Base de dados : MEDLINE
Pesquisa : D02.886.675.649 [Categoria DeCS]
Referências encontradas : 416 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 42 ir para página                         

  1 / 416 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29419686
[Au] Autor:Wang X; Lin H; Xu S; Jin Y; Zhang R
[Ad] Endereço:Shenzhen Bao'an Traditional Chinese Medicine Hospital Group, Guangzhou University of Chinese Medicine, Shenzhen.
[Ti] Título:The clinical efficacy of epalrestat combined with α-lipoic acid in diabetic peripheral neuropathy: Protocol for a systematic review and meta-analysis.
[So] Source:Medicine (Baltimore);97(6):e9828, 2018 Feb.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Diabetic peripheral neuropathy (DPN) is a common long-term complication of diabetes mellitus, affecting patients in the world. Epalrestat combined with α-lipoic acid (ALA) is the most frequent combine therapy used in the DPN researches. We aim to assess the effectiveness and safety of epalrestat combined with ALA in patients with DPN, compare with epalrestat alone. METHODS: We will search Cochrane Library, PubMed, Wanfang Data, China National Knowledge Infrastructure, VIP Chinese Science and Technology Journals Database, and Chinese Biomedical Database from inception until October 31th, 2017. Inclusion the randomized controlled trials and clinical control trials of combine therapy which evaluate clinical efficacy and side effect in people with DPN. Data extraction and risk of bias assessments will be independently conducted by 2 reviewers. The primary outcome measures will be total effective rate, motor nerve conduction velocity (MNCV), sensory nerve conduction velocity (SNCV), Toronto clinical scoring system (TCSS), and total symptom score (TSS). All statistical analyses will be performed using RevMan V.5.3 software. RESULTS: This review will evaluate the total effective rate, nerve conduction velocity, TCSS, TSS, and safety of ALA combined with epalrestat for patients with DPN, compare with epalrestat alone. CONCLUSION: Our study will provide evidence to assess whether epalrestat combined with ALA is an optional treatment for patients with DPN.
[Mh] Termos MeSH primário: Neuropatias Diabéticas/tratamento farmacológico
Metanálise como Assunto
Rodanina/análogos & derivados
Tiazolidinas
Ácido Tióctico
[Mh] Termos MeSH secundário: Antioxidantes/administração & dosagem
Antioxidantes/efeitos adversos
Quimioterapia Combinada
Inibidores Enzimáticos/administração & dosagem
Inibidores Enzimáticos/efeitos adversos
Seres Humanos
Ensaios Clínicos Controlados Aleatórios como Assunto
Projetos de Pesquisa
Rodanina/administração & dosagem
Rodanina/efeitos adversos
Tiazolidinas/administração & dosagem
Tiazolidinas/efeitos adversos
Ácido Tióctico/administração & dosagem
Ácido Tióctico/efeitos adversos
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antioxidants); 0 (Enzyme Inhibitors); 0 (Thiazolidines); 424DV0807X (epalrestat); 73Y7P0K73Y (Thioctic Acid); 7O50LKL2G8 (Rhodanine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180214
[Lr] Data última revisão:
180214
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180209
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009828


  2 / 416 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28935265
[Au] Autor:El-Sayed S; Metwally K; El-Shanawani AA; Abdel-Aziz LM; El-Rashedy AA; Soliman MES; Quattrini L; Coviello V; la Motta C
[Ad] Endereço:Department of Medicinal Chemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt.
[Ti] Título:Quinazolinone-based rhodanine-3-acetic acids as potent aldose reductase inhibitors: Synthesis, functional evaluation and molecular modeling study.
[So] Source:Bioorg Med Chem Lett;27(20):4760-4764, 2017 10 15.
[Is] ISSN:1464-3405
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:A series of quinazolinone-based rhodanine-3-acetic acids was synthesized and tested for in vitro aldose reductase inhibitory activity. All the target compounds displayed nanomolar activity against the target enzyme. Compounds 3a, 3b, and 3e exhibited almost 3-fold higher activity as compared to the only marketed reference drug epalrestat. Structure-activity relationship studies indicated that bulky substituents at the 3-phenyl ring of the quinazolinone moiety are generally not tolerated in the active site of the enzyme. Insertion of a methoxy group on the central benzylidene ring was found to have a variable effect on ALR-2 activity depending on the nature of peripheral quinazolinone ring substituents. Removal of the acetic acid moiety led to inactive or weakly active target compounds. Docking and molecular dynamic simulations of the most active rhodanine-3-acetic acid derivatives were also carried out, to provide the basis for further structure-guided design of novel inhibitors.
[Mh] Termos MeSH primário: Aldeído Redutase/antagonistas & inibidores
Inibidores Enzimáticos/síntese química
Quinazolinonas/química
Rodanina/química
[Mh] Termos MeSH secundário: Ácido Acético/química
Aldeído Redutase/metabolismo
Sítios de Ligação
Inibidores Enzimáticos/metabolismo
Concentração Inibidora 50
Simulação de Acoplamento Molecular
Rodanina/análogos & derivados
Rodanina/síntese química
Rodanina/metabolismo
Relação Estrutura-Atividade
Termodinâmica
Tiazolidinas/química
Tiazolidinas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Enzyme Inhibitors); 0 (Quinazolinones); 0 (Thiazolidines); 424DV0807X (epalrestat); 7O50LKL2G8 (Rhodanine); EC 1.1.1.21 (Aldehyde Reductase); Q40Q9N063P (Acetic Acid)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171125
[Lr] Data última revisão:
171125
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170923
[St] Status:MEDLINE


  3 / 416 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
[PMID]:28739687
[Au] Autor:Sawaguchi Y; Yamazaki R; Nishiyama Y; Sasai T; Mae M; Abe A; Yaegashi T; Nishiyama H; Matsuzaki T
[Ad] Endereço:Yakult Central Institute, Yakult Honsha Co., Ltd., Tokyo, Japan yuichi-sawaguchi@yakult.co.jp.
[Ti] Título:Rational Design of a Potent Pan-Pim Kinases Inhibitor with a Rhodanine-Benzoimidazole Structure.
[So] Source:Anticancer Res;37(8):4051-4057, 2017 08.
[Is] ISSN:1791-7530
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:BACKGROUND/AIM: The serine/threonine Pim kinases are overexpressed in various types of solid carcinomas and hematological malignancies, and contribute to regulating cell-cycle progression and cell survival. The aim of this study was to discover a novel pan-Pim kinases inhibitor with potent anti-proliferative activities against cancer cell lines. MATERIALS AND METHODS: We screened a panel of small molecule compounds for their ability to inhibit Pim-1 kinase activity, and the hit compound was optimized using the docking analysis to Pim-1. We evaluated kinase-inhibition activities of the rationally-designed compound against Pim-1, 2, 3 and another five kinases. Furthermore, in order to characterize the cellular activities, both solid and hematological cancer cell lines treated with the compound were subjected to anti-proliferative assay, western blotting, FACS and apoptosis assays. RESULTS: We discovered a pan-Pim kinases inhibitor, compound , with a rhodanine-benzylidene structure via Pim-1 inhibitor screening. Using docking analysis of compound and Pim-1, we optimized it and found a potent- and selective-Pim kinases inhibitor, compound , with a rhodanine-benzoimidazole structure. Compound inhibited Pim-1, 2, 3 with IC values of 16, 13, and 6.4 nM, respectively, and suppressed proliferation of solid and hematological cancer cell lines at submicromolar concentrations. In both types of cell lines, compound inhibited phosphorylation of Pim signaling substrates and cell-cycle progression and induced apoptosis. CONCLUSION: We identified a pan-Pim kinases inhibitor, compound , with a rhodanine-benzoimidazole structure. Our data suggest that compound can serve as a lead to novel anticancer agents, effective in the treatment of both solid carcinomas and hematological malignancies.
[Mh] Termos MeSH primário: Proliferação Celular/efeitos dos fármacos
Neoplasias/tratamento farmacológico
Inibidores de Proteínas Quinases/administração & dosagem
Proteínas Proto-Oncogênicas c-pim-1/antagonistas & inibidores
[Mh] Termos MeSH secundário: Apoptose/efeitos dos fármacos
Linhagem Celular Tumoral
Sobrevivência Celular/efeitos dos fármacos
Inibidores Enzimáticos/administração & dosagem
Inibidores Enzimáticos/química
Seres Humanos
Neoplasias/enzimologia
Neoplasias/patologia
Fosforilação/efeitos dos fármacos
Inibidores de Proteínas Quinases/química
Proteínas Proto-Oncogênicas c-pim-1/genética
Rodanina/química
Transdução de Sinais/efeitos dos fármacos
Bibliotecas de Moléculas Pequenas/administração & dosagem
Bibliotecas de Moléculas Pequenas/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Enzyme Inhibitors); 0 (Protein Kinase Inhibitors); 0 (Small Molecule Libraries); 7O50LKL2G8 (Rhodanine); EC 2.7.11.1 (Proto-Oncogene Proteins c-pim-1)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170906
[Lr] Data última revisão:
170906
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170726
[St] Status:MEDLINE


  4 / 416 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28445852
[Au] Autor:Huang J; Sun R; Feng S; He J; Fei F; Gao H; Zhao Y; Zhang Y; Gu H; Aa J; Wang G
[Ad] Endereço:State Key Laboratory of Natural Medicines, Jiangsu Province Key Laboratory of Drug Metabolism and Pharmacokinetics, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China.
[Ti] Título:Sensitive analysis and pharmacokinetic study of epalrestat in C57BL/6J mice.
[So] Source:J Chromatogr B Analyt Technol Biomed Life Sci;1055-1056:98-103, 2017 Jun 15.
[Is] ISSN:1873-376X
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Epalrestat is clinically applied for the management of diabetic peripheral neuropathy, yet its pharmacokinetic properties are not well understood. In this study, a rapid and sensitive LC-MS/MS method was established for assaying epalrestat in bio-samples of mice. The method was validated and it showed a good linearity over the range of 2-5000ng/mL, a precision of less than 12.3%, and recovery and matrix effects of 112.5-123.6% and 87.9-89.5%, respectively. After administration of a single dose of epalrestat administered, the exposure level of AUC was positively dose-dependent and the mean C , AUC , T , and MRT were 36.23±7.39µg/mL, 29,086.5µg/Lh, 1.2h and 1.8h, respectively. Epalrestat was highly exposed in stomach, intestine, liver and kidney, and only a small amount was detected in brain, urine and feces. Multi-dose of epalrestat significantly increased MRT and apparent volume of distribution (V ) relative to those of a single-dose.
[Mh] Termos MeSH primário: Cromatografia Líquida de Alta Pressão/métodos
Inibidores Enzimáticos/farmacocinética
Rodanina/análogos & derivados
Tiazolidinas/farmacocinética
[Mh] Termos MeSH secundário: Administração Oral
Animais
Inibidores Enzimáticos/administração & dosagem
Inibidores Enzimáticos/sangue
Inibidores Enzimáticos/urina
Feminino
Limite de Detecção
Masculino
Camundongos Endogâmicos C57BL
Rodanina/administração & dosagem
Rodanina/sangue
Rodanina/farmacocinética
Rodanina/urina
Espectrometria de Massas por Ionização por Electrospray/métodos
Tiazolidinas/administração & dosagem
Tiazolidinas/sangue
Tiazolidinas/urina
Distribuição Tecidual
[Pt] Tipo de publicação:JOURNAL ARTICLE; VALIDATION STUDIES
[Nm] Nome de substância:
0 (Enzyme Inhibitors); 0 (Thiazolidines); 424DV0807X (epalrestat); 7O50LKL2G8 (Rhodanine)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170619
[Lr] Data última revisão:
170619
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170427
[St] Status:MEDLINE


  5 / 416 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28390993
[Au] Autor:El-Miligy MMM; Hazzaa AA; El-Messmary H; Nassra RA; El-Hawash SAM
[Ad] Endereço:Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt. Electronic address: mostafa.elmiligy@alexu.edu.eg.
[Ti] Título:New hybrid molecules combining benzothiophene or benzofuran with rhodanine as dual COX-1/2 and 5-LOX inhibitors: Synthesis, biological evaluation and docking study.
[So] Source:Bioorg Chem;72:102-115, 2017 Jun.
[Is] ISSN:1090-2120
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:New molecular hybrids combining benzothiophene or its bioisostere benzofuran with rhodanine were synthesized as potential dual COX-2/5-LOX inhibitors. The benzothiophene or benzofuran scaffold was linked at position -2 with rhodanine which was further linked to various anti-inflammatory pharmacophores so as to investigate the effect of such molecular variation on the anti-inflammatory activity. The target compounds were evaluated for their in vitro COX/LOX inhibitory activity. The results revealed that, compound 5h exhibited significant COX-2 inhibition higher than celecoxib. Furthermore, compounds 5a, 5f and 5i showed COX-2 inhibitory activity comparable to celecoxib. Compound 5h showed selectivity index SI=5.1 which was near to that of celecoxib (SI=6.7). Compound 5h displayed LOX inhibitory activity twice than that of meclofenamate sodium. Moreover, compounds 5a, 5e and 5f showed significant LOX inhibitory activity higher than that of meclofenamate sodium. Compound 5h was screened for its in vivo anti-inflammatory activity using formalin-induced paw edema and gastric ulcerogenic activity tests. The results revealed that, it showed in vivo decrease in formalin-induced paw edema volume higher than celecoxib. It also displayed gastrointestinal safety profile as celecoxib. The biological results were also consistent with the docking studies at the active sites of the target enzymes COX-2 and 5-LOX. Also, compound 5h showed physicochemical, ADMET, and drug-like properties within those considered adequate for a drug candidate.
[Mh] Termos MeSH primário: Anti-Inflamatórios não Esteroides/farmacologia
Araquidonato 5-Lipoxigenase/metabolismo
Ciclo-Oxigenase 1/metabolismo
Ciclo-Oxigenase 2/metabolismo
Inibidores de Ciclo-Oxigenase/farmacologia
Inibidores de Lipoxigenase/farmacologia
[Mh] Termos MeSH secundário: Animais
Anti-Inflamatórios não Esteroides/síntese química
Anti-Inflamatórios não Esteroides/química
Benzofuranos/química
Benzofuranos/farmacologia
Domínio Catalítico/efeitos dos fármacos
Inibidores de Ciclo-Oxigenase/síntese química
Inibidores de Ciclo-Oxigenase/química
Relação Dose-Resposta a Droga
Edema/induzido quimicamente
Edema/tratamento farmacológico
Formaldeído
Inibidores de Lipoxigenase/síntese química
Inibidores de Lipoxigenase/química
Masculino
Simulação de Acoplamento Molecular
Estrutura Molecular
Ratos
Ratos Wistar
Rodanina/química
Rodanina/farmacologia
Relação Estrutura-Atividade
Tiofenos/química
Tiofenos/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents, Non-Steroidal); 0 (Benzofurans); 0 (Cyclooxygenase Inhibitors); 0 (Lipoxygenase Inhibitors); 0 (Thiophenes); 073790YQ2G (benzothiophene); 1HG84L3525 (Formaldehyde); 7O50LKL2G8 (Rhodanine); EC 1.13.11.34 (Arachidonate 5-Lipoxygenase); EC 1.14.99.1 (Cyclooxygenase 1); EC 1.14.99.1 (Cyclooxygenase 2); LK6946W774 (benzofuran)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170616
[Lr] Data última revisão:
170616
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170410
[St] Status:MEDLINE


  6 / 416 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28386557
[Au] Autor:El Gamal H; Eid AH; Munusamy S
[Ad] Endereço:College of Pharmacy, Qatar University, P.O. Box 2713, Doha, Qatar.
[Ti] Título:Renoprotective Effects of Aldose Reductase Inhibitor Epalrestat against High Glucose-Induced Cellular Injury.
[So] Source:Biomed Res Int;2017:5903105, 2017.
[Is] ISSN:2314-6141
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Diabetic nephropathy (DN) is the leading cause of end stage renal disease worldwide. Increased glucose flux into the aldose reductase (AR) pathway during diabetes was reported to exert deleterious effects on the kidney. The objective of this study was to investigate the renoprotective effects of AR inhibition in high glucose milieu in vitro. Rat renal tubular (NRK-52E) cells were exposed to high glucose (30 mM) or normal glucose (5 mM) media for 24 to 48 hours with or without the AR inhibitor epalrestat (1 M) and assessed for changes in Akt and ERK1/2 signaling, AR expression (using western blotting), and alterations in mitochondrial membrane potential (using JC-1 staining), cell viability (using MTT assay), and cell cycle. Exposure of NRK-52E cells to high glucose media caused acute activation of Akt and ERK pathways and depolarization of mitochondrial membrane at 24 hours. Prolonged high glucose exposure (for 48 hours) induced AR expression and 1 cell cycle arrest and decreased cell viability (84% compared to control) in NRK-52E cells. Coincubation of cells with epalrestat prevented the signaling changes and renal cell injury induced by high glucose. Thus, AR inhibition represents a potential therapeutic strategy to prevent DN.
[Mh] Termos MeSH primário: Aldeído Redutase/antagonistas & inibidores
Diabetes Mellitus Experimental/tratamento farmacológico
Nefropatias Diabéticas/tratamento farmacológico
Rodanina/análogos & derivados
Tiazolidinas/administração & dosagem
[Mh] Termos MeSH secundário: Aldeído Redutase/metabolismo
Animais
Diabetes Mellitus Experimental/metabolismo
Diabetes Mellitus Experimental/patologia
Nefropatias Diabéticas/metabolismo
Nefropatias Diabéticas/patologia
Inibidores Enzimáticos/administração & dosagem
Células Epiteliais/efeitos dos fármacos
Células Epiteliais/metabolismo
Células Epiteliais/patologia
Glucose/administração & dosagem
Glucose/metabolismo
Seres Humanos
Rim/efeitos dos fármacos
Rim/metabolismo
Rim/patologia
Túbulos Renais Proximais/efeitos dos fármacos
Túbulos Renais Proximais/enzimologia
Túbulos Renais Proximais/patologia
Sistema de Sinalização das MAP Quinases/efeitos dos fármacos
Proteínas Proto-Oncogênicas c-akt/biossíntese
Ratos
Rodanina/administração & dosagem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Enzyme Inhibitors); 0 (Thiazolidines); 424DV0807X (epalrestat); 7O50LKL2G8 (Rhodanine); EC 1.1.1.21 (Aldehyde Reductase); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt); IY9XDZ35W2 (Glucose)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170428
[Lr] Data última revisão:
170428
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170408
[St] Status:MEDLINE
[do] DOI:10.1155/2017/5903105


  7 / 416 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28196707
[Au] Autor:Krátký M; Vinsová J; Stolaríková J
[Ad] Endereço:Department of Organic and Bioorganic Chemistry, Faculty of Pharmacy, Charles University in Prague, Heyrovského 1203, 50005 Hradec Králové, Czech Republic. Electronic address: martin.kratky@faf.cuni.cz.
[Ti] Título:Antimicrobial activity of rhodanine-3-acetic acid derivatives.
[So] Source:Bioorg Med Chem;25(6):1839-1845, 2017 Mar 15.
[Is] ISSN:1464-3391
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Twenty-four 2-(4-oxo-2-thioxothiazolidin-3-yl)acetic acid (rhodanine-3-acetic acid)-based amides, esters and 5-arylalkylidene derivatives were synthesized, characterized and evaluated as potential antimicrobial agents against a panel of bacteria, mycobacteria and fungi. All of the derivatives were active against mycobacteria. N-(4-Chlorophenyl)-2-[5-(2-hydroxybenzylidene)-4-oxo-2-thioxothiazolidin-3-yl]acetamide demonstrated the highest activity against Mycobacterium tuberculosis with minimum inhibitory concentrations (MIC) of 8-16µM. Non-tuberculous mycobacteria were the most susceptible to 2-[5-(2-hydroxybenzylidene)-4-oxo-2-thioxothiazolidin-3-yl]acetic acids (MIC values ⩾32µM). The highest antibacterial activity against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus exhibited 4-(trifluoromethyl)phenyl 2-(4-oxo-2-thioxothiazolidin-3-yl)acetate (MIC⩾15.62µM). Several structure-activity relationships were identified. The activity against Gram-negative and fungal pathogens was marginal.
[Mh] Termos MeSH primário: Ácido Acético/química
Anti-Infecciosos/farmacologia
Rodanina/farmacologia
[Mh] Termos MeSH secundário: Candida/efeitos dos fármacos
Espectroscopia de Ressonância Magnética Nuclear de Carbono-13
Bactérias Gram-Positivas/efeitos dos fármacos
Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos
Testes de Sensibilidade Microbiana
Espectroscopia de Prótons por Ressonância Magnética
Rodanina/química
Espectrofotometria Infravermelho
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Infective Agents); 7O50LKL2G8 (Rhodanine); Q40Q9N063P (Acetic Acid)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171002
[Lr] Data última revisão:
171002
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170216
[St] Status:MEDLINE


  8 / 416 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28057038
[Au] Autor:Huang Z; Hong Q; Zhang X; Xiao W; Wang L; Cui S; Feng Z; Lv Y; Cai G; Chen X; Wu D
[Ad] Endereço:Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center of Kidney Diseases, Beijing, 100853, People's Republic of China.
[Ti] Título:Aldose reductase mediates endothelial cell dysfunction induced by high uric acid concentrations.
[So] Source:Cell Commun Signal;15(1):3, 2017 Jan 05.
[Is] ISSN:1478-811X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Uric acid (UA) is an antioxidant found in human serum. However, high UA levels may also have pro-oxidant functions. According to previous research, aldose reductase (AR) plays a vital role in the oxidative stress-related complications of diabetes. We sought to determine the mechanism by which UA becomes deleterious at high concentrations as well as the effect of AR in this process. METHOD: Endothelial cells were divided into three groups cultured without UA or with 300 µM or 600 µM UA. The levels of total reactive oxygen species (ROS), of four ROS components, and of NO and NOX4 expression were measured. Changes in the above molecules were detected upon inhibiting NOX4 or AR, and serum H O and vWF levels were measured in vivo. RESULTS: Increased AR expression in high UA-treated endothelial cells enhanced ROS production by activating NADPH oxidase. These effects were blocked by the AR inhibitor epalrestat. 300 µM UA decreased the levels of the three major reactive oxygen species (ROS) components: O •-, •OH, and O . However, when the UA concentration was increased, both O •- levels and downstream H O production significantly increased. Finally, an AR inhibitor reduced H O production in hyperuricemic mice and protected endothelial cell function. CONCLUSIONS: Our findings indicate that inhibiting AR or degrading H O could protect endothelial function and maintain the antioxidant activities of UA. These findings provide new insight into the role of UA in chronic kidney disease.
[Mh] Termos MeSH primário: Aldeído Redutase/metabolismo
Células Endoteliais da Veia Umbilical Humana/enzimologia
Células Endoteliais da Veia Umbilical Humana/patologia
Ácido Úrico/farmacologia
[Mh] Termos MeSH secundário: Aldeído Redutase/antagonistas & inibidores
Animais
Catalase/farmacologia
Citoproteção/efeitos dos fármacos
Inibidores Enzimáticos/farmacologia
Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos
Peróxido de Hidrogênio/metabolismo
Hiperuricemia/metabolismo
Camundongos
Modelos Biológicos
NADPH Oxidases/metabolismo
Óxido Nítrico/metabolismo
Estresse Oxidativo/efeitos dos fármacos
Polietilenoglicóis/farmacologia
Rodanina/análogos & derivados
Rodanina/farmacologia
Tiazolidinas/farmacologia
Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Enzyme Inhibitors); 0 (Thiazolidines); 0 (catalase-polyethylene glycol); 268B43MJ25 (Uric Acid); 30IQX730WE (Polyethylene Glycols); 31C4KY9ESH (Nitric Oxide); 424DV0807X (epalrestat); 7O50LKL2G8 (Rhodanine); BBX060AN9V (Hydrogen Peroxide); EC 1.1.1.21 (Aldehyde Reductase); EC 1.11.1.6 (Catalase); EC 1.6.3.- (NADPH Oxidases); EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170107
[St] Status:MEDLINE
[do] DOI:10.1186/s12964-016-0158-6


  9 / 416 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27835059
[Au] Autor:Senthilkumari S; Sharmila R; Chidambaranathan G; Vanniarajan A
[Ad] Endereço:1 Department of Ocular Pharmacology, Dr. G. Venkataswamy Eye Research Institute , Madurai, India .
[Ti] Título:Epalrestat, an Aldose Reductase Inhibitor Prevents Glucose-Induced Toxicity in Human Retinal Pigment Epithelial Cells In Vitro.
[So] Source:J Ocul Pharmacol Ther;33(1):34-41, 2017 Jan/Feb.
[Is] ISSN:1557-7732
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Aldose reductase (ALR), the first and rate-limiting enzyme involved in polyol pathway plays a central role in diabetes and its related complications, including diabetic retinopathy (DR). Inhibition of ALR may also be an ideal target for reducing the deleterious effects of DR. Therefore, the purpose of the present study was to investigate the protective effect of epalrestat (EPL), ALR inhibitor on glucose-induced toxicity in ARPE-19 cells. METHODS: ARPE-19 cells were challenged with normal glucose (NG, 5 mM) and high glucose (HG1, 25 mM and HG2, 50 mM) in the presence or absence of EPL. ALR and VEGF expression in retinal pigment epithelial (RPE) cells under experimental conditions were quantified by real-time polymerase chain reaction using SYBR Green chemistry. Vascular endothelial growth factor (VEGF) secretion in the cell supernatant was measured by Sandwich ELISA. Cytotoxicity of EPL was assessed by MTT assay. ALR inhibitory activity, apoptosis, and sorbitol accumulation were also investigated. RESULTS: EPL at studied concentration did not show any toxicity to RPE cells and showed as maximum as 65% ALR inhibition under high glucose condition (HG1). The presence of EPL significantly reduced ALR expression and VEGF levels as induced by high glucose in ARPE-19 cells. CONCLUSION: Inhibition of ALR appeared to be beneficial in reducing diabetes-related complications in RPE cells under high glucose condition.
[Mh] Termos MeSH primário: Aldeído Redutase/antagonistas & inibidores
Inibidores Enzimáticos/farmacologia
Glucose/antagonistas & inibidores
Epitélio Pigmentado da Retina/efeitos dos fármacos
Rodanina/análogos & derivados
Tiazolidinas/farmacologia
[Mh] Termos MeSH secundário: Aldeído Redutase/genética
Aldeído Redutase/metabolismo
Apoptose/efeitos dos fármacos
Células Cultivadas
Relação Dose-Resposta a Droga
Inibidores Enzimáticos/administração & dosagem
Glucose/toxicidade
Seres Humanos
Epitélio Pigmentado da Retina/patologia
Rodanina/administração & dosagem
Rodanina/farmacologia
Sorbitol/antagonistas & inibidores
Sorbitol/metabolismo
Relação Estrutura-Atividade
Tiazolidinas/administração & dosagem
Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores
Fatores de Crescimento do Endotélio Vascular/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Enzyme Inhibitors); 0 (Thiazolidines); 0 (Vascular Endothelial Growth Factors); 424DV0807X (epalrestat); 506T60A25R (Sorbitol); 7O50LKL2G8 (Rhodanine); EC 1.1.1.21 (Aldehyde Reductase); IY9XDZ35W2 (Glucose)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171110
[Lr] Data última revisão:
171110
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161112
[St] Status:MEDLINE
[do] DOI:10.1089/jop.2016.0103


  10 / 416 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27688192
[Au] Autor:Subhedar DD; Shaikh MH; Shingate BB; Nawale L; Sarkar D; Khedkar VM; Kalam Khan FA; Sangshetti JN
[Ad] Endereço:Department of Chemistry, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad 431 004, India.
[Ti] Título:Quinolidene-rhodanine conjugates: Facile synthesis and biological evaluation.
[So] Source:Eur J Med Chem;125:385-399, 2017 Jan 05.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:A series of rhodanine incorporated quinoline derivatives were efficiently synthesized using reusable DBU acetate as ionic liquid and evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Ra (MTB) (ATCC 25177) and Mycobacterium bovis BCG (ATCC 35743) both in active and dormant state. Compounds 3e, 3f, 3g, 3h and 3i exhibited very good antitubercular activity. The active compounds were studied for cytotoxicity against HUVEC, THP-1, macrophages, A549, PANC-1 and HeLa cell lines using modified MTT assay and were found to be noncytotoxic. Inactivity of all these compounds against Gram positive and Gram negative bacteria indicates their specificity towards the MTB. Further, the synthesized compounds have been screened for their in vitro antifungal activity. In addition, the molecular docking studies revealed the binding modes of these compounds in active site of Zmp1 enzyme, which in turn helped to establish a structural basis of inhibition of mycobacteria. The results of present study clearly indicate the identification of some novel, selective and specific inhibitors against MTB that can be explored further for potential antitubercular drug.
[Mh] Termos MeSH primário: Antituberculosos/química
Antituberculosos/farmacologia
Mycobacterium bovis/efeitos dos fármacos
Quinolinas/química
Quinolinas/farmacologia
Rodanina/análogos & derivados
Rodanina/química
Rodanina/farmacologia
[Mh] Termos MeSH secundário: Animais
Antituberculosos/síntese química
Proteínas de Bactérias/metabolismo
Linhagem Celular
Seres Humanos
Metaloproteases/metabolismo
Simulação de Acoplamento Molecular
Infecções por Mycobacterium/tratamento farmacológico
Infecções por Mycobacterium/veterinária
Mycobacterium bovis/metabolismo
Mycobacterium tuberculosis/efeitos dos fármacos
Mycobacterium tuberculosis/metabolismo
Quinolinas/síntese química
Rodanina/síntese química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antitubercular Agents); 0 (Bacterial Proteins); 0 (Quinolines); 7O50LKL2G8 (Rhodanine); EC 3.4.- (Metalloproteases); EC 3.4.- (Zmp1 protein, Mycobacterium tuberculosis)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170307
[Lr] Data última revisão:
170307
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161001
[St] Status:MEDLINE



página 1 de 42 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