Novel antioxidants' synthesis and their anti-oxidative activity through activating Nrf2 signaling pathway

Bioorg Med Chem Lett. 2017 Apr 1;27(7):1616-1619. doi: 10.1016/j.bmcl.2017.02.006. Epub 2017 Feb 4.

Abstract

Novel structure compounds (WS) containing 3,4,5-trimethoxyphenyl and acyl pyrazole were designed and synthesized based combination principles. Among them, WS13 was screened out to possess desirable anti-oxidative activity in vitro. Cell survival assay and apoptosis experiment in H2O2 induced PC12 cells injury model all showed that its cytoprotection exhibited a concentration-effect manner. WS13 at 10μM could remove ROS with equal effiency to edaravone. Further, it clearly activated Nrf2 nuclear translocation and upregulated GCLC mRNA transcription and protein expression in dose-dependent manner, and its cytoprotection was reversed by GCLC protein inhibitor. In total, WS13 with further promotion can serve as Nrf2-GCLC activator in anti-oxidative therapy.

Keywords: Antioxidant; GCLC; Nrf2; PC12.

MeSH terms

  • Animals
  • Antioxidants / chemical synthesis
  • Antioxidants / pharmacology*
  • Antipyrine / analogs & derivatives
  • Antipyrine / pharmacology
  • Apoptosis / drug effects
  • Buthionine Sulfoximine / pharmacology
  • Edaravone
  • Glutamate-Cysteine Ligase / antagonists & inhibitors
  • Glutamate-Cysteine Ligase / genetics
  • Glutamate-Cysteine Ligase / metabolism
  • Hydrogen Peroxide / pharmacology
  • NF-E2-Related Factor 2 / metabolism*
  • Oxidative Stress / drug effects
  • PC12 Cells
  • Protective Agents / chemical synthesis
  • Protective Agents / pharmacology*
  • Protein Transport
  • RNA, Messenger / metabolism
  • Rats
  • Reactive Oxygen Species / metabolism
  • Signal Transduction
  • Up-Regulation

Substances

  • Antioxidants
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, rat
  • Protective Agents
  • RNA, Messenger
  • Reactive Oxygen Species
  • Buthionine Sulfoximine
  • Hydrogen Peroxide
  • Glutamate-Cysteine Ligase
  • GCLC protein, rat
  • Edaravone
  • Antipyrine