2. Academic Validation
  3. Discovery of novel rivastigmine-hydroxycinnamic acid hybrids as multi-targeted agents for Alzheimer's disease

Discovery of novel rivastigmine-hydroxycinnamic acid hybrids as multi-targeted agents for Alzheimer's disease

  • Eur J Med Chem. 2017 Jan 5;125:784-792. doi: 10.1016/j.ejmech.2016.09.052.
Ziwei Chen 1,  Maria Digiacomo 2,  Yalin Tu 3,  Qiong Gu 4,  Shengnan Wang 3,  Xiaohong Yang 3,  Jiaqi Chu 3,  Qiuhe Chen 3,  Yifan Han 5,  Jingkao Chen 3,  Giulia Nesi 2,  Simona Sestito 2,  Marco Macchia 2,  Simona Rapposelli 6,  Rongbiao Pi 7
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences, SunYat-sen University, Guangzhou 510006, China; Zhejiang Pharmaceutical College, Ningbo 315000, China; International Joint Laboratory (SYSU-PolyU HK) of Novel Anti-dementia Drugs of Guangdong Province, Guangzhou 510006, China.
  • 2 Dipartimento di Farmacia, Università di Pisa, Via Bonanno, 6, 56126 Pisa, Italy.
  • 3 School of Pharmaceutical Sciences, SunYat-sen University, Guangzhou 510006, China; International Joint Laboratory (SYSU-PolyU HK) of Novel Anti-dementia Drugs of Guangdong Province, Guangzhou 510006, China.
  • 4 School of Pharmaceutical Sciences, SunYat-sen University, Guangzhou 510006, China.
  • 5 International Joint Laboratory (SYSU-PolyU HK) of Novel Anti-dementia Drugs of Guangdong Province, Guangzhou 510006, China; Department of Applied Biology and Chemical Technology, Hong Kong Polytechnic University, Hong Kong, China.
  • 6 Dipartimento di Farmacia, Università di Pisa, Via Bonanno, 6, 56126 Pisa, Italy. Electronic address: [email protected].
  • 7 School of Pharmaceutical Sciences, SunYat-sen University, Guangzhou 510006, China; International Joint Laboratory (SYSU-PolyU HK) of Novel Anti-dementia Drugs of Guangdong Province, Guangzhou 510006, China; National and Local United Engineering Lab of Drug Ability and New Drugs Evaluation, Sun Yat-sen University, Guangzhou 510080, China; Guangdong Province Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China. Electronic address: [email protected].
PMID: 27736684 DOI: 10.1016/j.ejmech.2016.09.052
Abstract

A series of rivastigmine-caffeic acid and rivastigmine-ferulic acid hybrids were designed, synthesized, and evaluated as multifunctional agents for Alzheimer's disease (AD) in vitro. The new compounds exerted antioxidant neuroprotective properties and good cholinesterases (ChE) inhibitory activities. Some of them also inhibited amyloid protein (Aβ) aggregation. In particular, compound 5 emerged as promising drug candidates endowed with neuroprotective potential, ChE inhibitory, Aβ self-aggregation inhibitory and copper chelation properties. These data suggest that compound 5 offers an attractive starting point for further lead optimization in the drug-discovery process against AD.

Keywords

Alzheimer's disease; Caffeic acid; Ferulic acid; Hybrid; Multifunctional agents; Rivastigmine.

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