Discovery and refinement of a new structural class of potent peptide deformylase inhibitors.
J Med Chem
; 50(1): 10-20, 2007 Jan 11.
Article
em En
| MEDLINE
| ID: mdl-17201406
ABSTRACT
New classes of antibiotics are urgently needed to counter increasing levels of pathogen resistance. Peptide deformylase (PDF) was originally selected as a specific bacterial target, but a human homologue, the inhibition of which causes cell death, was recently discovered. We developed a dual-screening strategy for selecting highly effective compounds with low inhibition effect against human PDF. We selected a new scaffold in vitro that discriminated between human and bacterial PDFs. Analyses of structure-activity relationships identified potent antibiotics such as 2-(5-bromo-1H-indol-3-yl)-N-hydroxyacetamide (6b) with the same mode of action in vivo as previously identified PDF inhibitors but without the apoptotic effects of these inhibitors in human cells.
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Base de dados:
MEDLINE
Assunto principal:
Amidoidrolases
/
Ácidos Hidroxâmicos
/
Indóis
/
Antibacterianos
Limite:
Humans
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article