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), Cu-2(adenine)(4)Cl-4 center dot 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 mu M)-dependant manner; an estimated IC50 of: 45 mu M with HepG2; 73 mu M with C2C12; 103 mu M with NIH3T3: and 108 mu M 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 mu M Cu-Ad; and (7) decreases ATP (80%) at 50 mu M Cu-Ad. The new compound Cu-2(adenine)(4)Cl-4 center dot 2EtOH (Cu-Ad), belongs to a class of copper-adenylate complexes that target many biochemical sites and with potential anti-cancer activity. (c) 2008 Elsevier Ireland Ltd. All rights reserved.