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


Loubıdı M., Jouha J., Tber Z., Khouılı M., Suzenet F., Akssıra M., ...More

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, vol.145, pp.113-123, 2018 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 145
  • Publication Date: 2018
  • Doi Number: 10.1016/j.ejmech.2017.12.081
  • Title of Journal : EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
  • Page Numbers: pp.113-123
  • Keywords: Oxidative stress, Apoptosis, Akt signaling, imidazo[2,1-c][1,2,4]triazines, C-H arylation, Regioselective, Cyclocondensation, CELL-DEATH, HYDROGEN-PEROXIDE, APOPTOSIS, DERIVATIVES, ACTIVATION, AUTOPHAGY, SURVIVAL, KINASE, BCL-2, H2O2

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 MIT assay and the changes in stress and apoptosis-related proteins, were investigated by PathScae (R) 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/Alct cascade and inhibiting the ERK pathway. (C) 2017 Published by Elsevier Masson SAS.