title: Biological activity of twenty-three hydantoin derivatives on intrinsic efflux pump system of Salmonella enterica serovar Enteritidis NCTC 13349.
abstract: BACKGROUND
  Hydantoin derivatives have important biochemical and pharmacological properties. In the present study, 23 hydantoin compounds were evaluated for their efflux-modulating effects in Salmonella enterica serovar Enteritidis NCTC 13349 using real-time fluorimetry based on the intracellular accumulation of ethidium bromide (EB), a universal substrate of efflux pumps.
  
  
  METHODS
  Twenty-three hydantoin derivatives were tested for intrinsic efflux pump modulation in S. enterica Enteritidis NCTC 13349 by an automated real-time fluorimetric method that monitors the intracellular accumulation of ethidium bromide.
  
  
  RESULTS
  None of the compounds were found to have antibacterial activities at concentrations as high as 200 mg/l. Among the hydantoin derivatives tested in our study, only compound SZ7 showed efflux modulating activity on S. enterica Enteritidis NCTC 13349 in the assays that contained or omitted glucose as the singular source of metabolic energy.
  
  
  CONCLUSIONS
  SZ7 is shown to be non-toxic and it could be evaluated to cure an efflux mediated MDR Salmonella infection, furthermore a quantitative activity-structural relationship is also planned in order to determine the site of the SZ7 molecule responsible for its efflux pump inhibitory activity.
authors.affiliation: Unit of Mycobacteriology, Institute of Hygiene and Tropical Medicine, Universidade Nova de Lisboa, Lisbon, Portugal.
authors.forename: Lisa
authors.initials: L
authors.lastname: Machado
authors.forename: Gabriella
authors.initials: G
authors.lastname: Spengler
authors.forename: Miguel
authors.initials: M
authors.lastname: Evaristo
authors.forename: Jadwiga
authors.initials: J
authors.lastname: Handzlik
authors.forename: Joseph
authors.initials: J
authors.lastname: Molnár
authors.forename: Miguel
authors.initials: M
authors.lastname: Viveiros
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kiec-Kononowicz
authors.forename: Leonard
authors.initials: L
authors.lastname: Amaral
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000378:metabolism*; D004996:Ethidium / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D006827:Hydantoins / Q000494:pharmacology*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008826:Microbial Sensitivity Tests; D012477:Salmonella enteritidis / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D005456:Fluorescent Dyes; D006827:Hydantoins; D026901:Membrane Transport Proteins; D004996:Ethidium