Targeting A549 cells: the synthesis and multi-omic characterization of a high-affinity hydrazone derivative

A novel hydrazone derivative, (E)-N'-(1-(4-(piperidin-1-yl) phenyl) ethylidene) benzohydrazide, was synthesized using an ultrasound-assisted method and characterized by FT-IR, ¹H NMR, and ¹³C NMR spectroscopy. DFT studies performed on the Rowan platform at the r²SCAN-D4/vDZP level revealed a stable molecular geometry with a HOMO-LUMO energy gap value of 2.63 eV to support the statement on balanced reactivity and stability. The moderate energy gap indicates that the compound possesses both reasonable molecular stability and favorable chemical reactivity. Molecular docking against the target protein (2YCF) showed strong binding affinity (- 7.9 kcal/mol). The compound also demonstrated promising anticancer activity against A549 lung cancer cells with an IC₅₀ value of 9.17 µM, accompanied by increased ROS generation and reduced mitochondrial membrane potential, indicating apoptosis induction. These results suggest that the synthesized hydrazone derivative may serve as a potential anticancer candidate.

The online version contains supplementary material available at 10.1007/s40203-026-00678-5.