Discovery of nitazoxanide-based derivatives as autophagy activators for the treatment of Alzheimer's disease
文献类型：期刊论文
| 作者 | Li, Xiaokang1; Lu, Jian2; Xu, Yixiang1; Wang, Jiaying2; Qiu, Xiaoxia1; Fan, Lei3; Li, Baoli1; Liu, Wenwen1; Mao, Fei1; Zhu, Jin1 |
| 刊名 | ACTA PHARMACEUTICA SINICA B
 |
| 出版日期 | 2020-04-01 |
| 卷号 | 10期号:4页码:646-666 |
| 关键词 | Alzheimer's disease Autophagy Nitazoxanide beta-amyloid Tau protein |
| ISSN号 | 2211-3835 |
| DOI | 10.1016/j.apsb.2019.07.006 |
| 通讯作者 | Shen, Xu(xshen@njucm.edu.cn) ; Li, Jian(jianli@ecust.edu.cn) |
| 英文摘要 | Drug repurposing is an efficient strategy for new drug discovery. Our latest study found that nitazoxanide (NTZ), an approved anti-parasite drug, was an autophagy activator and could alleviate the symptom of Alzheimer's disease (AD). In order to further improve the efficacy and discover new chemical entities, a series of NTZ-based derivatives were designed, synthesized, and evaluated as autophagy activator against AD. All compounds were screened by the inhibition of phosphorylation of p70S6K, which was the direct substrate of mammalian target of rapamycin (mTOR) and its phosphorylation level could reflect the mTOR-dependent autophagy level. Among these analogs, compound 22 exhibited excellent potency in promoting beta-amyloid (A beta) clearance, inhibiting tau phosphorylation, as well as stimulating autophagy both in vitro and in vivo. What's more, 22 could effectively improve the memory and cognitive impairments in APP/PS1 transgenic AD model mice. These results demonstrated that 22 was a potential candidate for the treatment of AD. (C) 2020 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. |
| WOS关键词 | AMYLOID-BETA-PROTEIN ; TAU ; SEMAGACESTAT ; SOLANEZUMAB ; HYPOTHESIS ; INHIBITOR ; TANGLES ; DESIGN ; SYSTEM ; TRIALS |
| 资助项目 | National Sciences and Technology Major Project of China[2018ZX09711002-003-010] ; National Natural Science Foundation of China[81872747] ; National Natural Science Foundation of China[21672064] ; 111 Project (China)[B07023] ; Chinese Postdoctoral Science Foundation[2018M641946] ; Shanghai Sailing Program (China)[19YF1412600] ; Shanghai Morning Light Program (China)[18CG33] ; National Special Fund for State Key Laboratory of Bioreactor Engineering (China)[2060204] ; Postgraduate Research & Practice Innovation Program of Jiangsu Province (China)[KYCX18_1600] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000526087100006 |
| 出版者 | INST MATERIA MEDICA, CHINESE ACAD MEDICAL SCIENCES |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/280991]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Shen, Xu; Li, Jian |
| 作者单位 | 1.East China Univ Sci & Technol, Sch Pharm, State Key Lab Bioreactor Engn, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China 2.Nanjing Univ Chinese Med, Sch Med & Life Sci, Nanjing 210023, Peoples R China 3.Chinese Acad Sci, Ctr Drug Safety Evaluat & Res, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Li, Xiaokang,Lu, Jian,Xu, Yixiang,et al. Discovery of nitazoxanide-based derivatives as autophagy activators for the treatment of Alzheimer's disease[J]. ACTA PHARMACEUTICA SINICA B,2020,10(4):646-666. |
| APA | Li, Xiaokang.,Lu, Jian.,Xu, Yixiang.,Wang, Jiaying.,Qiu, Xiaoxia.,...&Li, Jian.(2020).Discovery of nitazoxanide-based derivatives as autophagy activators for the treatment of Alzheimer's disease.ACTA PHARMACEUTICA SINICA B,10(4),646-666. |
| MLA | Li, Xiaokang,et al."Discovery of nitazoxanide-based derivatives as autophagy activators for the treatment of Alzheimer's disease".ACTA PHARMACEUTICA SINICA B 10.4(2020):646-666. |
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。