Fluorophenylalkyl-substituted cyanoguanidine derivatives as bacteria-selective MATE transporter inhibitors for the treatment of antibiotic-resistant infections.
Bioorg Med Chem
; 74: 117042, 2022 11 15.
Article
em En
| MEDLINE
| ID: mdl-36215813
ABSTRACT
Drug efflux pump inhibitors for the multidrug resistance protein HmrM, a member of the multidrug and toxin extrusion (MATE) family of transporters, were investigated to increase the drug susceptibility of multidrug-resistant bacteria and restore the antimicrobial effect of fluoroquinolones, such as norfloxacin. The lead inhibitor, prepared from the known hMATE1 inhibitor cimetidine, reduced the norfloxacin resistance of HmrM-expressing strains by 92% at non-cytotoxic concentrations in human cells, and multidrug resistance protein MdtK-expressing strains by 86%. These results indicated that the inhibitor is a lead candidate for the development of drugs with a novel mechanism of action against infections caused by multidrug-resistant bacteria that act synergistically with antimicrobial drugs.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Norfloxacino
/
Anti-Infecciosos
Limite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Japão