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  1 / 21922 MEDLINE  
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[PMID]:28471375
[Au] Autor:Zhao M; Shao GK; Huang DD; Lv XX; Guo DS
[Ad] Endereço:College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Shandong Normal University, Jinan 250014, China. chmeizhao@163.com.
[Ti] Título:Synthesis, Crystal Structures and Properties of Ferrocenyl Bis-Amide Derivatives Yielded via the Ugi Four-Component Reaction.
[So] Source:Molecules;22(5), 2017 May 04.
[Is] ISSN:1420-3049
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Ten ferrocenyl bis-amide derivatives were successfully synthesized via the Ugi four-component reaction by treating ferrocenecarboxylic acid with diverse aldehydes, amines, and isocyanides in methanol solution. Their chemical structures were fully characterized by IR, NMR, HR-MS, and X-ray diffraction analyses. They feature unique molecular morphologies and create a 14-membered ring motif in the centro-symmetric dimers generated in the solid state. Moreover, the electrochemical behavior of these ferrocenyl bis-amides was assessed by cyclic voltammetry.
[Mh] Termos MeSH primário: Amidas/química
Compostos Ferrosos/química
[Mh] Termos MeSH secundário: Amidas/síntese química
Cristalografia por Raios X
Técnicas Eletroquímicas
Ligações de Hidrogênio
Espectroscopia de Ressonância Magnética
Espectrometria de Massas
Espectrofotometria Infravermelho
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amides); 0 (Ferrous Compounds); 1271-42-7 (ferrocenecarboxylic acid)
[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:170505
[St] Status:MEDLINE


  2 / 21922 MEDLINE  
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[PMID]:28461446
[Au] Autor:Pequegnat B; Laird RM; Ewing CP; Hill CL; Omari E; Poly F; Monteiro MA; Guerry P
[Ad] Endereço:Department of Chemistry, University of Guelph, Guelph, Ontario, Canada.
[Ti] Título:Phase-Variable Changes in the Position of -Methyl Phosphoramidate Modifications on the Polysaccharide Capsule of Campylobacter jejuni Modulate Serum Resistance.
[So] Source:J Bacteriol;199(14), 2017 07 15.
[Is] ISSN:1098-5530
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:polysaccharide capsules (CPS) are characterized by the presence of nonstoichiometric -methyl phosphoramidate (MeOPN) modifications. The lack of stoichiometry is due to phase variation at homopolymeric tracts within the MeOPN transferase genes. strain 81-176 contains two MeOPN transferase genes and has been shown previously to contain MeOPN modifications at the 2 and 6 positions of the galactose (Gal) moiety in the CPS. We demonstrate here that one of the two MeOPN transferases, encoded by CJJ81176_1435, is bifunctional and is responsible for the addition of MeOPN to both the 2 and the 6 positions of Gal. A new MeOPN at the 4 position of Gal was observed in a mutant lacking the CJJ81176_1435 transferase and this was encoded by the CJJ81176_1420 transferase. During routine growth of 81-176, the CJJ81176_1420 transferase was predominantly in an off configuration, while the CJJ81176_1435 transferase was primarily on. However, exposure to normal human serum selected for cells expressing the CJJ81176_1420 transferase. MeOPN modifications appear to block binding of naturally occurring antibodies to the 81-176 CPS. The absence of MeOPN-4-Gal resulted in enhanced sensitivity to serum killing, whereas the loss of MeOPN-2-Gal and MeOPN-6-Gal resulted in enhanced resistance to serum killing, perhaps by allowing more MeOPN to be put onto the 4 position of Gal. undergoes phase variation in genes encoding surface antigens, leading to the concept that a strain of this organism consists of multiple genotypes that are selected for fitness in various environments. Methyl phosphoramidate modifications on the capsule of block access of preexisting antibodies in normal human sera to the polysaccharide chain, thus preventing activation of the classical arm of the complement cascade. We show that the capsule of strain 81-176 contains more sites of MeOPN modifications than previously recognized and that one site, on the 4 position of galactose, is more critical to complement resistance than the others. Exposure to normal human serum selects for variants in the population expressing this MeOPN modification.
[Mh] Termos MeSH primário: Amidas
Cápsulas Bacterianas/fisiologia
Campylobacter jejuni/metabolismo
Soros Imunes/imunologia
Ácidos Fosfóricos
Polissacarídeos Bacterianos/metabolismo
[Mh] Termos MeSH secundário: Animais
Anticorpos Antibacterianos
Clonagem Molecular
Regulação Bacteriana da Expressão Gênica/fisiologia
Epitopos Imunodominantes
Mutação
Polissacarídeos Bacterianos/química
Polissacarídeos Bacterianos/imunologia
Coelhos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Amides); 0 (Antibodies, Bacterial); 0 (Immune Sera); 0 (Immunodominant Epitopes); 0 (Phosphoric Acids); 0 (Polysaccharides, Bacterial); 9Q189608GB (phosphoramidic acid)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE


  3 / 21922 MEDLINE  
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[PMID]:29348070
[Au] Autor:Lovering F; Morgan P; Allais C; Aulabaugh A; Brodfuehrer J; Chang J; Coe J; Ding W; Dowty H; Fleming M; Frisbie R; Guzova J; Hepworth D; Jasti J; Kortum S; Kurumbail R; Mohan S; Papaioannou N; Strohbach JW; Vincent F; Lee K; Zapf CW
[Ad] Endereço:Medicine Design, Pfizer, Inc., 1 Portland Street, Cambridge, MA 02139, USA. Electronic address: frank.lovering@pfizer.com.
[Ti] Título:Rational approach to highly potent and selective apoptosis signal-regulating kinase 1 (ASK1) inhibitors.
[So] Source:Eur J Med Chem;145:606-621, 2018 Feb 10.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Many diseases are believed to be driven by pathological levels of reactive oxygen species (ROS) and oxidative stress has long been recognized as a driver for inflammatory disorders. Apoptosis signal-regulating kinase 1 (ASK1) has been reported to be activated by intracellular ROS and its inhibition leads to a down regulation of p38-and JNK-dependent signaling. Consequently, ASK1 inhibitors may have the potential to treat clinically important inflammatory pathologies including renal, pulmonary and liver diseases. Analysis of the ASK1 ATP-binding site suggested that Gln756, an amino acid that rarely occurs at the GK+2 position, offered opportunities for achieving kinase selectivity for ASK1 which was applied to the design of a parallel medicinal chemistry library that afforded inhibitors of ASK1 with nanomolar potency and excellent kinome selectivity. A focused optimization strategy utilizing structure-based design resulted in the identification of ASK1 inhibitors with low nanomolar potency in a cellular assay, high selectivity when tested against kinase and broad pharmacology screening panels, and attractive physicochemical properties. The compounds we describe are attractive tool compounds to inform the therapeutic potential of ASK1 inhibition.
[Mh] Termos MeSH primário: Amidas/farmacologia
MAP Quinase Quinase Quinase 5/antagonistas & inibidores
Inibidores de Proteínas Quinases/farmacologia
[Mh] Termos MeSH secundário: Amidas/síntese química
Amidas/química
Células Cultivadas
Cristalografia por Raios X
Relação Dose-Resposta a Droga
Células HEK293
Seres Humanos
MAP Quinase Quinase Quinase 5/metabolismo
Modelos Moleculares
Estrutura Molecular
Inibidores de Proteínas Quinases/síntese química
Inibidores de Proteínas Quinases/química
Proteínas Recombinantes/metabolismo
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amides); 0 (Protein Kinase Inhibitors); 0 (Recombinant Proteins); EC 2.7.11.25 (MAP Kinase Kinase Kinase 5); EC 2.7.11.25 (MAP3K5 protein, human)
[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:180120
[St] Status:MEDLINE


  4 / 21922 MEDLINE  
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[PMID]:29478638
[Au] Autor:Jin P; Song J; Wang XC; Jin X
[Ad] Endereço:School of Environmental and Municipal Engineering, Xi'an University of Architecture and Technology, Xi'an 710055, China. Electronic address: pkjin@xauat.edu.cn.
[Ti] Título:Two-dimensional correlation spectroscopic analysis on the interaction between humic acids and aluminum coagulant.
[So] Source:J Environ Sci (China);64:181-189, 2018 Feb.
[Is] ISSN:1001-0742
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:In this study, two-dimensional correlation spectroscopy integrated with synchronous fluorescence and infrared absorption spectroscopy was employed to investigate the interaction between humic acids and aluminum coagulant at slightly acidic and neutral pH. Higher fluorescence quenching was produced for fulvic-like and humic-like fractions at pH5. At pH5, the humic-like fractions originating from the carboxylic acid, carboxyl and polysaccharide compounds were bound to aluminum first, followed by the fulvic-like fractions originating from the carboxyl and polysaccharide compounds. This finding also demonstrated that the activated functional groups of HA were involved in forming the Al-HA complex, which was accompanied by the removal of other groups by co-precipitation. Meanwhile, at pH7, almost no fluorescence quenching occurred, and surface complexation was observed to occur, in which the activated functional groups were absorbed on the amorphous Al(OH) . Two-dimensional FT-IR correlation spectroscopy indicated the sequence of HA structural change during coagulation with aluminum, with IR bands affected in the order of COOH>COO >NH deformation of amide II>aliphatic hydroxyl COH at pH5, and COO >aliphatic hydroxyl COH at pH7. This study provides a promising pathway for analysis and insight into the priority of functional groups in the interaction between organic matters and metal coagulants.
[Mh] Termos MeSH primário: Alumínio/química
Substâncias Húmicas
Modelos Químicos
[Mh] Termos MeSH secundário: Amidas
Dióxido de Carbono
Ácidos Carboxílicos
Fluorescência
Concentração de Íons de Hidrogênio
Radical Hidroxila
Espectrofotometria Infravermelho
Espectroscopia de Infravermelho com Transformada de Fourier
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amides); 0 (Carboxylic Acids); 0 (Humic Substances); 142M471B3J (Carbon Dioxide); 14485-07-5 (carboxyl radical); 3352-57-6 (Hydroxyl Radical); CPD4NFA903 (Aluminum)
[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:180227
[St] Status:MEDLINE


  5 / 21922 MEDLINE  
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[PMID]:28595450
[Au] Autor:Jiang W; Zhou W; Othman R; Uchida H; Watanabe R; Suzuki T; Sakamoto B; Nagai H
[Ad] Endereço:a Department of Ocean Sciences , Tokyo University of Marine Science and Technology , Tokyo , Japan.
[Ti] Título:A new malyngamide from the marine cyanobacterium Moorea producens.
[So] Source:Nat Prod Res;32(1):97-104, 2018 Jan.
[Is] ISSN:1478-6427
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:A new malyngamide (1) was isolated along with seven known compounds (2-8) from the marine cyanobacterium Moorea producens collected in Hawaii. Compound 1 represented the first reported malyngamide with a hydroxy moiety at C-7 of the characteristic fatty acid portion of the compound. Compound 1 showed cytotoxicity against L1210 cell line at an IC value of 2.9 mM and lethal toxicity against the shrimp Palaemon paucidens at a LD value of 33.3 mg/kg. The bioactivity of compound 1 was approximately 10-100 times weaker than those of isomalyngamides A and B (3, 4). These results indicated that the methoxy group at C-7 of the fatty acid section confers a degree of bioactivity in malyngamides.
[Mh] Termos MeSH primário: Cianobactérias/química
Lipopeptídeos/química
Lipopeptídeos/farmacologia
[Mh] Termos MeSH secundário: Amidas/química
Amidas/farmacologia
Animais
Organismos Aquáticos/química
Linhagem Celular Tumoral
Leucemia L1210
Espectroscopia de Ressonância Magnética
Camundongos
Estrutura Molecular
Palaemonidae/efeitos dos fármacos
Pirróis/química
Pirróis/farmacologia
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amides); 0 (Lipopeptides); 0 (Pyrroles); 0 (isomalyngamide A); 0 (isomalyngamide B)
[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:170610
[St] Status:MEDLINE
[do] DOI:10.1080/14786419.2017.1338282


  6 / 21922 MEDLINE  
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[PMID]:28627259
[Au] Autor:Zhang X; Li D; Xue X; Zhang Y; Zhang J; Huang C; Guo Z; Tadesse N
[Ad] Endereço:a School of Pharmacy, Health Science Center , Xi'an Jiaotong University , Xi'an , P.R. China.
[Ti] Título:First total synthesis of a novel amide alkaloid derived from Aconitum taipeicum and its anticancer activity.
[So] Source:Nat Prod Res;32(2):128-132, 2018 Jan.
[Is] ISSN:1478-6427
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:A concise total synthesis of a naturally occurring 3-isopropyl-tetrahydropyrrolo[1, 2-a]pyrimidine-2, 4(1H, 3H)-dione (ITPD) isolated from Aconitum taipeicum with a three-step approach was depicted in this study for the first time. Two key intermediates, diethyl isopropylmalonate (2) and pyrrolidin-2-amine (3), being synthsesised separately from initial diethyl malonate (4) and 3, 4-dihydro-2H-pyrrol-5-amine (5), were utilised to obtain the compound entitled ITPD. ITPD showed a promising anticancer activity in vitro on SMMC-7721 cell lines. Flow cytometry and cell cycle analysis revealed that ITPD could induce apoptosis and cell cycle arrest in S phase. The occurrence of apoptosis possibly attributed to the mechanism that ITPD could mediate the mitochondrial pathway through activating caspase-3/9 and increasing the ratio of Bax/Bcl-2 to finally trigger cell apoptosis and DNA damage. Collectively, the possibility to produce sufficient quantity of synthetic ITPD provided the base for further bio-evaluation in vivo and in vitro. The bioactive assay suggested that it may be a potential candidate for further chemical optimisation and use in cancer therapy.
[Mh] Termos MeSH primário: Aconitum/química
Alcaloides/síntese química
Antineoplásicos Fitogênicos/síntese química
[Mh] Termos MeSH secundário: Alcaloides/farmacologia
Amidas/síntese química
Amidas/farmacologia
Antineoplásicos Fitogênicos/farmacologia
Apoptose/efeitos dos fármacos
Caspase 3/metabolismo
Pontos de Checagem do Ciclo Celular/efeitos dos fármacos
Linhagem Celular Tumoral
Dano ao DNA/efeitos dos fármacos
Seres Humanos
Mitocôndrias/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Alkaloids); 0 (Amides); 0 (Antineoplastic Agents, Phytogenic); EC 3.4.22.- (Caspase 3)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180228
[Lr] Data última revisão:
180228
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170620
[St] Status:MEDLINE
[do] DOI:10.1080/14786419.2017.1340283


  7 / 21922 MEDLINE  
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[PMID]:29316537
[Au] Autor:Bildziukevich U; Rárová L; Saman D; Wimmer Z
[Ad] Endereço:University of Chemistry and Technology, Department of Chemistry of Natural Compounds, Technická 5, 166 28 Prague 6, Czech Republic; Institute of Experimental Botany AS CR, v.v.i., Isotope Laboratory, Vídenská 1083, 142 20 Prague 4, Czech Republic.
[Ti] Título:Picolyl amides of betulinic acid as antitumor agents causing tumor cell apoptosis.
[So] Source:Eur J Med Chem;145:41-50, 2018 Feb 10.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:A series of picolyl amides of betulinic acid (3a-3c and 6a-6c) was prepared and subjected to the cytotoxicity screening tests. Structure-activity relationships studies resulted in finding differences in biological activity in dependence on o-, m- and p-substitution of the pyridine ring in the target amides, when cytotoxicity data of 3a-3c and 6a-6c were obtained and compared. The amides 3b and 3a displayed cytotoxicity (given in the IC values) in G-361 (0.5 ±â€¯0.1 µM and 2.4 ±â€¯0.0 µM, respectively), MCF7 (1.4 ±â€¯0.1 µM and 2.2 ±â€¯0.2 µM, respectively), HeLa (2.4 ±â€¯0.4 µM and 2.3 ±â€¯0.5 µM, respectively) and CEM (6.5 ±â€¯1.5 µM and 6.9 ±â€¯0.4 µM, respectively) tumor cell lines, and showed weak effect in the normal human fibroblasts (BJ). Selectivity against all tested cancer cells was determined and compared to normal cells with therapeutic index (TI) between 7 and 100 for compounds 3a and 3b. The therapeutic index (TI = 100) was calculated for human malignant melanoma cell line (G-361) versus normal human fibroblasts (BJ). The cytotoxicity of other target amides (3c and 6a-6c) revealed lower effects than 3a and 3b in the tested cancer cell lines.
[Mh] Termos MeSH primário: Amidas/farmacologia
Antineoplásicos/farmacologia
Apoptose/efeitos dos fármacos
Triterpenos/farmacologia
[Mh] Termos MeSH secundário: Amidas/síntese química
Amidas/química
Antineoplásicos/síntese química
Antineoplásicos/química
Linhagem Celular
Proliferação Celular/efeitos dos fármacos
Relação Dose-Resposta a Droga
Ensaios de Seleção de Medicamentos Antitumorais
Seres Humanos
Estrutura Molecular
Relação Estrutura-Atividade
Triterpenos/síntese química
Triterpenos/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amides); 0 (Antineoplastic Agents); 0 (Triterpenes); 4G6A18707N (betulinic acid)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180227
[Lr] Data última revisão:
180227
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180110
[St] Status:MEDLINE


  8 / 21922 MEDLINE  
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[PMID]:29349451
[Au] Autor:Habka S; Sohn WY; Vaquero-Vara V; Géléoc M; Tardivel B; Brenner V; Gloaguen E; Mons M
[Ad] Endereço:LIDYL, CEA, CNRS, Université Paris Saclay, CEA Saclay, Bât 522, 91191 Gif-sur-Yvette, France. michel.mons@cea.fr.
[Ti] Título:On the turn-inducing properties of asparagine: the structuring role of the amide side chain, from isolated model peptides to crystallized proteins.
[So] Source:Phys Chem Chem Phys;20(5):3411-3423, 2018 Jan 31.
[Is] ISSN:1463-9084
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Asparagine (Asn) is a powerful turn-inducer residue, with a large propensity to occupy the second position in the central region of ß-turns of proteins. The present work aims at investigating the role of a local anchoring between the Asn side chain and the main chain in this remarkable property. For this purpose, the H-bonding patterns of an asparagine residue in an isolated protein chain fragment forming a γ- or a ß-turn have been determined using IR/UV double resonance gas phase spectroscopy on laser-desorbed, jet-cooled short models in conjunction with relevant quantum chemistry calculations. These gas phase data provide evidence for an original double anchoring linking the Asn primary amide side chain (SC), which adopts a gauche+ rotameric form, to its main chain (MC) local environment. From both IR spectroscopic evidence (H-bond induced red shifts) and quantum chemistry, Asn SC is found to behave as a stronger H-bond acceptor than donor, resulting in stronger MC→SC H-bonds than SC→MC ones. These gas phase structural data, relevant to a hydrophobic environment, have been used as a reference to assess the anchoring taking place in high resolution crystallized proteins of the Protein Data Bank. This approach reveals that, when the SC adopts a gauche+ orientation, the stronger MC→SC bonds are preserved in many cases whereas the SC→MC bonds are always disrupted, in qualitative agreement with the gas phase ranking of these interactions. Most interestingly, when Asn occupies the second position of central part of a ß-turn (i.e., the very turn-inducer position), the MC→SC H-bonds are also disrupted and replaced by a water-mediated SC to MC anchoring. Owing to the specific features of the hydrated Asn side chain, we propose that it could be a turn precursor structure, able to facilitate turn formation in the early events of the folding process.
[Mh] Termos MeSH primário: Asparagina/química
Peptídeos/química
[Mh] Termos MeSH secundário: Amidas/química
Gases/química
Ligações de Hidrogênio
Estrutura Secundária de Proteína
Teoria Quântica
Espectrofotometria Infravermelho
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amides); 0 (Gases); 0 (Peptides); 7006-34-0 (Asparagine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180120
[St] Status:MEDLINE
[do] DOI:10.1039/c7cp07605c


  9 / 21922 MEDLINE  
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[PMID]:29288943
[Au] Autor:Qiu J; Gong Q; Gao J; Chen W; Zhang Y; Gu X; Tang D
[Ad] Endereço:Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, People's Republic of China; Department of Pharmaceutical Analysis, School of Pharmacy, Xuzhou Medical University, Xuzhou 221004, People's Republic of China.
[Ti] Título:Design, synthesis and evaluation of novel phenyl propionamide derivatives as non-nucleoside hepatitis B virus inhibitors.
[So] Source:Eur J Med Chem;144:424-434, 2018 Jan 20.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:As an ongoing search for potent non-nucleoside anti-HBV agents with novel structures, we described a series of phenyl propionamide derivatives (3a-b, 4a-e, 7a-g, 8a-h and 9a-b) by pharmacophore fusion strategy in the present work. All the compounds exhibited an anti-HBV activity to some extent. Among them, compounds 8d and 9b displayed most potent anti-HBV activity with IC values on HBV DNA replication of 0.46 and 0.14 µM, respectively. And the selective index values of 8d and 9b were more than 217.39 and 153.14, suggesting that 8d and 9b exhibited favorable safety profiles. Interestingly, 8d and 9b possessed significantly antiviral activities against lamivudine and entecavir resistant HBV mutants with IC values of 0.77 and 0.32 µM. Notably, preliminary anti-HBV action mechanism studies showed that 8d could inhibit intracellular HBV pgRNA and RT activity of the HBV polymerase. Molecular docking studies suggested that compound 8d could fit into the dimer-dimer interface of HBV core protein by hydrophobic interaction. In addition, in silico prediction of physicochemical properties showed that 8d conformed well to the Lipinski's rule of five, suggesting its potential for use as a drug like molecule. Taken together, 8d possessed significantly anti-HBV activity, low toxicity, diverse anti-HBV mechanism and favorable physicochemical properties, and warranted further investigation as a promising non-nucleoside anti-HBV candidate.
[Mh] Termos MeSH primário: Amidas/farmacologia
Antivirais/farmacologia
Desenho de Drogas
Vírus da Hepatite B/efeitos dos fármacos
[Mh] Termos MeSH secundário: Amidas/síntese química
Amidas/química
Antivirais/síntese química
Antivirais/química
Sobrevivência Celular/efeitos dos fármacos
Replicação do DNA/efeitos dos fármacos
Relação Dose-Resposta a Droga
Células Hep G2
Seres Humanos
Testes de Sensibilidade Microbiana
Simulação de Acoplamento Molecular
Estrutura Molecular
Relação Estrutura-Atividade
Replicação Viral/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amides); 0 (Antiviral Agents); QK07G0HP47 (propionamide)
[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


  10 / 21922 MEDLINE  
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[PMID]:29384888
[Au] Autor:Seo YG; Kim SH; Choi SS; Lee MK; Lee CH; Kim JE
[Ad] Endereço:Department of Family Medicine, Hallym University Sacred Heart Hospital, Anyang, Gyeonggi-do.
[Ti] Título:Effectiveness of continuous epidural analgesia on acute herpes zoster and postherpetic neuralgia: A retrospective study.
[So] Source:Medicine (Baltimore);97(5):e9837, 2018 Feb.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Despite early treatment of herpes zoster (HZ), postherpetic neuralgia (PHN) can persist. This study was designed to compare the therapeutic and pain relief effects of continuous epidural analgesia (CEA) on the chronic phase as well as the acute phase of HZ with standard medical treatment.Medical records of 227 patients with moderate to severe zoster-associated pain that had not responded to standard medications were retrospectively reviewed. Patients received standard treatment alone (medical group) or standard treatment plus concurrent CEA (epidural group). The acute and chronic groups were classified according to a 4-week cut-off with regard to time between the onset of the rash and the first treatment. Four groups were studied: Group A (acute/medical group); Group B (acute/epidural group); Group C (chronic/medical group); and Group D (chronic/epidural group). Pain was assessed using the visual analog scale (VAS) and measured every 2 weeks for 6 months. We compared the pain rating at 6 months after the first treatment with the initial pain rating. Response to treatment was defined as a ≥50% reduction in pain severity since the initial visit. Remission was considered complete for patients whose VAS pain score was ≤2 for >3 successive visits and who no longer needed medical support.Patients who received a combination of standard treatment plus CEA (Groups B and D) had significantly higher response to treatment (P = .001) than patients receiving standard treatment alone (Groups A and C). The adjusted odds ratio (OR) for response to treatment in the epidural group versus the medical group was 5.17 (95% confidence interval [CI]: 1.75-15.23) in the acute group and 5.37 (95% CI: 1.62-17.79) in the chronic groups. The adjusted OR for complete remission in the epidural group versus the medical group was 3.05 (95% CI: 1.20-7.73) in the acute group and 4.46 (95% CI: 1.20-16.54) in the chronic group.CEA can effectively relieve pain caused by PHN and acute HZ and increase remission rates. Combining CEA with standard medical treatment may offer a clinical advantage in the management of pain caused by PHN as well as acute HZ.
[Mh] Termos MeSH primário: Amidas/uso terapêutico
Analgesia Epidural
Anestésicos/uso terapêutico
Fentanila/uso terapêutico
Herpes Zoster/tratamento farmacológico
Neuralgia Pós-Herpética/tratamento farmacológico
[Mh] Termos MeSH secundário: Idoso
Feminino
Herpes Zoster/complicações
Herpes Zoster/diagnóstico
Seres Humanos
Masculino
Meia-Idade
Neuralgia Pós-Herpética/diagnóstico
Neuralgia Pós-Herpética/virologia
Medição da Dor
Estudos Retrospectivos
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; OBSERVATIONAL STUDY
[Nm] Nome de substância:
0 (Amides); 0 (Anesthetics); 7IO5LYA57N (ropivacaine); UF599785JZ (Fentanyl)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180221
[Lr] Data última revisão:
180221
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180201
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009837



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