Synthesis and investigation of dihydroxychalcones as calpain and cathepsin inhibitors

Kyung Hye Baek; Radha Karki; Eung Seok Lee; Younghwa Na; Youngjoo Kwon

doi:10.1016/j.bioorg.2013.09.002

Synthesis and investigation of dihydroxychalcones as calpain and cathepsin inhibitors

Kyung Hye Baek, Radha Karki, Eung Seok Lee, Younghwa Na, Youngjoo Kwon

Department of Pharmaceutical Sciences

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

10 Scopus citations

Abstract

In order to identify potential calpain and cathepsin inhibitors we prepared 12 dihydroxychalcone analogues and tested their ability to inhibit μ-calpain, m-calpain, cathepsins B and L. In the calpain inhibition test, compound 10 exhibited the most active inhibitory activity against m-calpain with an IC₅₀ value of 25.25 ± 0.901 μM. With respect to inhibition of cathepsins B and L, compound 13 exhibited the most potent inhibitory activity on cathepsin L and moderate inhibitory activity on cathepsin B with IC₅₀ values of 2.80 ± 0.100 and 11.47 ± 0.087 μM, respectively. Our results suggest the possibility of developing dual calpain and cathepsin inhibitors by properly modulating structures and/or combining the essential aspects of the functional group effective for specific calpain and cathepsin inhibition.

Original language	English
Pages (from-to)	24-30
Number of pages	7
Journal	Bioorganic Chemistry
Volume	51
DOIs	https://doi.org/10.1016/j.bioorg.2013.09.002
State	Published - 2013

Bibliographical note

Funding Information:
This work was financially supported by CHA University, Pocheon, and the Korea Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology ( 2011-0011007 ).

Keywords

B L Inhibitor
Calpain inhibitor
Cathepsin
Dihydroxychalcone

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title = "Synthesis and investigation of dihydroxychalcones as calpain and cathepsin inhibitors",

abstract = "In order to identify potential calpain and cathepsin inhibitors we prepared 12 dihydroxychalcone analogues and tested their ability to inhibit μ-calpain, m-calpain, cathepsins B and L. In the calpain inhibition test, compound 10 exhibited the most active inhibitory activity against m-calpain with an IC50 value of 25.25 ± 0.901 μM. With respect to inhibition of cathepsins B and L, compound 13 exhibited the most potent inhibitory activity on cathepsin L and moderate inhibitory activity on cathepsin B with IC50 values of 2.80 ± 0.100 and 11.47 ± 0.087 μM, respectively. Our results suggest the possibility of developing dual calpain and cathepsin inhibitors by properly modulating structures and/or combining the essential aspects of the functional group effective for specific calpain and cathepsin inhibition.",

keywords = "B L Inhibitor, Calpain inhibitor, Cathepsin, Dihydroxychalcone",

author = "Baek, {Kyung Hye} and Radha Karki and Lee, {Eung Seok} and Younghwa Na and Youngjoo Kwon",

note = "Funding Information: This work was financially supported by CHA University, Pocheon, and the Korea Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology ( 2011-0011007 ).",

year = "2013",

doi = "10.1016/j.bioorg.2013.09.002",

language = "English",

volume = "51",

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journal = "Bioorganic Chemistry",

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TY - JOUR

T1 - Synthesis and investigation of dihydroxychalcones as calpain and cathepsin inhibitors

AU - Baek, Kyung Hye

AU - Karki, Radha

AU - Lee, Eung Seok

AU - Na, Younghwa

AU - Kwon, Youngjoo

N1 - Funding Information: This work was financially supported by CHA University, Pocheon, and the Korea Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology ( 2011-0011007 ).

PY - 2013

Y1 - 2013

N2 - In order to identify potential calpain and cathepsin inhibitors we prepared 12 dihydroxychalcone analogues and tested their ability to inhibit μ-calpain, m-calpain, cathepsins B and L. In the calpain inhibition test, compound 10 exhibited the most active inhibitory activity against m-calpain with an IC50 value of 25.25 ± 0.901 μM. With respect to inhibition of cathepsins B and L, compound 13 exhibited the most potent inhibitory activity on cathepsin L and moderate inhibitory activity on cathepsin B with IC50 values of 2.80 ± 0.100 and 11.47 ± 0.087 μM, respectively. Our results suggest the possibility of developing dual calpain and cathepsin inhibitors by properly modulating structures and/or combining the essential aspects of the functional group effective for specific calpain and cathepsin inhibition.

AB - In order to identify potential calpain and cathepsin inhibitors we prepared 12 dihydroxychalcone analogues and tested their ability to inhibit μ-calpain, m-calpain, cathepsins B and L. In the calpain inhibition test, compound 10 exhibited the most active inhibitory activity against m-calpain with an IC50 value of 25.25 ± 0.901 μM. With respect to inhibition of cathepsins B and L, compound 13 exhibited the most potent inhibitory activity on cathepsin L and moderate inhibitory activity on cathepsin B with IC50 values of 2.80 ± 0.100 and 11.47 ± 0.087 μM, respectively. Our results suggest the possibility of developing dual calpain and cathepsin inhibitors by properly modulating structures and/or combining the essential aspects of the functional group effective for specific calpain and cathepsin inhibition.

KW - B L Inhibitor

KW - Calpain inhibitor

KW - Cathepsin

KW - Dihydroxychalcone

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DO - 10.1016/j.bioorg.2013.09.002

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AN - SCOPUS:84884920153

SN - 0045-2068

VL - 51

SP - 24

EP - 30

JO - Bioorganic Chemistry

JF - Bioorganic Chemistry

ER -

Synthesis and investigation of dihydroxychalcones as calpain and cathepsin inhibitors

Abstract

Bibliographical note

Keywords

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