Design, Synthesis, Anticancer Evaluation, and EGFR-Targeted Molecular Docking of Novel...

A new series of 4-(benzylidenehydrazone)-3-nitropyridine derivatives (MVK8-1 to MVK8-14) was synthesized via condensation of 4-hydrazinyl-3-nitropyridine with substituted aromatic aldehydes using acetic acid as an efficient and green catalyst. The anticancer potential of all derivatives was evaluated in vitro against MCF7 (breast), A549 (lung), and HepG2 (liver) cancer cell lines. Several compounds exhibited significant cytotoxic activity, with MVK8-9 showing the highest potency against A549 cells (IC₅₀ = 2.5 µM), MVK8-10 against MCF7 cells (IC₅₀ = 4.78 µM), and MVK8-3 against HepG2 cells (IC₅₀ = 3.712 µM). Molecular docking studies against wild-type and mutant EGFR structures (PDB IDs: 5D41, 6LUD, and 4I23) revealed strong binding affinities for key compounds, particularly MVK8-11, which showed consistent interactions across all EGFR variants with binding energies up to -7.401 kcal/mol. ADME predictions indicated that most compounds complied with Lipinski's Rule of Five and Jorgensen's Rule of Three, suggesting favorable oral bioavailability, permeability, and drug-likeness, except MVK8-12, which displayed poor pharmacokinetic properties.