Design, synthesis and antitumor evaluation of a new series of N-substituted-thiourea derivatives

doi:10.1111/j.1745-7254.2006.00437.x

	Design, synthesis and antitumor evaluation of a new series of N-substituted-thiourea derivatives
	Li, Jian ; Tan, Jin-zhi ; Chen, Li-li; Zhang, Jian ; Shen, Xu; Mei, Chang-lin ; Fu, Li-li ; Lin, Li-ping ; Ding, Jian; Xiong, Bing
刊名	ACTA PHARMACOLOGICA SINICA
	2006-09
卷号	27 期号:9 页码:1259-1271
关键词	N-substituted-thiourea derivatives anti-tumor SPAC1 tyrosine kinase inhibitor virtual screening
ISSN号	1671-4083
DOI	10.1111/j.1745-7254.2006.00437.x
文献子类	Article
英文摘要	Aim: To design and synthesize a novel class of protein tyrosine kinase inhibitors, featuring the N-(2-oxo-1,2-dihydroquinolin-3-yl-methyl)-thiourea framework. Methods: First, compounds 1 and 2 were identified using the virtual screening approach in conjunction with binding assay based on surface plasmon resonance. Subsequently, 3 regions of compounds 1 and 2 were selected for chemical modification. All compounds were characterized potent inhibitory activities toward the human lung adenocarcinoma cell line SPAC1. Results: Forty new compounds (1-2, 3a-g, 4a-w, and 5a-1) were designed, synthesized and bioassayed. Six compounds (1, 3e, 41, 4w, 5a, and 5b) were found to show promising inhibitory activity against the SPAC1 tumor cell line. The inhibitory activity of compound 5a increases approximately 10 times more than that of the original compound 1. Conclusion: This study provides a promising new template with potential antitumor activity.
WOS关键词	EPIDERMAL-GROWTH-FACTOR ; TYROSINE KINASE INHIBITORS ; STRUCTURE-BASED DISCOVERY ; FACTOR RECEPTOR EGFR ; IRREVERSIBLE INHIBITORS ; CHEMICAL INHIBITORS ; BINDING-SITE ; PROTEIN ; DOMAIN ; DOCKING
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
语种	英语
出版者	ACTA PHARMACOLOGICA SINICA
WOS记录号	WOS:000240554800021
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/273499]
专题	药物化学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
通讯作者	Liu, Hong
作者单位	1.Chinese Acad Sci, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai Inst Mat Med,Shanghai Inst Biol Sci, Shanghai 201203, Peoples R China 2.E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China 3.Second Mil Med Univ, Div Nephrol, Dept Internal Med, Changzheng Hosp, Shanghai 200003, Peoples R China 4.Shanghai Inst Mat Med, Div Antitumor Pharmacol, Shanghai, Peoples R China
推荐引用方式 GB/T 7714	Li, Jian,Tan, Jin-zhi,Chen, Li-li,et al. Design, synthesis and antitumor evaluation of a new series of N-substituted-thiourea derivatives[J]. ACTA PHARMACOLOGICA SINICA,2006,27(9):1259-1271.
APA	Li, Jian.,Tan, Jin-zhi.,Chen, Li-li.,Zhang, Jian.,Shen, Xu.,...&Jiang, Hua-liang.(2006).Design, synthesis and antitumor evaluation of a new series of N-substituted-thiourea derivatives.ACTA PHARMACOLOGICA SINICA,27(9),1259-1271.
MLA	Li, Jian,et al."Design, synthesis and antitumor evaluation of a new series of N-substituted-thiourea derivatives".ACTA PHARMACOLOGICA SINICA 27.9(2006):1259-1271.