Unveiling the multifaceted bioactivity of copper(ii)–Schiff base complexes: a comprehensive study of antioxidant, anti-bacterial, anti-inflammatory, enzyme inhibition and cytotoxic potentials with DFT insights

Abstract

The rise of various diseases demands the development of new agents with antioxidant, antimicrobial, anti-inflammatory, enzyme-inhibiting, and cytotoxic properties. In this study, heterocyclic Schiff base complexes of Cu(II) featuring a benzo[b]thiophene moiety were synthesized and their biological activities evaluated. The complexes were characterized using FT-IR, UV-Vis, and EPR spectroscopy, TG–DTG analysis, magnetic moment measurements, molar conductivity measurements, and elemental analyses. Density functional theory (DFT) calculations were used to optimize the theoretical molecular orbital energies of the copper complexes. The complexes exhibited square pyramidal and square planar geometries. Biological assays demonstrated that these complexes generally outperformed the Schiff base ligands for various activities. The antioxidant capacity, measured via the DPPH assay in methanol, was comparable to those of the BHT and ascorbic acid standards, with 4BNPC showing the lowest IC₅₀ value, which was attributed to the free OH group rather than coordination to the metal center. The anti-bacterial activity was assessed using the agar disc diffusion method against E. coli, P. aeruginosa, B. subtilis, and S. aureus, with BAC showing the largest inhibition zone compared to the others and ciprofloxacin as the reference. The anti-inflammatory activity, evaluated by the HRBC membrane stabilization method, showed that the 4BNPC Cu(II) complex had moderate activity similar to that of diclofenac. Enzyme inhibition studies against α-amylase revealed that the BAC complexes had the highest inhibition values, surpassing those of the Schiff base ligands. Cytotoxicity was assessed using Trypan blue exclusion for DLA and HepG2 cancer cell lines, and the MTT assay for H9c2 human cells. BMPC demonstrated superior cytotoxicity at both high and low concentrations against the normal H9c2 cell line. Among the tested compounds, BNPC showed moderate inhibition against HepG2 cells, while BMPC exhibited the greatest cytotoxicity at higher concentrations, particularly reaching nearly 100% cell death at 200 μg mL⁻¹ in DLA cell lines. This suggests that BMPC is a promising candidate for further pharmacological research, particularly against DLA cells.