title: Copper-adenine complex, a compound, with multi-biochemical targets and potential anti-cancer effect.
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.
authors.affiliation: Beirut Arab University, Department of Chemistry, Beirut, Lebanon.
authors.forename: Hassan H
authors.initials: HH
authors.lastname: Hammud
authors.forename: Georges
authors.initials: G
authors.lastname: Nemer
authors.forename: Walid
authors.initials: W
authors.lastname: Sawma
authors.forename: Jhonny
authors.initials: J
authors.lastname: Touma
authors.forename: Pascale
authors.initials: P
authors.lastname: Barnabe
authors.forename: Yolla
authors.initials: Y
authors.lastname: Bou-Mouglabey
authors.forename: Amer
authors.initials: A
authors.lastname: Ghannoum
authors.forename: Jida
authors.initials: J
authors.lastname: El-Hajjar
authors.forename: Julnar
authors.initials: J
authors.lastname: Usta
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors / Q000378:metabolism; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002152:Calorimetry, Differential Scanning; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003300:Copper / Q000737:chemistry / Q000494:pharmacology*; D042967:Electron Transport Complex I / Q000037:antagonists & inhibitors / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D050992:GATA5 Transcription Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013056:Spectrophotometry, Ultraviolet; D017550:Spectroscopy, Fourier Transform Infrared; D013385:Succinate Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D019914:Taq Polymerase / Q000037:antagonists & inhibitors / Q000378:metabolism; D013818:Thermogravimetry
chemical_list: D000970:Antineoplastic Agents; D050992:GATA5 Transcription Factor; D009942:Organometallic Compounds; D017382:Reactive Oxygen Species; D003300:Copper; D000255:Adenosine Triphosphate; D013385:Succinate Dehydrogenase; D019914:Taq Polymerase; D042967:Electron Transport Complex I; D000225:Adenine