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

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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.

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

Document Type: Research Article

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

Publication date: July 1, 2006

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  • Current Drug Targets aims to cover the latest and most outstanding developments on the medicinal chemistry and pharmacology of molecular drug targets e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal will be devoted to a single timely topic, with series of in-depth reviews, written by leaders in the field, covering a range of current topics on drug targets. These issues will be organized and led by a guest editor who is a recognized expert in the overall topic. As the discovery, identification, characterisation and validation of novel human drug targets for drug discovery continues to grow; this journal will be essential reading for all pharmaceutical scientists involved in drug discovery and development.
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