Journal article
Synthesis and evaluation of PSSRI-based inhibitors of Staphylococcus aureus multidrug efflux pumps
Bioorganic & medicinal chemistry letters, Vol.18(4), pp.1368-1373
02/15/2008
DOI: 10.1016/j.bmcl.2008.01.014
PMID: 18242086
Abstract
Phenylpiperidine selective serotonin reuptake inhibitors ( PSSRIs) block the function of selected multidrug efflux pumps of Staphylococcus aureus. In this study PSSRI-based piperidine derivatives were prepared, evaluated for inhibition of two multidrug resistance (MDR)-conferringe efflux pump systems, and tested for potentiation of antimicrobial activity of antibacterial efflux pump substrates. It is demonstrated that the 4-phenyl moiety of PSSRI-based efflux pump inhibitors (EPIs) is not an absolute structural requirement for inhibiting the NorA and MepA MDR efflux pumps. Potency of efflux inhibition is maintained or enhanced by replacing the aryloxymethyl substituent at position-3 of PSSRIs with arylalkene and arylthioether moieties. Novel 3-aryl piperidine EPIs that significantly increase substrate antibiotic activity against strains of S. aureus expressing NorA and MepA are described. (c) 2008 Elsevier Ltd. All rights reserved.
Details
- Title: Subtitle
- Synthesis and evaluation of PSSRI-based inhibitors of Staphylococcus aureus multidrug efflux pumps
- Creators
- Nadezhda German - University of IowaGlenn W. Kaatz - Wayne State UniversityRobert J. Kerns - Univ Iowa, Coll Pharm, Div Med & Nat Prod Chem, Iowa City, IA 52242 USA
- Resource Type
- Journal article
- Publication Details
- Bioorganic & medicinal chemistry letters, Vol.18(4), pp.1368-1373
- Publisher
- Elsevier
- DOI
- 10.1016/j.bmcl.2008.01.014
- PMID
- 18242086
- ISSN
- 0960-894X
- eISSN
- 1464-3405
- Number of pages
- 6
- Language
- English
- Date published
- 02/15/2008
- Academic Unit
- Pharmaceutical Sciences and Experimental Therapeutics; Medicinal and Natural Products Chemistry
- Record Identifier
- 9984365887302771
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