A thiosemicarbazone copper(II) complex as a potential anticancer agent

The preparation and the structure of a copper(II) complex, [Cu(4ML)Cl] (1) (H4ML = 2-acetylpyridine-4-methylthiosemicarbazone), are described. Complex 1 crystallizes in a monoclinic P2₁/c space group with a = 7.977(2) Å, b = 15.824(5) Å, c = 9.126(2) Å, α = γ = 90°, β = 91.974(2)°, V = 1151.26(5) Å³, Z = 4, F(0 0 0) = 620. According to X-ray crystallographic studies, each Cu(II) ion lies in a square planar coordination geometry based on the 4ML⁻ and Cl⁻ ligands. The complex displayed excellent inhibitory activity against various tumor cells (HeLa, HepG-2 and SGC-7901), offering lower IC₅₀ value of 3.2 ± 0.7 μM than cisplatin (10 ± 2 μM) on HeLa cells at 48 h. Complex 1 could significantly suppress HeLa cell viability in a dose-dependent manner. Flow cytometric analysis showed that 1 induced HeLa cell apoptosis, which might be associated with cell cycle arrests at S and G2 phases. Consistent with results of DNA cleavage experiments, comet assay indicated that 1 caused severe DNA fragmentation. The production of ROS was elevated with increasing concentration of 1, suggesting that 1 was capable of promoting HeLa cell apoptosis through an oxidative DNA damage pathway.