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

32 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

Access to Document

10.1016/j.ejmech.2016.06.008

Fingerprint

Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this

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

@article{4507cfd7a2564acfa58f4eee13709f88,

title = "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",

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.",

keywords = "Ab formation, Alzheimer's disease, Cathepsin B inhibitor, Chalcone, Tau hyperphosphorylation, μ-Calpain inhibitor",

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.",

year = "2016",

month = oct,

day = "4",

doi = "10.1016/j.ejmech.2016.06.008",

language = "English",

volume = "121",

pages = "433--444",

journal = "European Journal of Medicinal Chemistry",

issn = "0223-5234",

publisher = "Elsevier Masson s.r.l.",

}

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

TY - JOUR

T1 - 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

AU - Jeon, Kyung Hwa

AU - Lee, Eunyoung

AU - Jun, Kyu Yeon

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.

PY - 2016/10/4

Y1 - 2016/10/4

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.

KW - Ab formation

KW - Alzheimer's disease

KW - Cathepsin B inhibitor

KW - Chalcone

KW - Tau hyperphosphorylation

KW - μ-Calpain inhibitor

UR - https://www.scopus.com/pages/publications/84974661134

U2 - 10.1016/j.ejmech.2016.06.008

DO - 10.1016/j.ejmech.2016.06.008

M3 - Article

C2 - 27318120

AN - SCOPUS:84974661134

SN - 0223-5234

VL - 121

SP - 433

EP - 444

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

ER -