Development of a zinc(II) 2-pyridinecarboxaldehyde thiosemicarbazone complex with remarkable antitumor and antiangiogenic activities.

To develop the next-generation metal agents for efficiently inhibiting tumor growth, we synthesized a series of new Zn(II) complexes (C1-C5) derived from 2-pyridinecarboxaldehyde thiosemicarbazone and investigated their structure-activity relationships. C5 bearing two methyl groups at the N-4 position of the ligand exerted the strongest inhibition effect among all the Zn(II) complexes. Importantly, C5 exerted an effective inhibitory effect on tumor growth and produced few side effects . We further confirmed the antitumor mechanisms of C5, including arresting the cell cycle at the S phase, inducing apoptosis, inducing lethal autophagy, and suppressing angiogenesis.