title: Trypanocidal activity of salinomycin is due to sodium influx followed by cell swelling.
abstract: BACKGROUND
  The few currently available drugs for treatment of African trypanosomiasis are outdated and show problems with toxicity and resistance. Hence, there is an urgent need for the discovery and development of new anti-trypanosomal agents.
  
  
  RESULTS
  In this study, the ionophorous antibiotic salinomycin was investigated for its trypanocidal activity in vitro using culture-adapted bloodstream forms of Trypanosoma brucei. The concentrations of salinomycin to reduce the growth rate by 50% and to kill the parasites were 0.31 μM and 1 μM, respectively. The trypanocidal action of the ionophore was shown to be the result of an influx of Na+ resulting in an increased intracellular Na+ concentration followed by cell swelling. This mode of action differs from the mechanism for the anti-cancer activity of salinomycin reported to be by induction of apoptosis.
  
  
  CONCLUSIONS
  Here we have shown that salinomycin is an effective agent against bloodstream forms of T. brucei and might be a potential candidate for treatment of African trypanosomiasis.
authors.affiliation: BioMedical Research Centre, Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich, UK. D.Steverding@uea.ac.uk
authors.forename: Dietmar
authors.initials: D
authors.lastname: Steverding
authors.forename: Darren W
authors.initials: DW
authors.lastname: Sexton
mesh_terms: D000981:Antiprotozoal Agents / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D009997:Osmotic Pressure; D011714:Pyrans / Q000494:pharmacology*; D012964:Sodium / Q000378:metabolism* / Q000633:toxicity; D014346:Trypanosoma brucei brucei / Q000187:drug effects*; D000095662:Polyether Polyketides
chemical_list: D000981:Antiprotozoal Agents; D011714:Pyrans; D012964:Sodium; C010327:salinomycin; D000095662:Polyether Polyketides