Discovery of marine phidianidine-based Nrf2 activators and their potential against oxLDL- and HG-induced injury in HUVECs

  • Bioorg Med Chem Lett. 2023 Sep 7:95:129468. doi: 10.1016/j.bmcl.2023.129468.
Juan Zhang  1 ,  Yong-Si Cai  1 ,  Hua-Long Ji  1 ,  Mengqi Ma  1 ,  Jin-He Zhang  1 ,  Zhi-Qiang Cheng  1 ,  Kai-Ming Wang  1 ,  Cheng-Shi Jiang  2 ,  Chunlin Zhuang  3 ,  Yang Hu  4 ,  Ning Meng  5
Affiliations
  • 1. School of Biological Science and Technology, University of Jinan, Jinan 250022, China.
  • 2. School of Biological Science and Technology, University of Jinan, Jinan 250022, China. Electronic address: [email protected].
  • 3. School of Pharmacy, Second Military Medical University, Shanghai 200433, China. Electronic address: [email protected].
  • 4. School of Biological Science and Technology, University of Jinan, Jinan 250022, China. Electronic address: [email protected].
  • 5. School of Biological Science and Technology, University of Jinan, Jinan 250022, China. Electronic address: [email protected].
PMID: 37689216 DOI: 10.1016/j.bmcl.2023.129468
Abstract

One effective strategy for treating atherosclerosis is to inhibit the injury of vascular endothelial cells (VECs) induced by oxidized low-density lipoprotein (oxLDL) and high glucose (HG). This study synthesized and evaluated a series of novel Nrf2 activators derived from the marine natural product phidianidine for their ability to protect human umbilical VECs against oxLDL- and HG-induced injury. The results of in vitro bioassays demonstrated that compound D-36 was the most promising Nrf2 activator, effectively inhibiting the Apoptosis of HUVECs induced by oxLDL and HG. Furthermore, Nrf2 knockdown experiments confirmed that compound D-36 protected against oxLDL- and HG-induced Apoptosis in HUVECs by activating the Nrf2 pathway. These findings provide important insights into a new chemotype of marine-derived Nrf2 activators that could potentially be optimized to develop effective anti-atherosclerosis agents.

Keywords
High glucose; Nrf2 activator; Phidianidine B; Vascular endothelial cell; oxLDL.
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