Evaluating the in vitro antidiabetic, antibacterial and antioxidant properties of copper(II) Schiff base complexes: An experimental and computational studies

In recent years, metal-based compounds have been explored as potential remedies for major health issues such as diabetes, bacterial infections, and oxidative stress, which impact the general well-being of humans globally. Diabetes, bacterial infections, and oxidative stress are major health concerns affecting millions worldwide. Researchers have been exploring the use of metal-based compounds as potential treatments for these conditions. In our quest towards identifying biologically viable metal-based compounds, three novel Cu(II) complexes were synthesized from halogen-substituted ON donor Schiff base ligands. These ligands were obtained by condensing 2-hydroxybenzldehyde with three different halogen-substituted anilines. The ligands and their complexes were characterized using various spectroscopic techniques such as 1H and 13C nuclear magnetic resonance, Fourier Transform-Infrared, Ultraviolet-visible spectra, elemental analysis, mass spectrometry, and single-crystal X-ray spectroscopy to elucidate their structures. The compounds were screened for antidiabetic (& alpha;-glucose and & alpha;-amylase enzymes inhibition assay), antioxidant (2,2-diphenyl-1-picrylhydrazyl(DPPH), ferric reducing antioxidant potential (FRAP) assay, and nitric oxide(NO) radical scavenging), and antimicrobial activities. The pharmacological activity revealed that the efficacy of the ligands was enhanced upon coordination, and CuL3 is more potent among the complexes, having higher inhibition activity on & alpha;-glucosidase (IC50 = 100.1 & mu;M) than the control, whose IC50 is 112.4 & mu;M on the same enzyme. For radical scavenging activity, the results showed that the complexes have higher scavenging activity on DPPH radicals than their ligands and the control. For the FRAP assay, the complexes show higher activity than their ligands. Similarly, NO radical scavenging activity results indicate the ligands have higher activity than their complexes, while the complexes outperformed the control at all concentrations tested. The In vitro antibacterial results on some selected Gram-positive and Gram-negative bacteria revealed the complexes have higher antibacterial activity than their corresponding ligands, with CuL3 taking the lead, showing a MIC value of 4 g/mL on some of the bacteria tested. Also, density functional theory calculations at different levels of DFT and basis sets were used to investigate the optimized geometry, electronic structure (energy of HOMO and LUMO, Mulliken atomic charge, dipole moment, hardness, and softness, electrophilicity, and spectral properties) of the synthesized compounds. Molecular docking studies were carried out to investigate the binding affinity of the receptor proteins to other proteins and to establish the mechanism of action at the active sites.