Copper(II) complexes inducing apoptosis in cancer cells, and demonstrating DNA and HSA interactions

Hu, Jingyu; Liao, Chunli; Guo, Yan; Yang, Fan; Sang, Wei; Zhao, Jin’an

doi:10.1016/j.poly.2017.04.018

Cited by 23 publications

(19 citation statements)

References 40 publications

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“…On the contrary, copper overload has been related to several health disorders including Wilson's, Parkinson's, Alzheimer's, and Huntington's diseases . Altered copper levels, and OS, have been associated with cancer progression; while some Cu(II) complexes exhibit anticancer properties . In addition, the role of synthetic copper nucleases on OD‐related processes is an emerging field of investigation .…”

Section: Introductionmentioning

confidence: 99%

Role of purines on the copper‐catalyzed oxidative damage in biological systems: Protection versus promotion

Castañeda‐Arriaga

Pérez-González

Álvarez-Idaboy

et al. 2017

Int J of Quantum Chemistry

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Oxidative damage to biomolecules is a serious health-threatening issue, which leads to the development of several diseases. Oxidative conditions are frequently catalyzed by metal ions. In this study, the role of purines in the copper-catalyzed oxidative stress was investigated using the density functional theory. The obtained results indicate that purines can have a dual behavior, acting as both protectors and promoters of oxidative stress. Their protection role arises from their known radical scavenging activity, as well as their ability to chelate Cu(II) leading to complexes that areto some extent-harder to reduce than free Cu(II). Conversely, their pro-oxidant role is a consequence of their reductant behavior, when deprotonated. Thus, the purines' anions can reduce Cu (II) to Cu(I), making the latter available to be involved in Fenton-like reactions. Consequently, mixtures of purines and Cu(II), at pHs where the fraction of deprotonated purines is rather significant, would yield • OH radicals. In turn, these very reactive radicals would damage biological targets such as lipids, proteins, and DNA.antioxidants, kinetics, pro-oxidants, rate constants, reaction mechanism 1 | I N TR ODU C TI ON Oxidative damage (OD) to biological targets such as lipids, proteins, and DNA is a serious health-threatening phenomenon. It has been held responsible, at least in part, for the onset and development of several diseases including cancer [1][2][3] ; rheumatoid arthritis [4][5][6] ; neurodegenerative disorders such as Parkinson's and Alzheimer's diseases, depression, multiple sclerosis, and memory loss [7][8][9][10][11][12][13] ; cardiovascular diseases such as atherosclerosis, ischemia, hypertension, cardiac hypertrophy, heart failure, and cardiomyopathy [14][15][16][17] ; as well as renal [18][19][20] and pulmonary failure. [21][22][23] OD arises as a consequence of a chemical imbalance between the production and consumption of oxidants, known as oxidative stress (OS). [24] One of the most damaging oxidants in biological systems is the hydroxyl radical ( • OH). It can be produced, in the presence of metal ions such as Fe(II) or Cu(I), by Fenton or Fenton-like reactions (M q 1 H 2 O 2 ! M q11 1OH -1 • OH). However, the most stable and abundant forms of these two metals, under physiological conditions, are Fe(III) and Cu(II). Thus, • OH production would actually involve the metal-catalyzed Haber-Weiss recombination (HWR). It comprises two chemical steps. The first one is the reduction of the metal ions (M q11 1 O •2 2 ! M q 1 3 O 2 ) and the second one is the Fenton reaction. Consequently, redox active metal ions are of particular interest for the chemistry of living systems. These ions cannot only bind to DNA, but they can also promote OD to DNA by mediating the production of oxygen reactive species (ROS). [25] In fact metal-mediated OD to DNA has become an important topic in metal toxicity and carcinogenesis. [26][27][28][29]

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Section: Introductionmentioning

confidence: 99%

Role of purines on the copper‐catalyzed oxidative damage in biological systems: Protection versus promotion

Castañeda‐Arriaga

Pérez-González

Álvarez-Idaboy

et al. 2017

Int J of Quantum Chemistry

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“…Peak 1 for BSA ( λ ex = 280 nm, λ em = 310 nm) mainly revealed the spectral characteristics of tryptophan and tyrosine residues. It is closely related to the microenvironmental polarity around the residues . Peak 2 for BSA ( λ ex = 230 nm, λ em = 326 nm) predominantly displayed the polypeptide backbone which occurs mainly in the presence of л‐л* transition .…”

Section: Resultsmentioning

confidence: 99%

Anomalous coordination behaviour of 6‐methyl‐2‐oxo‐1,2‐dihydroquinoline‐3‐carboxaldehyde‐4(N)‐substituted Schiff bases in Cu(II) complexes: Studies of structure, biomolecular interactions and cytotoxicity

Elamathi

Butcher

Prabhakaran

2019

Applied Organom Chemis

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A series of copper(II) complexes containing 6‐methyl‐2‐oxo‐1,2‐dihydroquinoline‐3‐carboxaldehyde‐derived Schiff bases have been synthesized and characterised using various analytical and spectroscopic techniques. X‐ray crystallographic analysis confirmed the true coordinating nature of ligands with copper ion. The ligands exhibited ONS tridentate neutral and monobasic coordination. The spectroscopic results evidenced the interaction of the ligands and their copper(II) complexes with nucleic acid/serum albumin. Further, the complexes showed significant activity against human skin cancer cell line (A431) and less toxicity against human keratinocyte cell line (HaCaT). Acridine orange/propidium iodide dual staining studies indicated that the major cause of A431 cell death was through necrosis. By comparing the biological activity of all the ligands, Cu(II) complexes and standard (cisplatin), complex [Cu(H‐6MOQtsc‐Ph)(H2O)]⋅NO3 (4) exhibited better activity than others, the activity being arranged as follows: 4 > 1 > cisplatin > 3 > 2.

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“…Moreover, the number of binding sites (n) was determined from the slope and the intercept of the plot of log ( F 0 ‐ F )/ F versus log [ Q ], as depicted in Figure . Results indicated that the complexes 8 a, 8 b and 8 c had “n“ value of approximately equal to 1, which implied single binding site with BSA, suggesting that BSA could serve as a passive carrier for the delivery of the investigated complexes to the tumor cells …”

Section: Resultsmentioning

confidence: 99%

New Water‐Soluble N‐Heterocyclic Carbene‐Palladium Complexes as Promising Anti‐Tumor Agents: Investigating DNA and Protein Interactions

et al. 2018

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This investigation focuses on the synthesis and characterization of three new, water-soluble palladium complexes, with potential to overcome the drawbacks of platinum-based anti-cancer drugs. The complexes contain small N-heterocyclic carbene (NHC) ligands, having groups that impart water solubility. The anti-cancer effects of these complexes were evaluated in two different cancer cell lines, namely,HeLa, a cervical cancer cell line and A549,adenocarcinoma human alveolar basal epithelial cell line. Cytotoxicity of the complexes was compared with cisplatin, an established platinum-based anti-cancer moiety, using the MTT assay (MTT is 3-(4,5-dimethylthiazol-2-yl)-2,5diphenyltetrazolium bromide). Aqueous solutions of the synthesized complexes demonstrated significant cytotoxicity in both the cell lines. The synthesized metal complexes resulted in a stronger, cytotoxic effect in A549 cells (lung cancer cells), as compared to cisplatin. Furthermore, interaction of these palladium compounds with DNA was studied using gel electrophoresis and spectrometry methods. The result suggested that the complexes interacted with DNA via intercalation. Interaction with BSA (Bovine Serum Albumin) was investigated using UV-Vis spectroscopy suggesting positive interaction of palladium complex with BSA proteins. Furthermore, fluorescence studies revealed quenching of protein fluorescence thus, indicating dynamic quenching mechanism with the number of association sites being calculated as~1.

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Copper(II) complexes inducing apoptosis in cancer cells, and demonstrating DNA and HSA interactions

Cited by 23 publications

References 40 publications

Role of purines on the copper‐catalyzed oxidative damage in biological systems: Protection versus promotion

Role of purines on the copper‐catalyzed oxidative damage in biological systems: Protection versus promotion

Anomalous coordination behaviour of 6‐methyl‐2‐oxo‐1,2‐dihydroquinoline‐3‐carboxaldehyde‐4(N)‐substituted Schiff bases in Cu(II) complexes: Studies of structure, biomolecular interactions and cytotoxicity

New Water‐Soluble N‐Heterocyclic Carbene‐Palladium Complexes as Promising Anti‐Tumor Agents: Investigating DNA and Protein Interactions

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