Synthesis, crystal structure and antitumor effect of a novel copper(II) complex bearing zoledronic acid derivative

• Two novel copper(II) complexes were designed and synthesized.
• Antitumor activity of complex 2 was evaluated against several cancer cell lines.
• Complex 2 has good cytotoxic effect on HCT116 cells.
• The hepatotoxicity of complex 2 is far lower than that of cisplatin.
• Complex 2 interacts with CT-DNA through intercalation.

A great majority of Cu(II) complexes currently studied in the anticancer research field exert their antiproliferative activities through ligand exchange. In this work, we present the synthesis and structural characterization of two novel Cu(II) complexes, {[Cu3(ZL)2(H2O)6]·6H2O}n (1) (ZL = 1-hydroxy-2-(1H-imidazol-1-yl)ethane-1,1-diyldiphosphonic acid) and [Cu(IPrDP)2]·3H2O (2) (IPrDP = 1-hydroxy-3-(1H-imidazol-1-yl)propane-1,1-diyldiphosphonic acid). Due to the insolubility of polymer 1 in common solvents, only the biological activities of complex 2 were investigated. The antitumor activity of complex 2 was evaluated against a panel of human cancer cell lines, including U2OS, A549, HCT116, MDA-MB-231 and HepG2. Complex 2 exhibited comparable cytotoxic effect to cisplatin (CDDP) against the human colon carcinoma cells HCT116, and superior selectivity for inhibiting human hepatocarcinoma cells rather than normal liver cells. The cell cycle distribution analysis indicates that complex 2 inhibits human carcinoma cells by inducing the cell cycle arrest at the G2/M phase, showing a similar mechanism of action to that of CDDP. The binding interaction of complex 2 with calf thymus DNA (CT-DNA) has been explored by UV–vis absorption and circular dichroism (CD), demonstrating complex 2 has a moderate binding affinity for DNA through intercalation.

A novel copper(II) complex bearing zoledronic acid derivative with effective antitumor activity and low hepatotoxicity was designed and evaluated.Figure optionsDownload as PowerPoint slide