中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 上海药物研究所
  3. 中国科学院上海药物研究所
  4. 新药研究国家重点实验室
Synthesis and biological evaluation of multimodal monoaminergic arylpiperazine derivatives with potential antidepressant profile

文献类型：期刊论文

作者Zheng, Jiefang2,3; Zhou, Liping2,3; Gong, Xudong1; Yang, Feipu2,3; Cheng, Jiaxin2,3; Ma, Rui1; Wu, Chunhui1; Xu, Zhijian2,3; Zhu, Weiliang2,3; He, Yang2,3
刊名EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
出版日期2024-09-05
卷号275页码:16
关键词Triple reuptake inhibitors 5-HT 1A R agonists Antidepressants Multimodal serotonergic compounds
ISSN号0223-5234
DOI10.1016/j.ejmech.2024.116564
通讯作者Zhu, Weiliang(wlzhu@simm.ac.cn) ; He, Yang(heyang@simm.ac.cn)
英文摘要Depression is a common psychiatric disorder with an estimated global prevalence of 4.4 %. Here, we designed a series of new multimodal monoaminergic arylpiperazine derivatives using a pharmacophore hybrid approach and synthesized them for the treatment of depression. Molecular docking was employed to elucidate the differences in activity and selectivity of the corresponding compounds on SERT, NET, and DAT. In vitro experiments demonstrated that compound A3 has a relatively balanced multi-target activity profile with SERT reuptake inhibition (IC50 = 12 nM), NET reuptake inhibition (IC50 = 78 nM), DAT reuptake inhibition (IC50 = 135 nM), and 5-HT1AR agonism (EC50 = 34 nM). Pharmacokinetic experiments revealed that A3 exhibited excellent bioavailability and low clearance in mice. Subsequent behavioral experiments further confirmed its significant antidepressant effects. These results further highlight the rationality of our design strategy.
WOS关键词MAJOR DEPRESSIVE DISORDER ; TRIPLE REUPTAKE INHIBITORS ; SEROTONIN REUPTAKE ; ANTIOXIDANT ACTIVITIES ; ACCURATE DOCKING ; DOPAMINE ; RECEPTOR ; VILAZODONE ; VORTIOXETINE ; EFFICACY
资助项目National Science and Technology Innovation 2030 Major Program[2021ZD0200900] ; Lin Gang Laboratory[LG-GG-202204-01] ; Lin Gang Laboratory[LG202103-01-02]
WOS研究方向Pharmacology & Pharmacy
语种英语
WOS记录号WOS:001257576100001
出版者ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
源URL[http://119.78.100.183/handle/2S10ELR8/312062]  
专题新药研究国家重点实验室
通讯作者Zhu, Weiliang; He, Yang
作者单位1.Vigonvita Shanghai Co Ltd, Shanghai 201210, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Zheng, Jiefang,Zhou, Liping,Gong, Xudong,et al. Synthesis and biological evaluation of multimodal monoaminergic arylpiperazine derivatives with potential antidepressant profile[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2024,275:16.
APA Zheng, Jiefang.,Zhou, Liping.,Gong, Xudong.,Yang, Feipu.,Cheng, Jiaxin.,...&Shen, Jingshan.(2024).Synthesis and biological evaluation of multimodal monoaminergic arylpiperazine derivatives with potential antidepressant profile.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,275,16.
MLA Zheng, Jiefang,et al."Synthesis and biological evaluation of multimodal monoaminergic arylpiperazine derivatives with potential antidepressant profile".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 275(2024):16.

入库方式： OAI收割

来源：上海药物研究所

浏览0
下载0
收藏0
其他版本

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。