- Comprehensive kinetic and substrate specificity analysis of an arylsulfatase from Helix pomatia using mass spectrometry
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Sulfatases hydrolyze sulfated metabolites to their corresponding alcohols and are present in all domains of life. These enzymes have found major application in metabolic investigation of drugs, doping control analysis and recently in metabolomics. Interest in sulfatases has increased due to a link between metabolic processes involving sulfated metabolites and pathophysiological conditions in humans. Herein, we present the first comprehensive substrate specificity and kinetic analysis of the most commonly used arylsulfatase extracted from the snail Helix pomatia. In the past, this enzyme has been used in the form of a crude mixture of enzymes, however, recently we have purified this sulfatase for a new application in metabolomics-driven discovery of sulfated metabolites. To evaluate the substrate specificity of this promiscuous sulfatase, we have synthesized a series of new sulfated metabolites of diverse structure and employed a mass spectrometric assay for kinetic substrate hydrolysis evaluation. Our analysis of the purified enzyme revealed that the sulfatase has a strong preference for metabolites with a bi- or tricyclic aromatic scaffold and to a lesser extent for monocyclic aromatic phenols. This metabolite library and mass spectrometric method can be applied for the characterization of other sulfatases from humans and gut microbiota to investigate their involvement in disease development.
- Correia, Mário S.P.,Ballet, Caroline,Meistermann, Hannes,Conway, Louis P.,Globisch, Daniel
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p. 955 - 962
(2019/02/09)
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- C -Methylation of Alcohols, Ketones, and Indoles with Methanol Using Heterogeneous Platinum Catalysts
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A versatile, selective, and recyclable heterogeneous catalytic method for the methylation of C-H bonds in alcohols, ketones, and indoles with methanol under oxidant-free conditions using a Pt-loaded carbon (Pt/C) catalyst in the presence of NaOH is reported. This catalytic system is effective for various methylation reactions: (1) the β-methylation of primary alcohols, including aryl, aliphatic, and heterocyclic alcohols, (2) the α-methylation of ketones, and (3) the selective C3-methylation of indoles. The reactions are driven by a borrowing-hydrogen mechanism. The reaction begins with the dehydrogenation of the alcohol(s) to afford aldehydes, which subsequently undergo a condensation reaction with the nucleophile (aldehyde, ketone, or indole), followed by hydrogenation of the condensation product by Pt-H species to yield the desired product. In all of the methylation reactions explored in this study, the Pt/C catalyst exhibits a significantly higher turnover number than other previously reported homogeneous catalytic systems. Moreover, it is demonstrated that the high catalytic activity of Pt can be rationalized in terms of the adsorption energy of hydrogen on the metal surface, as revealed by density functional theory calculations on different metal surfaces.
- Siddiki, S. M. A. Hakim,Touchy, Abeda S.,Jamil, Md. A. R.,Toyao, Takashi,Shimizu, Ken-Ichi
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p. 3091 - 3103
(2018/04/14)
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- Design and synthesis of a novel series of [1-(4-hydroxy-benzyl)-1H-indol-5-yloxy]-acetic acid compounds as potent, selective, thyroid hormone receptor β agonists
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The design, synthesis, and structure activity relationships for a novel series of indoles as potent, selective, thyroid hormone receptor β (TRβ) agonists is described. Compounds with >50× binding selectivity for TRβ over TRα were generated and evaluation of compound 1c from this series in a model of dyslipidemia demonstrated positive effects on plasma lipid endpoints in vivo.
- Burkholder, Timothy P.,Cunningham, Brian E.,Clayton, Joshua R.,Lander, Peter A.,Brown, Matthew L.,Doti, Robert A.,Durst, Gregory L.,Montrose-Rafizadeh, Chahrzad,King, Constance,Osborne, Harold E.,Amos, Robert M.,Zink, Richard W.,Stramm, Lawrence E.,Burris, Thomas P.,Cardona, Guemalli,Konkol, Debra L.,Reidy, Charles,Christe, Michael E.,Genin, Michael J.
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p. 1377 - 1380
(2015/03/30)
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- VEGFR TYROSINE KINASE INHIBITORS
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Novel compounds, their prodrugs, and the pharmaceutically acceptable salts as pharmaceutical compositions containing such compounds useful in treating certain diseases modulated by the inhibition of vascular endothelial growth factors (VEGFs) receptor tyrosine kinases are provided. In particular, compounds and compositions and the methods for the prophylaxis, management and treatment of cancers through the inhibition of VEGF receptor tyrosine kinases are provided.
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Page/Page column 35
(2014/12/12)
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- Fast deprotection of phenoxy benzyl ethers in transfer hydrogenation assisted by microwave
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Phenoxy benzyl ethers are easily and quickly deprotected in the presence of ammonium formate and microencapsulated Pd(0)EnCat with the assistance of microwave irradiation. This procedure can be applied in the presence of other functional groups as well. The described protocol is particularly convenient for the preparation in a parallel and automatic fashion of libraries of compounds possessing a phenol type moiety.
- Quai, Monica,Repetto, Claudio,Barbaglia, Walter,Cereda, Enzo
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p. 1241 - 1245
(2007/10/03)
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- Novel heterocyclic thyromimetics
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Novel heterocycle-fused thyromimetics are presented carrying indoles or indazoles instead of the phenolic group in T3. Potent agonists were identified in both series. SAR trends are examined and found to be mostly consistent with previously published thyromimetics. Moderate THRβ selectivity (approx. 10-fold) was observed in the indole series using isoform-selective transient THR transfection assays
- Haning, Helmut,Woltering, Michael,Mueller, Ulrich,Schmidt, Gunter,Schmeck, Carsten,Voehringer, Verena,Kretschmer, Axel,Pernerstorfer, Josef
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p. 1835 - 1840
(2007/10/03)
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- Synthesis of 5-hydroxyoxaindan-2-ones and indol-5-ols from 1,4- cyclohexanedione
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1,4-Cyclohexanedione reacted with 2-oxocarboxylic acids to give 5- hydroxyoxaindan-2-ones including homogentisic lactone in one pot. The obtained aromatic compounds were transformed into indol-5-ols in a few steps. The sequential reactions showed a significance of 1,4-cyclohexanedione as a starting material in aromatic synthesis and an alternative access to the indol-5-ols.
- Ozaki, Yutaka,Quan, Zhe-Shan,Watabe, Kyouko,Kim, Sang-Won
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p. 727 - 731
(2007/10/03)
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- Product based on inorganic or organic lamellar particles, containing a melanotic pigment, process for preparing it and its use in cosmetics
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The invention relates to a product in powder form consisting of organic or inorganic particles having a lamellar structure, having a size of less than 50 microns and containing at least one synthetic melanotic pigment formed in situ by oxidation of an indole compound, and to its use for the protection of the human epidermis, in make-up products and for dyeing hair.
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- Process for dyeing keratin fibres with a monohydroxyindole associated with an iodide and hydrogen peroxide
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Process for dyeing keratin fibres consisting in applying on these fibres a composition (A) containing at least one indole colorant of formula: STR1 where R1 =H or C1 -C4 alkyl; R2 and R3, which may be identical or different, denote H, C1 -C4 alkyl, carboxyl or alkoxycarbonyl; or a salt or a precursor of a compound (I), associated, either with iodide ions, or with H2 O2 ; application of composition (A) being preceded or followed by the application of a compound (B) which contains, either H2 O2 at a pH of 2 to 12 when (A) contains iodide ions, or iodide ions at a pH of 2 to 11 when (A) contains H2 O2. This process allows particularly powerful and resistant dyes to be made.
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- HYDROXYLATION OF INDOLINES AND INDOLES BY HYDROGEN PEROXIDE IN SUPERACIDS
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In SbF5-HF, indolines and indoles are hydroxylated on the aromatic ring, protonated hydrogen peroxide H3O2+ reacting on the protonated substrates.
- Berrier, Christian,Jacquesy, Jean-Claude,Jouannetaud, Marie-Paule,Renoux, Alain
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p. 4565 - 4568
(2007/10/02)
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