Journal article
Synthesis and evaluation of fluoroquinolone derivatives as substrate-based inhibitors of bacterial efflux pumps
European journal of medicinal chemistry, Vol.43(11), pp.2453-2463
2008
DOI: 10.1016/j.ejmech.2008.01.042
PMID: 18358571
Abstract
Bacterial efflux pump systems contribute to antimicrobial resistance in pathogenic bacteria. The co-administration of bacterial efflux pump inhibitors with antibiotics is being pursued to overcome efflux-mediated resistance to antibiotics. In this study we investigated a strategy for converting broad-spectrum efflux pump substrates, fluoroquinolone antibacterial agents which are inherently recognized by most efflux transporters, into expanded spectrum efflux pump inhibitors. Employing this strategy against organisms expressing efflux pumps from the MFS, MATE and RND classes of pump systems, we report here the identification of an ofloxacin-based EPI that is a potent inhibitor of MFS (NorA) and MATE (MepA) efflux pumps in
Staphylococcus aureus. The methods described here outline a process that we feel will be broadly applicable to the systematic identification of bacterial efflux pump inhibitors.
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Details
- Title: Subtitle
- Synthesis and evaluation of fluoroquinolone derivatives as substrate-based inhibitors of bacterial efflux pumps
- Creators
- Nadezhda German - University of IowaPeng Wei - University of IowaGlenn W. Kaatz - Wayne State UniversityRobert J. Kerns - Division of Medicinal and Natural Products Chemistry, University of Iowa, College of Pharmacy, 115 S. Grand Avenue, Iowa City, IA 52242, USA
- Resource Type
- Journal article
- Publication Details
- European journal of medicinal chemistry, Vol.43(11), pp.2453-2463
- Publisher
- Elsevier Masson SAS
- DOI
- 10.1016/j.ejmech.2008.01.042
- PMID
- 18358571
- ISSN
- 0223-5234
- eISSN
- 1768-3254
- Language
- English
- Date published
- 2008
- Academic Unit
- Pharmaceutical Sciences and Experimental Therapeutics; Medicinal and Natural Products Chemistry
- Record Identifier
- 9984366017302771
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