Design, synthesis and biological evaluation of thienopyrimidine hydroxamic acid based derivatives as structurally novel histone deacetylase (HDAC) inhibitors

doi:10.1016/j.ejmech.2017.01.035

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	Design, synthesis and biological evaluation of thienopyrimidine hydroxamic acid based derivatives as structurally novel histone deacetylase (HDAC) inhibitors
	Wang, Jiang; Su, Mingbo; Li, Tingting; Gao, Anhui; Yang, Wei; Sheng, Li; Zang, Yi; Li, Jia; Liu, Hong
刊名	EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
	2017-03-10
卷号	128 页码:293-299
关键词	HDAC inhibitor Anti-proliferation Western blot Thienopyrimidine Structure-activity relationship
ISSN号	0223-5234
DOI	10.1016/j.ejmech.2017.01.035
文献子类	Article
英文摘要	New thienopyrimidine hydroxamic acid derivatives as HDACs inhibitors were designed, synthesized and evaluated. All compounds were evaluated for their ability to inhibit recombinant human HDAC1, HDAC3, and HDAC6 isoforms and in vitro anti-proliferative activity on tumor cell lines RMPI 8226 and HCT 116. Most of these compounds displayed good to excellent inhibitory activities against HDACs. The IC50 values of compound 9 m against HDAC1, HDAC3, and HDAC6 was 29.81 +/- 0.52 nM, 24.71 +/- 1.16 nM, and 21.29 +/- 0.32 nM. Most of these compounds showed strong anti-proliferative activity against human cancer cell lines including RMPI 8226 and HCT 116. The IC50 values of compound 9m against RPMI 8226 and HCT 116 proliferation were 0.97 +/- 0.072 mM and 1.01 +/- 0.033 mM, respectively. In addition, compound 9m noticeably up-regulated the level of histone H3 acetylation at the low concentration of 0.3 mM. (C) 2017 Elsevier Masson SAS. All rights reserved.
资助项目	National Natural Science Foundation of China[81620108027] ; National Natural Science Foundation of China[21632008] ; National Natural Science Foundation of China[91229204] ; National Natural Science Foundation of China[21472209] ; National Natural Science Foundation of China[81220108025] ; Major Project of Chinese National Programs for Fundamental Research and Development[2015CB910304] ; National S&T Major Projects[2014ZX09507002-001] ; National S&T Major Projects[2014ZX09507-002-005]
WOS关键词	IDENTIFICATION ; CHEMOTHERAPY ; COMBINATION ; ROMIDEPSIN ; VORINOSTAT ; LYMPHOMA ; DOCKING ; CANCER
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
WOS记录号	WOS:000397180600026
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/272742]
专题	国家新药筛选中心药物化学研究室药物安全性评价中心
通讯作者	Li, Jia; Liu, Hong
作者单位	Chinese Acad Sci, Shanghai Inst Mat Med, Key Lab Receptor Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Wang, Jiang,Su, Mingbo,Li, Tingting,et al. Design, synthesis and biological evaluation of thienopyrimidine hydroxamic acid based derivatives as structurally novel histone deacetylase (HDAC) inhibitors[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2017,128:293-299.
APA	Wang, Jiang.,Su, Mingbo.,Li, Tingting.,Gao, Anhui.,Yang, Wei.,...&Liu, Hong.(2017).Design, synthesis and biological evaluation of thienopyrimidine hydroxamic acid based derivatives as structurally novel histone deacetylase (HDAC) inhibitors.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,128,293-299.
MLA	Wang, Jiang,et al."Design, synthesis and biological evaluation of thienopyrimidine hydroxamic acid based derivatives as structurally novel histone deacetylase (HDAC) inhibitors".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 128(2017):293-299.