國家衛生研究院 NHRI:Item 3990099045/9316

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Title:	Novel oxime-bearing coumarin derivatives act as potent Nrf2/ARE activators in vitro and in mouse model
Authors:	Chang, KM;Chen, HH;Wang, TC;Chen, IL;Chen, YT;Yang, SC;Chen, YL;Chang, HH;Huang, CH;Chang, JY;Shih, C;Kuo, CC;Tzeng, CC
Contributors:	Institute of Biotechnology and Pharmaceutical Research;National Institute of Cancer Research
Abstract:	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.
Date:	2015-12
Relation:	European Journal of Medicinal Chemistry. 2015 Dec;106:60-74.
Link to:	http://dx.doi.org/10.1016/j.ejmech.2015.10.029
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0223-5234&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000366232100007
Cited Times(Scopus):	http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84946830412
Appears in Collections:	[Ching-Chuan Kuo] Periodical Articles [Chuan Shih(2014-2017)] Periodical Articles [Jang-Yang Chang] Periodical Articles

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