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1.
Microbiol Spectr ; 12(3): e0310223, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38289090

RESUMO

Tomatoes are readily available and affordable vegetables that offer a range of health benefits due to their bioactive molecules, such as antioxidants and antimicrobials. In contrast to the widely recognized antioxidant properties of tomatoes, their antimicrobial properties remain largely unexplored. Here, we present our findings on the antimicrobial properties of tomato juice and peptides, namely, tomato-derived antimicrobial peptides (tdAMPs), in relation to their effectiveness against typhoidal Salmonella. Our research has revealed that tomato juice demonstrates significant antimicrobial properties against Salmonella Typhi, a pathogen that specifically affects humans and is responsible for causing typhoid fever. By employing computational analysis of the tomato genome sequence, conducting molecular dynamics simulation, and performing functional analyses, we have successfully identified two tdAMPs, namely, tdAMP-1 and tdAMP-2. These tdAMPs have demonstrated potent antimicrobial properties by effectively disrupting bacterial membranes. The efficacy of tdAMP-2 is shown to be more effective than tdAMP-1. The efficacy of tdAMP-1 and tdAMP-2 has been demonstrated against drug-resistant S. Typhi, as well as hyper-capsular S. Typhi variants that possess hypervirulent characteristics, which are presently circulating in countries with endemicity. Tomato juice, along with the two tdAMPs, has demonstrated effectiveness against uropathogenic Escherichia coli as well. This underscores their potential as viable agents in combating certain Gram-negative pathogens. This study provides valuable insights into the development of effective and sustainable public health strategies that utilize tomato and its derivatives as lifestyle interventions.IMPORTANCEIn this study, we investigate the antimicrobial properties of tomato juice, the most widely consumed affordable vegetables, as well as tomato-derived antimicrobial peptides, in relation to their effectiveness against foodborne pathogens with an emphasis on Salmonella Typhi, a deadly human-specific pathogen.


Assuntos
Anti-Infecciosos , Solanum lycopersicum , Febre Tifoide , Humanos , Febre Tifoide/microbiologia , Salmonella/genética , Salmonella typhi/genética , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Peptídeos/farmacologia , Peptídeos Antimicrobianos
2.
Mar Drugs ; 13(6): 3836-48, 2015 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-26087023

RESUMO

Four new iodobenzene-containing dipeptides (1-4), a related bromotryptophan-containing dipeptide (5), and an iodophenethylamine (6) were isolated from the ascidian Aplidium sp. collected off the coast of Chuja-do, Korea. The structures of these novel compounds, designated as apliamides A-E (1-5) and apliamine A (6) were determined via combined spectroscopic analyses. The absolute configuration of the amino acid residue in 1 was determined by advanced Marfey's analysis. Several of these compounds exhibited moderate cytotoxicity and significant inhibition against Na+/K+-ATPase (4).


Assuntos
Aminoácidos/química , Dipeptídeos/farmacologia , Iodobenzenos/farmacologia , Urocordados/metabolismo , Animais , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Dipeptídeos/química , Dipeptídeos/isolamento & purificação , Humanos , Iodobenzenos/química , Iodobenzenos/isolamento & purificação , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores , Análise Espectral
3.
Bioorg Med Chem Lett ; 25(7): 1394-7, 2015 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-25746812

RESUMO

A new maltol derivative (2) along with three known maltol derivative (1) and flavonol glycosides (3 and 4) were isolated from the dried flowers of Sophora japonica. Based upon the results of combined spectroscopic methods, the structure of new compound (2) was determined to be maltol-3-O-(4'-O-cis-p-coumaroyl-6'-O-(3-hydroxy-3-methylglutaroyl))-ß-glucopyranoside, an isomer of 1. These compounds strongly inhibited the action of sortase A (SrtA) from Streptococcus mutans, a primary etiologic agent of human dental caries. The onset and magnitude of inhibition of the saliva-induced aggregation in S. mutans treated with compound 2 (4×IC50) were comparable to the behavior of untreated srtA-deletion mutant.


Assuntos
Aminoaciltransferases/antagonistas & inibidores , Proteínas de Bactérias/antagonistas & inibidores , Flores/química , Pironas/farmacologia , Sophora/química , Streptococcus mutans/efeitos dos fármacos , Aminoaciltransferases/genética , Aminoaciltransferases/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Cisteína Endopeptidases/genética , Cisteína Endopeptidases/metabolismo , Relação Dose-Resposta a Droga , Conformação Molecular , Pironas/química , Pironas/isolamento & purificação , Streptococcus mutans/crescimento & desenvolvimento , Streptococcus mutans/metabolismo , Relação Estrutura-Atividade
4.
J Nat Prod ; 78(4): 836-43, 2015 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-25700232

RESUMO

Salternamides A-D (1-4), the first secondary metabolites discovered from saltern-derived actinomycetes, were isolated from a halophilic Streptomyces strain isolated from a saltern on Shinui Island in the Republic of Korea. The planar structures of the salternamides, which are new members of the manumycin family, were elucidated by a combination of spectroscopic analyses. The absolute configurations of the salternamides were determined by chemical and spectroscopic methods, including the modified Mosher's method, J-based configuration analysis, and circular dichroism spectroscopy. Salternamide A (1), which is the first chlorinated compound in the manumycin family, exhibited potent cytotoxicity against a human colon cancer cell line (HCT116) and a gastric cancer cell line (SNU638) with submicromolar IC50 values. Salternamides A and D were also determined to be weak Na(+)/K(+) ATPase inhibitors.


Assuntos
Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Polienos/isolamento & purificação , Polienos/farmacologia , Alcamidas Poli-Insaturadas/isolamento & purificação , Alcamidas Poli-Insaturadas/farmacologia , Plantas Tolerantes a Sal/química , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores , Streptomyces/química , Actinobacteria , Antineoplásicos/química , Dicroísmo Circular , Neoplasias do Colo , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Concentração Inibidora 50 , Estrutura Molecular , Polienos/química , Alcamidas Poli-Insaturadas/química , República da Coreia
5.
Mar Drugs ; 12(6): 3754-69, 2014 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-24962272

RESUMO

Seven new amino alcohol compounds, pseudoaminols A-G (1-7), were isolated from the ascidian Pseudodistoma sp. collected off the coast of Chuja-do, Korea. Structures of these new compounds were determined by analysis of the spectroscopic data and from chemical conversion. The presence of an N-carboxymethyl group in two of the new compounds (6 and 7) is unprecedented among amino alcohols. Several of these compounds exhibited moderate antimicrobial activity and cytotoxicity, as well as weak inhibitory activity toward Na+/K+-ATPase.


Assuntos
Amino Álcoois/farmacologia , Urocordados/metabolismo , Amino Álcoois/química , Amino Álcoois/isolamento & purificação , Animais , Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificação , Anti-Infecciosos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Humanos , República da Coreia , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores , Análise Espectral
6.
J Microbiol Biotechnol ; 24(9): 1207-15, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24931501

RESUMO

Candida albicans, the major human fungal pathogen, undergoes morphological transition from the budding yeast form to filamentous growth in response to nitrogen starvation. In this study, we identified a new function of GST2, whose expression was required for filamentous growth of C. albicans under nitrogen-limiting conditions. The ΔGst2p showed Gst activity and required response to oxidative stress. The Δgst2 mutant displayed predominantly yeast phase growth in low ammonium media. Such morphological defect of Δgst2 mutants was not rescued by overexpression of Mep2p, Cph1p, or Efg1p, but was rescued by either overexpression of a hyperactive RAS1(G13V) allele or through exogenous addition of cyclic AMP. In addition, the Δgst2 mutants had lower levels of RAS1 transcripts than wild-type cells under conditions of nitrogen starvation. These results were consistent with the Ras1-cAMP pathway as a possible downstream target of Gst2p. These findings suggest that Gst2p is a significant component of nitrogen starvation-induced filamentation in C. albicans.


Assuntos
Candida albicans/crescimento & desenvolvimento , Candida albicans/genética , Proteínas Fúngicas/genética , Glutationa Transferase/genética , Nitrogênio/metabolismo , Estresse Oxidativo/genética , Candida albicans/metabolismo , AMP Cíclico/metabolismo , Proteínas Fúngicas/metabolismo , Glutationa Transferase/metabolismo , Hifas/genética , Hifas/crescimento & desenvolvimento , Mutação/genética , Estresse Oxidativo/fisiologia , Transdução de Sinais/genética , Proteínas ras/metabolismo
7.
J Nat Prod ; 75(12): 2055-61, 2012 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-23145909

RESUMO

Nine new compounds, tris-aromatic furanones (1, 2, 3a, 3b, and 4) and related bis-aromatic diesters (5a, 5b, 6a, and 6b), are described from the ascidian Synoicum sp. collected off the coast of Chuja-do, Korea. The structures of these compounds, designated as cadiolides E and G-I (1-4) and synoilides A and B (5 and 6), were determined by extensive spectroscopic analyses. The absolute configuration at the asymmetric center of cadiolide G (2) was assigned by ECD analysis. Of these new compounds, cadiolide I and the synoilides possess unprecedented carbon skeletons. Several of these compounds exhibited significant inhibition against diverse bacterial strains as well as moderate inhibition against the enzymes sortase A, isocitrate lyase, and Na(+)/K(+)-ATPase.


Assuntos
Furanos/isolamento & purificação , Hidrocarbonetos Bromados/isolamento & purificação , Aminoaciltransferases/antagonistas & inibidores , Animais , Proteínas de Bactérias/antagonistas & inibidores , Cisteína Endopeptidases , Ensaios de Seleção de Medicamentos Antitumorais , Ésteres , Furanos/química , Furanos/farmacologia , Hidrocarbonetos Bromados/química , Hidrocarbonetos Bromados/farmacologia , Isocitrato Liase/antagonistas & inibidores , Testes de Sensibilidade Microbiana , Estrutura Molecular , República da Coreia , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores , Staphylococcus aureus/efeitos dos fármacos , Urocordados/química
8.
Bioorg Med Chem ; 20(13): 4082-7, 2012 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-22652254

RESUMO

Six ß-carboline alkaloids (1-6) of the eudistomin Y class were isolated from the Korean ascidian Synoicum sp. These compounds were chemically converted to a known compound, eudistomin Y(1) (7) and six new derivatives, designated eudistomins Y(8)-Y(13) (8-13). Several of these natural and synthetic compounds exhibited moderate to significant antimicrobial activity, weak cytotoxic activity, and inhibitory activities toward sortase A, isocitrate lyase, and Na(+)/K(+)-ATPase. Structure-activity relationships were also deduced.


Assuntos
Alcaloides/química , Anti-Infecciosos/química , Carbolinas/química , Urocordados/química , Alcaloides/farmacologia , Alcaloides/toxicidade , Aminoaciltransferases/antagonistas & inibidores , Aminoaciltransferases/metabolismo , Animais , Anti-Infecciosos/farmacologia , Anti-Infecciosos/toxicidade , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/metabolismo , Carbolinas/síntese química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cisteína Endopeptidases/metabolismo , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Isocitrato Liase/antagonistas & inibidores , Isocitrato Liase/metabolismo , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores , ATPase Trocadora de Sódio-Potássio/metabolismo , Relação Estrutura-Atividade
9.
Biol Pharm Bull ; 35(3): 428-32, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22382332

RESUMO

Na(+)/K(+)-adenosine triphosphatase (ATPase) inhibitors have considerable therapeutic potential against some heart diseases like congestive heart failure and cardiac arrhythmias. Through bioassay-guided separation of the leaf extract of Laurus nobilis, six acylated kaempferol glycosides (compounds 1-6) were isolated. Their structures were determined on the basis of spectroscopic analysis and comparison with reported data. All the isolates were subjected to in vitro bioassays to evaluate their inhibitory activities against Na(+)/K(+)-ATPase from porcine cerebral cortex and bacterial growth. These studies led to the identification of compounds 1-6 as potent Na(+)/K(+)-ATPase inhibitors, with IC(50) values in the range of 4.0 ± 0.1-10.4 ± 0.6 µM. These compounds also exhibited a broad spectrum of antibacterial activity. In particular, compounds 4 and 6 showed potent inhibitory activities against several bacterial strains, except Escherichia coli, with minimum inhibitory concentration (MIC) values in the range of 0.65-2.08 µg/mL. Thus, L. nobilis-derived acylated kaempferol glycosides may have a potential to be leads for the development of Na(+)/K(+) ATPase inhibitors (1-6) and antibacterial agents (4, 6).


Assuntos
Antibacterianos/farmacologia , Inibidores Enzimáticos/farmacologia , Glicosídeos/farmacologia , Quempferóis/farmacologia , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores , Acilação , Animais , Antibacterianos/isolamento & purificação , Bactérias/efeitos dos fármacos , Córtex Cerebral/enzimologia , Inibidores Enzimáticos/isolamento & purificação , Glicosídeos/isolamento & purificação , Quempferóis/isolamento & purificação , Laurus/química , Testes de Sensibilidade Microbiana , Extratos Vegetais/química , Folhas de Planta/química , ATPase Trocadora de Sódio-Potássio/metabolismo , Suínos
10.
Bioorg Med Chem Lett ; 17(19): 5366-9, 2007 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-17716892

RESUMO

Four aaptamines (1-4), 1H-benzo[de][1,6]-naphthyridine alkaloids, were isolated from the marine sponge Aaptos aaptos and their inhibitory activities against sortase A (SrtA), an enzyme that plays a key role in cell wall protein anchoring and virulence in Staphylococcus aureus, were evaluated. Isoaaptamine (2) was a potent inhibitor of SrtA, with an IC(50) value of 3.7+/-0.2 microg/mL. The suppression of fibronectin-binding activity by isoaaptamine (2) highlights its potential for the treatment of S. aureus infections via inhibition of SrtA activity. Our studies have identified a series of SrtA inhibitors, providing the basis for further development of potent inhibitors.


Assuntos
Aminoaciltransferases/antagonistas & inibidores , Proteínas de Bactérias/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Naftiridinas/farmacologia , Poríferos/química , Animais , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Cromatografia em Gel , Cromatografia Líquida de Alta Pressão , Cisteína Endopeptidases , Inibidores Enzimáticos/isolamento & purificação , Fibronectinas/metabolismo , Testes de Sensibilidade Microbiana , Naftiridinas/isolamento & purificação , Ligação Proteica , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento
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