Azo-based multifunctional molecules and their copper(II) complexes as potential inhibitors against Alzheimer's disease: XRD/Hirshfeld analysis/DFT/molecular docking/cytotoxicity

In this article, new azo multifunctional ligands (E)-1-hexyl-4-methyl-6-(λ1-oxidaneyl)-2-oxo-5-(p-tolyldiazenyl)-1,2-dihydropyridine-3-carbonitrile(L1H), (E)-1-hexyl-4-methyl-5-((4-nitrophenyl)diazenyl)-6-(λ1-oxidaneyl)-2-oxo-1,2-dihydropyridine-3-carbonitrile) (L2H) and their copper(II) complexes were prepared and identified using various analytical and spectroscopic techniques such as CHN analysis, IR, mass spectra, UV–Vis, XRD and EPR methods. The spectroscopic data agree with the suggested molecular structures of the Cu(II) complexes. Single-crystal structure demonstrated elongated octahedral for both the copper complexes. In support, EPR exhibits a typical four-line spectral pattern assigned to monomeric copper (II) complexes. Interestingly upon docking with 1EVE, the copper complexes unveiled varying degrees of adjustment upon binding to fit and well-interact with the protease's active site. The hydrogen bonding and hydrophobic interactions entropy directly affect the structural reorganization. Donepezil and our compounds were assessed together for their potential inhibitory against Alzheimer's disease. The binding affinity of the ligand and copper complexes in this research paper with 1EVE ranges from −9.6 to −8.3 kcal/mol. In comparison, the Donepezil drug is −10.9 kcal/mol, suggesting possible successful drugs for Alzheimer's disease. Druglike nature, medicinal chemistry friendliness, and multiple toxicological were predicted using free SwissADME software and the ProTox-II platform for this study.