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  1 / 29816 MEDLINE  
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[PMID]:29364960
[Au] Autor:McCarthy K; Fielding K; Churchyard GJ; Grant AD
[Ad] Endereço:The Aurum Institute; Johannesburg, South Africa.
[Ti] Título:Empiric tuberculosis treatment in South African primary health care facilities - for whom, where, when and why: Implications for the development of tuberculosis diagnostic tests.
[So] Source:PLoS One;13(1):e0191608, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The extent and circumstances under which empiric tuberculosis (TB) treatment (treatment without microbiological confirmation at treatment initiation) is administered in primary health care settings in South Africa are not well described. METHODS: We used data from a pragmatic evaluation of Xpert MTB/RIF in which persons undergoing TB investigations by PHC nurses were followed for six months. Following Xpert or smear-microscopy at enrolment, investigations for tuberculosis were undertaken at the discretion of health care workers. We identified persons whose TB treatment was initiated empirically (no microbiological confirmation at time of treatment initiation at a primary health care facility) and describe pathways to treatment initiation. RESULTS: Of 4665 evaluable participants, 541 persons were initiated on treatment of whom 167 (31%) had negative sputum tests at enrolment. Amongst these 167, the median number of participant visits to health care providers prior to treatment initiation was 3 (interquartile range [IQR] 2-4). Chest radiography, sputum culture or hospital referral was done in 106/167 (63%). Reasons for TB treatment start were: 1) empiric (n = 82, 49%); 2) a positive laboratory test (n = 49, 29%); 3) referral and treatment start at a higher level of care (n = 28, 17%); and 4) indeterminable (n = 8, 5%). Empiric treatment accounted for 15% (82/541) of all TB treatment initiations and 1.7% (82/4665) of all persons undergoing TB investigations. Chest radiography findings compatible with TB (63/82 [77%]) were the basis for treatment initiation amongst the majority of empirically treated participants. Microbiological confirmation of TB was subsequently obtained for 11/82 (13%) empirically-treated participants. Median time to empiric treatment start was 3.9 weeks (IQR 1.4-11 weeks) after enrolment. CONCLUSION: Uncommon prescription of empiric TB treatment with reliance on chest radiography in a nurse-managed programme underscores the need for highly sensitive TB diagnostics suitable for point-of-care, and strong health systems to support TB diagnosis in this setting.
[Mh] Termos MeSH primário: Antituberculosos/uso terapêutico
Atenção Primária à Saúde
Tuberculose/tratamento farmacológico
[Mh] Termos MeSH secundário: Adulto
Feminino
Seres Humanos
Masculino
Meia-Idade
África do Sul
Tuberculose/diagnóstico
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antitubercular Agents)
[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:180125
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191608


  2 / 29816 MEDLINE  
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[PMID]:29458544
[Au] Autor:Aguilar-Ayala DA; Cnockaert M; Vandamme P; Palomino JC; Martin A; Gonzalez-Y-Merchand J
[Ad] Endereço:2​Laboratory of Microbiology, Department of Biochemistry and Microbiology, Ghent University, Ghent 9000, Belgium.
[Ti] Título:Antimicrobial activity against Mycobacterium tuberculosis under in vitro lipid-rich dormancy conditions.
[So] Source:J Med Microbiol;67(3):282-285, 2018 Mar.
[Is] ISSN:1473-5644
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Although tuberculosis treatment is dependent on drug-susceptibility testing (DST) and molecular drug-resistance detection, treatment failure and relapse remain a challenge. This could be partially due to the emergence of antibiotic-tolerant dormant mycobacteria, where host lipids have been shown to play an important role. This study evaluated the susceptibility of Mycobacterium tuberculosis to two antibiotic combinations - rifampicin, moxifloxacin, amikacin and metronidazole (RIF-MXF-AMK-MTZ), and rifampicin, moxifloxacin, amikacin and pretomanid (RIF-MXF-AMK-PA) - in a lipid-rich dormancy model. Although their effectiveness in in vitro cultures with dextrose as a carbon source has been proved, we observed that none of the antibiotic mixtures were bactericidal in the presence of lipids. The presence of lipids may confer tolerance to M. tuberculosis against the mixture of antibiotics tested and such tolerance could be even higher during the dormant stages. The implementation of lipids in DST on clinical isolates could potentially lead to a better treatment strategy.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Lipídeos/farmacologia
Mycobacterium tuberculosis/efeitos dos fármacos
Mycobacterium tuberculosis/fisiologia
[Mh] Termos MeSH secundário: Amicacina/farmacologia
Antituberculosos/farmacologia
Tolerância a Medicamentos
Fluoroquinolonas/farmacologia
Aptidão Genética
Genótipo
Seres Humanos
Metabolismo dos Lipídeos
Testes de Sensibilidade Microbiana
Modelos Biológicos
Infecções por Micobactéria não Tuberculosa/microbiologia
Mycobacterium tuberculosis/genética
Mycobacterium tuberculosis/crescimento & desenvolvimento
Nitroimidazóis/farmacologia
Rifampina/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (2-nitro-6-(4-(trifluoromethoxy)benzyloxy)-6,7-dihydro-5H-imidazo(2,1-b)(1,3)oxazine); 0 (Anti-Bacterial Agents); 0 (Antitubercular Agents); 0 (Fluoroquinolones); 0 (Lipids); 0 (Nitroimidazoles); 84319SGC3C (Amikacin); U188XYD42P (moxifloxacin); VJT6J7R4TR (Rifampin)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180221
[St] Status:MEDLINE
[do] DOI:10.1099/jmm.0.000681


  3 / 29816 MEDLINE  
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[PMID]:29220433
[Au] Autor:Malhotra S; Mugumbate G; Blundell TL; Higueruelo AP
[Ad] Endereço:Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1GA, UK.
[Ti] Título:TIBLE: a web-based, freely accessible resource for small-molecule binding data for mycobacterial species.
[So] Source:Database (Oxford);2017, 2017 Jan 01.
[Is] ISSN:1758-0463
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Database URL: http://www-cryst.bioc.cam.ac.uk/tible/.
[Mh] Termos MeSH primário: Antituberculosos/farmacologia
Proteínas de Bactérias
Bases de Dados de Produtos Farmacêuticos
Bases de Dados de Proteínas
Internet
Mycobacterium tuberculosis
[Mh] Termos MeSH secundário: Proteínas de Bactérias/química
Proteínas de Bactérias/metabolismo
Testes de Sensibilidade Microbiana
Mycobacterium tuberculosis/efeitos dos fármacos
Mycobacterium tuberculosis/enzimologia
Mycobacterium tuberculosis/metabolismo
Interface Usuário-Computador
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antitubercular Agents); 0 (Bacterial Proteins)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171209
[St] Status:MEDLINE
[do] DOI:10.1093/database/bax041


  4 / 29816 MEDLINE  
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[PMID]:29465582
[Au] Autor:Wang T; Zhao G; Rui YJ; Mi JY
[Ad] Endereço:Department of Hand Surgery, Wuxi NO.9 People's Hospital Affiliated to Soochow University, Wuxi, China.
[Ti] Título:Successfully treating hand primary tuberculous synovitis by synovectomy combined antituberculous therapy: A case report.
[So] Source:Medicine (Baltimore);97(8):e9938, 2018 Feb.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RATIONALE: Primary tuberculous infection in hand and wrist is a rare disease. Few articles reported on hand primary tuberculous synovitis. PATIENT CONCERNS: A 68-year-old Chinese male, without history of tuberculosis (TB), had complained of pain and swelling in right palm and little finger for 3 months. Patient came to our hospital on 9th Oct 2016. X-ray just showed soft tissue swelling in little finger. Magnetic resonance imaging (MRI) showed synovitis around flexor tendon of little finger, volar palm, and carpal tunnel. Notably, it also implied nodular images in little finger sizing 5 mm × 11 mm. Laboratory tests revealed C-reactive protein (CRP): 22 mg/L, erythrocyte sedimentation rate (ESR): 49 mm/h, and white blood cells (WBC): 11.8 × 10/L. DIAGNOSES: He was diagnosed with primary hand tuberculous synovitis. INTERVENTIONS: The patient received aspiration biopsy in right palm guided by ultrasound on 13rd Oct and pathological examination indicated Mycobacterium tuberculosis (MTB) infection. We performed radical synovetomy and collected abnormal tissue for pathological examination on 18th Oct. Finally, result showed MTB infection, which was the same with the result of first pathological examination. Then, this patient received antituberculous treatment. OUTCOMES: One year after operation, pain and swelling relieve and no recurrence of the clinical symptoms happened. LESSONS: Primary tuberculous synovitis of hand and wrist is rare, MTB infection should be considered as an infectious agent, especially in developing countries. Radical synovectomy and antituberculous treatment regain a satisfactory outcome.
[Mh] Termos MeSH primário: Antituberculosos/uso terapêutico
Articulação da Mão
Mycobacterium tuberculosis
Sinovectomia/métodos
Sinovite/terapia
Tuberculose Osteoarticular/terapia
Punho
[Mh] Termos MeSH secundário: Idoso
Terapia Combinada
Seres Humanos
Masculino
Sinovite/microbiologia
Resultado do Tratamento
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antitubercular Agents)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180222
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009938


  5 / 29816 MEDLINE  
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[PMID]:29335214
[Au] Autor:Poce G; Cocozza M; Alfonso S; Consalvi S; Venditti G; Fernandez-Menendez R; Bates RH; Barros Aguirre D; Ballell L; De Logu A; Vistoli G; Biava M
[Ad] Endereço:Department of Chemistry and Technology of Drugs, Sapienza University of Rome, Piazzale A. Moro 5, 00185 Rome, Italy. Electronic address: giovanna.poce@uniroma1.it.
[Ti] Título:In vivo potent BM635 analogue with improved drug-like properties.
[So] Source:Eur J Med Chem;145:539-550, 2018 Feb 10.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:BM635 is the hit compound of a promising anti-TB compound class. Herein we report systematic variations around the central pyrrole core of BM635 and we describe the design, synthesis, biological evaluation, pharmacokinetic analysis, as well as in vivo TB mouse efficacy studies of novel BM635 analogues that show improved physicochemical properties. This hit-to-lead campaign led to the identification of a new analogue, 4-((1-isopropyl-5-(4-isopropylphenyl)-2-methyl-1H-pyrrol-3-yl)methyl)morpholine (17), that shows excellent activity (MIC = 0.15 µM; SI = 133) against drug-sensitive Mycobacterium tuberculosis strains, as well as efficacy in a murine model of TB infection.
[Mh] Termos MeSH primário: Antituberculosos/farmacologia
Mycobacterium tuberculosis/efeitos dos fármacos
Pirróis/farmacologia
Tuberculose/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Antituberculosos/síntese química
Antituberculosos/química
Proliferação Celular/efeitos dos fármacos
Sobrevivência Celular/efeitos dos fármacos
Modelos Animais de Doenças
Relação Dose-Resposta a Droga
Desenho de Drogas
Células Hep G2
Seres Humanos
Camundongos
Camundongos Endogâmicos C57BL
Testes de Sensibilidade Microbiana
Estrutura Molecular
Pirróis/síntese química
Pirróis/química
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antitubercular Agents); 0 (BM635 compound); 0 (Pyrroles)
[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:180117
[St] Status:MEDLINE


  6 / 29816 MEDLINE  
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[PMID]:29280409
[Au] Autor:Schaaf HS; Garcia-Prats AJ; McKenna L; Seddon JA
[Ad] Endereço:a Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences , Stellenbosch University , Cape Town , South Africa.
[Ti] Título:Challenges of using new and repurposed drugs for the treatment of multidrug-resistant tuberculosis in children.
[So] Source:Expert Rev Clin Pharmacol;11(3):233-244, 2018 Mar.
[Is] ISSN:1751-2441
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: New and repurposed antituberculosis drugs are urgently needed to more safely and effectively treat multidrug-resistant (MDR) tuberculosis (TB) in children. Multiple challenges limit timely access to new MDR-TB treatments in children. Areas covered: Diagnosis of MDR-TB in children remains a barrier, with few children with MDR-TB diagnosed and treated. Other barriers to timely access to new and repurposed drugs are discussed, and include delayed initiation of paediatric trials, limited funding for paediatric drug development, fragmented regulatory systems and operational challenges. The status of access to current repurposed and novel drugs is presented. Expert commentary: More timely initiation of paediatric trials is needed and paediatric work should happen and be funded in parallel with each phase of adult trials. Better quality data, increased regulator resources and expertise, harmonization of regulatory requirements across borders/organisations and registration fee waivers would improve registration timelines. Improved diagnosis, recording and reporting will establish better demand. Improved systems for procurement and supply chain management would reduce in-country operational barriers to getting medications to children. The challenges must be addressed to ensure timely and equitable access to new drugs and regimens that are urgently needed for effective, safe and shorter treatment of children with MDR-TB.
[Mh] Termos MeSH primário: Antituberculosos/uso terapêutico
Acesso aos Serviços de Saúde
Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico
[Mh] Termos MeSH secundário: Adulto
Antituberculosos/efeitos adversos
Antituberculosos/provisão & distribuição
Criança
Desenho de Drogas
Reposicionamento de Medicamentos
Seres Humanos
Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antitubercular Agents)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171228
[St] Status:MEDLINE
[do] DOI:10.1080/17512433.2018.1421067


  7 / 29816 MEDLINE  
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[PMID]:29288945
[Au] Autor:Zhang HZ; Zhao ZL; Zhou CH
[Ad] Endereço:School of Pharmacy, Linyi University, Linyi 276000, China. Electronic address: zhanghuizhen@lyu.edu.cn.
[Ti] Título:Recent advance in oxazole-based medicinal chemistry.
[So] Source:Eur J Med Chem;144:444-492, 2018 Jan 20.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Oxazole compounds containing nitrogen and oxygen atoms in the five-membered aromatic ring are readily able to bind with a variety of enzymes and receptors in biological systems via diverse non-covalent interactions, and thus display versatile biological activities. The related researches in oxazole-based derivatives including oxazoles, isoxazoles, oxazolines, oxadiazoles, oxazolidones, benzoxazoles and so on, as medicinal drugs have been an extremely active topic, and numerous excellent achievements have been acquired. Noticeably, a large number of oxazole compounds as clinical drugs or candidates have been frequently employed for the treatment of various types of diseases, which have shown their large development value and wide potential as medicinal agents. This work systematically reviewed the recent researches and developments of the whole range of oxazole compounds as medicinal drugs, including antibacterial, antifungal, antiviral, antitubercular, anticancer, anti-inflammatory and analgesic, antidiabetic, antiparasitic, anti-obesitic, anti-neuropathic, antioxidative as well as other biological activities. The perspectives of the foreseeable future in the research and development of oxazole-based compounds as medicinal drugs are also presented. It is hoped that this review will serve as a stimulant for new thoughts in the quest for rational designs of more active and less toxic oxazole medicinal drugs.
[Mh] Termos MeSH primário: Oxazóis/farmacologia
[Mh] Termos MeSH secundário: Analgésicos/química
Analgésicos/farmacologia
Antibacterianos/química
Antibacterianos/farmacologia
Anti-Inflamatórios não Esteroides/química
Anti-Inflamatórios não Esteroides/farmacologia
Fármacos Antiobesidade/química
Fármacos Antiobesidade/farmacologia
Antifúngicos/química
Antifúngicos/farmacologia
Antineoplásicos/química
Antineoplásicos/farmacologia
Antioxidantes/química
Antioxidantes/farmacologia
Antiparasitários/química
Antiparasitários/farmacologia
Antituberculosos/química
Antituberculosos/farmacologia
Antivirais/química
Antivirais/farmacologia
Química Farmacêutica
Seres Humanos
Hipoglicemiantes/química
Hipoglicemiantes/farmacologia
Estrutura Molecular
Oxazóis/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Analgesics); 0 (Anti-Bacterial Agents); 0 (Anti-Inflammatory Agents, Non-Steroidal); 0 (Anti-Obesity Agents); 0 (Antifungal Agents); 0 (Antineoplastic Agents); 0 (Antioxidants); 0 (Antiparasitic Agents); 0 (Antitubercular Agents); 0 (Antiviral Agents); 0 (Hypoglycemic Agents); 0 (Oxazoles)
[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:171231
[St] Status:MEDLINE


  8 / 29816 MEDLINE  
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[PMID]:29395080
[Au] Autor:Gopalan A; Bhagavat R; Chandra N; Subbarao SH; Raja A; Bethunaickan R
[Ad] Endereço:Department of Immunology, National Institute for Research in Tuberculosis, Chennai, India.
[Ti] Título:Biophysical and biochemical characterization of Rv3405c, a tetracycline repressor protein from Mycobacterium tuberculosis.
[So] Source:Biochem Biophys Res Commun;496(3):799-805, 2018 02 12.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mycobacterium tuberculosis, the causative agent of tuberculosis disease, is one among the deadliest pathogens in the world. Due to long treatment regimen, HIV co-infection, persistence of bacilli in latent form and development of XDR and TDR strains of Mtb, tuberculosis has posed serious concerns for managing the disease, and calls for discovery of new drugs and drug targets. Using a computational pipeline involving analysis of the structural models of the Mtb proteome and an analysis of the ATPome, followed by a series of filters to identify druggable proteins, solubility and length of the protein, several candidate proteins were shortlisted. From this, Rv3405c, a tetR family of DNA binding protein involved in antibiotic resistance, was identified as one of the good drug targets. Rv3405c binds to the upstream non-coding region of Rv3406 and causes repression of Rv3406 activity there by affecting the downstream processes involved in antibiotic resistance was further characterized. The Rv3405c gene was cloned; the gene product was over-expressed in E. coli and purified by Ni NTA chromatography. DNA binding studies by EMSA showed that the recombinant Rv3405c protein binds to the DNA sequence corresponding to the promoter region of Rv3406 and upon addition of tetracycline, the DNA binding activity was lost. ß-galactosidase reporter assay in E. coli using both wild type and a DNA binding defective mutant protein indeed proved that Rv3405c acts as a repressor.
[Mh] Termos MeSH primário: Proteínas de Bactérias/química
Proteínas de Bactérias/metabolismo
Proteínas de Ligação a DNA/química
Proteínas de Ligação a DNA/metabolismo
Mycobacterium tuberculosis/metabolismo
Tetraciclina/química
Tetraciclina/metabolismo
[Mh] Termos MeSH secundário: Antituberculosos/química
Sítios de Ligação
Avaliação Pré-Clínica de Medicamentos
Resistência Microbiana a Medicamentos/fisiologia
Ligação Proteica
Proteínas Repressoras
Resistência a Tetraciclina/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antitubercular Agents); 0 (Bacterial Proteins); 0 (DNA-Binding Proteins); 0 (Repressor Proteins); 0 (Rv3405c protein, Mycobacterium tuberculosis); F8VB5M810T (Tetracycline)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180204
[St] Status:MEDLINE


  9 / 29816 MEDLINE  
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[PMID]:29182187
[Au] Autor:Tatum NJ; Liebeschuetz JW; Cole JC; Frita R; Herledan A; Baulard AR; Willand N; Pohl E
[Ad] Endereço:Department of Chemistry, Durham University, South Road, Durham DH1 3LE, UK. ehmke.pohl@durham.ac.uk.
[Ti] Título:New active leads for tuberculosis booster drugs by structure-based drug discovery.
[So] Source:Org Biomol Chem;15(48):10245-10255, 2017 Dec 13.
[Is] ISSN:1477-0539
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The transcriptional repressor EthR from Mycobacterium tuberculosis, a member of the TetR family of prokaryotic homo-dimeric transcription factors, controls the expression of the mycobacterial mono-oxygenase EthA. EthA is responsible for the bio-activation of the second-line tuberculosis pro-drug ethionamide, and consequently EthR inhibitors boost drug efficacy. Here, we present a comprehensive in silico structure-based screening protocol that led to the identification of a number of novel scaffolds of EthR inhibitors in subsequent biophysical screening by thermal shift assay. Growth inhibition assays demonstrated that five of the twenty biophysical hits were capable of boosting ethionamide activity in vitro, with the best novel scaffold displaying an EC of 34 µM. In addition, the co-crystal structures of EthR with four new ligands at resolution ranging from 2.1 to 1.4 Å confirm the binding and inactivation mode, and will enable future lead development.
[Mh] Termos MeSH primário: Antituberculosos/uso terapêutico
Descoberta de Drogas
Mycobacterium tuberculosis/efeitos dos fármacos
Tuberculose/tratamento farmacológico
[Mh] Termos MeSH secundário: Antituberculosos/síntese química
Antituberculosos/química
Testes de Sensibilidade Microbiana
Modelos Moleculares
Estrutura Molecular
Mycobacterium tuberculosis/crescimento & desenvolvimento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antitubercular Agents)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171129
[St] Status:MEDLINE
[do] DOI:10.1039/c7ob00910k


  10 / 29816 MEDLINE  
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[PMID]:28463762
[Au] Autor:Paixão DA; Marzano IM; Jaimes EHL; Pivatto M; Campos DL; Pavan FR; Deflon VM; Maia PIDS; Da Costa Ferreira AM; Uehara IA; Silva MJB; Botelho FV; Pereira-Maia EC; Guilardi S; Guerra W
[Ad] Endereço:Instituto de Química, Universidade Federal de Uberlândia, Uberlândia, MG, Brazil.
[Ti] Título:Novel copper(II) complexes with hydrazides and heterocyclic bases: Synthesis, structure and biological studies.
[So] Source:J Inorg Biochem;172:138-146, 2017 Jul.
[Is] ISSN:1873-3344
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Five new copper(II) complexes of the type [Cu(NO)(NN)(ClO ) ], in which NO=4-fluorophenoxyacetic acid hydrazide (4-FH) or 4-nitrobenzoic hydrazide (4-NH) and NN=1,10-phenanthroline (phen), 4-4'-dimethoxy-2-2'-bipyridine (dmb) or 2,2-bipyridine (bipy) were synthesized and characterized using various spectroscopic methods. The X-ray structural analysis of one representative compound indicates that the geometry around the copper ion is distorted octahedron, in which the ion is coordinated to hydrazide via the terminal nitrogen and the carbonyl oxygen, and to heterocyclic bases via their two nitrogen atoms. Two perchlorate anions occupy the apical positions, completing the coordination sphere. The cytotoxic activity of compounds was investigated in three tumor cell lines (K562, MDA-MB-231 and MCF-7). Concerning K562 cell line, the complexes with 1,10-phenanthroline exhibit high cytotoxic activity and are more active than carboplatin, free ligands and [Cu(phen) ] . Considering the cytotoxicity results, further investigations for the compounds [Cu(4-FH)(phen)(ClO ) ] I and [Cu(4-NH)(phen)(ClO ) ]∙H O III were performed. Flow cytometric analysis revealed that these complexes induce apoptotic cell death in MDA-MB-231 cell line and bind to DNA with K values of 4.38×10 and 2.62×10 , respectively. These compounds were also evaluated against wild type Mycobacterium tuberculosis (ATCC 27294) and exhibited antimycobacterial activity, displayed MIC values lower than those of the corresponding free ligands.
[Mh] Termos MeSH primário: Complexos de Coordenação/síntese química
Complexos de Coordenação/farmacologia
Cobre/química
Compostos Heterocíclicos/química
Hidrazinas/química
[Mh] Termos MeSH secundário: Antineoplásicos/síntese química
Antineoplásicos/farmacologia
Antituberculosos/síntese química
Antituberculosos/farmacologia
Apoptose/efeitos dos fármacos
Neoplasias da Mama/tratamento farmacológico
Linhagem Celular Tumoral
Complexos de Coordenação/química
Cristalografia por Raios X
Feminino
Seres Humanos
Concentração Inibidora 50
Células K562
Testes de Sensibilidade Microbiana
Estrutura Molecular
Mycobacterium/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Antitubercular Agents); 0 (Coordination Complexes); 0 (Heterocyclic Compounds); 0 (Hydrazines); 27RFH0GB4R (hydrazine); 789U1901C5 (Copper)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE



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