Synthesis and pharmacological evaluation of multifunctional tacrine derivatives against several disease pathways of AD

Maria Digiacomo, Ziwei Chen, Shengnan Wang, Annalina Lapucci, Marco Macchia, Xiaohong Yang, Jiaqi Chu, Yifan Han, Rongbiao Pi, Simona Rapposelli

Research output: Journal article publicationJournal articleAcademic researchpeer-review

46 Citations (Scopus)


A novel series of tacrine derivatives were designed and synthesized by combining caffeic acid (CA), ferulic acid (FA) and lipoic acid (LA) with tacrine. The antioxidant study revealed that all the hybrids have much more antioxidant capacities compared to CA. Among these compounds, 1b possessed a good ability to inhibit the β-amyloid protein (Aβ) self-aggregation, sub-micromole acetylcholinesterase (AChE)/butyrylcholinesterase (BuChE) inhibitory, modest BACE1 inhibitory. Moreover, compound 1b also was a DPPH radical scavenger and copper chelatory as well as had potent neuroprotective effects against glutamate-induced cell death with low toxicity in HT22 cells. Our findings suggest that the compound 1b might be a promising lead multi-targeted ligand and worthy of further developing for the therapy of Alzheimer's disease.
Original languageEnglish
Pages (from-to)807-810
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Issue number4
Publication statusPublished - 15 Feb 2015


  • Alzheimer's disease
  • Amyloid protein
  • BACE1
  • Caffeic acid
  • Copper
  • Multi-targeted ligands
  • Tacrine

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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