Innovative Approaches in the Synthesis and Optimization of Copper Complexes for Antitumor Therapies: A Comprehensive Review

Abstract

Cancer is the second leading cause of death worldwide. Late diagnosis, low drug selectivity, high toxicity, and treatment resistance are challenges associated with pharmacological interventions. The commonly used therapies include surgery, radiotherapy, hormonal therapy, immunotherapy, and chemotherapy. Recently, Cu complexes have been studied owing to their biological functions and effects on tumor angiogenesis. In this review, we examined 23 types of cancer and revealed the use of cell lines. The synthesis of Cu complexes with ligands such as phenanthroline and thiosemicarbazones has also been reported. Such co-ligation is promising because of its high cytotoxicity and selectivity. Compared with cisplatin, Cu complexes, especially mixed complexes, showed better interactions with DNA, generating reactive oxygen species and inducing apoptosis. Nanoformulations have also been adopted to improve the pharmacological activity of compounds. They enhance the efficacy of complexes by targeting them to the tumor tissue, thereby improving their safety. Studies have also explored Cu complexes with clinically relevant pharmacophores, suggesting a "hybrid chemotherapy" against resistant tumors. Overall, Cu complexes have demonstrated therapeutic versatility, antitumor efficacy, and reduced adverse effects, showing great potential as alternatives to conventional chemotherapy and justifying future clinical investigations to validate their use.

Keywords: anticancer; copper complexes; cytotoxic activity.

Figure 1

Chemical structure of the main copper-coupled ligands. (a)—pyridine (PYR), (b)—bipyridine (BYP), (c)—terpyridine (TERP), (d)—phenanthroline (PHEN), and (e)—thiosemicarbazone (TSC). Source: Own authorship.