Incorporation of Dihydroartemisinin into Memantine Through a Propriate Spacer to Make Hybrid with Enhanced Effects to Protect PC12 Cells from Corticosterone-caused Impairments
文献类型：期刊论文
| 作者 | Zhang Lei2; Zhou Fan2; Zhang Laitao2; Peng Lizhi2; Guo Cuiping2; Luo Cheng1 ; Chen Heru1,2,3
|
| 刊名 | CHEMICAL RESEARCH IN CHINESE UNIVERSITIES
 |
| 出版日期 | 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. |
| WOS关键词 | NMDA RECEPTOR ANTAGONIST ; ARTEMISIA-ANNUA L. ; ION CHANNELS ; MOOD DISORDERS ; DERIVATIVES ; DEPRESSION ; ACTIVATION ; ARTEMETHER ; SYSTEM |
| 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研究方向 | Chemistry |
| 语种 | 英语 |
| CSCD记录号 | CSCD:6037792 |
| WOS记录号 | WOS:000407988500017 |
| 出版者 | HIGHER EDUCATION PRESS |
| 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. |
入库方式： OAI收割
来源：上海药物研究所
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