Design and Bio Evaluation of Schiff Base and Their Metal Complexes: A Green Route to Potential Anticancer Agents

The present study reports the successful synthesis and characterization of a new Schiff base ligand using a natural acid catalyst and its transition metal complexes. The synthesized ligand was comprehensively characterized using advanced physicochemical techniques, including liquid chromatography-mass spectrometry (LC-MS), Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and ¹H and ¹³C nuclear magnetic resonance (NMR) spectroscopy. Subsequently, these Schiff base was complexed with various transition metals to generate innovative metal complexes. The resulting complexes were further analyzed through IR spectroscopy, confirming coordination and structural features. <i>In-vitro</i> cytotoxicity studies demonstrated that the complexes showed strong anticancer activity against the A549 lung carcinoma cell line, with significantly higher inhibition than the ligand alone. Among the synthesized derivatives, compound 4b exhibited the strongest anticancer activity with the lowest IC₅₀ value (84.71 μM). Antimicrobial evaluation further revealed broad-spectrum activity, particularly against Gram-negative bacteria. Among all tested derivatives, compound 4i demonstrated the highest antibacterial activity, showing the largest zones of inhibition across multiple bacterial strains compared to the other compounds. <i>In-silico</i> docking analysis supported these experimental findings by indicating favorable binding interactions and drug-likeness profiles. Based on the DFT results, compound 4b exhibited the highest HOMO-LUMO energy gap (Δ<i>E</i> = 8.75 eV) and the lowest IC₅₀ (IC₅₀ = 84.71 μM) value, indicating superior molecular stability and the strongest biological activity among the tested derivatives. Overall, the study establishes that Schiff base-metal complexes possess superior anticancer and antimicrobial potential, highlighting them as promising scaffolds for future therapeutic development.