Trypanocidal activity of salinomycin is due to sodium influx followed by cell swelling

Parasit Vectors. 2013 Mar 21:6:78. doi: 10.1186/1756-3305-6-78.

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Background: The few currently available drugs for treatment of African trypanosomiasis are outdated and show problems with toxicity and resistance.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.

Findings: 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.

Conclusion: 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.

MeSH terms

  • Antiprotozoal Agents / pharmacology*
  • Inhibitory Concentration 50
  • Osmotic Pressure*
  • Pyrans / pharmacology*
  • Sodium / metabolism*
  • Sodium / toxicity
  • Trypanosoma brucei brucei / drug effects*

Substances

  • Antiprotozoal Agents
  • Pyrans
  • salinomycin
  • Sodium