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. Epub 2016 Sep 17.

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.

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Amyloid beta-Peptides / drug effects
  • Amyloid beta-Peptides / metabolism
  • Antioxidants / chemistry
  • Cholinesterase Inhibitors / chemistry
  • Cholinesterase Inhibitors / pharmacokinetics
  • Coumaric Acids / chemistry
  • Coumaric Acids / pharmacology*
  • Drug Discovery / methods
  • Humans
  • In Vitro Techniques / methods
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / pharmacology
  • Rivastigmine / chemistry
  • Rivastigmine / pharmacology*
  • Structure-Activity Relationship

Substances

  • Amyloid beta-Peptides
  • Antioxidants
  • Cholinesterase Inhibitors
  • Coumaric Acids
  • Neuroprotective Agents
  • Rivastigmine