SIOC OpenIR  > 生命有机化学国家重点实验室
Development of 3-Phenyl-N-(2-(3-phenylureido)ethyl)-thiophene-2-sulfonamide Compounds as Inhibitors of Antiapoptotic Bcl-2 Family Proteins
其他题名Development of 3-Phenyl-N-(2-(3-phenylureido)ethyl)-thiophene-2-sulfonamide Compounds as Inhibitors of Antiapoptotic Bcl-2 Family Proteins
YANG CHENGWEN1; CHEN SHA1; ZHOU MI1; LI YAN1; LI YANGFENG1; ZHANG ZHENGXI1; LIU ZHEN1; BA QIAN1; LI JINGQUAN1; WANG HUI1; YAN XIAOMEI1; Ma DW(马大为)1; Wang RX(王任小)1
2014
发表期刊ChemMedChem
卷号9期号:7页码:1436-1452
摘要Antiapoptotic Bcl-2 family proteins, such as Bcl-x(L), Bcl-2, and Mcl-1, are often overexpressed in tumor cells, which contributes to tumor cell resistance to chemotherapies and radio-therapies. Inhibitors of these proteins thus have potential applications in cancer treatment. We discovered, through structure-based virtual screening, a lead compound with micromolar binding affinity to Mcl-1 (inhibition constant (K-i)=3 mu m). It contains a phenyltetrazole and a hydrazinecarbothioamide moiety, and it represents a structural scaffold not observed among known Bcl-2 inhibitors. This work presents the structural optimization of this lead compound. By following the scaf-fold-hopping strategy, we have designed and synthesized a total of 82 compounds in three sets. All of the compounds were evaluated in a fluorescence-polarization binding assay to measure their binding affinities to Bcl-x(L), Bcl-2, and Mcl-1. Some of the compounds with a 3-phenylthiophene-2-sulfonamide core moiety showed sub-micromolar binding affinities to Mcl-1 (K-i=0.3-0.4 mm) or Bcl-2 (K-i approximate to 1 mu m). They also showed obvious cytotoxicity on tumor cells (IC50 < 10 mu m). Two-dimensional heteronuclear single quantum coherence NMR spectra of three selected compounds, that is, YCW-E5, YCW-E10, and YCW-E11, indicated that they bind to the BH3-binding groove on Bcl-x(L) in a similar mode to ABT-737. Several apoptotic assays conducted on HL-60 cells demonstrated that these compounds are able to induce cell apoptosis through the mitochondrial pathway. We propose that the compounds with the 3-phenylthiophene-2-sulfonamide core moiety are worth further optimization as effective apoptosis inducers with an interesting selectivity towards Mcl-1 and Bcl-2.
学科领域生命有机化学
DOI10.1002/cmdc.201400058
URL查看原文
收录类别SCI
语种英语
引用统计
文献类型期刊论文
条目标识符http://ir.sioc.ac.cn/handle/331003/38951
专题生命有机化学国家重点实验室
通讯作者YAN XIAOMEI; Ma DW(马大为); Wang RX(王任小)
作者单位1.中科院上海有机化学研究所
2.厦门大学
3.中科院上海生命科学研究院
推荐引用方式
GB/T 7714
YANG CHENGWEN,CHEN SHA,ZHOU MI,et al. Development of 3-Phenyl-N-(2-(3-phenylureido)ethyl)-thiophene-2-sulfonamide Compounds as Inhibitors of Antiapoptotic Bcl-2 Family Proteins[J]. ChemMedChem,2014,9(7):1436-1452.
APA YANG CHENGWEN.,CHEN SHA.,ZHOU MI.,LI YAN.,LI YANGFENG.,...&王任小.(2014).Development of 3-Phenyl-N-(2-(3-phenylureido)ethyl)-thiophene-2-sulfonamide Compounds as Inhibitors of Antiapoptotic Bcl-2 Family Proteins.ChemMedChem,9(7),1436-1452.
MLA YANG CHENGWEN,et al."Development of 3-Phenyl-N-(2-(3-phenylureido)ethyl)-thiophene-2-sulfonamide Compounds as Inhibitors of Antiapoptotic Bcl-2 Family Proteins".ChemMedChem 9.7(2014):1436-1452.
条目包含的文件
文件名称/大小 文献类型 版本类型 开放类型 使用许可
2014336.pdf(1712KB)期刊论文作者接受稿开放获取CC BY-NC-SA请求全文
个性服务
推荐该条目
保存到收藏夹
查看访问统计
导出为Endnote文件
谷歌学术
谷歌学术中相似的文章
[YANG CHENGWEN]的文章
[CHEN SHA]的文章
[ZHOU MI]的文章
百度学术
百度学术中相似的文章
[YANG CHENGWEN]的文章
[CHEN SHA]的文章
[ZHOU MI]的文章
必应学术
必应学术中相似的文章
[YANG CHENGWEN]的文章
[CHEN SHA]的文章
[ZHOU MI]的文章
相关权益政策
暂无数据
收藏/分享
所有评论 (0)
暂无评论
 

除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。