Integrating experimental and computational approaches to explore the anticancer potential of a pyridine-based reduced Schiff base.

This study reports the design, synthesis, and comprehensive evaluation of a pyridine-based reduced Schiff base, 2-methoxy-5-methyl-N-(pyridin-2-ylmethyl) aniline (RSB), for its anticancer activity. The molecular structure was confirmed by spectroscopic techniques and single-crystal X-ray diffraction (CCDC: 2419398). Significant hydrogen bonding and π-interactions stabilising the crystal packing were found by Single Crystal XRD and Hirshfeld surface analysis. Compared with cisplatin (IC50 = 27.28 μg/mL), RSB exhibited moderate dose-dependent cytotoxicity with an IC50 of 161.27 μg/mL against the A549 lung carcinoma cell line. Molecular dynamics simulations verified stable and compact binding conformations, which supported the strong binding affinities of RSB toward 1MRV proteins (-7.1 kcal/mol) found in in-silico docking studies. A HOMO-LUMO gap of 6.70 eV was found by DFT analysis, demonstrating the electronic stability of the molecule. All of these results point to the potential of pyridine-based reduced Schiff bases as anticancer agents, indicating the need for additional research and optimisation.