Medicinal Chemistry Research

, Volume 26, Issue 11, pp 3057–3071 | Cite as

Synthesis and neuroprotective activity of novel 1,2,4-triazine derivatives with ethyl acetate moiety against H 2 O2 and Aβ-induced neurotoxicity

  • Tuba Tuylu Kucukkilinc
  • Kamaledin Safari Yanghagh
  • Beyza Ayazgok
  • Mohammad Ali Roknipour
  • Farshad Homayouni Moghadam
  • Alireza Moradi
  • Saeed Emami
  • Mohsen Amini
  • Hamid IrannejadEmail author
Original Research


A series of 5,6-diaryl-1,2,4-triazine-3-thioacetate derivatives 3af, 8ad and their regioisomer 8e were synthesized. Neuroprotective activity of compounds was assessed against H2O2 and β-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 µM 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 β-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.


Synthesis 1,2,4-triazine Alzheimer’s disease Apoptosis Neuroprotective activity 



This research was supported by grant from the Research Council of Mazandaran University of Medical Sciences. This study is related to the Pharm.D thesis of K. Safari Yanghagh and M.A. Roknipour.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Supplementary material

44_2017_2003_MOESM1_ESM.pdf (1.4 mb)
Supplementary Information


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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Tuba Tuylu Kucukkilinc
    • 1
  • Kamaledin Safari Yanghagh
    • 2
  • Beyza Ayazgok
    • 1
  • Mohammad Ali Roknipour
    • 2
  • Farshad Homayouni Moghadam
    • 3
  • Alireza Moradi
    • 4
  • Saeed Emami
    • 5
  • Mohsen Amini
    • 6
  • Hamid Irannejad
    • 5
    Email author
  1. 1.Department of Biochemistry, Faculty of PharmacyHacettepe UniversityAnkaraTurkey
  2. 2.Student Research Committee, Faculty of PharmacyMazandaran University of Medical SciencesSariIran
  3. 3.Department of Cellular Biotechnology at Cell Science Research CenterRoyan Institute for Biotechnology, ACECRIsfahanIran
  4. 4.Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research CenterShahid Sadoughi Yazd University of Medical SciencesYazdIran
  5. 5.Department of Medicinal Chemistry, Pharmaceutical Sciences Research Center, Faculty of PharmacyMazandaran University of Medical SciencesSariIran
  6. 6.Department of Medicinal Chemistry, Drug Design & Development Research Center, Faculty of PharmacyTehran University of Medical SciencesTehranIran

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