Crystal structure, cytotoxicity and action mechanism of Zn(II)/Mn(II) complexes with isoquinoline ligands

Four μ2-Cl bridged dinuclear metal complexes with isoquinoline ligands, (MPDQ)2Zn2Cl4 (1) (MPDQ=4.5-methylenedioxy-1-pyridinedihydroisoquinoline), (PYP)2Zn2Cl4 (2) (PYP=5-pyridin-2-yl-[1,3]dioxolo[4,5-g]isoquinoline), (MPDQ)2Mn2Cl4 (3),and (PYP)2Mn2Cl4 (4) were synthesized and characterized. All complexes exhibited strong proliferation inhibition activity against various cancer cells. The underlying molecular mechanisms through which they caused the cancer cell death were also elucidated. Induction of apoptosis in MGC-803 cells by complex 2 was evidenced by annexin V+/PI− detection and DiD/DAPI staining assay. Further investigation revealed that complex 2 was able to induce intrinsic pathway-dependent apoptosis in cancer cells by triggering DNA damage which was caused by the overproduction of reactive oxygen species. Based on these studies, we suggest that Zn(II) complexes containing isoquinoline ligands can be developed as candidates for anti-cancer chemotherapeutics. Four μ2-Cl bridged dinuclear Zn(II)/Mn(II) complexes with isoquinoline derivatives were synthesized and exhibited high cytotoxicity against various tumor cells with certain selectivity to tumor and normal cells, which induced intrinsic pathways-dependent apoptosis in cancer cells by triggering DNA damage which was caused by the reactive oxygen species (ROS) overproduction. [Display omitted] •Four μ2-Cl bridged dinuclear Zn/Mn complexes of isoquinoline derivatives were synthesized.•The complexes exhibited considerable cytotoxicity against human tumor cells.•The antitumor activity was achieved via DNA damage-mediated mitochondrial pathway.