Piperidylthiosemicarbazones Cu(II) complexes with a high anticancer activity by catalyzing hydrogen peroxide to degrade DNA and promote apoptosis.

Copper(II) complexes efficiently catalyze hydrogen peroxide to generate reactive oxygen species (ROS), which is the major reason for its significant anti-tumor activity. We synthesized three Cu(II) piperidylthiosemicarbazone complexes and examined their structures by X-ray single crystal diffraction. These Cu(II) complexes have significant apoptosis-promoting activity at nanomolar concentrations. The antitumor activity of these Cu(II) complexes is increased by more than 40-fold relative to that of the ligand. The binding experiment results demonstrated that the Cu(II) complexes interact with DNA with moderate binding affinity by in situ intercalation. Gel electrophoresis analysis indicated that DNA is degraded when the copper complex catalyzes hydrogen peroxide to produce reactive oxygen species (ROS). Apoptosis mechanism results showed that excessive ROS leads to mitochondrial membrane potential dissipation and promote the release of apoptotic factors from mitochondria.