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 language | English |
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Pages (from-to) | 433-444 |
Number of pages | 12 |
Journal | European Journal of Medicinal Chemistry |
Volume | 121 |
DOIs | |
State | Published - 4 Oct 2016 |
Keywords
- Ab formation
- Alzheimer's disease
- Cathepsin B inhibitor
- Chalcone
- Tau hyperphosphorylation
- μ-Calpain inhibitor