Base de dados : MEDLINE
Pesquisa : D02.455.426.559.389.140 [Categoria DeCS]
Referências encontradas : 3998 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 400 ir para página                         

  1 / 3998 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29409851
[Au] Autor:Tan M; Li G; Qi S; Liu X; Chen X; Ma J; Zhang D; Han M
[Ad] Endereço:College of Horticulture, Northwest A & F University, Yangling, Shaanxi 712100, China.
[Ti] Título:Identification and expression analysis of the IPT and CKX gene families during axillary bud outgrowth in apple (Malus domestica Borkh.).
[So] Source:Gene;651:106-117, 2018 Apr 20.
[Is] ISSN:1879-0038
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Cytokinins (CKs) play a crucial role in promoting axillary bud outgrowth and targeting the control of CK metabolism can be used to enhance branching in plants. CK levels are maintained mainly by CK biosynthesis (isopentenyl transferase, IPT) and degradation (dehydrogenase, CKX) genes in plants. A systematic study of the IPT and CKX gene families in apple, however, has not been conducted. In the present study, 12 MdIPTs and 12 MdCKXs were identified in the apple genome. Systematic phylogenetic, structural, and synteny analyses were performed. Expression analysis of these genes in different tissues was also assessed. MdIPT and MdCKX genes exhibit distinct expression patterns in different tissues. The response of MdIPT, MdCKX, and MdPIN1 genes to various treatments (6-BA, decapitation and Lovastatin, an inhibitor of CKs synthesis) that impact branching were also investigated. Results indicated that most of the MdIPT and MdCKX, and MdPIN1 genes were upregulated by 6-BA and decapitation treatment, but inhibited by Lovastatin, a compound that effectively suppresses axillary bud outgrowth induced by decapitation. These findings suggest that cytokinin biosynthesis is required for the activation of bud break and the export of auxin from buds in apple tree with intact primary shoot apex or decapitated apple tree. MdCKX8 and MdCKX10, however, exhibited little response to decapitation, but were significantly up-regulated by 6-BA and Lovastatin, a finding that warrants further investigation in order to understand their function in bud-outgrowth.
[Mh] Termos MeSH primário: Alquil e Aril Transferases/genética
Genes de Plantas
Malus/genética
Oxirredutases/genética
[Mh] Termos MeSH secundário: Arabidopsis/genética
Compostos de Benzil/farmacologia
Mapeamento Cromossômico
Cromossomos de Plantas
Evolução Molecular
Flores/genética
Perfilação da Expressão Gênica
Regulação da Expressão Gênica de Plantas
Genoma de Planta
Lovastatina/farmacologia
Malus/enzimologia
Malus/crescimento & desenvolvimento
Família Multigênica
Filogenia
Reguladores de Crescimento de Planta
Purinas/farmacologia
Sintenia
Regulação para Cima
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzyl Compounds); 0 (Plant Growth Regulators); 0 (Purines); 9LHU78OQFD (Lovastatin); EC 1.- (Oxidoreductases); EC 1.5.99.12 (cytokinin oxidase); EC 2.5.- (Alkyl and Aryl Transferases); EC 2.5.1.27 (adenylate isopentenyltransferase); KXG6A989PS (benzylaminopurine)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180208
[St] Status:MEDLINE


  2 / 3998 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29277574
[Au] Autor:Caspar AT; Meyer MR; Maurer HH
[Ad] Endereço:Department of Experimental and Clinical Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, Saarland University, Homburg, Germany.
[Ti] Título:Human cytochrome P450 kinetic studies on six N-2-methoxybenzyl (NBOMe)-derived new psychoactive substances using the substrate depletion approach.
[So] Source:Toxicol Lett;285:1-8, 2018 Mar 15.
[Is] ISSN:1879-3169
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:A huge number of new chemical derivatives of known drugs of abuse, so-called new psychoactive substances (NPS), are sold and consumed without prior preclinical and clinical testing. For assessing the elimination behaviors, determination of the kinetic constants K and V of the cytochrome P450 (CYP) isoforms involved in the hepatic metabolism of NPS could help to predict their contributions to hepatic clearance, drug-drug interactions and polymorphisms. Therefore, the aims of the present study were to determine the K and V values for CYP isoforms using the substrate depletion approach for the six N-2-methoxybenzyl (NBOMe)-derived NPS 25B-NBOMe, 25C-NBOMe, 25I-NBOMe, 3,4-DMA-NBOMe, 4-EA-NBOMe, and 4-MMA-NBOMe. Furthermore, the contributions of each CYP isozyme to the hepatic net clearance were elucidated using the relative activity factor approach. Several CYPs including CYP1A2, CYP2B6, CYP2C19, CYP2D6, and CYP3A4 were identified to be involved in the metabolism of the investigated compounds. The determined K values ranged from 0.010 µM (CYP2D6, 4-MMA-NBOMe) to 13 µM (CYP2B6, 4-EA-NBOMe). All NBOMes were good substrates of CYP2C19 and CYP2D6 resulting in very low K values in the nanomolar range. The main contributors to hepatic net clearance were CYP2D6 for 25B-NBOMe (69%), 25C-NBOMe (83%), 25I-NBOMe (61%), 3,4-DMA-NBOMe (89%) as well as for 4-EA-NBOMe (62%) and CYP2C19 for 4-MMA-NBOMe (64%). As more than one isoform was involved in the particular steps, the risk of harm associated with drug-drug interactions might be considered low. However, in cases where substances with high contributions from polymorphically expressed CYP2C19 and CYP2D6 are encountered, inter-individual variations in metabolism and excretion cannot be excluded.
[Mh] Termos MeSH primário: Compostos de Benzil/farmacocinética
Sistema Enzimático do Citocromo P-450/metabolismo
Microssomos Hepáticos/enzimologia
Psicotrópicos/farmacocinética
Drogas Ilícitas/farmacocinética
[Mh] Termos MeSH secundário: Animais
Compostos de Benzil/química
Sistema Enzimático do Citocromo P-450/genética
Interações Medicamentosas
Seres Humanos
Técnicas In Vitro
Cinética
Taxa de Depuração Metabólica
Microssomos Hepáticos/metabolismo
Modelos Biológicos
Psicotrópicos/química
Drogas Ilícitas/química
Especificidade por Substrato
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzyl Compounds); 0 (Psychotropic Drugs); 0 (Street Drugs); 9035-51-2 (Cytochrome P-450 Enzyme System)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180219
[Lr] Data última revisão:
180219
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171227
[St] Status:MEDLINE


  3 / 3998 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28887131
[Au] Autor:Misawa H; Ohashi W; Tomita K; Hattori K; Shimada Y; Hattori Y
[Ad] Endereço:Department of Molecular and Medical Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan; Department of Japanese Oriental Medicine, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
[Ti] Título:Prostacyclin mimetics afford protection against lipopolysaccharide/d-galactosamine-induced acute liver injury in mice.
[So] Source:Toxicol Appl Pharmacol;334:55-65, 2017 Nov 01.
[Is] ISSN:1096-0333
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Prostacyclin (PGI ) serves as a protective, anti-inflammatory mediator and PGI mimetics may be useful as a hepatoprotective agent. We examined whether two PGI mimetics, ONO-1301 and beraprost, are beneficial in acute liver injury and attempted to delineate the possible mechanism underlying the hepatoprotective effect. Acute liver injury was induced by lipopolysaccharide/d-galactosamine (LPS/GalN) in mice. Mice were given an intraperitoneal injection of PGI mimetics 1h before LPS/GalN challenge. Both ONO-1301 and beraprost significantly declined the LPS/GalN-induced increase in serum aminotransferase activity. ONO-1301 and, to a lesser extent, beraprost inhibited hepatic gene expression levels of pro-inflammatory cytokines, which were sharply elevated by LPS/GalN. The hepatoprotective effects of ONO-1301, to a lesser extent, of beraprost were also supported by liver histopathological examinations. The PGI receptor antagonist CAY10441 abrogated their hepatoprotective effects. The mechanisms behind the benefit of PGI mimetics in reducing LPS/GalN-induced liver injury involved, in part, their suppressive effects on increased generation of reactive oxygen species (ROS), since their ability to prevent LPS/GalN-induced hepatic apoptosis was mimicked by the antioxidant N-acetyl-l-cysteine. They significantly diminished LPS/GalN-induced activation of signal transducers and activators of transcription 3 (STAT3) in liver tissues, an effect which was highly associated with their hepatoprotective effects. We indicate that IP receptor activation with PGI mimetics can rescue the damage in the liver induced by LPS/GalN by undermining activation of STAT3 and leading to a lower production of ROS. Our findings point to PGI mimetics, especially ONO-1301, as a potential novel therapeutic modality for the treatment of acute liver injury.
[Mh] Termos MeSH primário: Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle
Epoprostenol/análogos & derivados
Galactosamina/toxicidade
Lipopolissacarídeos/toxicidade
Piridinas/farmacologia
[Mh] Termos MeSH secundário: Animais
Compostos de Benzil/farmacologia
Proteína de Ligação a CREB/genética
Proteína de Ligação a CREB/metabolismo
Epoprostenol/farmacologia
Galactosamina/administração & dosagem
Regulação da Expressão Gênica
Imidazóis/farmacologia
Lipopolissacarídeos/administração & dosagem
Camundongos
Quinases de Proteína Quinase Ativadas por Mitógeno/genética
Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo
Prostaglandinas I/química
Prostaglandinas I/farmacologia
Espécies Reativas de Oxigênio
Fator de Transcrição STAT3/genética
Fator de Transcrição STAT3/metabolismo
Transdução de Sinais
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 ((2-(4-(4-isopropoxybenzyl)-phenylamino) imidazoline)); 0 (Benzyl Compounds); 0 (Imidazoles); 0 (Lipopolysaccharides); 0 (Prostaglandins I); 0 (Pyridines); 0 (Reactive Oxygen Species); 0 (STAT3 Transcription Factor); 0 (Stat3 protein, mouse); 176391-41-6 (ONO 1301); 35E3NJJ4O6 (beraprost); 7535-00-4 (Galactosamine); DCR9Z582X0 (Epoprostenol); EC 2.3.1.48 (CREB-Binding Protein); EC 2.3.1.48 (Crebbp protein, mouse); EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171017
[Lr] Data última revisão:
171017
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170910
[St] Status:MEDLINE


  4 / 3998 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28866249
[Au] Autor:Akincioglu A; Kocaman E; Akincioglu H; Salmas RE; Durdagi S; Gülçin I; Supuran CT; Göksu S
[Ad] Endereço:Atatürk University, Faculty of Science, Department of Chemistry, Erzurum, Turkey; Agri Ibrahim Çeçen University, Central Researching Laboratory, Agri, Turkey.
[Ti] Título:The synthesis of novel sulfamides derived from ß-benzylphenethylamines as acetylcholinesterase, butyrylcholinesterase and carbonic anhydrase enzymes inhibitors.
[So] Source:Bioorg Chem;74:238-250, 2017 Oct.
[Is] ISSN:1090-2120
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In this study, a series of novel ß-benzylphenethylamines and their sulfamide derivatives were synthesized starting from (Z)-2,3-diphenylacrylonitriles. Pd-C catalysed hydrogenation of diphenylacrylonitriles, reduction of propanenitriles with LiAlH in the presence of AlCl followed by addition of conc. HCl afforded ß-benzylphenethylamine hydrochloride salts. The reactions of these amine hydrochloride salts with chlorosulfonyl isocyanate (CSI) in the presence of tert-BuOH and excess Et N gave sulfamoylcarbamates. Removing of Boc group from the synthesized sulfamoylcarbamates with trifluoroacetic acid (TFA) yielded novel sulfamides in good yields. These novel sulfamides derived from ß-benzylphenethylamines were effective inhibitors of the cytosolic carbonic anhydrase I and II isoenzymes (hCA I and II), acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with K values in the range of 0.278-2.260nM for hCA I, 0.187-1.478nM for hCA II, 0.127-2.452nM for AChE and 0.494-1.790nM for BChE. The inhibitory effects of the synthesized novel sulfamides derived from ß-benzylphenethylamines were compared to those of acetazolamide and dorzolamide as clinical hCA I and II isoenzymes inhibitors and tacrine as a clinical AChE and BChE enzymes inhibitors. In addition to in vitro tests, molecular modeling approaches are implemented not only for prediction of the binding affinities of the compounds but also to study their inhibition mechanisms in atomic level at the catalytic domains.
[Mh] Termos MeSH primário: Compostos de Benzil/farmacologia
Inibidores da Anidrase Carbônica/farmacologia
Inibidores da Colinesterase/farmacologia
Etilaminas/farmacologia
Sulfonamidas/farmacologia
[Mh] Termos MeSH secundário: Acetilcolinesterase/metabolismo
Compostos de Benzil/química
Butirilcolinesterase/metabolismo
Anidrase Carbônica I/metabolismo
Anidrase Carbônica II/metabolismo
Inibidores da Anidrase Carbônica/síntese química
Inibidores da Anidrase Carbônica/química
Inibidores da Colinesterase/síntese química
Inibidores da Colinesterase/química
Relação Dose-Resposta a Droga
Etilaminas/química
Seres Humanos
Modelos Moleculares
Estrutura Molecular
Relação Estrutura-Atividade
Sulfonamidas/síntese química
Sulfonamidas/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzyl Compounds); 0 (Carbonic Anhydrase Inhibitors); 0 (Cholinesterase Inhibitors); 0 (Ethylamines); 0 (Sulfonamides); 0 (beta-benzylphenethylamine); EC 3.1.1.7 (Acetylcholinesterase); EC 3.1.1.8 (Butyrylcholinesterase); EC 4.2.1.- (Carbonic Anhydrase I); EC 4.2.1.- (Carbonic Anhydrase II)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170904
[St] Status:MEDLINE


  5 / 3998 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28789893
[Au] Autor:Pagliero RJ; Kaiser M; Brun R; Nieto MJ; Mazzieri MR
[Ad] Endereço:Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
[Ti] Título:Lead selection of antiparasitic compounds from a focused library of benzenesulfonyl derivatives of heterocycles.
[So] Source:Bioorg Med Chem Lett;27(17):3945-3949, 2017 09 01.
[Is] ISSN:1464-3405
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:A library of 89 synthetic benzenesulfonyl derivatives of heterocycles with drug-like properties was assayed for in vitro antiparasitic activity and the results were added to our previously reported derivatives for a comprehensive SAR evaluation. Four compounds showed an IC between 0.25 and 3µM against Leishmania donovani and low cytotoxicity. Compound G{16} (1-(2,3,5,6-tetramethylphenylsulfonyl)-2-methylindoline), was particularly interesting with an IC similar to the reference drug miltefosine. Seven compounds showed an IC below 6µM against Trypanosoma cruzi, and three of them (E{3}, E{9} and G{3}) were identified as lead scaffolds for further optimization based on their activity-toxicity profile. Two promising structures (B{15} and G{15}) showed moderate inhibitory activity against Plasmodium falciparum. In general, the presence of a benzenesulfonyl moiety improves the antiparasitic activity of the heterocycles included in this study (with the exception of Trypanosoma brucei rhodesiense), validating the criteria used in the selection of the privileged structures and diversification used to generate this library. SAR analysis showed that the presence of lipophilic and electron withdrawing groups were favorable for the antiparasitic activity.
[Mh] Termos MeSH primário: Antiparasitários/farmacologia
Compostos de Benzil/farmacologia
Compostos Heterocíclicos/farmacologia
Mioblastos/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Antiparasitários/síntese química
Antiparasitários/química
Compostos de Benzil/síntese química
Compostos de Benzil/química
Relação Dose-Resposta a Droga
Compostos Heterocíclicos/síntese química
Compostos Heterocíclicos/química
Leishmania donovani/efeitos dos fármacos
Estrutura Molecular
Testes de Sensibilidade Parasitária
Plasmodium falciparum/efeitos dos fármacos
Ratos
Relação Estrutura-Atividade
Trypanosoma brucei rhodesiense/efeitos dos fármacos
Trypanosoma cruzi/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antiparasitic Agents); 0 (Benzyl Compounds); 0 (Heterocyclic Compounds)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171125
[Lr] Data última revisão:
171125
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170810
[St] Status:MEDLINE


  6 / 3998 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28489276
[Au] Autor:Zhou Y; Dun Y; Fu H; Wang L; Pan X; Yang X; Fang H
[Ad] Endereço:Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmacy, Shandong University, Ji'nan, Shandong, China.
[Ti] Título:Design, synthesis, and preliminary bioactivity evaluation of N-benzylpyrimidin-2-amine derivatives as novel histone deacetylase inhibitor.
[So] Source:Chem Biol Drug Des;90(5):936-942, 2017 Nov.
[Is] ISSN:1747-0285
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Histone deacetylase (HDAC) inhibitors have been identified for the treatment of cancer. Lately, we designed and synthesized a series of substituted N-benzylpyrimidin-2-amine derivatives as potent HDAC inhibitors. In vitro HDAC inhibitory activities and antiproliferative activities of target compounds were investigated. Some target compounds showed potent HDAC inhibitory activities and possessed obvious antiproliferative activity against tumor cells. Target compounds 6a, 6d, 8a, 8c, and 8f not only exhibited almost equally enzymatic inhibitory activity with SAHA, but showed better antiproliferative activities.
[Mh] Termos MeSH primário: Antineoplásicos/química
Antineoplásicos/farmacologia
Proliferação Celular/efeitos dos fármacos
Inibidores de Histona Desacetilases/química
Inibidores de Histona Desacetilases/farmacologia
Pirimidinas/química
Pirimidinas/farmacologia
[Mh] Termos MeSH secundário: Aminação
Antineoplásicos/síntese química
Compostos de Benzil/síntese química
Compostos de Benzil/química
Compostos de Benzil/farmacologia
Linhagem Celular Tumoral
Desenho de Drogas
Ensaios de Seleção de Medicamentos Antitumorais
Inibidores de Histona Desacetilases/síntese química
Histona Desacetilases/metabolismo
Seres Humanos
Neoplasias/tratamento farmacológico
Neoplasias/enzimologia
Pirimidinas/síntese química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Benzyl Compounds); 0 (Histone Deacetylase Inhibitors); 0 (Pyrimidines); EC 3.5.1.98 (Histone Deacetylases)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171113
[Lr] Data última revisão:
171113
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170511
[St] Status:MEDLINE
[do] DOI:10.1111/cbdd.13019


  7 / 3998 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28486552
[Au] Autor:Li Q; Deng C; Xia Y; Kong L; Zhang H; Zhang S; Wang J
[Ad] Endereço:Guangdong Key Laboratory for Innovative Development and Utilization of Forest Plant Germplasm, State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, College of Forestry and Landscape Architecture, South China Agricultural University, Guangzhou, China.
[Ti] Título:Identification of novel miRNAs and miRNA expression profiling in embryogenic tissues of Picea balfouriana treated by 6-benzylaminopurine.
[So] Source:PLoS One;12(5):e0176112, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Here, we compared miRNA expression profiles in embryonic cell cultures of the conifer Picea balfouriana following application of the synthetic cytokinin 6-benzylaminopurine (6-BAP). We used next-generation sequencing to analyze three libraries of small RNAs from the treated embryogenic cell cultures and generated 24,000,000 raw reads from each of the libraries. Over 70 differentially regulated micro RNA (miRNA) families (≥2 fold change in expression) were identified between pairs of treatments. A quantitative analysis showed that miR3633 and miR1026 were upregulated in tissues with the highest embryogenic ability. These two miRNAs were predicted to target genes encoding receptor-like protein kinase and GAMYB transcription factors, respectively. In one library, miR1160, miR5638, miR1315, and miR5225 were downregulated. These four miRNAs were predicted to target genes encoding APETALA2, calmodulin-binding protein, and calcium-dependent protein kinase transcription factors. The expression patterns of the miRNAs and their targets were negatively correlated. Approximately 181 potentially novel P. balfouriana miRNAs were predicted from the three libraries, and seven were validated during the quantitative analysis. This study is the first report of differential miRNA regulation in tissues treated with 6-BAP during somatic embryogenesis. The differentially expressed miRNAs will be of value for investigating the mechanisms of embryogenic processes that are responsive to 6-BAP in P. balfouriana.
[Mh] Termos MeSH primário: Compostos de Benzil/farmacologia
Perfilação da Expressão Gênica
MicroRNAs/genética
Picea/embriologia
Purinas/farmacologia
Sementes/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzyl Compounds); 0 (MicroRNAs); 0 (Purines); KXG6A989PS (benzylaminopurine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170915
[Lr] Data última revisão:
170915
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170510
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0176112


  8 / 3998 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28486208
[Au] Autor:Ahamed M; Attili B; van Veghel D; Ooms M; Berben P; Celen S; Koole M; Declercq L; Savinainen JR; Laitinen JT; Verbruggen A; Bormans G
[Ad] Endereço:Laboratory for Radiopharmaceutical Research, Department of Pharmaceutical and Pharmacological Sciences, Campus Gasthuisberg O&N2, Herestraat 49 Box 821, BE-3000 Leuven, Belgium.
[Ti] Título:Synthesis and preclinical evaluation of [ C]MA-PB-1 for in vivo imaging of brain monoacylglycerol lipase (MAGL).
[So] Source:Eur J Med Chem;136:104-113, 2017 Aug 18.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:MAGL is a potential therapeutic target for oncological and psychiatric diseases. Our objective was to develop a PET tracer for in vivo quantification of MAGL. We report [ C]MA-PB-1 as an irreversible MAGL inhibitor PET tracer. The in vitro inhibitory activity, ex vivo distribution, brain kinetics and specificity of [ C]MA-PB-1 binding were studied. Ex vivo biodistribution and microPET showed good brain uptake which could be blocked by pretreatment with both MA-PB-1 and a structurally non-related MAGL inhibitor MJN110. These initial results suggest that [ C]MA-PB-1 is a suitable tracer for in vivo imaging of MAGL.
[Mh] Termos MeSH primário: Compostos de Benzil/farmacologia
Encéfalo/enzimologia
Inibidores Enzimáticos/farmacologia
Monoacilglicerol Lipases/antagonistas & inibidores
Piperazinas/farmacologia
[Mh] Termos MeSH secundário: Animais
Compostos de Benzil/síntese química
Compostos de Benzil/química
Relação Dose-Resposta a Droga
Inibidores Enzimáticos/síntese química
Inibidores Enzimáticos/química
Feminino
Macaca mulatta
Camundongos
Estrutura Molecular
Monoacilglicerol Lipases/metabolismo
Piperazinas/síntese química
Piperazinas/química
Tomografia por Emissão de Pósitrons
Traçadores Radioativos
Ratos
Ratos Wistar
Relação Estrutura-Atividade
Distribuição Tecidual
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (((11)C)MA-PB-1); 0 (Benzyl Compounds); 0 (Enzyme Inhibitors); 0 (Piperazines); 0 (Radioactive Tracers); EC 3.1.1.23 (Monoacylglycerol Lipases)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170928
[Lr] Data última revisão:
170928
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170510
[St] Status:MEDLINE


  9 / 3998 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28443656
[Au] Autor:Dovgan I; Ursuegui S; Erb S; Michel C; Kolodych S; Cianférani S; Wagner A
[Ad] Endereço:Laboratory of Functional ChemoSystems (UMR 7199), LabEx Medalis, University of Strasbourg , 67087 Strasbourg, France.
[Ti] Título:Acyl Fluorides: Fast, Efficient, and Versatile Lysine-Based Protein Conjugation via Plug-and-Play Strategy.
[So] Source:Bioconjug Chem;28(5):1452-1457, 2017 May 17.
[Is] ISSN:1520-4812
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:We report a plug-and-play strategy for the preparation of functionally enhanced antibodies with a defined average degree of conjugation (DoC). The first stage (plug) allows the controllable and efficient installation of azide groups on lysine residues of a native antibody using 4-azidobenzoyl fluoride. The second step (play) allows for versatile antibody functionalization with a single payload or combination of payloads, such as a toxin, a fluorophore, or an oligonucleotide, via copper-free strain-promoted azide-alkyne cycloaddition (SPAAC). It is notable that in comparison to a classical N-hydroxysuccinimide ester (NHS) strategy, benzoyl fluorides show faster and more efficient acylation of lysine residues in a PBS buffer. This translates into better control of the DoC and enables the efficient and fast functionalization of delicate biomolecules at low temperature.
[Mh] Termos MeSH primário: Anticorpos Monoclonais/química
Compostos de Benzil/química
Fluoretos/química
Imunoconjugados/química
Lisina/química
Receptor ErbB-2/imunologia
[Mh] Termos MeSH secundário: Acilação
Alquinos/química
Anticorpos Monoclonais/imunologia
Azidas/química
Química Click
Reação de Cicloadição
Corantes Fluorescentes/química
Seres Humanos
Imunoconjugados/imunologia
Estrutura Molecular
Oligonucleotídeos/química
Succinimidas/química
Toxinas Biológicas/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Alkynes); 0 (Antibodies, Monoclonal); 0 (Azides); 0 (Benzyl Compounds); 0 (Fluorescent Dyes); 0 (Immunoconjugates); 0 (Oligonucleotides); 0 (Succinimides); 0 (Toxins, Biological); EC 2.7.10.1 (ERBB2 protein, human); EC 2.7.10.1 (Receptor, ErbB-2); K3Z4F929H6 (Lysine); MJE3791M4T (N-hydroxysuccinimide); Q80VPU408O (Fluorides)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170427
[St] Status:MEDLINE
[do] DOI:10.1021/acs.bioconjchem.7b00141


  10 / 3998 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28441580
[Au] Autor:Lazewska D; Kurczab R; Wiecek M; Kaminska K; Satala G; Jastrzebska-Wiesek M; Partyka A; Bojarski AJ; Wesolowska A; Kiec-Kononowicz K; Handzlik J
[Ad] Endereço:Department of Technology and Biotechnology of Drugs, Jagiellonian University, Medical College, Medyczna 9, PL 30-688 Kraków, Poland. Electronic address: dlazewska@cm-uj.krakow.pl.
[Ti] Título:The computer-aided discovery of novel family of the 5-HT serotonin receptor ligands among derivatives of 4-benzyl-1,3,5-triazine.
[So] Source:Eur J Med Chem;135:117-124, 2017 Jul 28.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:The work describes a discovery of new chemical family of potent ligands for the 5-HT serotonin receptors. During the search for new histamine H receptor antagonists among 1,3,5-triazine derivatives, compound 2 (4-benzyl-6-(4-methylpiperazin-1-yl)-1,3,5-triazin-2-amine) was found. Compound 2, weakly active for the H receptor but fitted in 3/4 of pharmacophore features of the 5-HT R ligand, occurred to be a moderate 5-HT R agent, useful as a lead structure for further modifications. A series of new derivatives (3-19) of the lead 2 was synthesized, evaluated in the radioligand binding assay (RBA) and explored in comprehensive molecular modelling, including both pharmacophore- and structure-based approaches with docking to the homology model of 5-HT R. The most active compounds displayed a potent affinity for the 5-HT R in the nanomolar range (K = 20-30 nM), some of them (4, 11 and 19) were tested in the rat forced swim test that revealed their antidepressant-like effect. SAR-analysis on the basis of both, RBA and docking results, indicated that action on the receptor is related to the hydrophobicity and the size of aromatic moiety substituted by a methylene linker at the position 4 of 1,3,5-triazine.
[Mh] Termos MeSH primário: Compostos de Benzil/farmacologia
Projeto Auxiliado por Computador
Descoberta de Drogas
Receptores de Serotonina/metabolismo
Antagonistas da Serotonina/farmacologia
Triazinas/farmacologia
[Mh] Termos MeSH secundário: Compostos de Benzil/síntese química
Compostos de Benzil/química
Relação Dose-Resposta a Droga
Seres Humanos
Ligantes
Modelos Moleculares
Estrutura Molecular
Antagonistas da Serotonina/síntese química
Antagonistas da Serotonina/química
Relação Estrutura-Atividade
Triazinas/síntese química
Triazinas/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (4-benzyl-1,3,5-triazine); 0 (Benzyl Compounds); 0 (Ligands); 0 (Receptors, Serotonin); 0 (Serotonin Antagonists); 0 (Triazines); 0 (serotonin 6 receptor)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170919
[Lr] Data última revisão:
170919
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170426
[St] Status:MEDLINE



página 1 de 400 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