The discovery and optimization of novel dual inhibitors of topoisomerase ii and histone deacetylase

doi:10.1016/j.bmc.2013.09.023

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药理学第一研究室

	The discovery and optimization of novel dual inhibitors of topoisomerase ii and histone deacetylase
	Zhang, Xuan 2; Bao, Bin 2; Yu, Xiuhua 2; Tong, Linjiang 3; Luo, Yu 1; Huang, Qingqing 2; Su, Mingbo 4; Sheng, Li 4; Li, Jia4 ; Zhu, Hong 5
刊名	BIOORGANIC & MEDICINAL CHEMISTRY
	2013-11-15
卷号	21 期号:22 页码:6981-6995
关键词	Podophyllotoxin HDAC Topoisomerase II Cancer Hybrid Synergistic effect
ISSN号	0968-0896
DOI	10.1016/j.bmc.2013.09.023
文献子类	Article
英文摘要	A novel class of podophyllotoxin derivatives have been designed and synthesized based on the synergistic antitumor effects of topoisomerase II and histone deacetylase inhibitors. Their inhibitory activities towards histone deacetylases and Topo II and their cytotoxicities in cancer cell lines were evaluated. The aromatic capping group connection, linker length and zinc-binding group were systematically varied and preliminary conclusions regarding structure-activity relationships are discussed. Among all of the synthesized hybrid compounds, compound 24d showed the most potent HDAC inhibitory activity at a low nanomolar level and exhibited powerful antiproliferative activity towards HCT116 colon carcinoma cells at a low micromolar level. Further exploration of this series led to the discovery of potent dual inhibitor 32, which exhibited the strongest in vitro cytotoxic activity. (C) 2013 Elsevier Ltd. All rights reserved.
资助项目	Youth Scientific Innovation Foundation of East China Normal University[78210157] ; Youth Scientific Innovation Foundation of East China Normal University[78210198] ; State Key Laboratory of Drug Research[SIMM1203KF-10] ; National Natural Science Foundation of China[81172936] ; National Natural Science Foundation of China[21102046] ; Fundamental Research Funds for the Central Universities[00000000]
WOS关键词	GROWTH-FACTOR RECEPTOR ; T-CELL LYMPHOMA ; ANTITUMOR AGENTS ; CANCER-CELLS ; POTENT INHIBITORS ; PHARMACOLOGICAL PROFILES ; BIOLOGICAL EVALUATION ; IN-VIVO ; DNA ; DERIVATIVES
WOS研究方向	Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Chemistry
语种	英语
出版者	PERGAMON-ELSEVIER SCIENCE LTD
WOS记录号	WOS:000325759800014
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277375]
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
通讯作者	Chen, Yi
作者单位	1.E China Normal Univ, Dept Chem, Shanghai 200062, Peoples R China; 2.E China Normal Univ, Inst Drug Discovery & Dev, Shanghai Engn Res Ctr Mol Therapeut & New Drug De, Shanghai 200062, Peoples R China; 3.Chinese Acad Sci, Div Antitumor Pharmacol, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 4.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, SIBS, Shanghai 201203, Peoples R China; 5.Zhejiang Univ, Inst Pharmacol & Toxicol, Coll Pharmaceut Sci, Hangzhou 310003, Zhejiang, Peoples R China
推荐引用方式 GB/T 7714	Zhang, Xuan,Bao, Bin,Yu, Xiuhua,et al. The discovery and optimization of novel dual inhibitors of topoisomerase ii and histone deacetylase[J]. BIOORGANIC & MEDICINAL CHEMISTRY,2013,21(22):6981-6995.
APA	Zhang, Xuan.,Bao, Bin.,Yu, Xiuhua.,Tong, Linjiang.,Luo, Yu.,...&Lu, Wei.(2013).The discovery and optimization of novel dual inhibitors of topoisomerase ii and histone deacetylase.BIOORGANIC & MEDICINAL CHEMISTRY,21(22),6981-6995.
MLA	Zhang, Xuan,et al."The discovery and optimization of novel dual inhibitors of topoisomerase ii and histone deacetylase".BIOORGANIC & MEDICINAL CHEMISTRY 21.22(2013):6981-6995.