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

doi:10.1016/j.bmcl.2014.12.084

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 publication › Journal article › Academic research › peer-review

74 Citations (Scopus)

Abstract

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 language	English
Pages (from-to)	807-810
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	25
Issue number	4
DOIs	https://doi.org/10.1016/j.bmcl.2014.12.084
Publication status	Published - 15 Feb 2015

Keywords

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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10.1016/j.bmcl.2014.12.084

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title = "Synthesis and pharmacological evaluation of multifunctional tacrine derivatives against several disease pathways of AD",

abstract = "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.",

keywords = "Alzheimer's disease, Amyloid protein, BACE1, Caffeic acid, Copper, Multi-targeted ligands, Tacrine",

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

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AU - Digiacomo, Maria

AU - Chen, Ziwei

AU - Wang, Shengnan

AU - Lapucci, Annalina

AU - Macchia, Marco

AU - Yang, Xiaohong

AU - Chu, Jiaqi

AU - Han, Yifan

AU - Pi, Rongbiao

AU - Rapposelli, Simona

PY - 2015/2/15

Y1 - 2015/2/15

N2 - 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.

AB - 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.

KW - Alzheimer's disease

KW - Amyloid protein

KW - BACE1

KW - Caffeic acid

KW - Copper

KW - Multi-targeted ligands

KW - Tacrine

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DO - 10.1016/j.bmcl.2014.12.084

M3 - Journal article

SN - 0960-894X

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SP - 807

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JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 4

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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