Trypanocidal and cell swelling activity of 20-deoxysalinomycin

Dietmar Steverding, Daniel Strand, Adam Huczyński

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number108414
JournalExperimental Parasitology
Volume243
Early online date21 Oct 2022
DOIs
Publication statusE-pub ahead of print - 21 Oct 2022

Keywords

  • 20-Deoxysalinomycin
  • African trypanosomiasis
  • Polyether ionophores
  • Trypanosoma brucei

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