1. Copper–adenine complex, a compound, with multi-biochemical targets and potential anti-cancer effect
- Author
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Walid Sawma, Johnny J. Touma, Pascale Barnabe, Jida El-Hajjar, Amer M. Ghannoum, Julnar Usta, Hassan H. Hammud, Yolla Bou-Mouglabey, and Georges Nemer
- Subjects
Cell Survival ,GATA5 Transcription Factor ,Stereochemistry ,Infrared spectroscopy ,chemistry.chemical_element ,Antineoplastic Agents ,Electrophoretic Mobility Shift Assay ,Toxicology ,Inhibitory Concentration 50 ,Adenosine Triphosphate ,Cell Line, Tumor ,Spectroscopy, Fourier Transform Infrared ,Organometallic Compounds ,Humans ,Taq Polymerase ,Electrophoretic mobility shift assay ,A549 cell ,chemistry.chemical_classification ,Reactive oxygen species ,Electron Transport Complex I ,Calorimetry, Differential Scanning ,biology ,Chemistry ,Adenine ,Succinate dehydrogenase ,General Medicine ,Molecular biology ,Copper ,In vitro ,Succinate Dehydrogenase ,Cell culture ,Thermogravimetry ,biology.protein ,Spectrophotometry, Ultraviolet ,Reactive Oxygen Species - Abstract
A series of adenine-copper complexes (1-6) with various ligands (Cl(-), SCN(-), BF(4)(-) 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).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 microM)-dependant manner; an estimated IC(50) of: 45 microM with HepG2; 73 microM with C2C12; 103 microM with NIH3T3; and 108 microM 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 IC(50) of 2.8 nmol, but had no effect on succinate dehydrogenase activity; (6) increases reactive oxygen species (60%) at 45 microM Cu-Ad; and (7) decreases ATP (80%) at 50 microM Cu-Ad. The new compound Cu(2)(adenine)(4)Cl(4).2EtOH (Cu-Ad), belongs to a class of copper-adenylate complexes that target many biochemical sites and with potential anti-cancer activity.
- Published
- 2008
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