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

Hassan H. Hammud, Georges Nemer, Walid Sawma, Jhonny Touma, Pascale Barnabe, Yolla Bou-Mouglabey, Amer Ghannoum, Jida El-Hajjar, Julnar Usta*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

45 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)84-96
Number of pages13
JournalChemico-Biological Interactions
Volume173
Issue number2
DOIs
Publication statusPublished - 28 May 2008
Externally publishedYes

Keywords

  • Copper-adenine
  • GATA-5
  • HepG2
  • PCR
  • TbX20
  • WND

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