An ether-linked halogenated phenazine-quinone prodrug model for antibacterial applications.
Org Biomol Chem
; 19(30): 6603-6608, 2021 08 05.
Article
em En
| MEDLINE
| ID: mdl-34286808
ABSTRACT
Antibiotic-resistant infections present significant challenges to patients. As a result, there is considerable need for new antibacterial therapies that eradicate pathogenic bacteria through non-conventional mechanisms. Our group has identified a series of halogenated phenazine (HP) agents that induce rapid iron starvation that leads to potent killing of methicillin-resistant Staphylococcus aureus biofilms. Here, we report the design, chemical synthesis and microbiological assessment of a HP-quinone ether prodrug model aimed to (1) eliminate general (off-target) iron chelation, and (2) release an active HP agent through the bioreduction of a quinone trigger. Here, we demonstrate prodrug analogue HP-29-Q to have a stable ether linkage that enables HP release and moderate to good antibacterial activities against lab strains and multi-drug resistant clinical isolates.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Staphylococcus aureus Resistente à Meticilina
Idioma:
En
Revista:
Org Biomol Chem
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos