In vitro and in vivo studies of the antineoplastic activity of copper (II) compounds against human leukemia THP-1 and murine melanoma B16-F10 cell lines

Borges, Layla J.H.; Bull, Érika Soares; Fernandes, Christiane; Horn, Adolfo; Azeredo, Nathália F. B.; Resende, Jackson A. L. C.; Freitas, William Rodrigues de; Carvalho, Eulógio Carlos Queiróz de; Lemos, Leandro Silva de; Jerdy, Hassan; Kanashiro, Milton

doi:10.1016/j.ejmech.2016.07.018

Cited by 40 publications

(19 citation statements)

References 70 publications

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“…Therefore, complex 1 was selected for further studies. Additionally, when compared to other Cu II complexes containing analogous ligands, complex 1 has already been shown to stand out as one of the most active copper-based compounds 25 , 26 with high selectivity 22 , as it can be confirmed by the present work.…”

Section: Discussionsupporting

confidence: 80%

A selective CuII complex with 4-fluorophenoxyacetic acid hydrazide and phenanthroline displays DNA-cleaving and pro-apoptotic properties in cancer cells

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et al. 2021

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The thin line between efficacy and toxicity has challenged cancer therapy. As copper is an essential micronutrient and is important to tumor biology, CuII complexes emerged as an alternative to chemotherapy; however, its biological properties need to be better understood. Thus, we report in vitro the antitumor effects of two CuII complexes named [Cu(4-fh)(phen)(ClO4)2] (complex 1) and [Cu(4-nh)(phen)(ClO4)2]·H2O (complex 2), in which 4-fh = 4-fluorophenoxyacetic acid hydrazide; 4-nh = 4-nitrobenzoic hydrazide and phen = 1,10-phenanthroline. Both complexes presented cytotoxic activity against tumor cells, but only complex 1 showed significant selectivity. Complex 1 also induced DNA-damage, led to G0/G1 arrest and triggered apoptosis, which was initiated by an autophagy dysfunction. The significant in vitro selectivity and the action mechanism of complex 1 are noteworthy and reveal this prodrug as promising for anticancer therapy.

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Section: Discussionsupporting

confidence: 80%

A selective CuII complex with 4-fluorophenoxyacetic acid hydrazide and phenanthroline displays DNA-cleaving and pro-apoptotic properties in cancer cells

Machado

Paixão

Lino

et al. 2021

Sci Rep

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“…For B16 cells, when treated with (2), the cell viability decreased to 5%, with IC 50 values of 6.88 µg/mL (7.6 µM) after 24 h treatment and 4.15 µg/mL (4.58 µM) after 48 h, respectively (Table 3). The ligand dmtp did not affect the viability of either BJ or B16 cells at 24 or 48 h. It is worth mentioning that for other copper compounds tested on melanoma cells, the reported IC 50 values were similar [35][36][37][38][39][40][41][42][43], and only one study reported lower values [38] compared with those found for complex (1).…”

Section: Biological Characterization 231 Cell Viability and Lactate Dehydrogenase Assaysmentioning

confidence: 95%

“…The Cu(II) systems represent beneficial species from this point of view, considering their reduced systemic toxicity [16]. Thus, several Cu(II) complexes were studied and proved to be as effective for melanoma treatment [18,29,[35][36][37][38][39][40][41][42][43]-some having, in addition, low toxicity on normal cells [18,29,[39][40][41][42][43].…”

Section: Biological Characterization 231 Cell Viability and Lactate Dehydrogenase Assaysmentioning

confidence: 99%

Biological Activity of Triazolopyrimidine Copper(II) Complexes Modulated by an Auxiliary N-N-Chelating Heterocycle Ligands

et al. 2021

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Novel complexes of type [Cu(N-N)(dmtp)2(OH2)](ClO4)2·dmtp ((1) N-N: 2,2′-bipyridine; (2) L: 1,10-phenantroline and dmtp: 5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine) were designed in order to obtain biologically active compounds. Complexes were characterized as mononuclear species that crystallized in the space group P-1 of the triclinic system with a square pyramidal geometry around the copper (II). In addition to the antiproliferative effect on murine melanoma B16 cells, complex (1) exhibited low toxicity on normal BJ cells and did not affect membrane integrity. Complex (2) proved to be a more potent antimicrobial in comparison with (1), but both compounds were more active in comparison with dmtp—both against planktonic cells and biofilms. A stronger antimicrobial and antibiofilm effect was noticed against the Gram-positive strains, including methicillin-resistant Staphylococcus aureus (MRSA). Both electron paramagnetic resonance (EPR) and Saccharomyces cerevisiae studies indicated that the complexes were scavengers rather than reactive oxygen species promoters. Their DNA intercalating capacity was evidenced by modifications in both absorption and fluorescence spectra. Furthermore, both complexes exhibited nuclease-like activity, which increased in the presence of hydrogen peroxide.

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“…Current research focuses on the design and synthesis of new complex metal antitumor agents with better biological activity and selectivity, reduced toxicity, and mechanisms of action other than those of platinum compounds, capable of overcoming the unresolved clinical problems of analogue drugs of cisplatin (serious side effects, general toxicity, and resistance) [ 5 , 6 ]. In this context, Cu +2 complexes present encouraging prospects [ 7 , 8 , 9 , 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

New Cu+2 Complexes with N-Sulfonamide Ligands: Potential Antitumor, Antibacterial, and Antioxidant Agents

et al. 2022

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Nowadays, the discovery of a new non-toxic metal complex with biological activity represents a very active area of research. Two Cu+2 complexes, [Cu(L1)2(H2O)3] (C1) (HL1= N-(5-(4-methylphenyl)-[1,3,4]–thiadiazole–2-yl)-naphtalenesulfonamide) and [Cu(L2)2(py)2(H2O)] (C2) (HL2= N-(5-ethyl-[1,3,4]–thiadiazole–2-yl)-naphtalenesulfonamide), with two new ligands were synthesized. The X-ray crystal structures of the complexes were determined. In both complexes, Cu+2 is five-coordinated, forming a CuN2O3 and CuN4O chromophore, respectively. The ligands act as monodentate, coordinating the metal ion through a single Nthiadiazole atom; for the C2 complex, the molecules from the reaction medium (pyridine and water) are also involved in the coordination of Cu+2. The complexes have a distorted square pyramidal square-planar geometry. The compounds were characterized by FT-IR, electronic EPR spectroscopy, and magnetic methods. The nuclease activity studies confirm the complexes’ capacity to cleave the DNA molecule. Using a xanthine-xanthine oxydase system, the SOD mimetic activity of the complexes was demonstrated. Cytotoxicity studies were carried out on two tumor cell lines (HeLa, WM35) and on a normal cell line (HFL1) using the MTT method, with cisplatin used as a positive control. The antibacterial activity of the complexes was investigated against two Gram-positive and two Gram-negative bacteria, and compared with Amoxicillin and Norfloxacin using the disk diffusion method. Both complexes showed in vitro biological activity but the C2 complex was more active. A lack of in vivo toxicity was demonstrated for the C2 complex by performing hepatic, renal, and hematological studies on Swiss mice.

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In vitro and in vivo studies of the antineoplastic activity of copper (II) compounds against human leukemia THP-1 and murine melanoma B16-F10 cell lines

Cited by 40 publications

References 70 publications

A selective CuII complex with 4-fluorophenoxyacetic acid hydrazide and phenanthroline displays DNA-cleaving and pro-apoptotic properties in cancer cells

A selective CuII complex with 4-fluorophenoxyacetic acid hydrazide and phenanthroline displays DNA-cleaving and pro-apoptotic properties in cancer cells

Biological Activity of Triazolopyrimidine Copper(II) Complexes Modulated by an Auxiliary N-N-Chelating Heterocycle Ligands

New Cu+2 Complexes with N-Sulfonamide Ligands: Potential Antitumor, Antibacterial, and Antioxidant Agents

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