Neuroprotective effect of synthetic chalcone derivatives as competitive dual inhibitors against μ-calpain and cathepsin B through the downregulation of tau phosphorylation and insoluble Aβ peptide formation

Kyung Hwa Jeon, Eunyoung Lee, Kyu Yeon Jun, Ji Eun Eom, Soo Yeon Kwak, Younghwa Na, Youngjoo Kwon

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

A series of chalcone derivatives were synthesized and evaluated for their μ-calpain and cathepsin B inhibitory activities. Among the tested chalcone derivatives, two compounds, 7 and 11, showed potent inhibitory activities against m-calpain and cathepsin B and were selected for further evaluation. Compounds 7 and 11 showed enzyme inhibitory activities at the cellular level and displayed neuroprotective effects against oxidative stress-induced apoptosis in SH-SY5Y cells, a human neuroblastoma cell line. Moreover, compounds 7 and 11 reduced p25 formation, tau phosphorylation and insoluble Aβ peptide formation. Enzyme kinetic experiments and docking studies revealed that compounds 7 and 11 competitively inhibited both μ-calpain and cathepsin B enzymes.

Original languageEnglish
Pages (from-to)433-444
Number of pages12
JournalEuropean Journal of Medicinal Chemistry
Volume121
DOIs
StatePublished - 4 Oct 2016

Keywords

  • Ab formation
  • Alzheimer's disease
  • Cathepsin B inhibitor
  • Chalcone
  • Tau hyperphosphorylation
  • μ-Calpain inhibitor

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