{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T06:13:24Z","timestamp":1791008004734,"version":"4.1.0"},"reference-count":70,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,2,5]],"date-time":"2021-02-05T00:00:00Z","timestamp":1612483200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006109","name":"Scientific Grant Agency","doi-asserted-by":"publisher","award":["VEGA Project 1\/0482\/20"],"award-info":[{"award-number":["VEGA Project 1\/0482\/20"]}],"id":[{"id":"10.13039\/501100006109","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Research and Development Support Agency","award":["APVV-15-0079 and APVV-19-0087"],"award-info":[{"award-number":["APVV-15-0079 and APVV-19-0087"]}]},{"name":"Slovak University of Technology","award":["Young Researcher Grant - FLAVMET"],"award-info":[{"award-number":["Young Researcher Grant - FLAVMET"]}]},{"name":"Slovak University of Techology","award":["Excellent Team of Young Researchers CUSPK"],"award-info":[{"award-number":["Excellent Team of Young Researchers CUSPK"]}]},{"name":"King Saud University, Riyadh, Saudi Arabia","award":["Researchers Supporting Project (RSP-2020\/59)"],"award-info":[{"award-number":["Researchers Supporting Project (RSP-2020\/59)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Kaempferol is a flavonoid that occurs in tea and in many vegetables and fruits, including broccoli, cabbage, beans, grapes, apples, and strawberries. The efficacy of Kaempferol has been demonstrated in the treatment of breast, esophageal, cervical, ovarian, and liver cancers and leukemia, which very likely arises from its prooxidant properties and the activation of pro-apoptotic pathways. Indeed, this matter has already been the focus of a number of published studies and reviews. The aim of the present study was to elucidate the antioxidant vs. prooxidant properties of flavonoids in the presence of the redox-active metal, copper (II) ion, by means of the Fenton reaction. The specific motivation of this work is that, since an increased level of Cu(II) ions is known to be associated with many disease states such as neurological conditions (Alzheimer\u2019s disease) and cancer, any interaction between these ions and flavonoids might affect the outcome of therapeutic uses of the latter. The structure of the Cu-kaempferol complex in DMSO was investigated by means of low temperature EPR spectroscopy, which confirmed the existence of at least two distinct coordination environments around the copper (II) ion. UV vis-spectra of kaempferol and its Cu(II) complex in DMSO revealed an interaction between the 5-OH (A ring) group and the 4-CO (C ring) group of kaempferol with Cu(II) ions. An ABTS assay confirmed that kaempferol acted as an effective radical scavenger, and that this effect was further enhanced in the form of the Cu(II)-kaempferol complex. Quantitative EPR spin trapping experiments, using DMPO as the spin trap, confirmed suppression of the formation of a mixture of hydroxyl, superoxide, and methyl radicals, in a Fenton reaction system, upon coordination of kaempferol to the redox-active Cu(II) ions, by 80% with respect to the free Cu(II) ions. A viscometric study revealed a better DNA-intercalating ability of the Cu-kaempferol complex than for free kaempferol, essential for conferring anticancer activity of these substances. The results of the viscometric measurements were compared with those from a DNA damage study of Cu-kaempferol complexes in a Fenton reaction system, using gel electrophoresis. At low concentrations of kaempferol (Cu\u2013kaempferol ratios of 1:1 and 1:2), a very weak protective effect on DNA was noted, whereas when kaempferol was present in excess, a significant DNA-protective effect was found. This can be explained if the weakly intercalated kaempferol molecules present at the surface of DNA provide protection against attack by ROS that originate from the Fenton reaction involving intercalated Cu(II)-kaempferol complexes. Following the application of ROS scavengers, L-histidine, DMSO, and SOD, gel electrophoresis confirmed the formation of singlet oxygen, hydroxyl radicals, and superoxide radical anions, respectively. We propose that the prooxidant properties of Cu-kaempferol complexes may provide anticancer activity of these substances. When present in excess, kaempferol displays antioxidant properties under Cu-Fenton conditions. This suggests that kaempferol might prove a suitable candidate for the prevention or treatment of oxidative stress related medical conditions that involve a disturbed metabolism of redox metals such as copper, for example, Menkes disease, and neurological disorders, including Alzheimer\u2019s disease. For the potential use of kaempferol in clinical practice, it will be necessary to optimize the dose size and critical age of the patient so that this flavonoid may be beneficial as a preventive drug against cancer and neurological disorders.<\/jats:p>","DOI":"10.3390\/ijms22041619","type":"journal-article","created":{"date-parts":[[2021,2,5]],"date-time":"2021-02-05T08:33:48Z","timestamp":1612514028000},"page":"1619","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":171,"title":["Antioxidant vs. Prooxidant Properties of the Flavonoid, Kaempferol, in the Presence of Cu(II) Ions: A ROS-Scavenging Activity, Fenton Reaction and DNA Damage Study"],"prefix":"10.3390","volume":"22","author":[{"given":"Miriama","family":"Simunkova","sequence":"first","affiliation":[{"name":"Institute of Physical Chemistry and Chemical Physics, Faculty of Chemical and Food Technology, Slovak University of Technology, 812 37 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuzana","family":"Barbierikova","sequence":"additional","affiliation":[{"name":"Institute of Physical Chemistry and Chemical Physics, Faculty of Chemical and Food Technology, Slovak University of Technology, 812 37 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaudia","family":"Jomova","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Natural Sciences, Constantine the Philosopher University in Nitra, 949 74 Nitra, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lenka","family":"Hudecova","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Natural Sciences, Constantine the Philosopher University in Nitra, 949 74 Nitra, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Lauro","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Natural Sciences, Constantine the Philosopher University in Nitra, 949 74 Nitra, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saleh H.","family":"Alwasel","sequence":"additional","affiliation":[{"name":"Zoology Department, College of Science, King Saud University, Riyadh 12372, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim","family":"Alhazza","sequence":"additional","affiliation":[{"name":"Zoology Department, College of Science, King Saud University, Riyadh 12372, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2929-4466","authenticated-orcid":false,"given":"Christopher J.","family":"Rhodes","sequence":"additional","affiliation":[{"name":"Fresh-Lands Environmental Actions, Reading, Berkshire RG4 5BE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marian","family":"Valko","sequence":"additional","affiliation":[{"name":"Institute of Physical Chemistry and Chemical Physics, Faculty of Chemical and Food Technology, Slovak University of Technology, 812 37 Bratislava, Slovakia"},{"name":"Zoology Department, College of Science, King Saud University, Riyadh 12372, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1016\/0891-5849(95)02227-9","article-title":"Structure-antioxidant activity relationships of flavonoids and phenolic acids","volume":"20","author":"Miller","year":"1996","journal-title":"Free Radic. Biol. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1016\/j.freeradbiomed.2004.01.001","article-title":"Flavonoids: Antioxidants or signalling molecules?","volume":"36","author":"Williams","year":"2004","journal-title":"Free Radic. Biol. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/j.fitote.2011.01.018","article-title":"Antioxidant and prooxidant properties of flavonoids","volume":"82","author":"Prochazkova","year":"2011","journal-title":"Fitoterapia"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.fct.2017.10.042","article-title":"Protective role of quercetin against copper(II)-induced oxidative stress: A spectroscopic, theoretical and DNA damage study","volume":"110","author":"Jomova","year":"2017","journal-title":"Food Chem. Toxicol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.1016\/j.saa.2008.07.030","article-title":"Synthesis, characterization and antioxidant activity copper-quercetin complex","volume":"71","author":"Bukhari","year":"2009","journal-title":"Spectrochim. Acta A Mol. Biomol. Spectrosc."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1016\/j.foodchem.2013.09.080","article-title":"Antioxidant study of quercetin and their metal complex and determination of stability constant by spectrophotometry method","volume":"146","author":"Ravichandran","year":"2014","journal-title":"Food Chem."},{"key":"ref_7","first-page":"1440","article-title":"Hydrolytic cleavage of DNA by ternary amino acid schiff base copper (II) complexes having planar heterocyclic ligands","volume":"7","author":"Pattubala","year":"2004","journal-title":"Eur. J. Inorg. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"0165575","DOI":"10.1371\/journal.pone.0165575","article-title":"In Vitro Antioxidant versus Metal Ion Chelating Properties of Flavonoids: A Structure-Activity Investigation","volume":"11","author":"Cherrak","year":"2016","journal-title":"PLoS ONE"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Jomova, L., Hudecova, L., Lauro, P., Simunkova, M., Alwasel, S.H., Alhazza, I.M., and Valko, M. (2019). A Switch between Antioxidant and Prooxidant Properties of the Phenolic Compounds Myricetin, Morin, 3\u2032,4\u2032-Dihydroxyflavone, Taxifolin and 4-Hydroxy-Coumarin in the Presence of Copper(II) Ions: A Spectroscopic, Absorption Titration and DNA Damage Study. Molecules, 23.","DOI":"10.3390\/molecules24234335"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1080\/152165400300001471","article-title":"Putative Mechanism for Anticancer and Apoptosis-Inducing Properties of Plant-Derived Polyphenolic Compounds","volume":"50","author":"Hadi","year":"2000","journal-title":"IUBMB Life"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"26754","DOI":"10.3390\/ijms161125992","article-title":"Mobilization of Copper ions by Flavonoids in Human Peripheral Lymphocytes Leads to Oxidative DNA Breakage: A Structure Activity Study","volume":"16","author":"Arif","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Borowska, S., Tomczyk, M., Strawa, J.W., and Brz\u00f3ska, M.M. (2020). Estimation of the Chelating Ability of an Extract from Aronia melanocarpa L. Berries and Its Main Polyphenolic Ingredients Towards Ions of Zinc and Copper. Molecules, 25.","DOI":"10.3390\/molecules25071507"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1007\/s00775-009-0486-8","article-title":"DNA binding and oxidative DNA damage induced by a quercetin copper(II) complex: Potential mechanism of its antitumor properties","volume":"14","author":"Tan","year":"2009","journal-title":"J. Biol. Inorg. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Kim, J.H., Kim, Y.S., Choi, J.G., Li, W., Lee, E.J., Park, J.W., Song, J., and Chung, H.S. (2020). Kaempferol and Its Glycoside, Kaempferol 7-O-rhamnoside, Inhibit PD-1\/PD-L1 Interaction In Vitro. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21093239"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Deng, S.P., Yang, Y.L., Cheng, X.X., Li, W.R., and Cai, J.Y. (2019). Synthesis, Spectroscopic Study and Radical Scavenging Activity of Kaempferol Derivatives: Enhanced Water Solubility and Antioxidant Activity. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20040975"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Budisan, L., Gulei, D., Jurj, A., Braicu, C., Zanoaga, O., Cojocneanu, R., Pop, L., Raduly, L., Barbat, A., and Moldovan, A. (2019). Inhibitory Effect of CAPE and Kaempferol in Colon Cancer Cell LinesPossible Implications in New Therapeutic Strategies. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20051199"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"11830","DOI":"10.3390\/ijms140611830","article-title":"Versatile Redox Chemistry Complicates Antioxidant Capacity Assessment: Flavonoids as Milieu-Dependent Anti- and Pro-Oxidants","volume":"14","author":"Chobot","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Chobot, V., Hadacek, F., Bachmann, G., Weckwerth, W., and Kubicova, L. (2016). Pro- and Antioxidant Activity of Three Selected Flavan Type Flavonoids: Catechin, Eriodictyol and Taxifolin. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17121986"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Alam, W., Khan, H., Shah, M.A., Cauli, O., and Saso, L. (2020). Kaempferol as a Dietary Anti-Inflammatory Agent: Current Therapeutic Standing. Molecules, 25.","DOI":"10.3390\/molecules25184073"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Yang, Z.Y., Qian, L.L., Xu, Y., Song, M.T., Liu, C., Han, R.M., Zhang, J.P., and Skibsted, L.H. (2020). Kinetic Studies on Radical Scavenging Activity of Kaempferol Decreased by Sn(II) Binding. Molecules, 25.","DOI":"10.3390\/molecules25081975"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Imran, M., Salehi, B., Sharifi-Rad, J., Aslam Gondal, T., Saeed, F., Imran, A., Shahbaz, M., Tsouh Fokou, P.V., Umair Arshad, M., and Khan, H. (2019). Kaempferol: A Key Emphasis to Its Anticancer Potential. Molecules, 24.","DOI":"10.3390\/molecules24122277"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Wu, P., Meng, X., Zheng, H., Zeng, Q., Chen, T., Wang, W., Zhang, X., and Su, J. (2018). Kaempferol Attenuates ROS-Induced Hemolysis and the Molecular Mechanism of Its Induction of Apoptosis on Bladder Cancer. Molecules, 23.","DOI":"10.3390\/molecules23102592"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2115","DOI":"10.3390\/molecules20022115","article-title":"Synthesis, crystal structure, spectroscopic properties and potential biological activities of salicylate-neocuproine ternary copper(II) complexes","volume":"20","author":"Kuckova","year":"2015","journal-title":"Molecules"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1016\/j.jinorgbio.2007.01.005","article-title":"New complexes of La(III), Ce(III), Pr(III), Nd(III), Sm(III), Eu(III) and Gd(III) ions with morin","volume":"101","author":"Kopacz","year":"2007","journal-title":"J. Inorg. Biochem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"45853","DOI":"10.1039\/C5RA05069C","article-title":"Properties and applications of flavonoid metal complexes","volume":"5","author":"Kasprzask","year":"2015","journal-title":"RSC Adv."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"921","DOI":"10.2298\/JSC0710921M","article-title":"Investigation of metal-flavonoid chelates and the determination of flavonoids via metal-flavonoid complexing reactions","volume":"72","author":"Malesev","year":"2007","journal-title":"J. Serb. Chem. Soc."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4846","DOI":"10.1021\/ja00090a032","article-title":"Flavonoids as Antioxidants","volume":"116","author":"Jovanovic","year":"1994","journal-title":"J. Am. Chem. Soc."},{"key":"ref_28","first-page":"12","article-title":"Bioactive flavonoids in medicinal plants: Structure, activity and biological fate","volume":"13","author":"Wang","year":"2018","journal-title":"Asian J. Pharmacol. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.molstruc.2009.12.037","article-title":"Synthesis, characterization, spectroscopic and antioxidation studies of Cu(II)\u2013morin complex","volume":"967","author":"Panhwar","year":"2010","journal-title":"J. Mol. Struct."},{"key":"ref_30","first-page":"730","article-title":"Structure Activity Relationship and Prediction of the Electron-Transfer Potential of the Xanthones Series","volume":"7","author":"Li","year":"2018","journal-title":"Chem. Open"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1021\/ed054p612","article-title":"Graphical display of the enthalpies of adduct formation for Lewis acids and bases","volume":"54","author":"Cramer","year":"1977","journal-title":"J. Chem. Educ."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s10534-010-9372-7","article-title":"Interaction of quercetin with copper ions: Complexation, oxidation and reactivity towards radicals","volume":"24","author":"Pekal","year":"2011","journal-title":"Biometals"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Szabados-Furjesi, P., Pajtas, D., Barta, D., Czepanyi, E., Kiss-Szikszai, A., Tosaki, A., and Bak, I. (2018). Synthesis, in vitro evaluation, and oxidative transformation of new flavonoid derivatives: The possible role of the phenyl-N,N dimethylamino group. Molecules, 23.","DOI":"10.3390\/molecules23123161"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1016\/j.carres.2006.01.014","article-title":"Degradation of high-molecular-weight hyaluronan by hydrogen peroxide in the presence of cupric ions","volume":"341","author":"Soltes","year":"2006","journal-title":"Carbohydr Res."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Hricov\u00edni, M., Maz\u00far, M., S\u00eerbu, A., Palamarciuc, O., Arion, V.B., and Brezov\u00e1, V. (2018). Copper(II) thiosemicarbazone complexes and their proligands upon UVA irradiation: An EPR and spectrophotometric steady-state study. Molecules, 23.","DOI":"10.3390\/molecules23040721"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.jcat.2013.01.025","article-title":"Fenton-like copper redox chemistry revisited: Hydrogen peroxide and superoxide mediation of copper-catalyzed oxidant production","volume":"301","author":"Pham","year":"2013","journal-title":"J. Catal."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2907","DOI":"10.1021\/ja903856t","article-title":"How Solvent Modulates Hydroxyl Radical Reactivity in Hydrogen Atom Abstractions","volume":"132","author":"Mitroka","year":"2010","journal-title":"J. Am. Chem. Soc."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1063\/1.555805","article-title":"Critical-review of rate constants for reactions of hydrated electrons, hydrogen-atoms and hydroxyl radicals (\u2022OH\/\u2022O\u2013) in aqueous-solution","volume":"17","author":"Buxton","year":"1988","journal-title":"J. Phys. Chem. Ref. Data"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1002\/ptr.5643","article-title":"Prooxidant Activity of Polyphenols, Flavonoids, Anthocyanins and Carotenoids: Updated Review of Mechanisms and Catalyzing Metals","volume":"30","author":"Eghbaliferiz","year":"2016","journal-title":"Phytother. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1002\/med.21301","article-title":"Flavonoid-metal ion complexes: A novel class of therapeutic agents","volume":"34","author":"Selvaraj","year":"2014","journal-title":"Med. Res. Rev."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"6128","DOI":"10.3390\/molecules18066128","article-title":"Superoxide scavenging effects of some novel bis-ligands and their solvated metal complexes prepared by the reaction of ligands with aluminum, copper and lanthanum ions","volume":"18","author":"Kobayashi","year":"2013","journal-title":"Molecules"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"516","DOI":"10.3390\/50300516","article-title":"Formation of complexes of flavonoids and metals. Determination of the Stoichiometry and Stability Constants","volume":"5","author":"Barolli","year":"2000","journal-title":"Molecules"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"8583","DOI":"10.3390\/molecules20058583","article-title":"Studies on transition metal-quercetin complexes using electrospray ionization tandem mass spectrometry","volume":"20","author":"Liu","year":"2015","journal-title":"Molecules"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1016\/j.jinorgbio.2005.02.020","article-title":"Copper(II) complexes of 1,10-phenanthroline-derived ligands: Studies on DNA binding properties and nuclease activity","volume":"99","author":"Hirohama","year":"2005","journal-title":"J. Inorg. Biochem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.jinorgbio.2012.03.005","article-title":"Copper(II) complexes with antimicrobial drug flumequine: Structure and biological evaluation","volume":"113","author":"Chalkidou","year":"2012","journal-title":"J. Inorg. Biochem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1016\/j.jinorgbio.2010.08.013","article-title":"Interaction of copper(II) with the non-steroidal anti-inflammatory drugs naproxenand diclofenac: Synthesis, structure, DNA- and albumin-binding","volume":"105","author":"Dimiza","year":"2011","journal-title":"J. Inorg. Biochem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.1016\/j.jinorgbio.2011.09.004","article-title":"Non-steroidal anti-inflammatory drug diflunisal interacting with Cu(II). Structure and biological features","volume":"105","author":"Fountoulaki","year":"2011","journal-title":"J. Inorg. Biochem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/S0010-8545(02)00027-9","article-title":"The interactions of metal ions with quinolone antibacterial agents","volume":"232","author":"Turel","year":"2002","journal-title":"Coord. Chem. Rev."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.jphotobiol.2009.03.006","article-title":"An overview of structural features of DNA and RNA complexes withsaffron compounds: Models and antioxidant activity","volume":"95","author":"Kanakis","year":"2009","journal-title":"J. Photochem. Photobiol. B"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s12013-009-9054-7","article-title":"Antioxidant activity of sulfur and selenium: A review of reactive oxygen species scavenging, glutathione peroxidase, and metal-binding antioxidant mechanisms","volume":"55","author":"Battin","year":"2009","journal-title":"Cell. Biochem. Biophys."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Lerner, A., Kornweitz, H., Zilberman, I., Yardeni, G., Saphier, M., Bar, R., and Meyerstein, D. (2020). Radicals in \u2018biologically relevant\u2019 concentrations behave differently: Uncovering new radical reactions following the reaction of hydroxyl radicals with DMSO. Free Radic. Biol. Med., in press.","DOI":"10.1016\/j.freeradbiomed.2020.11.012"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2415","DOI":"10.1021\/jp027743m","article-title":"Role of Radicals and Singlet Oxygen in Photoactivated DNA Cleavage by the Anticancer Drug Camptothecin:\u2009 An Electron Paramagnetic Resonance Study","volume":"107","author":"Brezova","year":"2003","journal-title":"J. Phys. Chem. B"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1016\/j.tips.2017.04.005","article-title":"Targeting Free Radicals in Oxidative Stress-Related Human Diseases","volume":"38","author":"Poprac","year":"2017","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1006\/jmre.1999.1915","article-title":"Analysis of the radial and longitudinal effect in a double TE(104) and a single TE(102) rectangular cavity","volume":"142","author":"Valko","year":"2000","journal-title":"J. Magn. Reson."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Ciulu, M., C\u00e1diz-Gurrea, M.L., and Segura-Carretero, A. (2018). Extraction and Analysis of Phenolic Compounds in Rice: A Review. Molecules, 23.","DOI":"10.3390\/molecules23112890"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1006\/jmrb.1994.1062","article-title":"Simulation of multiple isotropic spin-trap EPR spectra","volume":"104","author":"Duling","year":"1994","journal-title":"J. Magn. Reson. B"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.jmr.2005.08.013","article-title":"EasySpin, a comprehensive software package for spectral simulation and analysis in EPR","volume":"178","author":"Stoll","year":"2006","journal-title":"J. Magn. Reson."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/j.jinorgbio.2011.02.009","article-title":"Antioxidant and prooxidant effects of polyphenol compounds on copper-mediated DNA damage","volume":"105","author":"Perron","year":"2011","journal-title":"J. Inorg. Biochem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1007\/s00394-015-0910-5","article-title":"Fruit peel polyphenols demonstrate substantial anti-tumour effects in the model of breast cancer","volume":"55","author":"Kubatka","year":"2016","journal-title":"Eur. J. Nutr."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"891748","DOI":"10.1155\/2013\/891748","article-title":"Polyphenols: Multipotent therapeutic agents in neurodegenerative diseases","volume":"2013","author":"Bhullar","year":"2013","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3540","DOI":"10.3390\/ijms14023540","article-title":"Flavonoids as Antioxidants and Developmental Regulators: Relative Significance in Plants and Humans","volume":"14","author":"Brunetti","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Kostecka-Guga\u0142a, A., Kruczek, M., Ledwo\u017cyw-Smole\u0144, I., and Kaszycki, P. (2020). Antioxidants and Health-Beneficial Nutrients in Fruits of Eighteen Cucurbita Cultivars: Analysis of Diversity and Dietary Implications. Molecules, 25.","DOI":"10.3390\/molecules25081792"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Romanucci, V., Di Fabio, G., and Zarrelli, A. (2019). A new class of synthetic flavonolignan-like dimers: Still few molecules, but with attractive properties. Molecules, 24.","DOI":"10.3390\/molecules24010108"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez-Garc\u00eda, C., S\u00e1nchez-Quesada, C., Toledo, E., Delgado-Rodr\u00edguez, M., and Gaforio, J.J. (2019). Naturally lignan-rich foods: A dietary tool for health promotion?. Molecules, 24.","DOI":"10.3390\/molecules24050917"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Hussain, G., Zhang, L., Rasul, A., Anwar, H., Sohail, M.U., Razzaq, A., Aziz, N., Shabbir, A., Ali, M., and Sun, T. (2018). Role of plant-derived flavonoids and their mechanism in attenuation of Alzheimer\u2019s and Parkinson\u2019s diseases: An update of recent data. Molecules, 23.","DOI":"10.3390\/molecules23040814"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Martinez-Gonzalez, A.I., D\u00edaz-S\u00e1nchez, A.G., De La Rosa, L.A., Vargas-Requena, C.L., Bustos-Jaimes, I., and Alvarez-Parrilla, E. (2017). Polyphenolic compounds and digestive enzymes: In vitro non-covalent interactions. Molecules, 22.","DOI":"10.3390\/molecules22040669"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Kachlicki, P., Piasecka, A., Stobiecki, M., and Marczak, \u0141. (2016). Structural characterization of flavonoid glycoconjugates and their derivatives with mass spectrometric techniques. Molecules, 21.","DOI":"10.3390\/molecules21111494"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Cirmi, S., Ferlazzo, N., Lombardo, G.E., Ventura-Spagnolo, E., Gangemi, S., Calapai, G., and Navarra, M. (2016). Neurodegenerative diseases: Might citrus flavonoids play a protective role?. Molecules, 21.","DOI":"10.3390\/molecules21101312"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"16240","DOI":"10.3390\/molecules191016240","article-title":"Flavonoids as important molecules of plant interactions with the environment","volume":"19","author":"Mierziak","year":"2014","journal-title":"Molecules"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Kej\u00edk, Z., Kapl\u00e1nek, R., Masa\u0159\u00edk, M., Babula, P., Matkowski, A., Filipensk\u00fd, P., Vesela, K., Gburek, J., S\u00fdkora, D., and Martasek, P. (2021). Iron complexes of flavonoids\u2014Antioxidant capacity and beyond. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22020646"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/4\/1619\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:20:08Z","timestamp":1760160008000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/4\/1619"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,5]]},"references-count":70,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,2]]}},"alternative-id":["ijms22041619"],"URL":"https:\/\/doi.org\/10.3390\/ijms22041619","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,5]]}}}