Structural differences between paroxetine and femoxetine responsible for differential inhibition of Staphylococcus aureus efflux pumps

Bioorganic and Medicinal Chemistry Letters

Volumn 14, Issue 12, 2004, Pages 3093-3097

  Wei, Peng ^a   Kaatz, Glenn W ^b   Kerns, Robert J ^a  

^a UNIVERSITY OF IOWA   (United States)

^b WAYNE STATE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Antibiotic resistance; Efflux inhibitor; SSRI

Indexed keywords

FEMOXETINE; NNC 20 4962; NNC 20 7052; PAROXETINE; SEROTONIN UPTAKE INHIBITOR; UNCLASSIFIED DRUG;

ANTIBACTERIAL ACTIVITY; ANTIBIOTIC RESISTANCE; ARTICLE; CHEMICAL MODIFICATION; CONTROLLED STUDY; DRUG ACTIVITY; DRUG POTENCY; DRUG STRUCTURE; GRAM POSITIVE BACTERIUM; INHIBITION KINETICS; NONHUMAN; STAPHYLOCOCCUS AUREUS; STRUCTURE ACTIVITY RELATION; STRUCTURE ANALYSIS;

BACTERIAL PROTEINS; BIOLOGICAL TRANSPORT, ACTIVE; DRUG RESISTANCE, MULTIPLE, BACTERIAL; PAROXETINE; PIPERIDINES; STAPHYLOCOCCUS AUREUS; STRUCTURE-ACTIVITY RELATIONSHIP;

STAPHYLOCOCCUS; STAPHYLOCOCCUS AUREUS;

EID: 2442482533     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2004.04.018     Document Type: Article

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22. +) 312
23. +) 344
24. 3) δ 1.68-2.04 (m, 3H), 2.20 (s, 3H), 2.62-2.82 (m, 2H), 3.05-3.25 (m, 1H), 3.44-3.51 (m, 1H), 3.62-3.68 (m, 1H), 3.90-4.19 (m, 1H), 4.75-4.95 (m, 1H), 5.87 (s, 2H), 6.17 (m, 1H), 6.38 (s, 1H), 6.65 (d, 1H), 6.94 (m, 1H), 7.17 (m, 1H). MS, EI, calcd 371, found 371
25. 3) δ 1.43 (m, 2H), 1.82 (m, 2H), 2.20 (m, 1H), 2.71 (m, 1H), 2.82-2.92 (m, 2H), 3.28-3.42 (m, 4H), 5.97 (m, 1H), 6.24 (d, 1H), 6.56 (d, 1H), 6.76-6.86 (m, 2H), 6.96-7.04 (m, 2H). MS EI, calcd 317, found 317
26. 660 was adjusted to 0.4 using fresh MHB containing EtBr and CCCP. Cells in 1 mL of this dilution were pelleted and then resuspended in fresh MHB with or without various concentrations of inhibitors. The fluorescence of the suspension was monitored continuously for 5 min (excitation and emission wavelengths, 530 and 600 nm, respectively). Percent inhibition of efflux was calculated by determining the difference in total efflux versus that observed in the presence of an inhibitor