Design, synthesis and evaluation of a novel metal chelator as multifunctional agents for the treatment of Alzheimer's disease

Yingying Wang, Yue Yang, Kwon Ho Hong, Yao Ning, Ping Yu, Jinghui Ren, Min Ji, Jin Cai

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

A series of compounds following the lead compounds including deferasirox and tacrine were designed, synthesized and evaluated as multifunctional agents against Alzheimer's disease (AD). In vitro studies showed that most synthesized compounds exhibited good multifunctional activities in inhibiting acetylcholinesterase (bAChE), and chelating metal ions. Especially, compound TD e demonstrated significant metal chelating property, a moderate acetylcholinesterase (AChE) inhibitory activity and an antioxidant activity. Results from the molecular modeling indicated that TD compounds were mixed-type inhibitor, binding simultaneously to the catalytic anionic site (CAS) and the peripheral anionic site (PAS) of TcAChE. Moreover, TD e showed a low cytotoxicity but a good protective activity against the injury caused by H 2 O 2 . These results suggest that TD compounds might be considered as attractive multi-target cholinesterase inhibitor and will play important roles in the treatment of AD.

Original languageEnglish (US)
Pages (from-to)720-727
Number of pages8
JournalBioorganic Chemistry
Volume87
DOIs
StatePublished - Jun 2019

Bibliographical note

Funding Information:
This work was supported by Jiangsu Natural Science Foundation (BK20161438), the Southeast University's Basic Research Business Fee Innovation Foundation (3207048416).

Funding Information:
This work was supported by Jiangsu Natural Science Foundation ( BK20161438 ), the Southeast University's Basic Research Business Fee Innovation Foundation ( 3207048416 ).

Publisher Copyright:
© 2019 Elsevier Inc.

Keywords

  • Acetylcholinesterase inhibitors
  • Alzheimer's disease
  • Deferasirox
  • Metal chelator
  • Multifunctional agents
  • Tacrine

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