2. Academic Validation
  3. Design, synthesis and evaluation of flurbiprofen-clioquinol hybrids as multitarget-directed ligands against Alzheimer's disease

Design, synthesis and evaluation of flurbiprofen-clioquinol hybrids as multitarget-directed ligands against Alzheimer's disease

  • Bioorg Med Chem. 2020 Apr 1;28(7):115374. doi: 10.1016/j.bmc.2020.115374.
Ziyi Yang 1,  Qing Song 1,  Zhongcheng Cao 1,  Guangjun Yu 1,  Zhuoling Liu 1,  Zhenghuai Tan 2,  Yong Deng 3
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry, Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, PR China.
  • 2 Institute of Traditional Chinese Medicine Pharmacology and Toxicology, Sichuan Academy of Chinese Medicine Sciences, Chengdu 610041, PR China.
  • 3 Department of Medicinal Chemistry, Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, PR China. Electronic address: [email protected].
PMID: 32089390 DOI: 10.1016/j.bmc.2020.115374
Abstract

A series of novel flurbiprofen-clioquinol hybrids were designed and synthesized as multifunctional agents for Alzheimer's disease therapy, and their potential was evaluated through various biological experiments. In vitro studies showed that most target compounds exhibited significant ability to inhibit self- and Cu2+-induced β-amyloid aggregation. Furthermore, some target compounds, especially 7i and 7r, also showed biometal chelating abilities, antioxidant activity, anti-neuroinflammatory activity and appropriate BBB permeability. These biological activities indicated that the representative compound 7i and 7r might be promising multifunctional agents for AD treatment.

Keywords

Alzheimer’s disease; Anti-Aβ-aggregation; Anti-neuroinflammation; Antioxidantion; Biometal chelating; Flurbiprofen-clioquinol hybrids.

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