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, Z. Riedl, G. Hajós, J. Molnár, Miguel Viveiros, Isabel Couto, Leonard Amaral

Research output: Contribution to journalArticle

18 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 2011

Fingerprint

Salmonella enteritidis
Salmonella
Enterococcus faecalis
Escherichia coli
Staphylococcus aureus
Pumps
Derivatives
Bacteria
Phenothiazines
Multiple Drug Resistance
Gram-Negative Bacteria
Phenotype
Infection
phenothiazine
Pharmaceutical Preparations
Therapeutics

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

Cite this

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. / Takács, Daniella; Cerca, Pedro; Martins, Ana; Riedl, Z.; Hajós, G.; Molnár, J.; Viveiros, Miguel; Couto, Isabel; Amaral, Leonard.

In: In Vivo, Vol. 25, No. 5, 09.2011, p. 719-724.

Research output: Contribution to journalArticle

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