Synthesis and in vitro evaluation of novel 1,2,4-triazine derivatives as neuroprotective agents

Bioorg Med Chem. 2010 Jun 15;18(12):4224-30. doi: 10.1016/j.bmc.2010.04.097. Epub 2010 May 8.

Abstract

The role of novel triazine derivatives against oxidative stress exerted by hydrogen peroxide on differentiated rat pheochromocytoma (PC12) cell line was examined and a consistent protection from H(2)O(2)-induced cell death, associated with a marked reduction in caspase-3 activation, was observed. Moreover, activation of NF-kappaB, a known regulator of a host of genes that involves in specific stress and inflammatory responses by H(2)O(2), was greatly impaired by triazine pretreatment in differentiated PC12 cells. Neuroprotective effect of such compounds may represent a promising approach for treatment of neurodegenerative diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caspase 3 / metabolism
  • Hydrogen Peroxide / pharmacology
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism
  • Neuroprotective Agents / chemical synthesis*
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / pharmacology
  • Oxidative Stress / drug effects
  • PC12 Cells
  • Rats
  • Reactive Oxygen Species / metabolism
  • Triazines / chemical synthesis
  • Triazines / chemistry*
  • Triazines / pharmacology

Substances

  • NF-kappa B
  • Neuroprotective Agents
  • Reactive Oxygen Species
  • Triazines
  • 1,2,4-triazine
  • Hydrogen Peroxide
  • Caspase 3