Base de dados : MEDLINE
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Referências encontradas : 736 [refinar]
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[PMID]:28463568
[Au] Autor:Salinas G; Gao W; Wang Y; Bonilla M; Yu L; Novikov A; Virginio VG; Ferreira HB; Vieites M; Gladyshev VN; Gambino D; Dai S
[Ad] Endereço:1 Worm Biology Lab, Institut Pasteur de Montevideo , Montevideo, Uruguay .
[Ti] Título:The Enzymatic and Structural Basis for Inhibition of Echinococcus granulosus Thioredoxin Glutathione Reductase by Gold(I).
[So] Source:Antioxid Redox Signal;27(18):1491-1504, 2017 Dec 20.
[Is] ISSN:1557-7716
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:AIMS: New drugs are needed to treat flatworm infections that cause severe human diseases such as schistosomiasis. The unique flatworm enzyme thioredoxin glutathione reductase (TGR), structurally different from the human enzyme, is a key drug target. Structural studies of the flatworm Echinococcus granulosus TGR, free and complexed with Au -MPO, a novel gold inhibitor, together with inhibition assays were performed. RESULTS: Au -MPO is a potent TGR inhibitor that achieves 75% inhibition at a 1:1 TGR:Au ratio and efficiently kills E. granulosus in vitro. The structures revealed salient insights: (i) unique monomer-monomer interactions, (ii) distinct binding sites for thioredoxin and the glutaredoxin (Grx) domain, (iii) a single glutathione disulfide reduction site in the Grx domain, (iv) rotation of the Grx domain toward the Sec-containing redox active site, and (v) a single gold atom bound to Cys and Cys in the Au -TGR complex. Structural modeling suggests that these residues are involved in the stabilization of the Sec-containing C-terminus. Consistently, Cys→Ser mutations in these residues decreased TGR activities. Mass spectroscopy confirmed these cysteines are the primary binding site. INNOVATION: The identification of a primary site for gold binding and the structural model provide a basis for gold compound optimization through scaffold adjustments. CONCLUSIONS: The structural study revealed that TGR functions are achieved not only through a mobile Sec-containing redox center but also by rotation of the Grx domain and distinct binding sites for Grx domain and thioredoxin. The conserved Cys and Cys residues targeted by gold assist catalysis through stabilization of the Sec-containing redox center. Antioxid. Redox Signal. 27, 1491-1504.
[Mh] Termos MeSH primário: Echinococcus granulosus/enzimologia
Complexos Multienzimáticos/química
Complexos Multienzimáticos/metabolismo
NADH NADPH Oxirredutases/química
NADH NADPH Oxirredutases/metabolismo
Compostos Organoáuricos/farmacologia
[Mh] Termos MeSH secundário: Animais
Sítios de Ligação/efeitos dos fármacos
Cisteína/metabolismo
Echinococcus granulosus/química
Echinococcus granulosus/genética
Inibidores Enzimáticos/química
Inibidores Enzimáticos/farmacocinética
Glutarredoxinas/metabolismo
Proteínas de Helminto/química
Proteínas de Helminto/genética
Proteínas de Helminto/metabolismo
Modelos Moleculares
Complexos Multienzimáticos/genética
Mutação
NADH NADPH Oxirredutases/genética
Compostos Organoáuricos/química
Ligação Proteica
Conformação Proteica
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Enzyme Inhibitors); 0 (Glutaredoxins); 0 (Helminth Proteins); 0 (Multienzyme Complexes); 0 (Organogold Compounds); EC 1.6.- (NADH, NADPH Oxidoreductases); EC 1.6.4.- (thioredoxin glutathione reductase); K848JZ4886 (Cysteine)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.1089/ars.2016.6816


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[PMID]:29331752
[Au] Autor:Reddy TS; Privér SH; Mirzadeh N; Bhargava SK
[Ad] Endereço:Centre for Advanced Materials & Industrial Chemistry (CAMIC), School of Science, RMIT University, GPO BOX 2476, Melbourne 3001, Australia.
[Ti] Título:Synthesis of gold(I) phosphine complexes containing the 2-BrC F PPh ligand: Evaluation of anticancer activity in 2D and 3D spheroidal models of HeLa cancer cells.
[So] Source:Eur J Med Chem;145:291-301, 2018 Feb 10.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Newly synthesised mononuclear gold complexes containing the 2-BrC F PPh ligand have been fully characterised and their anticancer activity towards five human tumor [prostate (PC3), glioblastoma (U87MG), cervical (HeLa), fibrosarcoma (HT1080), ovarian (SKOV-3)] and normal human embryonic kidney (Hek-293T) cell lines investigated. Some of the synthesised gold complexes displayed higher cytotoxicity than cisplatin towards PC-3, HeLa and U87MG cells and inhibited the thioredoxin reductase (TrxR) enzyme, which is considered a potential target for new compounds in cancer treatment. The more physiologically relevant tumor spheroid assay demonstrated the superior potency of these gold phosphine complexes in inhibiting the growth of cervical carcinoma cell line HeLa (3D) spheroidal models. The mechanism of cell death was shown to be apoptotic cell death through cell cycle arrest, mitochondrial membrane depolarisation and increased ROS production.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Modelos Biológicos
Compostos Organoáuricos/farmacologia
Fosfinas/farmacologia
[Mh] Termos MeSH secundário: Antineoplásicos/síntese química
Antineoplásicos/química
Morte Celular/efeitos dos fármacos
Proliferação Celular/efeitos dos fármacos
Células Cultivadas
Cristalografia por Raios X
Relação Dose-Resposta a Droga
Ensaios de Seleção de Medicamentos Antitumorais
Células HeLa
Seres Humanos
Ligantes
Modelos Moleculares
Estrutura Molecular
Compostos Organoáuricos/síntese química
Compostos Organoáuricos/química
Fosfinas/química
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (2-BrC6F4PPh2); 0 (Antineoplastic Agents); 0 (Ligands); 0 (Organogold Compounds); 0 (Phosphines); FW6947296I (phosphine)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180115
[St] Status:MEDLINE


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[PMID]:28823538
[Au] Autor:Jürgens S; Scalcon V; Estrada-Ortiz N; Folda A; Tonolo F; Jandl C; Browne DL; Rigobello MP; Kühn FE; Casini A
[Ad] Endereço:Molecular Catalysis, Catalysis Research Centre and Department of Chemistry, Technische Universität München, Lichtenbergstr. 4, 85747 Garching bei München, Germany; School of Chemistry, Cardiff University, Park Place, Cardiff CF10 3AT, United Kingdom.
[Ti] Título:Exploring the C
[So] Source:Bioorg Med Chem;25(20):5452-5460, 2017 Oct 15.
[Is] ISSN:1464-3391
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:A family of cyclometalated Au(III) complexes featuring a tridentate C^N^C scaffold has been synthesized and characterized. Microwave assisted synthesis of the ligands has also been exploited and optimized. The biological properties of the thus formed compounds have been studied in cancer cells and demonstrate generally moderate antiproliferative effects. Initial mechanistic insights have also been gained on the gold complex [Au(C^N^C)(GluS)] (3), and support the idea that the thioredoxin system may be a target for this family of compounds together with other relevant intracellular thiol-containing molecules.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Inibidores Enzimáticos/farmacologia
Compostos Organoáuricos/farmacologia
[Mh] Termos MeSH secundário: Antineoplásicos/síntese química
Antineoplásicos/química
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Relação Dose-Resposta a Droga
Ensaios de Seleção de Medicamentos Antitumorais
Inibidores Enzimáticos/síntese química
Inibidores Enzimáticos/química
Seres Humanos
Estrutura Molecular
Compostos Organoáuricos/síntese química
Compostos Organoáuricos/química
Oxirredução
Relação Estrutura-Atividade
Tiorredoxina Dissulfeto Redutase/antagonistas & inibidores
Tiorredoxina Dissulfeto Redutase/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Enzyme Inhibitors); 0 (Organogold Compounds); EC 1.8.1.9 (Thioredoxin-Disulfide Reductase)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171108
[Lr] Data última revisão:
171108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170822
[St] Status:MEDLINE


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[PMID]:28260677
[Au] Autor:Pintus A; Aragoni MC; Cinellu MA; Maiore L; Isaia F; Lippolis V; Orrù G; Tuveri E; Zucca A; Arca M
[Ad] Endereço:Dipartimento di Scienze Chimiche e Geologiche, Università degli Studi di Cagliari, S.S. 554 bivio per Sestu, 09042 Monserrato, Cagliari, Italy.
[Ti] Título:[Au(py -H)(mnt)]: A novel gold(III) 1,2-dithiolene cyclometalated complex with antimicrobial activity (py -H=C-deprotonated 2-benzylpyridine; mnt=1,2-dicyanoethene-1,2-dithiolate).
[So] Source:J Inorg Biochem;170:188-194, 2017 May.
[Is] ISSN:1873-3344
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The novel heteroleptic cyclometalated complex [Au (py -H)(mnt)] (1; py -H=C-deprotonated 2-benzylpyridine; mnt =1,2-dicyanoethene-1,2-dithiolate) was tested against a panel of ten Gram positive (belonging to the Staphylococcus, Streptococcus spp. and Bacillus clausii), Gram negative (E. coli, K. pneumoniae, P. aeruginosa) bacteria and three yeasts belonging to the Candida spp. Complex 1 showed a remarkable bacteriostatic antimicrobial activity against staphylococci, with Minimum Inhibitory Concentration (MIC) values of 1.56 and 3.13µg/mL for S. haemoliticus and S. aureus, respectively. Spectroscopic and electrochemical measurements, supported by Density Functional Theory (DFT) calculations, were exploited to fully investigate the electronic structure of complex 1 and its relationship with the antimicrobial activity.
[Mh] Termos MeSH primário: Anti-Infecciosos
Bactérias/crescimento & desenvolvimento
Candida/crescimento & desenvolvimento
Compostos Organoáuricos
[Mh] Termos MeSH secundário: Anti-Infecciosos/síntese química
Anti-Infecciosos/química
Anti-Infecciosos/farmacologia
Compostos Organoáuricos/síntese química
Compostos Organoáuricos/química
Compostos Organoáuricos/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Infective Agents); 0 (Organogold Compounds)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170918
[Lr] Data última revisão:
170918
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170307
[St] Status:MEDLINE


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[PMID]:27865929
[Au] Autor:Ooi KK; Yeo CI; Mahandaran T; Ang KP; Akim AM; Cheah YK; Seng HL; Tiekink ERT
[Ad] Endereço:Department of Biomedical Science, Faculty of Medicine and Health Sciences, University Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia; Research Centre for Crystalline Materials, Faculty of Science and Technology, Sunway University, 47500 Bandar Sunway, Selangor Darul Ehsan, Malaysia.
[Ti] Título:G /M cell cycle arrest on HT-29 cancer cells and toxicity assessment of triphenylphosphanegold(I) carbonimidothioates, Ph PAu[SC(OR)=NPh], R=Me, Et, and iPr, during zebrafish development.
[So] Source:J Inorg Biochem;166:173-181, 2017 Jan.
[Is] ISSN:1873-3344
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Phosphanegold(I) thiolates, Ph PAu[SC(OR)=NPh], R=Me (1), Et (2) and iPr (3), were previously shown to be significantly cytotoxic toward HT-29 cancer cells and to induce cell death by both intrinsic and extrinsic apoptotic pathways whereby 1 activated the p73 gene, and each of 2 and 3 activated p53; 2 also caused apoptotic cell death via the c-Jun N-terminal kinase/mitogen-activated protein kinase pathway. Apoptosis pathways have been further evaluated by mitochondrial cytochrome c measurements and annexin V screening, confirming apoptotic pathways of cell death. Cell cycle analysis showed the majority of treated HT-29 cells were arrested at the G /M checkpoint after 24h; results of both assays were confirmed by changes in populations of relevant genes (PCR array analysis). Cell invasion studies showed inhibition of metastasis through Matrigel™ matrix to 17-22% cf. untreated cells. LC values were determined in zebrafish (8.36, 8.17, and 7.64µM for 1-3). Finally, the zebrafish tolerated doses of 1 and 2 up to 0.625µM, and 3 was tolerated at even higher doses of up to 1.25µM.
[Mh] Termos MeSH primário: Citotoxinas
Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos
Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos
Neoplasias/tratamento farmacológico
Compostos Organoáuricos
Peixe-Zebra/embriologia
[Mh] Termos MeSH secundário: Animais
Linhagem Celular Tumoral
Citotoxinas/síntese química
Citotoxinas/química
Citotoxinas/farmacologia
Ensaios de Seleção de Medicamentos Antitumorais
Seres Humanos
Invasividade Neoplásica
Neoplasias/metabolismo
Neoplasias/patologia
Compostos Organoáuricos/síntese química
Compostos Organoáuricos/química
Compostos Organoáuricos/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cytotoxins); 0 (Organogold Compounds)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170904
[Lr] Data última revisão:
170904
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161121
[St] Status:MEDLINE


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[PMID]:27823888
[Au] Autor:Chaves JD; Tunes LG; de J Franco CH; Francisco TM; Corrêa CC; Murta SM; Monte-Neto RL; Silva H; Fontes AP; de Almeida MV
[Ad] Endereço:Departamento de Química, ICE, Universidade Federal de Juiz de Fora, 36036-330, Juiz de Fora, MG, Brazil.
[Ti] Título:Novel gold(I) complexes with 5-phenyl-1,3,4-oxadiazole-2-thione and phosphine as potential anticancer and antileishmanial agents.
[So] Source:Eur J Med Chem;127:727-739, 2017 Feb 15.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:The current anticancer and antileishmanial drug arsenal presents several limitations concerning their specificity, efficacy, costs and the emergence of drug-resistant cells lines, which encourages the urgent need to search for new alternatives. Inspired by the fact that gold(I)-based compounds are promising antitumoral and antileishmanial drug candidates, we synthesized novel gold(I) complexes containing phosphine and 5-phenyl-1,3,4-oxadiazole-2-thione and evaluated their anticancer and antileishmanial activities. Synthesis was performed by reacting 5-phenyl-1,3,4-oxadiazole-2-thione derivatives with chloro(triphenylphosphine)gold(I) and chloro(triethylphosphine)gold(I). The novel compounds were characterized by infrared, Raman, H, C nuclear magnetic resonance, high-resolution mass spectra, and x-ray crystallography. The coordination of the ligands to gold(I) occurred through the exocyclic sulfur atom. All gold(I) complexes were active at low micromolar or nanomolar range with IC values ranging from <0.10 to 1.66 µM against cancer cell lines and from 0.9 to 4.2 µM for Leishmania infantum intracellular amastigotes. Compound (6-A) was very selective against murine melanoma B16F10, colon cancer CT26.WT cell lines and L. infantum intracellular amastigotes. Compound (7-B) presented the highest anticancer activity against both cancer cell lines while the promising antileishmanial lead was compound (6-A). Tiethylphosphine gold(I) complexes were more active than the conterparts triphenylphosphine derivatives for both anticancer and antileishmanial activities. Triethylphosphine gold(I) derivatives presented antimony cross-resistance in L. guyanensis demonstrating their potential to be used as chemical tools to better understand mechanisms of drug resistance and action. These findings revealed the anticancer and antileishmanial potential of gold(I) oxadiazole phosphine derivatives.
[Mh] Termos MeSH primário: Desenho de Drogas
Ouro/química
Leishmania infantum/efeitos dos fármacos
Compostos Organoáuricos/química
Compostos Organoáuricos/farmacologia
Oxidiazóis/química
Fosfinas/química
[Mh] Termos MeSH secundário: Antimônio/farmacologia
Antineoplásicos/química
Antineoplásicos/farmacologia
Antiprotozoários/química
Antiprotozoários/farmacologia
Linhagem Celular Tumoral
Resistência a Medicamentos/efeitos dos fármacos
Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Antiprotozoal Agents); 0 (Organogold Compounds); 0 (Oxadiazoles); 0 (Phosphines); 20O2F20OUR (1,3,4-oxadiazole); 7440-57-5 (Gold); 9IT35J3UV3 (Antimony)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161109
[St] Status:MEDLINE


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[PMID]:27858001
[Au] Autor:Spell SR; Mangrum JB; Peterson EJ; Fabris D; Ptak R; Farrell NP
[Ad] Endereço:Department of Chemistry, Virginia Commonwealth University, Richmond, VA 23284-2006, USA. npfarrell@vcu.edu.
[Ti] Título:Au(iii) compounds as HIV nucleocapsid protein (NCp7)-nucleic acid antagonists.
[So] Source:Chem Commun (Camb);53(1):91-94, 2016 12 20.
[Is] ISSN:1364-548X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The HIV nucleocapsid NCp7-SL2 RNA interaction is interrupted in the presence of a formally substitution-inert gold(dien)-nucleobase/N-heterocycle AuN compound where the N-heterocycle serves the dual purposes of a template for "non-covalent" molecular recognition of the essential tryptophan of the protein, mimicking the natural reaction and subsequent "fixation" by Au-Cys bond formation providing a chemotype for a new distinct class of nucleocapsid-nucleic acid antagonist.
[Mh] Termos MeSH primário: Compostos Organoáuricos/química
Compostos Organoáuricos/farmacologia
RNA Viral/antagonistas & inibidores
Produtos do Gene gag do Vírus da Imunodeficiência Humana/antagonistas & inibidores
[Mh] Termos MeSH secundário: Relação Dose-Resposta a Droga
Estrutura Molecular
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (NCP7 protein, Human immunodeficiency virus 1); 0 (Organogold Compounds); 0 (RNA, Viral); 0 (gag Gene Products, Human Immunodeficiency Virus)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170706
[Lr] Data última revisão:
170706
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161119
[St] Status:MEDLINE


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[PMID]:27529597
[Au] Autor:Chen BJ; Jamaludin NS; Khoo CH; See TH; Sim JH; Cheah YK; Halim SN; Seng HL; Tiekink ER
[Ad] Endereço:Department of Biomedical Science, Faculty of Medicine and Health Sciences, University Putra Malaysia, 43400 UPM Serdang, Selangor Darul Ehsan, Malaysia.
[Ti] Título:In vitro antibacterial and time kill evaluation of mononuclear phosphanegold(I) dithiocarbamates.
[So] Source:J Inorg Biochem;163:68-80, 2016 Oct.
[Is] ISSN:1873-3344
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Four compounds, R PAu[S CN(CH CH OH) ], R=Ph (1) and cyclohexyl (2), and Et PAuS CNRꞌ , Rꞌ=Rꞌ=Et (3) and Rꞌ =(CH ) (4), have been evaluated for antibacterial activity against a panel of 24 Gram positive (8) and Gram negative (16) bacteria. Based on minimum inhibitory concentration (MIC) scores, compounds 1 and 2 were shown to be specifically potent against Gram positive bacteria whereas compounds 3 and, to a lesser extent, 4 exhibited broad range activity. All four compounds were active against methicillin resistant Staphylococcus aureus (MRSA). Time kill assays revealed the compounds to exhibit both time- and concentration-dependent pharmacokinetics against susceptible bacteria. Each compound was bactericidal against one or more bacteria with 3 being especially potent after 8h exposure; compounds 1 and 3 were bactericidal against MRSA. Compound 3 was the most effective bactericide across the series especially toward B. subtilis, S. saprophyticus, A. hydrophila, P. vulgaris, and V. parahaemolyticus. This study demonstrates the potential of this class of compounds as antibacterial agents, either broad range or against specific bacteria.
[Mh] Termos MeSH primário: Antibacterianos
Bactérias Gram-Positivas/crescimento & desenvolvimento
Compostos Organoáuricos
Tiocarbamatos
[Mh] Termos MeSH secundário: Antibacterianos/síntese química
Antibacterianos/química
Antibacterianos/farmacologia
Compostos Organoáuricos/síntese química
Compostos Organoáuricos/química
Compostos Organoáuricos/farmacologia
Tiocarbamatos/síntese química
Tiocarbamatos/química
Tiocarbamatos/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Organogold Compounds); 0 (Thiocarbamates)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170904
[Lr] Data última revisão:
170904
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160817
[St] Status:MEDLINE


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[PMID]:27293145
[Au] Autor:Abbehausen C; Manzano CM; Corbi PP; Farrell NP
[Ad] Endereço:Institute of Chemistry, University of Campinas - UNICAMP, PO Box 6154, CEP 13083-970 Campinas, SP, Brazil. Electronic address: camabbehausen@iqm.unicamp.br.
[Ti] Título:Effects of coordination mode of 2-mercaptothiazoline on reactivity of Au(I) compounds with thiols and sulfur-containing proteins.
[So] Source:J Inorg Biochem;165:136-145, 2016 Dec.
[Is] ISSN:1873-3344
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Gold(I) based drugs are interesting for their potential medical use. The relatively facile ligand substitution in linear gold(I) compounds makes the identification of active species complicated. Ligands such as PR and CN are likely to be carrier ligands due to their strong trans-directing properties and will dictate the nature of substitution reactions. The 2-mercaptothiazoline (mtz) ligand is an N,S-heterocyclic compound which presents an exocyclic thiol sulfur as well as a heterocyclic nitrogen. The coordination of mtz to transition metals can be modulated by the trans ligand and complexes with metal bound through the nitrogen and/or the exocyclic sulfur are known. Therefore, the complexes [NCAu(N-mtz)] (N-coordinated) and [(Ph P)Au(S-mtz)] (S-coordinated) were investigated to compare the influence of CN and PR as well as the coordination mode of the mtz ligand on reactivity with thiols and sulfur-containing proteins. As a further comparison the compound [(Ph P)AuCN] was also studied. Human serum albumin, egg white lysozyme and, principally, the C-terminal zinc finger (ZF2) of the nucleocapsid NCp7protein of HIV-1 were studied. Results from zinc finger studies show that the coordination structure can determine the reactivity toward biomolecules. Due to ligand scrambling, the complex [NCAu(N-mtz)] forms very reactive species in solution generating [NC Au -biomolecule] adducts, where x,y≤3. The observation by mass spectrometry of [(CN)Au]-ZF confirms the ability of Au(I) compounds to form [(Ligand)Au] adducts on zinc fingers, in contrast to Au(III), where all ligands are lost upon reaction with the zinc finger. On the other hand, [(Ph P)Au(S-mtz)] also generates the [(Ph P) Au] species due to ligand scrambling, that showed lower reactivity, probably due to steric hindrance. For this complex [(Ph P)Au-biomolecule] and [Au-biomolecule] adducts are dominant. The results corroborate the hypothesis of modulation through coordination as the reactivity clearly depends on not only the ligand, but also the coordination mode.
[Mh] Termos MeSH primário: HIV-1/química
Muramidase/química
Compostos Organoáuricos
Albumina Sérica/química
Tiazolidinas/química
Produtos do Gene gag do Vírus da Imunodeficiência Humana/química
[Mh] Termos MeSH secundário: Animais
Galinhas
Seres Humanos
Compostos Organoáuricos/síntese química
Compostos Organoáuricos/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (NCP7 protein, Human immunodeficiency virus 1); 0 (Organogold Compounds); 0 (Serum Albumin); 0 (Thiazolidines); 0 (gag Gene Products, Human Immunodeficiency Virus); 96-53-7 (2-mercaptothiazoline); EC 3.2.1.17 (Muramidase)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170621
[Lr] Data última revisão:
170621
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160614
[St] Status:MEDLINE


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[PMID]:27279627
[Au] Autor:Owings JP; McNair NN; Mui YF; Gustafsson TN; Holmgren A; Contel M; Goldberg JB; Mead JR
[Ad] Endereço:Department of Pediatrics, 1760 Haygood, Emory University, Atlanta, GA 30022, USA.
[Ti] Título:Auranofin and N-heterocyclic carbene gold-analogs are potent inhibitors of the bacteria Helicobacter pylori.
[So] Source:FEMS Microbiol Lett;363(14), 2016 Jul.
[Is] ISSN:1574-6968
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Auranofin is an FDA-approved gold-containing compound used for the treatment of rheumatoid arthritis. Recent reports of antimicrobial activity against protozoa and bacteria indicate that auranofin targets the reductive enzyme thioredoxin reductase (TrxR). We evaluated auranofin as well as five auranofin analogs containing N-heterocyclic carbenes (instead of the triethylphosphane present in auranofin) and five gold-carbene controls for their ability to inhibit or kill Helicobacter pylori in vitro Auranofin completely inhibited bacterial growth at 1.2 µM. Purified H. pylori TrxR was inhibited by auranofin in a cell-free assay (IC50 ∼88 nM). The most active gold(I)-N-heterocyclic carbene compounds exhibited MICs comparable to auranofin against H. pylori (2 µM), while also exhibiting lower toxicities for human embryonic kidney cells (HEK-293T cells). Median toxic concentrations (TC50) were 13-20-fold higher compared to auranofin indicating that they were less cytotoxic. The N-heterocyclic carbene analogs maybe well tolerated, but further evaluation is needed in vivo Finally, auranofin was synergistic with the antibiotic amoxicillin, suggesting that targeting both the reductive enzyme TrxR and cell wall synthesis may be effective against H. pylori infections.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Auranofina/farmacologia
Helicobacter pylori/efeitos dos fármacos
Compostos Heterocíclicos/farmacologia
Metano/análogos & derivados
Compostos Organoáuricos/farmacologia
[Mh] Termos MeSH secundário: Antibacterianos/química
Auranofina/química
Linhagem Celular Transformada
Relação Dose-Resposta a Droga
Sinergismo Farmacológico
Compostos Heterocíclicos/química
Seres Humanos
Concentração Inibidora 50
Metano/química
Metano/farmacologia
Testes de Sensibilidade Microbiana
Estrutura Molecular
Compostos Organoáuricos/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Heterocyclic Compounds); 0 (Organogold Compounds); 2465-56-7 (carbene); 3H04W2810V (Auranofin); OP0UW79H66 (Methane)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171103
[Lr] Data última revisão:
171103
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160610
[St] Status:MEDLINE



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