Time-Dependent Cytotoxic Properties of Terpyridine-Based Copper Complexes

Five copper complexes supported by terpyridine ligands were prepared and characterized, viz. [Cu3Cl4(naphtpy)2][CuCl2] (1), [Cu2Cl2(naphtpy)2](ClO4)2 (2), [CuCl2(naphtpy)]2(MeOH)3(H2O) (3), [CuCl2(Cltpy)] (4) and [Cu(Cltpy)2](ClO4)2 (5); (where naphtpy stands for 4’-((naphthalen-2-yl)methoxy)-2, 2':6', 2''-terpyridine and Cltpy for 4'-chloro-2, 2':6', 2''-terpyridine). Their ability to interact with DNA was investigated, and their cytotoxic behaviour was examined with three cells lines, namely human ovarian carcinoma cells (A2780), their derived cisplatin-resistant line (A2780cis), and human cervix adenocarcinoma cells (HeLa). All compounds show good cytotoxic properties (especially after 72 h of incubation). Remarkably, two compounds, 4 and 5, are still almost inactive after 24 h (particularly 4), but are highly active after 72 h, with IC50 values in the low-micromolar to sub-micromolar range. Compounds 1 and 2 induce necrosis, whereas late apoptosis is observed with 3–5, 4 exhibiting a behaviour close to that of cisplatin.