MATERIALS & METHODS: The Schiff base ligand was synthesized by refluxing isatin and thiosemicarbazide for 3 hours. Complexes 2 and 3 were formed and characterized using elemental analysis, molar conductivity, IR, NMR, and UV-Visible spectroscopy. The geometry of complex 3 was determined via X-ray diffraction. Theoretical calculations were conducted using DFT with the hybrid GEN B3LYP method. Molecular docking was performed to assess binding energies with EGFR, and anticancer activity was evaluated against the A549 cell line.

RESULTS: Characterization confirmed successful synthesis of the compounds. Zinc complexation led to notable spectral shifts, and X-ray diffraction revealed complex 3 adopted a distorted tetrahedral geometry. DFT analysis highlighted complex 2 with the lowest energy gap (0.331 eV). Docking results showed strong EGFR binding energies (-5.70, -5.54, and -7.30 kcal/mol). Complex 2 demonstrated the highest anticancer efficacy with a cell viability of 1.35% after 48 h.

METHODS: The synthesized compounds were evaluated for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory potential by modified Ellman's method. The molecular interactions between the most active compound and the enzyme were analyzed by molecular docking.

RESULTS: Among them, 3j displayed higher inhibitory activities than reference drug, galanthamine, with IC50 values of 2.05 and 5.77 µM, for AChE and BChE, respectively. Interestingly, all the compounds except 3b displayed higher BChE inhibitions than galanthamine with IC50 values ranging from 5.77 to 18.52 µM. Molecular docking of compound 3j inside the TcAChE and hBChE completely coincided with the inhibitory activities observed. The compound forms strong hydrogen bonding at the peripheral anionic site of AChE whereas on BChE, it had hydrophobic and mild polar interactions.