Cancer is a common and highly threatening disease, and is one of the main causes of death in today's society. Its etiology is complicated and symptoms are difficult to detect, causing treatment is extremely difficult [1,2]. According to GLOBOCAN 2020 data, there were 19.29 million new cancer cases and 9.95 million new deaths worldwide [3]. In the research and development process of anticancer drugs, using complexes as anticancer drugs has always been a hot study field for researchers. Since Rosenberg found that cisplatin has the effect of inhibiting cell growth in 1969 [4], platinum complexes such as carboplatin and oxaliplatin have entered medical clinical trials and gradually been widely used [[5], [6], [7], [8]]. In addition, the complexes of metal ions such as zinc [9,10], palladium [11,12], copper [13,14] and gold [15,16] have also been found to have excellent anti-cancer capabilities.

New drugs that bind to biological macromolecules, such as thymosin β4, exhibits sensitivity when coordinating with metal ions, and such complexes actively participate in oxidative stress reactions and metal ion metabolism in the body [[17], [18], [19]]. Therefore, copper metal complexes have various advantages in anti-cancer biological studies. Copper ion is one of the essential trace elements in human body. It participates in many physiological processes, including gene expression, redox, immune regulation [20,21], etc. Therefore, copper complexes have good biocompatibility for human health. Secondly, copper complexes can exert anti-tumor effects on cancer cells through various mechanisms. For example, copper complexes can interfere with DNA replication and repair, leading to tumor cell death [22,23]. In addition, copper complexes can also exert anticancer effects by inhibiting angiogenesis [24], inducing tumor cell apoptosis [25], and enhancing the immune system [26]. Copper complexes can adjust their drug metabolism and distribution by changing their structures and ligands, thereby improving their efficacy and reducing side effects. This provides better prospects for the clinical application of copper complexes.

Substituted terpyridines are excellent ligands with good planarity and stability for metal ions. Three N atoms can coordinate with metal salts in a tridentate manner, and substituents can be added at different positions at the phenyl ring, thereby changing the chemical properties of complexes and affecting their biological activity. Based on the above advantages, substituted terpyridine complexes may become excellent potential anticancer drugs. According to research findings, substituted terpyridine ligands have excellent biological activity when combined with metal ions such as zinc [[27], [28], [29], [30], [31]], palladium [32] and silver [33]. Li and Guan's research works on copper (II) chloride terpyridine complexes have proved the anti-tumor activity of copper complexes that the change of the anions of metal salts may have a greater impact on the biological activity of the complexes [34,35].

Based on this observation, complexes 1–10 were designed and synthesized by using the substituted terpyridine ligands L1–10 and copper(II) nitrate. Their structural formula is [Cu(NO3)2LX (LX = L1–10)], and their structural diagram is shown in Scheme 1. Their structures were characterized and confirmed by mass spectrometry, elemental analysis, infrared spectroscopy and X-ray diffraction method. Their anticancer activities were investigated by in vitro antiproliferative activity measurement. The binding ability of the complexes with DNA was investigated by circular dichroism and ultraviolet spectroscopy. In addition, the binding modes of these complexes with biological macromolecules, such as DNA and DNA Topoisomerase, were calculated by molecular docking simulation. Through the above research, we aim to investigate whether they have the potential to become a new generation of anticancer drugs.