Trypanocidal and cell swelling activity of 20-deoxysalinomycin

  • Exp Parasitol. 2022 Dec:243:108414. doi: 10.1016/j.exppara.2022.108414.
Dietmar Steverding  1 ,  Daniel Strand  2 ,  Adam Huczyński  3
Affiliations
  • 1. Bob Champion Research & Education Building, Norwich Medical School, University of East Anglia, Norwich, UK. Electronic address: [email protected].
  • 2. Centre for Analysis and Synthesis, Department of Chemistry, Lund University, Lund, Sweden.
  • 3. Department of Medical Chemistry, Faculty of Chemistry, Adam Mickiewicz University, Poznań, Poland.
PMID: 36273616 DOI: 10.1016/j.exppara.2022.108414
Abstract

The naturally occurring polyether ionophore salinomycin was previously found to display promising anti-proliferative activity against bloodstream forms of Trypanosoma brucei. Here, we report the evaluation of 20-deoxysalinomycin, a naturally occurring homolog to salinomycin, for trypanocidal and cell swelling activity. The concentration of 20-deoxysalinomycin required to reduce the growth rate of bloodstream-form trypanosomes by 50% was determined to be 0.12 μM and found to be 8 times more trypanocidal than that of salinomycin. Moreover, 20-deoxysalinomycin and salinomycin displayed similar cytotoxic activity against human HL-60 cells. Measured as the ratio of cytotoxic to trypanocidal activity, 20-deoxysalinomycin thus exhibits a four-fold higher selectivity compared to salinomycin. The stronger trypanocidal activity of 20-deoxysalinomycin is attributed to an enhanced ability to induce cell swelling in trypanosomes. The findings support 20-deoxysalinomycin as a useful lead in the rational development of new and improved anti-trypanosomal drugs.

Keywords
20-Deoxysalinomycin; African trypanosomiasis; Polyether ionophores; Trypanosoma brucei.
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