TY - JOUR
T1 - 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
AU - Takács, Daniella
AU - Cerca, Pedro
AU - Martins, Ana
AU - Riedl, Zsuzsanna
AU - Hajós, György
AU - Molnár, Joseph
AU - Viveiros, Miguel
AU - Couto, Isabel
AU - Amaral, Leonard
PY - 2011/9
Y1 - 2011/9
N2 - 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.
AB - 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.
KW - Enterococcus faecalis
KW - Escherichia coli
KW - Inhibition of efflux pumps
KW - Multidrug resistance
KW - Over-expressed efflux pumps
KW - Pathogenic bacteria
KW - Phenothiazine derivatives
KW - Reduction of resistance
KW - Salmonella enteritidis
KW - Staphylococcus aureus
UR - http://www.scopus.com/inward/record.url?scp=79960639569&partnerID=8YFLogxK
M3 - Article
C2 - 21753124
AN - SCOPUS:79960639569
SN - 0258-851X
VL - 25
SP - 719
EP - 724
JO - In Vivo
JF - In Vivo
IS - 5
ER -