Redox-active first-row transition metal complexes of metformin: Structure, DNA binding and therapeutic potential

Abstract

Metformin (Met), a widely prescribed antidiabetic drug, has gained growing attention in oncology because of its dual roles in metabolic regulation and metal coordination. Its biguanide moiety offers a flexible chelating framework to form stable complexes with transition metals, influencing their redox potential and biological behaviour. In such systems, the metal centre dictates redox characteristics and geometry, while Met enhances aqueous solubility and biomolecular recognition. These synergistic features make metal-metformin complexes promising scaffolds for anticancer drug development through DNA/protein binding and cleavage activities. This review focuses on complexes of Met with bio-relevant first-row transition metals, particularly chromium (Cr), cobalt (Co), copper (Cu) and nickel (Ni), which have attracted increasing interest over the years, while also briefly addressing comparatively less explored Mn-, Fe- and Zn-based systems to highlight current limitations and future prospects. Consistent with their coordination geometries and electronic configurations, most reported complexes exhibit groove-type DNA binding. Here, we summarize recent progress in the synthesis, structural characterization and biological evaluation of these systems, highlighting how metal coordination modulates Met’s properties toward the rational design of redox-active metallodrugs with anticancer therapeutic potential.