Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 2 de 2
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
ACS Chem Biol ; 11(12): 3263-3267, 2016 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-27775338

RESUMO

Crystal structure analysis revealed key interactions of a 2-amino-benzimidazole viral translation inhibitor that captures an elongated conformation of an RNA switch target in the internal ribosome entry site (IRES) of hepatitis C virus (HCV). Here, we have designed and synthesized quinazoline derivatives with improved shape complementarity at the ligand binding site of the viral RNA target. A spiro-cyclopropyl modification aimed at filling a pocket in the back of the RNA binding site led to a 5-fold increase of ligand affinity while a slightly more voluminous dimethyl substitution at the same position did not improve binding. We demonstrate that precise shape complementarity based solely on hydrophobic interactions contributes significantly to ligand binding even at a hydrophilic RNA target site such as the HCV IRES conformational switch.


Assuntos
Antivirais/farmacologia , Benzimidazóis/farmacologia , Hepacivirus/efeitos dos fármacos , Sítios Internos de Entrada Ribossomal/efeitos dos fármacos , Quinazolinas/farmacologia , RNA Viral/metabolismo , Antivirais/química , Benzimidazóis/química , Desenho de Fármacos , Hepacivirus/química , Hepacivirus/metabolismo , Hepatite C/tratamento farmacológico , Hepatite C/virologia , Humanos , Ligantes , Modelos Moleculares , Conformação de Ácido Nucleico/efeitos dos fármacos , Quinazolinas/química , RNA Viral/química
2.
Bioorg Med Chem Lett ; 24(15): 3521-5, 2014 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-24930829

RESUMO

2-Aminobenzoxazoles have been synthesized as ligands for the hepatitis C virus (HCV) internal ribosome entry site (IRES) RNA. The compounds were designed to explore the less basic benzoxazole system as a replacement for the core scaffold in previously discovered benzimidazole viral translation inhibitors. Structure-activity relationships in the target binding of substituted benzoxazole ligands were investigated.


Assuntos
Antivirais/farmacologia , Benzoxazóis/farmacologia , Hepacivirus/efeitos dos fármacos , RNA Viral/antagonistas & inibidores , Ribossomos/efeitos dos fármacos , Antivirais/síntese química , Antivirais/química , Benzoxazóis/síntese química , Benzoxazóis/química , Hepacivirus/química , Ligantes , Modelos Moleculares , Estrutura Molecular , RNA Viral/metabolismo , Ribossomos/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...