Synthesis and neuroprotective activity of novel 1,2,4-triazine derivatives with ethyl acetate moiety against H2O2 and Aβ-induced neurotoxicity

Kucukkilinc T. T., Yanghagh K. S., AYAZGÖK B., Roknipour M. A., Moghadam F. H., Moradi A., ...More

Medicinal Chemistry Research, vol.26, no.11, pp.3057-3071, 2017 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 26 Issue: 11
  • Publication Date: 2017
  • Doi Number: 10.1007/s00044-017-2003-x
  • Journal Name: Medicinal Chemistry Research
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.3057-3071
  • Keywords: Synthesis, 1,2,4-triazine, Alzheimer's disease, Apoptosis, Neuroprotective activity, INDUCED NEURONAL APOPTOSIS, ALZHEIMERS-DISEASE, AMYLOID-BETA, TRIAZINE DERIVATIVES, PC12 CELLS, INHIBITORS, AGENTS, EXPRESSION, PATHWAY, PROTEIN
  • Hacettepe University Affiliated: Yes

Abstract

A series of 5,6-diaryl-1,2,4-triazine-3-thioacetate derivatives 3a-f, 8a-d and their regioisomer 8e were synthesized. Neuroprotective activity of compounds was assessed against H2O2 and beta-amyloid-induced toxicity in PC12 and SH-SY5Y cells respectively. Surprisingly, ethyl 2-(5-(4-chlorophenyl)-6-(4-methoxyphenyl)-3-thioxo-1,2,4-triazin-2(3H)-yl)acetate (8e) was the most potent compound in both tests with EC50 of 14 mu M in H2O2 induced apoptosis and also could increase 40% of cell viability revealed by cytometric analysis with Annexin V/PI staining. It was also shown that regioisomer 8e has more neuroprotective activity than Quercetin in beta-amyloid induced toxicity. Morphologic evaluation of cells by DAPI staining and TUNEL assay showed the effectiveness of this compound to improve neurite outgrowth in neuronal cells.