title: Novel antioxidants' synthesis and their anti-oxidative activity through activating Nrf2 signaling pathway.
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 H2O2induced 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.
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Jianzhang
authors.initials: J
authors.lastname: Wu
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Jiye
authors.initials: J
authors.lastname: Ren
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Song
authors.initials: S
authors.lastname: Yao
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Jiabing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Clinical Pharmacy, Taizhou Hospital, Zhejiang, Linhai 317000, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhou
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Di
authors.initials: D
authors.lastname: Yun
authors.affiliation: College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou, Zhejiang 325035, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Shoubiao
authors.initials: S
authors.lastname: Wu
authors.affiliation: Institute of Sports Science, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China; Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Zhankun
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China. Electronic address: wjzwzmc@126.com.
authors.forename: Peihong
authors.initials: P
authors.lastname: Qiu
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis / Q000494:pharmacology*; D000983:Antipyrine / Q000031:analogs & derivatives / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D000077553:Edaravone; D005721:Glutamate-Cysteine Ligase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D016716:PC12 Cells; D020011:Protective Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D021381:Protein Transport; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D000975:Antioxidants; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D020011:Protective Agents; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D019328:Buthionine Sulfoximine; D006861:Hydrogen Peroxide; D005721:Glutamate-Cysteine Ligase; C544143:GCLC protein, rat; D000077553:Edaravone; D000983:Antipyrine
keywords: Antioxidant; GCLC; Nrf2; PC12