Mixed ligand complexes of Co(II), Ni(II) and Cu(II) with quercetin and diimine ligands: synthesis, characterization, anti-cancer and anti-oxidant activity

Gençkal, Hasene Mutlu; Erkısa, Merve; Alper, Pınar; Şahin, Saliha; Ulukaya, Engin; Arı, Ferda

doi:10.1007/s00775-019-01749-z

Cited by 45 publications

(36 citation statements)

References 68 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Reactive oxygen species, including superoxide anion radical, hydrogen peroxide and hydroxyl radical, are produced within cells under normal aerobic growth conditions, but their production is increased under the influence of external stresses. Several recent reports suggest a role for ROS in drug-induced apoptosis through engagement of downstream proteins involved in the execution of apoptosis [ 25 , 68 ]. Modulation of oxidative stress is an important strategy in anticancer drug development.…”

Section: Discussionmentioning

confidence: 99%

Induction of Redox-Mediated Cell Death in ER-Positive and ER-Negative Breast Cancer Cells by a Copper(II)-Phenolate Complex: An In Vitro and In Silico Study

et al. 2020

View full text Add to dashboard Cite

This research was aimed at finding the cytotoxic potential of the mixed ligand copper(II) complex [Cu(tdp)(phen)](ClO4)—where H(tdp) is the tetradentate ligand 2-[(2-(2-hydroxyethylamino)-ethylimino)methyl]phenol, and phen is 1,10-phenanthroline—to two genotypically different breast cancer cells, MCF-7 (p53+ and ER+) and MDA-MB-231 (p53- and ER-). The complex has been already shown to be cytotoxic to ME180 cervical carcinoma cells. The special focus in this study was the induction of cell death by apoptosis and necrosis, and its link with ROS. The treatment brought about nuclear fragmentation, phosphatidylserine externalization, disruption of mitochondrial trans-membrane potential, DNA damage, cell cycle arrest at sub-G1 phase, and increase of ROS generation, followed by apoptotic death of cells during early hours and a late onset of necrosis in the cells surviving the apoptosis. The efficacy of the complex against genotypically different breast cancer cells is attributed to a strong association through p53-mitochondrial redox—cell cycle junction. The ADMET properties and docking of the complex at the active site of Top1 are desirable attributes of a lead molecule for development into a therapeutic. Thus, it is shown that the copper(II)–phenolate complex[Cu(tdp)(phen)]+ offers potential to be developed into a therapeutic for breast cancers in general and ER-negative ones in particular.

show abstract

Section: Discussionmentioning

confidence: 99%

Induction of Redox-Mediated Cell Death in ER-Positive and ER-Negative Breast Cancer Cells by a Copper(II)-Phenolate Complex: An In Vitro and In Silico Study

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Several such complexes that exhibit potential antitumor and/or DNA cleavage abilities have been reported. For example, complexes with ancillary ligands (an N-N-chelating heterocycle and a bioactive scaffold containing species [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ]), antibiotics [ 8 , 9 , 10 , 11 , 12 , 13 , 14 ], or anti-inflammatory drugs [ 15 , 16 , 17 , 18 ] have been shown to have potent anticancer effect, in some cases even better than the anti-tumor activity of cisplatin [ 2 , 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

Copper(II) Complexes with Mixed Heterocycle Ligands as Promising Antibacterial and Antitumor Species

et al. 2020

View full text Add to dashboard Cite

Complexes with mixed ligands [Cu(N-N)2(pmtp)](ClO4)2 ((1) N-N: 2,2′-bipyridine; (2) L: 1,10-phenanthroline and pmpt: 5-phenyl-7-methyl-1,2,4-triazolo[1,5-a]pyrimidine) were synthesized and structurally and biologically characterized. Compound (1) crystallizes into space group Pa and (2) in P-1. Both complexes display an intermediate stereochemistry between the two five-coordinated ones. The biological tests indicated that the two compounds exhibited superoxide scavenging capacity, intercalative DNA properties, and metallonuclease activity. Tests on various cell systems indicated that the two complexes neither interfere with the proliferation of Saccharomyces cerevisiae or BJ healthy skin cells, nor cause hemolysis in the active concentration range. Nevertheless, the compounds showed antibacterial potential, with complex (2) being significantly more active than complex (1) against all tested bacterial strains, both in planktonic and biofilm growth state. Both complexes exhibited a very good activity against B16 melanoma cells, with a higher specificity being displayed by compound (1). Taken together, the results indicate that complexes (1) and (2) have specific biological relevance, with potential for the development of antitumor or antimicrobial drugs.

show abstract

“…To further improve bioflavonoids in terms of their bioactivities, metal complexes with bioflavonoids as ligands to chelate transition metal ions have gained significant scientific interest (Thangavel et al, 2018 ; Gençkal et al, 2020 ; Silva et al, 2020 ; Wu et al, 2020 ). These complexes form five- and/or six-membered rings through the interaction of the metal ion with the hydroxyl moiety and/or single carbonyl group on the bioflavonoid skeleton ( Figure 2 ).…”

Section: Introductionmentioning

confidence: 99%

“…For instance, metal(II) complexes with quercetin (Gençkal et al, 2020 ; Silva et al, 2020 ), hesperitin (Tamayo et al, 2016 ), kaempferol (Tu et al, 2016 ; Thangavel et al, 2018 ), myricetin (Uivarosi et al, 2019 ), and dihydromyricetin (Li et al, 2016 ; Wu et al, 2020 ) as representative examples have been synthesized by following a general synthetic procedure for bioflavonoid–metal complexes (Tu et al, 2016 ; Maitera et al, 2018 ; Thangavel et al, 2018 ; Khater et al, 2019 ; Gençkal et al, 2020 ). The general procedure involves the deprotonation of the phenolic hydroxyl group(s) of the bioflavonoid into the corresponding phenolate, which then chelates the metal ion in an air-saturated alkaline solution.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of General Synthesis Procedures for Bioflavonoid–Metal Complexes in Air-Saturated Alkaline Solutions

Yao

Zhang

et al. 2020

Front. Chem.

View full text Add to dashboard Cite

The general synthesis methods of bioflavonoid-metal complexes are considered to be unreliable due to the instability of flavonoids in air-saturated alkaline solutions. In this study, dihydromyricetin (DHM), as a representative bioflavonoid, was selected for complexation with various transition metal ions in an air-saturated alkaline solution to form DHM-metal(II) complexes, following the general synthetic procedure. After characterization, the metal complexes were hydrolyzed to observe the stability of DHM under acidic conditions via HPLC. The effects of synthetic conditions (metal ion, alkalinity, and reflux time) on DHM stability were then investigated by UV-vis spectroscopy and HPLC. Finally, using electron paramagnetic resonance, DHM and its analogs were observed with DMPO (5,5-dimethyl-1-pyrroline-N-oxide) to form a relatively stable free radical adduct. Multiple peaks corresponding to unknown compounds appeared in the LC spectra of the DHM-metal(II) complexes after hydrolysis, indicating that some DHM reacted during synthesis. Subsequently, the transition metal ion and solution alkalinity were found to have notable effects on the stability of free DHM. Furthermore, DHM and several of its analogs generated the superoxide-anion radical in air-saturated alkaline solutions. Their capacities for generating the superoxide anion seemed to correspond to the number and/or location of hydroxyl groups or their configurations. Interestingly, DHM can react with the superoxide anion to transform into myricetin, which involves the abstraction of a C3-H atom from DHM by O 2 −. Therefore, the general synthetic procedure for bioflavonoid-metal complexes in air-saturated alkaline solutions should be improved.

show abstract

Mixed ligand complexes of Co(II), Ni(II) and Cu(II) with quercetin and diimine ligands: synthesis, characterization, anti-cancer and anti-oxidant activity

Cited by 45 publications

References 68 publications

Induction of Redox-Mediated Cell Death in ER-Positive and ER-Negative Breast Cancer Cells by a Copper(II)-Phenolate Complex: An In Vitro and In Silico Study

Induction of Redox-Mediated Cell Death in ER-Positive and ER-Negative Breast Cancer Cells by a Copper(II)-Phenolate Complex: An In Vitro and In Silico Study

Copper(II) Complexes with Mixed Heterocycle Ligands as Promising Antibacterial and Antitumor Species

Evaluation of General Synthesis Procedures for Bioflavonoid–Metal Complexes in Air-Saturated Alkaline Solutions

Contact Info

Product

Resources

About