Synthesis and neuroprotective activity of novel 1,2,4-triazine derivatives with ethyl acetate moiety against H 2 O2 and Aβ-induced neurotoxicity
- 258 Downloads
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.
KeywordsSynthesis 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.
- Koh SH, Kim SH, Kwon H, Park Y, Kim KS, Song CW, Kim J, Kim MH, Yu HJ, Henkel JS, Jung HK (2003) Epigallocatechin gallate protects nerve growth factor differentiated PC12 cells from oxidative-radical-stress-induced apoptosis through its effect on phosphoinositide 3-kinase/Akt and glycogen synthase kinase-3. Brain Res Mol Brain Res 118:72–81CrossRefPubMedGoogle Scholar
- Ozadali-Sari K, Tüylü Küçükkılınç T, Ayazgok B, Balkan A, Unsal-Tan O (2017) Novel multi-targeted agents for Alzheimer’s disease: Synthesis, biological evaluation, and molecular modeling of novel 2-[4-(4-substitutedpiperazin-1-yl)phenyl]benzimidazoles. Bioorg Chem 72:208–214CrossRefPubMedGoogle Scholar
- Sinha A, Tamboli RS, Seth B, Kanhed AM, Tiwari SK, Agarwal S, Nair S, Giridhar R, Chaturvedi RK, Yadav MR (2015) Neuroprotective role of novel triazine derivatives by activating Wnt/β catenin signaling pathway in rodent models of alzheimer’s disease. Mol Neurobiol 52:638–652CrossRefPubMedGoogle Scholar