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

Dietmar Steverding; Yzobelle Barcelos

doi:10.1055/a-1001-2036

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

Dietmar Steverding
, Yzobelle Barcelos

Research output: Contribution to journal › Article › peer-review

4 Citations (Scopus)

41 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 language	English
Pages (from-to)	57-60
Number of pages	4
Journal	Drug Research
Volume	70
Issue number	1
Early online date	11 Sept 2019
DOIs	https://doi.org/10.1055/a-1001-2036
Publication status	Published - 1 Jan 2020

Keywords

GROWTH
IDENTIFICATION
IRON
SUPEROXIDE-DISMUTASE
anticancer drugs
drug research
pharmacology

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title = "Cytotoxic activity of LCS-1 is not only due to inhibition of SOD1",

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.",

keywords = "GROWTH, IDENTIFICATION, IRON, SUPEROXIDE-DISMUTASE, anticancer drugs, drug research, pharmacology",

author = "Dietmar Steverding and Yzobelle Barcelos",

year = "2020",

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doi = "10.1055/a-1001-2036",

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T1 - Cytotoxic activity of LCS-1 is not only due to inhibition of SOD1

AU - Steverding, Dietmar

AU - Barcelos, Yzobelle

PY - 2020/1/1

Y1 - 2020/1/1

N2 - 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.

AB - 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.

KW - GROWTH

KW - IDENTIFICATION

KW - IRON

KW - SUPEROXIDE-DISMUTASE

KW - anticancer drugs

KW - drug research

KW - pharmacology

UR - https://www.scopus.com/pages/publications/85077475440

U2 - 10.1055/a-1001-2036

DO - 10.1055/a-1001-2036

M3 - Article

SN - 2194-9379

VL - 70

SP - 57

EP - 60

JO - Drug Research

JF - Drug Research

IS - 1

ER -

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

Abstract

Keywords

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