Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 3 de 3
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Biol Pharm Bull ; 37(2): 268-73, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24492724

RESUMO

Over-expression of the Candida drug resistance gene CDR1 is a common mechanism generating azole-resistant Candida albicans in clinical isolates. CDR1 is transcriptionally activated through the binding of the transcription factor Tac1p to the cis-acting drug-responsive element (DRE) in its promoter. We previously demonstrated that the combination of fluconazole (FLC) and berberine (BBR) produced significant synergy when used against FLC-resistant C. albicans in vitro. In this study, we found that BBR inhibited both the up-regulation of CDR1 mRNA and the transport function of Cdr1p induced by fluphenazine (FNZ). Further, electrophoretic mobility shift assays suggested that the transcription activation complex of protein-DRE was disrupted by BBR, and electrospray ionization mass spectrometry analysis showed that BBR bound to the DRE of CDR1. Thus we propose that BBR inhibits the FNZ-induced transcriptional activation of CDR1 in C. albicans by blocking transcription factor binding to the DRE of CDR1. These results contribute to our understanding of the mechanism of synergistic effect of BBR and FLC.


Assuntos
Antifúngicos/farmacologia , Berberina/farmacologia , Candida albicans/efeitos dos fármacos , Farmacorresistência Fúngica/efeitos dos fármacos , Flufenazina/efeitos adversos , Proteínas Fúngicas/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Extratos Vegetais/farmacologia , Candida albicans/metabolismo , Sinergismo Farmacológico , Flufenazina/uso terapêutico , Proteínas Fúngicas/genética , Regulação Fúngica da Expressão Gênica , Proteínas de Membrana Transportadoras/genética , RNA Mensageiro/metabolismo , Ativação Transcricional/efeitos dos fármacos , Regulação para Cima
2.
Acta Pharmacol Sin ; 31(7): 855-60, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20562904

RESUMO

AIM: To synthesize a novel polyamide SL-A92 and evaluate its bioactivity against drug resistance in Candida albicans. METHODS: SL-A92 was synthesized using N-hydroxybenzotriazole (HOBT)/N,N'-dicyclohexylcarbodiimide (DCC) in solution phase. Its antifungal activities and effects on strain growth were tested using the micro-broth dilution method and growth curves, respectively. Induced drug resistance in the C. albicans collection strain SC5314 was obtained by incubation with fluconazole (12 microg/mL) for 21 passages. Meanwhile, incubations with SL-A92 plus fluconazole were also carried out in SC5314 strains, and the MIC(80)s were used to evaluate the inhibitory effects of SL-A92 on drug resistance during the induction process. Real time RT-PCR was performed to investigate the CDR1 and CDR2 mRNA levels in induced SC5314 strains. RESULTS: SC5314 strain induced by the combination of fluconazole and SL-A92 (200 microg/mL) did not develop drug resistance. On day 24, the CDR1 and CDR2 mRNA levels in SC5314 strain co-treated with fluconazole and SL-A92 relative to fluconazole alone were 26% and 24%, respectively, and on day 30 the CDR1 and CDR2 mRNA levels were 43% and 31%, respectively. CONCLUSION: SL-A92 can block the development of drug resistance during the fluconazole induction process, which partially results from the down-regulation of CDR1 and CDR2.


Assuntos
Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Farmacorresistência Fúngica/efeitos dos fármacos , Imidazóis/farmacologia , Nylons/farmacologia , Regulação para Baixo/efeitos dos fármacos , Fluconazol/farmacologia , Proteínas Fúngicas/efeitos dos fármacos , Proteínas Fúngicas/genética , Imidazóis/síntese química , Proteínas de Membrana Transportadoras/efeitos dos fármacos , Proteínas de Membrana Transportadoras/genética , Testes de Sensibilidade Microbiana , Nylons/síntese química , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa
3.
Yao Xue Xue Bao ; 43(11): 1089-93, 2008 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-19239025

RESUMO

Polyamides, containing N-methylpyrrole (Py) and N-methyl-imidazole (Im) amino acids, are synthetic oligomers programmed to read the DNA double helix in the minor groove with high affinities and sequence specificities resulting in modulation of gene expression. They are cell permeable, stable and have no cytotoxicity, which provide a promising tool of gene regulation. We describe here recent advances in the field of DNA binding polyamides, including pairing rules, specifities and affinities to DNA, synthesis methods, cellular and nuclear uptake properties, gene regulation and effectiveness in vivo. The potential problems and difficulties in future research are also discussed.


Assuntos
DNA , Regulação da Expressão Gênica/efeitos dos fármacos , Nylons , Animais , Pareamento de Bases , DNA/química , DNA/genética , Pegada de DNA , Imidazóis/síntese química , Imidazóis/química , Imidazóis/metabolismo , Imidazóis/farmacologia , Nylons/síntese química , Nylons/química , Nylons/metabolismo , Nylons/farmacologia , Pirróis/síntese química , Pirróis/química , Pirróis/metabolismo , Pirróis/farmacologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...