Current Drug Targets

Francis J. Castellino
Kleiderer-Pezold Professor of Biochemistry
Director, W.M. Keck Center for Transgene Research
Dean Emeritus, College of Science
230 Raclin-Carmichael Hall, University of Notre Dame
Notre Dame, IN 46556
USA

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Quinoline Derivatives as Promising Inhibitors of Antibiotic Efflux Pump in Multidrug Resistant Enterobacter Aerogenes Isolates

Author(s): Abdallah Mahamoud, Jacqueline Chevalier, Anne Davin-Regli, Jacques Barbe and Jean-Marie Pages

Affiliation: EA2197, IFR48, Faculte de Medecine, 27 Boulevard Jean Moulin, 13385 Marseille Cedex 5, France.

Abstract:

Efflux pumps protect the bacterial cell by expelling toxic compounds before they reach intracellular targets. Because this mechanism actively contributes to the resistance of a given bacterium to more than one class of antibiotics, molecules that are able to block the relevant efflux pump are of potential significance to combat drug resistance caused by efflux pumps. Different quinoline derivatives including alkoxy, alkylamino, thioalkoxy and chloroquinolines have been previously reported to make Enterobacter aerogenes resistant isolates that over express the mechanism of efflux, noticeably more susceptible to structurally unrelated antibiotics. In addition, various quinoline derivatives significantly increase the intracellular concentration of chloramphenicol as reported with other inhibitors, thereby suggesting the inhibition of the drug transport by AcrAB-TolC pump, which is fully active in the clinicaly resistant isolates investigated. Here, we discuss the respective properties of this molecular family, taking into account the recent insights into the structural data of AcrB pump.

Keywords: Antibiotic resistance, CCCP (carbonyl cyanide m-chlorophenylhydrazone), quinoline derivatives, Drug efflux, pump, Efflux pump inhibitors, Enterobacter aerogenes, PAβN (phenylalanine arginine β-naphthylamide)

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Article Details

VOLUME: 7
ISSUE: 7
Page: [843 - 847]
Pages: 5
DOI: 10.2174/138945006777709557
Price: $58