Base de dados : MEDLINE
Pesquisa : D03.383.129.462 [Categoria DeCS]
Referências encontradas : 7938 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 794 ir para página                         

  1 / 7938 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29384903
[Au] Autor:De Anda C; Anuskiewicz S; Prokocimer P; Vazquez J
[Ad] Endereço:Merck & Co., Inc., Kenilworth, NJ, USA.
[Ti] Título:Outpatient treatment of acute bacterial skin and skin structure infections (ABSSSI) with tedizolid phosphate and linezolid in patients in the United States: Subgroup analysis of 2 randomized phase 3 trials.
[So] Source:Medicine (Baltimore);96(52):e9163, 2017 Dec.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Acute bacterial skin and skin structure infections (ABSSSI) are a frequent cause of hospital admissions in the United States. Safe and effective outpatient treatments may lower ABSSSI-associated health care costs by reducing unnecessary hospital admissions. Using data from 2 phase 3 trials (ESTABLISH-1, NCT01170221; ESTABLISH-2, NCT01421511), this post-hoc analysis explored the efficacy and safety of tedizolid in an outpatient setting. METHODS: Subgroup analysis was performed on US outpatients (defined as patients who were not in hospital at the time of treatment initiation) with ABSSSI caused by presumed or proven gram-positive pathogens. Patients were randomly assigned to receive tedizolid phosphate 200 mg once daily for 6 days (n = 403) or linezolid 600 mg twice daily for 10 days (n = 410). The primary end point was early clinical response (48-72 hours after the start of treatment). Secondary end points included investigator-assessed clinical response at end of therapy (EOT) and post-therapy evaluation (PTE; 7-14 days after therapy). Additional assessments included the patient-reported level of pain using a visual analog scale (VAS) and the per-pathogen favorable microbiological response rate at the PTE visit. Compliance with treatment and safety outcomes was also recorded. RESULTS: Early clinical response was similar between treatment groups (tedizolid, 82.4%; linezolid, 79.0%), as was investigator-assessed clinical response at EOT (tedizolid, 87.1%; linezolid, 86.1%) and PTE (tedizolid, 83.1%; linezolid, 83.7%). Mean changes from baseline to days 10 to 13 in VAS scores were identical between treatment groups (tedizolid, -51.9 mm; linezolid, -51.9 mm). Microbiological eradication rates were generally similar in both treatment groups for all key pathogens. Patients in both groups had favorable response at PTE. More tedizolid-treated patients (89.3%) than linezolid-treated patients (77.3%) were compliant with treatment. The most frequently reported drug-related treatment-emergent adverse events were nausea (tedizolid, 10.7%; linezolid, 13.8%), diarrhea (tedizolid, 4.5%; linezolid, 5.9%), and headache (tedizolid, 5.5%; linezolid, 4.4%). Treatment discontinuation rates were low for both treatment groups (tedizolid, 0.7%; linezolid, 1.0%). CONCLUSION: Short-course therapy with tedizolid can successfully treat patients with ABSSSI caused by presumed or proven gram-positive pathogens in an outpatient setting.
[Mh] Termos MeSH primário: Assistência Ambulatorial
Antibacterianos/uso terapêutico
Linezolida/uso terapêutico
Organofosfatos/uso terapêutico
Oxazóis/uso terapêutico
Dermatopatias Bacterianas/tratamento farmacológico
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Idoso de 80 Anos ou mais
Feminino
Seres Humanos
Masculino
Meia-Idade
Dermatopatias Bacterianas/patologia
Resultado do Tratamento
Estados Unidos
Adulto Jovem
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE III; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Organophosphates); 0 (Oxazoles); ISQ9I6J12J (Linezolid); O7DRJ6R4DW (torezolid phosphate)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180228
[Lr] Data última revisão:
180228
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180201
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009163


  2 / 7938 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[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


  3 / 7938 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29324854
[Au] Autor:Suroto DA; Kitani S; Arai M; Ikeda H; Nihira T
[Ad] Endereço:International Center for Biotechnology, Osaka University, Suita, Osaka, Japan.
[Ti] Título:Characterization of the biosynthetic gene cluster for cryptic phthoxazolin A in Streptomyces avermitilis.
[So] Source:PLoS One;13(1):e0190973, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Phthoxazolin A, an oxazole-containing polyketide, has a broad spectrum of anti-oomycete activity and herbicidal activity. We recently identified phthoxazolin A as a cryptic metabolite of Streptomyces avermitilis that produces the important anthelmintic agent avermectin. Even though genome data of S. avermitilis is publicly available, no plausible biosynthetic gene cluster for phthoxazolin A is apparent in the sequence data. Here, we identified and characterized the phthoxazolin A (ptx) biosynthetic gene cluster through genome sequencing, comparative genomic analysis, and gene disruption. Sequence analysis uncovered that the putative ptx biosynthetic genes are laid on an extra genomic region that is not found in the public database, and 8 open reading frames in the extra genomic region could be assigned roles in the biosynthesis of the oxazole ring, triene polyketide and carbamoyl moieties. Disruption of the ptxA gene encoding a discrete acyltransferase resulted in a complete loss of phthoxazolin A production, confirming that the trans-AT type I PKS system is responsible for the phthoxazolin A biosynthesis. Based on the predicted functional domains in the ptx assembly line, we propose the biosynthetic pathway of phthoxazolin A.
[Mh] Termos MeSH primário: Álcoois Graxos/metabolismo
Genes Bacterianos
Família Multigênica
Oxazóis/metabolismo
Alcamidas Poli-Insaturadas/metabolismo
Streptomyces/genética
[Mh] Termos MeSH secundário: Álcoois Graxos/química
Modelos Biológicos
Oxazóis/química
Alcamidas Poli-Insaturadas/química
Streptomyces/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Fatty Alcohols); 0 (Oxazoles); 0 (Polyunsaturated Alkamides); 130288-22-1 (phthoxazolin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180215
[Lr] Data última revisão:
180215
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180112
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190973


  4 / 7938 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29172749
[Au] Autor:Li Y; Baiyang L; Leran B; Zhen W; Yandong X; Baixiang D; Dandan Z; Yufu Z; Jun L; Rutong Y; Hongmei L
[Ad] Endereço:a Insititute of Nervous System Diseases , Xuzhou Medical University , Xuzhou , PR China.
[Ti] Título:Reduction-responsive PEtOz-SS-PCL micelle with tailored size to overcome blood-brain barrier and enhance doxorubicin antiglioma effect.
[So] Source:Drug Deliv;24(1):1782-1790, 2017 Nov.
[Is] ISSN:1521-0464
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:A series of novel reduction-responsive micelles with tailored size were designed and prepared to release doxorubicin (DOX) for treating glioma, which were developed based on amphiphilic block copolymer poly (2-ethyl-2-oxazoline)-b-poly (ε-caprolactone) (PEtOz-SS-PCL) and the micelle size could be regulated by designing the polymer structure. The DOX-loaded PEtOz-SS-PCL micelles had small size and rapid drug release in reductive intracellular environments. Biodistribution and in vivo imaging studies in C6 glioma mice tumor model showed that DOX loaded PEtOz-SS-PCL43 micelles with the smallest size had superior accumulation and fast drug release in tumor sites. In vivo antitumor activity demonstrated that DOX-loaded PEtOz-SS-PCL43 micelles improved antitumor efficacy in contrast to PEtOz-SS-PCL micelles with larger size toward the orthotopic C6-Luci cells-bearing mice. This study shows great potential in tailoring the micelle size and introducing the responsive bonds or compartment for intracellular drug delivery and release in glioma treatment by designing the architecture of the polymer.
[Mh] Termos MeSH primário: Antineoplásicos/química
Caproatos/química
Doxorrubicina/química
Doxorrubicina/farmacologia
Glioma/tratamento farmacológico
Lactonas/química
Oxazóis/química
[Mh] Termos MeSH secundário: Animais
Antineoplásicos/farmacologia
Transporte Biológico/fisiologia
Barreira Hematoencefálica/metabolismo
Sobrevivência Celular/efeitos dos fármacos
Portadores de Fármacos/química
Sistemas de Liberação de Medicamentos/métodos
Liberação Controlada de Fármacos/fisiologia
Masculino
Camundongos
Camundongos Endogâmicos ICR
Micelas
Tamanho da Partícula
Polímeros/química
Distribuição Tecidual/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Caproates); 0 (Drug Carriers); 0 (Lactones); 0 (Micelles); 0 (Oxazoles); 0 (Polymers); 56RE988L1R (caprolactone); 80168379AG (Doxorubicin); B8CD92T4P5 (2-ethyl-2-oxazoline)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180130
[Lr] Data última revisão:
180130
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE
[do] DOI:10.1080/10717544.2017.1402218


  5 / 7938 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28987565
[Au] Autor:Aquilino M; Sánchez-Argüello P; Martínez-Guitarte JL
[Ad] Endereço:Grupo de Biología y Toxicología Ambiental, Facultad de Ciencias, Universidad Nacional de Educación a Distancia (UNED), Senda del Rey 9, 28040 Madrid, Spain. Electronic address: maquilino@ccia.uned.es.
[Ti] Título:Genotoxic effects of vinclozolin on the aquatic insect Chironomus riparius (Diptera, Chironomidae).
[So] Source:Environ Pollut;232:563-570, 2018 Jan.
[Is] ISSN:1873-6424
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Vinclozolin (Vz) is a pollutant found in aquatic environments whose antiandrogenic effects in reproduction are well known in mammals. Although its reproductive effects have been less studied in invertebrates, other effects, including genotoxicity, have been described. Therefore, in this work, we studied the genotoxic effects of Vz in the freshwater benthic invertebrate Chironomus riparius. DNA damage was evaluated with the comet assay (tail area, olive moment, tail moment and % DNA in tail), and the transcriptional levels of different genes involved in DNA repair (ATM, NLK and XRCC1) and apoptosis (DECAY) were measured by RT-PCR. Fourth instar larvae of C. riparius, were exposed to Vz for 24 h at 20 and 200 µg/L. The Vz exposures affected the DNA integrity in this organism, since a dose-response relationship occurred, with DNA strand breaks significantly increased with increased dose for tail area, olive moment and tail moment parameters. Additionally, the lower concentration of Vz produced a significant induction of the transcripts of three genes under study (ATM, NLK and XRCC1) showing the activation of the cellular repair mechanism. In contrast, the expression of these genes with the highest concentration were downregulated, indicating failure of the cellular repair mechanism, which would explain the higher DNA damage. These data report for the first time the alterations of Vz on gene transcription of an insect and confirm the potential genotoxicity of this compound on freshwater invertebrates.
[Mh] Termos MeSH primário: Chironomidae/fisiologia
Fungicidas Industriais/toxicidade
Oxazóis/toxicidade
[Mh] Termos MeSH secundário: Animais
Chironomidae/efeitos dos fármacos
Ensaio Cometa
Dano ao DNA
Larva/efeitos dos fármacos
Poluentes Químicos da Água/toxicidade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Fungicides, Industrial); 0 (Oxazoles); 0 (Water Pollutants, Chemical); JJ258EZN1I (vinclozolin)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180119
[Lr] Data última revisão:
180119
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171009
[St] Status:MEDLINE


  6 / 7938 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28456300
[Au] Autor:Paporisch A; Rubin B
[Ad] Endereço:R. H. Smith Institute of Plant Science & Genetics in Agriculture, Faculty of Agriculture, Food and Environment, Hebrew University of Jerusalem, Rehovot 76100, Israel. Electronic address: amit.paporisch@mail.huji.ac.il.
[Ti] Título:Isoxadifen safening mechanism in sweet corn genotypes with differential response to P450-metabolized herbicides.
[So] Source:Pestic Biochem Physiol;138:22-28, 2017 May.
[Is] ISSN:1095-9939
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Three sweet corn genotypes, two inbred lines (IBER001 and IBER002) and their hybrid (ER00X), differ in their phenotypic responses to several P450-metabolized herbicides, used in sweet corn, namely, foramsulfuron, iodosulfuron, rimsulfuron and tembotrione. Foramsulfuron is a sulfonylurea herbicide commonly formulated with the safener isoxadifen that is used for selective post-emergence weed control in corn. Our goal was to elucidate the mechanism of these genotypes' responses to foramsulfuron and safener isoxadifen and examine the heritability of those responses. IBER001 was sensitive to foramsulfuron+isoxadifen, with an ED of 3.6gaiha , while IBER002 and ER00X were tolerant with ED values of 808 and 700gaiha , respectively. ALS enzyme extracted from each of the different genotypes was equally sensitive to foramsulfuron. Pre-treatment with malathion, a known cytochrome P450 inhibitor, increased foramsulfuron injury in IBER002 and ER00X, but had no effect on those lines when isoxadifen was applied with the herbicide. Foramsulfuron-treated IBER001 was severely injured regardless of the presence of malathion and/or isoxadifen. Pre-treatment with malathion similarly increased the phytotoxicity of iodosulfuron+safener (mefenpyr) and rimsulfuron to the tolerant genotypes, but did not increase the level of injury caused by the tembotrione+isoxadifen treatment. Segregation of F2 and backcross progenies according to their responses to foramsulfuron+isoxadifen revealed a pattern of inheritance typical of a trait controlled by a single gene inheritance, with a recessive allele conferring sensitivity. Our results support the hypothesis that foramsulfuron selectivity is associated with P450 metabolism and that isoxadifen positively affects P450 activity. The sensitive genotype that does not respond to isoxadifen is presumably homozygous for a deficient or non-functioning P450 gene.
[Mh] Termos MeSH primário: Sistema Enzimático do Citocromo P-450/metabolismo
Genótipo
Herbicidas/toxicidade
Oxazóis/toxicidade
Zea mays/genética
[Mh] Termos MeSH secundário: Inibidores da Colinesterase/metabolismo
Sistema Enzimático do Citocromo P-450/genética
Regulação Enzimológica da Expressão Gênica
Regulação da Expressão Gênica de Plantas
Malation/metabolismo
Pirazóis/farmacologia
Zea mays/classificação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (1-(2, 4-dichlorophenyl)-4, 5-dihydro-5-methyl-1H-pyrazole-3,5-dicarboxylic acid diethyl ester); 0 (Cholinesterase Inhibitors); 0 (Herbicides); 0 (Oxazoles); 0 (Pyrazoles); 0 (ethyl-4,5-dihydro-5,5-diphenylisoxazol-3-carboxylate); 9035-51-2 (Cytochrome P-450 Enzyme System); U5N7SU872W (Malathion)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171128
[Lr] Data última revisão:
171128
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170501
[St] Status:MEDLINE


  7 / 7938 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28462832
[Au] Autor:Thompson AM; Blaser A; Palmer BD; Anderson RF; Shinde SS; Launay D; Chatelain E; Maes L; Franzblau SG; Wan B; Wang Y; Ma Z; Denny WA
[Ad] Endereço:Auckland Cancer Society Research Centre, School of Medical Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand. Electronic address: am.thompson@auckland.ac.nz.
[Ti] Título:6-Nitro-2,3-dihydroimidazo[2,1-b][1,3]thiazoles: Facile synthesis and comparative appraisal against tuberculosis and neglected tropical diseases.
[So] Source:Bioorg Med Chem Lett;27(11):2583-2589, 2017 06 01.
[Is] ISSN:1464-3405
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:As part of a quest for backups to the antitubercular drug pretomanid (PA-824), we investigated the unexplored 6-nitro-2,3-dihydroimidazo[2,1-b][1,3]-thiazoles and related -oxazoles. The nitroimidazothiazoles were prepared in high yield from 2-bromo-4-nitroimidazole via heating with substituted thiiranes and diisopropylethylamine. Equivalent examples of these two structural classes provided broadly comparable MICs, with 2-methyl substitution and extended aryloxymethyl side chains preferred; albeit, S-oxidised thiazoles were ineffective for tuberculosis. Favourable microsomal stability data for a biaryl thiazole (45) led to its assessment in an acute Mycobacterium tuberculosis mouse model, alongside the corresponding oxazole (48), but the latter proved to be more efficacious. In vitro screening against kinetoplastid diseases revealed that nitroimidazothiazoles were inactive versus leishmaniasis but showed interesting activity, superior to that of the nitroimidazooxazoles, against Chagas disease. Overall, "thio-delamanid" (49) is regarded as the best lead.
[Mh] Termos MeSH primário: Antituberculosos/síntese química
Nitroimidazóis/química
Tiazóis/química
[Mh] Termos MeSH secundário: Animais
Antituberculosos/farmacologia
Antituberculosos/uso terapêutico
Doença de Chagas/tratamento farmacológico
Modelos Animais de Doenças
Camundongos
Testes de Sensibilidade Microbiana
Mycobacterium tuberculosis/efeitos dos fármacos
Nitroimidazóis/farmacologia
Nitroimidazóis/uso terapêutico
Oxazóis/química
Oxazóis/farmacologia
Oxazóis/uso terapêutico
Relação Estrutura-Atividade
Tiazóis/farmacologia
Tiazóis/uso terapêutico
Tuberculose/tratamento farmacológico
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (2-nitro-6-(4-(trifluoromethoxy)benzyloxy)-6,7-dihydro-5H-imidazo(2,1-b)(1,3)oxazine); 0 (Antitubercular Agents); 0 (Nitroimidazoles); 0 (OPC-67683); 0 (Oxazoles); 0 (Thiazoles)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171124
[Lr] Data última revisão:
171124
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE


  8 / 7938 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:25815898
[Au] Autor:Madigan CA; Martinot AJ; Wei JR; Madduri A; Cheng TY; Young DC; Layre E; Murry JP; Rubin EJ; Moody DB
[Ad] Endereço:Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
[Ti] Título:Lipidomic analysis links mycobactin synthase K to iron uptake and virulence in M. tuberculosis.
[So] Source:PLoS Pathog;11(3):e1004792, 2015 Mar.
[Is] ISSN:1553-7374
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The prolonged survival of Mycobacterium tuberculosis (M. tb) in the host fundamentally depends on scavenging essential nutrients from host sources. M. tb scavenges non-heme iron using mycobactin and carboxymycobactin siderophores, synthesized by mycobactin synthases (Mbt). Although a general mechanism for mycobactin biosynthesis has been proposed, the biological functions of individual mbt genes remain largely untested. Through targeted gene deletion and global lipidomic profiling of intact bacteria, we identify the essential biochemical functions of two mycobactin synthases, MbtK and MbtN, in siderophore biosynthesis and their effects on bacterial growth in vitro and in vivo. The deletion mutant, ΔmbtN, produces only saturated mycobactin and carboxymycobactin, demonstrating an essential function of MbtN as the mycobactin dehydrogenase, which affects antigenicity but not iron uptake or M. tb growth. In contrast, deletion of mbtK ablated all known forms of mycobactin and its deoxy precursors, defining MbtK as the essential acyl transferase. The mbtK mutant showed markedly reduced iron scavenging and growth in vitro. Further, ΔmbtK was attenuated for growth in mice, demonstrating a non-redundant role of hydroxamate siderophores in virulence, even when other M. tb iron scavenging mechanisms are operative. The unbiased lipidomic approach also revealed unexpected consequences of perturbing mycobactin biosynthesis, including extreme depletion of mycobacterial phospholipids. Thus, lipidomic profiling highlights connections among iron acquisition, phospholipid homeostasis, and virulence, and identifies MbtK as a lynchpin at the crossroads of these phenotypes.
[Mh] Termos MeSH primário: Proteínas de Bactérias/metabolismo
Ferro/metabolismo
Mycobacterium tuberculosis/metabolismo
Mycobacterium tuberculosis/patogenicidade
Oxazóis/metabolismo
Fatores de Virulência/metabolismo
[Mh] Termos MeSH secundário: Animais
Proteínas de Bactérias/genética
Camundongos
Mycobacterium tuberculosis/genética
Fatores de Virulência/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Oxazoles); 0 (Virulence Factors); 0 (mycobactins); E1UOL152H7 (Iron)
[Em] Mês de entrada:1602
[Cu] Atualização por classe:171127
[Lr] Data última revisão:
171127
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150328
[St] Status:MEDLINE
[do] DOI:10.1371/journal.ppat.1004792


  9 / 7938 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29045455
[Au] Autor:Wotanis CK; Brennan WP; Angotti AD; Villa EA; Zayner JP; Mozina AN; Rutkovsky AC; Sobe RC; Bond WG; Karatan E
[Ad] Endereço:Department of Biology, Appalachian State University, Boone, North Carolina, United States of America.
[Ti] Título:Relative contributions of norspermidine synthesis and signaling pathways to the regulation of Vibrio cholerae biofilm formation.
[So] Source:PLoS One;12(10):e0186291, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The polyamine norspermidine is one of the major polyamines synthesized by Vibrionales and has also been found in various aquatic organisms. Norspermidine is among the environmental signals that positively regulate Vibrio cholerae biofilm formation. The NspS/MbaA signaling complex detects extracellular norspermidine and mediates the response to this polyamine. Norspermidine binding to the NspS periplasmic binding protein is thought to inhibit the phosphodiesterase activity of MbaA, increasing levels of the biofilm-promoting second messenger cyclic diguanylate monophosphate, thus enhancing biofilm formation. V. cholerae can also synthesize norspermidine using the enzyme NspC as well as import it from the environment. Deletion of the nspC gene was shown to reduce accumulation of bacteria in biofilms, leading to the conclusion that intracellular norspermidine is also a positive regulator of biofilm formation. Because V. cholerae uses norspermidine to synthesize the siderophore vibriobactin it is possible that intracellular norspermidine is required to obtain sufficient amounts of iron, which is also necessary for robust biofilm formation. The objective of this study was to assess the relative contributions of intracellular and extracellular norspermidine to the regulation of biofilm formation in V. cholerae. We show the biofilm defect of norspermidine synthesis mutants does not result from an inability to produce vibriobactin as vibriobactin synthesis mutants do not have diminished biofilm forming abilities. Furthermore, our work shows that extracellular, but not intracellular norspermidine, is mainly responsible for promoting biofilm formation. We establish that the NspS/MbaA signaling complex is the dominant mediator of biofilm formation in response to extracellular norspermidine, rather than norspermidine synthesized by NspC or imported into the cell.
[Mh] Termos MeSH primário: Biofilmes/crescimento & desenvolvimento
Espermidina/análogos & derivados
Vibrio cholerae/genética
[Mh] Termos MeSH secundário: Catecóis/metabolismo
GMP Cíclico/análogos & derivados
GMP Cíclico/metabolismo
Ferro/metabolismo
Oxazóis/metabolismo
Proteínas Periplásmicas de Ligação/genética
Proteínas Periplásmicas de Ligação/metabolismo
Diester Fosfórico Hidrolases/genética
Diester Fosfórico Hidrolases/metabolismo
Transdução de Sinais
Espermidina/biossíntese
Espermidina/metabolismo
Vibrio cholerae/crescimento & desenvolvimento
Vibrio cholerae/patogenicidade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Catechols); 0 (Oxazoles); 0 (Periplasmic Binding Proteins); 56-18-8 (norspermidine); 61093-23-0 (bis(3',5')-cyclic diguanylic acid); 88217-23-6 (vibriobactin); E1UOL152H7 (Iron); EC 3.1.4.- (Phosphoric Diester Hydrolases); H2D2X058MU (Cyclic GMP); U87FK77H25 (Spermidine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171019
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0186291


  10 / 7938 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28936880
[Au] Autor:Granchi C; Caligiuri I; Bertelli E; Poli G; Rizzolio F; Macchia M; Martinelli A; Minutolo F; Tuccinardi T
[Ad] Endereço:a Department of Pharmacy , University of Pisa , Pisa , Italy.
[Ti] Título:Development of terphenyl-2-methyloxazol-5(4H)-one derivatives as selective reversible MAGL inhibitors.
[So] Source:J Enzyme Inhib Med Chem;32(1):1240-1252, 2017 Dec.
[Is] ISSN:1475-6374
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Monoacylglycerol lipase is a serine hydrolase that plays a major role in the degradation of the endocannabinoid neurotransmitter 2-arachidonoylglycerol. A wide number of MAGL inhibitors are reported in literature; however, many of them are characterised by an irreversible mechanism of action and this behavior determines an unwanted chronic MAGL inactivation, which acquires a functional antagonism of the endocannabinoid system. The possible use of reversible MAGL inhibitors has only recently been explored, due to the lack of known compounds possessing efficient reversible inhibitory activities. In this work, we report a new series of terphenyl-2-methyloxazol-5(4H)-one derivatives characterised by a reversible MAGL-inhibition mechanism. Among them, compound 20b showed to be a potent MAGL reversible inhibitor (IC = 348 nM) with a good MAGL/FAAH selectivity. Furthermore, this compound showed antiproliferative activities against two different cancer cell lines that overexpress MAGL.
[Mh] Termos MeSH primário: Monoacilglicerol Lipases/antagonistas & inibidores
Oxazóis/farmacologia
Compostos de Terfenil/farmacologia
[Mh] Termos MeSH secundário: Relação Dose-Resposta a Droga
Seres Humanos
Estrutura Molecular
Monoacilglicerol Lipases/metabolismo
Oxazóis/síntese química
Oxazóis/química
Proteínas Recombinantes/metabolismo
Relação Estrutura-Atividade
Compostos de Terfenil/síntese química
Compostos de Terfenil/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (4-((4,4'-dimethoxy-(1,1':4',1'-terphenyl)-2'-yl)methylene)-2-methyloxazol-5(4H)-one); 0 (Oxazoles); 0 (Recombinant Proteins); 0 (Terphenyl Compounds); EC 3.1.1.23 (Monoacylglycerol Lipases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171010
[Lr] Data última revisão:
171010
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170923
[St] Status:MEDLINE
[do] DOI:10.1080/14756366.2017.1375484



página 1 de 794 ir para página                         
   


Refinar a pesquisa
  Base de dados : MEDLINE Formulário avançado   

    Pesquisar no campo  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/OPAS/OMS - Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde