Synthesis and biological evaluation of 1,2,4-triazoloazines as potent anticancer agents

Abstract

The present study successfully synthesized 16 new derivatives of mono- and bis-1,2,4-triazoloazines through the condensation of mono- and dihydrazinylazines with (heteroaryl)carbaldehydes 6 followed by the oxidative cyclization of mono- and bis-azinylhydrazones in the presence of hypervalent iodine(III). The yields of these compounds ranged from 14% to 84%. The structural identification of the synthesized compounds was confirmed by elemental analyses, infrared spectroscopy (IR), and proton and carbon nuclear magnetic resonance spectroscopy (¹H-NMR and ¹³C-NMR) and mass spectrometry. The cytotoxic activity of the compounds 8, 12, and 14 obtained was evaluated against the cancer cell lines MCF7, DLD-1, and A549. Furthermore, the selectivity of the toxic effect of these triazoloazines on human dermal fibroblasts (DF-2) was studied. The semilethal concentration of each compound was determined after 24 hours of incubation for each cell line. The results showed that some of the new mono- and bis-1,2,4-triazoloazine derivatives exhibited significant toxicity towards tumor cells while having minimal effects on normal non-tumor fibroblasts. This selective cytotoxicity suggests the potential of these compounds as anticancer agents with reduced side effects on healthy cells.