A multivalent approach to drug discovery for novel antibiotics.
J Antibiot (Tokyo)
; 61(10): 595-602, 2008 Oct.
Article
em En
| MEDLINE
| ID: mdl-19168973
ABSTRACT
The design, synthesis and antibacterial activity of novel glycopeptide/beta-lactam heterodimers is reported. Employing a multivalent approach to drug discovery, vancomycin and cephalosporin synthons, A and B respectively, were chemically linked to yield heterodimer antibiotics. These novel compounds were designed to inhibit Gram-positive bacterial cell wall biosynthesis by simultaneously targeting the principal cellular targets of both glycopeptides and beta-lactams. The antibiotics 8a-f displayed remarkable potency against a wide range of Gram-positive organisms including methicillin-resistant Staphylococcus aureus (MRSA). Compound 8e demonstrated excellent bactericidal activity against MRSA (ATCC 33591) and initial evidence supports a multivalent mechanism of action for this important new class of antibiotic.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Descoberta de Drogas
/
Antibacterianos
Idioma:
En
Revista:
J Antibiot (Tokyo)
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Estados Unidos