Crystal structural characterization, molecular docking and ADMET analysis of new Cu(II) Schiff base complexes: Antiviral properties against SARS-CoV-2 and HPV

We synthesized and characterized two new mixed-ligand Cu(II) complexes: [Cu(SB¹)(py)]ClO₄ and [Cu(SB²)]ClO₄. The SB¹ ligand is a tridentate N₂O-type unsymmetrical Schiff base formed from the condensation of one amino group of 2,2-dimethyl-1,3-propanediamine with salicylaldehyde. In contrast, the tetradentate N₃O-type SB² is derived from further condensation of the remaining amino group with methyl-2-pyridyl ketone. The crystal structure of [Cu(SB²)]ClO₄ was confirmed via single-crystal X-ray crystallography (SCXRC). Molecular docking and ADMET analyses were employed to evaluate the interactions of these complexes and their Schiff base ligands with proteins associated with SARS-CoV-2 (PDB ID: 6LU7) and Human Papillomavirus (HPV, PDB ID: 4XR8). Additionally, the antiviral drugs famciclovir (for HPV) and baricitinib (for SARS-CoV-2) were included for comparison. The molecular docking results revealed that [Cu(SB¹)(py)]ClO₄ exhibited significant binding affinity, indicated by higher negative estimated free binding energy (EFBE) values with 6LU7 and the dimer form of [Cu(SB²)]ClO₄ shows the best performance with 4XR8. In silico ADMET assessments suggest that these complexes and their corresponding Schiff base ligands possess favorable drug-like properties, highlighting their potential as therapeutic candidates.