue within ONs are significantly influenced by flanking bases, especially by guanosine. By utilising the responsiveness of the nucleoside to changes in base environment, a DNA ON reporter labelled with the emissive nucleoside 2 was constructed; this signalled the presence of an abasic site in a model depurinated sarcin/ricin RNA motif of a eukaryotic 28S rRNA.

  7. Antithrombotic effects of bromophenol, an alga-derived thrombin inhibitor

    Science.gov (United States)

    Shi, Dayong; Li, Xiaohong; Li, Jing; Guo, Shuju; Su, Hua; Fan, Xiao

    2010-01-01

    Thrombin, the ultimate proteinase of the coagulation cascade, is an attractive target for the treatment of a variety of cardiovascular diseases. A bromophenol derivative named (+)-3-(2,3-dibromo-4, 5-dihydroxy-phenyl)-4-bromo-5,6-dihydroxy-1,3-dihydroiso-benzofuran 1, isolated from the brown alga Leathesia nana exhibited significant thrombin inhibitory activity. In this study, we investigated the inhibition of human thrombin in vitro with this bromophenol derivative, and its antithrombotic efficacy in vivo using the arteriovenous shunt model and the ferric chloride-induced arterial thrombosis model in rats. The results show that the bromophenol derivative is a potential inhibitor of thrombin (IC50=1.03 nmol/L). In antithrombotic experiments in vivo, the bromophenol derivative also shows good effect comparing with the control group. These data indicate that the bromophenol derivative is a potential drug for prophylaxis and the treatment of thrombotic diseases.

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

    Science.gov (United States)

    Miyabe, Hideto

    2015-07-09

    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.

  9. 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.

  10. 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).

  11. 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.

  12. Phytochemicals and biological studies of plants in genus Hedysarum

    Science.gov (United States)

    2013-01-01

    In China, several species (Hedysarum polybotrys Hand.-Mazz., Hedysarum limprichtii Hlbr., Hedysarum vicioider Turcz. var. Taipeicum Hand.-Mazz. Liu, Hedysarum smithianum, et al.) of genus Hedysarum have a long history of use in traditional Chinese medicine (TCM). In TCM, these plants are used to increase the energy of the body. To date, 155 compounds, including flavonoids, triterpenes, coumarins, lignanoids, nitrogen compounds, sterols, carbohydrates, fatty compounds, and benzofuran, have been isolated from plants of the genus Hedysarum. Various chemical constituents contribute to the antioxidant, anti-tumor, anti-aging, anti-diabetic, and anti-hypertensive properties of these plants. Hedysarum species are used to treat infestation with gastrointestinal nematodes and may support the immune system and peripheral nervous system. In the present review, we summarize the research on the phytochemistry and pharmacology of Hedysarum species, which will be useful for better utilization of these important species in TCM. PMID:23866043

  13. 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.

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

    Science.gov (United States)

    Nasser, Mohammad; Larsen, Timothy R; Waanbah, Barryton; Sidiqi, Ibrahim; McCullough, Peter A

    2013-01-01

    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.

  15. 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.

  16. 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)

  17. 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.

  18. 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.

  19. 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.

  20. Photochromic properties and reaction mechanism of naphthopyran

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The photochromic properties and reaction mechanism of title compounds have been examined with steady method on compounds 3-phenyl-3-[3-methylbenzothiophene-2-yl]-3H- naphtho[2,1-b]pyran (1) and 3-phenyl-3-[benzofuran-2-yl]-3H-naphtho[2,1-b]pyran (2) and nanosecond laser flash photolysis techniques on compound 3-phenyl-3-[1,2-dimethylindol-3-yl]- 3H-naphtho[2,1-b]pyran (3). The influence of oxygen on transient spectra and decay kinetics of compound 3 has been investigated. Both excited singlet state and triplet state are involved in the photochromic mechanism of compound 3. The influence of molecular structure on photochromic behavior has been studied also. Decay kinetics indicated that the lifetime of colored forms of 1 and 2 were several orders of magnitude longer than that of 3.

  1. Photochromic properties and reaction mechanism of naphthopyran

    Institute of Scientific and Technical Information of China (English)

    潘桂兰; 魏景强; 朱爱平; 明阳福; 樊美公; 姚思德

    2001-01-01

    The photochromic properties and reaction mechanism of title compounds have been examined with steady method on compounds 3-phenyl-3-[3-methylbenzothiophene-2-yl]-3H-naphtho[2,1-b]pyran (1) and 3-phenyl-3-[benzofuran-2-yl]-3H-naphtho[2,1-b]pyran (2) and nanosecond laser flash photolysis techniques on compound 3-phenyl-3-[1,2-dimethylindol-3-yl]-3H-naphtho[2,1-b]pyran (3). The influence of oxygen on transient spectra and decay kinetics of compound 3 has been investigated. Both excited singlet state and triplet state are involved in the photochromic mechanism of compound 3. The influence of molecular structure on photochromic behavior has been studied also. Decay kinetics indicated that the lifetime of colored forms of 1 and 2 were several orders of magnitude longer than that of 3.

  2. Diferulate content of maize sheaths is associated with resistance to the Mediterranean corn borer Sesamia nonagrioides (Lepidoptera: Noctuidae).

    Science.gov (United States)

    Santiago, Rogelio; Butrón, Ana; Reid, Lana M; Arnason, John T; Sandoya, German; Souto, Xose C; Malvar, Rosa A

    2006-11-29

    The leaf sheaths of selected inbred lines of maize (Zea mays L.) with variable levels of stem resistance to the Mediterranean corn borer Sesamia nonagrioides (Lefèvbre) were evaluated for antibiotic effect on insect development. Phytochemical analyses of leaf sheaths were conducted for cell wall phenylpropanoid content to gain a better understanding of maize-resistance mechanisms. Laboratory bioassays established that sheath tissues from different genotypes significantly affected the growth of neonate larvae. Three hydroxycinnamates, p-coumaric, trans-ferulic, and cis-ferulic acids, and three isomers of diferulic acid, 8-5', 8-O-4', and 8-5' b (benzofuran form), were identified. Significant negative correlations were found between larvae weight and diferulic acid content for six genotypes. These results are in agreement with previous studies concerning the role of cell wall structural components in stem borer resistance.

  3. Putative role of pith cell wall phenylpropanoids in Sesamia nonagrioides (Lepidoptera: Noctuidae) resistance.

    Science.gov (United States)

    Santiago, Rogelio; Butron, Ana; Arnason, John T; Reid, Lana M; Souto, Xose C; Malvar, Rosa A

    2006-03-22

    The stem borer Sesamia nonagrioides (Lefèbvre) is the most important insect pest that attacks maize, Zea mays L., in northwestern Spain. Host plant resistance to this borer was investigated in relation to the cell wall phenylpropanoids content in the pith. Eight inbred lines that differ in resistance were analyzed. Three major simple phenolic acids, p-coumaric, trans-ferulic, and cis-ferulic acids, and three isomers of diferulic acid, 8-5', 8-O-4', and 8-5'b (benzofuran form), were identified. The amount of all these compounds was correlated with the resistance level in the genotypes, with the resistant inbreds having the highest concentrations. The role of these compounds in cell wall fortification and lignification is well-documented, suggesting their possible intervention in S. nonagrioides resistance. Future studies that focus on these compounds could be useful to enhance S. nonagroides resistance.

  4. QIAD assay for quantitating a compound’s efficacy in elimination of toxic Aβ oligomers

    Science.gov (United States)

    Brener, Oleksandr; Dunkelmann, Tina; Gremer, Lothar; van Groen, Thomas; Mirecka, Ewa A.; Kadish, Inga; Willuweit, Antje; Kutzsche, Janine; Jürgens, Dagmar; Rudolph, Stephan; Tusche, Markus; Bongen, Patrick; Pietruszka, Jörg; Oesterhelt, Filipp; Langen, Karl-Josef; Demuth, Hans-Ulrich; Janssen, Arnold; Hoyer, Wolfgang; Funke, Susanne A.; Nagel-Steger, Luitgard; Willbold, Dieter

    2015-01-01

    Strong evidence exists for a central role of amyloid β-protein (Aβ) oligomers in the pathogenesis of Alzheimer’s disease. We have developed a fast, reliable and robust in vitro assay, termed QIAD, to quantify the effect of any compound on the Aβ aggregate size distribution. Applying QIAD, we studied the effect of homotaurine, scyllo-inositol, EGCG, the benzofuran derivative KMS88009, ZAβ3W, the D-enantiomeric peptide D3 and its tandem version D3D3 on Aβ aggregation. The predictive power of the assay for in vivo efficacy is demonstrated by comparing the oligomer elimination efficiency of D3 and D3D3 with their treatment effects in animal models of Alzheimer´s disease. PMID:26394756

  5. Development of an enantioseparation method for novel psychoactive drugs by HPLC using a Lux(®) Cellulose-2 column in polar organic phase mode.

    Science.gov (United States)

    Taschwer, Magdalena; Grascher, Jörg; Schmid, Martin G

    2017-01-01

    Since the last decade, the hype of the recreational use of novel psychoactive drugs is still on its top in entire Europe. Every year, new derivatives enter the drug market and enlarge the broad spectrum of misused drugs. Many of these compounds contain a stereogenic centre and therefore two enantiomers exist. It is obvious that the pharmacological potency of the isomers differ as it is already known from various pharmaceutical ingredients. Therefore, the development of analytical methods for the chiral separation of new psychoactive substances is of great medical and forensic interest. The aim of this study was to establish an enantioseparation method, which is applicable at equal conditions for different drug compound classes including cathinones, amphetamines, benzofurans, thiophenes, phenidine and phenidate derivatives. A commercially available Lux(®) Cellulose-2 column consisting of cellulose tris(3-chloro-4-methylphenylcarbamate) coated on silica gel was found to be appropriate for the chiral separation of the mentioned drug classes. Experiments were performed under isocratic conditions in polar organic phase mode using UV-detection. With a mobile phase consisting of acetonitrile:isopropanol:diethylamine:formic acid (100%) (95:5:0.1:0.1) 40 out of 43 psychoactive compounds were successfully baseline or partially separated. 3-Fluoroamphetamine, 4-fluoroamphetamine and 1-(benzofuran-6-yl)-N-ethylpropan-2-amine were not chirally separated. The established method enabled enantioseparation of a broad spectrum of different psychoactive compounds under equal conditions. Forty of forty-three compounds were separated in their enantiomers, thus this method has a wide applicability for the enantioseparation of novel psychoactive drugs.

  6. 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.

  7. 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.

  8. Key cytokines of adaptive immunity are differentially induced in rainbow trout kidney by a group of structurally related geranyl aromatic derivatives.

    Science.gov (United States)

    Valenzuela, Beatriz; Obreque, Javiera; Soto-Aguilera, Sarita; Maisey, Kevin; Imarai, Mónica; Modak, Brenda

    2016-02-01

    Filifolinone is a semi-synthetic terpenoid derivative obtained from Heliotropium filifolium that increases the expression level of pro-inflammatory and anti-inflammatory cytokines in kidney cells of salmon. Because cytokines are produced in response to a foreign organism and by distinct other signals modulating immune responses, we further studied the potential immunomodulatory effects of a group of structural related terpenoid derivatives from H. filifolium on salmonids to determine the relationship between the chemical structure of the derivatives and their ability to modify cytokine expression and the lymphoid content. The resin and four 3H-spiro 1-benzofuran-2,1'-cyclohexane derivatives were tested in vivo in rainbow trout (Oncorhynchus mykiss) by quantifying the transcript levels of antiviral and T helper-type cytokines and T and B cells in the kidney. Three of the four terpenoids differ only in the C-7'substituent of the cyclohexane and the presence of the ketone group at this position in Filifolinone appeared responsible of an important up-regulation of IFN-α1, IFN-γ, IL-4/13A and IL-17D in the kidney of the treated trout. In addition, the absence of a methoxy group in carbon 7 of the benzene ring, found in all compounds but not in Folifolinoic acid, produced a significant reduction of IFN-γ, IL-12 and IL-4/13A transcripts. B cells were not affected by the compound treatment but Filifolinoic acid and the resin induced a significant reduction of T cells. Altogether, results showed that immunomodulating responses observed in the trout by effect of 3H-spiro 1-benzofuran-2,1'-cyclohexane derivatives is related to the presence of the ketone group in the carbon 7' and the methoxy group in carbon 7 of the benzene ring, being Filifolinone the most active immunostimulatory compound identified.

  9. ENA of heterocyclic hydrocarbons by adding hydrogen peroxide in groundwater circulation wells - a field-based study on a large physical model scale

    Energy Technology Data Exchange (ETDEWEB)

    Sagner, A.; Tiehm, A. [Technologiezentrum Wasser, Karlsruhe (Germany); Trotschler, O.; Haslwimmer, Th.; Koschitzky, H.P. [Stuttgart Univ., VEGAS, Institut fur Wasserbau (Germany)

    2005-07-01

    Heterocyclic Hydrocarbons (NSO-HET) are ingredients of tar oil, commonly found down-gradient of former gasworks sites. Typical NSO-HET are benzofurans, methyl-benzofurans, methylquinoline, acridine or carbazole. During investigations of MNA (monitored natural attenuation) remediation strategies, it was found that most NSO-HET are highly mobile due to their high water solubility and low biodegradation rates. In addition, some were found to be highly toxic and carcinogenic. In particular under anaerobic conditions, NSO-HET biodegradation rates are low. However, aerobic biological degradation was found to be effective. Based on the extension and contaminant distribution of the plume ({approx} 800 m long) down-gradient of a former gasworks 'Testfeld Sued' (TFS) in Southern Germany, the most applicable technology for enhancing the natural degradation of PAH, BTEX and NSO-HET was selected and tested under controlled conditions in a large physical model (Large Flume of VEGAS). The investigations focused on a technology for a homogeneous infiltration of electron acceptor solutions such as oxygen and hydrogen peroxide to provide the bacteria with molecular oxygen. An initial infiltration of oxygen (air-saturated water) during the adaptation of microorganism to aerobic biodegradation was followed by a time-limited addition of hydrogen peroxide to achieve an oxygen concentration up to 23 mg/L in the model aquifer. An almost complete degradation of NSO-HET was found. On the basis of numerical simulations and lab experiments, it was found that natural dispersion will not lead to a wide-ranging homogeneous distribution and mixing of the oxygen in the aquifer. The Groundwater Circulation Wells technology (GCW) can be applied to achieve a maximum mixing of the electron acceptor solution with the groundwater. A spherical groundwater circulation is induced by means of ex- and infiltration ports in vertical wells. Infiltration and ex-filtration ports are located in

  10. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  12. 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.

  13. 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.

  14. The mechanism of allosteric inhibition of protein tyrosine phosphatase 1B.

    Directory of Open Access Journals (Sweden)

    Shuai Li

    Full Text Available As the prototypical member of the PTP family, protein tyrosine phosphatase 1B (PTP1B is an attractive target for therapeutic interventions in type 2 diabetes. The extremely conserved catalytic site of PTP1B renders the design of selective PTP1B inhibitors intractable. Although discovered allosteric inhibitors containing a benzofuran sulfonamide scaffold offer fascinating opportunities to overcome selectivity issues, the allosteric inhibitory mechanism of PTP1B has remained elusive. Here, molecular dynamics (MD simulations, coupled with a dynamic weighted community analysis, were performed to unveil the potential allosteric signal propagation pathway from the allosteric site to the catalytic site in PTP1B. This result revealed that the allosteric inhibitor compound-3 induces a conformational rearrangement in helix α7, disrupting the triangular interaction among helix α7, helix α3, and loop11. Helix α7 then produces a force, pulling helix α3 outward, and promotes Ser190 to interact with Tyr176. As a result, the deviation of Tyr176 abrogates the hydrophobic interactions with Trp179 and leads to the downward movement of the WPD loop, which forms an H-bond between Asp181 and Glu115. The formation of this H-bond constrains the WPD loop to its open conformation and thus inactivates PTP1B. The discovery of this allosteric mechanism provides an overall view of the regulation of PTP1B, which is an important insight for the design of potent allosteric PTP1B inhibitors.

  15. Subtle solvation behaviour of a biofuel additive: the methanol complex with 2,5-dimethylfuran.

    Science.gov (United States)

    Poblotzki, Anja; Altnöder, Jonas; Suhm, Martin A

    2016-10-05

    Methanol is shown to engage two nearly equivalent solvation sites in 2,5-dimethylfuran, the electron-rich π cloud and the electron-deficient oxygen site. The latter only wins by a slight margin, thanks to the methyl group undergoing secondary interactions with the ring. These secondary attractions reduce the hydrogen bond-induced OH frequency shift of the OH-O contact, whereas the π cloud allows for a combined action of both binding mechanisms in the OH-π arrangement. In total, the hydrophobic character of 2,5-dimethylfuran is well reflected in the weak pair interactions, as judged by the small solvation shifts. Methanol solvation of 2,3-benzofuran is revisited and shown to be more ambiguous than previously thought, involving competition between five- and six-ring π clouds and the oxygen site for the OH group. The six-ring π cloud is slightly preferred. FTIR spectroscopy in supersonic jets is in systematic agreement with dispersion-corrected harmonic B3LYP and also B2PLYP predictions for these competing furan docking sites. Deuteration of the OH group helps to identify the docking sites because of its attenuated zero-point energy weakening effect on localized hydrogen bonds. Extension to less methylated furans is proposed in the context of a future forecasting competition for the performance of quantum chemical methods for intermolecular interactions.

  16. Design of α7 nicotinic acetylcholine receptor ligands using the (het)Aryl-1,2,3-triazole core: Synthesis, in vitro evaluation and SAR studies.

    Science.gov (United States)

    Ouach, Aziz; Pin, Frederic; Bertrand, Emilie; Vercouillie, Johnny; Gulhan, Zuhal; Mothes, Céline; Deloye, Jean-Bernard; Guilloteau, Denis; Suzenet, Franck; Chalon, Sylvie; Routier, Sylvain

    2016-01-01

    We report here the synthesis of a large library of 1,2,3-triazole derivatives which were in vitro tested as α7 nAchR ligands. The SAR study revealed that several crucial factors are involved in the affinity of these compounds for α7 nAchR such as a (R) quinuclidine configuration and a mono C-3 quinuclidine substitution. The triazole ring was substituted by a phenyl ring bearing small OMe/CH2F groups or fluorine atom and by several heterocycles such as thiophenes, furanes, benzothiophenes or benzofuranes. Among the 30 derivatives tested, the two derivatives 10 and 39 with Ki in the nanomolar range were identified (2.3 and 3 nM respectively). They exhibited a strict selectivity toward the α4β2 nicotinic receptor (up to 1 μM) but interacted with the 5HT3 receptors with Ki around 3 nM. Synthesis, SAR studies and a full description of the derivatives are reported.

  17. 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.

  18. {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.

  19. 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 valuescancer 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).

  20. Double Intramolecular Transacetalization of Polyhydroxy Acetals: Synthesis of Conformationally-Restricted 1,3-Dioxanes with Axially-Oriented Phenyl Moiety

    Directory of Open Access Journals (Sweden)

    Samuel Asare-Nkansah

    2016-11-01

    Full Text Available The synthesis of conformationally-restricted 1,3-dioxanes with a phenyl moiety fixed in an axial orientation at the acetalic center is described. Starting with diethyl 3-hydroxyglutarate (15, benzaldehyde acetal 12a and acetophenone ketal 12b bearing a protected 1,3,5-trihydroxypentyl side chain in the o-position were prepared. The first acid-catalyzed intramolecular transacetalization gave a mixture of diastereomeric 2-benzofurans 18 (ratio of diastereomers 2:2:1:1. After OH group deprotection, the second intramolecular transacetalization afforded tricyclic alcohol 14a (2-(1,5-epoxy-1,3,4,5-tetrahydro-2-benzoxepin-3-yl]ethan-1-ol. Analogous cyclizations led to the corresponding silyl ether 22a (19% and azide 23a (13%. Whereas tricyclic alcohol 14a was obtained as a 1:1 mixture of diastereomers, the silyl ether 22a and the azide 23a afforded only one diastereomer. This observation indicates a faster cyclization of the minor diastereomers providing the thermodynamically-favored compounds with equatorially-oriented substituents in the 3-position of the tricyclic 1,5-epoxy-2-benzoxepine system. In general, acetophenone-derived ketalic compounds (b-series required very mild reaction conditions and gave lower yields than the corresponding acetalic compounds (a-series.

  1. 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.

  2. 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.

  3. 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%.

  4. 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.

  5. Lignan derivatives from Selaginella tamariscina and their nitric oxide inhibitory effects in LPS-stimulated RAW 264.7 cells.

    Science.gov (United States)

    Dat, Le Duc; Zhao, Bing Tian; Hung, Nguyen Duc; Lee, Jeong Hyung; Min, Byung Sun; Woo, Mi Hee

    2017-02-01

    The chemical characterization of Selaginella tamariscina leaves resulted in the isolation of five lignanoside derivatives (1-4 and 6) and one neolignan (5). These compounds include three new lignanosides, tamariscinosides D-F (1-3), and one liriodendrin (4) that were isolated for the first time from this plant, together with two known compounds, (2R,3S)-dihydro-2-(3,5-dimethoxy-4-hydroxyphenyl)-7-methoxy-5-acetyl-benzofuran (5) and moellenoside B (6). The chemical structures of these isolated compounds were determined using 1D and 2D NMR, MS, and CD spectroscopic data, and the results were compared to data previously reported in the literatures. These compounds were also evaluated in terms of their inhibition of NO production in lipopolysaccharide (LPS)-stimulated activity in the macrophage cell line RAW 264.7. Among them, compounds 1, 2, 5, and 6 exhibited a significant inhibition with IC50 values ranging from 32.3 to 55.8μM.

  6. 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...

  7. 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...

  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. 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.

  10. Identifying regulators for EAG1 channels with a novel electrophysiology and tryptophan fluorescence based screen.

    Directory of Open Access Journals (Sweden)

    Tinatin I Brelidze

    Full Text Available BACKGROUND: Ether-à-go-go (EAG channels are expressed throughout the central nervous system and are also crucial regulators of cell cycle and tumor progression. The large intracellular amino- and carboxy- terminal domains of EAG1 each share similarity with known ligand binding motifs in other proteins, yet EAG1 channels have no known regulatory ligands. METHODOLOGY/PRINCIPAL FINDINGS: Here we screened a library of small biologically relevant molecules against EAG1 channels with a novel two-pronged screen to identify channel regulators. In one arm of the screen we used electrophysiology to assess the functional effects of the library compounds on full-length EAG1 channels. In an orthogonal arm, we used tryptophan fluorescence to screen for binding of the library compounds to the isolated C-terminal region. CONCLUSIONS/SIGNIFICANCE: Several compounds from the flavonoid, indole and benzofuran chemical families emerged as binding partners and/or regulators of EAG1 channels. The two-prong screen can aid ligand and drug discovery for ligand-binding domains of other ion channels.

  11. Synthesis and characterization of iodobenzamide analogues: Potential D-2 dopamine receptor imaging agents

    Energy Technology Data Exchange (ETDEWEB)

    Murphy, R.A.; Kung, H.F.; Kung, M.P.; Billings, J. (Univ. of Pennsylvania, Philadelphia (USA))

    1990-01-01

    (S)-N-((1-Ethyl-2-pyrrolidinyl)methyl)-2-hydroxy-3-iodo-6- methoxybenzamide (({sup 123}I)IBZM) is a central nervous system (CNS) D-2 dopamine receptor imaging agent. In order to investigate the versatility of this parent structure in specific dopamine receptor localization and the potential for developing new dopamine receptor imaging agents, a series of new iodinated benzamides with fused ring systems, naphthalene (INAP) and benzofuran (IBF), was synthesized and radiolabeled, and the in vivo and in vitro biological properties were characterized. The best analogue of IBZM is IBF (21). The specific binding of ({sup 125}I)IBF (21) with rat striatal tissue preparation was found to be saturable and displayed a Kd of 0.106 {plus minus} 0.015 nM. Competition data of various receptor ligands for ({sup 125}I)IBF (21) binding show the following rank order of potency: spiperone greater than IBF (21) greater than IBZM greater than (+)-butaclamol greater than ({plus minus})-ADTN,6,7 greater than ketanserin greater than SCH-23390 much greater than propranolol. The in vivo biodistribution results confirm that ({sup 125}I)IBF (21) concentrated in the striatal area after iv injection into rats. The study demonstrates that ({sup 123}I)IBF (21) is a potential agent for imaging CNS D-2 dopamine receptors.

  12. 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

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

    Directory of Open Access Journals (Sweden)

    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

  14. Liquid–Liquid Equilibrium Measurements for Model Systems Related to Catalytic Fast Pyrolysis of Biomass

    Energy Technology Data Exchange (ETDEWEB)

    Jasperson, Louis V.; McDougal, Rubin J.; Diky, Vladimir; Paulechka, Eugene; Chirico, Robert D.; Kroenlein, Kenneth; Iisa, Kristiina; Dutta, Abhijit

    2017-01-12

    We report liquid-liquid mutual solubilities for binary aqueous mixtures involving 2-, 3-, and 4-ethylphenol, 2-, 3-, and 4-methoxyphenol, benzofuran, and 1H-indene for the temperature range (300 < T/K < 360). Measurements in the water-rich phase for (2-ethylphenol + water) were extended to T = 440 K to facilitate comparison with literature values. Liquid-liquid equilibrium tie-line determinations were made for four ternary systems involving (water + toluene) mixed with a third component; phenol, 3-ethylphenol, 4-methoxyphenol, or 2,4-dimethylphenol. Literature values at higher temperatures are available for the three (ethylphenol + water) systems, and, in general, good agreement is seen. The ternary system (water + toluene + phenol) has been studied previously with inconsistent results reported in the literature, and one report is shown to be anomalous. All systems are modeled with the predictive methods NIST-Modified-UNIFAC and NIST-COSMO-SAC, with generally good success in the temperature range of interest (300 < T/K < 360). This work is part of a larger project on the testing and development of predictive phase equilibrium models for compound types occurring in catalytic fast pyrolysis of biomass, and background information for the larger project is provided.

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

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    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.

  16. 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

  17. 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.

  18. Secondary metabolites from Ganoderma.

    Science.gov (United States)

    Baby, Sabulal; Johnson, Anil John; Govindan, Balaji

    2015-06-01

    Ganoderma is a genus of medicinal mushrooms. This review deals with secondary metabolites isolated from Ganoderma and their biological significance. Phytochemical studies over the last 40years led to the isolation of 431 secondary metabolites from various Ganoderma species. The major secondary compounds isolated are (a) C30 lanostanes (ganoderic acids), (b) C30 lanostanes (aldehydes, alcohols, esters, glycosides, lactones, ketones), (c) C27 lanostanes (lucidenic acids), (d) C27 lanostanes (alcohols, lactones, esters), (e) C24, C25 lanostanes (f) C30 pentacyclic triterpenes, (g) meroterpenoids, (h) farnesyl hydroquinones (meroterpenoids), (i) C15 sesquiterpenoids, (j) steroids, (k) alkaloids, (l) prenyl hydroquinone (m) benzofurans, (n) benzopyran-4-one derivatives and (o) benzenoid derivatives. Ganoderma lucidum is the species extensively studied for its secondary metabolites and biological activities. Ganoderma applanatum, Ganoderma colossum, Ganoderma sinense, Ganoderma cochlear, Ganoderma tsugae, Ganoderma amboinense, Ganoderma orbiforme, Ganoderma resinaceum, Ganoderma hainanense, Ganoderma concinna, Ganoderma pfeifferi, Ganoderma neo-japonicum, Ganoderma tropicum, Ganoderma australe, Ganoderma carnosum, Ganoderma fornicatum, Ganoderma lipsiense (synonym G. applanatum), Ganoderma mastoporum, Ganoderma theaecolum, Ganoderma boninense, Ganoderma capense and Ganoderma annulare are the other Ganoderma species subjected to phytochemical studies. Further phytochemical studies on Ganoderma could lead to the discovery of hitherto unknown biologically active secondary metabolites.

  19. Changes in phenolic concentrations during recurrent selection for resistance to the Mediterranean corn borer (Sesamia nonagrioides Lef.).

    Science.gov (United States)

    Santiago, Rogelio; Sandoya, German; Butrón, Ana; Barros, Jaime; Malvar, Rosa A

    2008-09-10

    Recurrent selection has been reported as successful for improving maize resistance against corn borers. This study was conducted to determine if phenolics concentration in maize changes during recurrent selection to improve stalk resistance to the Mediterranean corn borer. Three cycles of selection [EPS12(S)C0, ESP12(S)C2, and EPS12(S)C3] from the maize synthetic population EPS12 and test crosses to inbred lines A639, B93, and EP42 were field grown and artificially infested with Mediterranean corn borer larvae, and the pith tissues were sampled for biochemical analyses. Two major simple phenolic acids [p-coumaric (p-CA) and trans-ferulic (E-FA) acids] were identified in free and cell-wall fractions, whereas four isomers of diferulic acid (DFA) (8-5'l, 5-5', 8-o-4', and 8-5' benzofuran form) were present in the cell-wall bound fraction. The selection cycles EPS12(S)C0 and EPS12(S)C3 showed less damage and higher cell wall phenolics concentrations than the cycle EPS12(S)C2. In addition, higher concentrations of total DFAs were associated with shorter tunnel length and lower numbers of larvae per stem. The current study shows new and concrete evidence that the cell-wall bound phenolics could have a determinative role in the resistance to the Mediterranean corn borer, although future development of recurrent and divergent selection cycles will clarify this point.

  20. Antipoliovirus Activity of the Organic Extract of Eupatorium buniifolium: Isolation of Euparin as an Active Compound

    Directory of Open Access Journals (Sweden)

    María Florencia Visintini Jaime

    2013-01-01

    Full Text Available The antiviral activity of the organic extract (OE of Eupatorium buniifolium against poliovirus type 1 was determined by in vitro assays with an effective concentration 50 (EC50 of 23.3 ± 3.3 µg/mL. Bioassay-guided fractionation of the OE allowed the isolation of an active principle that was identified by spectroscopic methods (1H- and 13C-NMR, EI-MS, UV, and IR spectroscopy as the benzofuran euparin. The plaque reduction assay in Vero cells was used to assess the antiviral activity of euparin against poliovirus types 1, 2, and 3 with EC50 values of 0.47, 0.12, and 0.15 µg/mL, respectively. Moreover, this compound showed high selectivity indexes of 284.9, 1068, and 854.7, respectively. In order to identify the mechanism by which euparin exerts its antiviral activity, the virucidal effect, the pretreatment of Vero cells, and the time of action on one viral replication cycle were evaluated. Results obtained demonstrated that euparin exerts its effect during the early events of the replication cycle, from the virus adsorption to cells up to the first twenty minutes after infection. This is the first report on the presence of euparin in E. buniifolium and its antiviral activity.

  1. 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.

  2. 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%.

  3. Litter Quality of Populus Species as Affected by Free-Air CO2 Enrichment and N-Fertilization

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    Esther Vermue

    2009-01-01

    Full Text Available The effect of elevated CO2 and nitrogen fertilization on the molecular chemistry of litter of three Populus species and associated soil organic matter (SOM was investigated by pyrolysis-gas chromatography/mass spectrometry. The results are based on 147 quantified organic compounds in 24 litter samples. Litter of P. euramerica was clearly different from that of P. nigra and P. alba. The latter two had higher contents of proteins, polysaccharides, and cutin/cutan, while the former had higher contents of phenols and benzofurans/pyrans. The difference between replications was at least as large as the effect of treatments, so that no systematic chemical changes were attributable to CO2 effect or N-fertilization effect. The chemistry of SOM under the various species and treatments did not show significant changes either. The low number of available replicates that is two was clearly insufficient to overcome the effect of spatial variation on litter chemistry and detect small differences in molecular litter chemistry.

  4. Importance of heterocylic aromatic compounds in monitored natural attenuation for coal tar contaminated aquifers: A review

    Science.gov (United States)

    Blum, Philipp; Sagner, Anne; Tiehm, Andreas; Martus, Peter; Wendel, Thomas; Grathwohl, Peter

    2011-11-01

    NSO heterocycles (HET) are typical constituents of coal tars. However, HET are not yet routinely monitored, although HET are relatively toxic coal tar constituents. The main objectives of the study is therefore to review previous studies and to analyse HET at coal tar polluted sites in order to assess the relevance of HET as part of monitored natural attenuation (MNA) or any other long-term monitoring programme. Hence, natural attenuation of typical HET (indole, quinoline, carbazole, acridine, methylquinolines, thiophene, benzothiophene, dibenzothiophene, benzofuran, dibenzofuran, methylbenzofurans, dimethylbenzofurans and xanthene) were studied at three different field sites in Germany. Compound-specific plume lengths were determined for all main contaminant groups (BTEX, PAH and HET). The results show that the observed plume lengths are site-specific and are above 250 m, but less than 1000 m. The latter, i.e. the upper limit, however mainly depends on the level of investigation, the considered compound, the lowest measured concentration and/or the achieved compound-specific detection limit and therefore cannot be unequivocally defined. All downstream contaminant plumes exhibited HET concentrations above typical PAH concentrations indicating that some HET are generally persistent towards biodegradation compared to other coal tar constituents, which results in comparatively increased field-derived half-lives of HET. Additionally, this study provides a review on physicochemical and toxicological parameters of HET. For three well investigated sites in Germany, the biodegradation of HET is quantified using the centre line method (CLM) for the evaluation of bulk attenuation rate constants. The results of the present and previous studies suggest that implementation of a comprehensive monitoring programme for heterocyclic aromatic compounds is relevant at sites, if MNA is considered in risk assessment and for remediation.

  5. Integrated Strategy for Use of Positron Emission Tomography in Nonhuman Primates to Confirm Multitarget Occupancy of Novel Psychotropic Drugs: An Example with AZD3676.

    Science.gov (United States)

    Varnäs, Katarina; Juréus, Anders; Johnström, Peter; Ahlgren, Charlotte; Schött, Pär; Schou, Magnus; Gruber, Susanne; Jerning, Eva; Malmborg, Jonas; Halldin, Christer; Afzelius, Lovisa; Farde, Lars

    2016-09-01

    Positron emission tomography (PET) is widely applied in central nervous system (CNS) drug development for assessment of target engagement in vivo. As the majority of PET investigations have addressed drug interaction at a single binding site, findings of multitarget engagement have been less frequently reported and have often been inconsistent with results obtained in vitro. AZD3676 [N,N-dimethyl-7-(4-(2-(pyridin-2-yl)ethyl)piperazin-1-yl) benzofuran-2-carboxamide] is a novel combined serotonin (5-hydroxytryptamine) 5-HT1A and 5-HT1B receptor antagonist that was developed for the treatment of cognitive impairment in Alzheimer's disease. Here, we evaluated the properties of AZD3676 as a CNS drug by combining in vitro and ex vivo radioligand binding techniques, behavioral pharmacology in rodents, and PET imaging in nonhuman primates. Target engagement in the nonhuman primate brain was assessed in PET studies by determination of drug-induced occupancy using receptor-selective radioligands. AZD3676 showed preclinical properties consistent with CNS drug potential, including nanomolar receptor affinity and efficacy in rodent models of learning and memory. In PET studies of the monkey brain, AZD3676 inhibited radioligand binding in a dose-dependent manner with similar affinity at both receptors. The equally high affinity at 5-HT1A and 5-HT1B receptors as determined in vivo was not predicted from corresponding estimates obtained in vitro, suggesting more than 10-fold selectivity for 5-HT1A versus 5-HT1B receptors. These findings support the further integrated use of PET for confirmation of multitarget occupancy of CNS drugs. Importantly, earlier introduction of PET studies in nonhuman primates may reduce future development costs and the requirement for animal experiments in preclinical CNS drug development programs.

  6. Comparison of in Silico, Electrochemical, in Vitro and in Vivo Metabolism of a Homologous Series of (Radio)fluorinated σ1 Receptor Ligands Designed for Positron Emission Tomography.

    Science.gov (United States)

    Wiese, Christian; Große Maestrup, Eva; Galla, Fabian; Schepmann, Dirk; Hiller, Achim; Fischer, Steffen; Ludwig, Friedrich-Alexander; Deuther-Conrad, Winnie; Donat, Cornelius K; Brust, Peter; Büter, Lars; Karst, Uwe; Wünsch, Bernhard

    2016-09-28

    The imaging of σ1 receptors in the brain by fluorinated radiotracers will be used for the validation of σ1 receptors as drug targets as well as for differential diagnosis of diseases in the central nervous system. The biotransformation of four homologous fluorinated PET tracers 1'-benzyl-3-(ω-fluoromethyl to ω-fluorobutyl)-3H-spiro[2]benzofuran-1,4'-piperidine] ([(18) F]1-4) was investigated. In silico studies using fast metabolizer (FAME) software, electrochemical oxidations, in vitro studies with rat liver microsomes, and in vivo metabolism studies after application of the PET tracers [(18) F]1-4 to mice were performed. Combined liquid chromatography and mass spectrometry (HPLC-MS) analysis allowed structural identification of non-radioactive metabolites. Radio-HPLC and radio-TLC provided information about the presence of unchanged parent radiotracers and their radiometabolites. Radiometabolites were not found in the brain after application of [(18) F]2-4, but liver, plasma, and urine samples contained several radiometabolites. Less than 2 % of the injected dose of [(18) F]4 reached the brain, rendering [(18) F]4 less appropriate as a PET tracer than [(18) F]2 and [(18) F]3. Compounds [(18) F]2 and [(18) F]3 possess the most promising properties for imaging of σ1 receptors in the brain. High σ1 affinity (Ki =0.59 nm), low lipophilicity (logD7.4 =2.57), high brain penetration (4.6 % of injected dose after 30 min), and the absence of radiometabolites in the brain favor the fluoroethyl derivative [(18) F]2 slightly over the fluoropropyl derivative [(18) F]3 for human use.

  7. In vitro cytochrome P450 inhibition potential of methylenedioxy-derived designer drugs studied with a two-cocktail approach.

    Science.gov (United States)

    Dinger, Julia; Meyer, Markus R; Maurer, Hans H

    2016-02-01

    In vitro cytochrome P450 (CYP) inhibition assays are common approaches for testing the inhibition potential of drugs for predicting potential interactions. In contrast to marketed medicaments, drugs of abuse, particularly the so-called novel psychoactive substances, were not tested before distribution and consumption. Therefore, the inhibition potential of methylenedioxy-derived designer drugs (MDD) of different drug classes such as aminoindanes, amphetamines, benzofurans, cathinones, piperazines, pyrrolidinophenones, and tryptamines should be elucidated. The FDA-preferred test substrates, split in two cocktails, were incubated with pooled human liver microsomes and analysed after protein precipitation using LC-high-resolution-MS/MS. IC50 values were determined of MDD showing more than 50 % inhibition in the prescreening. Values were calculated by plotting the relative metabolite concentration formed over the logarithm of the inhibitor concentration. All MDD showed inhibition against CYP2D6 activity and most of them in the range of the clinically relevant CYP2D6 inhibitors quinidine and fluoxetine. In addition, the beta-keto compounds showed inhibition of the activity of CYP2B6, 5,6-MD-DALT of CYP1A2 and CYP3A, and MDAI of CYP2A6, all in the range of clinically relevant inhibitors. In summary, all MDD showed inhibition of the activity of CYP2D6, six of CYP1A2, three of CYP2A6, 13 of CYP2B6, two of CYP2C9, six of CYP2C19, one of CYP2E1, and six of CYP3A. These results showed that the CYP inhibition by MDD might be clinically relevant, but further studies are needed for final conclusions.

  8. 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).

  9. 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.

  10. 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.

  11. Rational design of novel anti-microtubule agent (9-azido-noscapine) from quantitative structure activity relationship (QSAR) evaluation of noscapinoids.

    Science.gov (United States)

    Santoshi, Seneha; Naik, Pradeep K; Joshi, Harish C

    2011-10-01

    An anticough medicine, noscapine [(S)-3-((R)4-methoxy-6-methyl-5,6,7,8-tetrahydro-[1,3]dioxolo[4,5-g]isoquinolin-5-yl)-6,7-dimethoxyiso-benzofuran-1(3H)-one], was discovered in the authors' laboratory as a novel type of tubulin-binding agent that mitigates polymerization dynamics of microtubule polymers without changing overall subunit-polymer equilibrium. To obtain systematic insight into the relationship between the structural framework of noscapine scaffold and its antitumor activity, the authors synthesized strategic derivatives (including two new ones in this article). The IC(50) values of these analogs vary from 1.2 to 56.0 µM in human acute lymphoblastic leukemia cells (CEM). Geometrical optimization was performed using semiempirical quantum chemical calculations at the 3-21G* level. Structures were in agreement with nuclear magnetic resonance analysis of molecular flexibility in solution and crystal structures. A genetic function approximation algorithm of variable selection was used to generate the quantitative structure activity relationship (QSAR) model. The robustness of the QSAR model (R(2) = 0.942) was analyzed by values of the internal cross-validated regression coefficient (R(2) (LOO) = 0.815) for the training set and determination coefficient (R(2) (test) = 0.817) for the test set. Validation was achieved by rational design of further novel and potent antitumor noscapinoid, 9-azido-noscapine, and reduced 9-azido-noscapine. The experimentally determined value of pIC(50) for both the compounds (5.585 M) turned out to be very close to predicted pIC(50) (5.731 and 5.710 M).

  12. 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.

  13. Antiviral activity of KR-23502 targeting nuclear export of influenza B virus ribonucleoproteins.

    Science.gov (United States)

    Jang, Yejin; Lee, Hye Won; Shin, Jin Soo; Go, Yun Young; Kim, Chonsaeng; Shin, Daeho; Malpani, Yashwardhan; Han, Soo Bong; Jung, Young-Sik; Kim, Meehyein

    2016-10-01

    The spiro compound 5,6-dimethyl-3H,3'H-spiro(benzofuran-2,1'-isobenzofuran)-3,3'-dione (KR-23502) has antiviral activity against influenza A and more potently B viruses. The aim of this study is to elucidate its mechanism of action. Subcellular localization and time-course expression of influenza B viral proteins, nucleoprotein (NP) and matrix protein 1 (M1), showed that KR-23502 reduced their amounts within 5 h post-infection. Early steps of virus life cycle, including virus entry, nuclear localization of NP and viral RNA-dependent RNA replication, were not affected by KR-23502. Instead it interrupted a later event corresponding to nuclear export of NP and M1 proteins. Delivery of viral ribonucleoprotein (vRNP)-M1 complex has been known to be mediated by the viral nuclear export protein (NEP) through interaction with cellular chromosomal maintenance 1 (CRM1) protein. In this study, we experimentally demonstrated that the compound targets the nuclear export of vRNP. Moreover, a single mutation (aspartate to glycine) at amino acid position 54 in M1 [M1(D54G)] was detected after 18 passages in the presence of KR-23502 with a 2-fold increase in 50% effective concentration indicating that this compound has a relatively high genetic barrier to resistance. Interestingly, it was observed that proteasome-mediated degradation of M1(D54G) was attenuated by KR-23502. In conclusion, we suggest that KR-23502 shows its anti-influenza activity by downregulating NEP/CRM1-mediated nuclear export of influenza vRNP and M1. KR-23502 provides a core chemical skeleton for further structure-based design of novel antivirals against influenza viruses.

  14. 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.

  15. 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.

  16. Zatosetron, a potent, selective, and long-acting 5HT3 receptor antagonist: synthesis and structure-activity relationships.

    Science.gov (United States)

    Robertson, D W; Lacefield, W B; Bloomquist, W; Pfeifer, W; Simon, R L; Cohen, M L

    1992-01-24

    Antagonists of 5HT3 receptors are clinically effective in treating nausea and emesis associated with certain oncolytic drugs, including cisplatin. Moreover, these agents may be useful in pharmacological management of several central nervous system disorders, including anxiety, schizophrenia, dementia, and substance abuse. Our studies on aroyltropanamides led to the discovery that dihydrobenzofuranyl esters and amides are potent 5HT3 receptor antagonists. Simple benzoyl derivatives of tropine and 3 alpha-aminotropane possessed weak 5HT3 receptor antagonist activity, as judged by blockade of bradycardia produced by iv injection of serotonin (5HT) to anesthetized rats. Within this series, use of benzofuran-7-carboxamide as the aroyl moiety led to a substantial increase of 5HT3 receptor affinity. The optimal 5HT3 receptor antagonist identified via extensive SAR studies was endo-5-chloro-2,3-dihydro-2,2-dimethyl-N-(8-methyl-8-azabicyclo[3.2.1]oc t- 3-yl)-7-benzofurancarboxamide (Z)-2-butenedioate (zatosetron maleate). The 7-carbamyl regiochemistry, dimethyl substitution, chloro substituent, and endo stereochemistry were all crucial elements of the SAR. Zatosetron maleate was a potent antagonist of 5HT-induced bradycardia in rats (ED50 = 0.86 micrograms/kg i.v.). Low oral doses of zatosetron (30 micrograms/kg) produced long-lasting antagonism of 5HT3 receptors, as evidenced by blockade of 5HT-induced bradycardia for longer than 6 h in rats. Moreover, this compound did not produce hemodynamic effects after i.v. administration to rats, nor did it block carbamylcholine-induced bradycardia in doses that markedly blocked 5HT3 receptors. Thus, zatosetron is a potent, selective, orally effective 5HT3 receptor antagonist with a long duration of action in rats.

  17. 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

  18. 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.

  19. Inhibitory effects of (2S, 3S)-3-[3-[4-(trifluoromethyl)benzoylamino]benzyloxy]aspartate (TFB-TBOA) on the astrocytic sodium responses to glutamate.

    Science.gov (United States)

    Bozzo, Luigi; Chatton, Jean-Yves

    2010-02-26

    Astrocytes are responsible for the majority of the clearance of extracellular glutamate released during neuronal activity. dl-threo-beta-benzyloxyaspartate (TBOA) is extensively used as inhibitor of glutamate transport activity, but suffers from relatively low affinity for the transporter. Here, we characterized the effects of (2S, 3S)-3-[3-[4-(trifluoromethyl)benzoylamino]benzyloxy]aspartate (TFB-TBOA), a recently developed inhibitor of the glutamate transporter on mouse cortical astrocytes in primary culture. The glial Na(+)-glutamate transport system is very efficient and its activation by glutamate causes rapid intracellular Na(+) concentration (Na(+)(i)) changes that enable real time monitoring of transporter activity. Na(+)(i) was monitored by fluorescence microscopy in single astrocytes using the fluorescent Na(+)-sensitive probe sodium-binding benzofuran isophtalate. When applied alone, TFB-TBOA, at a concentration of 1 microM, caused small alterations of Na(+)(i). TFB-TBOA inhibited the Na(+)(i) response evoked by 200 microM glutamate in a concentration-dependent manner with IC(50) value of 43+/-9 nM, as measured on the amplitude of the Na(+)(i) response. The maximum inhibition of glutamate-evoked Na(+)(i) increase by TFB-TBOA was >80%, but was only partly reversible. The residual response persisted in the presence of the AMPA/kainate receptor antagonist CNQX. TFB-TBOA also efficiently inhibited Na(+)(i) elevations caused by the application of d-aspartate, a transporter substrate that does not activate non-NMDA ionotropic receptors. TFB-TBOA was found not to influence the membrane properties of cultured cortical neurons recorded in whole-cell patch clamp. Thus, TFB-TBOA, with its high potency and its apparent lack of neuronal effects, appears to be one of the most useful pharmacological tools available so far for studying glial glutamate transporters.

  20. In situ fluorescence imaging of glutamate-evoked mitochondrial Na+ responses in astrocytes.

    Science.gov (United States)

    Bernardinelli, Yann; Azarias, Guillaume; Chatton, Jean-Yves

    2006-10-01

    Astrocytes can experience large intracellular Na+ changes following the activation of the Na+-coupled glutamate transport. The present study investigated whether cytosolic Na+ changes are transmitted to mitochondria, which could therefore influence their function and contribute to the overall intracellular Na+ regulation. Mitochondrial Na+ (Na+(mit)) changes were monitored using the Na+-sensitive fluorescent probe CoroNa Red (CR) in intact primary cortical astrocytes, as opposed to the classical isolated mitochondria preparation. The mitochondrial localization and Na+ sensitivity of the dye were first verified and indicated that it can be safely used as a selective Na+(mit) indicator. We found by simultaneously monitoring cytosolic and mitochondrial Na+ using sodium-binding benzofuran isophthalate and CR, respectively, that glutamate-evoked cytosolic Na+ elevations are transmitted to mitochondria. The resting Na+(mit) concentration was estimated at 19.0 +/- 0.8 mM, reaching 30.1 +/- 1.2 mM during 200 microM glutamate application. Blockers of conductances potentially mediating Na+ entry (calcium uniporter, monovalent cation conductances, K+(ATP) channels) were not able to prevent the Na+(mit) response to glutamate. However, Ca2+ and its exchange with Na+ appear to play an important role in mediating mitochondrial Na+ entry as chelating intracellular Ca2+ with BAPTA or inhibiting Na+/Ca2+ exchanger with CGP-37157 diminished the Na+(mit) response. Moreover, intracellular Ca2+ increase achieved by photoactivation of caged Ca2+ also induced a Na+(mit) elevation. Inhibition of mitochondrial Na/H antiporter using ethylisopropyl-amiloride caused a steady increase in Na+(mit) without increasing cytosolic Na+, indicating that Na+ extrusion from mitochondria is mediated by these exchangers. Thus, mitochondria in intact astrocytes are equipped to efficiently sense cellular Na+ signals and to dynamically regulate their Na+ content.

  1. Effects of glial glutamate transporter inhibitors on intracellular Na+ in mouse astrocytes.

    Science.gov (United States)

    Chatton, J Y; Shimamoto, K; Magistretti, P J

    2001-03-02

    The effects of inhibitors of the glial Na+/glutamate co-transporter on the intracellular Na+ concentration ([Na+](i)) were investigated in mouse cortical astrocytes. [Na+](i) was monitored by fluorescence microscopy on single astrocytes using the Na+-sensitive probe sodium-binding benzofuran isophtalate. Application of the competitive inhibitors threo-beta-hydroxyaspartate (THA) and trans-pyrrolidine-2,4-dicarboxylic acid (t-PDC) resulted in robust and reversible increases in [Na+](i) that were comparable in shape to the response to glutamate but about twice lower in amplitude. As previously observed with glutamate, the amplitude of the [Na+](i) response to these compounds was concentration-dependent with EC(50) values of 11.1 microM (THA) and 7.6 microM (t-PDC), as was the initial rate of [Na+](i) rise (EC(50) values of 14.8 microM for THA and 11.5 microM for t-PDC). Both compounds diminished the response to subsequent glutamate applications, possibly because of an inhibitory effect of the intracellularly-accumulated compounds. In comparison, the newly-developed compound threo-beta-benzyloxyaspartate (TBOA) alone did not cause any significant alteration of [Na+](i) up to a concentration of 500 microM . TBOA inhibited the [Na+](i) response evoked by 200 microM glutamate in a concentration-dependent manner with IC(50) values of 114 and 63 microM, as measured on the amplitude and the initial rate, respectively. The maximum inhibition of glutamate-evoked [Na+](i) increase by TBOA was approximately 70%. The residual response persisted in the presence of a non-NMDA receptor antagonist or the inhibitor of the GLT-1 glutamate transporters, dihydrokainate (DHK). In view of the complete reversibility of its effects, TBOA represents a very useful pharmacological tool for studies of glutamate transporters.

  2. 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

  3. Effects of the GABAB receptor-positive modulators CGP7930 and rac-BHFF in baclofen- and γ-hydroxybutyrate-discriminating pigeons.

    Science.gov (United States)

    Koek, Wouter; France, Charles P; Cheng, Kejun; Rice, Kenner C

    2012-05-01

    In vivo effects of GABA(B) receptor-positive modulators suggest them to have therapeutic potential to treat central nervous system disorders such as anxiety and drug abuse. Although these effects are thought to be mediated by positive modulation of GABA(B) receptors, such modulation has been examined primarily in vitro. This study further examined the in vivo properties of the GABA(B) receptor-positive modulators 2,6-di-tert-butyl-4-(3-hydroxy-2,2-dimethylpropyl) phenol (CGP7930) and (R,S)-5,7-di-tert-butyl-3-hydroxy-3-trifluoromethyl-3H-benzofuran-2-one (rac-BHFF). In pigeons discriminating baclofen from saline, γ-hydroxybutyrate (GHB) produced 100% baclofen-appropriate responding, and the GABA(B) antagonist 3-aminopropyl(dimethoxymethyl) phosphinic acid (CGP35348) blocked the effects of both drugs. CGP7930 and rac-BHFF produced at most 41 and 74% baclofen-appropriate responding, respectively, and enhanced the discriminative stimulus effects of baclofen, but not of GHB. In pigeons discriminating GHB from saline, CGP7930 and rac-BHFF produced at most 1 and 49% GHB-appropriate responding, respectively, and enhanced the effects of baclofen, but not of GHB. Enhancement of the discriminative stimulus effects of baclofen by rac-BHFF and CGP7930 is further evidence of their effectiveness as GABA(B) receptor-positive modulators in vivo. Furthermore, lack of complete substitution of the positive modulators rac-BHFF and CGP7930 for baclofen and GHB suggests that their discriminative stimulus effects differ from those of GABA(B) receptor agonists. Finally, together with converging evidence that the GABA(B) receptor populations mediating the effects of baclofen and GHB are not identical, the present findings suggest that these populations differ in their susceptibility to positive modulatory effects. Such differences could allow for more selective therapeutic targeting of the GABA(B) system.

  4. 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

  5. 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.}

  6. 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}.

  7. 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.

  8. 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.

  9. Angiotensin I conversion to angiotensin II stimulates cortical collecting duct sodium transport.

    Science.gov (United States)

    Komlosi, Peter; Fuson, Amanda L; Fintha, Attila; Peti-Peterdi, János; Rosivall, Laszlo; Warnock, David G; Bell, Phillip Darwin

    2003-08-01

    Angiotensin (Ang) II directly stimulates epithelial sodium channel activity in the rabbit cortical collecting duct. Because Ang I and converting enzyme analogues might be present in the distal nephron, this raises the possibility of intraluminal generation of Ang II. Conversion of Ang I to Ang II was monitored by Ang II-dependent changes in intracellular sodium concentration as a reflection of sodium transport across the apical membrane. This involved imaging-based fluorescence microscopy with sodium-binding benzofuran isophthalate in isolated, perfused, cortical collecting-duct segments from rabbit kidney. Principal and intercalated cells were differentiated by rhodamine-conjugated peanut lectin. Control principal cell intracellular sodium concentration, during perfusion with 25 mmol/L NaCl and zero sodium in the bath plus monensin (10(-5) mol/L) averaged 5.8+/-0.14 mmol/L (n=156). The increase in intracellular sodium concentration, when luminal NaCl was increased from 25 to 150 mmol/L, was elevated by 3.5-fold in the presence of intraluminal Ang I (10(-6) mol/L). Also, the effects of Ang I on sodium transport were not significantly different from the effects of Ang II (10(-9) mol/L). Ang I was used in micromolar concentrations to ensure that there was sufficient substrate available for conversion to Ang II. Inhibition of the angiotensin-converting enzyme with captopril reduced the stimulatory effect of Ang I. These results suggest that intraluminal conversion of Ang I to Ang II can occur in the cortical collecting duct, resulting in enhanced apical sodium entry.

  10. Angiotensin II directly stimulates macula densa Na-2Cl-K cotransport via apical AT(1) receptors.

    Science.gov (United States)

    Kovács, Gergely; Peti-Peterdi, János; Rosivall, László; Bell, P Darwin

    2002-02-01

    ANG II is a modulator of tubuloglomerular feedback (TGF); however, the site of its action remains unknown. Macula densa (MD) cells sense changes in luminal NaCl concentration ([NaCl](L)) via a Na-2Cl-K cotransporter, and these cells do possess ANG II receptors. We tested whether ANG II regulates Na-2Cl-K cotransport in MD cells. MD cell Na(+) concentration ([Na(+)](i)) was measured using sodium-binding benzofuran isophthalate with fluorescence microscopy. Resting [Na(+)](i) in MD cells was 27.7 +/- 1.05 mM (n = 138) and increased (Delta[Na(+)](i)) by 18.5 +/- 1.14 mM (n = 17) at an initial rate (Delta[Na(+)](i)/Deltat) of 5.54 +/- 0.53 x 10(-4) U/s with an increase in [NaCl](L) from 25 to 150 mM. Both Delta[Na(+)](i) and Delta[Na(+)](i)/Deltat were inhibited by 80% with 100 microM luminal furosemide. ANG II (10(-9) or 10(-12) M) added to the lumen increased MD resting [Na(+)](i) and [NaCl](L)-dependent Delta[Na(+)](i) and caused a twofold increase in Delta[Na(+)](i)/Deltat. Bath (10(-9) M) ANG II also stimulated cotransport activity, and there was no additive effect of simultaneous addition of ANG II to bath and lumen. The effects of luminal ANG II were furosemide sensitive and abolished by the AT(1) receptor blocker candesartan. ANG II at 10(-6) M failed to stimulate the cotransporter, whereas increased cotransport activity could be restored by blocking AT(2) receptors with PD-123, 319. Thus ANG II may modulate TGF responses via alterations in MD Na-2Cl-K cotransport activity.

  11. Pharmacoproteomic study of the natural product Ebenfuran III in DU-145 prostate cancer cells: the quantitative and temporal interrogation of chemically induced cell death at the protein level.

    Science.gov (United States)

    Roumeliotis, Theodoros I; Halabalaki, Maria; Alexi, Xanthippi; Ankrett, Dyan; Giannopoulou, Eugenia G; Skaltsounis, Alexios-Leandros; Sayan, Berna S; Alexis, Michael N; Townsend, Paul A; Garbis, Spiros D

    2013-04-05

    A naturally occurring benzofuran derivative, Ebenfuran III (Eb III), was investigated for its antiproliferative effects using the DU-145 prostate cell line. Eb III was isolated from Onobrychis ebenoides of the Leguminosae family, a plant endemic in Central and Southern Greece. We have previously reported that Eb III exerts significant cytotoxic effects on certain cancer cell lines. This effect is thought to occur via the isoprenyl moiety at the C-5 position of the molecule. The study aim was to gain a deeper understanding of the pharmacological effect of Eb III on DU-145 cell death at the translational level using a relative quantitative and temporal proteomics approach. Proteins extracted from the cell pellets were subjected to solution phase trypsin proteolysis followed by iTRAQ-labeling. The labeled tryptic peptide extracts were then fractionated using strong cation exchange chromatography and the fractions were analyzed by nanoflow reverse phase ultraperformance liquid chromatography-nanoelectrospray ionization-tandem mass spectrometry analysis using a hybrid QqTOF platform. Using this approach, we compared the expression levels of 1360 proteins analyzed at ≤ 1% global protein false discovery rate (FDR), commonly present in untreated (control, vehicle only) and Eb III-treated cells at the different exposure time points. Through the iterative use of Ingenuity Pathway Analysis with hierarchical clustering of protein expression patterns, followed by bibliographic research, the temporal regulation of the Calpain-1, ERK2, PAR-4, RAB-7, and Bap31 proteins were identified as potential nodes of multipathway convergence to Eb III induced DU-145 cell death. These proteins were further verified with Western blot analysis. This gel-free, quantitative 2DLC-MS/MS proteomics method effectively captured novel modulated proteins in the DU-145 cell line as a response to Eb III treatment. This approach also provided greater insight to the multifocal and combinatorial signaling

  12. GC-MS analysis of leaf extracts ofTerminalia macroptera andDioclea relfexa, two medicinal plants used for the treatment of respiratory tract disorders

    Institute of Scientific and Technical Information of China (English)

    Theresa Ibibia Edewor; Nimotalai Olabisi Kazeem; Stephen Oluwagbemiga Owa

    2016-01-01

    Objective: To analyze the phytochemicals that are present in two medicinal plants which are used for the treatment of respiratory tract infections by gas chromatography-mass spectrometer. Methods: The plant leaves were extracted withn-hexane and methanol separately. Both extracts were analyzed for present phytochemicals using the method described by Harborne, 1985 while only methanol extracts were subjected to gas chromatography-mass spectrometer analysis. Results:Phytochemical screening of the methanolic extracts ofTerminalia macroptera (T. macroptera) revealed the presence of glycosides, tannins, flavonoids, saponins and steroids while that ofDioclea reflexa (D. reflexa) showed the presence of flavonoids, saponins and steroids. Then-hexane extracts were devoid of the screened phytochemicals. Twelve and twenty-five compounds were identified in the leaves ofT. macroptera andD. reflexa respectively. These compounds were fatty acids, fatty acid esters, other esters, heterocyclics and phenolics. The most abundant compound inT. macroptera was benzenetriol (53.30%) while the predominant compounds inD. reflexa were dodecanoic acid, methyl ester (15.31%), 5, 5, 8a-trimethyl-3, 5, 6, 7, 8, 8a-hexahydro-2H-chromene (9.73%), 10-octadecenoic acid, methyl ester and 2-hexadecanoic acid, methyl ester (8.95%). Benzofuran, 2, 3-dihydro, 3, 7, 11, 15-tetramethyl-2-hexadecen-1-ol and hexadecanoic acid, methyl ester were common in both plant extracts. The antimicrobial properties of the leaves of these plants could be responsible for their use in the treatment of respiratory tract infections. Conclusions:Some of the identified phytochemicals in the plant leaves are responsible for its use in the treatment of respiratory tract infections.

  13. Biochemical fingerprint and pharmacological applications of Barleria noctiflora L.f. leaves.

    Science.gov (United States)

    Alagar Yadav, Sangilimuthu; Ramalingam, Sathishkumar; Jebamalairaj, Anitha; Subban, Ravi; Sundaram, Karpagavalli Mennakshi

    2016-12-01

    Background Antioxidant and antihistamine agents from Barleria noctiflora L.f. as natural source due to the existing modern medicine give various adverse effects to overcome these problems with natural products. MethodsB. noctiflora leaves extract was fractionated with column chromatography; the homogenized fractions were monitored with thin layer chromatography (TLC) and characterized by using UV-visible, FT-IR, 1H NMR, 13C NMR and mass spectrometry spectral studies. The volatile phytoconstituents of B. noctiflora extract were analysed by gas chromatography-mass spectrometry. Phytoconstituents from B. noctiflora leaves extract were screened for their antioxidant and antihistamine potential in vitro (2,2-diphenyl-1-picrylhydrazyl radical scavenging activity, 2,2'-azinobis-3-ethylbenzothiozoline-6-sulfonic acid radical decolouration assay, nitric oxide radical scavenging activity, superoxide radical scavenging activity and hydrogen peroxide radical scavenging activity) and in silico (molecular docking), respectively. Results Antioxidant and antihistamine barlerinoside has been isolated and characterized from the leaves of B. noctiflora L.f. Barlerinoside revealed their free-radical scavenging ability on OH-, OH•, NO-, O2- and H2O2 radicals and found high percentage inhibition against OH- radical at the IC50 value of 50.45±2.52  µg. The methanol (MeOH) extract of B. noctiflora leaves contains cyclotene; N,N-dimethylglycine; tetrahydrocyclopenta [1,3] dioxin-4-one; phenol, 2-methoxy-; benzofuran, 2-methyl-; 1,4:3,6-dianhydro-α-d-glucopyranose; 2-methoxy-4-vinylphenol; 1,3;2,5-dimethylene-l-rhamnitol; levoglucosan and bicyclo[2.2.2]oct-7-ene-2,5-dione as being the major compounds. Among phytoconstituents present in the extract, the hexestrol; 1,2-benzenedicarboxylic acid, bis(2-methylpropyl) ester; 1-(3,6,6-trimethyl-1,6,7,7a-tetrahydrocyclopenta[c]pyran-1-yl) ethanone; megastigmatrienone; furan interacted with histamine H1 receptor and bind at GLU-177 and ASP

  14. Anti-Inflammatory Effect of Red Piper Crocatum Leaves Extract Decrease TNF-α and IL-6 Levels in Wistar Rat with Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Sri Wahjuni

    2016-05-01

    Full Text Available Background: This research aims to find a cure for anti-inflammation, based on the utilization of red piper crocatum. The research was started with descriptive study to explore active components of red piper crocatum leaf and followed by experimental study to investigate red piper crocatum activity of the leaf extract in anti-inflammation induced Wistar rat. In this research observed three dominant components: caryophyllene bicyclo [5.2.0] none,2 methylene-4,8,8-trimethyl-4-vinyl; phytol; 5,9-propano-5H-benzocycloheptene,6,7,8,9-tetrahydro-7,11-bis(methylene; 4,4-ethynedioxy-2-hexadecen-15-15 olide 1,4,9-trioxaspiro [4,15] eic os-6-en-8-one, 10 methyl; 1H-1,2,4-triazole-5(H-thione,4-allyl-3-(3-furyl; Benzofuran,2,3-dihydro-2-methyl-7-phenyl which are possibly active to inhibit anti-inflammation to atherosclerosis. Bad eating habits also can cause various health problems, such as obesity, dyslipidemia, inflammation to atherosclerosis. This study was conducted to investigate of red piper crocatum leaves extract as an anti-inflammation through decrease of biochemistry markers TNF-α and IL-6 levels. Method: This is a true experimental with randomized pre-test and post-test control group design, using 50 Wistar rats that are divided into 5 groups: control group using 0 mg/kg BW red piper crocatum leaves extract, treatment group 1 using 50 mg/kg BW red piper crocatum leaves extract, treatment group 2 using 100 mg/kg BW red piper crocatum leaves extract, treatment group 3 using 150 mg/kg BW red piper crocatum leaves extract, and treatment group 4 200mg/kg BW red piper crocatum leaves extract. Results: It was observed that intake of 150 mg/BW red piper crocatum leaves extract results in the highest significance decrease of 45.63% of TNF-α levels from (28.62 ± 1.25 to 15.56 ± 7.20 рg/mL and a significance decrease of 15.42% of IL-6 level from (134.64 ± 1.98 to 113.87 ± 4.30 рg/mL. Conclusion: It can be concluded that intake of red piper crocatum

  15. 四个不同产地淫羊藿热裂解产物对比分析%Analysis of Pyrolysates from Four Herba Epimedii from Different Growing Areas

    Institute of Scientific and Technical Information of China (English)

    杜萍; 陈金素; 何素芳; 孙卉; 刘春侠

    2012-01-01

    采用裂解色谱法研究比较4个产地淫羊藿的裂解组分。结果表明:4个产地的淫羊藿裂解产物分别为云南68个、吉林48个、辽宁51个、四川56个,主要为酚类、酮类、醛类、烯烃、芳烃、萜类、杂环类化合物;主要裂解产物为苯酚(相对含量在5%~8%之间),其他为环戊烯酮类、苯酚衍生物、2,3-二氢-苯并呋喃等;不同地域的同种药材其裂解产物分布基本相同,但各组分的含量差异却很大;高效液相色谱法测定不同地域淫羊藿中淫羊藿甙含量表明:云南为5.49%、四川为12.85%、辽宁为1.95%、吉林为2.82%,差异比较大。%The pyrolysates of Herba Epimedii from four different growing areas were investigated by Pyrolysis-Gas Chromatography. The results indicated that 68, 48, 51 and 56 compounds were identified from the pyrolysates Herba Epimedii grown in Yunnan, Jilin, Liaoning and Sichuan, respectively, which were mainly phenols, ketones, aldehydes, alkenes, terpenoids and heterocyclic compounds. The most predominant compound was phenol (5% -- 8%) followed by cyclopenten-l-one, benzofuran, phenol derivatives, etc. The composition of pyrolysates of Herba Epimedii from four different growing areas was basically consistent, while the contents all identified compounds varied with growing areas. Greatly different lcariin contents were determined by HPLC in Herba Epimedii from Yunnan, Sichuan, Liaoning and Jilin, which were 5.49%, 12.85%, 1.95% and 2.82%, respectively.

  16. 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

  17. Evaluation of selective NK(1) receptor antagonist CI-1021 in animal models of inflammatory and neuropathic pain.

    Science.gov (United States)

    Gonzalez, M I; Field, M J; Hughes, J; Singh, L

    2000-08-01

    CI-1021 ([(2-benzofuran)-CH(2)OCO]-(R)-alpha-MeTrp-(S)-NHCH(CH (3))Ph) is a selective and competitive neurokinin-1 (NK(1)) receptor antagonist. This study examines its activity in animal models of inflammatory and neuropathic pain. In mice, CI-1021 (1-30 mg/kg, s.c.) dose dependently blocked the development of the late phase of the formalin response with a minimum effective dose (MED) of 3 mg/kg. Two chemically unrelated NK(1) receptor antagonists, CP-99,994 (3-30 mg/kg) and SR 140333 (1-100 mg/kg), also dose dependently blocked the late phase, with respective MEDs of 3 and 10 mg/kg. PD 156982, a NK(1) receptor antagonist with poor central nervous system penetration, failed to have any effect. However, when administered i. c.v., it selectively blocked the late phase of the formalin response. Chronic constrictive injury (CCI) to a sciatic nerve in the rat induced spontaneous pain, thermal and mechanical hyperalgesia, and cold, dynamic, and static allodynia. CI-1021 (10-100 mg/kg) and morphine (3 mg/kg) blocked all the responses except dynamic allodynia. Carbamazepine (100 mg/kg) was weakly effective against all the responses. Once daily administration of morphine (3 mg/kg, s. c.) in CCI rats led to the development of tolerance within 6 days. Similar administration of CI-1021 (100 mg/kg, s.c.) for up to 10 days did not induce tolerance. Moreover, the morphine tolerance failed to cross-generalize to CI-1021. CI-1021 blocked the CCI-induced hypersensitivity in the guinea pig, with a MED of 0.1 mg/kg, p.o. CI-1021 (10-100 mg/kg, s.c.) did not show sedative/ataxic action in the rat rota-rod test. It is suggested that NK(1) receptor antagonists possess a superior side effect profile to carbamazepine and morphine and may have a therapeutic use for the treatment of inflammatory and neuropathic pain.

  18. GABAB receptor-positive modulators: enhancement of GABAB receptor agonist effects in vivo.

    Science.gov (United States)

    Koek, Wouter; France, Charles P; Cheng, Kejun; Rice, Kenner C

    2010-10-01

    In vivo effects of GABA(B) receptor-positive modulators suggest that they have therapeutic potential for treating central nervous system disorders such as anxiety, depression, and drug abuse. Although these effects generally are thought to be mediated by positive modulation of GABA(B) receptors, such modulation has been examined primarily in vitro. The present study was aimed at further examining the in vivo positive modulatory properties of the GABA(B) receptor-positive modulators, 2,6-di-tert-butyl-4-(3-hydroxy-2,2-dimethylpropyl) phenol (CGP7930) and (R,S)-5,7-di-tert-butyl-3-hydroxy-3-trifluoromethyl-3H-benzofuran-2-one (rac-BHFF). Both compounds enhanced loss of righting induced by baclofen in mice. However, CGP7930 was less effective and rac-BHFF was less potent for enhancing loss of righting induced by γ-hydroxybutyrate (GHB), which, like baclofen, has GABA(B) receptor agonist properties. In contrast with baclofen- and GHB-induced loss of righting, the hypothermic effects of baclofen and GHB were not enhanced by rac-BHFF but were enhanced by CGP7930 only at doses that produced hypothermia when given alone. CGP7930-induced hypothermia was not attenuated by the GABA(B) receptor antagonist 3-aminopropyl(diethoxymethyl)phosphinic acid (CGP35348), at doses that blocked baclofen-induced hypothermia, and was not increased by the nitric-oxide synthase inhibitor N(ω)-nitro-L-arginine methyl ester, at doses that increased the hypothermic effects of baclofen and GHB. The results provide evidence that CGP7930 and rac-BHFF act in vivo as positive modulators at GABA(B) receptors mediating loss of righting, but not at GABA(B) receptors mediating hypothermia. Conceivably, CGP7930, but not rac-BHFF, acts as an allosteric agonist at these latter receptors. Taken together, the results provide further evidence of pharmacologically distinct GABA(B) receptor subtypes, possibly allowing for a more selective therapeutic interference with the GABA(B) system.

  19. Distribution and functional properties of glutamate receptors in the leech central nervous system.

    Science.gov (United States)

    Dierkes, P W; Hochstrate, P; Schlue, W R

    1996-06-01

    1. The effect of kainate and other glutamatergic agonists on the membrane potential (Em), the intracellular Na+ activity (aNai), and the intracellular free Ca2+ concentration ([Ca2+]i) of identified leech neurons and neuropile glial cells was measured with conventional and ion-sensitive microelectrodes, as well as with the use of the iontophoretically injected fluorescent indicators sodium-binding benzofuran isophthalate and Fura-2. 2. In Retzius neurons, AE, L, 8, and 101 motoneurons, and in the unclassified 50 neurons (Leydig cells) and AP neurons, as well as in neuropile glial cells, bath application of 100 microM kainate evoked a marked membrane depolarization and an increase in aNai and [Ca2+]i. The kainate-induced aNai increase persisted in solutions with high Mg2+ concentration in which synaptic transmission is blocked. 3. A membrane depolarization as well as an increase in aNai and [Ca2+]i was also evoked by L-glutamate, quisqualate, and L-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA). The agonist-induced [Ca2+]i increase was inhibited by 6,7-dinitroquinoxaline-2,3-dione (DNQX). 4. In Ca(2+)-free solution, the kainate-induced [Ca2+]i increase was abolished in the neurons and in neuropile glial cells, whereas membrane depolarization and aNai increase were unchanged. In Na(+)-free solution, kainate had no effect on Em, aNai, or [Ca2+]i in the neurons. 5. In the mechanosensory T, P, and N neurons, kainate induced considerably smaller membrane depolarizations than in the other neurons or in neuropile glial cells, and it had no significant effect on aNai or [Ca2+]i. 6. It is concluded that in leech segmental ganglia the majority of the neurons and the neuropile glial cells, but probably not the mechanosensory neurons, possess glutamate receptors of the AMPA-kainate type. In the neurons, the [Ca2+]i increase caused by glutamatergic agonists is due to Ca2+ influx through voltage-dependent Ca2+ channels that are activated by the agonist

  20. Neuronal nitric oxide synthase: its role and regulation in macula densa cells.

    Science.gov (United States)

    Kovács, Gergely; Komlósi, Péter; Fuson, Amanda; Peti-Peterdi, János; Rosivall, László; Bell, P Darwin

    2003-10-01

    Macula densa (MD) cells detect changes in distal tubular sodium chloride concentration ([NaCl](L)), at least in part, through an apical Na:2Cl:K co-transporter. This co-transporter may be a site for regulation of tubuloglomerular feedback (TGF), and recently angiotensin II (Ang II) was shown to regulate the MD Na:2Cl:K co-transporter. In addition, nitric oxide (NO) produced via neuronal NO synthase (nNOS) in MD cells attenuates MD-TGF signaling. This study investigated [NaCl](L)-dependent MD-NO production, the regulation of co-transporter activity by NO, and the possible interaction of NO with Ang II. MD cell Na(+) concentration ([Na(+)](i)) and NO production were measured using sodium-binding benzofuran isophthalate and 4-amino-5-methylamino-2',7'-difluorescein diacetate, respectively, using fluorescence microscopy. Na:2Cl:K co-transport activity was assessed as the initial rate of increase in [Na(+)](i) when [NaCl](L) was elevated from 25 to 150 mM. 10(-4) M 7-nitroindazole, a specific nNOS blocker, significantly increased by twofold the initial rate of rise in [Na(+)](i) when [NaCl](L) was increased from 25 to 150 mM, indicating co-transporter stimulation. There was no evidence for an interaction between the stimulatory effect of Ang II and the inhibitory effect of NO on co-transport activity, and, furthermore, Ang II failed to alter MD-NO production. NO production was sensitive to [NaCl](L) but increased only when [NaCl](L) was elevated from 60 to 150 mM. These studies indicate that MD-NO directly inhibits Na:2Cl:K co-transport and that NO and Ang II independently alter co-transporter activity. In addition, generation of MD-NO seems to occur only at markedly elevated [NaCl](L), suggesting that NO may serve as a buffer against high rates of MD cell transport and excessive TGF-mediated vasoconstriction.

  1. Angiotensin II directly stimulates ENaC activity in the cortical collecting duct via AT(1) receptors.

    Science.gov (United States)

    Peti-Peterdi, János; Warnock, David G; Bell, P Darwin

    2002-05-01

    Angiotensin II (AngII) helps to regulate overall renal tubular reabsorption of salt and water, yet its effects in the distal nephron have not been well studied. The purpose of these studies was to determine whether AngII stimulates luminal Na(+) transport in the cortical collecting duct (CCD). Intracellular Na(+) concentration ([Na(+)](i)), as a reflection of Na(+) transport across the apical membrane, was measured with fluorescence microscopy using sodium-binding benzofuran isophthalate (SBFI) in isolated, perfused CCD segments dissected from rabbit kidneys. Control [Na(+)](i), during perfusion with 25 mM NaCl and a Na(+)-free solution in the bath containing the Na(+)-ionophore monensin (10 microM, to eliminate basolateral membrane Na(+) transport) averaged 19.3 +/- 5.2 mM (n = 16). Increasing luminal [NaCl] to 150 mM elevated [Na(+)](i) by 9.87 +/- 1.5 mM (n = 7; P < 0.05). AngII (10(-9) M) added to the lumen significantly elevated baseline [Na(+)](i) by 6.3 +/- 1.0 mM and increased the magnitude (Delta = 25.2 +/- 3.7 mM) and initial rate ( approximately 5 fold) of change in [Na(+)](i) to increased luminal [NaCl]. AngII when added to the bath had similar stimulatory effects; however, AngII was much more effective from the lumen. Thus, AngII significantly increased the apical entry of Na(+) in the CCD. To determine if this apical entry step occurred via the epithelial Na(+) channel (ENaC), studies were performed using the specific ENaC blocker, benzamil hydrochloride (10(-6) M). When added to the perfusate, benzamil almost completely inhibited the elevations in [Na(+)](i) to increased luminal [NaCl] in both the presence and absence of AngII. These results suggest that AngII directly stimulates Na(+) channel activity in the CCD. AT(1) receptor blockade with candesartan or losartan (10(-6) M) prevented the stimulatory effects of AngII. Regulation of ENaC activity by AngII may play an important role in distal Na(+) reabsorption in health and disease.

  2. 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.

  3. 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),

  4. 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

  5. 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

  6. 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.

  7. Novel 99mTc labeled

    Institute of Scientific and Technical Information of China (English)

    FAN; Caiyun

    2006-01-01

    ,C.,Liu,Q.,Wang,R.,Investigation on the in vivo σ receptor locating property of 125I-4-(N-benzylpiperidin)-4-iodo-phenylsulfonamide,J.Isotopes (in Chinese),2004,17:198-203.[23]Maier,C.A.,Wünsch,B.,Novel spiropiperidines as highly potent and subtype selective sigma-receptor ligands,Part 1,J.Med.Chem.,2002,45:438-448.[24]Maier,C.A.,Wünsch,B.,Novel sigma receptor ligands,Part 2.SAR of spiro[[2]benzopyran-1,4′-piperidines] and spiro[[2]ben-zofuran-1,4′-piperidines] with carbon substituents in position 3,J.Med.Chem.,2002,45:4923-4930.[25]Ding,Y.S.,Fowler,J.S.,Dewey,S.L.et al.,Synthesis and PET studies of fluorine-18-BMY 14802:A potential antipsychotic drug,J.Nucl.Med.,1993,34:246-254.[26]Kiesewetter,D.O.,de Costa,B.,Synthesis of N1-3-[18F]fluoro-propyl-N4-2-([3,4-dichlorophenyl]ethyl)piperazine,a high affinity ligand for sigma receptor,J.Labelled Cpd.Radiopharm.,1993,33:639-643.[27]Van Waarde,A.,Buursma,A.R.,Hospers,G.A.P.Et al.,Tumor imaging with 2σ-receptor ligands,18F-FE-SA5845 and 11C-SA4503:A feasibility study,J.Nucl.Med.,2004,45:1939-1945.[28]Elsinga,P.H.,Kawamura,K.,Kobayashi,T.et al.,Synthesis and evaluation of [18F]fluoroethyl SA4503 and SA5845 as PET ligand for the sigma receptor,J.Labelled Cpd.Radiopharm.,2001,44(Suppl.1):S4-S6.[29]Kawamura,K.,Ishii,S.,Kobayashi,T.et al.,Synthesis and evaluation of 11C-labeled SA4503,SA5845,and their ethyl derivatives as PET sigma receptor ligands,J.Labelled Cpd.Radiopharm.,2001,44(Suppl.1):S233-S235.[30]Kawamura,K.,Ishiwata,K.,Tajima,H.et al.,Synthesis and in vivo evaluation of [11C]SA6298 as a PET sigma1 receptor ligand,Nucl.Med.Biol.,1999,26:915-922.[31]Kawamura,K.,Ishiwata,K.,Tajima,H.et al.,In vivo evaluation of [11C]SA4503 as a PET ligand for mapping CNS sigma1 receptor,Nucl.Med.Biol.,2000,27:255-261.[32]Kawamura,K.,Elsinga,P.H.,Kobayashi,T.et al.,Synthesis and evaluation of 11C-and 18F-labeled 1-[2-(4-alkoxy-3-methoxy-phenyl)ethyl]-4-(3-phenylpropyl)piperazines as sigma receptor ligands for positron emission tomography studies