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Synthesis and Neuroprotective Activity of Novel 1,2,4-Triazine Derivatives With Ethyl Acetate Moiety Against H2o2 and Aβ-Induced Neurotoxicity Publisher



Tuylu Kucukkilinc T1 ; Safari Yanghagh K2 ; Ayazgok B1 ; Ali Roknipour M2 ; Homayouni Moghadam F3 ; Moradi A4 ; Emami S5 ; Amini M6 ; Irannejad H5
Authors
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Authors Affiliations
  1. 1. Department of Biochemistry, Faculty of Pharmacy, Hacettepe University, Sihhiye, Ankara, 06100, Turkey
  2. 2. Student Research Committee, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran
  3. 3. Department of Cellular Biotechnology at Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran
  4. 4. Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Shahid Sadoughi Yazd University of Medical Sciences, Yazd, Iran
  5. 5. Department of Medicinal Chemistry, Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran
  6. 6. Department of Medicinal Chemistry, Drug Design & Development Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

Source: Medicinal Chemistry Research Published:2017


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 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. © 2017, Springer Science+Business Media, LLC.