Evaluation of forty new phenothiazine derivatives for activity against intrinsic efflux pump systems of reference Escherichia coli, Salmonella enteritidis, Enterococcus faecalis and Staphylococcus aureus strains

Daniella Takács, Pedro Cerca, Ana Martins, Zsuzsanna Riedl, György Hajós, Joseph Molnár, Miguel Viveiros, Isabel Couto, Leonard Amaral

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19 Citations (Scopus)

Abstract

Background: Because phenothiazines inhibit efflux pumps of bacteria, forty new phenothiazine derivatives were tested for their inhibition of the efflux pump systems of Gram-positive and Gram-negative pathogenic bacteria. Materials and Methods: Detection of efflux pump activity was conducted by a previously described automated fluorimetric method. Results: Although many of the compounds significantly inhibited efflux by distinct bacteria, four compounds had exceptional activity against the efflux pump systems of the pathogenic wild type bacteria Escherichia coli, Salmonella Enteritidis, Enterococcus faecalis and Staphylococcus aureus. These four compounds were then evaluated for ability to reduce or reverse resistance of multi-drug resistant members of Escherichia coli, Salmonella and Staphylococcus aureus whose MDR phenotypes are mediated by specific overexpressed efflux pumps. One of the compounds, 2173, significantly reduced resistance of MDR Staphylococcus aureus. Conclusion: These results suggest possible use of compound 2173 for therapy of infections caused by this organism.

Original languageEnglish
Pages (from-to)719-724
Number of pages6
JournalIn Vivo
Volume25
Issue number5
Publication statusPublished - Sep 1 2011

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Keywords

  • Enterococcus faecalis
  • Escherichia coli
  • Inhibition of efflux pumps
  • Multidrug resistance
  • Over-expressed efflux pumps
  • Pathogenic bacteria
  • Phenothiazine derivatives
  • Reduction of resistance
  • Salmonella enteritidis
  • Staphylococcus aureus

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology

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