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

摘要

A great majority of Cu(II) complexes currently studied in the anticancer research field exert their anti-proliferative activities through ligand exchange. In this work, we present the synthesis and structural characterization of two novel Cu(II) complexes, {[Cu-3(ZL)(2)(H2O)(6)]center dot 6H(2)O}(n) (1) (ZL = 1-hydroxy-2-(1H-imidazol-1-yl)ethane-1,1-diyldiphosphonic acid) and [Cu(IPrDP)(2)]center dot 3H(2)O (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 3binding affinity for DNA through intercalation. (C) 2014 Elsevier Masson SAS. All rights reserved.