- Coumarinyl-substituted sulfonamides strongly inhibit several human carbonic anhydrase isoforms: Solution and crystallographic investigations
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We investigated a series of coumarinyl-substituted aromatic sulfonamides as inhibitors of four carbonic anhydrase (CA, EC 4.2.1.1) isoforms with medical applications, the cytosolic hCA I, and II, and the transmembrane, tumor-associated hCA IX and XII. Compounds incorporating 7-methoxy-coumarin-4- yl-acetamide-tails and benzenesulfonamide and benzene-1,3-disulfonamide scaffolds showed medium potency inhibition of hCA I (KIs of 73-131 nM), effective hCA II inhibition (KIs of 9.1-36 nM) and less effective hCA IX and XII inhibition (KIs of 55-128 nM). Only one compound, the derivatized 4-amino-6-trifluoromethyl-benzene-1,3-disulfonamide with the coumarinyl tail, showed effective inhibition of the transmembrane isoforms, with KIs of 5.9-14.2 nM, although it was less effective as hCA I and II inhibitor (KIs of 36-120 nM). An X-ray crystal structure of hCA II in complex with 4-(7-methoxy-coumarin-4-yl-acetamido)- benzenesulfonamide (KI of 9.1 nM against hCA II) showed the intact inhibitor coordinated to the zinc ion from the enzyme active site by the sulfonamide moiety, and participating in a edge-to-face stacking with Phe131, in addition to other hydrophobic and hydrophilic interactions with water molecules and amino acid residues from the active site. Thus, sulfonamides incorporating coumarin rings have a distinct inhibition mechanism compared to the coumarins, and may lead to compounds with interesting inhibition profiles against various α-CAs found in mammals or parasites, such as Plasmodium falciparum.
- Wagner, Jason,Avvaru, Balendu Sankara,Robbins, Arthur H.,Scozzafava, Andrea,Supuran, Claudiu T.,McKenna, Robert
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- Palladium nanoparticles immobilized on amphiphilic and hyperbranched polymer-functionalized magnetic nanoparticles: An efficient semi-heterogeneous catalyst for Heck reaction
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To address the obstacles facing the use of palladium-based homogeneous and heterogeneous catalysts in C─C cross-coupling reactions, a novel semi-heterogeneous support was developed based on hyperbranched poly(ethylene glycol)-block-poly(citric acid)-functionalized Fe3O4 magnetic nanoparticles (Fe3O4@PCA-b-PEG). Because of the surface modification of the Fe3O4 nanoparticles with amphiphilic and hyperbranched polymers (PCA-b-PEG), these hybrid materials are not only soluble in a wide range of solvents (e.g. water, ethanol and dimethylformamide) but also are able to trap Pd2+ ions via complex formation of free carboxyl groups of the PCA dendrimer with metal ions. The reduction of trapped palladium ions in the dendritic shell of Fe3O4@PCA-b-PEG leads to immobilized palladium nanoparticles. The morphology and structural features of the catalyst were characterized using various microscopic and spectroscopic techniques. The catalyst was effectively used in the palladium-catalysed Mizoroki–Heck coupling reaction in water as a green solvent. In addition, the catalyst can be easily recovered from the reaction mixture by applying an external magnetic field and reused for more than ten consecutive cycles without much loss in activity, exhibiting an example of a sustainable and green methodology.
- Tabatabaei Rezaei, Seyed Jamal,Shamseddin, Azin,Ramazani, Ali,Mashhadi Malekzadeh, Asemeh,Azimzadeh Asiabi, Pegah
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- Linear polystyrene-stabilized PdO nanoparticle-catalyzed mizoroki-heck reactions in water
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Linear polystyrene-stabilized PdO nanoparticles (PS-PdONPs) were prepared by thermal decomposition of Pd(OAc)2 in the presence of polystyrene. X-ray diffraction (XRD) and transmission electron microscopy (TEM) indicated the production of PdO nanoparticles. The loading of palladium was determined by inductively coupled plasma-atomic emission spectroscopy (ICP-AES). PS-PdONPs exhibited high catalytic activity for Mizoroki-Heck reactions under air in water and could be recycled without loss of activity.
- Ohtaka, Atsushi,Yamaguchi, Tomohiro,Teratani, Takuto,Shimomura, Osamu,Nomura, Ryoki
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experimental part
p. 9067 - 9076
(2012/01/03)
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- Curcumin recognizes a unique binding site of tubulin
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Although curcumin is known for its anticarcinogenic properties, the exact mechanism of its action or the identity of the target receptor is not completely understood. Studies on a series of curcumin analogues, synthesized to investigate their tubulin binding affinities and tubulin self-assembly inhibition, showed that: (i) curcumin acts as a bifunctional ligand, (ii) analogues with substitution at the diketone and acetylation of the terminal phenolic groups of curcumin are less effective, (iii) a benzylidiene derivative, compound 7, is more effective than curcumin in inhibiting tubulin self-assembly. Cell-based studies also showed compound 7 to be more effective than curcumin. Using fluorescence spectroscopy we show that curcumin binds tubulin 32 ? away from the colchicine-binding site. Docking studies also suggests that the curcumin-binding site to be close to the vinblastine-binding site. Structure-activity studies suggest that the tridented nature of compound 7 is responsible for its higher affinity for tubulin compared to curcumin.
- Chakraborti, Soumyananda,Das, Lalita,Kapoor, Neha,Das, Amlan,Dwivedi, Vishnu,Poddar, Asim,Chakraborti, Gopal,Janik, Mark,Basu, Gautam,Panda, Dulal,Chakrabarti, Pinak,Surolia, Avadhesha,Bhattacharyya, Bhabatarak
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experimental part
p. 6183 - 6196
(2011/11/06)
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- 7,8-Disubstituted- but not 6,7-disubstituted coumarins selectively inhibit the transmembrane, tumor-associated carbonic anhydrase isoforms IX and XII over the cytosolic ones i and II in the low nanomolar/subnanomolar range
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Two series of disubstituted coumarins incorporating ether and acetyl/propionyl moieties in positions 6,7- and 7,8- of the heterocyclic ring were synthesized investigated for the inhibition of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1). All these
- Maresca, Alfonso,Scozzafava, Andrea,Supuran, Claudiu T.
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scheme or table
p. 7255 - 7258
(2011/01/12)
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- A facile method for synthesis of amine-functionalized mesoporous zirconia and its catalytic evaluation in Knoevenagel condensation
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Amine-functionalized mesoporous zirconia was prepared by a co-condensation method using silane (aminopropyltrimethoxysilane, APTES) and zirconium butoxide. The materials were characterized by X-ray diffraction, BET surface area analysis, 13C magic angle spinning-nuclear magnetic resonance (NMR), Fourier-transfer infrared spectroscopy (FTIR), transmittance electron micrography (TEM), and CHN analysis. FTIR and NMR results revealed the successful grafting of organic amines onto the surface of zirconia. The catalytic activities were investigated for liquid phase Knoevenagel condensation of various aromatic aldehydes with diethyl malonate. The catalysts showed excellent yield of products at room temperature in solvent-free condition.
- Parida,Mallick, Sujata,Sahoo,Rana
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experimental part
p. 226 - 232
(2010/08/06)
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- Hydroxyapatite supported caesium carbonate as a new recyclable solid base catalyst for the Knoevenagel condensation in water
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The Knoevenagel condensation between aromatic aldehydes and malononitrile, ethyl cyanoacetate or malonic acid with hydroxyapatite supported caesium carbonate in water is described. HAP-Cs2CO3 was found to be a highly active, stable and recyclable catalyst under the reaction conditions.
- Gupta, Monika,Gupta, Rajive,Anand, Medha
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experimental part
(2010/04/22)
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- Photocyclization reactions. Part 8 [1]. Synthesis of 2-quinolone, quinoline and coumarin derivatives using trans-cis isomerization by photoreaction
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2-Quinolone 2, quinoline 3, coumarin (2H-1-benzopyran-2-one) 5, and 2H-1-benzopyran hemiacetal 6 were synthesized by photocyclization reaction of trans-o-aminocinnamoyl derivatives trans-1 and trans-o-hydroxycinnamoyl derivatives trans-4. The reaction proceeds through trans-cis isomerization followed by intramolecular cyclization.
- Horaguchi, Takaaki,Hosokawa, Nobuyuki,Tanemura, Kiyoshi,Suzuki, Tsuneo
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- PHOTOREACTIVITE DES CARBOXYLATES DE CUIVRE II - ETUDE DE L'ACIDE ORTHO-COUMARIQUE ET DE SES SELS DE CUIVRE (I) ET (II)
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Photochemical and photophysical properties of copper (I) and (II) ortho-coumarate and ortho-coumaric acid as a reference have been studied in D.M.S.O. o-coumaric acid is characterized by high trans -> cis isomerization quantum yields and a dual fluorescence for the trans-isomer.The anionic species RH- and R2- formed by subsequent dissociation exhibit low trans -> cis quantum yields and quite different fluorescence quantum yields (0.0 for RH- and 0.5 for R2-).With copper o-coumarate in dilute solution, o-coumaric acid is prooved to be the species present in the solution (through absorption emission and photoisomerization properties).At concentration higher than 10-3 M, a probably dimeric structured complex is stabilized.Associated with such a complexation, a d-d type transition appears in the visible region, even with copper (I) salt.Simultaneously, an important inhibition of the photo isomerization and dual fluorescence of the ligand is observed.So, in such a complex, the copper atom is able to deactivate the singlet state of the ligand.
- Lorain, Christine,Guyot, Ghislain,Bolte, Michele
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p. 243 - 250
(2007/10/02)
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- Preparation of coumarins
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Coumarin compounds may be produced by the conversion of o-hydroxycinnamates or o-hydroxycinnamic acids in the presence of catalysts comprising compounds containing metals of Group VIII of the Periodic Table.
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