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[PMID]:28141779
[Au] Autor:Walker JA; Miller AD; Burdo TH; McGrath MS; Williams KC
[Ad] Endereço:*Department of Biology, Boston College, Chestnut Hill, MA; †Cornell University College of Veterinary Medicine, Ithaca, NY; and ‡Department of Pathology and Laboratory Medicine, UCSF, San Francisco, CA.
[Ti] Título:Direct Targeting of Macrophages With Methylglyoxal-Bis-Guanylhydrazone Decreases SIV-Associated Cardiovascular Inflammation and Pathology.
[So] Source:J Acquir Immune Defic Syndr;74(5):583-592, 2017 Apr 15.
[Is] ISSN:1944-7884
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Despite effective combination antiretroviral therapy, HIV-infected individuals develop comorbidities, including cardiovascular disease, where activated macrophages play a key role. To date, few therapies target activated monocytes and macrophages. METHODS: We evaluated a novel oral form of the polyamine biosynthesis inhibitor methylglyoxal-bis-guanylhydrazone (MGBG) on cardiovascular inflammation, carotid artery intima-media thickness (cIMT), and fibrosis in a simian immunodeficiency virus infection model of AIDS. Eleven simian immunodeficiency virus-infected animals received MGBG (30 mg/kg) once daily and 8 received a placebo control both beginning at 21 days postinfection (dpi). Animals were time sacrificed at 49 days post infection (dpi), when their matched placebo controls developed AIDS (63, 70, 77, 80), or at the study end-point (84 dpi). Aorta, carotid artery, and cardiac tissues were analyzed. Quantitative analyses of macrophage populations and T lymphocytes were done and correlated with cIMT and fibrosis. RESULTS: MGBG treatment resulted in 2.19-fold (CD163), 1.86-fold (CD68), 2.31-fold (CD206), and 2.12-fold (MAC387) decreases in macrophages in carotid arteries and significant 2.07-fold (CD163), 1.61-fold (CD68), 1.95-fold (MAC387), and 1.62-fold (CD206) decreases in macrophages in cardiac tissues. cIMT (1.49-fold) and fibrosis (2.05-fold) also were significantly decreased with MGBG treatment. Numbers of macrophage and the degree of fibrosis in treated animals were similar to uninfected animals. A positive correlation between decreased macrophage in the carotid artery and cIMT, and cardiac macrophages and fibrosis was found. CONCLUSIONS: These data demonstrate that directly targeting macrophages with MGBG can reduce cardiovascular inflammation, cIMT, and fibrosis. They suggest that therapies targeting macrophages with HIV could be used in conjunction with combination antiretroviral therapy.
[Mh] Termos MeSH primário: Doenças Cardiovasculares/tratamento farmacológico
Fatores Imunológicos/administração & dosagem
Inflamação/patologia
Macrófagos/efeitos dos fármacos
Mitoguazona/administração & dosagem
Síndrome de Imunodeficiência Adquirida dos Símios/complicações
[Mh] Termos MeSH secundário: Animais
Artérias Carótidas/patologia
Fibrose/patologia
Fatores Imunológicos/farmacologia
Macaca mulatta
Macrófagos/imunologia
Mitoguazona/farmacologia
Placebos/administração & dosagem
Resultado do Tratamento
Túnica Íntima/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Immunologic Factors); 0 (Placebos); OD5Q0L447W (Mitoguazone)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170606
[Lr] Data última revisão:
170606
[Sb] Subgrupo de revista:IM; X
[Da] Data de entrada para processamento:170201
[St] Status:MEDLINE
[do] DOI:10.1097/QAI.0000000000001297


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[PMID]:27780273
[Au] Autor:Zhang W; Cao Z; Zhou Q; Chen J; Xu G; Gu J; Liu L; Wang Z; Yang J; Zhang H
[Ad] Endereço:Jiangsu Key Laboratory of Crop Genetics and Physiology, Co-Innovation Center for Modern Production Technology of Grain Crops, Yangzhou University, Yangzhou, China.
[Ti] Título:Grain Filling Characteristics and Their Relations with Endogenous Hormones in Large- and Small-Grain Mutants of Rice.
[So] Source:PLoS One;11(10):e0165321, 2016.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:This study determined if the variation in grain filling parameters between two different spikelet types of rice (Oryza sativa L.) is regulated by the hormonal levels in the grains. Two rice mutants, namely, a large-grain mutant (AZU-M) and a small-grain mutant (ZF802-M), and their respective wild types (AZU-WT and ZF802-WT) were grown in the field. The endosperm cell division rate, filling rate, and hormonal levels: zeatin + zeatin riboside (Z+ZR), indo-3-acetic acid (IAA), polyamines (PAs), and abscisic acid (ABA) were determined. The results showed that there was no significant difference between the filling and endosperm cell division rates. These rates were synchronous between the superior and inferior spikelets for both mutants. However, the abovementioned parameters were significantly different between the two spikelet types for the two wild types. The superior spikelets filled faster and their filling rate was higher compared to the inferior ones. Changes in the concentrations of plant hormones were consistent with the observed endosperm cell division rate and the filling rate for both types of spikelets of mutant and wild type plants. Regression analysis showed a significant positive correlation between cell division and filling rates with the concentrations of the investigated hormones. Exogenous chemical application verified the role of ABA, IAA, and PAs in grain filling. The results indicate that poor filling of inferior spikelets in rice occurs primarily due to the reduced hormone concentrations therein, leading to lower division rate of endosperm cells, fewer endosperm cells, slower filling rate, and smaller grain weight.
[Mh] Termos MeSH primário: Oryza/metabolismo
Reguladores de Crescimento de Planta/análise
[Mh] Termos MeSH secundário: Ácido Abscísico/análise
Ácido Abscísico/isolamento & purificação
Grãos Comestíveis/crescimento & desenvolvimento
Grãos Comestíveis/metabolismo
Endosperma/efeitos dos fármacos
Endosperma/metabolismo
Ensaio de Imunoadsorção Enzimática
Mitoguazona/farmacologia
Oryza/crescimento & desenvolvimento
Reguladores de Crescimento de Planta/isolamento & purificação
Plantas Geneticamente Modificadas/crescimento & desenvolvimento
Plantas Geneticamente Modificadas/metabolismo
Poliaminas/análise
Poliaminas/isolamento & purificação
Putrescina/farmacologia
Espermidina/farmacologia
Zeatina/análise
Zeatina/isolamento & purificação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Plant Growth Regulators); 0 (Polyamines); 72S9A8J5GW (Abscisic Acid); 7I6OOJ9GR6 (Zeatin); OD5Q0L447W (Mitoguazone); U87FK77H25 (Spermidine); V10TVZ52E4 (Putrescine)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170614
[Lr] Data última revisão:
170614
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161026
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0165321


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[PMID]:26633377
[Au] Autor:Choi J; Jee JG
[Ad] Endereço:Research Institute of Pharmaceutical Sciences, College of Pharmacy, Kyungpook National University, 80 Daehak-ro, Buk-gu, Daegu 702-701, Korea. crowz124@naver.com.
[Ti] Título:Repositioning of Thiourea-Containing Drugs as Tyrosinase Inhibitors.
[So] Source:Int J Mol Sci;16(12):28534-48, 2015 Dec 02.
[Is] ISSN:1422-0067
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Tyrosinase catalyzes two distinct sequential reactions in melanin biosynthesis: The hydroxylation of tyrosine to dihydroxyphenylalanine (DOPA) and the oxidation of DOPA to dopaquinone. Developing functional modulators of tyrosinase is important for therapeutic and cosmetic purposes. Given the abundance of thiourea moiety in known tyrosinase inhibitors, we studied other thiourea-containing drugs as potential tyrosinase inhibitors. The thiourea-containing drugs in clinical use were retrieved and tested for their ability to inhibit tyrosinase. We observed that methimazole, thiouracil, methylthiouracil, propylthiouracil, ambazone, and thioacetazone inhibited mushroom tyrosinase. Except for methimazole, there was limited information regarding the activity of other drugs against tyrosinase. Both thioacetazone and ambazone significantly inhibited tyrosinase, with IC50 of 14 and 15 µM, respectively. Ambazone decreased melanin content without causing cellular toxicity at 20 µM in B16F10 cells. The activity of ambazone was stronger than that of kojic acid both in enzyme and melanin content assays. Kinetics of enzyme inhibition assigned the thiourea-containg drugs as non-competitive inhibitors. The complex models by docking simulation suggested that the intermolecular hydrogen bond via the nitrogen of thiourea and the contacts via thione were equally important for interacting with tyrosinase. These data were consistent with the results of enzyme assays with the analogues of thiourea.
[Mh] Termos MeSH primário: Reposicionamento de Medicamentos
Inibidores Enzimáticos/química
Inibidores Enzimáticos/farmacologia
Monofenol Mono-Oxigenase/antagonistas & inibidores
Tioureia/química
[Mh] Termos MeSH secundário: Animais
Linhagem Celular Tumoral
Sobrevivência Celular/efeitos dos fármacos
Relação Dose-Resposta a Droga
Seres Humanos
Cinética
Melaninas/metabolismo
Melanoma Experimental
Camundongos
Mitoguazona/análogos & derivados
Mitoguazona/farmacologia
Modelos Moleculares
Conformação Molecular
Monofenol Mono-Oxigenase/química
Ligação Proteica
Tioureia/análogos & derivados
Tioureia/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Enzyme Inhibitors); 0 (Melanins); BYK4592A3Q (1,4-benzoquinone guanylhydrazone thiosemicarbazone); EC 1.14.18.1 (Monophenol Monooxygenase); GYV9AM2QAG (Thiourea); OD5Q0L447W (Mitoguazone)
[Em] Mês de entrada:1609
[Cu] Atualização por classe:160107
[Lr] Data última revisão:
160107
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151204
[St] Status:MEDLINE
[do] DOI:10.3390/ijms161226114


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[PMID]:26223636
[Au] Autor:Jin X; McGrath MS; Xu H
[Ad] Endereço:Pathologica LLC, Burlingame, California, USA.
[Ti] Título:Inhibition of HIV Expression and Integration in Macrophages by Methylglyoxal-Bis-Guanylhydrazone.
[So] Source:J Virol;89(22):11176-89, 2015 Nov.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:UNLABELLED: Macrophages are a target for infection with HIV and represent one of the viral reservoirs that are relatively resistant to current antiretroviral drugs. Here we demonstrate that methylglyoxal-bis-guanylhydrazone (MGBG), a polyamine analog and potent S-adenosylmethionine decarboxylase inhibitor, decreases HIV expression in monocytes and macrophages. MGBG is selectively concentrated by these cells through a mechanism consistent with active transport by the polyamine transporter. Using a macrophage-tropic reporter virus tagged with the enhanced green fluorescent protein, we demonstrate that MGBG decreases the frequency of HIV-infected cells. The effect is dose dependent and correlates with the production of HIV p24 in culture supernatants. This anti-HIV effect was further confirmed using three macrophage-tropic primary HIV isolates. Viral life cycle mapping studies show that MGBG inhibits HIV DNA integration into the cellular DNA in both monocytes and macrophages. IMPORTANCE: Our work demonstrates for the first time the selective concentration of MGBG by monocytes/macrophages, leading to the inhibition of HIV-1 expression and a reduction in proviral load within macrophage cultures. These results suggest that MGBG may be useful in adjunctive macrophage-targeted therapy for HIV infection.
[Mh] Termos MeSH primário: Adenosilmetionina Descarboxilase/antagonistas & inibidores
Antirretrovirais/farmacologia
HIV-1/efeitos dos fármacos
Macrófagos/virologia
Mitoguazona/farmacologia
Monócitos/virologia
Integração Viral/efeitos dos fármacos
Replicação Viral/efeitos dos fármacos
[Mh] Termos MeSH secundário: Transporte Biológico Ativo
Antígenos CD4/biossíntese
Células Cultivadas
Proteínas de Fluorescência Verde/genética
Proteína do Núcleo p24 do HIV/biossíntese
Infecções por HIV/tratamento farmacológico
HIV-1/genética
HIV-1/crescimento & desenvolvimento
Seres Humanos
Receptores de Lipopolissacarídeos/metabolismo
Receptores CCR5/biossíntese
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Anti-Retroviral Agents); 0 (CCR5 protein, human); 0 (CD4 Antigens); 0 (HIV Core Protein p24); 0 (Lipopolysaccharide Receptors); 0 (Receptors, CCR5); 0 (enhanced green fluorescent protein); 147336-22-9 (Green Fluorescent Proteins); EC 4.1.1.50 (Adenosylmethionine Decarboxylase); OD5Q0L447W (Mitoguazone)
[Em] Mês de entrada:1601
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150731
[St] Status:MEDLINE
[do] DOI:10.1128/JVI.01692-15


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[PMID]:25187325
[Au] Autor:Muresan-Pop M; Braga D; Pop MM; Borodi G; Kacso I; Maini L
[Ad] Endereço:National Institute for Research and Development of Isotopic and Molecular Technologies, Cluj-Napoca R-400293, Romania.
[Ti] Título:Crystal structure and physicochemical characterization of ambazone monohydrate, anhydrous, and acetate salt solvate.
[So] Source:J Pharm Sci;103(11):3594-3601, 2014 Nov.
[Is] ISSN:1520-6017
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The crystal structures of the monohydrate and anhydrous forms of ambazone were determined by single-crystal X-ray diffraction (SC-XRD). Ambazone monohydrate is characterized by an infinite three-dimensional network involving the water molecules, whereas anhydrous ambazone forms a two-dimensional network via hydrogen bonds. The reversible transformation between the monohydrate and anhydrous forms of ambazone was evidenced by thermal analysis, temperature-dependent X-ray powder diffraction and accelerated stability at elevated temperature, and relative humidity (RH). Additionally, a novel ambazone acetate salt solvate form was obtained and its nature was elucidated by SC-XRD. Powder dissolution measurements revealed a substantial solubility and dissolution rate improvement of acetate salt solvated form in water and physiological media compared with ambazone forms. Also, the acetate salt solvate displayed good thermal and solution stability but it transformed to the monohydrate on storage at elevated temperature and RH. Our study shows that despite the requirement for controlled storage conditions, the acetate salt solvated form could be an alternative to ambazone when solubility and bioavailability improvement is critical for the clinical efficacy of the drug product.
[Mh] Termos MeSH primário: Acetatos/química
Mitoguazona/análogos & derivados
[Mh] Termos MeSH secundário: Química Farmacêutica
Cristalização
Cristalografia por Raios X
Estabilidade de Medicamentos
Umidade
Ligações de Hidrogênio
Cinética
Mitoguazona/química
Modelos Moleculares
Estrutura Molecular
Difração de Pó
Pós
Solubilidade
Tecnologia Farmacêutica/métodos
Temperatura Ambiente
Água/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Acetates); 0 (Powders); 059QF0KO0R (Water); BYK4592A3Q (1,4-benzoquinone guanylhydrazone thiosemicarbazone); OD5Q0L447W (Mitoguazone)
[Em] Mês de entrada:1506
[Cu] Atualização por classe:170917
[Lr] Data última revisão:
170917
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140905
[St] Status:MEDLINE


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[PMID]:24877669
[Au] Autor:Ikbal FE; Hernández JA; Barba-Espín G; Koussa T; Aziz A; Faize M; Diaz-Vivancos P
[Ad] Endereço:Laboratoire Biotechnologies Végétales, Ecologie et Valorisation des Ecosystèmes, Faculté des Sciences, Université Chouaib Doukkali, 24000 El Jadida, Morocco.
[Ti] Título:Enhanced salt-induced antioxidative responses involve a contribution of polyamine biosynthesis in grapevine plants.
[So] Source:J Plant Physiol;171(10):779-88, 2014 Jun 15.
[Is] ISSN:1618-1328
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:The possible involvement of polyamines in the salt stress adaptation was investigated in grapevine (Vitis vinifera L.) plantlets focusing on photosynthesis and oxidative metabolism. Salt stress resulted in the deterioration of plant growth and photosynthesis, and treatment of plantlets with methylglyoxal-bis(guanylhydrazone) (MGBG), a S-adenosylmethionine decarboxylase (SAMDC) inhibitor, enhanced the salt stress effect. A decrease in PSII quantum yield (Fv/Fm), effective PSII quantum yield (Y(II)) and coefficient of photochemical quenching (qP) as well as increases in non-photochemical quenching (NPQ) and its coefficient (qN) was observed by these treatments. Salt and/or MGBG treatments also triggered an increase in lipid peroxidation and reactive oxygen species (ROS) accumulation as well as an increase of superoxide dismutase (SOD) and peroxidase (POX) activities, but not ascorbate peroxidase (APX) activity. Salt stress also resulted in an accumulation of oxidized ascorbate (DHA) and a decrease in reduced glutathione. MGBG alone or in combination with salt stress increased monodehydroascorbate reductase (MDHAR), SOD and POX activities and surprisingly no accumulation of DHA was noticed following treatment with MGBG. These salt-induced responses correlated with the maintaining of high level of free and conjugated spermidine and spermine, whereas a reduction of agmatine and putrescine levels was observed, which seemed to be amplified by the MGBG treatment. These results suggest that maintaining polyamine biosynthesis through the enhanced SAMDC activity in grapevine leaf tissues under salt stress conditions could contribute to the enhanced ROS scavenging activity and a protection of photosynthetic apparatus from oxidative damages.
[Mh] Termos MeSH primário: Adenosilmetionina Descarboxilase/metabolismo
Antioxidantes/metabolismo
Fotossíntese/fisiologia
Poliaminas/metabolismo
Estresse Fisiológico
Vitis/fisiologia
[Mh] Termos MeSH secundário: Ácido Ascórbico/metabolismo
Clorofila/metabolismo
Glutationa/metabolismo
Peroxidação de Lipídeos/efeitos dos fármacos
Mitoguazona/farmacologia
Estresse Oxidativo
Reguladores de Crescimento de Planta/metabolismo
Proteínas de Plantas/metabolismo
Poliaminas/análise
Poliaminas/isolamento & purificação
Espécies Reativas de Oxigênio/metabolismo
Cloreto de Sódio/farmacologia
Vitis/efeitos dos fármacos
Vitis/enzimologia
Vitis/crescimento & desenvolvimento
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antioxidants); 0 (Plant Growth Regulators); 0 (Plant Proteins); 0 (Polyamines); 0 (Reactive Oxygen Species); 1406-65-1 (Chlorophyll); 451W47IQ8X (Sodium Chloride); EC 4.1.1.50 (Adenosylmethionine Decarboxylase); GAN16C9B8O (Glutathione); OD5Q0L447W (Mitoguazone); PQ6CK8PD0R (Ascorbic Acid)
[Em] Mês de entrada:1501
[Cu] Atualização por classe:151119
[Lr] Data última revisão:
151119
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140601
[St] Status:MEDLINE


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[PMID]:24589373
[Au] Autor:Gong B; Li X; Bloszies S; Wen D; Sun S; Wei M; Li Y; Yang F; Shi Q; Wang X
[Ad] Endereço:State Key Laboratory of Crop Biology, Huang-Huai-Hai Region Scientific Observation and Experimental Station of Environment-Controlled Agricultural Engineering, Ministry of Agriculture, People's Republic of China, College of Horticulture Science and Engineering, Shandong Agricultural University, Taia
[Ti] Título:Sodic alkaline stress mitigation by interaction of nitric oxide and polyamines involves antioxidants and physiological strategies in Solanum lycopersicum.
[So] Source:Free Radic Biol Med;71:36-48, 2014 Jun.
[Is] ISSN:1873-4596
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Nitric oxide (NO) and polyamines (PAs) are two kinds of important signal in mediating plant tolerance to abiotic stress. In this study, we observed that both NO and PAs decreased alkaline stress in tomato plants, which may be a result of their role in regulating nutrient balance and reactive oxygen species (ROS), thereby protecting the photosynthetic system from damage. Further investigation indicated that NO and PAs induced accumulation of each other. Furthermore, the function of PAs could be removed by a NO scavenger, cPTIO. On the other hand, application of MGBG, a PA synthesis inhibitor, did little to abolish the function of NO. To further elucidate the mechanism by which NO and PAs alleviate alkaline stress, the expression of several genes associated with abiotic stress was analyzed by qRT-PCR. NO and PAs significantly upregulated ion transporters such as the plasma membrane Na(+)/H(+) antiporter (SlSOS1), vacuolar Na(+)/H(+) exchanger (SlNHX1 and SlNHX2), and Na(+) transporter and signal components including ROS, MAPK, and Ca(2+) signal pathways, as well as several transcription factors. All of these play important roles in plant adaptation to stress conditions.
[Mh] Termos MeSH primário: Antioxidantes/metabolismo
Lycopersicon esculentum/metabolismo
Óxido Nítrico/metabolismo
Raízes de Plantas/metabolismo
Poliaminas/metabolismo
Hidróxido de Sódio/farmacologia
[Mh] Termos MeSH secundário: Adaptação Fisiológica
Benzoatos/farmacologia
Transporte Biológico
Cálcio/metabolismo
Regulação da Expressão Gênica de Plantas
Hidroponia
Imidazóis/farmacologia
Lycopersicon esculentum/efeitos dos fármacos
Lycopersicon esculentum/genética
Proteínas Quinases Ativadas por Mitógeno/genética
Proteínas Quinases Ativadas por Mitógeno/metabolismo
Mitoguazona/farmacologia
Óxido Nítrico/antagonistas & inibidores
Raízes de Plantas/efeitos dos fármacos
Raízes de Plantas/genética
Poliaminas/antagonistas & inibidores
Espécies Reativas de Oxigênio/antagonistas & inibidores
Espécies Reativas de Oxigênio/metabolismo
Plântulas/efeitos dos fármacos
Plântulas/genética
Plântulas/metabolismo
Transdução de Sinais
Trocadores de Sódio-Hidrogênio/genética
Trocadores de Sódio-Hidrogênio/metabolismo
Estresse Fisiológico
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antioxidants); 0 (Benzoates); 0 (Imidazoles); 0 (Polyamines); 0 (Reactive Oxygen Species); 0 (Sodium-Hydrogen Exchangers); 145757-47-7 (1,3-dihydroxy-4,4,5,5-tetramethyl-2-(4-carboxyphenyl)tetrahydroimidazole); 31C4KY9ESH (Nitric Oxide); 55X04QC32I (Sodium Hydroxide); EC 2.7.11.24 (Mitogen-Activated Protein Kinases); OD5Q0L447W (Mitoguazone); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1501
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140305
[St] Status:MEDLINE


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[PMID]:23795469
[Au] Autor:Lisitskaia KV; Sokueva NA; Malysheva IuG; Ivanov AV; Shishkin SS; Siatkin SP
[Ti] Título:[Identification of the functional activity of synthetic polyamine analogues using a biotest system based on highly proliferating cultured human cells].
[So] Source:Prikl Biokhim Mikrobiol;49(2):124-8, 2013 Mar-Apr.
[Is] ISSN:0555-1099
[Cp] País de publicação:Russia (Federation)
[La] Idioma:rus
[Ab] Resumo:A new biotest system was developed based on highly proliferating human cell cultures (lines LNCaP and PC-3). With the help of this system, two known synthetic polyamines--alpha-difluoromethylornithine (DFMO) and methylglioxalbis(guanylhydrason) (MGBG)--as well as four new synthetic analogues difenyl containing amines (DFCA-1-DFCA-4) with molecular weights of 725.5 (DFCA-1), 755.5 (DFCA-2), 655.5 (DFCA-3), and 681.5 Da (DFCA-4) were tested. In this biotest system, DFMO (0.1-400 microM) did not reveal functional activity, whereas for MGBG a cytotoxic effect was registered (100-200 microM). DFCA-1, DFCA-2, and DFCA-4 had a similar effect at concentrations of 10 microM and higher; DFCA-3, at a concentration of 50 microM and higher. Thus, DFCA-1 has a higher level of antiproliferating activity and may be considered as the most potent cytostatic agent.
[Mh] Termos MeSH primário: Compostos de Bifenilo/farmacologia
Citostáticos/farmacologia
Eflornitina/farmacologia
Mitoguazona/farmacologia
Poliaminas/farmacologia
[Mh] Termos MeSH secundário: Bioensaio
Compostos de Bifenilo/síntese química
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Citostáticos/síntese química
Eflornitina/síntese química
Seres Humanos
Masculino
Mitoguazona/síntese química
Poliaminas/síntese química
Relação Estrutura-Atividade
[Pt] Tipo de publicação:ENGLISH ABSTRACT; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Biphenyl Compounds); 0 (Cytostatic Agents); 0 (Polyamines); OD5Q0L447W (Mitoguazone); ZQN1G5V6SR (Eflornithine)
[Em] Mês de entrada:1307
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:130626
[St] Status:MEDLINE


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[PMID]:23500523
[Au] Autor:Yamashita T; Nishimura K; Saiki R; Okudaira H; Tome M; Higashi K; Nakamura M; Terui Y; Fujiwara K; Kashiwagi K; Igarashi K
[Ad] Endereço:Graduate School of Pharmaceutical Sciences, Chiba University, Chuo-ku, Chiba, Japan.
[Ti] Título:Role of polyamines at the G1/S boundary and G2/M phase of the cell cycle.
[So] Source:Int J Biochem Cell Biol;45(6):1042-50, 2013 Jun.
[Is] ISSN:1878-5875
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The role of polyamines at the G1/S boundary and in the G2/M phase of the cell cycle was studied using synchronized HeLa cells treated with thymidine or with thymidine and aphidicolin. Synchronized cells were cultured in the absence or presence of α-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase, plus ethylglyoxal bis(guanylhydrazone) (EGBG), an inhibitor of S-adenosylmethionine decarboxylase. When polyamine content was reduced by treatment with DFMO and EGBG, the transition from G1 to S phase was delayed. In parallel, the level of p27(Kip1) was greatly increased, so its mechanism was studied in detail. Synthesis of p27(Kip1) was stimulated at the level of translation by a decrease in polyamine levels, because of the existence of long 5'-untranslated region (5'-UTR) in p27(Kip1) mRNA. Similarly, the transition from the G2/M to the G1 phase was delayed by a reduction in polyamine levels. In parallel, the number of multinucleate cells increased by 3-fold. This was parallel with the inhibition of cytokinesis due to an unusual distribution of actin and α-tubulin at the M phase. Since an association of polyamines with chromosomes was not observed by immunofluorescence microscopy at the M phase, polyamines may have only a minor role in structural changes of chromosomes at the M phase. In general, the involvement of polyamines at the G2/M phase was smaller than that at the G1/S boundary.
[Mh] Termos MeSH primário: Poliaminas Biogênicas/metabolismo
Divisão Celular/fisiologia
Fase G1/fisiologia
Fase G2/fisiologia
Fase S/fisiologia
[Mh] Termos MeSH secundário: Adenosilmetionina Descarboxilase/antagonistas & inibidores
Adenosilmetionina Descarboxilase/metabolismo
Divisão Celular/efeitos dos fármacos
Inibidor de Quinase Dependente de Ciclina p27/metabolismo
Eflornitina/farmacologia
Inibidores Enzimáticos/farmacologia
Fase G1/efeitos dos fármacos
Fase G2/efeitos dos fármacos
Células HeLa
Seres Humanos
Mitoguazona/análogos & derivados
Mitoguazona/farmacologia
Ornitina Descarboxilase/metabolismo
Inibidores da Ornitina Descarboxilase
Fase S/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Biogenic Polyamines); 0 (CDKN1B protein, human); 0 (Enzyme Inhibitors); 0 (Ornithine Decarboxylase Inhibitors); 147604-94-2 (Cyclin-Dependent Kinase Inhibitor p27); 1945-68-2 (ethylglyoxal bis(guanylhydrazone)); EC 4.1.1.17 (Ornithine Decarboxylase); EC 4.1.1.50 (Adenosylmethionine Decarboxylase); OD5Q0L447W (Mitoguazone); ZQN1G5V6SR (Eflornithine)
[Em] Mês de entrada:1311
[Cu] Atualização por classe:141120
[Lr] Data última revisão:
141120
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:130319
[St] Status:MEDLINE


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[PMID]:23144800
[Au] Autor:Wang SY; Lee AY; Lee YL; Lai YH; Chen JJ; Wu WL; Yuann JM; Su WL; Chuang SM; Hou MH
[Ad] Endereço:Department of Life Science, National Chung Hsing University, Taichung, Taiwan.
[Ti] Título:Spermine attenuates the action of the DNA intercalator, actinomycin D, on DNA binding and the inhibition of transcription and DNA replication.
[So] Source:PLoS One;7(11):e47101, 2012.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The anticancer activity of DNA intercalators is related to their ability to intercalate into the DNA duplex with high affinity, thereby interfering with DNA replication and transcription. Polyamines (spermine in particular) are almost exclusively bound to nucleic acids and are involved in many cellular processes that require nucleic acids. Until now, the effects of polyamines on DNA intercalator activities have remained unclear because intercalation is the most important mechanism employed by DNA-binding drugs. Herein, using actinomycin D (ACTD) as a model, we have attempted to elucidate the effects of spermine on the action of ACTD, including its DNA-binding ability, RNA and DNA polymerase interference, and its role in the transcription and replication inhibition of ACTD within cells. We found that spermine interfered with the binding and stabilization of ACTD to DNA. The presence of increasing concentrations of spermine enhanced the transcriptional and replication activities of RNA and DNA polymerases, respectively, in vitro treated with ActD. Moreover, a decrease in intracellular polyamine concentrations stimulated by methylglyoxal-bis(guanylhydrazone) (MGBG) enhanced the ACTD-induced inhibition of c-myc transcription and DNA replication in several cancer cell lines. The results indicated that spermine attenuates ACTD binding to DNA and its inhibition of transcription and DNA replication both in vitro and within cells. Finally, a synergistic antiproliferative effect of MGBG and ACTD was observed in a cell viability assay. Our findings will be of significant relevance to future developments in combination with cancer therapy by enhancing the anticancer activity of DNA interactors through polyamine depletion.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Replicação do DNA/efeitos dos fármacos
DNA/metabolismo
Dactinomicina/farmacologia
Substâncias Intercalantes/farmacologia
Espermina/metabolismo
[Mh] Termos MeSH secundário: Bacteriófago T7/enzimologia
Linhagem Celular Tumoral
DNA Polimerase I/metabolismo
RNA Polimerases Dirigidas por DNA/metabolismo
Escherichia coli/enzimologia
Seres Humanos
Mitoguazona/farmacologia
Modelos Moleculares
Neoplasias/tratamento farmacológico
Neoplasias/metabolismo
Espermina/antagonistas & inibidores
Transcrição Genética/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Intercalating Agents); 1CC1JFE158 (Dactinomycin); 2FZ7Y3VOQX (Spermine); 9007-49-2 (DNA); EC 2.7.7.- (DNA Polymerase I); EC 2.7.7.6 (DNA-Directed RNA Polymerases); OD5Q0L447W (Mitoguazone)
[Em] Mês de entrada:1304
[Cu] Atualização por classe:150222
[Lr] Data última revisão:
150222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:121113
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0047101



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