Efficient synthesis and first regioselective C-6 direct arylation of imidazo[2,1-c][1,2,4]triazine scaffold and their evaluation in H2O2-induced oxidative stress

Eur J Med Chem. 2018 Feb 10:145:113-123. doi: 10.1016/j.ejmech.2017.12.081. Epub 2017 Dec 27.

Abstract

Oxidative stress and apoptosis are both associated with various acute and chronic disorders. Thus, the aim of the present study is to synthesize imidazo[2,1-c][1,2,4]triazines derivatives and to evaluate their effects in H2O2-induced oxidative stress in human neuroblastoma cell line (SH-SY5Y cells). The effects of the compounds on cell viability were measured by MTT assay and the changes in stress and apoptosis-related proteins were investigated by PathScan® Stress and Apoptosis Signaling Antibody Array kit and Western Blot technique. In particular, four compounds were found to protect SH-SY5Y cells from H2O2-induced toxicity by increasing Bcl-2/Bax ratio, regulating PI3-K/Akt cascade and inhibiting the ERK pathway.

Keywords: Akt signaling; Apoptosis; CH arylation; Cyclocondensation; Oxidative stress; Regioselective; imidazo[2,1-c][1,2,4]triazines.

MeSH terms

  • Apoptosis / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Humans
  • Hydrogen Peroxide / antagonists & inhibitors*
  • Hydrogen Peroxide / pharmacology
  • Imidazoles / chemical synthesis
  • Imidazoles / chemistry
  • Imidazoles / pharmacology*
  • Molecular Structure
  • Oxidative Stress / drug effects
  • Stereoisomerism
  • Structure-Activity Relationship
  • Triazines / chemical synthesis
  • Triazines / chemistry
  • Triazines / pharmacology*
  • Tumor Cells, Cultured

Substances

  • Imidazoles
  • Triazines
  • Hydrogen Peroxide