Base de dados : MEDLINE
Pesquisa : D03.383.663.283.446 [Categoria DeCS]
Referências encontradas : 10993 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 1100 ir para página                         

  1 / 10993 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29031765
[Au] Autor:Boakye YD; Groyer L; Heiss EH
[Ad] Endereço:Department of Pharmacognosy, University of Vienna, Althanstrasse 14, 1090 Vienna, Austria.
[Ti] Título:An increased autophagic flux contributes to the anti-inflammatory potential of urolithin A in macrophages.
[So] Source:Biochim Biophys Acta;1862(1):61-70, 2018 01.
[Is] ISSN:0006-3002
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: An extract of Phyllanthus muellerianus and its constituent geraniin have been reported to exert anti-inflammatory activity in vivo. However, orally consumed geraniin, an ellagitannin, shows low bioavailability and undergoes metabolization to urolithins by gut microbiota. This study aimed at comparing geraniin and urolithin A with respect to inhibition of M1 (LPS) polarization of murine J774.1 macrophages and shedding more light on possible underlying mechanisms. METHODS: Photometric, fluorimetric as well as luminescence-based assays monitored production of reactive oxygen species (ROS) and nitric oxide (NO), cell viability or reporter gene expression. Western blot analyses and confocal microscopy showed abundance and localization of target proteins, respectively. RESULTS: Urolithin A is a stronger inhibitor of M1 (LPS) macrophage polarization (production of NO, ROS and pro-inflammatory proteins) than geraniin. Urolithin A leads to an elevated autophagic flux in macrophages. Inhibition of autophagy in M1 (LPS) macrophages overcomes the suppressed nuclear translocation of p65 (NF-kB; nuclear factor kB), the reduced expression of pro-inflammatory genes as well as the diminished NO production brought about by urolithin A. The increased autophagic flux is furthermore associated with impaired Akt/mTOR (mammalian target of rapamycin) signaling in urolithin A-treated macrophages. CONCLUSIONS AND GENERAL SIGNIFICANCE: Intestinal metabolization may boost the potential health benefit of widely consumed dietary ellagitannins, as suggested by side by side comparison of geraniin and urolithin A in M1(LPS) macrophages. Increased activity of the autophagic cellular recycling machinery aids the anti-inflammatory bioactivity of urolithin A.
[Mh] Termos MeSH primário: Anti-Inflamatórios/farmacologia
Autofagia/efeitos dos fármacos
Cumarínicos/farmacologia
Macrófagos/metabolismo
[Mh] Termos MeSH secundário: Transporte Ativo do Núcleo Celular/efeitos dos fármacos
Animais
Células CHO
Núcleo Celular/metabolismo
Cricetinae
Cricetulus
Células HEK293
Seres Humanos
Lipopolissacarídeos/toxicidade
Camundongos
Óxido Nítrico/metabolismo
Espécies Reativas de Oxigênio/metabolismo
Fator de Transcrição RelA/metabolismo
Proteínas ral de Ligação ao GTP/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents); 0 (Coumarins); 0 (Lipopolysaccharides); 0 (RELA protein, human); 0 (Reactive Oxygen Species); 0 (Transcription Factor RelA); 1143-70-0 (3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one); 31C4KY9ESH (Nitric Oxide); EC 3.6.1.- (Rala protein, mouse); EC 3.6.5.2 (ral GTP-Binding Proteins)
[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:171017
[St] Status:MEDLINE


  2 / 10993 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29329091
[Au] Autor:Jiang J; Zhang Z; Zou X; Wang R; Bai J; Zhao S; Fan X; Sheng L; Li Y
[Ad] Endereço:Department of Drug Metabolism, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Xiannongtan Street, Beijing 100050, China; Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study, Institute of Materia Medica, Chinese Academy of Me
[Ti] Título:Determination of IMM-H004 and its active glucuronide metabolite in rat plasma and Ringer's solution by ultra-performance liquid chromatography-tandem mass spectrometry.
[So] Source:J Chromatogr B Analyt Technol Biomed Life Sci;1074-1075:16-24, 2018 Feb 01.
[Is] ISSN:1873-376X
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:IMM-H004 is a novel neuroprotective agent and its glucuronide metabolite IMM-H004G has similar protective effects against cerebral ischemic injury in vivo and in vitro. A specific and sensitive ultra-performance liquid chromatography-tandem mass spectrometry method was established and validated for determination of IMM-H004 and IMM-H004G simultaneously in rat plasma and Ringer's solution. Plasma samples containing IMM-H004, IMM-H004G and internal standard propranolol were prepared by direct protein precipitation in a sample-to-solvent ratio of 1:2:6 (plasma: water: acetonitrile), whereas no protein precipitation was required for Ringer's solution samples. Separation was performed with a gradient mobile phase of methanol/water with 0.5% formic acid (v/v) on Eclipse Plus C18 column (2.1×50mm, 3.5µm) at a flow rate of 0.3mL/min. The detection was operated on a triple quadrupole mass spectrometer in positive ion multiple reaction monitoring (MRM) mode. The monitored transitions were 305.1→248.1 for IMM-H004, 481.3→305.1 for IMM-H004G and 260.1→183.1 for propranolol. The linear ranges of IMM-H004 and IMM-H004G were 5 to 3000ng/mL and 10 to 3000ng/mL for plasma method and 0.5 to 500ng/mL for Ringer's solution method. All the intra-day and inter-day precision and accuracy for the two analytes in rat plasma were below 7.5% and the intra-day precision and accuracy for analytes in Ringer's solution were within ±14.7%. There was no obvious matrix effect and the recoveries of the analytes were higher than 94.2%. IMM-H004 and IMM-H004G were stable during one analytic process. The established method was applied successfully to plasma pharmacokinetic and brain microdialysis studies of IMM-H004 and IMM-H004G in rats after a single intravenous administration of IMM-H004.
[Mh] Termos MeSH primário: Cromatografia Líquida/métodos
Cumarínicos
Soluções Isotônicas/química
Espectrometria de Massas em Tandem/métodos
[Mh] Termos MeSH secundário: Animais
Química Encefálica
Cumarínicos/análise
Cumarínicos/sangue
Cumarínicos/química
Cumarínicos/farmacocinética
Estabilidade de Medicamentos
Glucuronídeos
Limite de Detecção
Modelos Lineares
Masculino
Ratos
Ratos Sprague-Dawley
Reprodutibilidade dos Testes
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Coumarins); 0 (Glucuronides); 0 (IMM-H004); 0 (Isotonic Solutions); 8026-10-6 (Ringer's solution)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180113
[St] Status:MEDLINE


  3 / 10993 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29366931
[Au] Autor:Yadav N; Agarwal D; Kumar S; Dixit AK; Gupta RD; Awasthi SK
[Ad] Endereço:Chemical Biology Laboratory, Department of Chemistry, University of Delhi, Delhi, 110007, India.
[Ti] Título:In vitro antiplasmodial efficacy of synthetic coumarin-triazole analogs.
[So] Source:Eur J Med Chem;145:735-745, 2018 Feb 10.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Twenty two diverse coumarin-triazole derivatives were synthesized by alkylation of 7-hydroxy-4-methyl-coumarin followed by click chemistry at 7-position. These compounds were evaluated for their in vitro antiplasmodial activity against chloroquine sensitive strain of Plasmodium falciparum (3D7). Compound 9 (7-[1-(2, 4-dimethoxy-phenyl)-1H- [1-3] triazol-4-ylmethoxy]-4-methyl-chromen-2-one) was found most active with IC value 0.763 ±â€¯0.0124 µg/mL. Further, the structure of compound 20 was characterized by single crystal X-ray diffraction. In view of impressive results, we considered it worthwhile to validate the results of in vitro antiplasmodial activity by assessing whether these compounds are capable of hampering the catalytic activity of DNA gyrase, thus preventing its supercoiling function.
[Mh] Termos MeSH primário: Antimaláricos/farmacologia
Cumarínicos/farmacologia
Plasmodium falciparum/efeitos dos fármacos
Triazóis/farmacologia
[Mh] Termos MeSH secundário: Antimaláricos/síntese química
Antimaláricos/química
Linhagem Celular Tumoral
Sobrevivência Celular
Cumarínicos/química
DNA Girase/metabolismo
Relação Dose-Resposta a Droga
Escherichia coli/enzimologia
Seres Humanos
Estrutura Molecular
Testes de Sensibilidade Parasitária
Relação Estrutura-Atividade
Inibidores da Topoisomerase II/síntese química
Inibidores da Topoisomerase II/química
Inibidores da Topoisomerase II/farmacologia
Triazóis/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antimalarials); 0 (Coumarins); 0 (Topoisomerase II Inhibitors); 0 (Triazoles); A4VZ22K1WT (coumarin); EC 5.99.1.3 (DNA Gyrase)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180126
[St] Status:MEDLINE


  4 / 10993 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29339250
[Au] Autor:Wei Q; Ning JY; Dai X; Gao YD; Su L; Zhao BX; Miao JY
[Ad] Endereço:Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Jinan, 250100, PR China.
[Ti] Título:Discovery of novel HSP90 inhibitors that induced apoptosis and impaired autophagic flux in A549 lung cancer cells.
[So] Source:Eur J Med Chem;145:551-558, 2018 Feb 10.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Heat shock protein 90 (HSP90) inhibition has aroused increasing enthusiasm in antitumor strategies in recent years. According to our previous studies, we synthesized a series of coumarin pyrazoline compounds HCP1-HCP6 that might be HSP90 inhibitors. Interactions between HCP1-HCP6 and HSP90 were examined and antitumor activities of them were investigated in A549 lung cancer cells. Results showed that all the six derivatives could interact with HSP90, in which HCP1 exhibited the best binding ability and inhibited the activity of HSP90. Meanwhile, HCP1-HCP6 reduced the cell viability of A549 cells and HCP1 possessed the lowest IC value. Above all HCP1 exerted better HSP90 inhibitory and anticancer effects than our initially identified HSP90 inhibitor DPB. As to the underlying mechanism, HCP1-HCP6 not only induced apoptosis as DPB but also blocked autophagic flux in A549 cells. Therefore, we discovered a novel HSP90 inhibitor HCP1 that had better biological activity and provided us a useful tool to explore the underlying mechanism of lung cancer therapy.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Apoptose/efeitos dos fármacos
Cumarínicos/farmacologia
Descoberta de Drogas
Proteínas de Choque Térmico HSP90/antagonistas & inibidores
Pirazóis/farmacologia
[Mh] Termos MeSH secundário: Antineoplásicos/síntese química
Antineoplásicos/química
Proliferação Celular/efeitos dos fármacos
Cumarínicos/síntese química
Cumarínicos/química
Cristalografia por Raios X
Relação Dose-Resposta a Droga
Ensaios de Seleção de Medicamentos Antitumorais
Seres Humanos
Modelos Moleculares
Estrutura Molecular
Pirazóis/síntese química
Pirazóis/química
Relação Estrutura-Atividade
Células Tumorais Cultivadas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Coumarins); 0 (HSP90 Heat-Shock Proteins); 0 (Pyrazoles); A4VZ22K1WT (coumarin)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180118
[St] Status:MEDLINE


  5 / 10993 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29329333
[Au] Autor:Mohri S; Takahashi H; Sakai M; Takahashi S; Waki N; Aizawa K; Suganuma H; Ara T; Matsumura Y; Shibata D; Goto T; Kawada T
[Ad] Endereço:Laboratory of Molecular Function of Food, Graduate School of Agriculture, Kyoto University, Uji, Kyoto, Japan.
[Ti] Título:Wide-range screening of anti-inflammatory compounds in tomato using LC-MS and elucidating the mechanism of their functions.
[So] Source:PLoS One;13(1):e0191203, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Obesity-induced chronic inflammation is a key factor in type 2 diabetes. A vicious cycle involving pro-inflammatory mediators between adipocytes and macrophages is a common cause of chronic inflammation in the adipose tissue. Tomato is one of the most popular vegetables and is associated with a reduced risk of diabetes. However, the molecular mechanism underlying the effect of tomato on diabetes is unclear. In this study, we focused on anti-inflammatory compounds in tomato. We found that the extract of tomato reduced plasma glucose and inflammatory markers in mice. We screened anti-inflammatory fractions in tomato using lipopolysaccharide-stimulated RAW264.7 macrophages, and active compounds were estimated by liquid chromatography-mass spectrometry over a wide range. Surprisingly, a large number of compounds including oxylipin and coumarin derivatives were estimated as anti-inflammatory compounds. Especially, 9-oxo-octadecadienoic acid and daphnetin suppressed pro-inflammatory cytokines in RAW264.7 macrophages inhibiting mitogen-activated protein kinase phosphorylation and inhibitor of kappa B α protein degradation. These findings suggest that tomato containing diverse anti-inflammatory compounds ameliorates chronic inflammation in obese adipose tissue.
[Mh] Termos MeSH primário: Anti-Inflamatórios/isolamento & purificação
Anti-Inflamatórios/farmacologia
Lycopersicon esculentum/química
[Mh] Termos MeSH secundário: Tecido Adiposo/efeitos dos fármacos
Tecido Adiposo/metabolismo
Animais
Anti-Inflamatórios/química
Glicemia/metabolismo
Cromatografia Líquida de Alta Pressão
Cumarínicos/química
Cumarínicos/isolamento & purificação
Cumarínicos/farmacologia
Citocinas/metabolismo
Avaliação Pré-Clínica de Medicamentos
Sistema de Sinalização das MAP Quinases/efeitos dos fármacos
Macrófagos/efeitos dos fármacos
Macrófagos/metabolismo
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Óxido Nítrico/biossíntese
Obesidade/tratamento farmacológico
Obesidade/metabolismo
Oxilipinas/química
Oxilipinas/isolamento & purificação
Oxilipinas/farmacologia
Extratos Vegetais/química
Extratos Vegetais/isolamento & purificação
Extratos Vegetais/farmacologia
Células RAW 264.7
Espectrometria de Massas por Ionização por Electrospray
Umbeliferonas/química
Umbeliferonas/isolamento & purificação
Umbeliferonas/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents); 0 (Blood Glucose); 0 (Coumarins); 0 (Cytokines); 0 (Oxylipins); 0 (Plant Extracts); 0 (Umbelliferones); 31C4KY9ESH (Nitric Oxide); XC84571RD2 (daphnetin)
[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:180113
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191203


  6 / 10993 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29269256
[Au] Autor:Ostrowska K; Grzeszczuk D; Gluch-Lutwin M; Grybos A; Siwek A; Lesniak A; Sacharczuk M; Trzaskowski B
[Ad] Endereço:Department of Organic Chemistry, Faculty of Pharmacy, Medical University of Warsaw, 1 Banacha Str., 02-097 Warsaw, Poland. Electronic address: kostrowska@wum.edu.pl.
[Ti] Título:5-HT and 5-HT receptors affinity, docking studies and pharmacological evaluation of a series of 8-acetyl-7-hydroxy-4-methylcoumarin derivatives.
[So] Source:Bioorg Med Chem;26(2):527-535, 2018 01 15.
[Is] ISSN:1464-3391
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:In this work we describe the synthesis, docking studies and biological evaluation of a focused library of novel arylpiperazinyl derivatives of 8-acetyl-7-hydroxy-4-methylcoumarin. The new compounds were screened for their 5-HT and 5-HT receptor affinity. Among the evaluated compounds, six displayed high affinities to 5-HT receptors (4a-0.9 nM, 6a-0.5 nM, 10a-0.6 nM, 3b-0.9 nM, 6b-1.5 nM, 10b-1 nM). Compound 6a and 10a bearing a bromo- or methoxy- substituent in ortho position of the piperazine phenyl ring, were identified as potent antagonists of the 5-HT receptors. In the tail suspension test, mice injected with 6a showed a dose-dependent increase in depressive-like behavior that was related to a decrease in locomotor activity. Compound 10a did not decrease or prolong immobility time nor did it affect home cage activity. Molecular docking studies using 5-HT and 5-HT homology models revealed structural basis of the high affinity of ortho-substituted derivatives and subtle changes in amino acid interactions patterns depending on the length of the alkyl linker.
[Mh] Termos MeSH primário: Cumarínicos/farmacologia
Simulação de Acoplamento Molecular
Receptor 5-HT1A de Serotonina/metabolismo
Receptor 5-HT2A de Serotonina/metabolismo
Antagonistas do Receptor 5-HT1 de Serotonina/farmacologia
Antagonistas do Receptor 5-HT2 de Serotonina/farmacologia
[Mh] Termos MeSH secundário: Animais
Cumarínicos/síntese química
Cumarínicos/química
Relação Dose-Resposta a Droga
Seres Humanos
Locomoção/efeitos dos fármacos
Masculino
Camundongos
Camundongos Endogâmicos BALB C
Estrutura Molecular
Antagonistas do Receptor 5-HT1 de Serotonina/síntese química
Antagonistas do Receptor 5-HT1 de Serotonina/química
Antagonistas do Receptor 5-HT2 de Serotonina/síntese química
Antagonistas do Receptor 5-HT2 de Serotonina/química
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (8-acetyl-7-hydroxy-4-methylcoumarin); 0 (Coumarins); 0 (Receptor, Serotonin, 5-HT2A); 0 (Serotonin 5-HT1 Receptor Antagonists); 0 (Serotonin 5-HT2 Receptor Antagonists); 112692-38-3 (Receptor, Serotonin, 5-HT1A)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171223
[St] Status:MEDLINE


  7 / 10993 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29309787
[Au] Autor:Ahmad S; St Hilaire VR; Dandepally SR; Johnson GL; Williams AL; Scott JE
[Ad] Endereço:Department of Pharmaceutical Sciences, Biomanufacturing Research Institute and Technology Enterprise (BRITE), North Carolina Central University, Durham, NC, USA.
[Ti] Título:Discovery and characterization of an iminocoumarin scaffold as an inhibitor of MEKK2 (MAP3K2).
[So] Source:Biochem Biophys Res Commun;496(1):205-211, 2018 01 29.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The kinase MEKK2 (MAP3K2) activates the MEK5/ERK5 cell signaling pathway and may play an important role in tumor growth and metastasis. Thus, MEKK2 may represent a novel kinase target for cancer. In order to identify inhibitors of MEKK2, we screened a library of compounds using a high throughput MEKK2 intrinsic ATPase enzyme assay. We identified two hits with validated structures and confirmed activity in the primary assay (IC values = 322 nM and 7.7 µM) and two orthogonal MEKK2 biochemical assays. Compound 1, the more potent hit, was the subject of further investigation. Limited structure-activity relationship (SAR) studies were performed on this iminocoumarin hit which resulted in ≥20-fold more potent analogs (e.g. 8 and 16 nM IC ). Two analogs had improved selectivity in a 50-member kinase profiling panel compared to the hit. These studies suggested that substitutions around the phenoxy ring of this scaffold can impart improved potency and selectivity for MEKK2. Analog Compound 1s (16 nM IC ) was further verified by external testing to inhibit MEKK2 and MEKK3 with similar potencies. Compound 1s displayed activity in cell-based assays in which it inhibited ERK5 pathway activation in cells and inhibited cell migration in a scratch assay. Thus, we have identified a scaffold that has promising potential to be developed into a highly selective and potent inhibitor of MEKK2. Information from these SAR studies provides specific guidance for the future design of MEKK2 inhibitor probes.
[Mh] Termos MeSH primário: Cumarínicos/química
Cumarínicos/metabolismo
MAP Quinase Quinase Quinase 2/antagonistas & inibidores
MAP Quinase Quinase Quinase 2/metabolismo
Mapeamento de Interação de Proteínas/métodos
Inibidores de Proteínas Quinases/química
Inibidores de Proteínas Quinases/metabolismo
[Mh] Termos MeSH secundário: Células Cultivadas
Cumarínicos/administração & dosagem
Sistemas de Liberação de Medicamentos/métodos
Descoberta de Drogas
Avaliação Pré-Clínica de Medicamentos/métodos
Seres Humanos
Inibidores de Proteínas Quinases/administração & dosagem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Coumarins); 0 (Protein Kinase Inhibitors); EC 2.7.11.25 (MAP Kinase Kinase Kinase 2)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180215
[Lr] Data última revisão:
180215
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180109
[St] Status:MEDLINE


  8 / 10993 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27771574
[Au] Autor:Roy SS; Kapoor M
[Ad] Endereço:Department of Biological Sciences, The University of Calgary, 2500 University Drive NW, Calgary, AB, T2N 1N4, Canada.
[Ti] Título:In silico identification and computational analysis of the nucleotide binding site in the C-terminal domain of Hsp90.
[So] Source:J Mol Graph Model;70:253-274, 2016 11.
[Is] ISSN:1873-4243
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Hsp90 contains two distinct Nucleotide Binding Sites (NBS), in its N-terminal domain (NTD) and C-terminal domain (CTD), respectively. The NTD site belongs to the GHKL super-family of ATPases and has been the subject of extensive characterization. However, a structure of the nucleotide-bound form of CTD is still unavailable. In this study molecular modeling was employed to incorporate experimental data using partial constructs of the CTD, from work published by many research groups, onto existing structural models of its apo- form. Our attempts to locate potential nucleotide ligand-binding sites or cavities yielded one major candidate-a structurally unconventional site-exhibiting the requisite shape and volume for accommodation of tri-phosphate nucleotides. Its structure was refined by molecular dynamics (MD)-based techniques. We reproducibly docked the Mg complexed form of ATP, GTP, CTP, TTP and UTP to this putative NBS. These docking simulations and calculated ligand-binding scores are in general agreement with published data about experimentally measured binding to the CTD. The overall pattern of interactions between residues lining the site and docked nucleotides is conserved and broadly similar to that of other nucleotide-binding sites. Our docking simulations suggest that nucleotide binding stabilizes the only structurally labile region, thereby providing a rationale for the increased resistance to thermal denaturation and proteolysis. The docked nucleotides do not intrude onto the surface of residues involved in dimerization or chaperoning. Our molecular modeling permitted recognition of larger structural changes in the nucleotide-bound CTD dimer, including stabilization of helix-2 in both chains and intra- and inter- chain interactions between three residues (I613, Q617, R620).
[Mh] Termos MeSH primário: Simulação por Computador
Proteínas de Choque Térmico HSP90/química
Proteínas de Choque Térmico HSP90/metabolismo
Nucleotídeos/metabolismo
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Sítios de Ligação
Sequência Conservada
Cumarínicos/química
Seres Humanos
Ligações de Hidrogênio
Interações Hidrofóbicas e Hidrofílicas
Ligantes
Modelos Moleculares
Simulação de Acoplamento Molecular
Domínios Proteicos
Multimerização Proteica
Estrutura Quaternária de Proteína
Estrutura Secundária de Proteína
Proteólise
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Coumarins); 0 (HSP90 Heat-Shock Proteins); 0 (Ligands); 0 (Nucleotides); A4VZ22K1WT (coumarin)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180216
[Lr] Data última revisão:
180216
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161025
[St] Status:MEDLINE


  9 / 10993 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29390901
[Au] Autor:Iqbal J; El-Gamal MI; Ejaz SA; Lecka J; Sévigny J; Oh CH
[Ad] Endereço:a Centre for Advanced Drug Research , COMSATS Institute of Information Technology , Abbottabad , Pakistan.
[Ti] Título:Tricyclic coumarin sulphonate derivatives with alkaline phosphatase inhibitory effects: in vitro and docking studies.
[So] Source:J Enzyme Inhib Med Chem;33(1):479-484, 2018 Dec.
[Is] ISSN:1475-6374
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Tissue-nonspecific alkaline phosphatase (TNAP) is an important isozyme of alkaline phosphatases, which plays different pivotal roles within the human body. Most importantly, it is responsible for maintaining the balanced ratio of phosphate and inorganic pyrophosphate, thus regulates the extracellular matrix calcification during bone formation and growth. The elevated level of TNAP has been linked to vascular calcification and end-stage renal diseases. Consequently, there is a need to search for highly potent and selective inhibitors of alkaline phosphatases (APs) for treatment of disorders associated with the over-expression of APs. Herein, a series of tricyclic coumarin sulphonate 1a-za with known antiproliferative activity, was evaluated for AP inhibition against human tissue nonspecific alkaline phosphatase (h-TNAP) and human intestinal alkaline phosphatase (h-IAP). The methylbenzenesulphonate derivative 1f (IC = 0.38 ± 0.01 µM) was found to be the most active h-TNAP inhibitor. Another 4-fluorobenzenesulphonate derivative 1i (IC = 0.45 ± 0.02 µM) was found as the strongest inhibitor of h-IAP. Some of the derivatives were also identified as highly selective inhibitors of APs. Detailed structure-activity relationship (SAR) was investigated to identify the functional groups responsible for the effective inhibition of AP isozymes. The study was also supported by the docking studies to rationalise the most possible binding site interactions of the identified inhibitors with the targeted enzymes.
[Mh] Termos MeSH primário: Fosfatase Alcalina/antagonistas & inibidores
Cumarínicos/farmacologia
Inibidores Enzimáticos/farmacologia
Simulação de Acoplamento Molecular
Ácidos Sulfônicos/farmacologia
[Mh] Termos MeSH secundário: Fosfatase Alcalina/metabolismo
Cumarínicos/síntese química
Cumarínicos/química
Relação Dose-Resposta a Droga
Inibidores Enzimáticos/síntese química
Inibidores Enzimáticos/química
Proteínas Ligadas por GPI/antagonistas & inibidores
Proteínas Ligadas por GPI/metabolismo
Seres Humanos
Estrutura Molecular
Relação Estrutura-Atividade
Ácidos Sulfônicos/síntese química
Ácidos Sulfônicos/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Coumarins); 0 (Enzyme Inhibitors); 0 (GPI-Linked Proteins); 0 (Sulfonic Acids); EC 3.1.3.1 (ALPI protein, human); EC 3.1.3.1 (ALPL protein, human); EC 3.1.3.1 (Alkaline Phosphatase)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180212
[Lr] Data última revisão:
180212
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180203
[St] Status:MEDLINE
[do] DOI:10.1080/14756366.2018.1428193


  10 / 10993 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29216566
[Au] Autor:Sahin Ö; Özdemir ÜÖ; Seferoglu N; Genc ZK; Kaya K; Aydiner B; Tekin S; Seferoglu Z
[Ad] Endereço:Department of Chemistry, Faculty of Science, Gazi University, Teknikokullar, Ankara 06500, Turkey.
[Ti] Título:New platinum (II) and palladium (II) complexes of coumarin-thiazole Schiff base with a fluorescent chemosensor properties: Synthesis, spectroscopic characterization, X-ray structure determination, in vitro anticancer activity on various human carcinoma cell lines and computational studies.
[So] Source:J Photochem Photobiol B;178:428-439, 2018 Jan.
[Is] ISSN:1873-2682
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:A new coumarin-thiazole based Schiff base (Ligand, L) and its Pd(II), Pt(II) complexes; ([Pd(L) ] and [Pt(L) ]), were synthesized and characterized using spectrophotometric techniques (NMR, IR, UV-vis, LC-MS), magnetic moment, and conductivity measurements. A single crystal X-ray analysis for only L was done. The crystals of L have monoclinic crystal system and P21/c space group. To gain insight into the structure of L and its complexes, we used density functional theory (DFT) method to optimize the molecules. The photophysical properties changes were observed after deprotonation of L with CN via intermolecular charge transfer (ICT). Additionally, as the sensor is a colorimetric and fluorimetric cyanide probe containing active sites such as coumarin-thiazole and imine (CH=N), it showed fast color change from yellow to deep red in the visible region, and yellow fluorescence after CN addition to the imine bond, in DMSO. The reaction mechanisms of L with CN , F and AcO ions were evaluated using H NMR shifts. The results showed that, the reaction of L with CN ion was due to the deprotonation and addition mechanisms at the same time. The anti-cancer activity of L and its Pd(II) and Pt(II) complexes were evaluated in vitro using MTT assay on the human cancer lines MCF-7 (human breast adenocarcinoma), LS174T (human colon carcinoma), and LNCAP (human prostate adenocarcinoma). The anti-cancer effects of L and its complexes, on human cells, were determined by comparing the half maximal inhibitory concentration (IC ) values. The activity results showed that, the Pd(II) complex of L has higher anti-tumor effect than L and its Pt(II) complex against the tested human breast adenocarcinoma (MCF-7), human prostate adenocarcinoma (LNCAP), and human colon carcinoma (LS174T) cell lines.
[Mh] Termos MeSH primário: Complexos de Coordenação/síntese química
Paládio/química
Platina/química
Bases de Schiff/química
[Mh] Termos MeSH secundário: Antineoplásicos/síntese química
Antineoplásicos/química
Antineoplásicos/toxicidade
Linhagem Celular Tumoral
Sobrevivência Celular/efeitos dos fármacos
Complexos de Coordenação/química
Complexos de Coordenação/toxicidade
Cumarínicos/química
Cristalografia por Raios X
Seres Humanos
Ligações de Hidrogênio
Células MCF-7
Espectroscopia de Ressonância Magnética
Magnetismo
Conformação Molecular
Teoria Quântica
Espectrofotometria Ultravioleta
Eletricidade Estática
Tiazóis/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Coordination Complexes); 0 (Coumarins); 0 (Schiff Bases); 0 (Thiazoles); 49DFR088MY (Platinum); 5TWQ1V240M (Palladium); A4VZ22K1WT (coumarin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180212
[Lr] Data última revisão:
180212
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171208
[St] Status:MEDLINE



página 1 de 1100 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