PMID- 32322468
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 2211-3835 (Print)
IS  - 2211-3843 (Electronic)
IS  - 2211-3835 (Linking)
VI  - 10
IP  - 4
DP  - 2020 Apr
TI  - Discovery of nitazoxanide-based derivatives as autophagy activators for the 
      treatment of Alzheimer's disease.
PG  - 646-666
LID - 10.1016/j.apsb.2019.07.006 [doi]
AB  - 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 (Abeta) 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.
CI  - (c) 2020 Chinese Pharmaceutical Association and Institute of Materia Medica, 
      Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.
FAU - Li, Xiaokang
AU  - Li X
AD  - State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New 
      Drug Design, School of Pharmacy, East China University of Science and Technology, 
      Shanghai 200237, China.
FAU - Lu, Jian
AU  - Lu J
AD  - School of Medicine and Life Sciences, Nanjing University of Chinese Medicine, 
      Nanjing 210023, China.
FAU - Xu, Yixiang
AU  - Xu Y
AD  - State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New 
      Drug Design, School of Pharmacy, East China University of Science and Technology, 
      Shanghai 200237, China.
FAU - Wang, Jiaying
AU  - Wang J
AD  - School of Medicine and Life Sciences, Nanjing University of Chinese Medicine, 
      Nanjing 210023, China.
FAU - Qiu, Xiaoxia
AU  - Qiu X
AD  - State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New 
      Drug Design, School of Pharmacy, East China University of Science and Technology, 
      Shanghai 200237, China.
FAU - Fan, Lei
AU  - Fan L
AD  - Center for Drug Safety Evaluation and Research, State Key Laboratory of Drug 
      Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 
      Shanghai 201203, China.
FAU - Li, Baoli
AU  - Li B
AD  - State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New 
      Drug Design, School of Pharmacy, East China University of Science and Technology, 
      Shanghai 200237, China.
FAU - Liu, Wenwen
AU  - Liu W
AD  - State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New 
      Drug Design, School of Pharmacy, East China University of Science and Technology, 
      Shanghai 200237, China.
FAU - Mao, Fei
AU  - Mao F
AD  - State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New 
      Drug Design, School of Pharmacy, East China University of Science and Technology, 
      Shanghai 200237, China.
FAU - Zhu, Jin
AU  - Zhu J
AD  - State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New 
      Drug Design, School of Pharmacy, East China University of Science and Technology, 
      Shanghai 200237, China.
FAU - Shen, Xu
AU  - Shen X
AD  - School of Medicine and Life Sciences, Nanjing University of Chinese Medicine, 
      Nanjing 210023, China.
FAU - Li, Jian
AU  - Li J
AD  - State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New 
      Drug Design, School of Pharmacy, East China University of Science and Technology, 
      Shanghai 200237, China.
LA  - eng
PT  - Journal Article
DEP - 20190729
PL  - Netherlands
TA  - Acta Pharm Sin B
JT  - Acta pharmaceutica Sinica. B
JID - 101600560
PMC - PMC7161708
OTO - NOTNLM
OT  - AChEIs, acetylcholinesterase inhibitors
OT  - AD, Alzheimer's disease
OT  - APP, amyloid precursor protein
OT  - Alzheimer's disease
OT  - Autophagy
OT  - Abeta, beta-amyloid
OT  - BBB, blood-brain barrier
OT  - CNS, central nervous system
OT  - MWM, Morris Water Maze
OT  - NCEs, new chemical entities
OT  - NFTs, neurofibrillary tangles
OT  - NMDA, N-methyl-d-aspartate
OT  - NTZ, nitazoxanide
OT  - Nitazoxanide
OT  - PAMPA, parallel artificial membrane permeation assay
OT  - PBL, porcine brain lipid
OT  - SPs, senile plaques
OT  - Tau protein
OT  - WORT, wortmannin
OT  - mTOR, mammalian target of rapamycin
OT  - beta-amyloid
EDAT- 2020/04/24 06:00
MHDA- 2020/04/24 06:01
PMCR- 2019/07/29
CRDT- 2020/04/24 06:00
PHST- 2019/05/12 00:00 [received]
PHST- 2019/07/03 00:00 [revised]
PHST- 2019/07/17 00:00 [accepted]
PHST- 2020/04/24 06:00 [entrez]
PHST- 2020/04/24 06:00 [pubmed]
PHST- 2020/04/24 06:01 [medline]
PHST- 2019/07/29 00:00 [pmc-release]
AID - S2211-3835(19)30654-9 [pii]
AID - 10.1016/j.apsb.2019.07.006 [doi]
PST - ppublish
SO  - Acta Pharm Sin B. 2020 Apr;10(4):646-666. doi: 10.1016/j.apsb.2019.07.006. Epub 
      2019 Jul 29.