Syntheses and biological evaluation of 1-heteroaryl-2-aryl-1H-benzimidazole derivatives as c-Jun N-terminal kinase inhibitors with neuroprotective effects

Mi Hyun Kim; Junghun Lee; Kyungjin Jung; Minjung Kim; Yun Jin Park; Heechul Ahn; Young Hye Kwon; Jung Mi Hah

doi:10.1016/j.bmc.2013.02.021

Syntheses and biological evaluation of 1-heteroaryl-2-aryl-1H-benzimidazole derivatives as c-Jun N-terminal kinase inhibitors with neuroprotective effects

Mi Hyun Kim, Junghun Lee, Kyungjin Jung, Minjung Kim, Yun Jin Park, Heechul Ahn, Young Hye Kwon, Jung Mi Hah

Department of Pharmacy

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

36 Scopus citations

Abstract

1-Heteroaryl-2-aryl-1H-benzimidazole derivatives were synthesized as inhibitors of c-Jun N-terminal kinases, JNK3. Their activities were evaluated through measurement of K_d using SPR, JNK3 kinase assay, and cell-viability of human neuroblastoma cells. Most tested compounds showed high affinity (10 μM-46 nM) to JNK3. Among them, compound 16f exhibited potent activities (K_d = 46 nM). Especially, 16f was also found to present a potent cell protective effect (IC₅₀ = 1.09 μM) against toxicity induced by anisomycin, showing a possibility as protective therapeutics in neuronal cell apoptosis.

Original language	English
Pages (from-to)	2271-2285
Number of pages	15
Journal	Bioorganic and Medicinal Chemistry
Volume	21
Issue number	8
DOIs	https://doi.org/10.1016/j.bmc.2013.02.021
State	Published - 15 Apr 2013

Keywords

Benzimidazole
JNK
Kinase inhibitor
Neuroblastoma cell line
Neurodegenerative disease
Neuroprotective effect

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10.1016/j.bmc.2013.02.021

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title = "Syntheses and biological evaluation of 1-heteroaryl-2-aryl-1H-benzimidazole derivatives as c-Jun N-terminal kinase inhibitors with neuroprotective effects",

abstract = "1-Heteroaryl-2-aryl-1H-benzimidazole derivatives were synthesized as inhibitors of c-Jun N-terminal kinases, JNK3. Their activities were evaluated through measurement of Kd using SPR, JNK3 kinase assay, and cell-viability of human neuroblastoma cells. Most tested compounds showed high affinity (10 μM-46 nM) to JNK3. Among them, compound 16f exhibited potent activities (Kd = 46 nM). Especially, 16f was also found to present a potent cell protective effect (IC50 = 1.09 μM) against toxicity induced by anisomycin, showing a possibility as protective therapeutics in neuronal cell apoptosis.",

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author = "Kim, {Mi Hyun} and Junghun Lee and Kyungjin Jung and Minjung Kim and Park, {Yun Jin} and Heechul Ahn and Kwon, {Young Hye} and Hah, {Jung Mi}",

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AU - Kim, Mi Hyun

AU - Lee, Junghun

AU - Jung, Kyungjin

AU - Kim, Minjung

AU - Park, Yun Jin

AU - Ahn, Heechul

AU - Kwon, Young Hye

AU - Hah, Jung Mi

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AB - 1-Heteroaryl-2-aryl-1H-benzimidazole derivatives were synthesized as inhibitors of c-Jun N-terminal kinases, JNK3. Their activities were evaluated through measurement of Kd using SPR, JNK3 kinase assay, and cell-viability of human neuroblastoma cells. Most tested compounds showed high affinity (10 μM-46 nM) to JNK3. Among them, compound 16f exhibited potent activities (Kd = 46 nM). Especially, 16f was also found to present a potent cell protective effect (IC50 = 1.09 μM) against toxicity induced by anisomycin, showing a possibility as protective therapeutics in neuronal cell apoptosis.

KW - Benzimidazole

KW - JNK

KW - Kinase inhibitor

KW - Neuroblastoma cell line

KW - Neurodegenerative disease

KW - Neuroprotective effect

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Syntheses and biological evaluation of 1-heteroaryl-2-aryl-1H-benzimidazole derivatives as c-Jun N-terminal kinase inhibitors with neuroprotective effects

Abstract

Keywords

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