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.
authors.affiliation: Department of Pharmacy, College of Pharmacy, Hanyang University, 1271 Sa 3-Dong, Sangnok-gu, Ansan-si, Gyunggi-do 426-791, Republic of Korea.
authors.forename: Mi-Hyun
authors.initials: MH
authors.lastname: Kim
authors.affiliation: Department of Pharmacy, College of Pharmacy, Hanyang University, 1271 Sa 3-Dong, Sangnok-gu, Ansan-si, Gyunggi-do 426-791, Republic of Korea.
authors.forename: Junghun
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Pharmacy, College of Pharmacy, Hanyang University, 1271 Sa 3-Dong, Sangnok-gu, Ansan-si, Gyunggi-do 426-791, Republic of Korea.
authors.forename: Kyungjin
authors.initials: K
authors.lastname: Jung
authors.affiliation: Department of Pharmacy, College of Pharmacy, Hanyang University, 1271 Sa 3-Dong, Sangnok-gu, Ansan-si, Gyunggi-do 426-791, Republic of Korea.
authors.forename: Minjung
authors.initials: M
authors.lastname: Kim
authors.affiliation: Department of Food and Nutrition, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul 151-742, Republic of Korea.
authors.forename: Yun-Jin
authors.initials: YJ
authors.lastname: Park
authors.affiliation: Department of Pharmacy, Dongguk University, 32 Dongguk-ro, Ilsandong-gu, Goyang, Geonggi 410-820, Republic of Korea.
authors.forename: Heechul
authors.initials: H
authors.lastname: Ahn
authors.affiliation: Department of Food and Nutrition, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul 151-742, Republic of Korea.
authors.forename: Young Hye
authors.initials: YH
authors.lastname: Kwon
authors.affiliation: Department of Pharmacy, College of Pharmacy, Hanyang University, 1271 Sa 3-Dong, Sangnok-gu, Ansan-si, Gyunggi-do 426-791, Republic of Korea. Electronic address: jhah@hanyang.ac.kr.
authors.forename: Jung-Mi
authors.initials: JM
authors.lastname: Hah
mesh_terms: D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006801:Humans; D048057:Mitogen-Activated Protein Kinase 10 / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D009447:Neuroblastoma; D018696:Neuroprotective Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D001562:Benzimidazoles; D018696:Neuroprotective Agents; D047428:Protein Kinase Inhibitors; D048057:Mitogen-Activated Protein Kinase 10