Elucidating anti‐Alzheimer role of 4‐anisaldehyde thiosemicarbazone and its zinc and cadmium complexes: DFT calculation and molecular docking studies

Abstract In this work, the synthesis of 4‐anisaldehyde thiosemicarbazone and its zinc and cadmium complexes, followed by structural characterization using X‐ray powder diffraction and spectroscopic techniques, is reported. Further, density functional theory calculations and molecular docking studies against the Human M1 muscarinic acetylcholine receptor (HM1CR) and the ATP gated P2 × 7 ion channel (AGP2 × 7IC) of Alzheimer's disease are performed. Electronic structure, frontier molecular orbital and molecular electrostatic potential of the molecules have been determined. Further, the drug likeness and ADMET properties of the ligand and two metal complexes have been predicted. The ligand 4‐HAntsc ( 1 ) and the metal complexes [Zn(4‐Antsc) 2 (SO 4 )] ( 2 ) and [Cd(4‐HAnTsc) 2 Cl 2 ] ( 3 ) have O, N, and S as binding atoms which participate in binding and exhibit biological activity. ADMET studies confirm the non‐toxic behavior of the complexes. Molecular docking studies reveal that the zinc complex with a binding energy of −52 kcal/mol is a better inhibitor than the cadmium complex (−50 kcal/mol) against the HM1CR, one of the potential protein receptors involved in Alzheimer's disease. Molecular docking studies confirm that both the zinc and cadmium complexes bind more strongly with Alzheimer's proteins as compared with two standard drugs, Rivastiginin and Donepezil.