题名 | Synthetic Chalcones with Potent Antioxidant Ability on H2O2-Induced Apoptosis in PC12 Cells |
作者 | |
发表日期 | 2014-10 |
发表期刊 | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 影响因子和分区 |
语种 | 英语 |
原始文献类型 | Article |
关键词 | chalcone derivatives antioxidant PC12 cells Nrf2-ARE pathway GCLC HO-1 |
其他关键词 | HEME OXYGENASE-1 ; ANTICANCER ; ANALOGS ; PROTECTS ; STRESS ; AGENTS |
摘要 | Chalcone derivatives (E)-3-(4-hydroxy-3-methoxyphenyl)-1-(4-methoxyphenyl) prop-2-en-1-one and (E)-3-(4-hydroxyphenyl)-1-(4-methoxyphenyl) prop-2-en-1-one (Compounds 1 and 2) have been demonstrated to be potent anti-inflammatory agents in our previous study. In light of the relationship of intracellular mechanisms between anti-inflammatories and antioxidants, we further designed and synthesized a series of chalcone derivatives based on 1 and 2, to explore their antioxidant efficacy. The majority of the derivatives exhibited strong protective effects on PC12 (PC12 rat pheochromocytoma) cells exposed to H2O2, and all compounds were nontoxic. A preliminary structure-activity relationship was proposed. Compounds 1 and 1d ((E)-2-methoxy-4-(3-(4-methoxyphenyl)-3-oxoprop-1-en-1-yl) phenyl acrylate) exerted the action in a good dose-dependent manner. Quantitative RT-PCR (qRT-PCR) and western blot analysis showed that 1 and 1d significantly improve the expression of nuclear factor erythroid 2 p45-related factor 2 (Nrf2)-dependent antioxidant genes g-Glutamylcysteine Ligase Catalytic Subunit (GCLC) and heme oxygenase-1 (HO-1) and their corresponding proteins (gamma-glutamyl cysteine synthase (gamma-GCS) and HO-1) in PC12 cells. Inhibition of GCLC and HO-1 by specific inhibitors, L-buthionine-S-sulfoximine (BSO) and zinc protoporphyrin (ZnPP), respectively, partially reduce the protective effect of 1 and 1d. These data present a series of novel chalcone analogs, especially compounds 1 and 1d, as candidates for treating oxidative stress-related disease by activating the Nrf2-antioxidant responsive element (ARE) pathway. |
资助项目 | Zhejiang Province Natural Science Funding of China [Y13H300005, LY12H30004]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81272462, 81102310]; Technology Foundation for Medical Science of Zhejiang Province [2012KYA129] |
出版者 | MDPI AG |
出版地 | BASEL |
ISSN | 1422-0067 |
EISSN | 1422-0067 |
卷号 | 15期号:10页码:18525-18539 |
DOI | 10.3390/ijms151018525 |
页数 | 15 |
WOS类目 | Biochemistry & Molecular Biology ; Chemistry, Multidisciplinary |
WOS研究方向 | Biochemistry & Molecular Biology ; Chemistry |
WOS记录号 | WOS:000344457200053 |
收录类别 | SCIE ; PUBMED ; SCOPUS |
URL | 查看原文 |
PubMed ID | 25318055 |
PMC记录号 | PMC4227230 |
SCOPUSEID | 2-s2.0-84907822244 |
通讯作者地址 | [Wu, Jian-Zhang]Chemical Biology Research Center,School of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou,325035,China |
Scopus学科分类 | Catalysis;Molecular Biology;Spectroscopy;Computer Science Applications;Physical and Theoretical Chemistry;Organic Chemistry;Inorganic Chemistry |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | https://kms.wmu.edu.cn/handle/3ETUA0LF/18905 |
专题 | 药学院(分析测试中心) 第一临床医学院(信息与工程学院)、附属第一医院_计算机与信息管理系 |
通讯作者 | Wu, Jian-Zhang |
作者单位 | 1.Chemical Biology Research Center,School of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou,325035,China; 2.Institute of Sports Science,Wenzhou Medical University,Wenzhou,325035,China; 3.College of Information Science and Computer Engineering,Wenzhou Medical University,Wenzhou,325035,China |
第一作者单位 | 药学院(分析测试中心); 生物有机与药物化学研究中心 |
通讯作者单位 | 药学院(分析测试中心); 生物有机与药物化学研究中心 |
第一作者的第一单位 | 药学院(分析测试中心) |
推荐引用方式 GB/T 7714 | Wu, Jian-Zhang,Cheng, Chan-Chan,Shen, Lai-Lai,et al. Synthetic Chalcones with Potent Antioxidant Ability on H2O2-Induced Apoptosis in PC12 Cells[J]. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES,2014,15(10):18525-18539. |
APA | Wu, Jian-Zhang., Cheng, Chan-Chan., Shen, Lai-Lai., Wang, Zhan-Kun., Wu, Shou-Biao., ... & Qiu, Pei-Hong. (2014). Synthetic Chalcones with Potent Antioxidant Ability on H2O2-Induced Apoptosis in PC12 Cells. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 15(10), 18525-18539. |
MLA | Wu, Jian-Zhang,et al."Synthetic Chalcones with Potent Antioxidant Ability on H2O2-Induced Apoptosis in PC12 Cells".INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 15.10(2014):18525-18539. |
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