Discovery of novel lipophilic inhibitors of OXA-10 enzyme (class D beta-lactamase) by screening amino analogs and homologs of citrate and isocitrate.
Bioorg Med Chem Lett
; 19(13): 3593-7, 2009 Jul 01.
Article
em En
| MEDLINE
| ID: mdl-19467869
ABSTRACT
Aminocitrate (and homolog) derivatives have been prepared by bis-alkylation of glycinate Schiff bases with bromoacetates (and ethyl acrylate), followed by N-acylation and esters (partial or complete) deprotection. Aminoisocitrate was similarly obtained by mono-alkylation with diethyl fumarate. Evaluation against representative beta-lactamases revealed that the free acid derivatives are modest inhibitors of class A enzymes, whilst their benzyl esters showed a good inhibition of OXA-10 (class D enzyme). A docking experiment featured hydrophobic interactions in the active site.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Citratos
/
Inibidores Enzimáticos
/
Inibidores de beta-Lactamases
/
Isocitratos
/
Antibacterianos
Tipo de estudo:
Diagnostic_studies
/
Screening_studies
Idioma:
En
Revista:
Bioorg Med Chem Lett
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Bélgica