Mechanism of the antitumor action of complex compounds of copper(II) with ?-amino acids

Chapurina, L. F.; Budnikov, S. S.; Gurevich, S. M.; Nagler, L. G.

doi:10.1007/bf00531173

Cited by 2 publications

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“…Several anticancer agents have been developed with numerous transition metals and screened for their antineoplastic properties. Cu(II) complexes have recently attracted attention, as they can be designed as anticancer agents in an effort to overcome the severe side effects of known drugs like cisplatin, bleomycin, etc. − Redox active compounds such as Cu(II) can cleave the phosphodiester backbone of DNA molecules and have a wide range of biological activities, and some of them have known antimicrobial, , antinflammatory, antiviral, and antitumor , activities. Several other compounds such as bleomycin, pyrrole, thioether, oxime, peptides, and imidazole type ligands, have been complexed with copper ions, exhibit DNA cleavage activities. , …”

Section: Introductionmentioning

confidence: 99%

DNA Binding Ability and Hydrogen Peroxide Induced Nuclease Activity of a Novel Cu(II) Complex with Malonate as the Primary Ligand and Protonated 2-Amino-4-picoline as the Counterion

et al. 2010

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The DNA binding property of a Cu(II) complex, viz., [Cu(mal)(2)](picH)(2).2H(2)O, (mal)(2) = malonic acid, picH = protonated 2-amino-4-picoline, has been investigated in this study. The binding of this complex with plasmid and chromosomal DNA has been characterized by different biophysical techniques. From the absorption and fluorescence spectroscopic studies, it has been observed that the said copper complex binds strongly with pUC19 plasmid and CT DNA with a binding affinity of 2.368 x 10(3) and 4.0 x 10(3) M(-1), respectively, in 10 mM citrate-phosphate buffer, pH 7.4. Spectrofluorimetric studies reveal that the copper complex exhibits partial DNA intercalation as well as partial DNA minor groove binding properties. Consequently, in agarose gel electrophoresis study, it has been observed that the complex alone induces positive supercoiling in plasmid DNA while in the presence of H(2)O(2) it exhibits nuclease activity. The induction of the breakage in DNA backbone depends upon the relative concentrations of H(2)O(2) and copper complex followed by the time of incubation with DNA. Optical DNA melting study, isothermal titration calorimetry, and absorption spectroscopy have been used to characterize the nuclease activity of this complex in the presence of H(2)O(2). Further, (1)H NMR study indicates that Cu(II) in the complex is converted into the Cu(I) state by the reduction of H(2)O(2). Finally, agarose gel electrophoresis study with different radical scavengers concludes that the production of both hydroxyl radicals and reactive oxygen species is responsible for this nuclease activity.

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