Synthesis of chromone carboxamide derivatives with antioxidative and calpain inhibitory properties

Sang Hoon Kim; Young Hoon Lee; Seo Yun Jung; Hyoung Ja Kim; Changbae Jin; Yong Sup Lee

doi:10.1016/j.ejmech.2011.02.025

Synthesis of chromone carboxamide derivatives with antioxidative and calpain inhibitory properties

Sang Hoon Kim, Young Hoon Lee, Seo Yun Jung, Hyoung Ja Kim, Changbae Jin, Yong Sup Lee

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

30 Citations (Scopus)

Abstract

The overactivation of μ-calpain can cause serious cell damage in several diseases. Furthermore, cell death in a number of neurodegenerative disorders is linked to the overproduction of reactive oxygen species. Therefore, antioxidants and μ-calpain inhibitors could have the therapeutic potentials to treat cell death related diseases. New chromone carboxamide derivatives 3 were synthesized to provide alternative μ-calpain inhibitors to compound 2, a conformationally constrained structural variant of MDL 28,170. Compounds 3h and 3l exhibited the most potent μ-calpain inhibitory activities (IC ₅₀ = 0.09-0.10 μM), and were comparable to 2 in this respect (IC₅₀ = 0.07 μM). Compound 3i showed both potent μ-calpain inhibitory activity (IC₅₀ = 0.28 μM) and antioxidant activities in DPPH scavenging and lipid peroxidation inhibition assays.

Original language	English
Pages (from-to)	1721-1728
Number of pages	8
Journal	European Journal of Medicinal Chemistry
Volume	46
Issue number	5
DOIs	https://doi.org/10.1016/j.ejmech.2011.02.025
Publication status	Published - May 2011

Bibliographical note

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

Keywords

Antioxidant
Calpain inhibitor
Cell death
Chromone carboxamide
Neurodegenerative disease

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10.1016/j.ejmech.2011.02.025

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title = "Synthesis of chromone carboxamide derivatives with antioxidative and calpain inhibitory properties",

abstract = "The overactivation of μ-calpain can cause serious cell damage in several diseases. Furthermore, cell death in a number of neurodegenerative disorders is linked to the overproduction of reactive oxygen species. Therefore, antioxidants and μ-calpain inhibitors could have the therapeutic potentials to treat cell death related diseases. New chromone carboxamide derivatives 3 were synthesized to provide alternative μ-calpain inhibitors to compound 2, a conformationally constrained structural variant of MDL 28,170. Compounds 3h and 3l exhibited the most potent μ-calpain inhibitory activities (IC 50 = 0.09-0.10 μM), and were comparable to 2 in this respect (IC50 = 0.07 μM). Compound 3i showed both potent μ-calpain inhibitory activity (IC50 = 0.28 μM) and antioxidant activities in DPPH scavenging and lipid peroxidation inhibition assays.",

keywords = "Antioxidant, Calpain inhibitor, Cell death, Chromone carboxamide, Neurodegenerative disease",

author = "Kim, {Sang Hoon} and Lee, {Young Hoon} and Jung, {Seo Yun} and Kim, {Hyoung Ja} and Changbae Jin and Lee, {Yong Sup}",

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

year = "2011",

month = may,

doi = "10.1016/j.ejmech.2011.02.025",

language = "English",

volume = "46",

pages = "1721--1728",

journal = "European Journal of Medicinal Chemistry",

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T1 - Synthesis of chromone carboxamide derivatives with antioxidative and calpain inhibitory properties

AU - Kim, Sang Hoon

AU - Lee, Young Hoon

AU - Jung, Seo Yun

AU - Kim, Hyoung Ja

AU - Jin, Changbae

AU - Lee, Yong Sup

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

PY - 2011/5

Y1 - 2011/5

N2 - The overactivation of μ-calpain can cause serious cell damage in several diseases. Furthermore, cell death in a number of neurodegenerative disorders is linked to the overproduction of reactive oxygen species. Therefore, antioxidants and μ-calpain inhibitors could have the therapeutic potentials to treat cell death related diseases. New chromone carboxamide derivatives 3 were synthesized to provide alternative μ-calpain inhibitors to compound 2, a conformationally constrained structural variant of MDL 28,170. Compounds 3h and 3l exhibited the most potent μ-calpain inhibitory activities (IC 50 = 0.09-0.10 μM), and were comparable to 2 in this respect (IC50 = 0.07 μM). Compound 3i showed both potent μ-calpain inhibitory activity (IC50 = 0.28 μM) and antioxidant activities in DPPH scavenging and lipid peroxidation inhibition assays.

AB - The overactivation of μ-calpain can cause serious cell damage in several diseases. Furthermore, cell death in a number of neurodegenerative disorders is linked to the overproduction of reactive oxygen species. Therefore, antioxidants and μ-calpain inhibitors could have the therapeutic potentials to treat cell death related diseases. New chromone carboxamide derivatives 3 were synthesized to provide alternative μ-calpain inhibitors to compound 2, a conformationally constrained structural variant of MDL 28,170. Compounds 3h and 3l exhibited the most potent μ-calpain inhibitory activities (IC 50 = 0.09-0.10 μM), and were comparable to 2 in this respect (IC50 = 0.07 μM). Compound 3i showed both potent μ-calpain inhibitory activity (IC50 = 0.28 μM) and antioxidant activities in DPPH scavenging and lipid peroxidation inhibition assays.

KW - Antioxidant

KW - Calpain inhibitor

KW - Cell death

KW - Chromone carboxamide

KW - Neurodegenerative disease

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M3 - Article

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AN - SCOPUS:79953171480

SN - 0223-5234

VL - 46

SP - 1721

EP - 1728

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

IS - 5

ER -

Synthesis of chromone carboxamide derivatives with antioxidative and calpain inhibitory properties

Abstract

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Keywords

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