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.
Copyright © 2017 Elsevier Ltd. All rights reserved.
MeSH terms
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Animals
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Antioxidants / chemical synthesis
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Antioxidants / pharmacology*
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Antipyrine / analogs & derivatives
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Antipyrine / pharmacology
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Apoptosis / drug effects
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Buthionine Sulfoximine / pharmacology
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Edaravone
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Glutamate-Cysteine Ligase / antagonists & inhibitors
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Glutamate-Cysteine Ligase / genetics
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Glutamate-Cysteine Ligase / metabolism
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Hydrogen Peroxide / pharmacology
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NF-E2-Related Factor 2 / metabolism*
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Oxidative Stress / drug effects
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PC12 Cells
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Protective Agents / chemical synthesis
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Protective Agents / pharmacology*
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Protein Transport
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RNA, Messenger / metabolism
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Rats
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Reactive Oxygen Species / metabolism
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Signal Transduction
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Up-Regulation
Substances
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Antioxidants
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NF-E2-Related Factor 2
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Nfe2l2 protein, rat
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Protective Agents
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RNA, Messenger
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Reactive Oxygen Species
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Buthionine Sulfoximine
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Hydrogen Peroxide
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Glutamate-Cysteine Ligase
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GCLC protein, rat
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Edaravone
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Antipyrine