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

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Steverding, Dietmar and Barcelos, Yzobelle (2020) Cytotoxic activity of LCS-1 is not only due to inhibition of SOD1. Drug Research, 70 (1). pp. 57-60. ISSN 2194-9379

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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.

Item Type: Article
Uncontrolled Keywords: growth,identification,iron,superoxide-dismutase,anticancer drugs,drug research,pharmacology
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups: Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology
Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health
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Depositing User: LivePure Connector
Date Deposited: 21 Aug 2019 15:30
Last Modified: 23 Sep 2026 07:30
URI: https://ueaeprints.uea.ac.uk/id/eprint/72028
DOI: 10.1055/a-1001-2036

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