In silico screening with benzofurane- and benzopyrane-type MDR-modulators.
Farmaco
; 58(3): 185-91, 2003 Mar.
Article
em En
| MEDLINE
| ID: mdl-12620414
ABSTRACT
Development of inhibitors of the drug efflux pump P-glycoprotein is a versatile approach to overcome multi drug resistance (MDR) in tumor therapy. In an approach to lower the conformational flexibility of the lead compound propafenone, we synthesized a set of dihydrobenzofuranes and benzopyranones. In the case of the 4 diastereomeric dihydrobenzofuranes, no significant differences in activity regarding the configuration on the side-chains at the dihydrofurane moiety (cis or trans) was observed. This may be due to the high flexibility of the side-chains, which still allow mutually overlap of pharmacophores. The benzopyranones showed a good correlation between lipophilicity and activity with gnerally lower logpotency/logP ratios. This decrease may be due to the rigidization of the molecules. In an in silico screening approach, a set of diverse propafenone-type compounds was used to establish a pharmacophore model, which was used to screen the world drug index. Among the hits retrieved there are several compounds, which were previously described as MDR-modulators. This demonstrates the validity of the model.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Benzofuranos
/
Benzopiranos
/
Membro 1 da Subfamília B de Cassetes de Ligação de ATP
Tipo de estudo:
Diagnostic_studies
/
Screening_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2003
Tipo de documento:
Article