Synthesis and structural characterization of a series of ternary copper(II)-L-dipeptide-neocuproine complexes. Study of their cytotoxicity against cancer cells including MDA-MB-231, triple negative breast cancer cells

Álvarez, Natalia; Viña, Diana; Leite, Celisnolia M.; Mendes, Luis Felipe Santos; Batista, Alzir A.; Ellena, Javier; Costa-Filho, Antonio J.; Facchin, Gianella

doi:10.1016/j.jinorgbio.2019.110930

Cited by 23 publications

(21 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Copper complexes incorporating Schiff bases, amino acids, peptides, azoles, terpyridines, or polypyridyls as ligands as well as dinuclear copper complexes and copper complexes incorporating natural products or bioactive ligands showing metallonuclease activity have been reviewed [ 68 ]. Recently, a series of ternary copper(II)-L-dipeptide-neocuproine complexes have shown cytotoxicity against cancer cells, including MDA-MB-231, triple-negative breast cancer [ 69 ]. The complex bis[(μ2-chloro)chloro(1,10-phenanthroline)copper(II)] exhibited a potent anticancer activity against B16, MDA-MB-32, A549, HT-29 and SF, cell lines, with an average IC 50 value of 0.726 μg/mL (1.15 μM), compared to 4.88 μg/mL (16.3 μM) for cisplatin.…”

Section: Discussionmentioning

confidence: 99%

Synthesis, Crystal Structure, and Computational Methods of Vanadium and Copper Compounds as Potential Drugs for Cancer Treatment

et al. 2020

View full text Add to dashboard Cite

Transition metal-based compounds have shown promising uses as therapeutic agents. Among their unique characteristics, these compounds are suitable for interaction with specific biological targets, making them important potential drugs to treat various diseases. Copper compounds, of which Casiopeinas® are an excellent example, have shown promising results as alternatives to current cancer therapies, in part because of their intercalative properties with DNA. Vanadium compounds have been extensively studied for their pharmacological properties and application, mostly in diabetes, although recently, there is a growing interest in testing their activity as anti-cancer agents. In the present work, two compounds, [Cu(Metf)(bipy)Cl]Cl·2H2O and [Cu(Impy)(Gly)(H2O)]VO3, were obtained and characterized by visible and FTIR spectroscopies, single-crystal X-ray diffraction, and theoretical methods. The structural and electronic properties of the compounds were calculated through the density functional theory (DFT) using the Austin–Frisch–Petersson functional with dispersion APFD, and the 6-311 + G(2d,p) basis set. Non-covalent interactions were analyzed using Hirshfeld surface analysis (HSA) and atom in molecules analysis (AIM). Additionally, docking analysis to test DNA/RNA interactions with the Casiopeina-like complexes were carried out. The compounds provide metals that can interact with critical biological targets. In addition, they show interesting non-covalent interactions that are responsible for their supramolecular arrangements.

show abstract

Section: Discussionmentioning

confidence: 99%

Synthesis, Crystal Structure, and Computational Methods of Vanadium and Copper Compounds as Potential Drugs for Cancer Treatment

et al. 2020

View full text Add to dashboard Cite

show abstract

“…1,10-phenantrolines are typical copper ionofores, and copper complexes of 1,10-phenantrolines show antineoplastic properties [20]. Both the Cu(I) and Cu(II) complexes of 2,9-dimethyl-1,10-phenantroline (neocuproine) have been shown to be potent cytotoxic agents against different cell lines [21,22], and their activity was potentiated by adding Cu(II) ions to the cell culture medium [23][24][25]. The lipophilic Cu(I)-specific chelator neocuproine is frequently used as an inhibitor of Cu-mediated damage in biological systems [26].…”

Section: Introductionmentioning

confidence: 99%

Development and In Vivo Application of a Water-Soluble Anticancer Copper Ionophore System Using a Temperature-Sensitive Liposome Formulation

et al. 2020

View full text Add to dashboard Cite

Liposomes containing copper and the copper ionophore neocuproine were prepared and characterized for in vitro and in vivo anticancer activity. Thermosensitive PEGylated liposomes were prepared with different molar ratios of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) and hydrogenated soybean phosphatidylcholine (HSPC) in the presence of copper(II) ions. Optimal, temperature dependent drug release was obtained at 70:30 DPPC to HSPC weight ratio. Neocuproine (applied at 0.2 mol to 1 mol phospholipid) was encapsulated through a pH gradient while using unbuffered solution at pH 4.5 inside the liposomes, and 100 mM HEPES buffer pH 7.8 outside the liposomes. Copper ions were present in excess, yielding 0.5 mM copper-(neocuproine)2 complex and 0.5 mM free copper. Pre-heating to 45 °C increased the toxicity of the heat-sensitive liposomes in short-term in vitro experiments, whereas at 72 h all investigated liposomes exhibited similar in vitro toxicity to the copper(II)-neocuproine complex (1:1 ratio). Thermosensitive liposomes were found to be more effective in reducing tumor growth in BALB/c mice engrafted with C26 cancer cells, regardless of the mild hyperthermic treatment. Copper uptake of the tumor was verified by PET/CT imaging following treatment with [64Cu]Cu-neocuproine liposomes. Taken together, our results demonstrate the feasibility of targeting a copper nanotoxin that was encapsulated in thermosensitive liposomes containing an excess of copper.

show abstract

“…However, there is a consensus among researchers that the labile Cu fractions exert their toxicity by generating reactive oxygen species (ROS) via the Haber-Weiss reaction, which is related to the presence of the Cu(II)/Cu(I) redox couple [3,6,7]. Therefore, the Cu(II)/Cu(I) interaction with DNA and oxidative stress induction due to reactive oxygen species (ROS) production are the two most considered modes of copper compounds' actions [5,8].…”

Section: Introductionmentioning

confidence: 99%

The Bright and Dark Sides of Reactive Oxygen Species Generated by Copper–Peptide Complexes

et al. 2022

View full text Add to dashboard Cite

Copper ions bind to biomolecules (e.g., peptides and proteins) playing an essential role in many biological and physiological pathways in the human body. The resulting complexes may contribute to the initiation of neurodegenerative diseases, cancer, and bacterial and viral diseases, or act as therapeutics. Some compounds can chemically damage biological macromolecules and initiate the development of pathogenic states. Conversely, a number of these compounds may have antibacterial, antiviral, and even anticancer properties. One of the most significant current discussions in Cu biochemistry relates to the mechanisms of the positive and negative actions of Cu ions based on the generation of reactive oxygen species, including radicals that can interact with DNA molecules. This review aims to analyze various peptide–copper complexes and the mechanism of their action.

show abstract

Synthesis and structural characterization of a series of ternary copper(II)-L-dipeptide-neocuproine complexes. Study of their cytotoxicity against cancer cells including MDA-MB-231, triple negative breast cancer cells

Cited by 23 publications

References 74 publications

Synthesis, Crystal Structure, and Computational Methods of Vanadium and Copper Compounds as Potential Drugs for Cancer Treatment

Synthesis, Crystal Structure, and Computational Methods of Vanadium and Copper Compounds as Potential Drugs for Cancer Treatment

Development and In Vivo Application of a Water-Soluble Anticancer Copper Ionophore System Using a Temperature-Sensitive Liposome Formulation

The Bright and Dark Sides of Reactive Oxygen Species Generated by Copper–Peptide Complexes

Contact Info

Product

Resources

About