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., ...Daha Fazla

Medicinal Chemistry Research, cilt.26, sa.11, ss.3057-3071, 2017 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 26 Sayı: 11
  • Basım Tarihi: 2017
  • Doi Numarası: 10.1007/s00044-017-2003-x
  • Dergi Adı: Medicinal Chemistry Research
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.3057-3071
  • Anahtar Kelimeler: 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 Üniversitesi Adresli: Evet

Özet

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.