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.
Bibliographical noteFunding Information:
This research was supported by the Health Fellowship Foundation, the National Research Foundation of Korea (NRF) grant funded by the Korean government ( MEST ) ( NRF-2013R1A1A2060408 and NRF-2014M3A9A9073908 ) and the grant from the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea ( HI14C2469 ). Appendix A
© 2016 Elsevier Masson SAS.
- Ab formation
- Alzheimer's disease
- Cathepsin B inhibitor
- Tau hyperphosphorylation
- μ-Calpain inhibitor