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

doi:10.1016/j.ejmech.2016.06.008

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

Department of Pharmaceutical Sciences

Research output: Contribution to journal › Article › peer-review

25 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 language	English
Pages (from-to)	433-444
Number of pages	12
Journal	European Journal of Medicinal Chemistry
Volume	121
DOIs	https://doi.org/10.1016/j.ejmech.2016.06.008
State	Published - 4 Oct 2016

Bibliographical note

Funding 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

Publisher Copyright:
© 2016 Elsevier Masson SAS.

Keywords

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

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Jeon, K. H., Lee, E., Jun, K. Y., Eom, J. E., Kwak, S. Y., Na, Y., & Kwon, Y. (2016). 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. European Journal of Medicinal Chemistry, 121, 433-444. https://doi.org/10.1016/j.ejmech.2016.06.008

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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.",

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author = "Jeon, {Kyung Hwa} and Eunyoung Lee and Jun, {Kyu Yeon} and Eom, {Ji Eun} and Kwak, {Soo Yeon} and Younghwa Na and Youngjoo Kwon",

note = "Funding 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 Publisher Copyright: {\textcopyright} 2016 Elsevier Masson SAS.",

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Jeon, KH, Lee, E, Jun, KY, Eom, JE, Kwak, SY, Na, Y & Kwon, Y 2016, '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', European Journal of Medicinal Chemistry, vol. 121, pp. 433-444. https://doi.org/10.1016/j.ejmech.2016.06.008

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. / Jeon, Kyung Hwa; Lee, Eunyoung; Jun, Kyu Yeon et al.
In: European Journal of Medicinal Chemistry, Vol. 121, 04.10.2016, p. 433-444.

Research output: Contribution to journal › Article › peer-review

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AU - Eom, Ji Eun

AU - Kwak, Soo Yeon

AU - Na, Younghwa

AU - Kwon, Youngjoo

N1 - Funding 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 Publisher Copyright: © 2016 Elsevier Masson SAS.

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N2 - 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.

AB - 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.

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