In vitro activity of salinomycin and monensin derivatives against Trypanosoma brucei. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Steverding, Dietmar; Antoszczak, Michał; Huczyński, Adam
• Is Part Of: Parasites & vectors. Volume 9:Issue 1(2016)
• Page Start: 1
• Page End: 6
• Publication Date: 2016-12
• Subjects: Trypanosoma brucei -- Salinomycin derivatives -- Monensin derivatives -- African trypanosomaisis -- Drug screening; Parasitism -- Periodicals; Parasites -- Periodicals; Vector-pathogen relationships -- Periodicals; Animals as carriers of disease -- Periodicals; Insects as carriers of disease -- Periodicals; 616.96
• DOI: 10.1186/s13071-016-1698-8
• Languages: English
• ISSNs: 1756-3305

Abstract

Abstract Background African trypanosomes are the causative agents of sleeping sickness in humans and nagana disease in livestock animals. As the few drugs available for treatment of the diseases have limited efficacy and produce adverse reactions, new and better tolerated therapies are required. Polyether ionophores have been shown to display anti-cancer, anti-microbial and anti-parasitic activity. In this study, derivatives of the polyether ionophores, salinomycin and monensin were tested for theirin vitro activity against bloodstream forms ofTrypanosoma brucei and human HL-60 cells. Results Most polyether ionophore derivatives were less trypanocidal than their corresponding parent compounds. However, two salinomycin derivatives (salinomycin n-butyl amide and salinomycin 2, 2, 2-trifluoroethyl ester) were identified that showed increased anti-trypanosomal activity with 50 % growth inhibition values in the mid nanomolar range and minimum inhibitory concentrations of below 1 μM similar to suramin, a drug used in the treatment of sleeping sickness. In contrast, human HL-60 cells were considerably less sensitive towards all polyether ionophore derivatives. The cytotoxic to trypanocidal activity ratio (selectivity) of the two promising compounds was greater than 250. Conclusions The data indicate that polyether ionophore derivatives are interesting lead compounds for rational anti-trypanosomal drug development.