Incorporation of Dihydroartemisinin into Memantine Through a Propriate Spacer to Make Hybrid with Enhanced Effects to Protect PC12 Cells from Corticosterone-caused Impairments

doi:10.1007/s40242-017-6465-7

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	Incorporation of Dihydroartemisinin into Memantine Through a Propriate Spacer to Make Hybrid with Enhanced Effects to Protect PC12 Cells from Corticosterone-caused Impairments
	Zhang Lei 2; Zhou Fan 2; Zhang Laitao 2; Peng Lizhi 2; Guo Cuiping 2; Luo Cheng1 ; Chen Heru 1,2,3
刊名	CHEMICAL RESEARCH IN CHINESE UNIVERSITIES
	2017-08
卷号	33 期号:4 页码:611-622
关键词	Artemisinin Memantine Neuroprotection N-Methyl-D-aspartate(NMDA) receptor Depression
ISSN号	1005-9040
DOI	10.1007/s40242-017-6465-7
文献子类	Article
英文摘要	Ten memantine(Mema)-dihydroartemisinin(DHA) ligands were designed and synthesized. Three types of isomers including alpha, beta, and a defined gamma isomer were found in each intermediates(1a-1e). Type gamma isomer was firstly reported here and confirmed as a less stable eclipsed conformation. The bonding of Mema with DHA through different carbon chains generally makes the new entities more cytotoxic than either Mema or artemisinin(Arte). The beta Mema/DHA ligands are a little bit more cytotoxic than alpha ligands. By applying corticosterone(Cort)-impaired PC12 cells models, it was found that Mema and those ligands with more than 3 carbon chains showed weak or no neuroprotective activities against the insults. However, two ligands, 2a(beta) and 2b(beta) showed better effects than either Arte or their combination(Mema/Arte in 1:1 molar ratio) at a dose of 5 mu mol/L. Furthermore, ligands 2a(beta), 2b(beta) and 2c(beta) were confirmed as mild N-methyl-D-aspartate(NMDA) antagonists, and their corresponding alpha isomers are weak NMDA antagonists. All the data indicate that the bonding of Mema/DHA in compacted beta conformation mode results in enhanced effects against Cort-induced insults in PC12 cells and might reverse memantine as an anti-depression NMDA antagonist.
资助项目	National Natural Science Foundation of China[81172982] ; Natural Science Foundation of Guangdong Province of China[2015A030311012] ; Fundamental Research Funds for the Central Universities of China[11615323]
WOS关键词	NMDA RECEPTOR ANTAGONIST ; ARTEMISIA-ANNUA L. ; ION CHANNELS ; MOOD DISORDERS ; DERIVATIVES ; DEPRESSION ; ACTIVATION ; ARTEMETHER ; SYSTEM
WOS研究方向	Chemistry
语种	英语
CSCD记录号	CSCD:6037792
出版者	HIGHER EDUCATION PRESS
WOS记录号	WOS:000407988500017
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/272539]
专题	新药研究国家重点实验室中科院受体结构与功能重点实验室
通讯作者	Chen Heru
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 2.Jinan Univ, Coll Pharm, Inst Tradit Chinese Med & Nat Prod, Guangzhou 510632, Guangdong, Peoples R China; 3.Jinan Univ, Guangdong Prov Key Lab Pharmacodynam Constituents, Guangzhou 510632, Guangdong, Peoples R China
推荐引用方式 GB/T 7714	Zhang Lei,Zhou Fan,Zhang Laitao,et al. Incorporation of Dihydroartemisinin into Memantine Through a Propriate Spacer to Make Hybrid with Enhanced Effects to Protect PC12 Cells from Corticosterone-caused Impairments[J]. CHEMICAL RESEARCH IN CHINESE UNIVERSITIES,2017,33(4):611-622.
APA	Zhang Lei.,Zhou Fan.,Zhang Laitao.,Peng Lizhi.,Guo Cuiping.,...&Chen Heru.(2017).Incorporation of Dihydroartemisinin into Memantine Through a Propriate Spacer to Make Hybrid with Enhanced Effects to Protect PC12 Cells from Corticosterone-caused Impairments.CHEMICAL RESEARCH IN CHINESE UNIVERSITIES,33(4),611-622.
MLA	Zhang Lei,et al."Incorporation of Dihydroartemisinin into Memantine Through a Propriate Spacer to Make Hybrid with Enhanced Effects to Protect PC12 Cells from Corticosterone-caused Impairments".CHEMICAL RESEARCH IN CHINESE UNIVERSITIES 33.4(2017):611-622.