Transition metal complexes with 6,7-dichloro-5,8-quinolinedione as mitochondria-targeted anticancer agents

Abstract

Herein, a series of transition metal complexes, [Zn(DQ)2(CH3OH)2] (1), [Zn(DMQ)2(CH3OH)2] (2), [Co(DQ)2(CH3OH)2] (3), [Co(DMQ)2(CH3OH)2] (4), [Ni(DQ)2(CH3OH)2] (5), [Cu(DMQ)2(CH3OH)2] (6), [Mn(DQ)2(H2O)2] (7) and [Mn(DMQ)2(H2O)2] (8), containing 6,7-dichloro-5,8-quinolinedione (DQ) and 6,7-dichloro-2-methyl-5,8-quinolinedione (DMQ) ligands have been synthesized and characterized as potential antitumor agents. These complexes 1–8 exhibited evident anti-tumor activity in HeLa (cervical), MCF-7 (breast), Hep-G2 (hepatoma), T-24 (bladder), and SK-OV-3 (ovarian) human cancer cells. Interestingly, complexes 1–8 showed higher cytotoxicity than cisplatin against human cervical HeLa cells, and less cytotoxicity on the HL-7702 nontumorigenic cells. Mechanism studies suggested that complexes 1 and 2 arrested the cell cycle in the G1 phase and induced cancer cell death through mitochondrial dysfunction pathways. The cytotoxicity of 2 was higher than that of 1. The different biological behavior of 1 and 2 may correlate with the presence of a 2-methyl group in 6,7-dichloro-2-methyl-5,8-quinolinedione (DMQ) ligand. In general, our study demonstrated that Zn(II) complex 2 with 6,7-dichloro- 2-methyl-5,8-quinolinedione showed high potential to be developed as a mitochondria-targeted metal antitumor agent.