Cytotoxic activity of LCS-1 is not only due to inhibition of SOD1

Dietmar Steverding, Yzobelle Barcelos

Research output: Contribution to journalArticle

4 Downloads (Pure)

Abstract

Background The cytotoxic activity of the pyridazin-3-one derivative LCS-1 was previously suggested to be due to the inhibition of superoxide dismutase 1 (SOD1). However, no direct evidence was provided that LCS-1 inhibits SOD1 within cells.
Methods In this study, we investigated the cytotoxic activity of LCS-1 against bloodstream forms of Trypanosoma brucei, a protozoan parasite that does not express copper/zinc-containing SOD1, but an iron-containing superoxide dismutase (FeSOD).
Results At 250 µM, LCS-1 did not inhibit the activity of FeSOD in cell lysates of bloodstream forms of T. brucei, confirming that the compound is a specific inhibitor of SOD1. However, LCS-1 displayed substantial trypanocidal activity with a minimum inhibitory concentration of 10 µM and a half-maximal effective concentration of 1.36 µM, indicating that the cytotoxic action of the compound cannot solely be due to inhibition of SOD1.
Conclusion The results of this study is an important finding as it shows that LCS-1 has more than one cytotoxic mode of action.
Original languageEnglish
Pages (from-to)57-60
Number of pages4
JournalDrug Research
Volume70
Issue number1
Early online date11 Sep 2019
DOIs
Publication statusPublished - 1 Jan 2020

Keywords

  • GROWTH
  • IDENTIFICATION
  • IRON
  • SUPEROXIDE-DISMUTASE
  • anticancer drugs
  • drug research
  • pharmacology

Cite this