Vectorization efforts to increase Gram-negative intracellular drug concentration: a case study on HldE-K inhibitors.
J Med Chem
; 56(5): 1908-21, 2013 Mar 14.
Article
em En
| MEDLINE
| ID: mdl-23445125
ABSTRACT
In this paper, we present different strategies to vectorize HldE kinase inhibitors with the goal to improve their gram-negative intracellular concentration. Syntheses and biological effects of siderophoric, aminoglycosidic, amphoteric, and polycationic vectors are discussed. While siderophoric and amphoteric vectorization efforts proved to be disappointing in this series, aminoglycosidic and polycationic vectors were able for the first time to achieve synergistic effects of our inhibitors with erythromycin. Although these effects proved to be nonspecific, this study provides information about the required stereoelectronic arrangement of the polycationic amines and their basicity requirements to fulfill outer membrane destabilization resulting in better erythromycin synergies.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Eritromicina
/
Fosfotransferases (Aceptor do Grupo Álcool)
/
Escherichia coli
/
Complexos Multienzimáticos
/
Nucleotidiltransferases
Idioma:
En
Revista:
J Med Chem
Assunto da revista:
QUIMICA
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
França