北京大学医学部机构知识库
Advanced  
IR@PKUHSC  > 北京大学药学院  > 期刊论文
学科主题: 药学
题名:
Inhibition of thioredoxin reductase by a novel series of bis-1,2-benzisoselenazol-3(2H)-ones: Organoselenium compounds for cancer therapy
作者: He, Jie1,2; Li, Dongdong3; Xiong, Kun1,2; Ge, Yongjie1,2; Jin, Hongwei1; Zhang, Guozhou1,2; Hong, Mengshi1,2; Tian, Yongliang1,2; Yin, Jin1,2; Zeng, Huihui1,2,3
关键词: Organoselenium compound ; Thioredoxin reductase ; Anticancer drug ; Structure-activity relationship
刊名: BIOORGANIC & MEDICINAL CHEMISTRY
发表日期: 2012-06-15
DOI: 10.1016/j.bmc.2012.04.033
卷: 20, 期:12, 页:3816-3827
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology ; Chemistry, Medicinal ; Chemistry, Organic
研究领域[WOS]: Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Chemistry
关键词[WOS]: CELL LUNG-CANCER ; MOTEXAFIN GADOLINIUM ; GROWTH-INHIBITION ; IN-VITRO ; MECHANISM ; SELENOCYSTEINE ; CARCINOMA ; ETHASELEN ; RADIOTHERAPY ; PROGRESSION
英文摘要:

Thioredoxin reductase (TrxR) is critical for cellular redox regulation and is involved in tumor proliferation, apoptosis and metastasis. Its C-terminal redox-active center contains a cysteine (Cys497) and a unique selenocysteine (Sec498), which are exposed to solvent and easily accessible. Thus, it is becoming an important target for anticancer drugs. Selective inhibition of TrxR by 1,2-(bis-1,2-benzisoselenazol-3(2H)-one)ethane (4a) prevents proliferation of several cancer cell lines both in vivo and in vitro. Using the structure of 4a as a starting point, a series of novel bis-1,2-benzisoselenazol-3(2H)-ones was designed, prepared and tested to explore the structure-activity relationships (SARs) for this class of inhibitor and to improve their potency. Notably, 1,2-(5,5′-dimethoxybis(1,2-benzisoselenazol-3(2H)-one))ethane (12) was found to be more potent than 4a in both in vitro and in vivo evaluation. Its binding sites were confirmed by biotin-conjugated iodoacetamide assay and a SAR model was generated to guide further structural modification. (C) 2012 Elsevier Ltd. All rights reserved.

语种: 英语
所属项目编号: 2011M500526
项目资助者: China Postdoctoral Science Foundation
WOS记录号: WOS:000304486500015
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/60938
Appears in Collections:北京大学药学院_期刊论文

Files in This Item:

There are no files associated with this item.


作者单位: 1.Peking Univ, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
2.Peking Univ, Sch Pharmaceut Sci, Beijing 100191, Peoples R China
3.Tianjin Int Joint Acad Biotechnol & Med, Tianjin 300457, Peoples R China

Recommended Citation:
He, Jie,Li, Dongdong,Xiong, Kun,et al. Inhibition of thioredoxin reductase by a novel series of bis-1,2-benzisoselenazol-3(2H)-ones: Organoselenium compounds for cancer therapy[J]. BIOORGANIC & MEDICINAL CHEMISTRY,2012,20(12):3816-3827.
Service
Recommend this item
Sava as my favorate item
Show this item's statistics
Export Endnote File
Google Scholar
Similar articles in Google Scholar
[He, Jie]'s Articles
[Li, Dongdong]'s Articles
[Xiong, Kun]'s Articles
CSDL cross search
Similar articles in CSDL Cross Search
[He, Jie]‘s Articles
[Li, Dongdong]‘s Articles
[Xiong, Kun]‘s Articles
Related Copyright Policies
Null
Social Bookmarking
Add to CiteULike Add to Connotea Add to Del.icio.us Add to Digg Add to Reddit

Items in IR are protected by copyright, with all rights reserved, unless otherwise indicated.

 

 

Valid XHTML 1.0!
Copyright © 2007-2017  北京大学医学部 - Feedback
Powered by CSpace