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Corresponding Acids (corresponding + acid)
Selected AbstractsSynthesis of N -Acetylglucosamine-Derived Nagstatin Analogues and Their Evaluation as Glycosidase InhibitorsHELVETICA CHIMICA ACTA, Issue 1 2005Miroslav Terinek The gluco -configured analogue 15 of nagstatin (1) and the methyl ester 14 were synthesized via condensation of the thionolactams 17 or 18 with the , -amino ester 19. The silyl ethers 20 and 21 resulting from 17 were desilylated to 22 and 23; these alcohols were directly obtained by condensing 18 and 19. The attempted substitution of the C(8)OH group of 22 by azide under Mitsunobu conditions led unexpectedly to the deoxygenated , -azido esters 24. The desired azide 25 was obtained by treating the manno -configured alcohol 23 with diphenyl phosphorazidate. The azide was transformed to the debenzylated acetamido ester 14 that was hydrolyzed to the nagstatin analogue 15. The imidazole-2-acetates 14 and 15 are nanomolar inhibitors of the N -acetyl- , -glucosaminidases from Jack beans and from bovine kidney, submicromolar to micromolar inhibitors of the , -glucosidase from Caldocellum saccharolyticum, and rather weak inhibitors of the snail , -mannosidase. In all cases, the ester was a stronger inhibitor than the corresponding acid. As expected from their gluco -configuration, both imidazopyridines 14 and 15 are stronger inhibitors of the , - N -acetylglucosaminidase from bovine kidney than nagstatin. [source] Studies on the metabolism and toxicological detection of the designer drug 2,5-dimethoxy-4-methyl-,- phenethylamine (2C-D) in rat urine using gas chromatographic/mass spectrometric techniquesJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 11 2006Denis S. Theobald Abstract The phenethylamine-derived designer drug 2,5-dimethoxy-4-methyl-,-phenethylamine (2C-D) was found to be metabolized in rats by O -demethylation at position 2 or 5 followed by N -acetylation or by deamination with oxidation to the corresponding acids or reduction to the corresponding alcohol. Furthermore, 2C-D was hydroxylated at the methyl group or deaminated followed by reduction to the corresponding alcohol or by oxidation to the corresponding acid. Most of the metabolites were excreted in conjugated form. The authors' systematic toxicological analysis (STA) procedure using full-scan GC/MS allowed the detection of an intake of a dose of 2C-D in rat urine that corresponds to a common drug user's dose. Assuming similar metabolism, the described STA procedure should be suitable for proof of an intake of 2C-D in human urine. Copyright © 2006 John Wiley & Sons, Ltd. [source] New designer drug, 2,5-dimethoxy-4-propylthio-,-phenethylamine (2C-T-7): studies on its metabolism and toxicological detection in rat urine using gas chromatography/mass spectrometry,JOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 1 2005Denis S. Theobald Abstract Studies are described on the metabolism and toxicological analysis of the phenethylamine-derived designer drug 2,5-dimethoxy-4-propylthio-,-phenethylamine (2C-T-7) in rat urine using gas chromatography/mass spectrometry (GC/MS). The identified metabolites indicated that 2C-T-7 was metabolized by hydroxylation of the propyl side chain followed by N -acetylation and sulfoxidation and also by deamination followed by oxidation to the corresponding acid or by reduction to the corresponding alcohol. To a minor extent, 2C-T-7 was also metabolized by S -dealkylation followed by N -acetylation, S -methylation and sulfoxidation. The authors' systematic toxicological analysis (STA) procedure using full-scan GC/MS after acid hydrolysis, liquid,liquid extraction microwave-assisted acetylation allowed the detection of an intake of a dose of 2C-T-7 in rat urine that corresponds to a common drug users' dose. Assuming similar metabolism, the described STA procedure should be suitable for proof of an intake of 2C-T-7 in human urine. Copyright © 2005 John Wiley & Sons, Ltd. [source] Mitochondrial oxidation of 4-hydroxy-2-nonenal in rat cerebral cortexJOURNAL OF NEUROCHEMISTRY, Issue 6 2003Tonya C. Murphy Abstract 4-Hydroxy- trans -2-nonenal (HNE) is a neurotoxic product of lipid peroxidation whose levels are elevated in multiple neurodegenerative diseases and CNS trauma. The detoxification of HNE may take the route of glutathione conjugation to the C3 carbon and the oxidation or reduction of the C1 aldehyde. In this work, we examined whether the oxidation of HNE to its corresponding carboxylic acid, 4-hydroxy- trans -2-nonenoate (HNEAcid) was detoxifying event, if it occurred in rat cerebral cortex, and in which subcellular compartments. Our results show that HNEAcid did not form protein adducts and was non-toxic to Neuro 2A cells. HNEAcid formation occurred in rat cerebral cortex slices following exposure to HNE in a time-dependent and dose-dependent fashion. Homogenate studies indicated that HNEAcid formation was NAD+ dependent. Subcellular fractionation demonstrated that mitochondria had the highest specific activity for HNEAcid formation with a KM of 21 µm HNE. These data indicate that oxidation of HNE to its corresponding acid is a major detoxification pathway of HNE in the CNS and that mitochondria play a role in this process. [source] Crystallization and preliminary X-ray diffraction studies of a fungal hydrolase from Ophiostoma novo-ulmiACTA CRYSTALLOGRAPHICA SECTION D, Issue 10 2004Michail N. Isupov Dutch elm disease fungus Ophiostoma novo-ulmi contains a hydrolase activity which catalyses the resolution of racemic ethyl naproxen to the corresponding acid. The recombinant enzyme has been crystallized by the vapour-diffusion method in two crystal forms. The crystals of the first form belong to space group P21212, with unit-cell parameters a = 115.9, b = 174.4, c = 62.1,Å. The enzyme also crystallizes in space group P21212, with unit-cell parameters a = 72.9, b = 212.7, c = 61.7,Å. Synchrotron data have been collected for both crystal forms to 2.6 and 2.3,Å, respectively. A molecular-replacement solution has been found using a remote starting model of a bacterial esterase (23% sequence identity) for both crystal forms. Multicrystal averaging has resulted in interpretable electron-density maps. [source] Reinvestigation of the Mechanism of gem -Diacylation: Chemoselective Conversion of Aldehydes to Various gem -Diacylates and Their Cleavage under Acidic and Basic ConditionsEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 2 2005Veerababurao Kavala Abstract The mechanism of gem -diacylate formation has been studied extensively using tetrabutylammonium tribromide (TBATB) as the catalyst. The reaction proceeds by a nucleophilic attack of an anhydride on an aldehydic carbonyl group, nucleophilic attack of the hemiacylate intermediate on a second molecule of the anhydride, followed by an intermolecular attack of a second acetate group to regenerate the anhydride. gem -Diacylates of various aliphatic and aromatic aldehydes were obtained directly from the reaction of a variety of aliphatic and aromatic acid anhydrides in the presence of a catalytic quantity of tetrabutylammonium tribromide (TBATB) under solvent-free conditions. A significant electronic effect was observed during its formation as well as deprotection to the corresponding aldehyde. Chemoselective gem -diacylation of the aromatic aldehyde containing an electron-donating group has been achieved in the presence of an aldehyde containing an electron-withdrawing group. Deprotection of the gem -diacylate to the parent carbonyl compound can be accomplished in methanol in presence of the same catalyst. Here again, chemoselective deprotection of the gem -diacylate of a substrate containing an electrondonating group has been achieved in the presence of a substrate containing an electron-withdrawing group. Both the acid and base stability order of the various gem -diacylates examined follow a similar order. The stability order determined from the present study is: gem -dibenzoate > gemdipivalate > gem -diisobutyrate > gem -diacetate > gem -dipropionate. All the gem -diacylals are more stable under basic conditions than acidic condition. No correlation was found between the stability order and the pKa's of the corresponding acids; rather, the stability order is directly related to the steric crowding around the carbonyl carbon. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005) [source] Nitrilase of Rhodococcus rhodochrous J1FEBS JOURNAL, Issue 1 2000Conversion into the active form by subunit association Nitrilase-containing resting cells of Rhodococcus rhodochrous J1 converted acrylonitrile and benzonitrile to the corresponding acids, but the purified nitrilase hydrolyzed only benzonitrile, and not acrylonitrile. The activity of the purified enzyme towards acrylonitrile was recovered by preincubation with 10 mm benzonitrile, but not by preincubation with aliphatic nitriles such as acrylonitrile. It was shown by light-scattering experiments, that preincubation with benzonitrile led to the assembly of the inactive, purified and homodimeric 80-kDa enzyme to its active 410-kDa aggregate, which was proposed to be a decamer. Furthermore, the association concomitant with the activation was reached after dialysis of the enzyme against various salts and organic solvents, with the highest recovery reached at 10% saturated ammonium sulfate and 50% (v/v) glycerol, and by preincubation at increased temperatures or enzyme concentrations. [source] Studies on the metabolism and toxicological detection of the designer drug 2,5-dimethoxy-4-methyl-,- phenethylamine (2C-D) in rat urine using gas chromatographic/mass spectrometric techniquesJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 11 2006Denis S. Theobald Abstract The phenethylamine-derived designer drug 2,5-dimethoxy-4-methyl-,-phenethylamine (2C-D) was found to be metabolized in rats by O -demethylation at position 2 or 5 followed by N -acetylation or by deamination with oxidation to the corresponding acids or reduction to the corresponding alcohol. Furthermore, 2C-D was hydroxylated at the methyl group or deaminated followed by reduction to the corresponding alcohol or by oxidation to the corresponding acid. Most of the metabolites were excreted in conjugated form. The authors' systematic toxicological analysis (STA) procedure using full-scan GC/MS allowed the detection of an intake of a dose of 2C-D in rat urine that corresponds to a common drug user's dose. Assuming similar metabolism, the described STA procedure should be suitable for proof of an intake of 2C-D in human urine. Copyright © 2006 John Wiley & Sons, Ltd. [source] Methyl esters of N -(dicyclohexyl)acetyl-piperidine-4-(benzylidene-4-carboxylic acids) as drugs and prodrugs: A new strategy for dual inhibition of 5,-reductase type 1 and type 2JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 3 2005Martina Streiber Abstract Steroid 5,-reductase (5,R) inhibitory potency of three N -(dicyclohexyl)acetyl-piperidine-4-(benzylidene-4-carboxylic acids) and their corresponding methyl esters was monitored for type 2 isoenzyme in a benign prostatic hyperplasia cell free preparation and for type 1 isoenzyme in DU145 cells and in a cell free assay. The hydrolytic stability of the esters and their bioconversion to the corresponding acids was assessed in aqueous buffered solution (pH 7.4) and in selected biological media having measurable esterase activities. The carboxylic acids 1, 2, and 3 with high type 2 inhibitory potencies displayed only little type 1 inhibition. The esters 1a, 2a, and 3a, originally designed as prodrugs to enhance cell permeation, proved to be potent type 1 inhibitors and are therefore acting as drugs themselves. They are stable in buffered salt solution (pH 7.4), Caco-2 cells, and human plasma, whereas all esters are cleaved into the corresponding acids in benign prostatic hyperplasia tissue homogenate. Methyl esters, applied as hydrolytically stable precursor drugs to facilitate cell permeation, will yield the corresponding carboxylic acids as type 2 inhibitors after hydrolysis in the target organ. The esters themselves,stable in human plasma and Caco-2 cells,are acting as potent drugs toward 5,R type 1. Thus, dual inhibition of 5,R type 1 and type 2 can be achieved by applying a single parent compound. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 94:473,480, 2005 [source] Characterization of an acyl-CoA: carboxylate CoA-transferase from Aspergillus nidulans involved in propionyl-CoA detoxificationMOLECULAR MICROBIOLOGY, Issue 3 2008Christian B. Fleck Summary Filamentous fungi metabolize toxic propionyl-CoA via the methylcitrate cycle. Disruption of the methylcitrate synthase gene leads to an accumulation of propionyl-CoA and attenuates virulence of Aspergillus fumigatus. However, addition of acetate, but not ethanol, to propionate-containing medium strongly reduces the accumulation of propionyl-CoA and restores growth of the methylcitrate synthase mutant. Therefore, the existence of a CoA-transferase was postulated, which transfers the CoASH moiety from propionyl-CoA to acetate and, thereby, detoxifying the cell. In this study, we purified the responsible protein from Aspergillus nidulans and characterized its biochemical properties. The enzyme used succinyl-, propionyl- and acetyl-CoA as CoASH donors and the corresponding acids as acceptor molecules. Although the protein displayed high sequence similarity to acetyl-CoA hydrolases this activity was hardly detectable. We additionally identified and deleted the coding DNA sequence of the CoA-transferase. The mutant displayed weak phenotypes in the presence of propionate and behaved like the wild type when no propionate was present. However, when a double-deletion mutant defective in both methylcitrate synthase and CoA-transferase was constructed, the resulting strain was unable to grow on media containing acetate and propionate as sole carbon sources, which confirmed the in vivo activity of the CoA-transferase. [source] The quaternary structure of the amidase from Geobacillus pallidus RAPc8 is revealed by its crystal packingACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 12 2006Vinod B. Agarkar The amidase from Geobacillus pallidus RAPc8, a moderate thermophile, is a member of the nitrilase enzyme superfamily. It converts amides to the corresponding acids and ammonia and has application as an industrial catalyst. RAPc8 amidase has been cloned and functionally expressed in Escherichia coli and has been purified by heat treatment and a number of chromatographic steps. The enzyme was crystallized using the hanging-drop vapour-diffusion method. Crystals produced in the presence of 1.2,M sodium citrate, 400,mM NaCl, 100,mM sodium acetate pH 5.6 were selected for X-ray diffraction studies. A data set having acceptable statistics to 1.96,Å resolution was collected under cryoconditions using an in-house X-ray source. The space group was determined to be primitive cubic P4232, with unit-cell parameter a = 130.49 (±0.05) Å. The structure was solved by molecular replacement using the backbone of the hypothetical protein PH0642 from Pyrococcus horikoshii (PDB code 1j31) with all non-identical side chains substituted with alanine as a probe. There is one subunit per asymmetric unit. The subunits are packed as trimers of dimers with D3 point-group symmetry around the threefold axis in such a way that the dimer interface seen in the homologues is preserved. [source] General Method for the 11C-Labeling of 2-Arylpropionic Acids and Their Esters: Construction of a PET Tracer Library for a Study of Biological Events Involved in COXs ExpressionCHEMISTRY - A EUROPEAN JOURNAL, Issue 14 2010Misato Takashima-Hirano Abstract Cyclooxygenase (COX) is a critical enzyme in prostaglandin biosynthesis that modulates a wide range of biological functions, such as pain, fever, and so on. To perform in vivo COX imaging by positron emission tomography (PET), we developed a method to incorporate 11C radionuclide into various 2-arylpropionic acids that have a common methylated structure, particularly among nonsteroidal anti-inflammatory drugs (NSAIDs). Thus, we developed a novel 11C-radiolabeling methodology based on rapid C -[11C]methylation by the reaction of [11C]CH3I with enolate intermediates generated from the corresponding esters under basic conditions. One-pot hydrolysis of the above [11C]methylation products also allows the synthesis of desired 11C-incorporated acids. We demonstrated the utility of this method in the syntheses of six PET tracers, [11C]Ibuprofen, [11C]Naproxen, [11C]Flurbiprofen, [11C]Fenoprofen, [11C]Ketoprofen, and [11C]Loxoprofen. Notably, we found that their methyl esters were particularly useful as proradiotracers for a study of neuroinflammation. The microPET studies of rats with lipopolysaccharide (LPS)-induced brain inflammation clearly showed that the radioactivity of PET tracers accumulated in the inflamed region. Among these PET tracers, the specificity of [11C]Ketoprofen methyl ester was demonstrated by a blocking study. Metabolite analysis in the rat brain revealed that the methyl esters were initially taken up in the brain and then underwent hydrolysis to form pharmacologically active forms of the corresponding acids. Thus, we succeeded in general 11C-labeling of 2-arylpropionic acids and their methyl esters as PET tracers of NSAIDs to construct a potentially useful PET tracer library for in vivo imaging of inflammation involved in COXs expression. [source] From the Linden Flower to Linden Honey , Volatile Constituents of Linden Nectar, the Extract of Bee-Stomach and Ripe HoneyCHEMISTRY & BIODIVERSITY, Issue 12 2004Regula Naef Honey is produced by honeybees (Apis mellifera), which collect nectar from flowers, digest it in their bodies, and deposit it in honeycombs, where it develops into ripe honey. We studied the evolution of the volatile constituents from the nectar of linden blossoms (Tilia cordata) to honey via the ,intermediate' honeybee. The sampling of the contents of the honey stomach or honey sack of the bee is unique. Extracts were prepared from nectar, from the liquid of the honey stomach, and from ripe honey. The chemistry is extremely complex, and compounds spanning from monoterpenes (hydrocarbons, ethers, aldehydes, acids, and bifunctional derivatives), isoprenoids, aromatic compounds (phenylpropanoids, phenols), and products degraded from fatty acids to alkaloids, were identified. Some compounds definitely stem from the plants, whereas other interesting constituents can be attributed to animal origin. Two derivatives of decanoic acid, 9-oxodec-2-enoic acid (12) and 9-hydroxydec-2-enoic acid, identified in the honey are known to be constituents of the so-called ,Queen's pheromone'. Two metabolites of these acids were identified in the extract of the honey stomach: 8-oxononanal (10), a new natural product, and 8-oxononanol (11). There structures were confirmed by synthesis. Nectar and honey stomach contain many aldehydes, which, due to the highly oxidative atmosphere in the honeycomb, are found as corresponding acids in the honey. Two acids were newly identified as 4-isopropenylcyclohexa-1,3-diene-1-carboxylic acid (14) and 4-(1-hydroxy-1-methylethyl)-cyclohexa-1,3-diene-1-carboxylic acid (15). [source] | ||||||||||||||||||||||