Base de dados : MEDLINE
Pesquisa : D27.505.519.389.745.325 [Categoria DeCS]
Referências encontradas : 7125 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 713 ir para página                         

  1 / 7125 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29366749
[Au] Autor:Gonzalez EA; Martins GR; Tavares AMV; Viegas M; Poletto E; Giugliani R; Matte U; Baldo G
[Ad] Endereço:Gene Therapy Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil; Post-Graduation Program in Genetics and Molecular Biology, UFRGS, Porto Alegre, Brazil.
[Ti] Título:Cathepsin B inhibition attenuates cardiovascular pathology in mucopolysaccharidosis I mice.
[So] Source:Life Sci;196:102-109, 2018 Mar 01.
[Is] ISSN:1879-0631
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disorder with multisystemic features, including heart enlargement, heart valve dysfunction, and aortic stiffness and dilatation. Previous studies have shown that MPS I mice overexpress cathepsin B (CtsB) in multiple tissues, including those from the cardiovascular system. Here, we hypothesized that inhibition of CtsB could ameliorate cardiac function parameters, as well as aorta and valve abnormalities found in MPS I. First, we found that total elastase activity in an MPS I aorta is elevated. Following that, we demonstrated that CtsB leaks from the lysosome in MPS I human fibroblasts, possibly acting as a degradative agent of extracellular matrix components from the aorta, cardiac muscle, and heart valves. We then used a CtsB inhibitor in vivo in the MPS I mouse model. After 4 months of treatment, partial inhibition of CtsB activity in treated mice reduced aortic dilatation, as well as heart valve thickening, and led to improvements in cardiac function parameters, although none of these were completely normalized. Based on these results, we conclude that lysosomal alterations in this disease promote leakage of CtsB to outside the organelle, where this protein can have multiple pathological roles. CtsB inhibition improved cardiovascular parameters in MPS I mice and can have a potential benefit in this disease.
[Mh] Termos MeSH primário: Sistema Cardiovascular/patologia
Catepsina B/antagonistas & inibidores
Inibidores de Cisteína Proteinase/uso terapêutico
Dipeptídeos/uso terapêutico
Mucopolissacaridose I/diagnóstico por imagem
Mucopolissacaridose I/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Aorta/patologia
Aorta/fisiopatologia
Sistema Cardiovascular/diagnóstico por imagem
Catepsina B/metabolismo
Colagenases/metabolismo
Feminino
Fibroblastos/metabolismo
Testes de Função Cardíaca
Doenças das Valvas Cardíacas/diagnóstico por imagem
Doenças das Valvas Cardíacas/tratamento farmacológico
Doenças das Valvas Cardíacas/patologia
Seres Humanos
Lisossomos/metabolismo
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Mucopolissacaridose I/patologia
Elastase Pancreática/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cysteine Proteinase Inhibitors); 0 (Dipeptides); 134448-10-5 (N-(3-propylcarbamoyloxirane-2-carbonyl)-isoleucyl-proline); EC 3.4.21.36 (Pancreatic Elastase); EC 3.4.22.1 (Cathepsin B); EC 3.4.24.- (Collagenases)
[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:180126
[St] Status:MEDLINE


  2 / 7125 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29223717
[Au] Autor:Wang Y; Xue S; Li R; Zheng Z; Yi H; Li Z
[Ad] Endereço:Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China.
[Ti] Título:Synthesis and biological evaluation of novel synthetic chalcone derivatives as anti-tumor agents targeting Cat L and Cat K.
[So] Source:Bioorg Med Chem;26(1):8-16, 2018 01 01.
[Is] ISSN:1464-3391
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:A series of chalcone derivatives bearing benzamide or benzenesulfonamide moieties were synthesized and evaluated for their anti-tumor effect on HCT116, MCF7 and 143B cell lines in vitro. SAR analysis showed that compounds bearing a benzenesulfonamide group had greater potency than those bearing a benzamide group. It was also shown that compounds with a mono-methyl or mono-halogen group at the 3-position on the terminal phenyl ring were more effective than those with trifluoromethyl or methoxy groups. Compound 8e exhibited the most potent anti-tumor activities against HCT116, MCF7 and 143B cell lines, with IC values of 0.597, 0.886 and 0.791µM, respectively. Molecular docking studies and enzymatic assays demonstrated that the anti-tumor activity of compound 8e might be regulated by Cat L and Cat K.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Catepsina K/antagonistas & inibidores
Catepsina L/antagonistas & inibidores
Chalcona/farmacologia
Inibidores de Cisteína Proteinase/farmacologia
[Mh] Termos MeSH secundário: Antineoplásicos/síntese química
Antineoplásicos/química
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Chalcona/síntese química
Chalcona/química
Inibidores de Cisteína Proteinase/síntese química
Inibidores de Cisteína Proteinase/química
Relação Dose-Resposta a Droga
Ensaios de Seleção de Medicamentos Antitumorais
Seres Humanos
Simulação de Acoplamento Molecular
Estrutura Molecular
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Cysteine Proteinase Inhibitors); 5S5A2Q39HX (Chalcone); EC 3.4.22.15 (CTSL1 protein, human); EC 3.4.22.15 (Cathepsin L); EC 3.4.22.38 (CTSK protein, human); EC 3.4.22.38 (Cathepsin K)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180106
[Lr] Data última revisão:
180106
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171211
[St] Status:MEDLINE


  3 / 7125 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28468944
[Au] Autor:Montgomery DS; Yu L; Ghazi ZM; Thai TL; Al-Khalili O; Ma HP; Eaton DC; Alli AA
[Ad] Endereço:Department of Physiology and Functional Genomics and Department of Medicine Division of Nephrology, Hypertension, and Renal Transplantation, University of Florida College of Medicine, Gainesville, Florida.
[Ti] Título:ENaC activity is regulated by calpain-2 proteolysis of MARCKS proteins.
[So] Source:Am J Physiol Cell Physiol;313(1):C42-C53, 2017 Jul 01.
[Is] ISSN:1522-1563
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:We previously demonstrated a role for the myristoylated alanine-rich C kinase substrate (MARCKS) to serve as an adaptor protein in the anionic phospholipid phosphate-dependent regulation of the epithelial sodium channel (ENaC). Both MARCKS and ENaC are regulated by proteolysis. Calpains are a family of ubiquitously expressed intracellular Ca -dependent cysteine proteases involved in signal transduction. Here we examine the role of calpain-2 in regulating MARCKS and ENaC in cultured renal epithelial cells and in the mouse kidney. Using recombinant fusion proteins, we show that MARCKS, but not the ENaC subunits, are a substrate of calpain-2 in the presence of Ca Pharmacological inhibition of calpain-2 alters MARCKS protein expression in light-density sucrose gradient fractions from cell lysates of mouse cortical collecting duct cells. Calpain-dependent cleaved products of MARCKS are detectable in cultured renal cells. Ca mobilization and calpain-2 inhibition decrease the association between ENaC and MARCKS. The inhibition of calpain-2 reduces ENaC activity as demonstrated by single-channel patch-clamp recordings and transepithelial current measurements. These results suggest that calpain-2 proteolysis of MARCKS promotes its interaction with lipids and ENaC at the plasma membrane to allow for the phosphatidylinositol 4,5-bisphosphate (PIP2)-dependent regulation of ENaC activity in the kidney.
[Mh] Termos MeSH primário: Calpaína/genética
Canais Epiteliais de Sódio/genética
Peptídeos e Proteínas de Sinalização Intracelular/genética
Proteínas de Membrana/genética
Fosfatidilinositol 4,5-Difosfato/metabolismo
[Mh] Termos MeSH secundário: Potenciais de Ação/efeitos dos fármacos
Amilorida/farmacologia
Animais
Cálcio/metabolismo
Calpaína/metabolismo
Fracionamento Celular
Linhagem Celular
Membrana Celular/efeitos dos fármacos
Membrana Celular/metabolismo
Inibidores de Cisteína Proteinase/farmacologia
Citocalasina D/farmacologia
Células Epiteliais/citologia
Células Epiteliais/efeitos dos fármacos
Células Epiteliais/metabolismo
Canais Epiteliais de Sódio/metabolismo
Regulação da Expressão Gênica
Peptídeos e Proteínas de Sinalização Intracelular/metabolismo
Túbulos Renais Coletores/citologia
Túbulos Renais Coletores/efeitos dos fármacos
Túbulos Renais Coletores/metabolismo
Proteínas de Membrana/metabolismo
Camundongos
Substrato Quinase C Rico em Alanina Miristoilada
Técnicas de Patch-Clamp
Proteólise/efeitos dos fármacos
Proteínas Recombinantes de Fusão/genética
Proteínas Recombinantes de Fusão/metabolismo
Transdução de Sinais
Xenopus laevis
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cysteine Proteinase Inhibitors); 0 (Epithelial Sodium Channels); 0 (Intracellular Signaling Peptides and Proteins); 0 (Marcks protein, mouse); 0 (Membrane Proteins); 0 (Phosphatidylinositol 4,5-Diphosphate); 0 (Recombinant Fusion Proteins); 125267-21-2 (Myristoylated Alanine-Rich C Kinase Substrate); 22144-77-0 (Cytochalasin D); 7DZO8EB0Z3 (Amiloride); EC 3.4.22.- (Calpain); EC 3.4.22.53 (Capn2 protein, mouse); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171212
[Lr] Data última revisão:
171212
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.1152/ajpcell.00244.2016


  4 / 7125 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28922424
[Au] Autor:Hopp CS; Bennett BL; Mishra S; Lehmann C; Hanson KK; Lin JW; Rousseau K; Carvalho FA; van der Linden WA; Santos NC; Bogyo M; Khan SM; Heussler V; Sinnis P
[Ad] Endereço:Department of Molecular Microbiology & Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.
[Ti] Título:Deletion of the rodent malaria ortholog for falcipain-1 highlights differences between hepatic and blood stage merozoites.
[So] Source:PLoS Pathog;13(9):e1006586, 2017 Sep.
[Is] ISSN:1553-7374
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Proteases have been implicated in a variety of developmental processes during the malaria parasite lifecycle. In particular, invasion and egress of the parasite from the infected hepatocyte and erythrocyte, critically depend on protease activity. Although falcipain-1 was the first cysteine protease to be characterized in P. falciparum, its role in the lifecycle of the parasite has been the subject of some controversy. While an inhibitor of falcipain-1 blocked erythrocyte invasion by merozoites, two independent studies showed that falcipain-1 disruption did not affect growth of blood stage parasites. To shed light on the role of this protease over the entire Plasmodium lifecycle, we disrupted berghepain-1, its ortholog in the rodent parasite P. berghei. We found that this mutant parasite displays a pronounced delay in blood stage infection after inoculation of sporozoites. Experiments designed to pinpoint the defect of berghepain-1 knockout parasites found that it was not due to alterations in gliding motility, hepatocyte invasion or liver stage development and that injection of berghepain-1 knockout merosomes replicated the phenotype of delayed blood stage growth after sporozoite inoculation. We identified an additional role for berghepain-1 in preparing blood stage merozoites for infection of erythrocytes and observed that berghepain-1 knockout parasites exhibit a reticulocyte restriction, suggesting that berghepain-1 activity broadens the erythrocyte repertoire of the parasite. The lack of berghepain-1 expression resulted in a greater reduction in erythrocyte infectivity in hepatocyte-derived merozoites than it did in erythrocyte-derived merozoites. These observations indicate a role for berghepain-1 in processing ligands important for merozoite infectivity and provide evidence supporting the notion that hepatic and erythrocytic merozoites, though structurally similar, are not identical.
[Mh] Termos MeSH primário: Cisteína Endopeptidases/metabolismo
Hepatócitos/metabolismo
Malária/metabolismo
Merozoítos/metabolismo
Plasmodium falciparum/metabolismo
[Mh] Termos MeSH secundário: Animais
Inibidores de Cisteína Proteinase/farmacologia
Eritrócitos/parasitologia
Hepatócitos/parasitologia
Fígado/metabolismo
Malária/parasitologia
Plasmodium falciparum/genética
Proteínas de Protozoários/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cysteine Proteinase Inhibitors); 0 (Protozoan Proteins); EC 3.4.22.- (Cysteine Endopeptidases); EC 3.4.22.- (falcipain)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171017
[Lr] Data última revisão:
171017
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170919
[St] Status:MEDLINE
[do] DOI:10.1371/journal.ppat.1006586


  5 / 7125 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28820254
[Au] Autor:Qi Q; Obianyo O; Du Y; Fu H; Li S; Ye K
[Ad] Endereço:Department of Pathology and Laboratory Medicine ‡Department of Pharmacology, Emory Chemical Biology Discovery Center Emory University School of Medicine Atlanta, Georgia 30322, United States.
[Ti] Título:Blockade of Asparagine Endopeptidase Inhibits Cancer Metastasis.
[So] Source:J Med Chem;60(17):7244-7255, 2017 Sep 14.
[Is] ISSN:1520-4804
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Asparagine endopeptidase (AEP), also called legumain, is highly expressed in various solid tumors, promoting cancer cell invasion, migration, and metastasis. It has been proposed to be a prognostic marker and therapeutic target for cancer treatment. However, an effective nonpeptide, small-molecule inhibitor against this protease has not yet been identified. Here we show that a family of xanthine derivatives selectively inhibit AEP and suppress matrix metalloproteinase (MMP) cleavage, leading to the inhibition of cancer metastasis. Through structure-activity relationship (SAR) analysis, we obtained an optimized lead compound (38u) that represses breast cancer invasion and migration. Chronic treatment of nude mice, which had been inoculated with MDA-MB-231 cells, with inhibitor 38u via oral administration robustly inhibits breast cancer lung metastasis in a dose-dependent manner, associated with blockade of MMP-2 by AEP. Therefore, our study supports that 38u might act as a potent and specific AEP inhibitor useful for cancer treatment.
[Mh] Termos MeSH primário: Antineoplásicos/uso terapêutico
Neoplasias da Mama/patologia
Cisteína Endopeptidases/metabolismo
Inibidores de Cisteína Proteinase/uso terapêutico
Neoplasias Pulmonares/prevenção & controle
Neoplasias Pulmonares/secundário
Xantina/uso terapêutico
[Mh] Termos MeSH secundário: Animais
Antineoplásicos/química
Antineoplásicos/farmacologia
Mama/efeitos dos fármacos
Mama/metabolismo
Mama/patologia
Neoplasias da Mama/tratamento farmacológico
Neoplasias da Mama/metabolismo
Linhagem Celular Tumoral
Inibidores de Cisteína Proteinase/química
Inibidores de Cisteína Proteinase/farmacologia
Feminino
Seres Humanos
Pulmão/efeitos dos fármacos
Pulmão/metabolismo
Pulmão/patologia
Neoplasias Pulmonares/metabolismo
Neoplasias Pulmonares/patologia
Camundongos
Camundongos Nus
Invasividade Neoplásica/patologia
Invasividade Neoplásica/prevenção & controle
Relação Estrutura-Atividade
Xantina/química
Xantina/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Cysteine Proteinase Inhibitors); 1AVZ07U9S7 (Xanthine); EC 3.4.22.- (Cysteine Endopeptidases); EC 3.4.22.34 (asparaginylendopeptidase)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170819
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jmedchem.7b00228


  6 / 7125 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28797057
[Au] Autor:Farizatto KLG; Ikonne US; Almeida MF; Ferrari MFR; Bahr BA
[Ad] Endereço:Biotechnology Research and Training Center, William C. Friday Laboratory, University of North Carolina-Pembroke, Pembroke, North Carolina, United States of America.
[Ti] Título:Aß42-mediated proteasome inhibition and associated tau pathology in hippocampus are governed by a lysosomal response involving cathepsin B: Evidence for protective crosstalk between protein clearance pathways.
[So] Source:PLoS One;12(8):e0182895, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Impaired protein clearance likely increases the risk of protein accumulation disorders including Alzheimer's disease (AD). Protein degradation through the proteasome pathway decreases with age and in AD brains, and the Aß42 peptide has been shown to impair proteasome function in cultured cells and in a cell-free model. Here, Aß42 was studied in brain tissue to measure changes in protein clearance pathways and related secondary pathology. Oligomerized Aß42 (0.5-1.5 µM) reduced proteasome activity by 62% in hippocampal slice cultures over a 4-6-day period, corresponding with increased tau phosphorylation and reduced synaptophysin levels. Interestingly, the decrease in proteasome activity was associated with a delayed inverse effect, >2-fold increase, regarding lysosomal cathepsin B (CatB) activity. The CatB enhancement did not correspond with the Aß42-mediated phospho-tau alterations since the latter occurred prior to the CatB response. Hippocampal slices treated with the proteasome inhibitor lactacystin also exhibited an inverse effect on CatB activity with respect to diminished proteasome function. Lactacystin caused earlier CatB enhancement than Aß42, and no correspondence was evident between up-regulated CatB levels and the delayed synaptic pathology indicated by the loss of pre- and postsynaptic markers. Contrasting the inverse effects on the proteasomal and lysosomal pathways by Aß42 and lactacystin, such were not found when CatB activity was up-regulated two-fold with Z-Phe-Ala-diazomethylketone (PADK). Instead of an inverse decline, proteasome function was increased marginally in PADK-treated hippocampal slices. Unexpectedly, the proteasomal augmentation was significantly pronounced in Aß42-compromised slices, while absent in lactacystin-treated tissue, resulting in >2-fold improvement for nearly complete recovery of proteasome function by the CatB-enhancing compound. The PADK treatment also reduced Aß42-mediated tau phosphorylation and synaptic marker declines, corresponding with the positive modulation of both proteasome activity and the lysosomal CatB enzyme. These findings indicate that proteasomal stress contributes to AD-type pathogenesis and that governing such pathology occurs through crosstalk between the two protein clearance pathways.
[Mh] Termos MeSH primário: Peptídeos beta-Amiloides/metabolismo
Catepsina B/metabolismo
Hipocampo/metabolismo
Lisossomos/metabolismo
Fragmentos de Peptídeos/metabolismo
Complexo de Endopeptidases do Proteassoma/metabolismo
Proteínas tau/metabolismo
[Mh] Termos MeSH secundário: Acetilcisteína/análogos & derivados
Acetilcisteína/farmacologia
Animais
Inibidores de Cisteína Proteinase/farmacologia
Hipocampo/efeitos dos fármacos
Hipocampo/patologia
Neurônios/efeitos dos fármacos
Neurônios/metabolismo
Neurônios/patologia
Fosforilação/efeitos dos fármacos
Ratos
Ratos Sprague-Dawley
Sinaptofisina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amyloid beta-Peptides); 0 (Cysteine Proteinase Inhibitors); 0 (Peptide Fragments); 0 (Synaptophysin); 0 (amyloid beta-protein (1-42)); 0 (tau Proteins); 133343-34-7 (lactacystin); EC 3.4.22.1 (Cathepsin B); EC 3.4.25.1 (Proteasome Endopeptidase Complex); WYQ7N0BPYC (Acetylcysteine)
[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:170811
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0182895


  7 / 7125 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28763614
[Au] Autor:Previti S; Ettari R; Cosconati S; Amendola G; Chouchene K; Wagner A; Hellmich UA; Ulrich K; Krauth-Siegel RL; Wich PR; Schmid I; Schirmeister T; Gut J; Rosenthal PJ; Grasso S; Zappalà M
[Ad] Endereço:Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina , Viale Annunziata, 98168 Messina, Italy.
[Ti] Título:Development of Novel Peptide-Based Michael Acceptors Targeting Rhodesain and Falcipain-2 for the Treatment of Neglected Tropical Diseases (NTDs).
[So] Source:J Med Chem;60(16):6911-6923, 2017 Aug 24.
[Is] ISSN:1520-4804
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:This paper describes the development of a class of peptide-based inhibitors as novel antitrypanosomal and antimalarial agents. The inhibitors are based on a characteristic peptide sequence for the inhibition of the cysteine proteases rhodesain of Trypanosoma brucei rhodesiense and falcipain-2 of Plasmodium falciparum. We exploited the reactivity of novel unsaturated electrophilic functions such as vinyl-sulfones, -ketones, -esters, and -nitriles. The Michael acceptors inhibited both rhodesain and falcipain-2, at nanomolar and micromolar levels, respectively. In particular, the vinyl ketone 3b has emerged as a potent rhodesain inhibitor (k = 67 × 10 M min ), endowed with a picomolar binding affinity (K = 38 pM), coupled with a single-digit micromolar activity against Trypanosoma brucei brucei (EC = 2.97 µM), thus being considered as a novel lead compound for the discovery of novel effective antitrypanosomal agents.
[Mh] Termos MeSH primário: Antimaláricos/farmacologia
Carbamatos/farmacologia
Cisteína Endopeptidases/metabolismo
Inibidores de Cisteína Proteinase/farmacologia
Dipeptídeos/farmacologia
Fenilalanina/análogos & derivados
Tripanossomicidas/farmacologia
[Mh] Termos MeSH secundário: Antimaláricos/síntese química
Antimaláricos/toxicidade
Carbamatos/síntese química
Carbamatos/toxicidade
Catepsina L/metabolismo
Inibidores de Cisteína Proteinase/síntese química
Inibidores de Cisteína Proteinase/toxicidade
Dipeptídeos/síntese química
Dipeptídeos/toxicidade
Células HeLa
Seres Humanos
Ligações de Hidrogênio
Malária/tratamento farmacológico
Simulação de Acoplamento Molecular
Simulação de Dinâmica Molecular
Doenças Negligenciadas/tratamento farmacológico
Fenilalanina/síntese química
Fenilalanina/farmacologia
Fenilalanina/toxicidade
Plasmodium falciparum/efeitos dos fármacos
Estereoisomerismo
Relação Estrutura-Atividade
Tripanossomicidas/síntese química
Tripanossomicidas/toxicidade
Trypanosoma brucei brucei/efeitos dos fármacos
Tripanossomíase Africana/tratamento farmacológico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antimalarials); 0 (Carbamates); 0 (Cysteine Proteinase Inhibitors); 0 (Dipeptides); 0 (Trypanocidal Agents); 0 (benzyl (1-oxo-1-((6-oxo-1-phenylhept-4-en-3-yl)amino)-3-phenylpropan-2-yl)carbamate); 47E5O17Y3R (Phenylalanine); EC 3.4.22.- (Cysteine Endopeptidases); EC 3.4.22.- (falcipain 2); EC 3.4.22.- (rhodesain); EC 3.4.22.15 (Cathepsin L)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170802
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jmedchem.7b00405


  8 / 7125 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28759231
[Au] Autor:Kling A; Jantos K; Mack H; Hornberger W; Drescher K; Nimmrich V; Relo A; Wicke K; Hutchins CW; Lao Y; Marsh K; Moeller A
[Ad] Endereço:Neuroscience Research, AbbVie Deutschland GmbH & Co. KG , Knollstrasse, 67061 Ludwigshafen, Germany.
[Ti] Título:Discovery of Novel and Highly Selective Inhibitors of Calpain for the Treatment of Alzheimer's Disease: 2-(3-Phenyl-1H-pyrazol-1-yl)-nicotinamides.
[So] Source:J Med Chem;60(16):7123-7138, 2017 Aug 24.
[Is] ISSN:1520-4804
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Calpain overactivation has been implicated in a variety of pathological disorders including ischemia/reperfusion injury, cataract formation, and neurodegenerative diseases such as Alzheimer's disease (AD). Herein we describe our efforts leading to the identification of ketoamide-based 2-(3-phenyl-1H-pyrazol-1-yl)nicotinamides as potent and reversible inhibitors of calpain with high selectivity versus related cysteine protease cathepsins, other proteases, and receptors. Broad efficacy in a set of preclinical models relevant to AD suggests that inhibition of calpain represents an attractive approach with potential benefit for the treatment of AD.
[Mh] Termos MeSH primário: Doença de Alzheimer/tratamento farmacológico
Aminobutiratos/farmacologia
Calpaína/antagonistas & inibidores
Inibidores de Cisteína Proteinase/farmacologia
Niacinamida/análogos & derivados
Niacinamida/farmacologia
Pirazóis/farmacologia
[Mh] Termos MeSH secundário: Aminobutiratos/síntese química
Aminobutiratos/farmacocinética
Animais
Catepsinas
Inibidores de Cisteína Proteinase/síntese química
Inibidores de Cisteína Proteinase/farmacocinética
Cães
Hipocampo/metabolismo
Seres Humanos
Concentração Inibidora 50
Macaca fascicularis
Masculino
Microssomos Hepáticos/metabolismo
Niacinamida/síntese química
Niacinamida/farmacocinética
Pirazóis/síntese química
Pirazóis/farmacocinética
Ratos Endogâmicos F344
Ratos Sprague-Dawley
Ratos Wistar
Sono REM/efeitos dos fármacos
Espectrina/metabolismo
Estereoisomerismo
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (A-933548); 0 (Aminobutyrates); 0 (Cysteine Proteinase Inhibitors); 0 (Pyrazoles); 12634-43-4 (Spectrin); 25X51I8RD4 (Niacinamide); EC 3.4.- (Cathepsins); EC 3.4.22.- (Calpain); EC 3.4.22.52 (CAPN1 protein, human)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170801
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jmedchem.7b00731


  9 / 7125 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28720327
[Au] Autor:Dos Santos DA; Deobald AM; Cornelio VE; Ávila RMD; Cornea RC; Bernasconi GCR; Paixão MW; Vieira PC; Corrêa AG
[Ad] Endereço:Centre of Excellence for Research in Sustainable Chemistry - CERSusChem, Department of Chemistry, Federal University of São Carlos, 13565-905 São Carlos, SP, Brazil.
[Ti] Título:Asymmetric synthesis and evaluation of epoxy-α-acyloxycarboxamides as selective inhibitors of cathepsin L.
[So] Source:Bioorg Med Chem;25(17):4620-4627, 2017 Sep 01.
[Is] ISSN:1464-3391
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Cathepsin L plays important roles in physiological processes as well as in the development of many pathologies. Recently the attentions were turned to its association with tumor progress what makes essential the development of more potent and selective inhibitors. In this work, epoxipeptidomimetics were investigated as new cathepsin inhibitors. This class of compounds is straightforward obtained by using a green one-pot asymmetric epoxidation/Passerini 3-MCR. A small library of 17 compounds was evaluated against cathepsin L, and among them LSPN423 showed to be the most potent. Investigations of the mechanism suggested a tight binding uncompetitive inhibition.
[Mh] Termos MeSH primário: Amidas/química
Catepsina L/antagonistas & inibidores
Inibidores de Cisteína Proteinase/síntese química
[Mh] Termos MeSH secundário: Amidas/metabolismo
Amidas/farmacologia
Animais
Antiparasitários/química
Antiparasitários/metabolismo
Antiparasitários/farmacologia
Catepsina L/metabolismo
Inibidores de Cisteína Proteinase/metabolismo
Inibidores de Cisteína Proteinase/farmacologia
Concentração Inibidora 50
Parasitos/efeitos dos fármacos
Parasitos/enzimologia
Estereoisomerismo
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amides); 0 (Antiparasitic Agents); 0 (Cysteine Proteinase Inhibitors); EC 3.4.22.15 (Cathepsin L)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170720
[St] Status:MEDLINE


  10 / 7125 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28671827
[Au] Autor:Galasiti Kankanamalage AC; Kim Y; Rathnayake AD; Alliston KR; Butler MM; Cardinale SC; Bowlin TL; Groutas WC; Chang KO
[Ad] Endereço:Department of Chemistry, Wichita State University , Wichita, Kansas 67260, United States.
[Ti] Título:Design, Synthesis, and Evaluation of Novel Prodrugs of Transition State Inhibitors of Norovirus 3CL Protease.
[So] Source:J Med Chem;60(14):6239-6248, 2017 Jul 27.
[Is] ISSN:1520-4804
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Ester and carbamate prodrugs of aldehyde bisulfite adduct inhibitors were synthesized in order to improve their pharmacokinetic and pharmacodynamic properties. The inhibitory activity of the compounds against norovirus 3C-like protease in enzyme and cell-based assays was determined. The ester and carbamate prodrugs displayed equivalent potency to those of the precursor aldehyde bisulfite adducts and precursor aldehydes. Furthermore, the rate of ester cleavage was found to be dependent on alkyl chain length. The generated prodrugs exhibited low cytotoxicity and satisfactory liver microsomes stability and plasma protein binding. The methodology described herein has wide applicability and can be extended to the bisulfite adducts of common warheads employed in the design of transition state inhibitors of serine and cysteine proteases of medical relevance.
[Mh] Termos MeSH primário: Antivirais/química
Compostos Aza/química
Carbamatos/química
Cisteína Endopeptidases/metabolismo
Inibidores de Cisteína Proteinase/química
Norovirus/efeitos dos fármacos
Pró-Fármacos/química
Pirrolidinas/química
Proteínas Virais/antagonistas & inibidores
[Mh] Termos MeSH secundário: Animais
Antivirais/síntese química
Antivirais/farmacologia
Compostos Aza/síntese química
Compostos Aza/farmacologia
Proteínas Sanguíneas/metabolismo
Carbamatos/síntese química
Carbamatos/farmacologia
Linhagem Celular
Inibidores de Cisteína Proteinase/síntese química
Inibidores de Cisteína Proteinase/farmacologia
Ésteres/síntese química
Ésteres/química
Ésteres/farmacologia
Seres Humanos
Hidrólise
Camundongos
Microssomos Hepáticos/metabolismo
Modelos Moleculares
Pró-Fármacos/síntese química
Pró-Fármacos/farmacologia
Ligação Proteica
Pirrolidinas/síntese química
Pirrolidinas/farmacologia
Estereoisomerismo
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiviral Agents); 0 (Aza Compounds); 0 (Blood Proteins); 0 (Carbamates); 0 (Cysteine Proteinase Inhibitors); 0 (Esters); 0 (Prodrugs); 0 (Pyrrolidines); 0 (Viral Proteins); EC 3.4.22.- (Cysteine Endopeptidases)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170906
[Lr] Data última revisão:
170906
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170704
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jmedchem.7b00497



página 1 de 713 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