Base de dados : MEDLINE
Pesquisa : D02.886.675.867 [Categoria DeCS]
Referências encontradas : 2206 [refinar]
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  1 / 2206 MEDLINE  
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[PMID]:29268128
[Au] Autor:Jafari B; Ospanov M; Ejaz SA; Yelibayeva N; Khan SU; Amjad ST; Safarov S; Abilov ZA; Turmukhanova MZ; Kalugin SN; Ehlers P; Lecka J; Sévigny J; Iqbal J; Langer P
[Ad] Endereço:Institut für Chemie, Universität Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany.
[Ti] Título:2-Substituted 7-trifluoromethyl-thiadiazolopyrimidones as alkaline phosphatase inhibitors. Synthesis, structure activity relationship and molecular docking study.
[So] Source:Eur J Med Chem;144:116-127, 2018 Jan 20.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Alkaline Phosphatases (APs) play a key role in maintaining a ratio of phosphate to inorganic pyrophosphate (P /PP ) and thus regulate extracellular matrix calcification during bone formation and growth. Among different isozymes of AP, aberrant increase in the level of tissue non-specific alkaline phosphatase (TNAP) is strongly associated with vascular calcification and end-stage renal diseases. In this context, we synthesized a novel series of fluorinated pyrimidone derivatives, i.e., 2-bromo-7-trifluoromethyl-5-oxo-5H-1,3,4-thiadiazolepyrimidones. The bromine functionality was further used for derivatisation by nucleophilic aromatic substitution using amines as nucleophiles as well as by Palladium catalysed Suzuki-Miyaura reactions. The synthesized derivatives were found potent but non-selective inhibitors of both isozymes of AP. Arylated thiadiazolopyrimidones exhibited stronger inhibitory activities than 2-amino-thiadiazolopyrimidones. The binding modes and possible interactions of the most active inhibitor within the active site of the enzyme were observed by molecular docking studies.
[Mh] Termos MeSH primário: Fosfatase Alcalina/antagonistas & inibidores
Inibidores Enzimáticos/química
Inibidores Enzimáticos/farmacologia
Pirimidinonas/química
Pirimidinonas/farmacologia
Tiadiazóis/química
Tiadiazóis/farmacologia
[Mh] Termos MeSH secundário: Fosfatase Alcalina/metabolismo
Inibidores Enzimáticos/síntese química
Halogenação
Seres Humanos
Simulação de Acoplamento Molecular
Pirimidinonas/síntese química
Relação Estrutura-Atividade
Tiadiazóis/síntese química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Enzyme Inhibitors); 0 (Pyrimidinones); 0 (Thiadiazoles); EC 3.1.3.1 (Alkaline Phosphatase)
[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:171222
[St] Status:MEDLINE


  2 / 2206 MEDLINE  
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[PMID]:29310025
[Au] Autor:Madhu Sekhar M; Nagarjuna U; Padmavathi V; Padmaja A; Reddy NV; Vijaya T
[Ad] Endereço:Department of Chemistry, Sri Venkateswara University, Tirupati 517 502, Andhra Pradesh, India.
[Ti] Título:Synthesis and antimicrobial activity of pyrimidinyl 1,3,4-oxadiazoles, 1,3,4-thiadiazoles and 1,2,4-triazoles.
[So] Source:Eur J Med Chem;145:1-10, 2018 Feb 10.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:A new class of methylthio linked pyrimidinyl 1,3,4-oxadiazoles, 1,3,4-thiadiazoles and 1,2,4-triazoles were prepared under conventional and ultrasound irradiation methods. All the compounds were obtained in higher yields and in shorter reaction times in ultrasound irradiation method when compared with the conventional method. The title compounds were tested for antimicrobial activity. The compounds 12c and 12f exhibited promising antibacterial activity against P. aeruginosa whereas the compounds 13c and 13f showed pronounced antifungal activity against A. niger.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Antifúngicos/farmacologia
Aspergillus niger/efeitos dos fármacos
Oxidiazóis/farmacologia
Pseudomonas aeruginosa/efeitos dos fármacos
Pirimidinas/farmacologia
Tiadiazóis/farmacologia
Triazóis/farmacologia
[Mh] Termos MeSH secundário: Antibacterianos/síntese química
Antibacterianos/química
Antifúngicos/síntese química
Antifúngicos/química
Relação Dose-Resposta a Droga
Testes de Sensibilidade Microbiana
Estrutura Molecular
Oxidiazóis/síntese química
Oxidiazóis/química
Pirimidinas/síntese química
Pirimidinas/química
Relação Estrutura-Atividade
Tiadiazóis/síntese química
Tiadiazóis/química
Triazóis/síntese química
Triazóis/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Antifungal Agents); 0 (Oxadiazoles); 0 (Pyrimidines); 0 (Thiadiazoles); 0 (Triazoles); 14IAC3GH7G (1,3,4-thiadiazole)
[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:180109
[St] Status:MEDLINE


  3 / 2206 MEDLINE  
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[PMID]:29431064
[Au] Autor:Mathuram TL; Ravikumar V; Reece LM; Sasikumar CS; Cherian KM
[Ad] Endereço:Department of Stem Cell and Tissue Engineering, Frontier Mediville (A Unit of Frontier Lifeline and Dr. K. M. Cherian Heart Foundation), Affiliated to University of Madras, Chennai-601201, Tamil Nadu, India.
[Ti] Título:Correlative Studies Unravelling the Possible Mechanism of Cell Death in Tideglusib-Treated Human Ovarian Teratocarcinoma-Derived PA-1 Cells.
[So] Source:J Environ Pathol Toxicol Oncol;36(4):321-344, 2017.
[Is] ISSN:2162-6537
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:This study aims to unravel the use of GSK-3 inhibitors as viable apoptotic inducers for teratocarcinoma-derived ovarian PA-1 cells. MTT assay was carried out to assess inhibitory concentrations of LiCl and TDG. AO/EB staining and Hoechst 33258 staining were employed to assess the damage. Mitochondrial membrane potential (ΔΨm) and ROS generation were assessed with IC50 concentrations of LiCl and TDG. Tumor-related genes (p53, p21, IL-8, TNF-α, MMP-2, Fas-L, Cox-2, and caspase-3) were assessed with 1/4 IC50, 1/2 IC50, IC50 concentrations by semi-quantitative RT- PCR. Cell cycle analysis was performed with IC50 concentration of LiCl and TDG. Western blot analysis was performed for caspase-3, caspase-7, caspase-9, PARP to estimate the possible damage induced by GSK-3 inhibitors and regulation of GSK-3ß, pGSK-3ß, Cox-2. GSK-3 inhibitors demonstrated a concentration and time-dependent reduction in cell viability, exhibiting significant ROS generation and reduced ΔΨm at their IC50 values. Substantial concentration-dependent gene expression changes with significant upregulation of P21, Cox-2, TNF-α, caspase-3, Fas-L were observed. Protein expression of caspase-3 caspase-7, caspase-9, PARP exhibited significant cleavage in LiCl and TDG-treated cells. Protein expression of Cox-2 was significantly increased in IC50 concentration of TDG. Cell cycle analysis showed significant accumulation of cells at sub-G0-G1.
[Mh] Termos MeSH primário: Apoptose/efeitos dos fármacos
Quinase 3 da Glicogênio Sintase/antagonistas & inibidores
Neoplasias Ovarianas/tratamento farmacológico
Teratocarcinoma/tratamento farmacológico
Tiadiazóis/farmacologia
[Mh] Termos MeSH secundário: Linhagem Celular Tumoral
Inibidor de Quinase Dependente de Ciclina p21/genética
Relação Dose-Resposta a Droga
Feminino
Seres Humanos
Cloreto de Lítio/farmacologia
Metaloproteinase 2 da Matriz/genética
Potencial da Membrana Mitocondrial
Neoplasias Ovarianas/patologia
Espécies Reativas de Oxigênio/metabolismo
Teratocarcinoma/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CDKN1A protein, human); 0 (Cyclin-Dependent Kinase Inhibitor p21); 0 (NP 031112); 0 (Reactive Oxygen Species); 0 (Thiadiazoles); EC 2.7.11.26 (Glycogen Synthase Kinase 3); EC 3.4.24.24 (Matrix Metalloproteinase 2); G4962QA067 (Lithium Chloride)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180216
[Lr] Data última revisão:
180216
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180213
[St] Status:MEDLINE
[do] DOI:10.1615/JEnvironPatholToxicolOncol.2017025018


  4 / 2206 MEDLINE  
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[PMID]:29311510
[Au] Autor:Takai K; Enomoto T
[Ad] Endereço:Drug Research Division, Sumitomo Dainippon Pharma Co., Ltd.
[Ti] Título:Discovery and Development of Muscarinic Acetylcholine M Activators as Promising Therapeutic Agents for CNS Diseases.
[So] Source:Chem Pharm Bull (Tokyo);66(1):37-44, 2018.
[Is] ISSN:1347-5223
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:Among the muscarinic acetylcholine receptor (mAChR) subtypes, the M receptor has been investigated as a promising drug target for the treatment of schizophrenia. These investigations have been based on findings from M -deficient mice studies as well as on the results of a clinical trial that used xanomeline, an M /M mAChRs-preferring agonist. Both orthosteric agonists and positive allosteric modulators of M mAChR have been reported as promising ligands that not only have antipsychotic effects, but can also improve cognitive impairment and motor dysfunction. However, challenges remain due to the high homology of the orthosteric binding site among all muscarinic receptors. In this review, we summarize our approach to the identification of M mAChR activators, orthosteric agonists, and positive allosteric modulators based on M mAChR structural information and structure-activity relationship studies. These findings indicate that selective M mAChR activators are promising potential therapeutic agents for several central nervous system conditions.
[Mh] Termos MeSH primário: Doenças do Sistema Nervoso Central/tratamento farmacológico
Descoberta de Drogas
Piridinas/farmacologia
Receptor Muscarínico M4/agonistas
Tiadiazóis/farmacologia
[Mh] Termos MeSH secundário: Animais
Doenças do Sistema Nervoso Central/metabolismo
Seres Humanos
Estrutura Molecular
Piridinas/química
Receptor Muscarínico M4/deficiência
Receptor Muscarínico M4/metabolismo
Relação Estrutura-Atividade
Tiadiazóis/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Pyridines); 0 (Receptor, Muscarinic M4); 0 (Thiadiazoles); 9ORI6L73CJ (xanomeline)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180213
[Lr] Data última revisão:
180213
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180110
[St] Status:MEDLINE
[do] DOI:10.1248/cpb.c17-00413


  5 / 2206 MEDLINE  
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[PMID]:28465426
[Au] Autor:Pryke KM; Abraham J; Sali TM; Gall BJ; Archer I; Liu A; Bambina S; Baird J; Gough M; Chakhtoura M; Haddad EK; Kirby IT; Nilsen A; Streblow DN; Hirsch AJ; Smith JL; DeFilippis VR
[Ad] Endereço:Vaccine and Gene Therapy Institute, Oregon Health and Science University, Portland, Oregon, USA.
[Ti] Título:A Novel Agonist of the TRIF Pathway Induces a Cellular State Refractory to Replication of Zika, Chikungunya, and Dengue Viruses.
[So] Source:MBio;8(3), 2017 May 02.
[Is] ISSN:2150-7511
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The ongoing concurrent outbreaks of Zika, Chikungunya, and dengue viruses in Latin America and the Caribbean highlight the need for development of broad-spectrum antiviral treatments. The type I interferon (IFN) system has evolved in vertebrates to generate tissue responses that actively block replication of multiple known and potentially zoonotic viruses. As such, its control and activation through pharmacological agents may represent a novel therapeutic strategy for simultaneously impairing growth of multiple virus types and rendering host populations resistant to virus spread. In light of this strategy's potential, we undertook a screen to identify novel interferon-activating small molecules. Here, we describe 1-(2-fluorophenyl)-2-(5-isopropyl-1,3,4-thiadiazol-2-yl)-1,2-dihydrochromeno[2,3- ]pyrrole-3,9-dione, which we termed AV-C. Treatment of human cells with AV-C activates innate and interferon-associated responses that strongly inhibit replication of Zika, Chikungunya, and dengue viruses. By utilizing genome editing, we investigated the host proteins essential to AV-C-induced cellular states. This showed that the compound requires a TRIF-dependent signaling cascade that culminates in IFN regulatory factor 3 (IRF3)-dependent expression and secretion of type I interferon to elicit antiviral responses. The other canonical IRF3-terminal adaptor proteins STING and IPS-1/MAVS were dispensable for AV-C-induced phenotypes. However, our work revealed an important inhibitory role for IPS-1/MAVS, but not TRIF, in flavivirus replication, implying that TRIF-directed viral evasion may not occur. Additionally, we show that in response to AV-C, primary human peripheral blood mononuclear cells secrete proinflammatory cytokines that are linked with establishment of adaptive immunity to viral pathogens. Ultimately, synthetic innate immune activators such as AV-C may serve multiple therapeutic purposes, including direct antimicrobial responses and facilitation of pathogen-directed adaptive immunity. The type I interferon system is part of the innate immune response that has evolved in vertebrates as a first line of broad-spectrum immunological defense against an unknowable diversity of microbial, especially viral, pathogens. Here, we characterize a novel small molecule that artificially activates this response and in so doing generates a cellular state antagonistic to growth of currently emerging viruses: Zika virus, Chikungunya virus, and dengue virus. We also show that this molecule is capable of eliciting cellular responses that are predictive of establishment of adaptive immunity. As such, this agent may represent a powerful and multipronged therapeutic tool to combat emerging and other viral diseases.
[Mh] Termos MeSH primário: Proteínas Adaptadoras de Transporte Vesicular/agonistas
Antivirais/farmacologia
Benzopiranos/farmacologia
Vírus Chikungunya/fisiologia
Vírus da Dengue/fisiologia
Tiadiazóis/farmacologia
Replicação Viral
Zika virus/fisiologia
[Mh] Termos MeSH secundário: Proteínas Adaptadoras de Transporte Vesicular/metabolismo
Antivirais/química
Antivirais/isolamento & purificação
Benzopiranos/química
Benzopiranos/isolamento & purificação
Linhagem Celular
Febre de Chikungunya/tratamento farmacológico
Vírus Chikungunya/efeitos dos fármacos
Citocinas/biossíntese
Replicação do DNA/efeitos dos fármacos
Dengue/tratamento farmacológico
Vírus da Dengue/efeitos dos fármacos
Vírus da Dengue/metabolismo
Descoberta de Drogas
Edição de Genes
Interações Hospedeiro-Patógeno
Seres Humanos
Evasão da Resposta Imune
Imunidade Inata/efeitos dos fármacos
Fator Regulador 3 de Interferon/genética
Fator Regulador 3 de Interferon/metabolismo
Interferon Tipo I/efeitos dos fármacos
Interferon Tipo I/metabolismo
Interferon Tipo I/secreção
Leucócitos Mononucleares/efeitos dos fármacos
Leucócitos Mononucleares/imunologia
Tiadiazóis/química
Tiadiazóis/isolamento & purificação
Zika virus/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adaptor Proteins, Vesicular Transport); 0 (Antiviral Agents); 0 (Benzopyrans); 0 (Cytokines); 0 (Interferon Regulatory Factor-3); 0 (Interferon Type I); 0 (TICAM1 protein, human); 0 (Thiadiazoles)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180126
[Lr] Data última revisão:
180126
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE


  6 / 2206 MEDLINE  
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[PMID]:27777004
[Au] Autor:Temple KJ; Duvernay MT; Maeng JG; Blobaum AL; Stauffer SR; Hamm HE; Lindsley CW
[Ad] Endereço:Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
[Ti] Título:Identification of the minimum PAR4 inhibitor pharmacophore and optimization of a series of 2-methoxy-6-arylimidazo[2,1-b][1,3,4]thiadiazoles.
[So] Source:Bioorg Med Chem Lett;26(22):5481-5486, 2016 11 15.
[Is] ISSN:1464-3405
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:This letter describes the further deconstruction of the known PAR4 inhibitor chemotypes (MWs 490-525 and with high plasma protein binding) to identify a minimum PAR4 pharmacophore devoid of metabolic liabilities and improved properties. This exercise identified a greatly simplified 2-methoxy-6-arylimidazo[2,1-b][1,3,4]thiadiazole scaffold that afforded nanomolar inhibition of both activating peptide and γ-thrombin mediated PAR4 stimulation, while reducing both molecular weight and the number of hydrogen bond donors/acceptors by ∼50%. This minimum PAR4 pharmacophore, with competitive inhibition, versus non-competitive of the larger chemotypes, allows an ideal starting point to incorporate desired functional groups to engender optimal DMPK properties towards a preclinical candidate.
[Mh] Termos MeSH primário: Agregação Plaquetária/efeitos dos fármacos
Receptores de Trombina/antagonistas & inibidores
Tiadiazóis/química
Tiadiazóis/farmacologia
[Mh] Termos MeSH secundário: Plaquetas/citologia
Plaquetas/efeitos dos fármacos
Plaquetas/metabolismo
Seres Humanos
Inibidores da Agregação de Plaquetas/química
Inibidores da Agregação de Plaquetas/farmacologia
Receptores de Trombina/metabolismo
Trombina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Platelet Aggregation Inhibitors); 0 (Receptors, Thrombin); 0 (Thiadiazoles); 0 (protease-activated receptor 4); EC 3.4.21.5 (Thrombin)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:171128
[Lr] Data última revisão:
171128
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161026
[St] Status:MEDLINE
[do] DOI:10.1016/j.bmcl.2016.10.020


  7 / 2206 MEDLINE  
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[PMID]:28966280
[Au] Autor:Zhang S; Liu XJ; Tang R; Wang HX; Liu HY; Liu YM; Chen BQ
[Ad] Endereço:Tianjin Key Laboratory of Organic Solar Cells and Photochemical Conversion, School of Chemistry & Chemical Engineering, Tianjin University of Technology.
[Ti] Título:Design, Synthesis and Antiproliferative Evaluation of Novel Disulfides Containing 1,3,4-Thiadiazole Moiety.
[So] Source:Chem Pharm Bull (Tokyo);65(10):950-958, 2017.
[Is] ISSN:1347-5223
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:A series of novel disulfides containing 1,3,4-thiadiazole moiety were designed, synthesized, and the structures of all products were identified by spectral data (IR, NMR, and high resolution (HR)-MS). Their in vitro antiproliferative activities were evaluated using 2-(2-methoxy-4-nitro-phenyl)-3-(4-nitro-phenyl)-5-(2,4-disulfopheyl)-2H-tetrazolium monosodium salt (CCK-8) assay against human cancer cell lines, A549 (human lung cancer cell), HeLa (human cervical cancer cell), SMMC-7721 (human liver cancer cell) and normal cell lines L929. The bioassay results indicated that most of the tested compounds 6a-k, 7a-k and 8a-k exhibited antiproliferation with different degrees, and some compounds showed better effects than positive control 5-fluorouracil (5-FU) against various cancer cell lines. Among these compounds, compound 6e exhibited the most potent inhibitory activity against A549 cells with IC value of 3.62 µM. Compounds 6i, 7a, 7g, 8a and 8b showed significantly antiproliferative activities against HeLa cells with IC values of 3.88, 3.76, 3.59, 3.38 and 3.12 µM, respectively. Compounds 6a, 7a and 8a owned high antiproliferative activities against SMMC-7721 cells with IC values of 2.54, 2.69 and 2.31 µM, respectively. Furthermore, all of the tested compounds showed weak cytotoxic effect against the normal cell lines L929. Based on the preliminary results, the substituent groups are vital for improving the potency and selectivity of this class of compounds.
[Mh] Termos MeSH primário: Antineoplásicos/síntese química
Antineoplásicos/farmacologia
Desenho de Drogas
Tiadiazóis/química
Tiadiazóis/farmacologia
[Mh] Termos MeSH secundário: Células A549
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Dissulfetos/química
Ensaios de Seleção de Medicamentos Antitumorais
Células HeLa
Seres Humanos
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Disulfides); 0 (Thiadiazoles); 14IAC3GH7G (1,3,4-thiadiazole)
[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.c17-00485


  8 / 2206 MEDLINE  
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[PMID]:28938138
[Au] Autor:Krasavin M; Lukin A; Bakholdina A; Zhurilo N; Onopchenko O; Borysko P; Zozulya S; Moore D; Tikhonova IG
[Ad] Endereço:Saint Petersburg State University, Saint Petersburg 199034 Russia. Electronic address: m.krasavin@spbu.ru.
[Ti] Título:Continued SAR exploration of 1,2,4-thiadiazole-containing scaffolds in the design of free fatty acid receptor 1 (GPR40) agonists.
[So] Source:Eur J Med Chem;140:229-238, 2017 Nov 10.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:An earlier reported series of 1,2,4-thiadiazole-based agonists of FFA1 (GPR40) was evolved into two structurally distinct series of compounds. One of the series (structurally related to known FFA1 agonist GW9508) displayed low micromolar potency while the other (representing a truncated version of the earlier reported potent FFA1 agonists) was, surprisingly, found to be devoid of agonist potency. In silico docking of representative compounds into the crystal structure of FFA1 revealed possible structural grounds for the observed SAR.
[Mh] Termos MeSH primário: Desenho de Drogas
Receptores Acoplados a Proteínas-G/agonistas
Tiadiazóis/farmacologia
[Mh] Termos MeSH secundário: Animais
Células CHO
Cricetulus
Relação Dose-Resposta a Droga
Seres Humanos
Simulação de Acoplamento Molecular
Estrutura Molecular
Relação Estrutura-Atividade
Tiadiazóis/síntese química
Tiadiazóis/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (FFAR1 protein, human); 0 (Receptors, G-Protein-Coupled); 0 (Thiadiazoles)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171106
[Lr] Data última revisão:
171106
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170923
[St] Status:MEDLINE


  9 / 2206 MEDLINE  
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[PMID]:28838690
[Au] Autor:Gan X; Hu D; Chen Z; Wang Y; Song B
[Ad] Endereço:State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Research, and Development Center for Fine Chemicals, Guizhou University, Guiyang 550025, China; College of Chemistry and Li
[Ti] Título:Synthesis and antiviral evaluation of novel 1,3,4-oxadiazole/thiadiazole-chalcone conjugates.
[So] Source:Bioorg Med Chem Lett;27(18):4298-4301, 2017 09 15.
[Is] ISSN:1464-3405
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:A series of novel 1,3,4-oxadiazole/thiadiazole-chalcone conjugates were synthesized and their in vitro and in vivo antiviral activities were evaluated via microscale thermophoresis method and half-leaf method, respectively. The in vitro results indicated that compounds 7g, 7l, 8h, and 8l displayed good antiviral activity against TMV, with the binding constant values of 5.93, 6.15, 6.02, and 5.04µM, respectively, which were comparable to that of Ninnanmycin (6.78µM) and even better than that of Ribavirin (99.25µM). The in vivo results demonstrated that compounds 7g, 7l, 8h, and 8l exhibited remarkable anti-TMV activity with the EC values of 33.66, 33.97, 33.87 and 30.57µg/mL, respectively, which were comparable to that of Ningnanmycin (36.85µg/mL) and superior to that of Ribavirin (88.52µg/mL). Interestingly, the trend of antiviral activity in vivo was consistent with the in vitro results.
[Mh] Termos MeSH primário: Antivirais/farmacologia
Chalcona/farmacologia
Oxidiazóis/farmacologia
Tiadiazóis/farmacologia
Vírus do Mosaico do Tabaco/efeitos dos fármacos
[Mh] Termos MeSH secundário: Antivirais/síntese química
Antivirais/química
Chalcona/química
Relação Dose-Resposta a Droga
Testes de Sensibilidade Microbiana
Estrutura Molecular
Oxidiazóis/química
Relação Estrutura-Atividade
Tiadiazóis/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antiviral Agents); 0 (Oxadiazoles); 0 (Thiadiazoles); 20O2F20OUR (1,3,4-oxadiazole); 5S5A2Q39HX (Chalcone)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171125
[Lr] Data última revisão:
171125
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170826
[St] Status:MEDLINE


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[PMID]:28835457
[Au] Autor:Roewe J; Higer M; Riehl DR; Gericke A; Radsak MP; Bosmann M
[Ad] Endereço:Center for Thrombosis and Hemostasis, University Medical Center, Johannes Gutenberg University Mainz, 55131 Mainz, Germany.
[Ti] Título:Neuroendocrine Modulation of IL-27 in Macrophages.
[So] Source:J Immunol;199(7):2503-2514, 2017 Oct 01.
[Is] ISSN:1550-6606
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Heterodimeric IL-27 (p28/EBV-induced gene 3) is an important member of the IL-6/IL-12 cytokine family. IL-27 is predominantly synthesized by mononuclear phagocytes and exerts immunoregulatory functional activities on lymphocytic and nonlymphocytic cells during infection, autoimmunity or neoplasms. There is a great body of evidence on the bidirectional interplay between the autonomic nervous system and immune responses during inflammatory disorders, but so far IL-27 has not been defined as a part of these multifaceted neuroendocrine networks. In this study, we describe the role of catecholamines (as mediators of the sympathetic nervous system) related to IL-27 production in primary mouse macrophages. Noradrenaline and adrenaline dose-dependently suppressed the release of IL-27p28 in LPS/TLR4-activated macrophages, which was independent of α adrenoceptors. Instead, ß adrenoceptor activation was responsible for mediating gene silencing of IL-27p28 and EBV-induced gene 3. The ß adrenoceptor agonists formoterol and salbutamol mediated suppression of IL-27p28 production, when triggered by zymosan/TLR2, LPS/TLR4, or R848/TLR7/8 activation, but selectively spared the polyinosinic-polycytidylic acid/TLR3 pathway. Mechanistically, ß adrenergic signaling reinforced an autocrine feedback loop of macrophage-derived IL-10 and this synergized with inhibition of the JNK pathway for limiting IL-27p28. The JNK inhibitors SP600125 and AEG3482 strongly decreased intracellular IL-27p28 in F4/80 CD11b macrophages. In endotoxic shock of C57BL/6J mice, pharmacologic activation of ß adrenoceptors improved the severity of shock, including hypothermia and decreased circulating IL-27p28. Conversely, IL-27p28 was 2.7-fold increased by removal of the catecholamine-producing adrenal glands prior to endotoxic shock. These data suggest a novel role of the sympathetic neuroendocrine system for the modulation of IL-27-dependent acute inflammation.
[Mh] Termos MeSH primário: Epinefrina/farmacologia
Interleucinas/imunologia
Interleucinas/metabolismo
Macrófagos/efeitos dos fármacos
Macrófagos/imunologia
Norepinefrina/farmacologia
[Mh] Termos MeSH secundário: Albuterol/farmacologia
Animais
Antracenos/farmacologia
Células Cultivadas
Fumarato de Formoterol/farmacologia
Inflamação
Interleucina-10/biossíntese
Interleucina-10/imunologia
Interleucinas/sangue
Interleucinas/genética
Lipopolissacarídeos/farmacologia
Ativação de Macrófagos/efeitos dos fármacos
Camundongos
Camundongos Endogâmicos C57BL
Poli I-C/metabolismo
Receptores Adrenérgicos/efeitos dos fármacos
Choque Séptico
Transdução de Sinais/efeitos dos fármacos
Sulfonamidas/farmacologia
Sistema Nervoso Simpático/imunologia
Sistema Nervoso Simpático/fisiologia
Tiadiazóis/farmacologia
Receptor 3 Toll-Like/metabolismo
Zimosan/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (AEG 3482); 0 (Anthracenes); 0 (Il27 protein, mouse); 0 (Interleukins); 0 (Lipopolysaccharides); 0 (Receptors, Adrenergic); 0 (Sulfonamides); 0 (Thiadiazoles); 0 (Toll-Like Receptor 3); 130068-27-8 (Interleukin-10); 1TW30Y2766 (pyrazolanthrone); 9010-72-4 (Zymosan); O84C90HH2L (Poly I-C); QF8SVZ843E (Albuterol); W34SHF8J2K (Formoterol Fumarate); X4W3ENH1CV (Norepinephrine); YKH834O4BH (Epinephrine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170825
[St] Status:MEDLINE
[do] DOI:10.4049/jimmunol.1700687



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