Design, synthesis, and structure-activity relationships of novel 4,7,12,12a-tetrahydro-5H-thieno[3 ',2 ':3,4]pyrido[1,2-b]isoquinoline and 5,8,12,12a-tetrahydro-6H-thieno[2 ',3 ': 4,5]pyrido[2,1-a]isoquinoline derivatives as cellular activators of adenosine 5 '-monophosphate-activated protein kinase (AMPK)

doi:10.1016/j.bmc.2018.02.052

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药物发现与设计中心

	Design, synthesis, and structure-activity relationships of novel 4,7,12,12a-tetrahydro-5H-thieno[3 ',2 ':3,4]pyrido[1,2-b]isoquinoline and 5,8,12,12a-tetrahydro-6H-thieno[2 ',3 ': 4,5]pyrido[2,1-a]isoquinoline derivatives as cellular activators of adenosine 5 '-monophosphate-activated protein kinase (AMPK)
	Gu, Zhanni 1,2,4,5; Wu, Lingyan 1,4; Duan, Yanan 3; Wang, Jiang1,4,5 ; Zhou, Shengbin 1,4,5; Li, Jingya1,4 ; Chen, Kaixian1,2,4,5 ; Li, Jia1,4 ; Liu, Hong1,2,4,5
刊名	BIOORGANIC & MEDICINAL CHEMISTRY
	2018-05-01
卷号	26 期号:8 页码:2017-2027
关键词	Adenosine 5 '-monophosphate-activated protein kinase AMPK activators Berberine Tetrahydroberberine T2DM
ISSN号	0968-0896
DOI	10.1016/j.bmc.2018.02.052
文献子类	Article
英文摘要	To discover more derivatives with better glucose-lowering efficacy compared with berberine, twenty-three novel compounds with 4,7,12,12a-tetrahydro-5H-thieno[3',2': 3,4]pyrido[1,2-b]isoquinoline or 5,8,12,12a-tetrahydro-6H-thieno[2',3': 4,5]pyrido[2,1-a] isoquinoline cores were designed, synthesized, and biologically evaluated in vitro in continuation of our previous work on indirect activators of adenosine 5 '-monophosphate-activated protein kinase (AMPK). Nine compounds effectively stimulated glucose consumption (>2.3-fold at 10 mu M) in L6 myotube cells, and two compounds (4d and 4s) exhibited superior inhibitory activity (<57.6% at 5 mu M) compared with berberine on gluconeogenesis in rat primary hepatocytes. Additionally, these compounds significantly up-regulated the phosphorylation of AMPK and its substrate, acetyl-CoA carboxylase (ACC) and slightly decreased the mitochondrial membrane potential in L6 myotube cells. (C) 2018 Published by Elsevier Ltd.
资助项目	National Natural Science Foundation of China[81620108027] ; National Natural Science Foundation of China[81673493] ; National Natural Science Foundation of China[81673489] ; National Natural Science Foundation of China[21632008] ; Major Project of Chinese National Programs for Fundamental Research and Development[2015CB910304] ; Shanghai Municipal Science and Technology Commission[16JC1405000]
WOS关键词	TETRAHYDROPROTOBERBERINE DERIVATIVES ; DOPAMINE D-1 ; BERBERINE DERIVATIVES ; BIOLOGICAL EVALUATION ; IDENTIFICATION ; ANTAGONISTS ; METABOLISM ; MECHANISM ; EFFICACY ; RECEPTOR
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:000429533300059
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279786]
专题	药物发现与设计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国家新药筛选中心
通讯作者	Chen, Kaixian; Li, Jia; Liu, Hong
作者单位	1.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China; 2.China Pharmaceut Univ, Sch Pharm, Nanjing 210009, Jiangsu, Peoples R China; 3.East China Normal Univ, Coll Chem & Mol Engn, 3663 North Zhongshan Rd, Shanghai 200062, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 555 Zu Chong Zhi Rd, Shanghai 201203, Peoples R China; 5.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, 555 Zu Chong Zhi Rd, Shanghai 201203, Peoples R China;
推荐引用方式 GB/T 7714	Gu, Zhanni,Wu, Lingyan,Duan, Yanan,et al. Design, synthesis, and structure-activity relationships of novel 4,7,12,12a-tetrahydro-5H-thieno[3 ',2 ':3,4]pyrido[1,2-b]isoquinoline and 5,8,12,12a-tetrahydro-6H-thieno[2 ',3 ': 4,5]pyrido[2,1-a]isoquinoline derivatives as cellular activators of adenosine 5 '-monophosphate-activated protein kinase (AMPK)[J]. BIOORGANIC & MEDICINAL CHEMISTRY,2018,26(8):2017-2027.
APA	Gu, Zhanni.,Wu, Lingyan.,Duan, Yanan.,Wang, Jiang.,Zhou, Shengbin.,...&Liu, Hong.(2018).Design, synthesis, and structure-activity relationships of novel 4,7,12,12a-tetrahydro-5H-thieno[3 ',2 ':3,4]pyrido[1,2-b]isoquinoline and 5,8,12,12a-tetrahydro-6H-thieno[2 ',3 ': 4,5]pyrido[2,1-a]isoquinoline derivatives as cellular activators of adenosine 5 '-monophosphate-activated protein kinase (AMPK).BIOORGANIC & MEDICINAL CHEMISTRY,26(8),2017-2027.
MLA	Gu, Zhanni,et al."Design, synthesis, and structure-activity relationships of novel 4,7,12,12a-tetrahydro-5H-thieno[3 ',2 ':3,4]pyrido[1,2-b]isoquinoline and 5,8,12,12a-tetrahydro-6H-thieno[2 ',3 ': 4,5]pyrido[2,1-a]isoquinoline derivatives as cellular activators of adenosine 5 '-monophosphate-activated protein kinase (AMPK)".BIOORGANIC & MEDICINAL CHEMISTRY 26.8(2018):2017-2027.