Copper(II) complexes with new fluoroquinolones: Synthesis, structure, spectroscopic and theoretical study, DNA damage, cytotoxicity and antiviral activity

Dorotíková, Sandra; Kožíšková, Júlia; Malček, Michal; Jomová, Klaudia; Herich, Peter; Plevová, Kristína; Briestenská, Katarína; Chalupková, A; Mistríková, J; Milata, Viktor; Dvoranová, Dana; Bučinský, Lukáš

doi:10.1016/j.jinorgbio.2015.06.017

Cited by 31 publications

(10 citation statements)

References 74 publications

(86 reference statements)

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“…The CC 50 indicated that the compounds 1-3 had low toxicity to Vero cells, which is an important predictor of safety since the majority of clinically available antimicrobials are excreted primarily via the urinary tract, where they tend to accumulate. 47 In contrast to our findings, another study 48 showed that copper (II) complexes with fluoroquinolonas exhibit high cytotoxicity against Vero cell (CC 50 ranging from 2.19 to 2.45 µg mL -1 ). Such effect was attributed to the transition metal.…”

Section: Resultscontrasting

confidence: 99%

SYNTHESIS, CHARACTERIZATION AND ANTIMICROBIAL ACTIVITY OF NEW Cu (II), Co (II) AND Sn (II) COMPLEXES WITH THE SODIUM HYDROTRIS(2-MERCAPTOTHIAZOLYL)BORATE LIGAND

Ferreira¹,

Andrade²,

Lima³

et al. 2020

Quim. Nova

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Recebido em 27/11/2019; aceito em 05/02/2020; publicado na web em 16/04/2020 The emergence of antibiotic resistance among microbial pathogens is a serious public health problem, resulting in a constant need of discovering new antibiotics. For this purpose, we synthetized and determined the antimicrobial activity of copper (Cu), cobalt (Co), and tin (Sn) complexes coordinated with scorpionate ligand in a tridentate mode against microorganisms of clinical importance. New complexes with the sodium hydrotris(2-mercaptothiazolyl)borate ligand were characterized by physicochemical and spectroscopic techniques (UV-vis, IR, 1 H and 13 C NMR). Moreover, their antimicrobial activity was evaluated using microdilution broth method. Cytotoxicity was determined in Vero cells and the selectivity index (SI) was calculated. The coordination with metals increased the ligand antimicrobial activity, which showed no activity when evaluated alone (MIC>1,080 µM). Cu-complex (1) had activity against Candida albicans and C. krusei, with MICs of 130 and 66 µM, respectively. The compounds had low toxicity on Vero cells and chemo-informatics assays corroborated a low systemic toxic effect. The SI revealed that the compound 1 was 16 times more selective for C. krusei and 8 times more selective for C. albicans in relation to Vero cells. The Cu-complex stands out as a potential prototype for the development of new antifungal agents.

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Section: Resultscontrasting

confidence: 99%

SYNTHESIS, CHARACTERIZATION AND ANTIMICROBIAL ACTIVITY OF NEW Cu (II), Co (II) AND Sn (II) COMPLEXES WITH THE SODIUM HYDROTRIS(2-MERCAPTOTHIAZOLYL)BORATE LIGAND

Ferreira¹,

Andrade²,

Lima³

et al. 2020

Quim. Nova

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“…Complex 1 exhibited a pentacoordinated structure in keeping with most examples found in the literature for Cu(II)-fluoroquinolone-N,N-donor complexes. These presented a square pyramidal geometry which was confirmed by X-ray crystallographic structures [ 7 – 10 , 26 ]. Complex 2 was hexacoordinated and presented an octahedral geometry which is not common for this type of complexes.…”

Section: Resultsmentioning

confidence: 70%

Norfloxacin and N-Donor Mixed-Ligand Copper(II) Complexes: Synthesis, Albumin Interaction, and Anti-Trypanosoma cruziActivity

Martins

Gouvea

Muniz

et al. 2016

Bioinorganic Chemistry and Applications

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Copper(II) complexes with the first-generation quinolone antibacterial agent norfloxacin containing a nitrogen donor heterocyclic ligand 2,2′-bipyridine (bipy) or 1,10-phenanthroline (phen) were prepared and characterized by IR, EPR spectra, molar conductivity, and elemental analyses. The experimental data suggest that norfloxacin was coordinated to copper(II) through the carboxylato and ketone oxygen atoms. The interaction of the copper(II) complexes with bovine serum albumin (BSA) and human serum albumin (HSA) was investigated using fluorescence quenching of the tryptophan residues and copper(II) EPR spectroscopy. The results of fluorescence titration revealed that copper(II) complexes have a moderate ability to quench the intrinsic fluorescence of the albumins through a static quenching mechanism. EPR experiments showed that BSA and HSA Cu(II) sites compete with NOR for Cu(II)-bipy and Cu(II)-phen to form protein mixed-ligand complexes. Copper(II) complexes, together with the corresponding ligands, were evaluated for their trypanocidal activity in vitro against Trypanosoma cruzi, the causative agent of Chagas disease. The tests performed using bloodstream trypomastigotes showed that the Cu(II)-N-donor precursors and the metal complexes were more active than the free fluoroquinolone.

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“…If oxidative cleavage to the covalent DNA bonds occurs, new conformations of pDNA can arise: cleavage in one strand of the native superspiralized (SC) form of pDNA results in an open circular conformation (OC), while cleavage in both strands results in a linear form (LIN). Both these DNA conformations differ in their mobility in the gel and are made visible by staining with ethidium bromide [46]. From the band intensities of the DNA conformational states, their relative abundances may be determined.…”

Section: Resultsmentioning

confidence: 99%

A Switch between Antioxidant and Prooxidant Properties of the Phenolic Compounds Myricetin, Morin, 3′,4′-Dihydroxyflavone, Taxifolin and 4-Hydroxy-Coumarin in the Presence of Copper(II) Ions: A Spectroscopic, Absorption Titration and DNA Damage Study

et al. 2019

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The beneficial effects of polyphenols, predominantly in the context of oxidative stress-related diseases such as cancer, cardiovascular diseases and neurological conditions including Alzheimer’s and Parkinson’s diseases, have been documented by a number of papers and reviews. The antioxidant/prooxidant properties of phenolic compounds are related mainly to the number and positions of hydroxyl groups and to their redox metal (Cu, Fe) chelating capacity. In this work we studied structurally distinct phenolic molecules such as myricetin, morin, 3′,4′-dihydroxy-flavone, taxifolin and 4-hydroxycoumarin, either alone or as interacting with Cu2+ ions. EPR and UV-Vis spectroscopy confirmed that the effective binding of cupric ions to phenolic compounds requires the presence of the 3-OH and 4-CO groups on the flavonoid C ring and unsaturated C2-C3 bond of the C-ring, which permits through-conjugation with the B-ring. An ABTS assay revealed that radical scavenging activities of phenolic compounds are related to their number of hydroxyl groups, planarity of the molecular skeleton, extent of delocalization and they decrease in the order: myricetin > morin > 3′,4′-dihydroxyflavone ~ 4-hydroxy coumarin > taxifolin. Absorption titrations indicate that copper ions can modulate the DNA binding affinity of flavonoids via the formation of their Cu-chelates. Gel electrophoresis measurements indicated that the protective effect of the phenolic compounds decreases in the order: 3′,4′-dihydroxyflavone > 4-OH coumarin > morin > taxifolin ~ myricetin. This can be explained by the fact that myricetin, taxifolin and morin form stable Cu(II) complexes capable of causing DNA damage via interaction with DNA and ROS formation via the Fenton reaction. Application of ROS scavengers revealed the formation of singlet oxygen, superoxide and hydroxyl radicals and their concerted synergistic effect on the DNA. The overall results suggest that the most pronounced DNA damage has been observed for flavonoids containing higher number of hydroxyl groups (including 3-OH group of the C ring), such as myricetin (six hydroxyl groups), morin and taxifolin (five hydroxyl groups) in the presence of Cu(II) ions. The proposed mechanism of action by which Cu(II) complexes of myricetin, morin and taxifolin interact with DNA predispose these substances to act as potential anticancer agents. The anticancer activity of phenolic compounds can be explained by their moderate prooxidant properties, which can boost ROS formation and kill cancer cells. Alternatively, slight prooxidant properties may activate antioxidant systems, including antioxidant enzymes and low molecular antioxidants such as glutathione and thus act as preventive anticancer agents.

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Copper(II) complexes with new fluoroquinolones: Synthesis, structure, spectroscopic and theoretical study, DNA damage, cytotoxicity and antiviral activity

Cited by 31 publications

References 74 publications

SYNTHESIS, CHARACTERIZATION AND ANTIMICROBIAL ACTIVITY OF NEW Cu (II), Co (II) AND Sn (II) COMPLEXES WITH THE SODIUM HYDROTRIS(2-MERCAPTOTHIAZOLYL)BORATE LIGAND

SYNTHESIS, CHARACTERIZATION AND ANTIMICROBIAL ACTIVITY OF NEW Cu (II), Co (II) AND Sn (II) COMPLEXES WITH THE SODIUM HYDROTRIS(2-MERCAPTOTHIAZOLYL)BORATE LIGAND

Norfloxacin and N-Donor Mixed-Ligand Copper(II) Complexes: Synthesis, Albumin Interaction, and Anti-Trypanosoma cruziActivity

A Switch between Antioxidant and Prooxidant Properties of the Phenolic Compounds Myricetin, Morin, 3′,4′-Dihydroxyflavone, Taxifolin and 4-Hydroxy-Coumarin in the Presence of Copper(II) Ions: A Spectroscopic, Absorption Titration and DNA Damage Study

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