Synthesis and in vitro evaluation of novel 1,2,4-triazine derivatives as neuroprotective agents.
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.
Department of Medicinal Chemistry, Faculty of Pharmacy, and Drug Design & Development Research Center, Tehran University of Medical Sciences, Tehran, Iran. ashafiee@ams.ac.ir
Hamid
H
Irannejad
Mohsen
M
Amini
Fariba
F
Khodagholi
Niloufar
N
Ansari
Solaleh Khoramian
SK
Tusi
Mohammad
M
Sharifzadeh
Abbas
A
Shafiee
D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D018696:Neuroprotective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D016716:PC12 Cells; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D014227:Triazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
D016328:NF-kappa B; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D014227:Triazines; C093444:1,2,4-triazine; D006861:Hydrogen Peroxide; D053148:Caspase 3