Synthesis, Spectral Characterization and Theoretical Evaluation of Azo-Metal Complexes for Potential Antioxidant and Anticancer Activities

The synthesis and evaluation of azo-metal complexes derived from m-aminophenol and 2,4-dihydroxyacetophenone were conducted to investigate their antioxidant and anticancer potential. Ligand, 3-(2′,4′-dihydroxy-5-acetylphenylazo)-1-hydroxybenzene (LH2) was synthesized and complexed with Cu(II), Ni(II), Co(II) and Zn(II) ions. The compounds were characterized with different spectroscopic methods, including FTIR, 1H NMR, 13C NMR, ESR, ESI-MS and XRD, along with thermal analysis (TGA/DTA) and SEM-EDS. Antioxidant activity assessed through the DPPH assay revealed that Cu(II) complex showed the highest radical scavenging activity with an IC50 of 13.38 µg/mL, outperforming the free ligand (IC50 = 34.57 µg/mL). Anticancer activity was evaluated against MCF-7 (breast cancer cell line) and HepG2 (liver cancer cell line) cell lines using the MTT assay. Ni(II) and Co(II) complexes demonstrated superior cytotoxicity with IC50 values of 13.48 µg/mL and 14.42 µg/mL, respectively, at 48 h, compared to the standard drug doxorubicin (IC50 = 10.31 µg/mL). Molecular docking studies against 17-β-HSD1 indicated strong binding affinities, particularly for Ni(II) complex (-9.81 kcal/mol), attributed to favourable coordination and electronic properties. Computational analyses, including molecular dynamics simulations and HOMO-LUMO energy evaluations, highlighted the stability, reactivity and interaction potential of the metal complexes. ADME profiling confirmed their drug-likeness, with Cu(II) and Ni(II) complexes showing promising pharmacokinetic attributes, including high gastrointestinal absorption and blood-brain barrier permeability.