Novel oxime-bearing coumarin derivatives act as potent Nrf2/ARE activators in vitro and in mouse model

Ken Ming Chang, Huang Hui Chen, Tai Chi Wang, I. Li Chen, Yu Tsen Chen, Shyh Chyun Yang, Yeh Long Chen, Hsin Huei Chang, Chih Hsiang Huang, Jang Yang Chang, Chuan Shih, Ching Chuan Kuo, Cherng Chyi Tzeng

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)


We have designed and synthesized certain novel oxime- and amide-bearing coumarin derivatives as nuclear factor erythroid 2 p45-related factor 2 (Nrf2) activators. The potency of these compounds was measured by antioxidant responsive element (ARE)-driven luciferase activity, level of Nrf2-related cytoprotective genes and proteins, and antioxidant activity. Among them, (Z)-3-(2-(hydroxyimino)-2-phenylethoxy)-2H-chromen-2-one (17a) was the most active, and more potent than the positive t-BHQ in the induction of ARE-driven luciferase activity. Exposure of HSC-3 cells to various concentrations of 17a strongly increased Nrf2 nuclear translocation and the expression level of Nrf2-mediated cytoprotective proteins in a concentration-dependent manner. HSC-3 cells pretreated with 17a significantly reduced t-BOOH-induced oxidative stress. In the animal experiment, Nrf2-mediated cytoprotective proteins, such as aldo-keto reductase 1 subunit C-1 (AKR1C1), glutathione reductase (GR), and heme oxygenase (HO-1), were obviously elevated in the liver of 17a-treated mice than that of control. These results suggested that novel oxime-bearing coumarin 17a is able to activate Nrf2/ARE pathway in vivo and are therefore seen as a promising candidate for further investigation.

Original languageEnglish
Pages (from-to)60-74
Number of pages15
JournalEuropean Journal of Medicinal Chemistry
Publication statusPublished - Dec 2015
Externally publishedYes


  • Antioxidant activity
  • Cytoprotection
  • Nrf2/ARE activators
  • Oxime-bearing coumarins

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry


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