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[PMID]:28566208
[Au] Autor:Ishigami-Yuasa M; Watanabe Y; Mori T; Masuno H; Fujii S; Kikuchi E; Uchida S; Kagechika H
[Ad] Endereço:Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University (TMDU), 2-3-10 Kanda-Surugadai, Chiyodaku, Tokyo 101-0062, Japan.
[Ti] Título:Development of WNK signaling inhibitors as a new class of antihypertensive drugs.
[So] Source:Bioorg Med Chem;25(14):3845-3852, 2017 Jul 15.
[Is] ISSN:1464-3391
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Pseudohypoaldosteronism type II (PHAII) is characterized by hyperkalemia and hypertension despite a normal glomerular filtration rate. Abnormal activation of the signal cascade of with-no-lysine kinase (WNK) with OSR1 (oxidative stress-responsive kinase 1)/SPAK (STE20/SPS1-related proline/alanine-rich kinase) and NCC (NaCl cotransporter) results in characteristic salt-sensitive hypertension. Thus, inhibitors of the WNK-OSR1/SPAK-NCC cascade are candidates for a new class of antihypertensive drugs. In this study, we developed novel inhibitors of this signal cascade from the 9-aminoacridine lead compound 1, one of the hit compounds obtained by screening our chemical library for WNK-SPAK binding inhibitors. Among the synthesized acridine derivatives, several acridine-3-amide and 3-urea derivatives, such as 10 (IC : 6.9µM), 13 (IC : 2.6µM), and 20 (IC : 4.8µM), showed more potent inhibitory activity than the lead compound 1 (IC : 15.4µM). Compounds 10 and 20 were confirmed to inhibit phosphorylation of NCC in vivo.
[Mh] Termos MeSH primário: Anti-Hipertensivos/química
Peptídeos e Proteínas de Sinalização Intracelular/metabolismo
Antígenos de Histocompatibilidade Menor/metabolismo
Proteínas Serina-Treonina Quinases/metabolismo
[Mh] Termos MeSH secundário: Aminacrina/química
Aminacrina/metabolismo
Aminacrina/farmacologia
Animais
Anti-Hipertensivos/metabolismo
Anti-Hipertensivos/farmacologia
Sobrevivência Celular/efeitos dos fármacos
Células HEK293
Seres Humanos
Immunoblotting
Concentração Inibidora 50
Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores
Rim/efeitos dos fármacos
Rim/metabolismo
Camundongos
Camundongos Endogâmicos C57BL
Fosforilação/efeitos dos fármacos
Proteínas Serina-Treonina Quinases/antagonistas & inibidores
Transdução de Sinais/efeitos dos fármacos
Simportadores de Cloreto de Sódio-Potássio/química
Simportadores de Cloreto de Sódio-Potássio/metabolismo
Relação Estrutura-Atividade
Proteína Quinase 1 Deficiente de Lisina WNK
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antihypertensive Agents); 0 (Intracellular Signaling Peptides and Proteins); 0 (Minor Histocompatibility Antigens); 0 (Sodium-Potassium-Chloride Symporters); 78OY3Z0P7Z (Aminacrine); EC 2.7.11.1 (OSR1 kinase, human); EC 2.7.11.1 (Protein-Serine-Threonine Kinases); EC 2.7.11.1 (STK39 protein, human); EC 2.7.11.1 (WNK Lysine-Deficient Protein Kinase 1); EC 2.7.11.1 (WNK1 protein, human)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170602
[St] Status:MEDLINE


  2 / 431 MEDLINE  
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[PMID]:27903755
[Au] Autor:Campbell AP; Wakelin LP; Denny WA; Finch AM
[Ad] Endereço:Department of Pharmacology, School of Medical Sciences, UNSW Australia, Kensington, Australia (A.P.C., L.P.G.W., A.M.F.); Auckland Cancer Society Research Centre, Faculty of Medicine and Health Science, University of Auckland, Auckland, New Zealand (W.A.D.).
[Ti] Título:Homobivalent Conjugation Increases the Allosteric Effect of 9-aminoacridine at the α1-Adrenergic Receptors.
[So] Source:Mol Pharmacol;91(2):135-144, 2017 Feb.
[Is] ISSN:1521-0111
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The α -adrenergic receptors are targets for a number of cardiovascular and central nervous system conditions, but the current drugs for these receptors lack specificity to be of optimal clinical value. Allosteric modulators offer an alternative mechanism of action to traditional α -adrenergic ligands, yet there is little information describing this drug class at the α -adrenergic receptors. We have identified a series of 9-aminoacridine compounds that demonstrate allosteric modulation of the α - and α -adrenergic receptors. The 9-aminoacridines increase the rate of [ H]prazosin dissociation from the α - and α -adrenergic receptors and noncompetitively inhibit receptor activation by the endogenous agonist norepinephrine. The structurally similar compound, tacrine, which is a known allosteric modulator of the muscarinic receptors, is also shown to be a modulator of the α -adrenergic receptors, which suggests a general lack of selectivity for allosteric binding sites across aminergic G protein-coupled receptor. Conjugation of two 9-aminoacridine pharmacophores, using linkers of varying length, increases the potency and efficacy of the allosteric effects of this ligand, likely through optimization of bitopic engagement of the allosteric and orthosteric binding sites of the receptor. Such a bivalent approach may provide a mechanism for fine tuning the efficacy of allosteric compounds in future drug design efforts.
[Mh] Termos MeSH primário: Aminacrina/farmacologia
Receptores Adrenérgicos alfa 1/metabolismo
[Mh] Termos MeSH secundário: Antagonistas de Receptores Adrenérgicos alfa 1/farmacologia
Regulação Alostérica/efeitos dos fármacos
Sítio Alostérico/efeitos dos fármacos
Aminacrina/química
Animais
Bioensaio
Células COS
Cercopithecus aethiops
Seres Humanos
Cinética
Norepinefrina/farmacologia
Prazosina/farmacologia
Trítio/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adrenergic alpha-1 Receptor Antagonists); 0 (Receptors, Adrenergic, alpha-1); 10028-17-8 (Tritium); 78OY3Z0P7Z (Aminacrine); X4W3ENH1CV (Norepinephrine); XM03YJ541D (Prazosin)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170509
[Lr] Data última revisão:
170509
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161202
[St] Status:MEDLINE
[do] DOI:10.1124/mol.116.105874


  3 / 431 MEDLINE  
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[PMID]:27567075
[Au] Autor:Kava HW; Murray V
[Ad] Endereço:School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, Australia.
[Ti] Título:CpG methylation increases the DNA binding of 9-aminoacridine carboxamide Pt analogues.
[So] Source:Bioorg Med Chem;24(19):4701-4710, 2016 Oct 01.
[Is] ISSN:1464-3391
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:This study investigated the effect of CpG methylation on the DNA binding of cisplatin analogues with an attached aminoacridine intercalator. DNA-targeted 9-aminoacridine carboxamide Pt complexes are known to bind at 5'-CpG sequences. Their binding to methylated and non-methylated 5'-CpG sequences was determined and compared with cisplatin. The damage profiles of each platinum compound were quantified via a polymerase stop assay with fluorescently labelled primers and capillary electrophoresis. Methylation at 5'-CpG was shown to significantly increase the binding intensity for the 9-aminoacridine carboxamide compounds, whereas no significant increase was found for cisplatin. 5'-CpG methylation had the largest effect on the 9-ethanolamine-acridine carboxamide Pt complex, followed by the 9-aminoacridine carboxamide Pt complex and the 7-fluoro complex. The methylation state of a cell's genome is important in maintaining normal gene expression, and is often aberrantly altered in cancer cells. An analogue of cisplatin which differentially targets methylated DNA may be able to improve its therapeutic activity, or alter its range of targets and evade the chemoresistance which hampers cisplatin efficacy in clinical use.
[Mh] Termos MeSH primário: Aminacrina/farmacologia
Cisplatino/farmacologia
DNA/metabolismo
Substâncias Intercalantes/farmacologia
Compostos Organoplatínicos/farmacologia
[Mh] Termos MeSH secundário: Aminacrina/análogos & derivados
Cisplatino/análogos & derivados
Ilhas de CpG/efeitos dos fármacos
DNA/química
Metilação de DNA
Substâncias Intercalantes/química
Compostos Organoplatínicos/química
Plasmídeos/química
Plasmídeos/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Intercalating Agents); 0 (Organoplatinum Compounds); 78OY3Z0P7Z (Aminacrine); 9007-49-2 (DNA); Q20Q21Q62J (Cisplatin)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170919
[Lr] Data última revisão:
170919
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160828
[St] Status:MEDLINE


  4 / 431 MEDLINE  
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[PMID]:27451786
[Au] Autor:Knezevic Nikola Z
[Ti] Título:Magnetic Field-Induced Accentuation of Drug Release from Core/Shell Magnetic Mesoporous Silica Nanoparticles for Anticancer Treatment.
[So] Source:J Nanosci Nanotechnol;16(4):4195-9, 2016 Apr.
[Is] ISSN:1533-4880
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Drug (9-aminoacridine) loaded core/shell magnetic iron oxide-containing mesoporous silica nanoparticles (MMSN) were treated with HeLa cells and the drug carriers were agitated by expo- sure to magnetic field. Viability studies show the applicability of drug loaded magnetic material for anticancer treatment, which is enhanced upon stimulation with magnetic field. Confocal micrographs of fluorescein grafted MMSN-treated HeLa cells confirmed the ability of magnetic field to concentrate the synthesized material in the exposed area of the cells. The synthesized material and the applied drug delivery method may find application in magnetic field-responsive targeted treatment of cancer.
[Mh] Termos MeSH primário: Aminacrina/administração & dosagem
Preparações de Ação Retardada/administração & dosagem
Nanopartículas de Magnetita/química
Nanocápsulas/administração & dosagem
Neoplasias Experimentais/tratamento farmacológico
Dióxido de Silício/química
[Mh] Termos MeSH secundário: Aminacrina/química
Antineoplásicos/administração & dosagem
Antineoplásicos/química
Apoptose/efeitos dos fármacos
Linhagem Celular Tumoral
Preparações de Ação Retardada/síntese química
Preparações de Ação Retardada/efeitos da radiação
Difusão
Seres Humanos
Campos Magnéticos
Nanopartículas de Magnetita/administração & dosagem
Nanopartículas de Magnetita/efeitos da radiação
Nanocápsulas/química
Nanocápsulas/efeitos da radiação
Neoplasias Experimentais/patologia
Porosidade
Dióxido de Silício/efeitos da radiação
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Delayed-Action Preparations); 0 (Magnetite Nanoparticles); 0 (Nanocapsules); 7631-86-9 (Silicon Dioxide); 78OY3Z0P7Z (Aminacrine)
[Em] Mês de entrada:1609
[Cu] Atualização por classe:160725
[Lr] Data última revisão:
160725
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160726
[St] Status:MEDLINE


  5 / 431 MEDLINE  
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[PMID]:27414759
[Au] Autor:Ly A; Buck A; Balluff B; Sun N; Gorzolka K; Feuchtinger A; Janssen KP; Kuppen PJ; van de Velde CJ; Weirich G; Erlmeier F; Langer R; Aubele M; Zitzelsberger H; McDonnell L; Aichler M; Walch A
[Ad] Endereço:Research Unit Analytical Pathology, Helmholtz Zentrum München, Neuherberg, Germany.
[Ti] Título:High-mass-resolution MALDI mass spectrometry imaging of metabolites from formalin-fixed paraffin-embedded tissue.
[So] Source:Nat Protoc;11(8):1428-43, 2016 Aug.
[Is] ISSN:1750-2799
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Formalin-fixed and paraffin-embedded (FFPE) tissue specimens are the gold standard for histological examination, and they provide valuable molecular information in tissue-based research. Metabolite assessment from archived tissue samples has not been extensively conducted because of a lack of appropriate protocols and concerns about changes in metabolite content or chemical state due to tissue processing. We present a protocol for the in situ analysis of metabolite content from FFPE samples using a high-mass-resolution matrix-assisted laser desorption/ionization fourier-transform ion cyclotron resonance mass spectrometry imaging (MALDI-FT-ICR-MSI) platform. The method involves FFPE tissue sections that undergo deparaffinization and matrix coating by 9-aminoacridine before MALDI-MSI. Using this platform, we previously detected ∼1,500 m/z species in the mass range m/z 50-1,000 in FFPE samples; the overlap compared with fresh frozen samples is 72% of m/z species, indicating that metabolites are largely conserved in FFPE tissue samples. This protocol can be reproducibly performed on FFPE tissues, including small samples such as tissue microarrays and biopsies. The procedure can be completed in a day, depending on the size of the sample measured and raster size used. Advantages of this approach include easy sample handling, reproducibility, high throughput and the ability to demonstrate molecular spatial distributions in situ. The data acquired with this protocol can be used in research and clinical practice.
[Mh] Termos MeSH primário: Formaldeído/metabolismo
Metabolômica/métodos
Inclusão em Parafina
Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos
Fixação de Tecidos
[Mh] Termos MeSH secundário: Aminacrina/metabolismo
Análise de Fourier
Seres Humanos
Peso Molecular
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
1HG84L3525 (Formaldehyde); 78OY3Z0P7Z (Aminacrine)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170529
[Lr] Data última revisão:
170529
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160715
[St] Status:MEDLINE
[do] DOI:10.1038/nprot.2016.081


  6 / 431 MEDLINE  
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[PMID]:26876105
[Au] Autor:Kang JY; Kwon O; Gil JY; Oh DB
[Ad] Endereço:Synthetic Biology and Bioengineering Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea.
[Ti] Título:Comparison of fluorescent tags for analysis of mannose-6-phosphate glycans.
[So] Source:Anal Biochem;501:1-3, 2016 May 15.
[Is] ISSN:1096-0309
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mannose-6-phosphate (M-6-P) glycan analysis is important for quality control of therapeutic enzymes for lysosomal storage diseases. Here, we found that the analysis of glycans containing two M-6-Ps was highly affected by the hydrophilicity of the elution solvent used in high-performance liquid chromatography (HPLC). In addition, the performances of three fluorescent tags--2-aminobenzoic acid (2-AA), 2-aminobenzamide (2-AB), and 3-(acetyl-amino)-6-aminoacridine (AA-Ac)--were compared with each other for M-6-P glycan analysis using HPLC and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The best performance for analyzing M-6-P glycans was shown by 2-AA labeling in both analyses.
[Mh] Termos MeSH primário: Corantes Fluorescentes/química
Manosefosfatos/análise
Polissacarídeos/química
[Mh] Termos MeSH secundário: Aminacrina/análogos & derivados
Aminobenzoatos/química
Cromatografia Líquida de Alta Pressão/métodos
Interações Hidrofóbicas e Hidrofílicas
Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos
ortoaminobenzoatos/química
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Aminobenzoates); 0 (Fluorescent Dyes); 0 (Mannosephosphates); 0 (Polysaccharides); 0 (ortho-Aminobenzoates); 3672-15-9 (mannose-6-phosphate); 78OY3Z0P7Z (Aminacrine); Q1M2WEK6VA (anthranilamide)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160216
[St] Status:MEDLINE


  7 / 431 MEDLINE  
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[PMID]:26671412
[Au] Autor:Bebawy LI; Elghobashy MR; Abbas SS; Shokry RF
[Ad] Endereço:National Organization for Drug Control and Research (NODCAR), 51 Wezaret El-Zeraa st. Dokki, Cairo, Egypt.
[Ti] Título:Chromatographic Determination of Aminoacridine Hydrochloride, Lidocaine Hydrochloride and Lidocaine Toxic Impurity in Oral Gel.
[So] Source:J Chromatogr Sci;54(4):492-9, 2016 Apr.
[Is] ISSN:1945-239X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Two sensitive and selective analytical methods were developed for simultaneous determination of aminoacridine hydrochloride and lidocaine hydrochloride in bulk powder and pharmaceutical formulation. Method A was based on HPLC separation of the cited drugs with determination of the toxic lidocaine-related impurity 2,6-dimethylaniline. The separation was achieved using reversed-phase column C18, 250 × 4.6 mm, 5 µm particle size and mobile phase consisting of 0.05 M disodium hydrogen phosphate dihydrate (pH 6.0 ± 0.2 adjusted with phosphoric acid) and acetonitrile (55 : 45, v/v). Quantitation was achieved with UV detection at 240 nm. Linear calibration curve was in the range of 1.00-10.00, 13.20-132.00 and 1.32-13.20 µg mL(-1) for aminoacridine hydrochloride, lidocaine hydrochloride and 2,6-dimethylaniline, respectively. Method B was based on TLC separation of the cited drugs followed by densitometric measurement at 365 nm on the fluorescent mode for aminoacridine hydrochloride and 220 nm on the absorption mode for lidocaine hydrochloride. The separation was carried out using ethyl acetate-methanol-acetic acid (65 : 30 : 5 by volume) as a developing system. The calibration curve was in the range of 25.00-250.00 ng spot(-1) and 0.99-9.90 µg spot(-1) for aminoacridine hydrochloride and lidocaine hydrochloride, respectively. The results obtained were statistically analyzed and compared with those obtained by applying the manufacturer's method.
[Mh] Termos MeSH primário: Aminacrina/análise
Contaminação de Medicamentos
Lidocaína/análise
[Mh] Termos MeSH secundário: Administração Oral
Cromatografia Líquida de Alta Pressão
Géis
Lidocaína/administração & dosagem
Lidocaína/química
Preparações Farmacêuticas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Gels); 0 (Pharmaceutical Preparations); 78OY3Z0P7Z (Aminacrine); 98PI200987 (Lidocaine)
[Em] Mês de entrada:1611
[Cu] Atualização por classe:170403
[Lr] Data última revisão:
170403
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151217
[St] Status:MEDLINE
[do] DOI:10.1093/chromsci/bmv170


  8 / 431 MEDLINE  
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[PMID]:26385945
[Au] Autor:Munawar R; Mushtaq N; Arif S; Ahmed A; Akhtar S; Ansari S; Meer S; Saify ZS; Arif M
[Ad] Endereço:Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Karachi, Karachi, Pakistan pharmacistrabya@gmail.com.
[Ti] Título:Synthesis of 9-Aminoacridine Derivatives as Anti-Alzheimer Agents.
[So] Source:Am J Alzheimers Dis Other Demen;31(3):263-9, 2016 May.
[Is] ISSN:1938-2731
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In the present study, some 9-aminoacridine derivatives have been synthesized by condensation of 9-aminoacridine with substituted phenacyl, benzoyl, and benzyl halides (RM1-RM6). Compounds were investigated for acetylcholinesterase and butyrylcholinesterase inhibition potential, considering these enzymes playing a key role in Alzheimer's disease. All derivatives showed better inhibition of enzymes than the standard galantamine, whereas except RM4, all exhibit better results than tacrine, a well-known acridine derivative used for the treatment of Alzheimer's disease.
[Mh] Termos MeSH primário: Doença de Alzheimer/enzimologia
Aminacrina/síntese química
Inibidores da Colinesterase/síntese química
[Mh] Termos MeSH secundário: Doença de Alzheimer/tratamento farmacológico
Seres Humanos
Técnicas In Vitro
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Cholinesterase Inhibitors); 78OY3Z0P7Z (Aminacrine)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:170117
[Lr] Data última revisão:
170117
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150920
[St] Status:MEDLINE
[do] DOI:10.1177/1533317515603115


  9 / 431 MEDLINE  
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[PMID]:26408679
[Au] Autor:Ferguson DM; Jacobson BA; Jay-Dixon J; Patel MR; Kratzke RA; Raza A
[Ad] Endereço:Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN, U.S.A. Department of Pharmacology, University of Minnesota, Minneapolis, MN, U.S.A.
[Ti] Título:Targeting Topoisomerase II Activity in NSCLC with 9-Aminoacridine Derivatives.
[So] Source:Anticancer Res;35(10):5211-7, 2015 Oct.
[Is] ISSN:1791-7530
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Etoposide and other type-II human topoisomerase (TOPOII) poisons are widely used for the treatment of many different cancer types, including non-small cell lung cancer (NSCLC). However, there is a risk for the development of therapy-related secondary leukemia following treatment with these TOPOII poisons. Five to seven years is the typical latency period for the development of secondary leukemia. One of the strategies to overcome this issue is to develop agents that do not act as poisons but still effectively inhibit topoisomerase activity. This has led to the development of acridine-based agents, which are catalytic TOPOII inhibitors, that do not generate DNA strand breaks that can lead to secondary malignancies in in vitro tests. MATERIALS AND METHODS: In this study, we showd antiproliferative activity of a series of acridine-based catalytic inhibitors of TOPOII using four NSCLC cell lines (H460, A549, H2009 and H2030). Cells were treated with four acridine-based compounds for 72 h. RESULTS: The results indicate that these compounds inhibit NSCLC cell proliferation with half-maximal effective concentration (EC50) ranging from 8.15 to 42.09 µM. Combination therapy with cisplatin resulted in increased potency. Poly (ADP-ribose) polymerase cleavage and Guava Nexin assays confirm that the primary mode of cell death was by apoptosis. CONCLUSION: This current work is part of a series of studies for this panel of acridine-based compounds bearing TOPOII-inhibitory activity against different solid tumor types. The acridine-based agents were found to substantially reduce NSCLC cell viability and induce apoptosis. In addition, the acridine-based compounds sensitized cells to cisplatin as measured by cell viability. The results are consistent with prior work on mesothelioma, small-cell lung cancer and pancreatic cancer with this same panel of 9-aminoacridine derivatives. These findings support further development of this type of catalytic TOPOII inhibitor as a novel agent for NSCLC therapy.
[Mh] Termos MeSH primário: Aminacrina/farmacologia
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico
DNA Topoisomerases Tipo II/metabolismo
Neoplasias Pulmonares/tratamento farmacológico
Inibidores da Topoisomerase II/farmacologia
[Mh] Termos MeSH secundário: Aminacrina/análogos & derivados
Carcinoma Pulmonar de Células não Pequenas/enzimologia
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Cisplatino/farmacologia
Sinergismo Farmacológico
Seres Humanos
Neoplasias Pulmonares/enzimologia
Terapia de Alvo Molecular
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Topoisomerase II Inhibitors); 78OY3Z0P7Z (Aminacrine); EC 5.99.1.3 (DNA Topoisomerases, Type II); Q20Q21Q62J (Cisplatin)
[Em] Mês de entrada:1601
[Cu] Atualização por classe:150926
[Lr] Data última revisão:
150926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150927
[St] Status:MEDLINE


  10 / 431 MEDLINE  
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[PMID]:26212310
[Au] Autor:Uno Y; Omori T
[Ad] Endereço:Mitsubishi Tanabe Pharma Co., Chiba, Japan. Electronic address: Uno.Yoshifumi@ma.mt-pharma.co.jp.
[Ti] Título:Re-analysis results using medians of the data from the JaCVAM-organized international validation study of the in vivo rat alkaline comet assay.
[So] Source:Mutat Res Genet Toxicol Environ Mutagen;786-788:182-7, 2015 Jul.
[Is] ISSN:1879-3592
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The data from the JaCVAM-organized international validation study of the in vivo rat alkaline comet assay were reported and analyzed statistically using the simple means of % tail DNA. However, OECD test guideline TG 489 recommends use of the median for data analysis due to the hierarchical nature of the data. Comparison between the simple mean approach and the median based approach for positive/negative/equivocal chemical calls was conducted using the % tail DNA data for the 40 chemicals tested in the JaCVAM-organized international validation study of the in vivo rat alkaline comet assay, using liver and stomach as target organs. In the liver, two genotoxic chemicals, o-anisidine and 9-aminoacridine hydrochloride monohydrate, were positive using the median based approach but negative using the simple mean approach, and two genotoxic chemicals, 2-acetylaminofluorene and busulfan were equivocal using the median based approach but negative using the simple mean approach. In contrast, cadmium chloride (genotoxic carcinogen) was equivocal in both organs using the median based approach, while positive and equivocal in liver and stomach, respectively, using the simple mean approach. Two data sets of sodium arsenite showed equivocal and negative results for liver using the median based approach, although both data sets were equivocal using the simple mean approach. Overall, there are no large differences in terms of the genotoxic call between both approaches. However, the median based approach recommended in OECD TG 489 has an advantage toward higher precision within the groups treated with a test chemical, whereas the approach might show the lower values for the effect.
[Mh] Termos MeSH primário: Ensaio Cometa/métodos
[Mh] Termos MeSH secundário: 2-Acetilaminofluoreno/toxicidade
Administração Oral
Aminacrina/toxicidade
Compostos de Anilina/toxicidade
Animais
Carcinógenos/toxicidade
Dano ao DNA/efeitos dos fármacos
Masculino
Ratos
Ratos Sprague-Dawley
Reprodutibilidade dos Testes
[Pt] Tipo de publicação:JOURNAL ARTICLE; VALIDATION STUDIES
[Nm] Nome de substância:
0 (Aniline Compounds); 0 (Carcinogens); 78OY3Z0P7Z (Aminacrine); 9M98QLJ2DL (2-Acetylaminofluorene); NUX042F201 (2-anisidine)
[Em] Mês de entrada:1510
[Cu] Atualização por classe:150727
[Lr] Data última revisão:
150727
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150728
[St] Status:MEDLINE



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