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A Series of alpha-Heterocyclic Carboxaldehyde Thiosemicarbazones Inhibit Topoisomerase II alpha Catalytic Activity

文献类型：期刊论文

作者Huang, He2; Chen, Qin1; Ku, Xin2; Meng, Linghua1; Lin, Liping1; Wang, Xiang1; Zhu, Caihua1; Wang, Yi1; Chen, Zhi2; Li, Ming1
刊名JOURNAL OF MEDICINAL CHEMISTRY
出版日期2010-04-22
卷号53期号:8页码:3048-3064
ISSN号0022-2623
DOI10.1021/jm9014394
文献子类Article
英文摘要A series of novel thiosemicarbazone derivatives bearing condensed heterocyclic carboxaldehyde moieties were designed and synthesized. Among them, TSC24 exhibited broad antiproliferative activity in a panel of human tumor cells and suppressed tumor growth in mice. The mechanism research revealed that TSC24 was not only an iron chelator but also a topoisomerase II alpha catalytic inhibitor. Its inhibition on topoisomerase II alpha was due to direct interaction with the ATPase domain of topoisomerase I la which led to the block of ATP hydrolysis. Molecular docking predicted that TSC24 might bind at the ATP binding site, which was confirmed by the competitive inhibition assay. These results about the mechanisms involved in the anticancer activities of thiosemicarbazones will aid in the rational design of novel topoisomerase II-targeted drugs and will provide insights into the discovery and development of novel cancer therapeutics based on the dual activity to chelate iron and to inhibit the catalytic activity of topoisomerase II alpha.
WOS关键词MEDIATED DNA CLEAVAGE ; HERPES-SIMPLEX VIRUS ; BREAST-CANCER CELLS ; GYRASE-B PROTEIN ; IRON CHELATORS ; ANTITUMOR-ACTIVITY ; 2-ACETYLPYRIDINE THIOSEMICARBAZONES ; ANTIPROLIFERATIVE AGENTS ; ANTILEUKEMIC ACTIVITY ; MULTIDRUG-RESISTANCE
资助项目National Natural Science Foundation of China[20721003] ; National Natural Science Foundation of China[20872153] ; 863 Hi-Tech Program of China[2006AA020602] ; State Key Program of Basic Research of China[2009CB918502] ; Science and Technology Commission of Shanghai Municipality[07dz05906]
WOS研究方向Pharmacology & Pharmacy
语种英语
WOS记录号WOS:000276562400005
出版者AMER CHEMICAL SOC
源URL[http://119.78.100.183/handle/2S10ELR8/278915]  
专题药理学第一研究室
中科院受体结构与功能重点实验室
新药研究国家重点实验室
药物发现与设计中心
药物化学研究室
通讯作者Meng, Linghua
作者单位1.Chinese Acad Sci, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China;
2.Chinese Acad Sci, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Huang, He,Chen, Qin,Ku, Xin,et al. A Series of alpha-Heterocyclic Carboxaldehyde Thiosemicarbazones Inhibit Topoisomerase II alpha Catalytic Activity[J]. JOURNAL OF MEDICINAL CHEMISTRY,2010,53(8):3048-3064.
APA Huang, He.,Chen, Qin.,Ku, Xin.,Meng, Linghua.,Lin, Liping.,...&Liu, Hong.(2010).A Series of alpha-Heterocyclic Carboxaldehyde Thiosemicarbazones Inhibit Topoisomerase II alpha Catalytic Activity.JOURNAL OF MEDICINAL CHEMISTRY,53(8),3048-3064.
MLA Huang, He,et al."A Series of alpha-Heterocyclic Carboxaldehyde Thiosemicarbazones Inhibit Topoisomerase II alpha Catalytic Activity".JOURNAL OF MEDICINAL CHEMISTRY 53.8(2010):3048-3064.

入库方式： OAI收割

来源：上海药物研究所

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