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

41 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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doi = "10.1016/j.bmc.2013.02.021",

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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

PY - 2013/4/15

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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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M3 - Article

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JO - Bioorganic and Medicinal Chemistry

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ER -

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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