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

Bioorg Med Chem. 2013 Apr 15;21(8):2271-2285. doi: 10.1016/j.bmc.2013.02.021. Epub 2013 Feb 21.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzimidazoles / chemical synthesis*
  • Benzimidazoles / pharmacology*
  • Cell Line, Tumor
  • Humans
  • Mitogen-Activated Protein Kinase 10 / antagonists & inhibitors*
  • Models, Molecular
  • Neuroblastoma
  • Neuroprotective Agents / chemical synthesis*
  • Neuroprotective Agents / pharmacology*
  • Phosphorylation
  • Protein Kinase Inhibitors / chemical synthesis*
  • Protein Kinase Inhibitors / pharmacology*
  • Structure-Activity Relationship

Substances

  • Benzimidazoles
  • Neuroprotective Agents
  • Protein Kinase Inhibitors
  • Mitogen-Activated Protein Kinase 10