Design, synthesis and biological evaluation of isoquinoline-based derivatives as novel histone deacetylase inhibitors

doi:10.1016/j.bmc.2015.06.071

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	Design, synthesis and biological evaluation of isoquinoline-based derivatives as novel histone deacetylase inhibitors
	Yang, Wei 2; Li, Lixuan 1,3; Wang, Yulan 1; Wu, Xiaowei 2; Li, Tingting ; Yang, Nan; Su, Mingbo 1; Sheng, Li 1; Zheng, Mingyue1 ; Zang, Yi1
刊名	BIOORGANIC & MEDICINAL CHEMISTRY
	2015-09-01
卷号	23 期号:17 页码:5881-5890
关键词	HDACs HDACs inhibitor Hydroxamic acid Isoquinoline
ISSN号	0968-0896
DOI	10.1016/j.bmc.2015.06.071
文献子类	Article
英文摘要	The design, synthesis and biological evaluation of a series of isoquinoline-based hydroxamic acid compounds as novel HDACs inhibitors were reported herein. A detailed SAR study showed most of the compounds displayed good to excellent inhibitory activities against HDAC1, 3, 6. The IC50 values of compound 10c against HDAC1, 3, 6 were 4.17 +/- 0.11 nM, 4.00 +/- 0.10 nM, 3.77 +/- 0.07 nM, respectively. Most of the compounds showed great anti-proliferative activities against RPMI 8226, HCT 116 and Hep G2 cells. The IC50 values of compounds 10a-h against RPMI 8226 cancer cell proliferation were all below 1 mu M. HCT 116 cell was sensitive to the compounds 10a, 10f-g and 18a with the IC50 values <0.3 mu M. The active compounds 10a-d did not show inhibitory activity against hERG channel. All these evidence indicated these compounds had great potential as HDACs inhibitors for the further development. (C) 2015 Elsevier Ltd. All rights reserved.
资助项目	National Natural Science Foundation of China[21021063] ; National Natural Science Foundation of China[91229204] ; National Natural Science Foundation of China[81125023] ; National Natural Science Foundation of China[81173033] ; National Natural Science Foundation of China[81025017] ; National S&T Major Projects[2012ZX09103101-072] ; National S&T Major Projects[2012ZX09301001-005] ; National S&T Major Projects[2013ZX09507-001] ; Chinese Academy of Science 'strategic leader in science and technology projects'[XDA01040303] ; Program of Shanghai Subject Chief Scientist[12XD1407100] ; Program of Shanghai Subject Chief Scientist[13XD1404300] ; National Science & Technology Major Project 'Key New Drug Creation and Manufacturing Program' of China[2014ZX09507-002]
WOS关键词	HDAC INHIBITORS ; THERAPY ; CANCER ; SAHA ; DEPSIPEPTIDE ; ACETYLATION ; DISEASES ; AGENT
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:000360349900067
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/276422]
专题	国家新药筛选中心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化学研究室药物安全性评价中心
通讯作者	Li, Jia
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China; 3.E China Normal Univ, Inst Adv Interdisciplinary Res, Shanghai 200062, Peoples R China
推荐引用方式 GB/T 7714	Yang, Wei,Li, Lixuan,Wang, Yulan,et al. Design, synthesis and biological evaluation of isoquinoline-based derivatives as novel histone deacetylase inhibitors[J]. BIOORGANIC & MEDICINAL CHEMISTRY,2015,23(17):5881-5890.
APA	Yang, Wei.,Li, Lixuan.,Wang, Yulan.,Wu, Xiaowei.,Li, Tingting.,...&Liu, Hong.(2015).Design, synthesis and biological evaluation of isoquinoline-based derivatives as novel histone deacetylase inhibitors.BIOORGANIC & MEDICINAL CHEMISTRY,23(17),5881-5890.
MLA	Yang, Wei,et al."Design, synthesis and biological evaluation of isoquinoline-based derivatives as novel histone deacetylase inhibitors".BIOORGANIC & MEDICINAL CHEMISTRY 23.17(2015):5881-5890.