LCS-1的细胞毒性活性不仅归因于对超氧化物歧化酶1（SOD1）的抑制。
Cytotoxic Activity of LCS-1 is not Only due to Inhibition of SOD1.
作者信息
Steverding Dietmar, Barcelos Yzobelle
机构信息
Bob Champion Research and Education Building, Norwich Medical School, University of East Anglia, Norwich, United Kingdom.
出版信息
Drug Res (Stuttg). 2020 Jan;70(1):57-60. doi: 10.1055/a-1001-2036. Epub 2019 Sep 11.
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 , 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 , 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.
背景
先前有研究表明哒嗪-3-酮衍生物LCS-1的细胞毒性活性是由于其对超氧化物歧化酶1（SOD1）的抑制作用。然而，并没有直接证据表明LCS-1在细胞内抑制SOD1。
方法
在本研究中，我们研究了LCS-1对布氏锥虫血流形式的细胞毒性活性，布氏锥虫是一种原生动物寄生虫，不表达含铜/锌的SOD1，而是表达含铁超氧化物歧化酶（FeSOD）。
结果
在250µM浓度下，LCS-1并未抑制布氏锥虫血流形式细胞裂解物中FeSOD的活性，证实该化合物是SOD1的特异性抑制剂。然而，LCS-1表现出显著的杀锥虫活性，最低抑制浓度为10µM，半数最大有效浓度为1.36µM，表明该化合物的细胞毒性作用不能仅仅归因于对SOD1的抑制。
结论
本研究结果是一项重要发现，因为它表明LCS-1具有不止一种细胞毒性作用模式。
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