
pmid: 29916702
pmc: PMC6030684
Metal coordination complexes can display interesting biological activity, as illustrated by the bleomycins (BLMs), a family of natural antibiotics that when coordinated to a redox-active metal ion, show antitumor activity. Yet, which metal ion is required for the activity in cells is still subject to debate. In this study, we described how different metal ions affect the intracellular behavior and activity of the synthetic BLM-mimic N, N-bis(2-pyridylmethyl)- N-bis(2-pyridyl)methylamine (N4Py). Our study shows that a mixture of iron(II), copper(II), and zinc(II) complexes can be generated when N4Py is added to cell cultures but that the metal ion can also be exchanged by other metal ions present in cells. Moreover, the combination of chemical data, together with the performed biological experiments, shows that the active complex causing oxidative damage to cells is the FeII-N4Py complex and not per se the metal complex that was initially added to the cell culture medium. Finally, it is proposed that the high activity observed upon the addition of the free N4Py ligand is the result of a combination of scavenging of biologically relevant metals and oxidative damage caused by the iron(II) complex.
Models, Molecular, Tumor, Intracellular Space/drug effects, Pyridines, Intracellular Space, Molecular Conformation, Molecular, Coordination Complexes/chemistry, Ligands, Cell Line, Structure-Activity Relationship, Metals, Heavy/chemistry, Models, Pyridines/chemistry, Coordination Complexes, Cell Line, Tumor, Metals, Heavy, Humans
Models, Molecular, Tumor, Intracellular Space/drug effects, Pyridines, Intracellular Space, Molecular Conformation, Molecular, Coordination Complexes/chemistry, Ligands, Cell Line, Structure-Activity Relationship, Metals, Heavy/chemistry, Models, Pyridines/chemistry, Coordination Complexes, Cell Line, Tumor, Metals, Heavy, Humans
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| popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network. | Top 10% | |
| influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically). | Average | |
| impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network. | Top 10% |
