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Fluorophenylalkyl-substituted cyanoguanidine derivatives as bacteria-selective MATE transporter inhibitors for the treatment of antibiotic-resistant infections.
Shinya, Susumu; Kawai, Kentaro; Kobayashi, Naoki; Karuo, Yukiko; Tarui, Atsushi; Sato, Kazuyuki; Otsuka, Masato; Omote, Masaaki.
Afiliação
  • Shinya S; Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka 573-0101, Japan.
  • Kawai K; Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka 573-0101, Japan. Electronic address: kentaro.kawai@pharm.setsunan.ac.jp.
  • Kobayashi N; Department of Food Science and Human Nutrition, Faculty of Agriculture, Setsunan University, Hirakata, Osaka 573-0101, Japan.
  • Karuo Y; Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka 573-0101, Japan.
  • Tarui A; Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka 573-0101, Japan.
  • Sato K; Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka 573-0101, Japan.
  • Otsuka M; Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka 573-0101, Japan.
  • Omote M; Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka 573-0101, Japan. Electronic address: omote@pharm.setsunan.ac.jp.
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.
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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

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