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

Abstract

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.

Thiosemicarbazone Cu(II) complex exhibited great growth inhibition and induction of apoptosis in HeLa cells via oxidative DNA damage pathway which can act as a potential anticancer agent.

Keywords:

• Thiosemicarbazone
• Copper(II) complex
• Anticancer
• Apoptosis
• Biological evaluation

Additional information

Funding

Funding. This work was supported by National Natural Science Foundation of China [grant number 21371135] and Tianjin Municipal Natural Science Foundation [grant number 13JCZDJC28200] [grant number 11JCYBJC14900].