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Discovery of a coumarin derivative as Nrf2 activator mitigating oxidative stress and fibrosis in mesangial cells under high glucose.

Authors
  • Yao, Huankai1
  • Zhang, Nan1
  • Zhang, Wenting2
  • Li, Jindong3
  • Hua, Huilian3
  • Li, Yan4
  • 1 School of Pharmacy & Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China. , (China)
  • 2 Department of Laboratory Medicine, Xuzhou Center for Disease Control and Prevention, Xuzhou, Jiangsu 221006, China. , (China)
  • 3 Department of Pharmacy, Taizhou People's Hospital, Taizhou, Jiangsu 225300, China. , (China)
  • 4 School of Pharmacy & Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China. Electronic address: [email protected] , (China)
Type
Published Article
Journal
Bioorganic & medicinal chemistry letters
Publication Date
Aug 11, 2020
Volume
30
Issue
20
Pages
127490–127490
Identifiers
DOI: 10.1016/j.bmcl.2020.127490
PMID: 32791195
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Diabetic nephropathy (DN) is a severe microvascular complication of diabetes mellitus. Oxidative stress and fibrosis largely contribute to the progression of DN. Recently, Nrf2 was found to be a potential target preventing DN. In the discovery of novel Nrf2 activators for the treatment of DN, we have evaluated coumarin derivatives from Wikstroemi indiaca. Molecular docking results have shown compound 4 could bind to Keap1 and activate Nrf2 significantly. Cell-based assays have revealed compound 4 activated Nrf2 and attenuated oxidative stress and fibrosis induced by high glucose in mesangial cells. Meanwhile, it was validated that disruption of the interaction between Keap1 and Nrf2 was involved in the activation of Nrf2 by compound 4 in mesangial cells under high glucose. Copyright © 2020 Elsevier Ltd. All rights reserved.

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