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  1 / 11207 MEDLINE  
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[PMID]:28521570
[Au] Autor:Li M; Wu X; Wang X; Shen T; Ren D
[Ad] Endereço:a Department of Natural Product Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences , Shandong University , Jinan , P. R. China.
[Ti] Título:Two novel compounds from the root bark of Morus alba L.
[So] Source:Nat Prod Res;32(1):36-42, 2018 Jan.
[Is] ISSN:1478-6427
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Chemical investigation of the root bark of Morus alba led to the isolation of a new flavone, dioxycudraflavone A (1) and a new 2-arylbenzofuran, 5-hydroxyethyl moracin M (2), together with seven known compounds namely sanggenon V (3), morusin (4), morusignin L (5), licoflavone C (6), moracin C (7), alfafuran (8) and mulberrofuran G (9). The structure elucidation of these compounds was based on analyses of spectroscopic data including 1D, 2D NMR and HR-ESI-MS. All compounds were evaluated for the α-glucosidase inhibitory and cytotoxic activities. Compounds 2-4, 8 and 9 exhibited strong α-glucosidase inhibitory activities with IC less than 10 µM, while only 4 and 9 showed moderate cytotoxic effects against lung cancer cells.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Benzofuranos/farmacologia
Flavonas/farmacologia
Inibidores de Glicosídeo Hidrolases/farmacologia
Morus/química
[Mh] Termos MeSH secundário: Células A549
Antineoplásicos/química
Benzofuranos/química
Flavonas/química
Flavonoides/química
Flavonoides/farmacologia
Inibidores de Glicosídeo Hidrolases/química
Seres Humanos
Espectroscopia de Ressonância Magnética
Estrutura Molecular
Casca de Planta/química
Espectrometria de Massas por Ionização por Electrospray
Estilbenos/química
Estilbenos/farmacologia
Terpenos/química
Terpenos/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Benzofurans); 0 (Flavones); 0 (Flavonoids); 0 (Glycoside Hydrolase Inhibitors); 0 (Stilbenes); 0 (Terpenes); 0 (licoflavone C); 0 (moracin C); 62596-29-6 (morusin); 87085-00-5 (mulberrofuran G)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170520
[St] Status:MEDLINE
[do] DOI:10.1080/14786419.2017.1327862


  2 / 11207 MEDLINE  
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[PMID]:28669223
[Au] Autor:Chokpaiboon S; Unagul P; Nithithanasilp S; Komwijit S; Somyong W; Ratiarpakul T; Isaka M; Bunyapaiboonsri T
[Ad] Endereço:a National Center for Genetic Engineering and Biotechnology (BIOTEC) , National Science and Technology Development Agency (NSTDA) , Pathum Thani , Thailand.
[Ti] Título:Salicylaldehyde and dihydroisobenzofuran derivatives from the marine fungus Zopfiella marina.
[So] Source:Nat Prod Res;32(2):149-153, 2018 Jan.
[Is] ISSN:1478-6427
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Two salicylaldehyde derivatives (1 and 2), a hydroxymethylphenol (3), five dihydroisobenzofuran (4-8) derivatives, and a 5-chloro-3-deoxyisoochracinic acid (9), together with a known 3-deoxyisoochracinic acid (10) were isolated from the marine fungus Zopfiella marina BCC 18240 (or NBRC 30420). The structures of these compounds were elucidated by extensive spectroscopic analysis. Compound 1 showed weak antituberculous activity against Mycobacterium tuberculosis H37Ra, and antibacterial activity against Bacillus cereus with MIC values of 25 and 12.5 µg/mL, respectively.
[Mh] Termos MeSH primário: Aldeídos/isolamento & purificação
Antibacterianos/isolamento & purificação
Benzofuranos/isolamento & purificação
Fungos/química
[Mh] Termos MeSH secundário: Aldeídos/farmacologia
Antibacterianos/química
Antibacterianos/farmacologia
Bacillus cereus/efeitos dos fármacos
Biologia Marinha
Testes de Sensibilidade Microbiana
Estrutura Molecular
Mycobacterium tuberculosis/efeitos dos fármacos
Análise Espectral
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Aldehydes); 0 (Anti-Bacterial Agents); 0 (Benzofurans); 17K64GZH20 (salicylaldehyde)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180228
[Lr] Data última revisão:
180228
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170704
[St] Status:MEDLINE
[do] DOI:10.1080/14786419.2017.1342083


  3 / 11207 MEDLINE  
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[PMID]:29311461
[Au] Autor:Nambu H
[Ad] Endereço:Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama.
[Ti] Título:[Novel Methods for the Synthesis of Heterocycles Using Highly Reactive Spirocyclopropanes].
[So] Source:Yakugaku Zasshi;138(1):19-25, 2018.
[Is] ISSN:1347-5231
[Cp] País de publicação:Japan
[La] Idioma:jpn
[Ab] Resumo:This review describes our recent efforts to develop efficient methods for the synthesis of heterocyclic compounds, such as indoles and benzofurans, employing ring-opening cyclization of cyclohexane-1,3-dione-2-spirocyclopropanes, which were prepared by the reaction of 1,3-cyclohexanediones with sulfonium salts. Ring-opening cyclization of cyclohexane-1,3-dione-2-spirocyclopropanes with primary amines proceeded at room temperature to provide 2-substituted tetrahydroindol-4(5H)-ones in good to excellent yield. The obtained product was readily converted into a 2-substituted 4-hydroxyindole derivative. Furthermore, acid-catalyzed ring-opening cyclization of cyclohexane-1,3-dione-2-spirocyclopropanes proceeded smoothly at room temperature to provide 2-substituted tetrahydrobenzofuran-4(2H)-ones in excellent yield. The obtained product was converted into a 2-substituted 4-hydroxybenzofuran derivative. The synthetic utility of this catalytic protocol was demonstrated by the total synthesis of cuspidan B.
[Mh] Termos MeSH primário: Química Orgânica/métodos
Compostos Heterocíclicos/síntese química
[Mh] Termos MeSH secundário: Aminas/química
Benzofuranos/síntese química
Catálise
Ciclização
Cicloexanos/síntese química
Cicloexanonas/química
Ciclopropanos/síntese química
Indóis/síntese química
Fenômenos de Química Orgânica
Alimentos de Soja
Estilbenos/síntese química
Compostos de Sulfônio/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Amines); 0 (Benzofurans); 0 (Cyclohexanes); 0 (Cyclohexanones); 0 (Cyclopropanes); 0 (Heterocyclic Compounds); 0 (Indoles); 0 (Stilbenes); 0 (Sulfonium Compounds); 0 (cuspidan B); 6UK3D2BXJT (1,3-cyclohexanedione)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180110
[St] Status:MEDLINE
[do] DOI:10.1248/yakushi.17-00188


  4 / 11207 MEDLINE  
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[PMID]:28744886
[Au] Autor:Zhao A; Zhang L; Li R; Shang J; Yi H; Wang Y; Zhang D; Wang S; Fang M
[Ad] Endereço:Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, Xi'an, China.
[Ti] Título:Development and validation of an LC-MS/MS method for the simultaneous quantification of seven constituents in rat plasma and application in a pharmacokinetic study of the Zaoren Anshen prescription.
[So] Source:Biomed Chromatogr;32(2), 2018 Feb.
[Is] ISSN:1099-0801
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:A sensitive, specific and accurate liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous determination of seven constituents of the Zaoren Anshen prescription (ZAP) in rat plasma after oral administration of the ZAP: spinosin, salvianic acid A, 6'''-feruloylspinosin, protocatechualdehyde, salvianolic acid B, schisandrin and deoxyschisandrin. The plasma samples and the internal standard (IS) sulfamethoxazole were extracted using acetonitrile. Chromatographic separation was performed with an Agilent HC-C column using a gradient elution profile and a mobile phase consisting of 0.01% formic acid in water (A) and acetonitrile (B). The analytes were quantified simultaneously in a single run using an ion trap mass spectrometer operated in the multiple reaction monitoring mode and electrospray ion-source polarity in the positive and negative modes. The calibration curves for spinosin, salvianic acid A, 6'''-feruloylspinosin, protocatechualdehyde, salvianolic acid B, schisandrin and deoxyschisandrin were linear over the concentration ranges of 2.90-1160, 2.50-1000, 1.80-720, 0.65-260, 2.50-1000, 8.00-1600 and 1.30-520 ng/mL, respectively. The intra- and inter-day precisions in terms of relative standard deviation were <18.9%, and the accuracies in terms of relative error were within ±14.2%. Consequently, the proposed method was successfully applied to the pharmacokinetic analysis of these seven major active compounds in rats administered ZAP. These results will facilitate research aiming to predict the effectiveness of the optimal dose of ZAP and might be beneficial for the therapeutic use of ZAP in the clinical setting.
[Mh] Termos MeSH primário: Benzaldeídos/sangue
Benzofuranos/sangue
Catecóis/sangue
Ciclo-Octanos/sangue
Medicamentos de Ervas Chinesas/farmacocinética
Flavonoides/sangue
Lignanas/sangue
Compostos Policíclicos/sangue
[Mh] Termos MeSH secundário: Animais
Benzaldeídos/química
Benzaldeídos/farmacocinética
Benzofuranos/química
Benzofuranos/farmacocinética
Catecóis/química
Catecóis/farmacocinética
Cromatografia Líquida/métodos
Ciclo-Octanos/química
Ciclo-Octanos/farmacocinética
Estabilidade de Medicamentos
Medicamentos de Ervas Chinesas/análise
Medicamentos de Ervas Chinesas/química
Flavonoides/química
Flavonoides/farmacocinética
Lignanas/química
Lignanas/farmacocinética
Limite de Detecção
Modelos Lineares
Masculino
Compostos Policíclicos/química
Compostos Policíclicos/farmacocinética
Ratos
Ratos Sprague-Dawley
Reprodutibilidade dos Testes
Espectrometria de Massas em Tandem/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzaldehydes); 0 (Benzofurans); 0 (Catechols); 0 (Cyclooctanes); 0 (Drugs, Chinese Herbal); 0 (Flavonoids); 0 (Lignans); 0 (Polycyclic Compounds); 4PVP2HCH4T (protocatechualdehyde); 72063-39-9 (spinosin); C1GQ844199 (salvianolic acid B); G01BQC0879 (schizandrin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170727
[St] Status:MEDLINE
[do] DOI:10.1002/bmc.4055


  5 / 11207 MEDLINE  
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[PMID]:29374712
[Au] Autor:Kurita M; Takada T; Wakabayashi N; Asami S; Ono S; Uchiyama T; Suzuki T
[Ad] Endereço:Department of Clinical Medicine, School of Pharmacy, Nihon University, Funabashi, Japan.
[Ti] Título:Antitumor Effect of Burchellin Derivatives Against Neuroblastoma.
[So] Source:Anticancer Res;38(2):855-862, 2018 02.
[Is] ISSN:1791-7530
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Neuroblastoma is one of the most commonly encountered malignant solid tumors in the pediatric age group. We examined the antitumor effects of five burchellin derivatives against human neuroblastoma cell lines. MATERIALS AND METHODS: We evaluated cytotoxicity by the MTT assay for four human neuroblastoma and two normal cell lines. We also performed analysis of the apoptotic induction effect by flow cytometry, and examined the expression levels of apoptosis- and cell growth-related proteins by western blot analysis. RESULTS: We found that one of the burchellin derivatives (compound ) exerted cytotoxicity against the neuroblastoma cell lines. Compound induced caspase-dependent apoptosis via a mitochondrial pathway. The apoptosis mechanisms induced by compound involved caspase-3, -7 and -9 activation and poly (ADP-ribose) polymerase cleavage. In addition, compound induced cell death through inhibition of the cell growth pathway (via extracellular signal-regulated kinase 1 and 2, AKT8 virus oncogene cellular homolog, and signal transducer and activator of transcription 3). CONCLUSION: Compound exerted cellular cytotoxicity against neuroblastoma cells via induction of caspase-dependent apoptosis, and may offer promise for further development as a useful drug for the treatment of advanced neuroblastoma.
[Mh] Termos MeSH primário: Antineoplásicos Fitogênicos/farmacologia
Benzofuranos/farmacologia
Medicamentos de Ervas Chinesas/farmacologia
Neuroblastoma/tratamento farmacológico
[Mh] Termos MeSH secundário: Benzofuranos/química
Linhagem Celular Tumoral
Ensaios de Seleção de Medicamentos Antitumorais
Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents, Phytogenic); 0 (Benzofurans); 0 (Drugs, Chinese Herbal); 38276-59-4 (burchellin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180221
[Lr] Data última revisão:
180221
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180129
[St] Status:MEDLINE


  6 / 11207 MEDLINE  
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[PMID]:29209932
[Au] Autor:Marsh KJ; Ward J; Wallis IR; Foley WJ
[Ad] Endereço:Research School of Biology, The Australian National University, ACT, Canberra, 2601, Australia. karen.marsh@anu.edu.au.
[Ti] Título:Intraspecific Variation in Nutritional Composition Affects the Leaf Age Preferences of a Mammalian Herbivore.
[So] Source:J Chem Ecol;44(1):62-71, 2018 Jan.
[Is] ISSN:1573-1561
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Ecologists have long been interested in how the nutritional composition of leaves changes as they age, and whether this affects herbivore feeding preferences. As a consequence, the literature abounds with reports that younger leaves contain higher concentrations of nitrogen and plant secondary metabolites (PSMs) than do older leaves. Most of these studies, however, base their conclusions on average values that often mean little to herbivores. We examined this issue in the well-studied marsupial-eucalypt system, using Eucalyptus melliodora and captive common brushtail possums (Trichosurus vulpecula) offered branches from individual trees containing both young and mature leaves. Like many plants, the concentrations of N and PSMs differed among individual E. melliodora. Although young leaves were, on average, "better defended" by the PSM sideroxylonal than were mature leaves, some trees produced leaves that were relatively undefended at both ages. In response, possums chose different proportions of young and mature leaves depending on the chemistry of the individual tree. Possums did not always prefer leaves with lower concentrations of sideroxylonal (mature leaves) or those with higher concentrations of available N (young leaves). Instead, the sideroxylonal concentration of young leaves dictated their choice: possums preferred young leaves with low sideroxylonal concentrations, but not with high concentrations. By skewing their feeding toward trees producing young leaves with low concentrations of PSMs, possums may influence plant fitness. Researchers will detect these potentially important interactions only if they are aware that measuring variation among plants discloses more information than do average relationships.
[Mh] Termos MeSH primário: Eucalyptus/química
Trichosurus/fisiologia
[Mh] Termos MeSH secundário: Animais
Benzofuranos/análise
Benzofuranos/farmacologia
Cromatografia Líquida de Alta Pressão
Eucalyptus/metabolismo
Comportamento Alimentar/efeitos dos fármacos
Herbivoria
Masculino
Nitrogênio/análise
Floroglucinol/análogos & derivados
Floroglucinol/análise
Floroglucinol/farmacologia
Folhas de Planta/química
Folhas de Planta/metabolismo
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzofurans); 0 (sideroxylonal C); DHD7FFG6YS (Phloroglucinol); N762921K75 (Nitrogen)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180221
[Lr] Data última revisão:
180221
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171207
[St] Status:MEDLINE
[do] DOI:10.1007/s10886-017-0911-3


  7 / 11207 MEDLINE  
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[PMID]:28467930
[Au] Autor:Park SJ; Gavrilova O; Brown AL; Soto JE; Bremner S; Kim J; Xu X; Yang S; Um JH; Koch LG; Britton SL; Lieber RL; Philp A; Baar K; Kohama SG; Abel ED; Kim MK; Chung JH
[Ad] Endereço:Laboratory of Obesity and Aging Research, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
[Ti] Título:DNA-PK Promotes the Mitochondrial, Metabolic, and Physical Decline that Occurs During Aging.
[So] Source:Cell Metab;25(5):1135-1146.e7, 2017 May 02.
[Is] ISSN:1932-7420
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Hallmarks of aging that negatively impact health include weight gain and reduced physical fitness, which can increase insulin resistance and risk for many diseases, including type 2 diabetes. The underlying mechanism(s) for these phenomena is poorly understood. Here we report that aging increases DNA breaks and activates DNA-dependent protein kinase (DNA-PK) in skeletal muscle, which suppresses mitochondrial function, energy metabolism, and physical fitness. DNA-PK phosphorylates threonines 5 and 7 of HSP90α, decreasing its chaperone function for clients such as AMP-activated protein kinase (AMPK), which is critical for mitochondrial biogenesis and energy metabolism. Decreasing DNA-PK activity increases AMPK activity and prevents weight gain, decline of mitochondrial function, and decline of physical fitness in middle-aged mice and protects against type 2 diabetes. In conclusion, DNA-PK is one of the drivers of the metabolic and fitness decline during aging, and therefore DNA-PK inhibitors may have therapeutic potential in obesity and low exercise capacity.
[Mh] Termos MeSH primário: Envelhecimento
Proteína Quinase Ativada por DNA/metabolismo
Metabolismo Energético
Músculo Esquelético/fisiologia
[Mh] Termos MeSH secundário: Proteínas Quinases Ativadas por AMP/metabolismo
Animais
Benzofuranos
Diabetes Mellitus Tipo 2/metabolismo
Macaca mulatta
Camundongos SCID
Mitocôndrias Musculares/metabolismo
Condicionamento Físico Animal
Quinolinas
Ratos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 ((3aS,4S,9bS)-N-(2-(8-cyano-1-formyl-2,3,3a,4,5,9b-hexahydro-1H-pyrrolo(3,2-c)quinolin-4-yl)-2-methylpropyl)-4,6-difluorobenzofuran-2-carboxyamide); 0 (Benzofurans); 0 (Quinolines); EC 2.7.11.1 (DNA-Activated Protein Kinase); EC 2.7.11.31 (AMP-Activated Protein Kinases)
[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:170504
[St] Status:MEDLINE


  8 / 11207 MEDLINE  
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[PMID]:29191557
[Au] Autor:Hagimori M; Temma T; Kudo S; Sano K; Kondo N; Mukai T
[Ad] Endereço:Kobe Pharmaceutical University, 4-19-1 Motoyamakita Machi, Higashinada-ku, Kobe 658-8558, Japan; Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
[Ti] Título:Synthesis of radioiodinated probes targeted toward matrix metalloproteinase-12.
[So] Source:Bioorg Med Chem Lett;28(2):193-195, 2018 01 15.
[Is] ISSN:1464-3405
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Matrix metalloproteinase-12 (MMP-12, macrophage elastase) is a member of the MMP family that is responsible for the degradation of extracellular matrix, and is associated with the inflammatory process of chronic obstructive pulmonary disease (COPD). COPD, characterized by progressive and irreversible airflow obstruction, is recently a major cause of mortality and morbidity worldwide. Herein, to develop radioiodinated probes for the early diagnosis of COPD, we designed and synthesized novel MMP-12-targeted dibenzofuran compounds (1-3) with a variety of linker structures (carbamate, amide, and sulfonamide). In competitive enzyme activity assays, it was revealed that the linker structures significantly affected the inhibitory activity against and selectivity for MMP-12. Compound 1, with carbamate linker, demonstrated potent MMP-12 inhibitory activity (IC = 8.5 nM) compared to compound 2, with amide linker, and compound 3, with sulfonamide linker. Using bromo-substituted carbamate 13 as a radioiodination precursor, [ I]1 was successfully prepared to high radiochemical purity (over 98%) and good specific radioactivity (4.1 GBq/µmol). These results suggest that radioiodinated compound 1 is potent as a novel MMP-12-targeted probe.
[Mh] Termos MeSH primário: Benzofuranos/farmacologia
Metaloproteinase 12 da Matriz/metabolismo
[Mh] Termos MeSH secundário: Benzofuranos/síntese química
Benzofuranos/química
Relação Dose-Resposta a Droga
Seres Humanos
Radioisótopos do Iodo
Estrutura Molecular
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Benzofurans); 0 (Iodine Radioisotopes); EC 3.4.24.65 (Matrix Metalloproteinase 12)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180216
[Lr] Data última revisão:
180216
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171202
[St] Status:MEDLINE


  9 / 11207 MEDLINE  
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[PMID]:27770561
[Au] Autor:Lawitz E; Poordad F; Gutierrez JA; Wells JT; Landaverde CE; Evans B; Howe A; Huang HC; Li JJ; Hwang P; Dutko FJ; Robertson M; Wahl J; Barr E; Haber B
[Ad] Endereço:Texas Liver Institute, University of Texas Health Science Center, San Antonio, TX.
[Ti] Título:Short-duration treatment with elbasvir/grazoprevir and sofosbuvir for hepatitis C: A randomized trial.
[So] Source:Hepatology;65(2):439-450, 2017 02.
[Is] ISSN:1527-3350
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Direct-acting antiviral agents (DAAs) represent the standard of care for patients with hepatitis C virus (HCV) infection. Combining DAAs with different mechanisms may allow for shorter treatment durations that are effective across multiple genotypes. The aim of the C-SWIFT study was to identify the minimum effective treatment duration across multiple genotypes. C-SWIFT was an open-label, single-center trial in treatment-naïve patients with chronic HCV genotype (GT)1 or 3 infection. All patients received elbasvir (EBR) 50 mg/grazoprevir (GZR) 100 mg with sofosbuvir (SOF) 400 mg for 4-12 weeks. Patients with GT1 infection who failed therapy were eligible for retreatment with EBR/GZR+SOF and ribavirin for 12 weeks. The primary efficacy endpoint was sustained virological response [SVR]12 (SVR of HCV RNA <15 IU/mL 12 weeks after the end of therapy). Rates of SVR12 were 32% (10 of 31) and 87% (26 of 30) in patients without cirrhosis with GT1 infection treated for 4 and 6 weeks and 80% (16 of 20) and 81% (17 of 21) in GT1-infected patients with cirrhosis treated for 6 and 8 weeks. Among GT3-infected patients without cirrhosis, SVR12 was 93% (14 of 15) and 100% (14 of 14) after 8 and 12 weeks. SVR12 in GT3-infected patients with cirrhosis was 83% (10 of 12) after 12 weeks of treatment. Twenty-three GT1-infected patients who relapsed following initial treatment completed retreatment; all achieved SVR12. In the initial treatment phase, there was one serious adverse event of pneumonia, which led to treatment discontinuation, and during retreatment, 1 patient discontinued ribavirin because of pruritus. CONCLUSION: Data from this study support the use of 8-week treatment regimens that maintain high efficacy, even for patients with HCV GT3 infection. Retreatment of patients who failed short-duration therapy was achieved through extended treatment duration and addition of ribavirin. (Hepatology 2017;65:439-450).
[Mh] Termos MeSH primário: Benzofuranos/administração & dosagem
Hepatite C/tratamento farmacológico
Imidazóis/administração & dosagem
Quinoxalinas/administração & dosagem
Carga Viral/efeitos dos fármacos
[Mh] Termos MeSH secundário: Adulto
Idoso
Intervalos de Confiança
Relação Dose-Resposta a Droga
Esquema de Medicação
Quimioterapia Combinada
Feminino
Seguimentos
Hepacivirus/efeitos dos fármacos
Hepacivirus/genética
Hepatite C/diagnóstico
Hepatite C Crônica/diagnóstico
Hepatite C Crônica/tratamento farmacológico
Seres Humanos
Masculino
Meia-Idade
Estudos Prospectivos
RNA Viral/análise
Fatores de Tempo
Resultado do Tratamento
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (2-(pyrrolidin-2-yl)-5-(2-(4-(5-(pyrrolidin-2-yl)-1H-imidazol-2-yl)phenyl)benzofuran-5-yl)-1H-imidazole); 0 (Benzofurans); 0 (Imidazoles); 0 (Quinoxalines); 0 (RNA, Viral); 8YE81R1X1J (MK-5172)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:180209
[Lr] Data última revisão:
180209
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161023
[St] Status:MEDLINE
[do] DOI:10.1002/hep.28877


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[PMID]:28471454
[Au] Autor:Gao J; Fan M; Xiang G; Wang J; Zhang X; Guo W; Wu X; Sun Y; Gu Y; Ge H; Tan R; Qiu H; Shen Y; Xu Q
[Ad] Endereço:State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China.
[Ti] Título:Diptoindonesin G promotes ERK-mediated nuclear translocation of p-STAT1 (Ser727) and cell differentiation in AML cells.
[So] Source:Cell Death Dis;8(5):e2765, 2017 May 04.
[Is] ISSN:2041-4889
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Exploration of a new differentiation therapy that extends the range of differentiation for treating acute myeloid leukemia (AML) is attractive to researchers and clinicians. Here we report that diptoindonesin G (Dip G), a natural resveratrol aneuploid, exerts antiproliferative activity by inducing G2/M phase arrest and cell differentiation in AML cell lines and primary AML cells. Gene-profiling experiments showed that treating human leukemia HL-60 cells with Dip G was associated with a remarkable upregulation of STAT1 target gene expression, including IFIT3 and CXCL10. Mechanistically, Dip G activated ERK, which caused phosphorylation of STAT1 at Ser727 and selectively enhanced the interaction of p-STAT1 (Ser727) and p-ERK, further promoting their nuclear translocation. The nuclear translocation of p-STAT1 and p-ERK enhanced the transactivation of STAT1-targeted genes in AML cells. Furthermore, in vivo treatment of HL-60 xenografts demonstrated that Dip G significantly inhibited tumor growth and reduced tumor weight by inducing cell differentiation. Taken together, these results shed light on an essential role for ERK-mediated nuclear translocation of p-STAT1 (Ser727) and its full transcriptional activity in Dip G-induced differentiation of AML cells. Furthermore, these results demonstrate that Dip G could be used as a differentiation-inducing agent for AML therapy, particularly for non-acute promyelocytic leukemia therapy.
[Mh] Termos MeSH primário: Benzofuranos/farmacologia
Diferenciação Celular/efeitos dos fármacos
MAP Quinases Reguladas por Sinal Extracelular/metabolismo
Fator de Transcrição STAT1/metabolismo
[Mh] Termos MeSH secundário: Animais
Antineoplásicos/farmacologia
Antineoplásicos/uso terapêutico
Antineoplásicos/toxicidade
Benzofuranos/uso terapêutico
Caspase 3/química
Caspase 3/metabolismo
Inibidores de Caspase/farmacologia
Linhagem Celular Tumoral
Núcleo Celular/metabolismo
Proliferação Celular/efeitos dos fármacos
Quimiocina CXCL10/metabolismo
Células HL-60
Seres Humanos
Peptídeos e Proteínas de Sinalização Intracelular/metabolismo
Leucemia Mieloide Aguda/tratamento farmacológico
Leucemia Mieloide Aguda/metabolismo
Leucemia Mieloide Aguda/patologia
Camundongos
Camundongos Endogâmicos NOD
Camundongos SCID
Fosforilação/efeitos dos fármacos
Fator de Transcrição STAT1/genética
Regulação para Cima/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Benzofurans); 0 (Caspase Inhibitors); 0 (Chemokine CXCL10); 0 (IFIT3 protein, human); 0 (Intracellular Signaling Peptides and Proteins); 0 (STAT1 Transcription Factor); 0 (diptoindonesin G); EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases); EC 3.4.22.- (Caspase 3)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180129
[Lr] Data última revisão:
180129
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.1038/cddis.2017.159



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