- Acetylcholinesterase and carbonic anhydrase isoenzymes i and II inhibition profiles of taxifolin
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Taxifolin, also known as dihydroquercetin, is a flavonoid commonly found in plants. Carbonic anhydrase (CA, EC 4.2.1.1) plays an important role in many critical physiological events including carbon dioxide (CO2)/bicarbonate () respiration and pH regulation. There are 16 known CA isoforms in humans, of which human hCA isoenzymes I and II (hCA I and II) are ubiquitous cytosolic isoforms. In this study, the inhibition properties of taxifolin against the slow cytosolic isoenzyme hCA I, and the ubiquitous and dominant rapid cytosolic isoenzyme hCA II were studied. Taxifolin, as a naturally bioactive flavonoid, has a Ki of 29.2 nM against hCA I, and 24.2 nM against hCA II. For acetylcholinesterase enzyme (AChE) inhibition, Ki parameter of taxifolin was determined to be 16.7 nM. These results clearly show that taxifolin inhibited both CA isoenzymes and AChE at the nM levels.
- Gocer, Hulya,Topal, Fevzi,Topal, Meryem,Kü?ük, Murat,Teke, Dilek,Gül?in, Ilhami,Alwasel, Saleh H.,Supuran, Claudiu T.
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- Swan probe: A nanoliter-scale and high-throughput sampling interface for coupling electrospray ionization mass spectrometry with microfluidic droplet array and multiwell plate
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Mass spectrometry provides a versatile detection method for high-throughput drug screening because it permits the use of native biological substrates and the direct quantification of unlabeled reaction products. This paper describes the design and application of a Swan-shaped probe for high-throughput and nanoliter-scale analysis of biological samples in both a microfluidic droplet array and a multiwell plate with electrospray ionization mass spectrometry (ESI-MS). The Swan probe is fabricated using a single capillary with quite low cost, and it consists of a U-shaped section with a micrometer-sized hole for sampling and a tapered tip for sample electrospray ionization. Continuous sample introduction was carried out under both sampling modes of push-pull and spontaneous injection by sequentially dipping the probe in the sample solutions and then removing them. High-throughput and reliable ESI-MS analysis was achieved in analyzing 256 droplets within 90 min with a peak height RSD of 12.6% (n = 256). To validate its potential in drug discovery, the present system was applied in the screening of inhibitors of acetylcholinesterase (AchE) and the measurement of the IC50 values of identified inhibitors.
- Jin, Di-Qiong,Zhu, Ying,Fang, Qun
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- Cleaner enzymatic production of biodiesel with easy separation procedures triggered by a biocompatible hydrophilic ionic liquid
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The great challenges of modern industry and the environment make it important to develop sustainable energy resources with low cost. In this work, a cleaner enzymatic procedure for biodiesel production was developed through the utilization of a biocompatible and hydrophilic ionic liquid [Choline][H2PO4]. This ionic liquid can be synthesized from cheap raw materials through simple neutralization procedures, and it has been proved to be well biocompatible. The utilization of this ionic liquid in Novozym 435 catalyzed biodiesel production makes the reaction and work-up procedures very simple, because its hydrophilicity can lead to the implementation of a pseudo homogeneous reaction and then heterogeneous separation. Various oil resources such as triolein, sunflower oil and castor oil can all be converted to biodiesels with high yields. After the completion of reaction, both the ionic liquid and Novozym 435 can be recycled and reutilized for at least five cycles without a significant activity decrease. In addition, this reaction system can be conveniently scaled up to the multi-gram level with high efficiency and feasible separation. Overall, the above mentioned benefits make this ionic liquid based enzymatic system cleaner for the production of biodiesel and promising for further industrial applications.
- Chen, Qianhan,Cheng, Shuang,Fan, Dongshuang,Feng, Wanlu,Guo, Yuanyang,Li, Lingjun,Li, Zhiyong,Wang, Jianji,Zhu, Anlian
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p. 1944 - 1951
(2020/04/09)
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- Synthesis and hypergolic activity evaluation of some new ammonium-imidazolium based ionic liquids
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In this study, a new class of dicyanamide-based ionic liquids containing mono and dicationic counterparts was synthesized and characterized. Results demonstrate that the physical properties of these salts, including thermal stability, melting point, density and viscosity, are highly dependent on the structure of cation and type of anion. It was observed that the thermal stability of dicationic ionic liquids is higher for the monocationic ones. Furthermore, droplet tests were used to investigate the hypergolic properties of these ionic liquids. All of the synthesized compounds showed hypergolic activity upon contact with white fuming nitric acid, suggesting that some may have potential for application as bipropellants or energetic additives.
- Fareghi-Alamdari, Reza,Ghorbani-Zamani, Faezeh,Zekri, Negar
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p. 26386 - 26391
(2016/03/25)
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- Synthesis of Novel Quaternary Ammonium Salts and Their in Vitro Antileishmanial Activity and U-937 Cell Cytotoxicity
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This work describes the synthesis of a series of quaternary ammonium salts and the assessment of their in vitro antileishmanial activity and cytotoxicity. A preliminary discussion on a structure-activity relationship of the compounds is also included. Three series of quaternary ammonium salts were prepared: (i) halomethylated quaternary ammonium salts (series I); (ii) non-halogenated quaternary ammonium salts (series II) and (iii) halomethylated choline analogs (series III). Assessments of their in vitro cytotoxicity in human promonocytic cells U-937 and antileishmanial activity in axenic amastigotes of L. (Viannia) panamensis (M/HOM/87/UA140-pIR-eGFP) were carried out using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide) micromethod. Antileishmanial activity was also tested in intracellular amastigotes of L. (V) panamensis using flow cytometry. High toxicity for human U937 cells was found with most of the compounds, which exhibited Lethal Concentration 50 (LC50 ) values in the range of 9 to 46 μg/mL. Most of the compounds evidenced antileishmanial activity. In axenic amastigotes, the antileishmanial activity varied from 14 to 57 μg/mL, while in intracellular amastigotes their activity varied from 17 to 50 μg/mL. N-Chloromethyl-N,N-dimethyl-N-(4,4-diphenylbut-3-en-1-yl)ammonium iodide (1a), N-iodomethyl-N,N-dimethyl-N-(4,4-diphenylbut-3-en-1-yl)ammonium iodide (2a), N,N,N-trimethyl-N-(4,4-diphenylbut-3-en-1-yl)ammonium iodide (3a) and N,N,N-trimethyl-N-(5,5-diphenylpent-4-en-1-yl)ammonium iodide (3b) turned out to be the most active compounds against intracellular amastigotes of L. (V) panamensis, with EC50 values varying between 24.7 for compound 3b and 38.4 μg/mL for compound 1a. Thus, these compounds represents new "hits" in the development of leishmanicidal drugs.
- Duque-Benítez, Sandra M.,Ríos-Vásquez, Luz Amalia,Ocampo-Cardona, Rogelio,Cede?o, David L.,Jones, Marjorie A.,Vélez, Iván D.,Robledo, Sara M.
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- Hydrophobic interactions in the pillar[5]arene-based host-guest complexation and their application in the inhibition of acetylcholine hydrolysis
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The host-guest complexations between a water-soluble pillar[5]arenes (WP5) and choline derivatives with different alkyl chain lengths were investigated. The hydrophobic interactions played a significant role in these pillar[5]arene-based host-guest complexations. By taking advantage of hydrophobic interactions, the cavity of WP5 could be further employed to inhibit the hydrolysis of acetylcholine in the presence of acetylcholinesterase.
- Hua, Bin,Zhou, Jiong,Yu, Guocan
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supporting information
p. 986 - 989
(2015/02/19)
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- Synthesis of bifunctional cyclic carbonates from CO2 catalysed by choline-based systems
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Easily prepared choline iodide is an active catalyst for the synthesis of cyclic carbonates through the coupling reaction of CO2 and epoxides using low pressure (1 MPa), moderate temperature (85 °C) and green solvents (ethanol and propan-2-ol). The effects of reaction temperature, pressure, reaction time and amount of catalyst used were also investigated. The results showed moderate to high yields and excellent selectivities of cyclic carbonates with vinyl or acrylate groups under mild reaction conditions. The heterogenization of choline over a Merrifield resin gives access to a supported catalyst with good recyclability and reactivity that can be extended to a variety of terminal epoxide substrates.
- Amaral, Adérito J.R.,Coelho, Jorge F.J.,Serra, Arménio C.
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p. 5518 - 5522
(2013/09/23)
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- FIRE RESISTANT GLAZINGS
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An additive for alkali metal silicate solutions, comprising a quaternary ammonium compound having the general formula (1) R1R2R3R4N+OH?, wherein R1, R2, R3 and R4 which may be the same or different represent alkyl groups, hydroxy-substituted alkyl groups, alkaryl groups, hydroxy-substituted alkaryl groups comprising from 1 to 12 carbon atoms, or groups having the general formula —[CH2]n-N+R5R6R7 wherein n is an integer having a value of from 1 to 12, the group —[CH2]n may be hydroxy-substituted, and R5, R6 and R7 which may be the same or different represent alkyl groups, hydroxy-substituted alkyl groups, alkaryl groups or hydroxy-substituted alkaryl groups comprising from 1 to 12 carbon atoms; with the proviso that at least one of the groups R1, R2, R3, R4, R5, R6 and R7 represents a hydroxy-substituted alkyl group or a hydroxy-substituted alkaryl group comprising at least 2 carbon atoms wherein the hydroxy substituent is not located on a carbon atom which is bonded to a nitrogen atom.
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Page/Page column 5
(2012/10/23)
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- Catalysis by a synthetic receptor sealed at one end and functionalized at the other
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A deep cavitand bearing a zinc (II) salen wall catalyzes the hydrolysis of para-nitrophenylcholine carbonate. The closed end of the cavitand properly positions the carbonyl function of the substrate for activation by the metal center. Substrate specificity for acetylcholine derivatives results from simultaneous cation-π interactions and a C≡O...Zn coordination bond. Copyright
- Richeter, Sebastien,Rebek Jr., Julius
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p. 16280 - 16281
(2007/10/03)
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- N-Methyl-N-(o-nitrophenyl)carbamates as photolabile alcohol protecting groups
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N-Methyl-N-(o-nitrophenyl)carbamates represent new photoremovable alcohol protecting groups. This protecting group is easily incorporated by chemical coupling of the corresponding alcohol to N-methyl-N-(o-nitrophenyl)carbamoyl chloride. High yield and clean deprotection are induced by photolysis in protic solvents (water, ethanol or ethanol/water mixtures) from 254 to 365 nm.
- Loudwig, Sandra,Goeldner, Maurice
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p. 7957 - 7959
(2007/10/03)
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- Hydrolysis of phosphotriesters: Determination of transition states in parallel reactions by heavy-atom isotope effects
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The remote label method was used to measure primary and secondary 18O isotope effects in the alkaline hydrolysis of O,O-diethylphosphorylcholine iodide (DEPC) and the primary 18O effect in the alkaline hydrolysis of O,O-diethyl-m-nitrobenzyl phosphate (DEmNBP). Both the leaving group of interest (choline or m-nitrobenzyl alcohol) and ethanol can be ejected during hydrolysis due to the similarity of their pK values. The heavy-atom isotope effects were measured by isotope ratio mass spectrometry. Parallel reaction and incomplete labeling corrections were made for both systems. DEPC has a primary 18O isotope effect of 1.041 ± 0.003 and a secondary 18O isotope effect of 1.033 ± 0.002. The primary 18O isotope effect for DEmNBP was 1.052 ± 0.003. These large effects suggest a highly associative transition state in which the nucleophile approaches very close to the phosphorus atom to eject the leaving group. The large values are also indicative of a large compression, or general movement, on the reaction coordinate.
- Anderson,Shim,Raushel,Cleland
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p. 9246 - 9253
(2007/10/03)
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- Toward an artificial acetylcholinesterase
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The methanolysis of choline p-nitrophenylcarbonate in chloroform containing 1% methanol is catalyzed with turnover by ditopic receptors 1 and 2, consisting of a calix[6]arene connected to a bicyclic guanidinium by means of a short spacer. The calix[6]aren
- Cuevas, Felix,Di Stefano, Stefano,Magrans, J. Oriol,Prados, Pilar,Mandolini, Luigi,De Mendoza, Javier
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p. 3228 - 3234
(2007/10/03)
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- Synthesis and characterization of photolabile choline precursors as reversible inhibitors of cholinesterase: Release of choline in the microsecond time range
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Three o-nitrobenzyl ether derivatives of choline (compounds A-C) were synthesized as photolabile cholinesterase inhibitors in order to study the mechanism of choline release from the enzyme active site. The key step of the synthesis was a simple and efficient Lewis acid-catalyzed opening of dioxolane rings derived from o-nitrobenzaldehyde and o-nitroacetophenone. Laser flash photolyses of compounds A-C were analyzed by UV spectroscopy, HPLC, and an enzymatic assay for choline. The quantum yields of photoconversion were determined, and the kinetics of choline release were analyzed by studying the decay of the transient aci-nitro intermediate at 405 nm.The observed rates varied considerably in function of both pH and the substituent at the α-benzylic position. Furthermore, we demonstrated that all three compounds possessed reversible inhibitory properties on both purified Torpedo acetylcholinesterase and purified human plasma butyrylcholinesterase. Compound A, O-[1-(2-nitrophenyl)ethyl]choline iodide, which displayed the highest quantum yield (0.27) and the most rapid photolysis rate (6.8 x 104 s-1 at pH 6.5), represents therefore an interesting tool for the study of the fast process of choline release from cholinesterases by time-resolved Laue crystallography.
- Peng,Goeldner
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p. 185 - 191
(2007/10/03)
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- CONFORMATION OF DIMETHYLAMINOETHANOL, ITS METHYL ETHER AND OF THE CORRESPONDING TRIMETHYLAMMONIUM IODIDES. NMR AND VIBRATIONAL SPECTRA
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By analysis of fully coupled 13C NMR spectra and of 1H NMR spectra of dimethylaminoethanol, its methyl ether, and of the corresponding trimethylammonium iodides, populations of isomers generated by rotation about the bonds N-CH2, CH2-CH2, and CH2-O in these compounds in solution were determined.By analysis of Raman and infrared spectra of these compounds in the solid and liquid states it was found that in the crystalline state these compounds form structures with parallel N-CH3 and O-CH2 bonds, which are also preffered in the liquid state.
- Stokr, Jan,Schneider, Bohdan,Doskocilova, Danica,Sevcik, Stanislav,Pradny, Martin
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p. 1256 - 1271
(2007/10/02)
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