Inhibition of amyloid fibril formation and cytotoxicity by caffeic acid-conjugated amyloid-β C-terminal peptides

Bioorg Med Chem Lett. 2016 Nov 15;26(22):5468-5471. doi: 10.1016/j.bmcl.2016.10.027. Epub 2016 Oct 12.

Abstract

Amyloid-β (Aβ) deposition and oxidative stress observed in the brains of patients with Alzheimer's disease (AD) are important targets for therapeutic intervention. In this study, we conjugated the antioxidants caffeic acid (CA) and dihydrocaffeic acid (DHCA) to Aβ1-42 C-terminal motifs (Aβx-42: x=38, 40) to synthesize CA-Aβx-42 and DHCA-Aβx-42, respectively. Among the compounds, CA-Aβ38-42 exhibited potent inhibitory activity against Aβ1-42 aggregation and scavenged Aβ1-42-induced intracellular oxidative stress. Moreover, CA-Aβ38-42 significantly protected human neuroblastoma SH-SY5Y cells against Aβ1-42-induced cytotoxicity, with an IC50 of 4μM. These results suggest that CA-Aβ38-42 might be a potential lead for the treatment of AD.

Keywords: Aggregation inhibitor; Alzheimer’s disease; Amyloid-β; Antioxidative activity; Caffeic acid; Cytotoxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / metabolism
  • Amyloid / antagonists & inhibitors*
  • Amyloid / metabolism
  • Amyloid beta-Peptides / chemistry
  • Amyloid beta-Peptides / metabolism*
  • Amyloid beta-Peptides / pharmacology*
  • Antioxidants / chemistry
  • Antioxidants / pharmacology*
  • Caffeic Acids / chemistry
  • Caffeic Acids / pharmacology*
  • Cell Line, Tumor
  • Humans
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / pharmacology*
  • Oxidative Stress / drug effects
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism*
  • Peptide Fragments / pharmacology*
  • Protein Aggregates / drug effects*

Substances

  • Amyloid
  • Amyloid beta-Peptides
  • Antioxidants
  • Caffeic Acids
  • Neuroprotective Agents
  • Peptide Fragments
  • Protein Aggregates
  • amyloid beta-protein (1-42)
  • 3,4-dihydroxyphenylpropionic acid
  • caffeic acid