5-(3-(N-(Carboxymethyl)naphthalene-2-sulfonamido)phenyl)-1-ethyl-1H-pyrrole-2-carboxylic acid as a Keap1–Nrf2 inhibitor for cerebral ischemia/reperfusion injury treatment

IF 4.6 3区化学 Q2 CHEMISTRY, MULTIDISCIPLINARY RSC Advances Pub Date : 2025-01-13 DOI:10.1039/D4RA06512C

Nanjia Cairang, Yanran Wu, Shumeng Zhi, Jiaqin Tang, Xin Tie, Dui Zhan, Guangyuan Lu, Ying Shi and Qipeng Zhao

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Abstract

The Keap1 (Kelch-like ECH-Associating Protein 1)–Nrf2 (Nuclear Factor Erythroid 2-Related Factor 2)-ARE (Antioxidant Response Element) signaling pathway plays a crucial role in the oxidative stress response and has been linked to the development and progression of various diseases. Its influence on cerebral ischemia/reperfusion (I/R) injury has garnered significant attention. In our study, we investigated the effect of compound 2, a non-covalent inhibitor of the Keap1–Nrf2 interaction, which was previously discovered by our research group. Specifically, we used 5-(3-(N-(carboxymethyl)naphthalene-2-sulfonamido)phenyl)-1-ethyl-1H-pyrrole-2-carboxylic acid (compound 2) to assess its therapeutic potential in a cerebral I/R injury model. The results demonstrated that compound 2 had a significant therapeutic effect, promoting the translocation of Nrf2 from the cytoplasm to the nucleus in diseased tissue. Additionally, it increased the production of key antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH).

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5-（3-（N-（羧甲基）萘-2-磺酰胺）苯基）-1-乙基- 1h -吡罗-2-羧酸作为Keap1-Nrf2抑制剂治疗脑缺血/再灌注损伤

Keap1 (Kelch-like ech - associated Protein 1) -Nrf2 (Nuclear Factor Erythroid 2- related Factor 2)-ARE （oxidative Response Element）信号通路在氧化应激反应中起着至关重要的作用，与多种疾病的发生和进展有关。其对脑缺血再灌注（I/R）损伤的影响已引起广泛关注。在我们的研究中，我们研究了化合物2的作用，这是我们课题组之前发现的Keap1-Nrf2相互作用的非共价抑制剂。具体来说，我们使用5-（3-（N-（羧甲基）萘-2-磺酰胺）苯基）-1-乙基- 1h -吡咯-2-羧酸（化合物2）来评估其在脑I/R损伤模型中的治疗潜力。结果表明，化合物2具有显著的治疗作用，可促进Nrf2在病变组织中由细胞质向细胞核的易位。此外，它还增加了关键抗氧化酶的产生，如超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和谷胱甘肽（GSH）。

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来源期刊

RSC Advances chemical sciences-

CiteScore

7.50

自引率

2.60%

发文量

3116

审稿时长

1.6 months

期刊介绍： An international, peer-reviewed journal covering all of the chemical sciences, including multidisciplinary and emerging areas. RSC Advances is a gold open access journal allowing researchers free access to research articles, and offering an affordable open access publishing option for authors around the world.