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Pesquisa : D02.886.904 [Categoria DeCS]
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[PMID]:28452454
[Au] Autor:Wibowo A; Park JM; Liu SC; Khosla C; Spielman DM
[Ad] Endereço:Department of Biochemistry, Stanford University , Stanford, California 94305, United States.
[Ti] Título:Real-Time in Vivo Detection of H O Using Hyperpolarized C-Thiourea.
[So] Source:ACS Chem Biol;12(7):1737-1742, 2017 Jul 21.
[Is] ISSN:1554-8937
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Reactive oxygen species (ROS) are essential cellular metabolites widely implicated in many diseases including cancer, inflammation, and cardiovascular and neurodegenerative disorders. Yet, ROS signaling remains poorly understood, and their measurements are a challenge due to high reactivity and instability. Here, we report the development of C-thiourea as a probe to detect and measure H O dynamics with high sensitivity and spatiotemporal resolution using hyperpolarized C magnetic resonance spectroscopic imaging. In particular, we show C-thiourea to be highly polarizable and to possess a long spin-lattice relaxation time (T ), which enables real-time monitoring of ROS-mediated transformation. We also demonstrate that C-thiourea reacts readily with H O to give chemically distinguishable products in vitro and validate their detection in vivo in a mouse liver. This study suggests that C-thiourea is a promising agent for noninvasive detection of H O in vivo. More broadly, our findings outline a viable clinical application for H O detection in patients with a range of diseases.
[Mh] Termos MeSH primário: Peróxido de Hidrogênio/análise
Tioureia/química
[Mh] Termos MeSH secundário: Animais
Isótopos de Carbono/análise
DNA/química
Lipídeos/química
Fígado/metabolismo
Imagem por Ressonância Magnética
Camundongos
Estresse Oxidativo
Proteínas/química
Espécies Reativas de Oxigênio
Análise Espectral
Tioureia/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Carbon Isotopes); 0 (Lipids); 0 (Proteins); 0 (Reactive Oxygen Species); 9007-49-2 (DNA); BBX060AN9V (Hydrogen Peroxide); GYV9AM2QAG (Thiourea)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180207
[Lr] Data última revisão:
180207
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1021/acschembio.7b00130


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[PMID]:27779337
[Au] Autor:Duan J; Cheng Y; Cheng J; Li R; Li P
[Ad] Endereço:Department of Chemistry, South University of Science and Technology of China, 1088 Xueyuan Blvd., Nanshan District, Shenzhen, Guangdong, 518055, P. R. China.
[Ti] Título:Organocatalytic Asymmetric Benzylation and Aldol-Hemiacetalization of α,ß-Unsaturated Trifluoromethyl Ketones: Efficient Enantioselective Construction of 3,4-Dihydroisocoumarins.
[So] Source:Chemistry;23(3):519-523, 2017 01 12.
[Is] ISSN:1521-3765
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:A new method has been developed for the organocatalytic enantioselective benzylation and aldol-hemiacetalization of α,ß-unsaturated trifluoromethyl ketones with toluene derivatives in the presence of a tertiary amine-thiourea catalyst. This method represents a facile and efficient strategy for the asymmetric synthesis of optically active 3,4-dihydroisocoumarins bearing a trifluoromethylated tetrasubstituted carbon stereocenter with high enantioselectivity. Notably, this strategy was used to synthesize several chiral trifluoromethylated analogues of typharin with high efficiency.
[Mh] Termos MeSH primário: Cumarínicos/química
Cetonas/química
[Mh] Termos MeSH secundário: Aldeídos
Aminas/química
Carbono/química
Catálise
Cumarínicos/síntese química
Cristalografia por Raios X
Isocumarinas/química
Cetonas/síntese química
Conformação Molecular
Estereoisomerismo
Tioureia/química
Tolueno/análogos & derivados
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Aldehydes); 0 (Amines); 0 (Coumarins); 0 (Isocoumarins); 0 (Ketones); 0 (typharin); 3FPU23BG52 (Toluene); 7440-44-0 (Carbon); 8C6G962B53 (3-hydroxybutanal); A4VZ22K1WT (coumarin); GYV9AM2QAG (Thiourea)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171205
[Lr] Data última revisão:
171205
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161026
[St] Status:MEDLINE
[do] DOI:10.1002/chem.201604920


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[PMID]:28873584
[Au] Autor:Zhao Y; Xu L; Liu M; Duan Z; Wang H
[Ad] Endereço:Institute of Medicine and Materials Applied Technologies, College of Chemistry and Chemical Engineering, Qufu Normal University, Qufu City 273165, PR China; College of Chemistry and Pharmaceutical Science, Qingdao Agricultural University, Qingdao 266109, PR China. Electronic address: zyftoday@163.co
[Ti] Título:Magnetic mesoporous thiourea-formaldehyde resin as selective adsorbent: A simple and highly-sensitive electroanalysis strategy for lead ions in drinking water and milk by solid state-based anodic stripping.
[So] Source:Food Chem;239:40-47, 2018 Jan 15.
[Is] ISSN:0308-8146
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:A simple and sensitive electroanalysis method has been developed for the direct determination of lead ions of nanomolar levels in real samples of drinking water and milk by employing magnetic mesoporous thiourea-formaldehyde resin (TUF@Fe O ) nanocomposites as the capturing absorbents. Here, the prepared TUF@Fe O with the large-surface-area mesoporous structure and strong Pb -binding ligands could facilitate the selective and large-scale adsorption of Pb ions from the complex sample matrices to be further magnetically separated onto the magnetic electrodes. Moreover, the Pb ions magnetically accumulated were electrochemically measured alternatively by the solid state-based anodic stripping of PbCl . The detection limit was found to be 0.0070nmolL . The as-developed Pb electroanalysis method with the magnetic electrodes and TUF@Fe O nanocomposites could avoid the complicated sample preparation and electrode modification, thus holding the great potential of applications for the Pb detection in different real samples.
[Mh] Termos MeSH primário: Água Potável/química
Leite/química
[Mh] Termos MeSH secundário: Animais
Eletrodos
Formaldeído
Chumbo
Tioureia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Drinking Water); 1HG84L3525 (Formaldehyde); 2P299V784P (Lead); GYV9AM2QAG (Thiourea)
[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:170907
[St] Status:MEDLINE


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[PMID]:28988108
[Au] Autor:Ji C; Yang B; Huang SY; Huang JW; Cheng B
[Ad] Endereço:Department of Dermatology, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, Fujian, China.
[Ti] Título:Salubrinal protects human skin fibroblasts against UVB-induced cell death by blocking endoplasmic reticulum (ER) stress and regulating calcium homeostasis.
[So] Source:Biochem Biophys Res Commun;493(4):1371-1376, 2017 Dec 02.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The role of UVB in skin photo damages has been widely reported. Overexposure to UVB will induce severe DNA damages in epidermal cells and cause most cytotoxic symptoms. In the present study, we tested the potential activity of salubrinal, a selective inhibitor of Eukaryotic Initiation Factor 2 (eIF2) -alpha phosphatase, against UV-induced skin cell damages. We first exposed human fibroblasts to UVB radiation and evaluated the cytosolic Ca level as well as the induction of ER stress. We found that UVB radiation induced the depletion of ER Ca and increased the expression of ER stress marker including phosphorylated PERK, CHOP, and phosphorylated IRE1α. We then determined the effects of salubrinal in skin cell death induced by UVB radiation. We observed that cells pre-treated with salubrinal had a higher survival rate compared to cells treated with UVB alone. Pre-treatment with salubrinal successfully re-established the ER function and Ca homeostasis. Our results suggest that salubrinal can be a potential therapeutic agents used in preventing photoaging and photo damages.
[Mh] Termos MeSH primário: Cinamatos/farmacologia
Protetores contra Radiação/farmacologia
Envelhecimento da Pele/efeitos dos fármacos
Pele/efeitos dos fármacos
Pele/efeitos da radiação
Tioureia/análogos & derivados
[Mh] Termos MeSH secundário: Cálcio/metabolismo
Morte Celular/efeitos dos fármacos
Morte Celular/efeitos da radiação
Células Cultivadas
Cinamatos/administração & dosagem
Relação Dose-Resposta a Droga
Estresse do Retículo Endoplasmático/efeitos dos fármacos
Estresse do Retículo Endoplasmático/efeitos da radiação
Fibroblastos/efeitos dos fármacos
Fibroblastos/metabolismo
Fibroblastos/patologia
Homeostase/efeitos dos fármacos
Seres Humanos
Protetores contra Radiação/administração & dosagem
Pele/metabolismo
Envelhecimento da Pele/patologia
Envelhecimento da Pele/fisiologia
Protetores Solares/administração & dosagem
Protetores Solares/farmacologia
Tioureia/administração & dosagem
Tioureia/farmacologia
Raios Ultravioleta/efeitos adversos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cinnamates); 0 (Radiation-Protective Agents); 0 (Sunscreening Agents); 0 (salubrinal); GYV9AM2QAG (Thiourea); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171030
[Lr] Data última revisão:
171030
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171009
[St] Status:MEDLINE


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[PMID]:28966275
[Au] Autor:Viana GM; Soares DC; Santana MV; do Amaral LH; Meireles PW; Nunes RP; da Silva LCRP; Aguiar LCS; Rodrigues CR; de Sousa VP; Castro HC; Abreu PA; Sathler PC; Saraiva EM; Cabral LM
[Ad] Endereço:Universidade Federal do Rio de Janeiro, LabTIF, Faculdade de Farmácia, Ilha do Fundão.
[Ti] Título:Antileishmanial Thioureas: Synthesis, Biological Activity and in Silico Evaluations of New Promising Derivatives.
[So] Source:Chem Pharm Bull (Tokyo);65(10):911-919, 2017.
[Is] ISSN:1347-5223
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:Leishmaniasis is a neglected tropical disease caused by protozoan parasites belonging to the genus Leishmania. Currently, the drugs available for treatment of this disease present high toxicity, along with development of parasite resistance. In order to overcome these problems, efforts have been made to search for new and more effective leishmanicidal drugs. The aim of this study was to synthesize and investigate the leishmanicidal effect of N,N'-disubstituted thioureas against Leishmania amazonensis, with evaluation of their in silico pharmacokinetics and toxicity profiles. Our results showed that different thioureas could be obtained in high to moderate yields using simple reaction conditions. Nine thiourea derivatives (3e, 3i, 3k, 3l, 3p, 3q, 3v, 3x and 3z) were active against parasite promastigotes (IC 21.48-189.10 µM), with low cytotoxicity on mice peritoneal macrophages (CC >200 µM), except for thiourea 3e (CC =49.22 µM). After that, the most promising thioureas (3k, 3l, 3p, 3q and 3v) showed IC ranging from 70 to 150 µM against L. amazonensis amastigotes in infected macrophages. Except for thiourea 3p, the leishmanicidal activity of the derivatives were independent of nitric oxide (NO) production. Thioureas 3q and 3v affected promastigotes cell cycle without disturbing the mitochondrial membrane potential. Furthermore, our derivatives showed satisfactory theoretical absorption, distribution, metabolism, excretion, toxicity (ADMET) properties. These data indicate that thiourea derivatives are good candidates as leading compounds for the development of new leishmanicidal drugs.
[Mh] Termos MeSH primário: Antiprotozoários/síntese química
Antiprotozoários/farmacologia
Leishmania/efeitos dos fármacos
Tioureia/química
Tioureia/farmacologia
[Mh] Termos MeSH secundário: Animais
Pontos de Checagem do Ciclo Celular/efeitos dos fármacos
Concentração Inibidora 50
Macrófagos Peritoneais/efeitos dos fármacos
Potencial da Membrana Mitocondrial/efeitos dos fármacos
Camundongos
Óxido Nítrico/metabolismo
Teoria Quântica
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiprotozoal Agents); 31C4KY9ESH (Nitric Oxide); GYV9AM2QAG (Thiourea)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171030
[Lr] Data última revisão:
171030
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171003
[St] Status:MEDLINE
[do] DOI:10.1248/cpb.c17-00293


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[PMID]:28863355
[Au] Autor:Li ZH; Liu XQ; Zhao TQ; Geng PF; Guo WG; Yu B; Liu HM
[Ad] Endereço:Key Laboratory of Advanced Drug Preparation Technologies (Zhengzhou University), Ministry of Education; School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, PR China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, PR China; Key Labor
[Ti] Título:Design, synthesis and preliminary biological evaluation of new [1,2,3]triazolo[4,5-d]pyrimidine/thiourea hybrids as antiproliferative agents.
[So] Source:Eur J Med Chem;139:741-749, 2017 Oct 20.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:A series of new [1,2,3]triazolo[4,5-d]pyrimidine/thiourea hybrids were designed and synthesized through the scaffold replacement/ring cleavage strategy. SARs studies revealed that the N-heteroarene moiety attached to the thiourea is preferred over the phenyl ring for the R substituents, while the hydrophobic aromatic group is beneficial for improving the activity. Among these compounds, compound 5r significantly inhibited cell growth of lung cancer cell lines H1650 and A549 (IC = 1.91, 3.28 µM, respectively), but was less toxic against the normal cell line GES-1 (IC = 27.43 µM). Mechanistic studies showed that compound 5r could remarkably inhibit the colony formation of H1650 cells, induced apoptosis possibly through the intrinsic apoptotic pathways, and arrested the cell cycle at G2/M phase. Our studies suggest that the [1,2,3]triazolo[4,5-d]pyrimidine/thiourea hybrids are a new class of chemotypes possessing interesting antiproliferative activity against lung cancer cells and could be potentially utilized for designing new antitumor agents.
[Mh] Termos MeSH primário: Desenho de Drogas
Tioureia/análogos & derivados
Tioureia/farmacologia
Triazóis/farmacologia
[Mh] Termos MeSH secundário: Apoptose/efeitos dos fármacos
Linhagem Celular
Proliferação Celular/efeitos dos fármacos
Relação Dose-Resposta a Droga
Seres Humanos
Estrutura Molecular
Relação Estrutura-Atividade
Tioureia/química
Triazóis/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (1-(2-((3-(2-(1H-indol-3-yl)ethyl)-5-(propylthio)-3H-(1,2,3)triazolo(4,5-d)pyrimidin-7-yl)amino)ethyl)-3-(pyridin-3-yl)thiourea); 0 (Triazoles); GYV9AM2QAG (Thiourea)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170902
[St] Status:MEDLINE


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[PMID]:28844711
[Au] Autor:Fallatah MM; Liu S; Sevigny MB; Zou H; Louie MC
[Ad] Endereço:Department of Natural Sciences and Mathematics, Dominican University of California, 50 Acacia Avenue, San Rafael, CA 94901, USA.
[Ti] Título:Novel flexible heteroarotinoid, SL-1-18, promotes ERα degradation to inhibit breast cancer cell growth.
[So] Source:Cancer Lett;408:82-91, 2017 Nov 01.
[Is] ISSN:1872-7980
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:SL-1-18 (1-(chrysen-6-yl)-3-(4-nitrophenyl)thiourea) is new flexible heteroarotinoid (Flex-Het) analog derived from the parent compound, SHetA2, and our previous study showed comparable activity to SHetA2 in terms of inhibiting ER+ breast cancer cell growth. This current study aims to determine the molecular mechanism underlying SL-1-18's effect on breast cancer cell growth. Our results indicate that SL-1-18 inhibits cell proliferation of ER+ breast cancer cells (MCF-7 and T-47D) by preventing cell cycle progression. SL-1-18 treatment correlated positively with decreased expression of key cell-cycle regulators, such as cyclin D1, as well as other ERα-target genes at both the transcript and protein levels. Interestingly, decreased expression of ERα was also observed, with a significant reduction at the protein level within 2 h of SL-1-18 treatment, while the decrease in mRNA occurred at a later time point. ERα degradation was shown to be mediated by the ubiquitination-proteasome pathway. In summary, this is the first study to show that a Flex-Het- SL-1-18- can promote the degradation of ERα via the ubiquitin-proteasome pathway and should be further developed as a therapeutic option for ER+ breast cancer.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Neoplasias da Mama/tratamento farmacológico
Cromanos/farmacologia
Crisenos/farmacologia
Receptor alfa de Estrogênio/metabolismo
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
Proteólise/efeitos dos fármacos
Tioureia/análogos & derivados
[Mh] Termos MeSH secundário: Apoptose/efeitos dos fármacos
Neoplasias da Mama/metabolismo
Neoplasias da Mama/patologia
Ciclo Celular/efeitos dos fármacos
Proliferação Celular/efeitos dos fármacos
Feminino
Seres Humanos
Complexo de Endopeptidases do Proteassoma
Tionas/farmacologia
Tioureia/farmacologia
Células Tumorais Cultivadas
Ubiquitinação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 ((((4-nitrophenyl)amino)(2,2,4,4-tetramethyl thiochroman-6-yl)amino) methane-1-thione); 0 (1-(chrysen-6-yl)-3-(4-nitrophenyl)thiourea); 0 (Antineoplastic Agents); 0 (Chromans); 0 (Chrysenes); 0 (Estrogen Receptor alpha); 0 (Thiones); 0 (estrogen receptor alpha, human); EC 3.4.25.1 (Proteasome Endopeptidase Complex); GYV9AM2QAG (Thiourea)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171101
[Lr] Data última revisão:
171101
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170829
[St] Status:MEDLINE


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[PMID]:28776440
[Au] Autor:Zengin Kurt B; Sonmez F; Durdagi S; Aksoydan B; Ekhteiari Salmas R; Angeli A; Kucukislamoglu M; Supuran CT
[Ad] Endereço:a Faculty of Pharmacy, Department of Pharmaceutical Chemistry , Bezmialem Vakif University , Istanbul , Turkey.
[Ti] Título:Synthesis, biological activity and multiscale molecular modeling studies for coumaryl-carboxamide derivatives as selective carbonic anhydrase IX inhibitors.
[So] Source:J Enzyme Inhib Med Chem;32(1):1042-1052, 2017 Dec.
[Is] ISSN:1475-6374
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:New coumaryl-carboxamide derivatives with the thiourea moiety as a linker between the alkyl chains and/or the heterocycle nucleus were synthesized and their inhibitory activity against the human carbonic anhydrase (hCA) isoforms hCA I, II, VII and IX were evaluated. While the hCA I, II and VII isoforms were not inhibited by the investigated compounds, the tumour-associated isoform hCA IX was inhibited in the high nanomolar range. 2-Oxo-N-((2-(pyrrolidin-1-yl)ethyl)carbamothioyl)-2H-chromene-3-carboxamide (e11) exhibited a selective inhibitory action against hCA IX with the K of 107.9 nM. In order to better understand the inhibitory profiles of studied molecules, multiscale molecular modeling approaches were used. Different molecular docking algorithms were used to investigate binding poses and predicted binding energies of studied compounds at the active sites of the CA I, II, VII and IX isoforms.
[Mh] Termos MeSH primário: Anidrase Carbônica IX/antagonistas & inibidores
Inibidores da Anidrase Carbônica/farmacologia
Ácidos Cumáricos/farmacologia
Tioureia/farmacologia
[Mh] Termos MeSH secundário: Algoritmos
Anidrase Carbônica IX/metabolismo
Inibidores da Anidrase Carbônica/síntese química
Inibidores da Anidrase Carbônica/química
Ácidos Cumáricos/síntese química
Ácidos Cumáricos/química
Relação Dose-Resposta a Droga
Seres Humanos
Modelos Moleculares
Estrutura Molecular
Relação Estrutura-Atividade
Tioureia/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Carbonic Anhydrase Inhibitors); 0 (Coumaric Acids); EC 4.2.1.1 (Carbonic Anhydrase IX); GYV9AM2QAG (Thiourea)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171009
[Lr] Data última revisão:
171009
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170805
[St] Status:MEDLINE
[do] DOI:10.1080/14756366.2017.1354857


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[PMID]:28750057
[Au] Autor:Shen Q; Zhou W; Hu L; Qi Y; Ning H; Chen J; Mo H
[Ad] Endereço:Department of Food Science, Henan Institute of Science and Technology, Xinxiang, China.
[Ti] Título:Bactericidal activity of alpha-bromocinnamaldehyde against persisters in Escherichia coli.
[So] Source:PLoS One;12(7):e0182122, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Persisters are tolerant to multiple antibiotics, and widely distributed in bacteria, fungi, parasites, and even cancerous human cell populations, leading to recurrent infections and relapse after therapy. In this study, we investigated the potential of cinnamaldehyde and its derivatives to eradicate persisters in Escherichia coli. The results showed that 200 µg/ml of alpha-bromocinnamaldehyde (Br-CA) was capable of killing all E. coli cells during the exponential phase. Considering the heterogeneous nature of persisters, multiple types of persisters were induced and exposed to Br-CA. Our results indicated that no cells in the ppGpp-overproducing strain or TisB-overexpressing strain survived the treatment of Br-CA although considerable amounts of persisters to ampicillin (Amp) and ciprofloxacin (Cip) were induced. Chemical induction by carbonyl cyanide m-chlorophenylhydrazone (CCCP) led to the formation of more than 10% persister to Amp and Cip in the entire population, and Br-CA still completely eradicated them. In addition, the cells in the stationary phase, which are usually highly recalcitrant to antibiotics treatment, were also completely eradicated by 400 µg/ml of Br-CA. Further studies showed that neither thiourea (hydroxyl-radical scavenger) nor DPTA (Fe3+ chelator to block the hydroxyl-radical) affected the bactericidal efficiency of the Br-CA to kill E. coli, indicating a ROS-independent bactericidal mechanism. Taken together, we concluded that Br-CA compound has a novel bactericidal mechanism and the potential to mitigate antibiotics resistance crisis.
[Mh] Termos MeSH primário: Aldeídos/farmacologia
Antibacterianos/farmacologia
Escherichia coli/efeitos dos fármacos
[Mh] Termos MeSH secundário: Toxinas Bacterianas/metabolismo
Análise por Conglomerados
Testes de Sensibilidade Microbiana
Viabilidade Microbiana/efeitos dos fármacos
Ácido Pentético/farmacologia
Espécies Reativas de Oxigênio/metabolismo
Tioureia/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Aldehydes); 0 (Anti-Bacterial Agents); 0 (Bacterial Toxins); 0 (Reactive Oxygen Species); 5443-49-2 (alpha-bromocinnamaldehyde); 7A314HQM0I (Pentetic Acid); GYV9AM2QAG (Thiourea)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171004
[Lr] Data última revisão:
171004
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170728
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0182122


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[PMID]:28722191
[Au] Autor:Konno S; Ishikawa F; Suzuki T; Dohmae N; Kakeya H; Tanabe G
[Ad] Endereço:Department of System Chemotherapy and Molecular Sciences, Division of Bioinformatics and Chemical Genomics, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo, Kyoto, 606-8501, Japan.
[Ti] Título:A Chemoproteomics Approach to Investigate Phosphopantetheine Transferase Activity at the Cellular Level.
[So] Source:Chembiochem;18(18):1855-1862, 2017 Sep 19.
[Is] ISSN:1439-7633
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Phosphopantetheinylation is an essential post-translational protein modification to primary and secondary metabolic pathways that ensures bacterial cell viability and virulence, and it is used in the production of many pharmaceuticals. Traditional methods have not provided a comprehensive understanding of these modifications. By using chemical proteomic probes for adenylation and thiolation domains in nonribosomal peptide synthetases (NRPSs), chemoproteomics has been applied to survey and validate the cellular activity of 4-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]-N-(4-methoxypyridin-2-yl)piperazine-1-carbothioamide (ML267), which is a potent and selective small-molecule 4'-phosphopantetheinyl transferase (PPTase) inhibitor that attenuates secondary metabolism and viability of bacterial cells. ML267 inhibited Sfp-type PPTase and antagonized phosphopantetheinylation in cells, which resulted in a decrease in phosphopantetheinylated NRPSs and the attenuation of Sfp-PPTase-dependent metabolite production. These results indicate that this chemoproteomics platform should enable a precise interpretation of the cellular activities of Sfp-type PPTase inhibitors.
[Mh] Termos MeSH primário: Proteínas de Bactérias/metabolismo
Proteômica
Transferases (Outros Grupos de Fosfato Substituídos)/metabolismo
[Mh] Termos MeSH secundário: Antibacterianos/química
Antibacterianos/metabolismo
Antibacterianos/farmacologia
Bacillus subtilis/efeitos dos fármacos
Bacillus subtilis/enzimologia
Proteínas de Bactérias/antagonistas & inibidores
Lipopeptídeos/metabolismo
Peptídeo Sintases/análise
Peptídeo Sintases/metabolismo
Peptídeos Cíclicos/metabolismo
Ligação Proteica
Processamento de Proteína Pós-Traducional
Piridinas/química
Piridinas/metabolismo
Piridinas/farmacologia
Tioureia/análogos & derivados
Tioureia/química
Tioureia/metabolismo
Tioureia/farmacologia
Transferases (Outros Grupos de Fosfato Substituídos)/antagonistas & inibidores
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (4-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)-N-(4-methoxypyridin-2-yl)piperazine-1-carbothioamide); 0 (Anti-Bacterial Agents); 0 (Bacterial Proteins); 0 (Lipopeptides); 0 (Peptides, Cyclic); 0 (Pyridines); 0 (phosphopantetheinyl transferase); 24730-31-2 (surfactin peptide); EC 2.7.8.- (Transferases (Other Substituted Phosphate Groups)); EC 6.3.2.- (Peptide Synthases); EC 6.3.2.- (non-ribosomal peptide synthase); GYV9AM2QAG (Thiourea)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170928
[Lr] Data última revisão:
170928
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170720
[St] Status:MEDLINE
[do] DOI:10.1002/cbic.201700301



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