Abstract

In this work, 1,2,4-triazine derivatives were synthesized and evaluated for anticancer activities. Series of 1,2,4-triazine derivatives (4a, b) were prepared via the reaction of N-benzoyl glycine (1) with aromatic aldehydes in the presence of fused sodium acetate and acetic anhydride to give 1,3- oxazolinone derivatives (2a, b), followed by condensation with 1-(ethoxycarbonyl) hydrazine (3) in glacial acetic acid. Compounds (4a, b) then reacted with acetic anhydride, ethyl chloroacetate and 2,4- dinitrophenyl hydrazine yielded the corresponding N-acetyl derivatives (5a, b), N-(ethoxycarbonyl) methyl derivative (6) and 1,2-disubstituted hydrazine (7), respectively. The structures of the 1,2,4- triazine derivatives were confirmed by IR, ¹H, ¹³C NMR, MS, and elemental analyses. Anticancer activity of some 1,2,4-triazine derivatives (4-7) has been investigated. The results revealed that compounds 4a (IC50= 2.7μM), 5a (IC50= 1.5μM), and 5b (IC50= 3.9μM) show promising inhibitory growth efficacy compared to a standard antitumor drug (IC50= 4.6μM). These three compounds can be considered as potential agents against human hepatocellular carcinoma cell lines (HepG-2).

Keywords: Cell lines, triazine, antitumor activity, liver cancer, vinblastine, HePG-2, IC₅₀, aromatic aldehydes, benzoyl glycine.

Graphical Abstract