Synthesis of cinnamoyl ketoamides as hybrid structures of antioxidants and calpain inhibitors

Yeong Jae Yoo; Dong Hyuk Nam; Seo Yun Jung; Jae Wan Jang; Hyoung Ja Kim; Changbae Jin; Ae Nim Pae; Yong Sup Lee

doi:10.1016/j.bmcl.2011.03.077

Synthesis of cinnamoyl ketoamides as hybrid structures of antioxidants and calpain inhibitors

Yeong Jae Yoo, Dong Hyuk Nam, Seo Yun Jung, Jae Wan Jang, Hyoung Ja Kim, Changbae Jin, Ae Nim Pae, Yong Sup Lee

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

17 Citations (Scopus)

Abstract

The excessive calpain activation causes serious cellular damage or even cell death in neurological disorders such as stroke and Alzheimer's disease. Oxidative stress has also been implicated in the initiation or progression of neurodegenerative diseases. In the present studies, a series of cinnamoyl ketoamides 4a-4j were synthesized as hybrid structures of antioxidants and calpain inhibitors. Cinnamoyl ketoamides, possessing an alkyl chain at the α-position, showed potent μ-calpain inhibitory activities indicating that the cinnamoyl skeleton can be regarded as an acyclic variant of calpain inhibitory chromone carboxamide 2. Among synthesized, compound 4e was the most potent inhibitor of μ-calpain (IC₅₀ = 0.13 μM) and also exhibited strong antioxidant activities in DPPH and superoxide anion radical scavenging and lipid peroxidation inhibition assay systems.

Original language	English
Pages (from-to)	2850-2854
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	21
Issue number	10
DOIs	https://doi.org/10.1016/j.bmcl.2011.03.077
Publication status	Published - 15 May 2011

Bibliographical note

Funding Information:
This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by MEST ( 2010-0016080 ).

Keywords

Antioxidant
Calpain inhibitor
Cell death
Cinnamoyl ketoamides
Docking

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abstract = "The excessive calpain activation causes serious cellular damage or even cell death in neurological disorders such as stroke and Alzheimer's disease. Oxidative stress has also been implicated in the initiation or progression of neurodegenerative diseases. In the present studies, a series of cinnamoyl ketoamides 4a-4j were synthesized as hybrid structures of antioxidants and calpain inhibitors. Cinnamoyl ketoamides, possessing an alkyl chain at the α-position, showed potent μ-calpain inhibitory activities indicating that the cinnamoyl skeleton can be regarded as an acyclic variant of calpain inhibitory chromone carboxamide 2. Among synthesized, compound 4e was the most potent inhibitor of μ-calpain (IC50 = 0.13 μM) and also exhibited strong antioxidant activities in DPPH and superoxide anion radical scavenging and lipid peroxidation inhibition assay systems.",

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note = "Funding Information: This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by MEST ( 2010-0016080 ). ",

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AU - Yoo, Yeong Jae

AU - Nam, Dong Hyuk

AU - Jung, Seo Yun

AU - Jang, Jae Wan

AU - Kim, Hyoung Ja

AU - Jin, Changbae

AU - Pae, Ae Nim

AU - Lee, Yong Sup

N1 - Funding Information: This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by MEST ( 2010-0016080 ).

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Y1 - 2011/5/15

N2 - The excessive calpain activation causes serious cellular damage or even cell death in neurological disorders such as stroke and Alzheimer's disease. Oxidative stress has also been implicated in the initiation or progression of neurodegenerative diseases. In the present studies, a series of cinnamoyl ketoamides 4a-4j were synthesized as hybrid structures of antioxidants and calpain inhibitors. Cinnamoyl ketoamides, possessing an alkyl chain at the α-position, showed potent μ-calpain inhibitory activities indicating that the cinnamoyl skeleton can be regarded as an acyclic variant of calpain inhibitory chromone carboxamide 2. Among synthesized, compound 4e was the most potent inhibitor of μ-calpain (IC50 = 0.13 μM) and also exhibited strong antioxidant activities in DPPH and superoxide anion radical scavenging and lipid peroxidation inhibition assay systems.

AB - The excessive calpain activation causes serious cellular damage or even cell death in neurological disorders such as stroke and Alzheimer's disease. Oxidative stress has also been implicated in the initiation or progression of neurodegenerative diseases. In the present studies, a series of cinnamoyl ketoamides 4a-4j were synthesized as hybrid structures of antioxidants and calpain inhibitors. Cinnamoyl ketoamides, possessing an alkyl chain at the α-position, showed potent μ-calpain inhibitory activities indicating that the cinnamoyl skeleton can be regarded as an acyclic variant of calpain inhibitory chromone carboxamide 2. Among synthesized, compound 4e was the most potent inhibitor of μ-calpain (IC50 = 0.13 μM) and also exhibited strong antioxidant activities in DPPH and superoxide anion radical scavenging and lipid peroxidation inhibition assay systems.

KW - Antioxidant

KW - Calpain inhibitor

KW - Cell death

KW - Cinnamoyl ketoamides

KW - Docking

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IS - 10

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Synthesis of cinnamoyl ketoamides as hybrid structures of antioxidants and calpain inhibitors

Abstract

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Keywords

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