Copper–adenine complex, a compound, with multi-biochemical targets and potential anti-cancer effect

A series of adenine–copper complexes (1–6) with various ligands (Cl−, SCN−, BF4− and acac [acetylacetonate ion]) have been synthesized and characterized by elemental analysis, infrared spectroscopy and thermal analysis. Among the six complexes only complex (1), Cu2(adenine)4Cl4·2EtOH (abbreviated as Cu–Ad), demonstrated some toxic effect on different cell lines. In vitro investigations of the biological effect of Cu–Ad complex have shown that it: (1) binds genomic DNA; (2) decreases significantly, the viability of cells in culture in a concentration (15–125 μM)-dependant manner; an estimated IC50 of: 45 μM with HepG2; 73 μM with C2C12; 103 μM with NIH3T3; and 108 μM with MCF7. Cu–Ad had no effect on A549 cells; (3) inhibits Taq polymerase-catalyzed reaction; (4) inhibits the binding of the transcription factor GATA-5 to labeled DNA probes; (5) inhibits mitochondrial NADH-UQ-reductase with an estimated IC50 of 2.8 nmol, but had no effect on succinate dehydrogenase activity; (6) increases reactive oxygen species (60%) at 45 μM Cu–Ad; and (7) decreases ATP (80%) at 50 μM Cu–Ad. The new compound Cu2(adenine)4Cl4·2EtOH (Cu–Ad), belongs to a class of copper–adenylate complexes that target many biochemical sites and with potential anti-cancer activity.