- Synthesis, biological activity and multiscale molecular modeling studies for coumaryl-carboxamide derivatives as selective carbonic anhydrase IX inhibitors
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New coumaryl-carboxamide derivatives with the thiourea moiety as a linker between the alkyl chains and/or the heterocycle nucleus were synthesized and their inhibitory activity against the human carbonic anhydrase (hCA) isoforms hCA I, II, VII and IX were evaluated. While the hCA I, II and VII isoforms were not inhibited by the investigated compounds, the tumour-associated isoform hCA IX was inhibited in the high nanomolar range. 2-Oxo-N-((2-(pyrrolidin-1-yl)ethyl)carbamothioyl)-2H-chromene-3-carboxamide (e11) exhibited a selective inhibitory action against hCA IX with the Ki of 107.9 nM. In order to better understand the inhibitory profiles of studied molecules, multiscale molecular modeling approaches were used. Different molecular docking algorithms were used to investigate binding poses and predicted binding energies of studied compounds at the active sites of the CA I, II, VII and IX isoforms.
- Zengin Kurt, Belma,Sonmez, Fatih,Durdagi, Serdar,Aksoydan, Busecan,Ekhteiari Salmas, Ramin,Angeli, Andrea,Kucukislamoglu, Mustafa,Supuran, Claudiu T.
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p. 1042 - 1052
(2017/08/16)
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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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- Design, synthesis and biological evaluation of novel trimethylpyrazine-2- carbonyloxy-cinnamic acids as potent cardiovascular agents
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A series of novel trimethylpyrazine-2-carbonyloxy-cinnamic acids and esters were designed, synthesized and evaluated for their inhibitory effect on adenosine diphosphate (ADP)-induced platelet aggregation in vitro and also assayed for their protective effect against hydrogen peroxide (H 2O2)-induced oxidative damage on Ea.hy926 cells. The results showed that many compounds exhibited high activity in one or both of the assays, of which, compound F′10 displayed the highest protective effect on the proliferation of the damaged Ea.hy926 cells (EC50 = 1.7 μM), presenting almost 40 times higher potency than that of lipoic acid, and compound F3 was the most active anti-platelet aggregation agent with IC 50 = 9.6 μM, comparable to that of clopidogrel. The structure-activity relationships of these compounds were also discussed.
- Chen, Hongfei,Li, Guoning,Zhan, Peng,Li, Hong,Wang, Shouxun,Liu, Xinyong
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supporting information
p. 711 - 718
(2014/06/10)
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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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- 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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scheme or table
p. 4873 - 4878
(2010/09/10)
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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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- Ecdysteroids and a sucrose phenylpropanoid ester from Froelichia floridana
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Phytoecdysteroid glycosides (1-5) and a phenylpropanoid ester of sucrose (6) were isolated from the whole plant of Froelichia floridana, along with eight known compounds including three ecdysteroids (7-9), four flavonoids (10-13), and one phenolic compoun
- Wang, Ping,Li, Shiyou,Ownby, Stacy,Zhang, Zhizhen,Yuan, Wei,Zhang, Wanli,Scott Beasley
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experimental part
p. 430 - 436
(2009/07/18)
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- Preparation of vinylphenols from 2- and 4-hydroxybenzaldehydes
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A straightforward, high-yielding procedure has been developed for the manufacture of substituted vinylphenols from 2- and 4-hydroxybenzaldehydes utilising classical Knoevenagel condensation reaction conditions.
- Simpson, Carol J.,Fitzhenry, Matthew J.,Stamford, N. Patrick J.
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p. 6893 - 6896
(2007/10/03)
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- Aryl-acrylic acid esters
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The acrylic acid esters of Formula I are useful for the delivery of organoleptic compounds, especially for flavors, fragrances, masking agents and antimicrobial compounds. They can also deliver fluorescent whitening agents.
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- Associative and Dissociative Pathways in the Alkaline Hydrolysis of Aryl 2-Hydroxycinnamates
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Aryl 2-hydroxycinnamate esters hydrolyze in alkaline solutions (20percent dioxane-water v/v) obeying the rate law kobs = ka + kb/(1 + aH/Ka), where Ka is the ionization constant of the hydroxy group of the ester and kb is the second-order rate constant for the attack of hydroxide ion on the ionized ester.Kinetic data and activation parameters for the hydrolysis of the 2,4-dinitrophenyl ester show that the mechanism giving rise to the ka term cannot be a simple BAc2 type process and suggest the occurrence of a E1cB mechanism involving an "extended" o-oxoketene intermediate.The Broensted plot of the apparent second-order rate constante (kaKa/kw) versus the pK of the leaving group indicates that the reaction mechanism changes from E1cB to BAc2 for esters with leaving groups having pK higher than about 6.
- Cevasco, Giorgio,Thea, Sergio
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- PHASE TRANSFER CATALYSED WITTIG-HORNER SYNTHESIS PREPARATION OF HYDROXYCINNAMIC ESTERS FROM ORTHO HYDROXY AROMATIC ALDEHYDES OBTENTION OF HYDROXYCINNAMIC ACIDS
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Reaction between (carbethoxymethyl)-triphenylphosphonium bromide and ortho hydroxyaromatic aldehydes gives hydroxycinnamic esters in a liquid-solid two phases system (potassium carbonate-methanol) with a good yield.
- Dupin, J. F. E.,Chenault, J.
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p. 581 - 586
(2007/10/02)
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- THE PREPARATION OF COUMARIC ACIDS VIA STYRYLISOXAZOLES
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The preparation of coumaric acids (2a-f) by hydrolysis of the requisite 3-methyl-4-nitro-5-styrylisoxazoles (1a-f) is reported.
- Chimichi, Stefano,Sio, Francesco De,Donati, Donato,Fina, Giuseppe,Pepino, Roberto,Sarti-Fantoni, Piero
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p. 263 - 267
(2007/10/02)
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- Pulse Radiolytic and Product Analysis Studies of the Reaction of Hydroxyl Radicals with Cinnamic Acid. The Relative Extent of Addition to the Ring and Side Chain
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Using pulse radiolysis with optical detection and high-pressure liquid chromatography (HPLC), we show that reaction of OH radicals with cinnamic acid (CA) in aqueous solutions leads to addition to both the ring and the olefinic group.The relative extent of the above two pathways was estimated as 3:7, respectively.Benzyl- and hydroxycyclohexadienyl-type radicals were observed with absorption maxima at 320 (310) and 370 (365) nm depending on the pH of the solution.In the pH region 4.9 - 5.7 the absorption at 305 - 315 nm decays during the first 5 μs after the pulse.The dependence of the rate constants and absorption spectra on pH suggests that this decay is due to an equilibration process between acid-base forms of benzyl-type radicals formed through OH addition to the olefinic group.
- Bobrowski, K.,Raghavan, N. V.
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p. 4432 - 4435
(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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