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

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.