Designing coumarin-acenaphthenequinone metal complexes as dual therapeutic scaffolds: insights from bioassays and molecular docking

In recent years, metallodrugs have garnered considerable attention as potential therapeutic agents for cancer treatment and diabetes management. In this study, a novel Schiff base ligand, 3,3′-(((1E,2E)-acenaphthylene-1,2-diylidene)bis(azaneylylidene))bis(2H-chromen-2-one) (L), and its Mn(II) (1), Co(II) (2), Ni(II) (3), Cu(II) (4), and Zn(II) (5) complexes were synthesized and characterized. Spectral and magnetic moment data suggest octahedral geometries for complexes 1–4, whereas complex 5 adopts a tetrahedral geometry. Biological evaluation showed that the Cu(II) complex (4) exhibited remarkable antidiabetic activity, with IC50 values of 18.00 ± 0.26 μM (α-glucosidase) and 38.27 ± 0.23 μM (α-amylase), surpassing the standard drug acarbose. Anticancer studies against the MCF-7 breast cancer cell line demonstrated that the metal complexes possessed strong cytotoxic effects, with IC50 values below 10 μM, comparable to the reference drug Adriamycin (<10 ± 3.0 μM). Furthermore, Cu(II) and Zn(II) complexes exhibited superior antioxidant activity. DNA cleavage experiments using pBR322 plasmid DNA confirmed the efficient nuclease activity of the complexes. Molecular docking studies with the human estrogen receptor revealed high binding affinities, particularly for Cu(II) and Ni(II) complexes (−10.6 kcal mol−1), which exceeded that of adriamycin (−7.8 kcal mol−1). ADMET predictions suggested favorable pharmacokinetic profiles, highlighting these complexes as promising candidates for further pharmacological development.