DNA cleavage induced by [Cu(L)x(NO3)2] (L=2,2′-dipyridylamine, 2,2′-bipyridine, dipicolylamine, x=1 or 2): Effect of the ligand structure

Kwon, Ji Hye; Park, Hyojin; Chitrapriya, Nataraj; Cho, Tae Sub; Kim, Soojin; Kim, Jinheung; Hwang, In Hong; Kim, Cheal; Kim, Seog K.

doi:10.1016/j.jinorgbio.2013.10.023

Cited by 13 publications

(7 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Additionally, the analogous zinc complex 2, with no redox properties, exhibited similar cytotoxic effects against the same tumor cells. The ligand structure can be crucial for metal activity toward DNA, as exemplified in comparative studies of copper(II) complexes with correlated ligands, 2,2 -bipyridine (bpy), 2,2 -dipyridylamine (dpa) or dipicolylamine (dpca), where [Cu(bpy) 2 ] 2+ complex was the most active in double cleavage reaction [46].…”

Section: Discussionmentioning

confidence: 99%

Oxidative Assets Toward Biomolecules and Cytotoxicity of New Oxindolimine-Copper(II) and Zinc(II) Complexes

et al. 2019

View full text Add to dashboard Cite

A new oxindolimine ligand derived from isatin (1H-indole-2,3-dione) and 2-aminomethylbenzimidazole was synthesized, leading to two novel complexes after metalation with copper(II) perchlorate or zinc(II) chloride, [Cu(isambz)2](ClO4)2 (complex 1) and [Zn(isambz)Cl2] (complex 2). This new ligand was designed as a more lipophilic compound, in a series of oxindolimine–metal complexes with antitumor properties, having DNA, mitochondria, and some proteins, such as CDK1 kinase and topoisomerase IB, as key targets. The new complexes had their reactivity to human serum albumin (HSA) and DNA, and their cytotoxicity toward tumor cells investigated. The binding to CT-DNA was monitored by circular dichroism (CD) spectroscopy and fluorescence measurements using ethidium bromide in a competitive assay. Consequent DNA cleavage was verified by gel electrophoresis with complex 1, in nmolar concentrations, with formation of linear DNA (form III) after 60 min incubation at 37 °C, in the presence of hydrogen peroxide, which acts as a reducing agent. Formation of reactive oxygen species (ROS) was observed, monitored by spin trapping EPR. Interaction with HSA lead to α-helix structure disturbance, and formation of a stable radical species (HSA–Tyr·) and carbonyl groups in the protein. Despite showing oxidative ability to damage vital biomolecules such as HSA and DNA, these new complexes showed moderate cytotoxicity against hepatocellular carcinoma (HepG2) and neuroblastoma (SHSY5Y) cells, similarly to previous compounds in this series. These results confirm DNA as an important target for these compounds, and additionally indicate that oxidative damage is not the leading mechanism responsible for their cytotoxicity. Additionally, this work emphasizes the importance of ligand characteristics and of speciation in activity of metal complexes.

show abstract

Section: Discussionmentioning

confidence: 99%

Oxidative Assets Toward Biomolecules and Cytotoxicity of New Oxindolimine-Copper(II) and Zinc(II) Complexes

et al. 2019

View full text Add to dashboard Cite

show abstract

“…The use of LD as a tool for detecting dsDNA cleavage in real-time is described elsewhere [19,[33][34][35]39]. The electrochemical measurements were conducted using an Ag/AgCl reference electrode, coiled platinum counter electrode and glassy carbon electrode (Bioanalytical Systems Inc., A = 0.071 cm 2 ).…”

Section: Ld and Other Spectroscopic Measurementsmentioning

confidence: 99%

“…Cu(II) complexes of phenanthrolines and other heteroaromatic ligands have been studied widely as a transition metal based complexes because of their catalytic effect on nucleic acid cleavage [19][20][21][22][23][24][25][26][27][28][29][30][33][34][35]. As an example, bis(1,10-phnanthroline)Cu(II) complexes, which can recognize a specific sequence with high affinity, showed high DNA cleavage efficiency through direct abstraction of the H1´ hydrogen of the deoxyribose moiety.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Oxidative DNA cleavage by Cu(II) complexes: Effect of periphery substituent groups

Wang

Lee

Kim

et al. 2015

Journal of Inorganic Biochemistry

Self Cite

View full text Add to dashboard Cite

“…Copper, as a fundamental micronutrient of cells, plays an important role in biological functions of the human body. Since the reduction of the Cu(II) to Cu(I) can induce DNA cleavage, copper complexes might be promising alternatives to platinum agents. , Many Cu(II) complexes can effectively cleave DNA by the generated reactive oxygen species (ROS), for example, singlet oxygen ( 1 O 2 ), superoxide anion radical (O 2 •– ), hydroxyl radical (OH • ), etc. − It is widely believed that Cu(II) reduced to Cu(I) can lead to the generation of ROS. ,, Some researchers believe that the generated OH • play an important role in DNA-cleavage, with the following reaction manner: (a) Cu(I) + H 2 O 2 → Cu(II) + OH – + OH • . Some regard O 2 •– as crucial to DNA-cleavage, with the following reaction manner: (b) Cu(I) + O 2 → [Cu(I)–O 2 ⇌ Cu(II)–O 2 •– ] → Cu(II) + O 2 •– .…”

Section: Introductionmentioning

confidence: 99%

Theoretical Studies on DNA-Cleavage Mechanism of Copper(II) Complexes: Probing Generation of Reactive Oxygen Species

Miao

Deng

Gao

et al. 2018

J. Chem. Inf. Model.

View full text Add to dashboard Cite

Theoretical studies on DNA-cleavage properties of [Cu(bba)(diimine)] 1-4 have been carried out using density functional theory (DFT) and docking methods. The optimized structures of Cu(II) complexes were docked into DNA, glutathiones (GSH), and ascorbic acids (VC) so that the corresponding docking models were obtained. To explore DNA-cleavage properties of Cu(II) complexes, the docking models of complexes with GSH and VC were further optimized using DFT method, while the docking models of complexes with DNA were optimized using QM/MM method because DNA is a supramolecular system. The rate constants k between complexes and DNA, GSH, and VC, oxidation-reduction potentials of complexes, and binding energies of complexes with GSH and VC were computed. The DNA-cleavage abilities of Cu(II) complexes in the presence VC, GSH, and HO were explored and the experimental results could be reasonably explained. Finally, the DNA-cleavage mechanism of Cu(II) complexes was described in detail, which would contribute to future design of novel anticancer Cu(II) complexes.

show abstract

DNA cleavage induced by [Cu(L)x(NO3)2] (L=2,2′-dipyridylamine, 2,2′-bipyridine, dipicolylamine, x=1 or 2): Effect of the ligand structure

Cited by 13 publications

References 57 publications

Oxidative Assets Toward Biomolecules and Cytotoxicity of New Oxindolimine-Copper(II) and Zinc(II) Complexes

Oxidative Assets Toward Biomolecules and Cytotoxicity of New Oxindolimine-Copper(II) and Zinc(II) Complexes

Oxidative DNA cleavage by Cu(II) complexes: Effect of periphery substituent groups

Theoretical Studies on DNA-Cleavage Mechanism of Copper(II) Complexes: Probing Generation of Reactive Oxygen Species

Contact Info

Product

Resources

About