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[PMID]:29289880
[Au] Autor:Ansari MF; Idrees D; Hassan MI; Ahmad K; Avecilla F; Azam A
[Ad] Endereço:Department of Chemistry, Jamia Millia Islamia, Jamia Nagar, 110 025, New Delhi, India.
[Ti] Título:Design, synthesis and biological evaluation of novel pyridine-thiazolidinone derivatives as anticancer agents: Targeting human carbonic anhydrase IX.
[So] Source:Eur J Med Chem;144:544-556, 2018 Jan 20.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:In order to obtain novel Human carbonic anhydrase IX (CAIX) inhibitors, a series of pyridine-thiazolidinone derivatives was synthesized and characterized by various spectroscopic techniques. The binding affinity of the compounds was measured by fluorescence binding studies and enzyme inhibition activity using esterase assay of CAIX. It was observed that compound 8 and 11 significantly inhibit the CAIX activity with the IC value, 1.61 µM and 1.84 µM, respectively. The binding-affinity of compound 8 and 11 for CAIX was significantly high with their K values 11.21 µM and 2.32 µM, respectively. Docking studies revealed that compound 8 and 11 efficiently binds in the active site cavity of CA IX by forming sufficient numbers of H-bonds and van der Waals interactions with active side residues. All the compounds were further screened in vitro for anticancer activity and found that compound 8 and 11 exhibit considerable anticancer activity against MCF-7 and HepG-2 cell lines. All these findings suggest that compound 8 and 11 may be further exploited as a novel pharmacophore model for the development of anticancer agents.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Anidrase Carbônica IX/antagonistas & inibidores
Inibidores da Anidrase Carbônica/farmacologia
Desenho de Drogas
Piridinas/farmacologia
Tiazolidinas/farmacologia
[Mh] Termos MeSH secundário: Antígenos de Neoplasias/metabolismo
Antineoplásicos/síntese química
Antineoplásicos/química
Anidrase Carbônica II/antagonistas & inibidores
Anidrase Carbônica II/metabolismo
Anidrase Carbônica IX/metabolismo
Inibidores da Anidrase Carbônica/síntese química
Inibidores da Anidrase Carbônica/química
Proliferação Celular/efeitos dos fármacos
Relação Dose-Resposta a Droga
Ensaios de Seleção de Medicamentos Antitumorais
Seres Humanos
Simulação de Acoplamento Molecular
Estrutura Molecular
Piridinas/síntese química
Piridinas/química
Relação Estrutura-Atividade
Tiazolidinas/síntese química
Tiazolidinas/química
Células Tumorais Cultivadas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, Neoplasm); 0 (Antineoplastic Agents); 0 (Carbonic Anhydrase Inhibitors); 0 (Pyridines); 0 (Thiazolidines); EC 4.2.1.- (Carbonic Anhydrase II); EC 4.2.1.1 (CA9 protein, human); EC 4.2.1.1 (Carbonic Anhydrase IX); NH9L3PP67S (pyridine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180223
[Lr] Data última revisão:
180223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180101
[St] Status:MEDLINE


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[PMID]:27775704
[Au] Autor:Brasó-Maristany F; Filosto S; Catchpole S; Marlow R; Quist J; Francesch-Domenech E; Plumb DA; Zakka L; Gazinska P; Liccardi G; Meier P; Gris-Oliver A; Cheang MC; Perdrix-Rosell A; Shafat M; Noël E; Patel N; McEachern K; Scaltriti M; Castel P; Noor F; Buus R; Mathew S; Watkins J; Serra V; Marra P; Grigoriadis A; Tutt AN
[Ad] Endereço:Breast Cancer Now Research Unit, Division of Cancer Studies, Faculty of Life Sciences and Medicine, King's College London, Guy's Hospital, London, UK.
[Ti] Título:PIM1 kinase regulates cell death, tumor growth and chemotherapy response in triple-negative breast cancer.
[So] Source:Nat Med;22(11):1303-1313, 2016 11.
[Is] ISSN:1546-170X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Triple-negative breast cancers (TNBCs) have poor prognosis and lack targeted therapies. Here we identified increased copy number and expression of the PIM1 proto-oncogene in genomic data sets of patients with TNBC. TNBC cells, but not nonmalignant mammary epithelial cells, were dependent on PIM1 for proliferation and protection from apoptosis. PIM1 knockdown reduced expression of the anti-apoptotic factor BCL2, and dynamic BH3 profiling of apoptotic priming revealed that PIM1 prevents mitochondrial-mediated apoptosis in TNBC cell lines. In TNBC tumors and their cellular models, PIM1 expression was associated with several transcriptional signatures involving the transcription factor MYC, and PIM1 depletion in TNBC cell lines decreased, in a MYC-dependent manner, cell population growth and expression of the MYC target gene MCL1. Treatment with the pan-PIM kinase inhibitor AZD1208 impaired the growth of both cell line and patient-derived xenografts and sensitized them to standard-of-care chemotherapy. This work identifies PIM1 as a malignant-cell-selective target in TNBC and the potential use of PIM1 inhibitors for sensitizing TNBC to chemotherapy-induced apoptotic cell death.
[Mh] Termos MeSH primário: Apoptose/genética
Proliferação Celular/genética
Regulação Neoplásica da Expressão Gênica
Proteínas Proto-Oncogênicas c-pim-1/genética
Neoplasias de Mama Triplo Negativas/genética
[Mh] Termos MeSH secundário: Animais
Apoptose/efeitos dos fármacos
Compostos de Bifenilo/farmacologia
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Sobrevivência Celular/efeitos dos fármacos
Sobrevivência Celular/genética
Variações do Número de Cópias de DNA
Feminino
Técnicas de Silenciamento de Genes
Seres Humanos
Camundongos
Mitocôndrias/metabolismo
Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo
Transplante de Neoplasias
Inibidores de Proteínas Quinases/farmacologia
Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
Proteínas Proto-Oncogênicas c-myc/metabolismo
Proteínas Proto-Oncogênicas c-pim-1/antagonistas & inibidores
Reação em Cadeia da Polimerase em Tempo Real
Tiazolidinas/farmacologia
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (AZD1208); 0 (BCL2 protein, human); 0 (Biphenyl Compounds); 0 (MCL1 protein, human); 0 (MYC protein, human); 0 (Myeloid Cell Leukemia Sequence 1 Protein); 0 (Protein Kinase Inhibitors); 0 (Proto-Oncogene Proteins c-bcl-2); 0 (Proto-Oncogene Proteins c-myc); 0 (Thiazolidines); EC 2.7.11.1 (PIM1 protein, human); EC 2.7.11.1 (Proto-Oncogene Proteins c-pim-1)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:180221
[Lr] Data última revisão:
180221
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161108
[St] Status:MEDLINE
[do] DOI:10.1038/nm.4198


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[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


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[PMID]:28741385
[Au] Autor:Kadowaki T; Kondo K; Sasaki N; Miyayama K; Yokota S; Terata R; Gouda M
[Ad] Endereço:a Department of Diabetes and Metabolic Diseases, Graduate School of Medicine , The University of Tokyo , Tokyo , Japan.
[Ti] Título:Efficacy and safety of teneligliptin add-on to insulin monotherapy in Japanese patients with type 2 diabetes mellitus: a 16-week, randomized, double-blind, placebo-controlled trial with an open-label period.
[So] Source:Expert Opin Pharmacother;18(13):1291-1300, 2017 Sep.
[Is] ISSN:1744-7666
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: To assess the efficacy and safety of teneligliptin as add-on to insulin monotherapy in patients with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: In a 16-week, double-blind period, 148 Japanese T2DM patients with inadequate glycemic control with insulin and diet/exercise therapies were randomized to placebo or teneligliptin 20 mg. In a subsequent 36-week, open-label period, all patients received teneligliptin once daily. The primary outcome measure was change in HbA1c at the end of the double-blind period. RESULTS: The difference between placebo and teneligliptin in change in HbA1c in the double-blind period (least squares mean ± SE) was -0.80% ± 0.11%; teneligliptin was superior (ANCOVA, P < 0.001). The HbA1c-lowering effect of teneligliptin was maintained throughout the open-label period. The incidence of adverse events was 53.5% with placebo and 44.2% with teneligliptin in the double-blind period, 66.7% in the placebo/teneligliptin group in the open-label period, and 77.9% in the teneligliptin/teneligliptin group over both double-blind/open-label periods. The incidence of hypoglycemic symptoms was 11.1% in the placebo/teneligliptin group in the open-label period and 27.3% in the teneligliptin/teneligliptin group over both double-blind/open-label periods. CONCLUSION: Teneligliptin was effective and well tolerated in Japanese T2DM patients with inadequate glycemic control. CLINICAL TRIAL REGISTRATION: NCT02081599.
[Mh] Termos MeSH primário: Diabetes Mellitus Tipo 2/tratamento farmacológico
Hipoglicemiantes/uso terapêutico
Insulina/uso terapêutico
Pirazóis/uso terapêutico
Tiazolidinas/uso terapêutico
[Mh] Termos MeSH secundário: Glicemia/efeitos dos fármacos
Terapia Combinada
Dietoterapia
Método Duplo-Cego
Quimioterapia Combinada
Terapia por Exercício
Feminino
Hemoglobina A Glicada/análise
Seres Humanos
Hipoglicemiantes/administração & dosagem
Hipoglicemiantes/efeitos adversos
Insulina/administração & dosagem
Insulina/efeitos adversos
Japão
Masculino
Meia-Idade
Pirazóis/administração & dosagem
Pirazóis/efeitos adversos
Tiazolidinas/administração & dosagem
Tiazolidinas/efeitos adversos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (3-(4-(4-(3-methyl-1-phenyl-1H-pyrazol-5-yl)piperazin-1-yl)pyrrolidin-2-ylcarbonyl)thiazolidine); 0 (Blood Glucose); 0 (Glycated Hemoglobin A); 0 (Hypoglycemic Agents); 0 (Insulin); 0 (Pyrazoles); 0 (Thiazolidines)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180124
[Lr] Data última revisão:
180124
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170726
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE
[do] DOI:10.1080/14656566.2017.1359259


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[PMID]:29179216
[Au] Autor:Sakai G; Tokuda H; Fujita K; Kainuma S; Kawabata T; Matsushima-Nishiwaki R; Kozawa O; Otsuka T
[Ad] Endereço:Department of Orthopedic Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
[Ti] Título:Heat Shock Protein 70 Negatively Regulates TGF-ß-Stimulated VEGF Synthesis via p38 MAP Kinase in Osteoblasts.
[So] Source:Cell Physiol Biochem;44(3):1133-1145, 2017.
[Is] ISSN:1421-9778
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:BACKGROUND/AIMS: We previously demonstrated that transforming growth factor-ß (TGF-ß) stimulates the synthesis of vascular endothelial growth factor (VEGF) through the activation of p38 mitogen-activated protein (MAP) kinase in osteoblast-like MC3T3-E1 cells. Heat shock protein70 (HSP70) is a ubiquitously expressed molecular chaperone. In the present study, we investigated the involvement of HSP70 in the TGF-ß-stimulated VEGF synthesis and the underlying mechanism in these cells. METHODS: Culture MC3T3-E1 cells were stimulated by TGF-ß. Released VEGF was measured using an ELISA assay. VEGF mRNA level was quantified by RT-PCR. Phosphorylation of each protein kinase was analyzed by Western blotting. RESULTS: VER-155008 and YM-08, both of HSP70 inhibitors, significantly amplified the TGF-ß-stimulated VEGF release. In addition, the expression level of VEGF mRNA induced by TGF-ß was enhanced by VER-155008. These inhibitors markedly strengthened the TGF-ß-induced phosphorylation of p38 MAP kinase. The TGF-ß-induced phosphorylation of p38 MAP kinase was amplified in HSP70-knockdown cells. SB203580, an inhibitor of p38 MAP kinase, significantly suppressed the amplification by these inhibitors of the TGF-ß-induced VEGF release. CONCLUSION: These results strongly suggest that HSP70 acts as a negative regulator in the TGF-ß-stimulated VEGF synthesis in osteoblasts, and that the inhibitory effect of HSP70 is exerted at a point upstream of p38 MAP kinase.
[Mh] Termos MeSH primário: Proteínas de Choque Térmico HSP70/metabolismo
Fator de Crescimento Transformador beta/farmacologia
Fator A de Crescimento do Endotélio Vascular/metabolismo
Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
[Mh] Termos MeSH secundário: Animais
Benzotiazóis/farmacologia
Linhagem Celular
Ensaio de Imunoadsorção Enzimática
Proteínas de Choque Térmico HSP70/antagonistas & inibidores
Proteínas de Choque Térmico HSP70/genética
Imidazóis/farmacologia
Camundongos
Osteoblastos/citologia
Osteoblastos/efeitos dos fármacos
Osteoblastos/metabolismo
Fosforilação/efeitos dos fármacos
Nucleosídeos de Purina/farmacologia
Piridinas/farmacologia
Interferência de RNA
RNA Interferente Pequeno
Reação em Cadeia da Polimerase em Tempo Real
Proteína Smad2/metabolismo
Proteína Smad3/metabolismo
Tiazolidinas/farmacologia
Fator A de Crescimento do Endotélio Vascular/análise
Fator A de Crescimento do Endotélio Vascular/genética
Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzothiazoles); 0 (HSP70 Heat-Shock Proteins); 0 (Imidazoles); 0 (Purine Nucleosides); 0 (Pyridines); 0 (RNA, Small Interfering); 0 (Smad2 Protein); 0 (Smad3 Protein); 0 (Thiazolidines); 0 (Transforming Growth Factor beta); 0 (VER 155008); 0 (Vascular Endothelial Growth Factor A); 0 (YM-08 compound); EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases); OU13V1EYWQ (SB 203580)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180118
[Lr] Data última revisão:
180118
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE
[do] DOI:10.1159/000485418


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[PMID]:29179179
[Au] Autor:Shi R; Xiao ZT; Zheng YJ; Zhang YL; Xu JW; Huang JH; Zhou WL; Li PB; Su WW
[Ad] Endereço:Guangdong Engineering & Technology Research Center for Quality and Efficacy Re-evaluation of Post-market Traditional Chinese Medicine, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
[Ti] Título:Naringenin Regulates CFTR Activation and Expression in Airway Epithelial Cells.
[So] Source:Cell Physiol Biochem;44(3):1146-1160, 2017.
[Is] ISSN:1421-9778
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:BACKGROUND/AIMS: Sputum symptoms are commonly seen in the elderly. This study aimed to identify an efficacious expectorant treatment stratagem through evaluating the secretion-promoting activation and cystic fibrosis transmembrane conductance regulator (CFTR) expression of the bioactive herbal monomer naringenin. METHODS: Vectorial Cl- transport was determined by measuring short-circuit current (ISC) in rat airway epithelium. cAMP content was measured by ELISA in primary cultured epithelial cells and Calu-3 cells. CFTR expression in Calu-3 cells was determined by qPCR. RESULTS: Addition of naringenin to the basolateral side of the rat airway led to a concentration-dependent sustained increase in ISC. The current was suppressed when exposed to Cl--free solution or by bumetanide, BaCl2, and DPC but not by DIDS and IBMX. Forskolin-induced ISC increase and CFTRinh-172/MDL-12330A-induced ISC inhibition were not altered by naringenin. Intracellular cAMP content was significantly increased by naringenin. With lipopolysaccharide stimulation, CFTR expression was significantly reduced, and naringenin dose-dependently enhanced CFTR mRNA expression. CONCLUSION: These results demonstrate that naringenin has the ability to stimulate Cl- secretion, which is mediated by CFTR through a signaling pathway by increasing cAMP content. Moreover, naringenin can increase CFTR expression when organism CFTR expression is seriously hampered. Our data suggest a potentially effective treatment strategy for sputum.
[Mh] Termos MeSH primário: Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo
Células Epiteliais/efeitos dos fármacos
Flavanonas/farmacologia
[Mh] Termos MeSH secundário: Animais
Compostos de Bário/farmacologia
Benzoatos/farmacologia
Células Cultivadas
Canais de Cloreto/antagonistas & inibidores
Canais de Cloreto/metabolismo
Cloretos/farmacologia
Colforsina/farmacologia
AMP Cíclico/análise
Regulador de Condutância Transmembrana em Fibrose Cística/antagonistas & inibidores
Regulador de Condutância Transmembrana em Fibrose Cística/genética
Células Epiteliais/citologia
Células Epiteliais/metabolismo
Feminino
Seres Humanos
Iminas/farmacologia
Transporte de Íons/efeitos dos fármacos
Masculino
Microscopia de Fluorescência
Ratos
Ratos Sprague-Dawley
Reação em Cadeia da Polimerase em Tempo Real
Tiazolidinas/farmacologia
Traqueia/citologia
ortoaminobenzoatos/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (3-((3-trifluoromethyl)phenyl)-5-((3-carboxyphenyl)methylene)-2-thioxo-4-thiazolidinone); 0 (Barium Compounds); 0 (Benzoates); 0 (Chloride Channels); 0 (Chlorides); 0 (Flavanones); 0 (Imines); 0 (Thiazolidines); 0 (ortho-Aminobenzoates); 0VK51DA1T2 (barium chloride); 126880-72-6 (Cystic Fibrosis Transmembrane Conductance Regulator); 1F7A44V6OU (Colforsin); 82985-31-7 (RMI 12330A); 952VN06WBB (fenamic acid); E0399OZS9N (Cyclic AMP); HN5425SBF2 (naringenin)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180118
[Lr] Data última revisão:
180118
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE
[do] DOI:10.1159/000485419


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[PMID]:29227079
[Au] Autor:Kоbyli nska LI; Havrylyuk DY; Mitina NE; Zaichenko AS; Lesyk RB; Zіme nkovsky BS; Stoika RS
[Ti] Título:Biochemical indicators of nephrotoxicity in blood serum of rats treated with novel 4-thiazolidinone derivatives or their complexes with polyethylene glycol-containing nanoscale polymeric carrier
[So] Source:Ukr Biochem J;88(1):51-60, 2016 Jan-Feb.
[Is] ISSN:2409-4943
[Cp] País de publicação:Ukraine
[La] Idioma:eng
[Ab] Resumo:The aim of this study was to compare the effect of new synthetic 4-thiazolidinone derivatives (potential anticancer compounds denoted as 3882, 3288 and 3833) and doxorubicin (positive control) in free form and in their complexes with synthetic polyethylene glycol-containing nanoscale polymeric carrier on the biochemical indicators of nephrotoxicity in blood serum of rats. The concentration of total protein, urea, creatinine, glucose, ions of sodium, potassium, calcium, iron and chloride was measured. It was found that after injection of the investigated compounds, the concentration of sodium cations and chloride anions in blood serum was increased compared with control (untreated animals). Doxorubicin's injection was accompanied by a decrease in the concentration of iron cations. The concentration of total protein, urea and creatinine decreased under the influence of the studied compounds. Complexation of these аntineoplastic substances with a synthetic polymeric nanocarrier lowered the concentration of the investigated metabolites substantially compared to the effect of these compounds in free form. The normalization of concentration of total protein, urea and creatinine in blood serum of rats treated with complexes of the studied compounds with the polymeric carrier comparing with increased concentration of these indicators at the introduction of such compounds in free form was found.
[Mh] Termos MeSH primário: Antineoplásicos/toxicidade
Rim/efeitos dos fármacos
Nanoestruturas/administração & dosagem
Polietilenoglicóis/química
Tiazolidinas/toxicidade
[Mh] Termos MeSH secundário: Animais
Animais não Endogâmicos
Antineoplásicos/síntese química
Glicemia/metabolismo
Proteínas Sanguíneas/metabolismo
Cálcio/sangue
Cloretos/sangue
Creatinina/sangue
Doxorrubicina/toxicidade
Portadores de Fármacos/administração & dosagem
Compostos de Epóxi/química
Ferro/sangue
Rim/metabolismo
Masculino
Metacrilatos/química
Nanoestruturas/química
Poliacetilenos/química
Potássio/sangue
Ratos
Sódio/sangue
Tiazolidinas/síntese química
Testes de Toxicidade Aguda
Ureia/sangue
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Blood Glucose); 0 (Blood Proteins); 0 (Chlorides); 0 (Drug Carriers); 0 (Epoxy Compounds); 0 (Methacrylates); 0 (Thiazolidines); 25067-58-7 (Polyacetylenes); 30IQX730WE (Polyethylene Glycols); 80168379AG (Doxorubicin); 8W8T17847W (Urea); 9NEZ333N27 (Sodium); AYI8EX34EU (Creatinine); E1UOL152H7 (Iron); R8WN29J8VF (glycidyl methacrylate); RWP5GA015D (Potassium); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180116
[Lr] Data última revisão:
180116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171212
[St] Status:MEDLINE
[do] DOI:10.15407/ubj88.01.051


  8 / 2899 MEDLINE  
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[PMID]:28941802
[Au] Autor:Valdivieso ÁG; Mori C; Clauzure M; Massip-Copiz M; Santa-Coloma TA
[Ad] Endereço:Institute for Biomedical Research (BIOMED, UCA-CONICET), Laboratory of Cellular and Molecular Biology, School of Medical Sciences, Pontifical Catholic University of Argentina (UCA) and The National Scientific and Technical Research Council of Argentina (CONICET), Buenos Aires, C1107AFF, Argentina.
[Ti] Título:CFTR modulates RPS27 gene expression using chloride anion as signaling effector.
[So] Source:Arch Biochem Biophys;633:103-109, 2017 Nov 01.
[Is] ISSN:1096-0384
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In Cystic Fibrosis (CF), the impairment of the CFTR channel activity leads to a variety of alterations, including differential gene expression. However, the CFTR signaling mechanisms remain unclear. Recently, culturing IB3-1 CF cells under different intracellular Cl concentrations ([Cl ] ), we observed several Cl -dependent genes and further characterized one of them as RPS27. Thus, we hypothesized that Cl might act as a signaling effector for CFTR signaling. Here, to test this idea, we study RPS27 expression in T84 cells modulating the CFTR activity by using CFTR inhibitors. First, we observed that incubation of T84 cells with increasing concentrations of the CFTR inhibitors CFTR(inh)-172 or GlyH-101 determined a progressive increase in the relative [Cl ] (using the Cl fluorescent probe SPQ). The [Cl ] rise was concomitant with a dose-dependent down-regulation of RPS27. These results imply that CFTR inhibition produce Cl accumulation and that RPS27 expression can be modulated by CFTR inhibition. Therefore, Cl behaves as a signaling effector for CFTR in the modulation of RPS27 expression. In addition, the IL-1ß receptor antagonist IL1RN or the JNK inhibitor SP600125, both restored the down-regulation of RPS27 induced by CFTRinh-172, implying a role of autocrine IL-1ß and JNK signaling downstream of Cl in RPS27 modulation.
[Mh] Termos MeSH primário: Cloretos/metabolismo
Regulador de Condutância Transmembrana em Fibrose Cística/genética
Células Epiteliais/metabolismo
Metaloproteínas/genética
Proteínas Nucleares/genética
Proteínas de Ligação a RNA/genética
Proteínas Ribossômicas/genética
Transdução de Sinais
[Mh] Termos MeSH secundário: Antracenos/farmacologia
Comunicação Autócrina
Benzoatos/farmacologia
Linhagem Celular Tumoral
Regulador de Condutância Transmembrana em Fibrose Cística/antagonistas & inibidores
Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo
Células Epiteliais/citologia
Células Epiteliais/efeitos dos fármacos
Corantes Fluorescentes/metabolismo
Regulação da Expressão Gênica
Glicina/análogos & derivados
Glicina/farmacologia
Seres Humanos
Hidrazinas/farmacologia
Proteína Antagonista do Receptor de Interleucina 1/farmacologia
Interleucina-1beta/antagonistas & inibidores
Interleucina-1beta/genética
Interleucina-1beta/metabolismo
Transporte de Íons/efeitos dos fármacos
MAP Quinase Quinase 4/antagonistas & inibidores
MAP Quinase Quinase 4/genética
MAP Quinase Quinase 4/metabolismo
Metaloproteínas/metabolismo
Proteínas Nucleares/metabolismo
Inibidores de Proteínas Quinases/farmacologia
Proteínas de Ligação a RNA/metabolismo
Proteínas Ribossômicas/metabolismo
Tiazolidinas/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (3-((3-trifluoromethyl)phenyl)-5-((3-carboxyphenyl)methylene)-2-thioxo-4-thiazolidinone); 0 (Anthracenes); 0 (Benzoates); 0 (CFTR protein, human); 0 (Chlorides); 0 (Fluorescent Dyes); 0 (Hydrazines); 0 (IL1B protein, human); 0 (IL1RN protein, human); 0 (Interleukin 1 Receptor Antagonist Protein); 0 (Interleukin-1beta); 0 (Metalloproteins); 0 (N-(2-naphthalenyl)-((3,5-dibromo-2,4-dihydroxyphenyl)methylene)glycine hydrazide); 0 (Nuclear Proteins); 0 (Protein Kinase Inhibitors); 0 (RNA-Binding Proteins); 0 (RPS27 protein, human); 0 (Ribosomal Proteins); 0 (Thiazolidines); 126880-72-6 (Cystic Fibrosis Transmembrane Conductance Regulator); 1TW30Y2766 (pyrazolanthrone); EC 2.7.12.2 (MAP Kinase Kinase 4); TE7660XO1C (Glycine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170925
[St] Status:MEDLINE


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[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


  10 / 2899 MEDLINE  
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[PMID]:28925739
[Au] Autor:El-Miligy MM; Abd El Razik HA; Abu-Serie MM
[Ad] Endereço:Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt.
[Ti] Título:Synthesis of piperazine-based thiazolidinones as VEGFR2 tyrosine kinase inhibitors inducing apoptosis.
[So] Source:Future Med Chem;9(15):1709-1729, 2017 Oct.
[Is] ISSN:1756-8927
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:AIM: VEGFR2 tyrosine kinase is a main target in suppressing cancer growth and metastasis. Materials & methods: Piperazine-based thiazolidinones were synthesized and screened for their anticancer and VEGFR2 tyrosine kinase inhibitory activity. Results: Compounds 11, 13 and 16 displayed potent anticancer activity against HepG-2 with IC values 0.03-0.06 µM. They were safe on normal human fibroblasts with selectivity indices 8.09, 11.40 and 4.37, respectively. Also, these compounds showed VEGFR2 tyrosine kinase inhibitory activities more than the reference staurosporine with IC values <0.3 µM. Lineweaver-Burk plot revealed that these compounds behaved as uncompetitive VEGFR2 tyrosine kinase inhibitors. They also induced caspase-dependent apoptosis in HepG-2. In addition, these compounds revealed good binding within VEGFR2 tyrosine kinase enzyme in comparison with sorafenib reference. CONCLUSION: Compounds 11, 13 and 16 comprise a new promising scaffold of selective VEGFR2 tyrosine kinase inhibitors with caspase-dependent apoptotic activities.
[Mh] Termos MeSH primário: Apoptose/efeitos dos fármacos
Piperazinas/química
Inibidores de Proteínas Quinases/síntese química
Inibidores de Proteínas Quinases/farmacologia
Tiazolidinas/química
Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores
[Mh] Termos MeSH secundário: Sítios de Ligação
Caspases/metabolismo
Linhagem Celular Tumoral
Células Hep G2
Seres Humanos
Simulação de Acoplamento Molecular
Niacinamida/análogos & derivados
Niacinamida/química
Niacinamida/metabolismo
Niacinamida/farmacologia
Compostos de Fenilureia/química
Compostos de Fenilureia/metabolismo
Compostos de Fenilureia/farmacologia
Inibidores de Proteínas Quinases/química
Estrutura Terciária de Proteína
Estaurosporina/síntese química
Estaurosporina/química
Estaurosporina/farmacologia
Tiazolidinas/síntese química
Tiazolidinas/farmacologia
Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Phenylurea Compounds); 0 (Piperazines); 0 (Protein Kinase Inhibitors); 0 (Thiazolidines); 1RTM4PAL0V (piperazine); 25X51I8RD4 (Niacinamide); 9ZOQ3TZI87 (sorafenib); EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-2); EC 3.4.22.- (Caspases); H88EPA0A3N (Staurosporine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171025
[Lr] Data última revisão:
171025
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170920
[St] Status:MEDLINE
[do] DOI:10.4155/fmc-2017-0072



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