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[PMID]:28209403
[Au] Autor:Johnson BK; Abramovitch RB
[Ad] Endereço:Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA.
[Ti] Título:Small Molecules That Sabotage Bacterial Virulence.
[So] Source:Trends Pharmacol Sci;38(4):339-362, 2017 Apr.
[Is] ISSN:1873-3735
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The continued rise of antibiotic-resistant bacterial infections has motivated alternative strategies for target discovery and treatment of infections. Antivirulence therapies function through inhibition of in vivo required virulence factors to disarm the pathogen instead of directly targeting viability or growth. This approach to treating bacteria-mediated diseases may have advantages over traditional antibiotics because it targets factors specific for pathogenesis, potentially reducing selection for resistance and limiting collateral damage to the resident microbiota. This review examines vulnerable molecular mechanisms used by bacteria to cause disease and the antivirulence compounds that sabotage these virulence pathways. By expanding the study of antimicrobial targets beyond those that are essential for growth, antivirulence strategies offer new and innovative opportunities to combat infectious diseases.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Bactérias/patogenicidade
Virulência/efeitos dos fármacos
[Mh] Termos MeSH secundário: Artemisininas/farmacologia
Bactérias/metabolismo
Aderência Bacteriana/efeitos dos fármacos
Proteínas de Bactérias/antagonistas & inibidores
Etoxzolamida/farmacologia
Fímbrias Bacterianas/efeitos dos fármacos
Histidina Quinase/fisiologia
Sulfonamidas/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Artemisinins); 0 (Bacterial Proteins); 0 (LED209); 0 (Sulfonamides); 148349-72-8 (Crl protein, Bacteria); 9RMU91N5K2 (artemisinine); EC 2.7.13.1 (Histidine Kinase); Z52H4811WX (Ethoxzolamide)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171111
[Lr] Data última revisão:
171111
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170218
[St] Status:MEDLINE


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[PMID]:27600313
[Au] Autor:Kazokaite J; Aspatwar A; Kairys V; Parkkila S; Matulis D
[Ad] Endereço:a Department of Biothermodynamics and Drug Design , Institute of Biotechnology, Vilnius University , Vilnius , Lithuania.
[Ti] Título:Fluorinated benzenesulfonamide anticancer inhibitors of carbonic anhydrase IX exhibit lower toxic effects on zebrafish embryonic development than ethoxzolamide.
[So] Source:Drug Chem Toxicol;40(3):309-319, 2017 Jul.
[Is] ISSN:1525-6014
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The toxic effects of two recently discovered inhibitors (VD12-09 and VD11-4-2) that selectively and with extraordinary strong, picomolar binding affinity to human carbonic anhydrase (CA) isoform IX were investigated on zebrafish embryonic development. CA IX has been recently introduced as an anticancer target since it is highly overexpressed in numerous human cancers but nearly absent in normal tissues. Morphological changes in zebrafish treated by the compounds were studied by light-field microscopy and histological analysis. Homology models of zebrafish CA II and CA IX were built to identify the conserved amino acid residues in the active site of zebrafish CAs. The toxicity studies here showed that the LC values at 120 hours post-fertilization (hpf) were 13 µM for VD12-09, 120 µM for VD11-4-2, and 9 µM for ethoxzolamide (EZA), a non-selective CA inhibitor commonly used as a drug in clinics. Thus, EZA was the most toxic of the three compounds. The zebrafish embryos exposed to LC doses of VD12-09 and VD11-4-2 showed fewer phenotypic abnormalities compared with the embryos exposed to the corresponding dose of EZA. Histochemical studies did not show any gross morphological changes in the embryos treated with VD12-09 and VD11-4-2 unlike EZA. The results of our study indicate that the compounds exhibited 10-fold lower toxicity and induced fewer side effects in zebrafish than EZA. Therefore, the exposure to VD11-4-2 and VD12-09 at concentrations below LC did not lead to deleterious effects on the zebrafish embryonic development and thus both inhibitors may be further developed as drugs.
[Mh] Termos MeSH primário: Antineoplásicos/toxicidade
Anidrase Carbônica IX/antagonistas & inibidores
Inibidores da Anidrase Carbônica/toxicidade
Desenvolvimento Embrionário/efeitos dos fármacos
Etoxzolamida/toxicidade
Sulfonamidas/toxicidade
Peixe-Zebra/embriologia
[Mh] Termos MeSH secundário: Animais
Antineoplásicos/síntese química
Antineoplásicos/química
Inibidores da Anidrase Carbônica/síntese química
Inibidores da Anidrase Carbônica/química
Relação Dose-Resposta a Droga
Embrião não Mamífero/efeitos dos fármacos
Etoxzolamida/química
Dose Letal Mediana
Sulfonamidas/síntese química
Sulfonamidas/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Carbonic Anhydrase Inhibitors); 0 (Sulfonamides); EC 4.2.1.1 (Carbonic Anhydrase IX); Z52H4811WX (Ethoxzolamide)
[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:160908
[St] Status:MEDLINE
[do] DOI:10.1080/01480545.2016.1223095


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[PMID]:27614168
[Au] Autor:Vargas LA; Pinilla OA; Díaz RG; Sepúlveda DE; Swenson ER; Pérez NG; Álvarez BV
[Ad] Endereço:Centro de Investigaciones Cardiovasculares, Consejo Nacional de Investigaciones Científicas y Técnicas, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, 1900 La Plata, Buenos Aires, Argentina.
[Ti] Título:Carbonic anhydrase inhibitors reduce cardiac dysfunction after sustained coronary artery ligation in rats.
[So] Source:Cardiovasc Pathol;25(6):468-477, 2016 Nov - Dec.
[Is] ISSN:1879-1336
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Two potent carbonic anhydrase (CA) inhibitors with widely differing membrane permeability, poorly diffusible benzolamide (BZ), and highly diffusible ethoxzolamide (ETZ) were assessed to determine whether they can reduce cardiac dysfunction in rats subjected to coronary artery ligation (CAL)-induced myocardial infarction. METHODS AND RESULTS: Rats with evidence of heart failure (HF) at 32 weeks following a permanent left anterior coronary artery occlusion were treated with placebo, BZ, or ETZ (4 mg kgday ) for 4 weeks at which time left ventricular function and structure were evaluated. Lung weight/body weight (LW/BW) ratio increased in CAL rats by 17±1% vs. control, suggesting pulmonary edema. There was a trend for BZ and ETZ to ameliorate the increase in LW/BW by almost 50% (9±5% and 9±8%, respectively, versus CAL) (P=.16, NS). Echocardiographic assessment showed decreased left ventricular midwall shortening in HF rats, 21±1% vs. control 32±1%, which was improved by BZ to 29±1% and ETZ to 27±1%, and reduced endocardial shortening in HF rats 38±3% vs. control 62±1%, partially restored by BZ and ETZ to ~50%. Expression of the hypoxia-inducible membrane-associated CAIX isoform increased by ~60% in HF rat hearts, and this effect was blocked by ETZ. CONCLUSIONS: We conclude that CAL-induced myocardial interstitial fibrosis and associated decline in left ventricular function were diminished with BZ or ETZ treatment. The reductions in cardiac remodeling in HF with both ETZ and BZ CA inhibitors suggest that inhibition of a membrane-bound CA appears to be the critical site for this protection.
[Mh] Termos MeSH primário: Benzolamida/farmacologia
Inibidores da Anidrase Carbônica/farmacologia
Etoxzolamida/farmacologia
Coração/efeitos dos fármacos
Infarto do Miocárdio/patologia
[Mh] Termos MeSH secundário: Animais
Vasos Coronários/cirurgia
Modelos Animais de Doenças
Immunoblotting
Ligadura
Masculino
Ratos
Ratos Wistar
Função Ventricular Esquerda/efeitos dos fármacos
Remodelação Ventricular/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Carbonic Anhydrase Inhibitors); FC5AAH89R5 (Benzolamide); Z52H4811WX (Ethoxzolamide)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:170124
[Lr] Data última revisão:
170124
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160911
[St] Status:MEDLINE


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[PMID]:26785169
[Au] Autor:Das MC; Paul S; Gupta P; Tribedi P; Sarkar S; Manna D; Bhattacharjee S
[Ad] Endereço:Department of Molecular Biology & Bioinformatics, Tripura University, Agartala, Tripura, India.
[Ti] Título:3-Amino-4-aminoximidofurazan derivatives: small molecules possessing antimicrobial and antibiofilm activity against Staphylococcus aureus and Pseudomonas aeruginosa.
[So] Source:J Appl Microbiol;120(4):842-59, 2016 Apr.
[Is] ISSN:1365-2672
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:AIM: The therapeutic treatment of microbial infections involving biofilm becomes quite challenging because of its increasing antibiotic resistance capacities. Towards this direction, in the present study we have evaluated the antibiofilm property of synthesized 3-amino-4-aminoximidofurazan compounds having polyamine skeleton. These derivatives were synthesized by incorporating furazan and biguanide moieties. METHODS AND RESULTS: Different 3-amino-4-aminoximidofurazan derivatives (PI1-4) were synthesized via protic acid catalysis and subsequently characterized by (1) H NMR and (13) C NMR spectra, recorded at 400 and 100 MHz respectively. We have tested the antimicrobial and antibiofilm activities of these synthetic derivatives (PI1-4) against both Staphylococcus aureus and Pseudomonas aeruginosa. The compounds so tested were also compared with standard antibiotics namely Tobramycin (Ps. aeruginosa) and Azithromycin (Staph. aureus) which were used as a positive control in all experimental sets. All these compounds (PI1-4) exhibited moderate to significant antimicrobial activities against both micro-organisms wherein compound PI3 showed maximum activity. Biofilm inhibition of both micro-organisms was then evaluated by crystal violet and safranin staining, estimation of biofilm total protein and microscopy methods using sub-MIC dose of these compounds. Results showed that all compounds executed anti biofilm activity against both Staph. aureus and Ps. aeruginosa wherein compound PI3 exhibited maximum activity. In relation with microbial biofilm inhibition, we have observed reduction in bacterial motility, proteolytic activity and secreted exo-polysaccharide (EPS) from both Staph. aureus and Ps. aeruginosa when they were grown in presence of these compounds. While addressing the issue of toxicity on host, we have observed that these molecules exhibited minimum level of R.B.C degradation. CONCLUSION: These findings establish the antibacterial and anti biofilm properties of 3-amino-4-aminoximidofurazan derivatives (PI1-4). SIGNIFICANCE AND IMPACT OF THE STUDY: Therefore, our current findings demonstrate that 3-amino-4-aminoximidofurazan derivatives (PI1-4) may hold promise to be effective biofilm and microbial inhibitors that may be clinically significant.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Biofilmes/efeitos dos fármacos
Etoxzolamida/análogos & derivados
Pseudomonas aeruginosa/efeitos dos fármacos
Staphylococcus aureus/efeitos dos fármacos
[Mh] Termos MeSH secundário: Antibacterianos/química
Etoxzolamida/química
Etoxzolamida/farmacologia
Seres Humanos
Testes de Sensibilidade Microbiana
Infecções por Pseudomonas/microbiologia
Pseudomonas aeruginosa/fisiologia
Infecções Estafilocócicas/microbiologia
Staphylococcus aureus/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 94641-11-9 (aminozolamide); Z52H4811WX (Ethoxzolamide)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:161230
[Lr] Data última revisão:
161230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160120
[St] Status:MEDLINE
[do] DOI:10.1111/jam.13063


  5 / 167 MEDLINE  
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[PMID]:26470855
[Au] Autor:Klier M; Jamali S; Ames S; Schneider HP; Becker HM; Deitmer JW
[Ad] Endereço:Abteilung für Allgemeine Zoologie, FB Biologie, University of Kaiserslautern, Germany.
[Ti] Título:Catalytic activity of human carbonic anhydrase isoform IX is displayed both extra- and intracellularly.
[So] Source:FEBS J;283(1):191-200, 2016 Jan.
[Is] ISSN:1742-4658
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Most carbonic anhydrases catalyse the reversible conversion of carbon dioxide to protons and bicarbonate, either as soluble cytosolic enzymes, in or at intracellular organelles, or at the extracellular face of the cell membrane as membrane-anchored proteins. Carbonic anhydrase isoform IX (CA IX), a membrane-bound enzyme with catalytic activity at the extracellular membrane surface, has come to prominence in recent years because of its association with hypoxic tissue, particularly tumours, often indicating poor prognosis. We have evaluated the catalytic activity of CA IX heterologously expressed in Xenopus laevis oocytes by measuring the amplitude and rate of cytosolic pH changes as well as pH changes at the outer membrane surface (pHs ) during addition and removal of 5% CO2 /25 mm HCO3-, and by mass spectrometry. Our results indicate both extracellular and intracellular catalytic activity of CA IX. Reduced rates of CO2 -dependent intracellular pH changes after knockdown of CA IX confirmed these findings in two breast cancer cell lines: MCF-7 and MDA-MB-231. Our results demonstrate a new function of CA IX that may be important in the search for therapeutic cancer drugs targeting CA IX.
[Mh] Termos MeSH primário: Antígenos de Neoplasias/metabolismo
Biocatálise
Anidrases Carbônicas/metabolismo
Espaço Extracelular/enzimologia
Espaço Intracelular/enzimologia
[Mh] Termos MeSH secundário: Animais
Bicarbonatos/química
Dióxido de Carbono/química
Anidrase Carbônica IX
Linhagem Celular Tumoral
Etoxzolamida/farmacologia
Seres Humanos
Concentração de Íons de Hidrogênio
Isoenzimas/metabolismo
Células MCF-7
Oócitos/citologia
Oócitos/enzimologia
Xenopus laevis
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antigens, Neoplasm); 0 (Bicarbonates); 0 (Isoenzymes); 142M471B3J (Carbon Dioxide); EC 4.2.1.1 (CA9 protein, human); EC 4.2.1.1 (Carbonic Anhydrase IX); EC 4.2.1.1 (Carbonic Anhydrases); Z52H4811WX (Ethoxzolamide)
[Em] Mês de entrada:1606
[Cu] Atualização por classe:161126
[Lr] Data última revisão:
161126
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151017
[St] Status:MEDLINE
[do] DOI:10.1111/febs.13562


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[PMID]:25987613
[Au] Autor:Johnson BK; Colvin CJ; Needle DB; Mba Medie F; Champion PA; Abramovitch RB
[Ad] Endereço:Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan, USA.
[Ti] Título:The Carbonic Anhydrase Inhibitor Ethoxzolamide Inhibits the Mycobacterium tuberculosis PhoPR Regulon and Esx-1 Secretion and Attenuates Virulence.
[So] Source:Antimicrob Agents Chemother;59(8):4436-45, 2015 Aug.
[Is] ISSN:1098-6596
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mycobacterium tuberculosis must sense and adapt to host environmental cues to establish and maintain an infection. The two-component regulatory system PhoPR plays a central role in sensing and responding to acidic pH within the macrophage and is required for M. tuberculosis intracellular replication and growth in vivo. Therefore, the isolation of compounds that inhibit PhoPR-dependent adaptation may identify new antivirulence therapies to treat tuberculosis. Here, we report that the carbonic anhydrase inhibitor ethoxzolamide inhibits the PhoPR regulon and reduces pathogen virulence. We show that treatment of M. tuberculosis with ethoxzolamide recapitulates phoPR mutant phenotypes, including downregulation of the core PhoPR regulon, altered accumulation of virulence-associated lipids, and inhibition of Esx-1 protein secretion. Quantitative single-cell imaging of a PhoPR-dependent fluorescent reporter strain demonstrates that ethoxzolamide inhibits PhoPR-regulated genes in infected macrophages and mouse lungs. Moreover, ethoxzolamide reduces M. tuberculosis growth in both macrophages and infected mice. Ethoxzolamide inhibits M. tuberculosis carbonic anhydrase activity, supporting a previously unrecognized link between carbonic anhydrase activity and PhoPR signaling. We propose that ethoxzolamide may be pursued as a new class of antivirulence therapy that functions by modulating expression of the PhoPR regulon and Esx-1-dependent virulence.
[Mh] Termos MeSH primário: Antígenos de Bactérias/metabolismo
Proteínas de Bactérias/metabolismo
Inibidores da Anidrase Carbônica/farmacologia
Etoxzolamida/farmacologia
Mycobacterium tuberculosis/efeitos dos fármacos
Mycobacterium tuberculosis/genética
Regulon/efeitos dos fármacos
Virulência/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Antígenos de Bactérias/genética
Proteínas de Bactérias/genética
Anidrases Carbônicas/genética
Anidrases Carbônicas/metabolismo
Células Cultivadas
Regulação para Baixo/efeitos dos fármacos
Regulação para Baixo/genética
Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos
Regulação Bacteriana da Expressão Gênica/genética
Macrófagos/efeitos dos fármacos
Macrófagos/metabolismo
Macrófagos/microbiologia
Camundongos
Camundongos Endogâmicos C57BL
Mutação/efeitos dos fármacos
Mutação/genética
Mycobacterium tuberculosis/metabolismo
Tuberculose/tratamento farmacológico
Tuberculose/genética
Tuberculose/metabolismo
Tuberculose/microbiologia
Virulência/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antigens, Bacterial); 0 (Bacterial Proteins); 0 (Carbonic Anhydrase Inhibitors); 0 (ESAT-6 protein, Mycobacterium tuberculosis); EC 4.2.1.1 (Carbonic Anhydrases); Z52H4811WX (Ethoxzolamide)
[Em] Mês de entrada:1604
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150520
[St] Status:MEDLINE
[do] DOI:10.1128/AAC.00719-15


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[PMID]:25706567
[Au] Autor:Gao S; Zhao J; Yin T; Ma Y; Xu B; Moore AN; Dash PK; Hu M
[Ad] Endereço:Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, The University of Houston, 1441 Moursund Street, Houston, TX 77030, USA. Electronic address: sgao3@uh.edu.
[Ti] Título:Development and validation of an UPLC-MS/MS method for the quantification of ethoxzolamide in blood, brain tissue, and bioequivalent buffers: applications to absorption, brain distribution, and pharmacokinetic studies.
[So] Source:J Chromatogr B Analyt Technol Biomed Life Sci;986-987:54-9, 2015 Apr 01.
[Is] ISSN:1873-376X
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The purpose of this study is to develop and validate an UPLC-MS/MS method to quantify ethoxzolamide in plasma (EZ) and apply the method to absorption, brain distribution, as well as pharmacokinetic studies. A C18 column was used with 0.1% of formic acid in acetonitrile and 0.1% of formic acid in water as the mobile phases to resolve EZ. The mass analysis was performed in a triple quadrupole mass spectrometer using multiple reaction monitoring (MRM) with positive scan mode. The results show that the linear range of EZ is 4.88-10,000.00 nM. The intra-day variance is less than 12.43% and the accuracy is between 88.88 and 108.00%. The inter-day variance is less than 12.87% and accuracy is between 89.27 and 115.89%. Protein precipitation was performed using methanol to extract EZ from plasma and brain tissues. Only 40 µL of plasma is needed for analysis due to the high sensitivity of this method, which could be completed in less than three minutes. This method was used to study the pharmacokinetics of EZ in SD rats, and the transport of EZ in Caco-2 and MDCK-MDR1 overexpressing cell culture models. Our data show that EZ is not a substrate for p-glycoprotein (P-gp) and its entry into the brain may not limited by the blood-brain barrier.
[Mh] Termos MeSH primário: Cromatografia Líquida de Alta Pressão/métodos
Etoxzolamida/análise
Etoxzolamida/farmacocinética
Espectrometria de Massas em Tandem/métodos
[Mh] Termos MeSH secundário: Administração Intravenosa
Animais
Química Encefálica
Células CACO-2
Etoxzolamida/administração & dosagem
Etoxzolamida/química
Seres Humanos
Modelos Lineares
Masculino
Ratos
Ratos Sprague-Dawley
Reprodutibilidade dos Testes
Sensibilidade e Especificidade
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
Z52H4811WX (Ethoxzolamide)
[Em] Mês de entrada:1511
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150224
[St] Status:MEDLINE


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[PMID]:25652363
[Au] Autor:Pilipuityte V; Matulis D
[Ad] Endereço:Department of Biothermodynamics and Drug Design, Institute of Biotechnology, Vilnius University, Graiciuno 8, Vilnius, LT-02241, Lithuania.
[Ti] Título:Intrinsic thermodynamics of trifluoromethanesulfonamide and ethoxzolamide binding to human carbonic anhydrase VII.
[So] Source:J Mol Recognit;28(3):166-72, 2015 Mar.
[Is] ISSN:1099-1352
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Human carbonic anhydrase (CA) isozyme VII is a cytosolic protein that is highly expressed in the cortex, hippocampus, and thalamus regions within mammalian brain, and expression disorders can cause epilepsy and several cases of malignant brain tumors. Therefore, CA VII is a potential antiepileptic and anticancer drug target. There are numerous sulfonamides that target CAs nonspecifically. It is important to understand the thermodynamics of inhibitor binding and the structural features of the protein-inhibitor complex in order to design specific inhibitors against CA VII. Isothermal titration calorimetry and fluorescent thermal shift assay were used to characterize the intrinsic thermodynamic parameters of trifluoromethanesulfonamide and ethoxzolamide binding to CA VII. Binding experiments were carried out at various pH in different buffers in order to dissect linked protonation of the water molecule bound to the CA VII active site, deprotonation of the sulfonamide group of the inhibitor, and protonation-deprotonation of buffer. Dissection of all those contributions yielded the intrinsic thermodynamic parameters of binding, such as Gibbs free energy, binding enthalpy, entropy, and protein pKa value. Thermal shift assay was also used to determine CA VII stability at various pH.
[Mh] Termos MeSH primário: Inibidores da Anidrase Carbônica/química
Anidrases Carbônicas/metabolismo
Sulfonamidas/química
Sulfonamidas/farmacocinética
[Mh] Termos MeSH secundário: Sítios de Ligação
Calorimetria/métodos
Inibidores da Anidrase Carbônica/farmacocinética
Etoxzolamida/química
Etoxzolamida/farmacocinética
Seres Humanos
Concentração de Íons de Hidrogênio
Modelos Moleculares
Termodinâmica
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Carbonic Anhydrase Inhibitors); 0 (Sulfonamides); EC 4.2.1.1 (Carbonic Anhydrases); EC 4.2.1.1 (carbonic anhydrase VI); Z52H4811WX (Ethoxzolamide)
[Em] Mês de entrada:1511
[Cu] Atualização por classe:150224
[Lr] Data última revisão:
150224
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150206
[St] Status:MEDLINE
[do] DOI:10.1002/jmr.2404


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[PMID]:24127518
[Au] Autor:Olischläger M; Wiencke C
[Ad] Endereço:Alfred Wegener Institute for Polar and Marine Research, Section of Functional Ecology, Department of Seaweed Biology, Am Handelshafen 12, D-27570 Bremerhaven, Germany.
[Ti] Título:Ocean acidification alleviates low-temperature effects on growth and photosynthesis of the red alga Neosiphonia harveyi (Rhodophyta).
[So] Source:J Exp Bot;64(18):5587-97, 2013 Dec.
[Is] ISSN:1460-2431
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:This study aimed to examine interactive effects between ocean acidification and temperature on the photosynthetic and growth performance of Neosiphonia harveyi. N. harveyi was cultivated at 10 and 17.5 °C at present (~380 µatm), expected future (~800 µatm), and high (~1500 µatm) pCO2. Chlorophyll a fluorescence, net photosynthesis, and growth were measured. The state of the carbon-concentrating mechanism (CCM) was examined by pH-drift experiments (with algae cultivated at 10 °C only) using ethoxyzolamide, an inhibitor of external and internal carbonic anhydrases (exCA and intCA, respectively). Furthermore, the inhibitory effect of acetazolamide (an inhibitor of exCA) and Tris (an inhibitor of the acidification of the diffusive boundary layer) on net photosynthesis was measured at both temperatures. Temperature affected photosynthesis (in terms of photosynthetic efficiency, light saturation point, and net photosynthesis) and growth at present pCO2, but these effects decreased with increasing pCO2. The relevance of the CCM decreased at 10 °C. A pCO2 effect on the CCM could only be shown if intCA and exCA were inhibited. The experiments demonstrate for the first time interactions between ocean acidification and temperature on the performance of a non-calcifying macroalga and show that the effects of low temperature on photosynthesis can be alleviated by increasing pCO2. The findings indicate that the carbon acquisition mediated by exCA and acidification of the diffusive boundary layer decrease at low temperatures but are not affected by the cultivation level of pCO2, whereas the activity of intCA is affected by pCO2. Ecologically, the findings suggest that ocean acidification might affect the biogeographical distribution of N. harveyi.
[Mh] Termos MeSH primário: Fotossíntese
Rodófitas/fisiologia
Água do Mar/química
[Mh] Termos MeSH secundário: Acetazolamida/farmacologia
Dióxido de Carbono/metabolismo
Inibidores da Anidrase Carbônica/farmacologia
Clorofila/análogos & derivados
Clorofila/metabolismo
Temperatura Baixa
Etoxzolamida/farmacologia
Fluorescência
Concentração de Íons de Hidrogênio
Oxigênio/metabolismo
Rodófitas/efeitos dos fármacos
Rodófitas/crescimento & desenvolvimento
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Carbonic Anhydrase Inhibitors); 1406-65-1 (Chlorophyll); 142M471B3J (Carbon Dioxide); 22309-13-3 (chlorophyll a'); O3FX965V0I (Acetazolamide); S88TT14065 (Oxygen); Z52H4811WX (Ethoxzolamide)
[Em] Mês de entrada:1408
[Cu] Atualização por classe:131225
[Lr] Data última revisão:
131225
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:131016
[St] Status:MEDLINE
[do] DOI:10.1093/jxb/ert329


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[PMID]:24076121
[Au] Autor:Shah GN; Morofuji Y; Banks WA; Price TO
[Ad] Endereço:Division of Endocrinology, Department of Internal Medicine, Saint Louis University School of Medicine, Edward A. Doisy Research Center, 1100 South Grand Blvd., DRC 354, St. Louis, MO 63104, USA. Electronic address: shahgn@slu.edu.
[Ti] Título:High glucose-induced mitochondrial respiration and reactive oxygen species in mouse cerebral pericytes is reversed by pharmacological inhibition of mitochondrial carbonic anhydrases: Implications for cerebral microvascular disease in diabetes.
[So] Source:Biochem Biophys Res Commun;440(2):354-8, 2013 Oct 18.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Hyperglycemia-induced oxidative stress leads to diabetes-associated damage to the microvasculature of the brain. Pericytes in close proximity to endothelial cells in the brain microvessels are vital to the integrity of the blood-brain barrier and are especially susceptible to oxidative stress. According to our recently published results, streptozotocin-diabetic mouse brain exhibits oxidative stress and loose pericytes by twelve weeks of diabetes, and cerebral pericytes cultured in high glucose media suffer intracellular oxidative stress and apoptosis. Oxidative stress in diabetes is hypothesized to be caused by reactive oxygen species (ROS) produced during hyperglycemia-induced enhanced oxidative metabolism of glucose (respiration). To test this hypothesis, we investigated the effect of high glucose on respiration rate and ROS production in mouse cerebral pericytes. Previously, we showed that pharmacological inhibition of mitochondrial carbonic anhydrases protects the brain from oxidative stress and pericyte loss. The high glucose-induced intracellular oxidative stress and apoptosis of pericytes in culture were also reversed by inhibition of mitochondrial carbonic anhydrases. Therefore, we extended our current study to determine the effect of these inhibitors on high glucose-induced increases in pericyte respiration and ROS. We now report that both the respiration and ROS are significantly increased in pericytes challenged with high glucose. Furthermore, inhibition of mitochondrial carbonic anhydrases significantly slowed down both the rate of respiration and ROS production. These data provide new evidence that pharmacological inhibitors of mitochondrial carbonic anhydrases, already in clinical use, may prove beneficial in protecting the brain from oxidative stress caused by ROS produced as a consequence of hyperglycemia-induced enhanced respiration.
[Mh] Termos MeSH primário: Inibidores da Anidrase Carbônica/farmacologia
Glucose/administração & dosagem
Mitocôndrias/efeitos dos fármacos
Estresse Oxidativo/efeitos dos fármacos
Pericitos/efeitos dos fármacos
Espécies Reativas de Oxigênio/metabolismo
[Mh] Termos MeSH secundário: Animais
Barreira Hematoencefálica/efeitos dos fármacos
Respiração Celular/efeitos dos fármacos
Células Cultivadas
Diabetes Mellitus Experimental/metabolismo
Etoxzolamida/farmacologia
Frutose/análogos & derivados
Frutose/farmacologia
Hiperglicemia/fisiopatologia
Camundongos
Mitocôndrias/metabolismo
Pericitos/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Carbonic Anhydrase Inhibitors); 0 (Reactive Oxygen Species); 0H73WJJ391 (topiramate); 30237-26-4 (Fructose); IY9XDZ35W2 (Glucose); Z52H4811WX (Ethoxzolamide)
[Em] Mês de entrada:1312
[Cu] Atualização por classe:161019
[Lr] Data última revisão:
161019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:131001
[St] Status:MEDLINE



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