Base de dados : MEDLINE
Pesquisa : D02.886.640 [Categoria DeCS]
Referências encontradas : 2251 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 226 ir para página                         

  1 / 2251 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28708375
[Au] Autor:Silvaroli JA; Pleshinger MJ; Banerjee S; Kiser PD; Golczak M
[Ad] Endereço:Department of Pharmacology, School of Medicine, Case Western Reserve University , Cleveland, Ohio, United States.
[Ti] Título:Enzyme That Makes You Cry-Crystal Structure of Lachrymatory Factor Synthase from Allium cepa.
[So] Source:ACS Chem Biol;12(9):2296-2304, 2017 Sep 15.
[Is] ISSN:1554-8937
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The biochemical pathway that gives onions their savor is part of the chemical warfare against microbes and animals. This defense mechanism involves formation of a volatile lachrymatory factor (LF) ((Z)-propanethial S-oxide) that causes familiar eye irritation associated with onion chopping. LF is produced in a reaction catalyzed by lachrymatory factor synthase (LFS). The principles by which LFS facilitates conversion of a sulfenic acid substrate into LF have been difficult to experimentally examine owing to the inherent substrate reactivity and lability of LF. To shed light on the mechanism of LF production in the onion, we solved crystal structures of LFS in an apo-form and in complex with a substrate analogue, crotyl alcohol. The enzyme closely resembles the helix-grip fold characteristic for plant representatives of the START (star-related lipid transfer) domain-containing protein superfamily. By comparing the structures of LFS to that of the abscisic acid receptor, PYL10, a representative of the START protein superfamily, we elucidated structural adaptations underlying the catalytic activity of LFS. We also delineated the architecture of the active site, and based on the orientation of the ligand, we propose a mechanism of catalysis that involves sequential proton transfer accompanied by formation of a carbanion intermediate. These findings reconcile chemical and biochemical information regarding thioaldehyde S-oxide formation and close a long-lasting gap in understanding of the mechanism responsible for LF production in the onion.
[Mh] Termos MeSH primário: Oxirredutases Intramoleculares/química
Cebolas/enzimologia
[Mh] Termos MeSH secundário: Butanóis/metabolismo
Cristalografia por Raios X
Oxirredutases Intramoleculares/metabolismo
Simulação de Acoplamento Molecular
Cebolas/química
Cebolas/metabolismo
Conformação Proteica
Sulfóxidos/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Butanols); 0 (Sulfoxides); 94Z73U61UH (thiopropanal S-oxide); D7F26UNN0B (crotonyl alcohol); EC 5.3.- (Intramolecular Oxidoreductases); EC 5.3.- (lachrymatory factor synthase, Allium cepa)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171119
[Lr] Data última revisão:
171119
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170715
[St] Status:MEDLINE
[do] DOI:10.1021/acschembio.7b00336


  2 / 2251 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28404372
[Au] Autor:West C; Konjaria ML; Shashviashvili N; Lemasson E; Bonnet P; Kakava R; Volonterio A; Chankvetadze B
[Ad] Endereço:Institut de Chimie Organique et Analytique (ICOA), Université d'Orléans et CNRS, UMR7311, BP 6759, 45067 Orléans, France. Electronic address: caroline.west@univ-orleans.fr.
[Ti] Título:Enantioseparation of novel chiral sulfoxides on chlorinated polysaccharide stationary phases in supercritical fluid chromatography.
[So] Source:J Chromatogr A;1499:174-182, 2017 May 26.
[Is] ISSN:1873-3778
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Asymmetric sulfoxides is a particular case of chirality that may be found in natural as well as synthetic products. Twenty-four original molecules containing a sulfur atom as a centre of chirality were analyzed in supercritical fluid chromatography on seven polysaccharide-based chiral stationary phases (CSP) with carbon dioxide - methanol mobile phases. While all the tested CSP provided enantioseparation for a large part of the racemates, chlorinated cellulosic phases proved to be both highly retentive and highly enantioselective towards these species. Favourable structural features were determined by careful comparison of the enantioseparation of the probe molecules. Molecular modelling studies indicate that U-shaped (folded) conformations were most favorable to achieve high enantioresolution on these CSP, while linear (extended) conformations were not so clearly discriminated. For a subset of these species adopting different conformations, a broad range of mobile phase compositions, ranging from 20 to 100% methanol in carbon dioxide, were investigated. While retention decreased continuously in this range, enantioseparation varied in a non-monotonous fashion. Abrupt changes in the tendency curves of retention and selectivity were observed when methanol proportion reaches about 60%, suggesting that a change in the conformation of the analytes and/or chiral selector is occurring at this point.
[Mh] Termos MeSH primário: Cromatografia com Fluido Supercrítico/métodos
Polissacarídeos/química
Sulfóxidos/química
[Mh] Termos MeSH secundário: Dióxido de Carbono/química
Cromatografia com Fluido Supercrítico/instrumentação
Halogenação
Metanol/química
Estereoisomerismo
Sulfóxidos/isolamento & purificação
[Pt] Tipo de publicação:EVALUATION STUDIES; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Polysaccharides); 0 (Sulfoxides); 142M471B3J (Carbon Dioxide); Y4S76JWI15 (Methanol)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170414
[St] Status:MEDLINE


  3 / 2251 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28398015
[Au] Autor:D'Orazio G; Kakava R; Volonterio A; Fanali S; Chankvetadze B
[Ad] Endereço:Institute of Chemical Methodologies, Italian National Research Council (CNR), Monterotondo, Italy.
[Ti] Título:An attempt for fast separation of enantiomers in nano-liquid chromatography and capillary electrochromatography.
[So] Source:Electrophoresis;38(15):1932-1938, 2017 08.
[Is] ISSN:1522-2683
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:In the present study, an attempt was made to achieve separation of enantiomers within a minute in nano-LC and CEC. In order to achieve this goal several parameters were optimized from the viewpoint of the property of chiral analytes, concentration of the chiral selector in the packing material, capillary dimensions, and separation mode. The enantiomers of several of the applied chiral sulfoxides could be resolved with the analysis time <1 min. Some instrumental obstacles hindering further reduction of analysis time are also highlighted.
[Mh] Termos MeSH primário: Eletrocromatografia Capilar/métodos
Cromatografia Líquida/métodos
Nanotecnologia/métodos
[Mh] Termos MeSH secundário: Modelos Químicos
Estereoisomerismo
Sulfóxidos/análise
Sulfóxidos/química
Sulfóxidos/isolamento & purificação
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Sulfoxides)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171106
[Lr] Data última revisão:
171106
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170412
[St] Status:MEDLINE
[do] DOI:10.1002/elps.201700126


  4 / 2251 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
[PMID]:28358695
[Au] Autor:Epperly MW; Rhieu BH; Franicola D; Dixon T; Cao S; Zhang X; Shields D; Wang H; Wipf P; Greenberger JS
[Ad] Endereço:Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, U.S.A.
[Ti] Título:Induction of TGF-ß by Irradiation or Chemotherapy in Fanconi Anemia (FA) Mouse Bone Marrow Is Modulated by Small Molecule Radiation Mitigators JP4-039 and MMS350.
[So] Source:In Vivo;31(2):159-168, 2017 Mar-Apr.
[Is] ISSN:1791-7549
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:BACKGROUND/AIM: Total-body irradiation and/or administration of chemotherapy drugs in bone marrow transplantation induce cytokines that can suppress engraftment. Fanconi Anemia (FA) patients have a hyperactive responsiveness to the inhibitory cytokine, transforming growth factor-beta (TGF-ß). Small molecule radiation mitigator drugs, JP4-039 and MMS350, were evaluated for suppression of irradiation or drug-induced TGF-ß. MATERIALS AND METHODS: In vivo induction of TGF-ß by total-body ionizing irradiation (TBI), L-phenylalanine mustard (L-PAM), busulfan or fludarabine, was quantified. In parallel, mitigator drug amelioration of TGF-ß induction in FA D2 (FANCD2 ) mouse bone marrow, was studied in vitro. Tissue culture medium, cell lysates, and mouse plasma were analyzed for TGF-ß levels. RESULTS: Induction of TGF-ß levels in FANCD2 and FANCD2 mice and in mouse bone marrow were modulated by both JP4-039 and MMS350. CONCLUSION: Bone marrow transplantation in FA recipients may benefit from administration of small molecule agents that suppress TGF-ß induction.
[Mh] Termos MeSH primário: Medula Óssea/efeitos dos fármacos
Éteres Cíclicos/farmacologia
Anemia de Fanconi/tratamento farmacológico
Anemia de Fanconi/radioterapia
Óxidos de Nitrogênio/farmacologia
Sulfóxidos/farmacologia
Fator de Crescimento Transformador beta/metabolismo
[Mh] Termos MeSH secundário: Animais
Western Blotting
Medula Óssea/metabolismo
Bussulfano/farmacologia
Linhagem Celular
Células Cultivadas
Tratamento Farmacológico/métodos
Anemia de Fanconi/metabolismo
Melfalan/farmacologia
Camundongos da Linhagem 129
Camundongos Endogâmicos C57BL
Camundongos Knockout
Agonistas Mieloablativos/farmacologia
Protetores contra Radiação/farmacologia
Técnicas de Cultura de Tecidos
Fator de Crescimento Transformador beta/sangue
Fator de Crescimento Transformador beta/genética
Vidarabina/análogos & derivados
Vidarabina/farmacologia
Irradiação Corporal Total/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Ethers, Cyclic); 0 (JP4-039); 0 (MMS350); 0 (Myeloablative Agonists); 0 (Nitrogen Oxides); 0 (Radiation-Protective Agents); 0 (Sulfoxides); 0 (Transforming Growth Factor beta); FA2DM6879K (Vidarabine); G1LN9045DK (Busulfan); P2K93U8740 (fludarabine); Q41OR9510P (Melphalan)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170601
[Lr] Data última revisão:
170601
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170331
[St] Status:MEDLINE


  5 / 2251 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28320863
[Au] Autor:Lavall D; Schuster P; Jacobs N; Kazakov A; Böhm M; Laufs U
[Ad] Endereço:From the Universität des Saarlandes, Klinik für Innere Medizin III-Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätsklinikum des Saarlandes, D-66421 Homburg/Saar, Germany daniel.lavall@uks.eu.
[Ti] Título:Rac1 GTPase regulates 11ß hydroxysteroid dehydrogenase type 2 and fibrotic remodeling.
[So] Source:J Biol Chem;292(18):7542-7553, 2017 May 05.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The aim of the study was to characterize the role of Rac1 GTPase for the mineralocorticoid receptor (MR)-mediated pro-fibrotic remodeling. Transgenic mice with cardiac overexpression of constitutively active Rac1 (RacET) develop an age-dependent phenotype with atrial dilatation, fibrosis, and atrial fibrillation. Expression of MR was similar in RacET and WT mice. The expression of 11ß hydroxysteroid dehydrogenase type 2 (11ß-HSD2) was age-dependently up-regulated in the atria and the left ventricles of RacET mice on mRNA and protein levels. Statin treatment inhibiting Rac1 geranylgeranylation reduced 11ß-HSD2 up-regulation. Samples of human left atrial myocardium showed a positive correlation between Rac1 activity and 11ß-HSD2 expression ( = 0.7169). Immunoprecipitation showed enhanced Rac1-bound 11ß-HSD2 relative to Rac1 expression in RacET mice that was diminished with statin treatment. Both basal and phorbol 12-myristate 13-acetate (PMA)-induced NADPH oxidase activity were increased in RacET and correlated positively with 11ß-HSD2 expression ( = 0.788 and = 0.843, respectively). In cultured H9c2 cardiomyocytes, Rac1 activation with l-buthionine sulfoximine increased; Rac1 inhibition with NSC23766 decreased 11ß-HSD2 mRNA and protein expression. Connective tissue growth factor (CTGF) up-regulation induced by aldosterone was prevented with NSC23766. Cardiomyocyte transfection with 11ß-HSD2 siRNA abolished the aldosterone-induced CTGF up-regulation. Aldosterone-stimulated MR nuclear translocation was blocked by the 11ß-HSD2 inhibitor carbenoxolone. In cardiac fibroblasts, nuclear MR translocation induced by aldosterone was inhibited with NSC23766 and spironolactone. NSC23766 prevented the aldosterone-induced proliferation and migration of cardiac fibroblasts and the up-regulation of CTGF and fibronectin. In conclusion, Rac1 GTPase regulates 11ß-HSD2 expression, MR activation, and MR-mediated pro-fibrotic signaling.
[Mh] Termos MeSH primário: 11-beta-Hidroxiesteroide Desidrogenase Tipo 2/biossíntese
Fibrose Endomiocárdica/enzimologia
Fibroblastos/enzimologia
Miocárdio/enzimologia
Miócitos Cardíacos/enzimologia
Neuropeptídeos/biossíntese
Transdução de Sinais
Proteínas rac1 de Ligação ao GTP/biossíntese
[Mh] Termos MeSH secundário: 11-beta-Hidroxiesteroide Desidrogenase Tipo 2/genética
Aldosterona/farmacologia
Animais
Linhagem Celular
Fator de Crescimento do Tecido Conjuntivo/biossíntese
Fator de Crescimento do Tecido Conjuntivo/genética
Fibrose Endomiocárdica/patologia
Fibroblastos/patologia
Fibronectinas/biossíntese
Fibronectinas/genética
Regulação da Expressão Gênica/efeitos dos fármacos
Seres Humanos
Metionina/análogos & derivados
Metionina/farmacologia
Camundongos
Camundongos Mutantes
Miocárdio/patologia
Miócitos Cardíacos/patologia
Neuropeptídeos/genética
Ratos
Ratos Sprague-Dawley
Sulfóxidos/farmacologia
Acetato de Tetradecanoilforbol/farmacologia
Proteínas rac1 de Ligação ao GTP/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CTGF protein, human); 0 (Ctgf protein, mouse); 0 (Ctgf protein, rat); 0 (Fibronectins); 0 (Neuropeptides); 0 (RAC1 protein, human); 0 (Rac1 protein, mouse); 0 (Sulfoxides); 0 (buthionine sulfoxide); 139568-91-5 (Connective Tissue Growth Factor); 4964P6T9RB (Aldosterone); AE28F7PNPL (Methionine); EC 1.1.1.146 (11-beta-Hydroxysteroid Dehydrogenase Type 2); EC 3.6.1.- (Rac1 protein, rat); EC 3.6.5.2 (rac1 GTP-Binding Protein); NI40JAQ945 (Tetradecanoylphorbol Acetate)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170607
[Lr] Data última revisão:
170607
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170322
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M116.764449


  6 / 2251 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28279874
[Au] Autor:Bevan MJ; Wogen MT; Lunda MD; Saravia SA
[Ad] Endereço:Public Health Laboratory Division, Minnesota Department of Health, 601 Robert St. N, P.O. Box 64899, Saint Paul, MN, 55164, United States. Electronic address: martin.bevan@state.mn.us.
[Ti] Título:High throughput quantitative analysis of the ß-lyase sulfur mustard metabolite, 1,1'-sulfonylbis[2-(methylsulfinyl)ethane] in urine via high performance liquid chromatography tandem mass spectrometry.
[So] Source:J Chromatogr B Analyt Technol Biomed Life Sci;1051:1-8, 2017 Apr 15.
[Is] ISSN:1873-376X
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Sulfur Mustard (HD) has a 100year history of use as a chemical warfare agent and recent events in the Middle East are causing it to once again be a potential concern. We report a new high-throughput method for the determination of HD exposure by the analysis of the ß-lyase metabolite 1,1'-sulfonylbis[2-(methylsulfinyl)ethane] (SBMSE) in human urine. This method features a hydrogen peroxide (H O ) oxidative conversion of the ß-lyase metabolites to SBMSE, followed by sample extraction and concentration using solid phase extraction in 96-well plate format. Subsequent high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) analysis gave linear quantitation over a calibration range of 0.1-100ng/mL, with a method detection limit of 0.03ng/mL. Liquid chromatographic separation was achieved using a hydrophilic interaction liquid chromatography (HILIC) column with an analyte retention time of 0.9min and method time of 1.5min (cycle time=2.0min). Users of this method could prepare and analyze approximately 650 samples in 24h which would be important for an emergency response.
[Mh] Termos MeSH primário: Substâncias para a Guerra Química/metabolismo
Cromatografia Líquida de Alta Pressão/métodos
Gás de Mostarda/metabolismo
Sulfonas/urina
Sulfóxidos/urina
Espectrometria de Massas em Tandem/métodos
[Mh] Termos MeSH secundário: Cromatografia Líquida de Alta Pressão/instrumentação
Desenho de Equipamento
Ensaios de Triagem em Larga Escala
Seres Humanos
Peróxido de Hidrogênio/metabolismo
Limite de Detecção
Liases/metabolismo
Oxirredução
Extração em Fase Sólida/métodos
Sulfonas/metabolismo
Sulfóxidos/metabolismo
Espectrometria de Massas em Tandem/instrumentação
[Pt] Tipo de publicação:JOURNAL ARTICLE; VALIDATION STUDIES
[Nm] Nome de substância:
0 (Chemical Warfare Agents); 0 (Sulfones); 0 (Sulfoxides); 137371-96-1 (1,1'-sulfonylbis(2-(methylsulfinyl)ethane)); BBX060AN9V (Hydrogen Peroxide); EC 4.- (Lyases); T8KEC9FH9P (Mustard Gas)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170601
[Lr] Data última revisão:
170601
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170311
[St] Status:MEDLINE


  7 / 2251 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28272044
[Au] Autor:Wasim AA; Khan MN
[Ad] Endereço:Department of Chemistry, University of Karachi, Karachi 75270, Pakistan E-mail: nasiruk@uok.edu.pk.
[Ti] Título:Physicochemical effect of activation temperature on the sorption properties of pine shell activated carbon.
[So] Source:Water Sci Technol;75(5-6):1158-1168, 2017 03.
[Is] ISSN:0273-1223
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Activated carbons produced from a variety of raw materials are normally selective towards a narrow range of pollutants present in wastewater. This study focuses on shifting the selectivity of activated carbon from inorganic to organic pollutants using activation temperature as a variable. The material produced from carbonization of pine shells substrate was activated at 250°C and 850°C. Both adsorbents were compared with commercial activated carbon for the sorption of lead, cadmium, methylene blue, methyl blue, xylenol orange, and crystal violet. It was observed that carbon activated at 250°C was selective for lead and cadmium whereas the one activated at 850°C was selective for the organic dyes. The Fourier transform infrared spectroscopy study revealed that AC850 had less surface functional groups as compared to AC250. Point of zero charge and point of zero salt effect showed that AC250 had acidic groups at its surface. Scanning electron microscopy depicted that increase in activation temperature resulted in an increase in pore size of activated carbon. Both AC250 and AC850 followed pseudo-second-order kinetics. Temkin isotherm model was a best fit for empirical data obtained at equilibrium. The model also showed that sorption process for both AC250 and AC850 was physisorption.
[Mh] Termos MeSH primário: Carvão Vegetal/química
Fenômenos Químicos
Pinus/química
Temperatura Ambiente
[Mh] Termos MeSH secundário: Adsorção
Cádmio/isolamento & purificação
Corantes/isolamento & purificação
Difusão
Violeta de Genciana/química
Violeta de Genciana/isolamento & purificação
Concentração de Íons de Hidrogênio
Cinética
Chumbo/isolamento & purificação
Azul de Metileno/química
Azul de Metileno/isolamento & purificação
Microscopia Eletrônica de Varredura
Compostos Orgânicos/isolamento & purificação
Fenóis/química
Fenóis/isolamento & purificação
Sais/química
Sementes/química
Espectroscopia de Infravermelho com Transformada de Fourier
Sulfóxidos/química
Sulfóxidos/isolamento & purificação
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Coloring Agents); 0 (Organic Chemicals); 0 (Phenols); 0 (Salts); 0 (Sulfoxides); 00BH33GNGH (Cadmium); 16291-96-6 (Charcoal); 2P299V784P (Lead); J4Z741D6O5 (Gentian Violet); S2VDY878QD (xylenol orange); T42P99266K (Methylene Blue)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171102
[Lr] Data última revisão:
171102
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170309
[St] Status:MEDLINE
[do] DOI:10.2166/wst.2016.609


  8 / 2251 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28221724
[Au] Autor:Sirvent JA; Lücking U
[Ad] Endereço:Drug Discovery, Bayer AG, Müllerstr. 178, 13353, Berlin, Germany.
[Ti] Título:Novel Pieces for the Emerging Picture of Sulfoximines in Drug Discovery: Synthesis and Evaluation of Sulfoximine Analogues of Marketed Drugs and Advanced Clinical Candidates.
[So] Source:ChemMedChem;12(7):487-501, 2017 Apr 06.
[Is] ISSN:1860-7187
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Sulfoximines have gained considerable recognition as an important structural motif in drug discovery of late. In particular, the clinical kinase inhibitors for the treatment of cancer, roniciclib (pan-CDK inhibitor), BAY 1143572 (P-TEFb inhibitor), and AZD 6738 (ATR inhibitor), have recently drawn considerable attention. Whilst the interest in this underrepresented functional group in drug discovery is clearly on the rise, there remains an incomplete understanding of the medicinal-chemistry-relevant properties of sulfoximines. Herein we report the synthesis and in vitro characterization of a variety of sulfoximine analogues of marketed drugs and advanced clinical candidates to gain a better understanding of this neglected functional group and its potential in drug discovery.
[Mh] Termos MeSH primário: Desenho de Drogas
Inibidores de Proteínas Quinases/química
Sulfóxidos/química
[Mh] Termos MeSH secundário: Aminopiridinas/síntese química
Aminopiridinas/química
Aminopiridinas/metabolismo
Proteínas Mutadas de Ataxia Telangiectasia/antagonistas & inibidores
Proteínas Mutadas de Ataxia Telangiectasia/metabolismo
Quinases Ciclina-Dependentes/antagonistas & inibidores
Quinases Ciclina-Dependentes/metabolismo
Estradiol/análogos & derivados
Estradiol/síntese química
Estradiol/química
Estradiol/metabolismo
Mesilato de Imatinib/síntese química
Mesilato de Imatinib/química
Mesilato de Imatinib/metabolismo
Piperazinas/síntese química
Piperazinas/química
Piperazinas/metabolismo
Piperidinas/síntese química
Piperidinas/química
Piperidinas/metabolismo
Inibidores de Proteínas Quinases/síntese química
Inibidores de Proteínas Quinases/metabolismo
Purinas/síntese química
Purinas/química
Purinas/metabolismo
Pirazóis/síntese química
Pirazóis/química
Pirazóis/metabolismo
Piridinas/síntese química
Piridinas/química
Piridinas/metabolismo
Sulfóxidos/síntese química
Sulfóxidos/metabolismo
Dicloridrato de Vardenafila/síntese química
Dicloridrato de Vardenafila/química
Dicloridrato de Vardenafila/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (4-(2,6-dichlorobenzoylamino)-1H-pyrazole-3-carboxylic acid piperidin-4-ylamide); 0 (Aminopyridines); 0 (Piperazines); 0 (Piperidines); 0 (Protein Kinase Inhibitors); 0 (Purines); 0 (Pyrazoles); 0 (Pyridines); 0 (Sulfoxides); 22X328QOC4 (fulvestrant); 4TI98Z838E (Estradiol); 5O8R96XMH7 (Vardenafil Dihydrochloride); 8A1O1M485B (Imatinib Mesylate); EC 2.7.11.1 (Ataxia Telangiectasia Mutated Proteins); EC 2.7.11.22 (Cyclin-Dependent Kinases); G9ZF61LE7G (palbociclib); TK8ERE8P56 (ribociclib)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170714
[Lr] Data última revisão:
170714
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170222
[St] Status:MEDLINE
[do] DOI:10.1002/cmdc.201700044


  9 / 2251 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28213176
[Au] Autor:Kiesel BF; Shogan JC; Rachid M; Parise RA; Vendetti FP; Bakkenist CJ; Beumer JH
[Ad] Endereço:Cancer Therapeutics Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA; Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, USA.
[Ti] Título:LC-MS/MS assay for the simultaneous quantitation of the ATM inhibitor AZ31 and the ATR inhibitor AZD6738 in mouse plasma.
[So] Source:J Pharm Biomed Anal;138:158-165, 2017 May 10.
[Is] ISSN:1873-264X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The ATM kinase inhibitor AZ31 and ATR kinase inhibitor AZD6738 are in various phases of preclinical and clinical evaluation for their ability to potentiate chemoradiation. To support the preclinical evaluation of their pharmacokinetics, we developed and validated an LC-MS/MS assay for the simultaneous quantification of AZ31 and AZD6738 in mouse plasma. A "dilute and shoot" method was used to precipitate proteins from a sample volume of 50µL. Chromatographic separation was achieved using a Phenomenex Polar-RP column and a gradient mobile phase consisting of methanol-water with 0.1% formic acid. Detection was accomplished using a Waters Quattro Micro mass spectrometer in positive ionization mode. The assay utilizing 50µL sample was linear from 10 to 5000ng/mL and determined to be both accurate (-8.2 to 8.6%) and precise (<5.4% CV) and achieved the criteria for U.S. FDA guidance for bioanalytical method validation. Quantification was achieved in mouse tissue homogenate using a separate 200µL sample preparation. This LC-MS/MS assay will be essential for determining the tissue distribution and pharmacokinetics in future mouse studies.
[Mh] Termos MeSH primário: Ligas/química
Proteínas Mutadas de Ataxia Telangiectasia/antagonistas & inibidores
Cromatografia Líquida/métodos
Plasma/química
Pirimidinas/química
Sulfóxidos/química
Espectrometria de Massas em Tandem/métodos
[Mh] Termos MeSH secundário: Animais
Bioensaio/métodos
Estabilidade de Medicamentos
Formiatos/química
Metanol/química
Camundongos
Pirimidinas/sangue
Reprodutibilidade dos Testes
Sulfóxidos/sangue
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (AZD6738); 0 (Alloys); 0 (Formates); 0 (Mg-Al-Zn-Mn-Si-Cu alloy); 0 (Pyrimidines); 0 (Sulfoxides); 0YIW783RG1 (formic acid); EC 2.7.1.- (Atr protein, mouse); EC 2.7.11.1 (Ataxia Telangiectasia Mutated Proteins); Y4S76JWI15 (Methanol)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170628
[Lr] Data última revisão:
170628
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170219
[St] Status:MEDLINE


  10 / 2251 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28164865
[Au] Autor:Welch ML; Jaffray DA
[Ad] Endereço:Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
[Ti] Título:The correction of time and temperature effects in MR-based 3D Fricke xylenol orange dosimetry.
[So] Source:Phys Med Biol;62(8):3221-3236, 2017 Apr 21.
[Is] ISSN:1361-6560
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Previously developed MR-based three-dimensional (3D) Fricke-xylenol orange (FXG) dosimeters can provide end-to-end quality assurance and validation protocols for pre-clinical radiation platforms. FXG dosimeters quantify ionizing irradiation induced oxidation of Fe ions using pre- and post-irradiation MR imaging methods that detect changes in spin-lattice relaxation rates (R = [Formula: see text]) caused by irradiation induced oxidation of Fe . Chemical changes in MR-based FXG dosimeters that occur over time and with changes in temperature can decrease dosimetric accuracy if they are not properly characterized and corrected. This paper describes the characterization, development and utilization of an empirical model-based correction algorithm for time and temperature effects in the context of a pre-clinical irradiator and a 7 T pre-clinical MR imaging system. Time and temperature dependent changes of R values were characterized using variable TR spin-echo imaging. R -time and R -temperature dependencies were fit using non-linear least squares fitting methods. Models were validated using leave-one-out cross-validation and resampling. Subsequently, a correction algorithm was developed that employed the previously fit empirical models to predict and reduce baseline R shifts that occurred in the presence of time and temperature changes. The correction algorithm was tested on R -dose response curves and 3D dose distributions delivered using a small animal irradiator at 225 kVp. The correction algorithm reduced baseline R shifts from -2.8 × 10 s to 1.5 × 10 s . In terms of absolute dosimetric performance as assessed with traceable standards, the correction algorithm reduced dose discrepancies from approximately 3% to approximately 0.5% (2.90 ± 2.08% to 0.20 ± 0.07%, and 2.68 ± 1.84% to 0.46 ± 0.37% for the 10 × 10 and 8 × 12 mm fields, respectively). Chemical changes in MR-based FXG dosimeters produce time and temperature dependent R values for the time intervals and temperature changes found in a typical small animal imaging and irradiation laboratory setting. These changes cause baseline R shifts that negatively affect dosimeter accuracy. Characterization, modeling and correction of these effects improved in-field reported dose accuracy to less than 1% when compared to standardized ion chamber measurements.
[Mh] Termos MeSH primário: Corantes Fluorescentes/química
Fenóis/química
Contagem de Cintilação/métodos
Sulfóxidos/química
Temperatura Ambiente
[Mh] Termos MeSH secundário: Oxirredução
Contagem de Cintilação/instrumentação
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Fluorescent Dyes); 0 (Phenols); 0 (Sulfoxides); S2VDY878QD (xylenol orange)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171003
[Lr] Data última revisão:
171003
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170207
[St] Status:MEDLINE
[do] DOI:10.1088/1361-6560/aa5e63



página 1 de 226 ir para página                         
   


Refinar a pesquisa
  Base de dados : MEDLINE Formulário avançado   

    Pesquisar no campo  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/OPAS/OMS - Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde