Biological activity of curcumin coordination complexes with second and third-row transition metals

The active components of the turmeric rhizome, primarily curcumin, have demonstrated remarkable pharmacological activity against a wide range of diseases. Among its most notable properties are its anti-Alzheimer’s, anti-arthritic, anti-cancer, antidepressant, anti-diabetic, anti-inflammatory, antimicrobial, anti-osteoporotic, antioxidant, hepatoprotective, neuroprotective, renoprotective, and immunomodulatory activities. Furthermore, curcumin is a highly bioactive natural compound that exhibits multiple biological interactions and therapeutic targets, possesses fluorescent properties, and shows low toxicity even at high doses. However, its medical application is limited by several physicochemical and pharmacokinetic disadvantages, including low solubility and bioavailability, hydrophobicity, rapid metabolism and systemic elimination, and low absorption and high photosensitivity. A promising strategy to overcome these limitations involves coordinating curcumin with metal ions through its β-dicarbonyl fragment, allowing it to act as a bidentate ligand. The formation of metal complexes can improve the solubility, bioavailability, and cellular uptake of curcumin, enhancing its pharmacological, chemopreventive, and therapeutic activities compared to the free molecule and its uncoordinated derivatives. In particular, coordination with second- and third-row transition metals (4d and 5d series) is especially attractive due to the high stability of their complexes under physiological conditions. Numerous curcumin complexes with these metals have been described; however, there is still a notable lack of representatives of some elements, such as molybdenum and osmium. To date, the most studied biomedical applications for these complexes include antibacterial, anticancer, and antifungal activities, although anti-arthritic, anti-inflammatory, anti-osteoporotic, antioxidant, anti-rheumatic, and antiviral properties have also been investigated. Therefore, curcumin complexes with second- and third-row transition metals represent a promising platform for the development of new therapeutic agents, and increasing interest in their study is expected to define their potential preventive and medical applications in the future.