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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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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Due to the lack of conjugation, flavanones usually have lower antioxidant activity.
“Due to the lack of conjugation, flavanones usually have lower antioxidant activity (Jomova et al. 2019).”
From Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging (2023) · cites this paper as Jomova et al. 2019
Many natural antioxidants taken from diet or from supplements have very limited bioavailability and their in vitro antioxidant activity and ability to regenerate themselves have not been confirmed in cells or tissues.
“Many natural antioxidants taken from diet or from supplements have very limited bioavailability and their in vitro antioxidant activity and ability to regenerate themselves have not been confirmed in cells or tissues (Jomova et al. 2019).”
From Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging (2023) · cites this paper as Jomova et al. 2019
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Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging
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Lomozová, Z., Hrubša, M., Conte, P. F., Papastefanaki, E., Moravcová, M., Catapano, M. C., Proietti Silvestri, I., Karlíčková, J., Kučera, R., Macáková, K., et al. (2022) · Food Chemistry · doi:10.1016/j.foodchem.2022.133461 · Cited by 44 · see citing works
- Authors
- Jomová, K., Hudecova, L., Lauro, P., Simunkova, M., Alwasel, S. H., Alhazza, I. M., & Valko, M.
- Affiliations
- Constantine the Philosopher University in Nitra (SK)
- Department of Chemistry, Constantine the Philosopher University in Nitra, 949 74 Nitra, Slovakia
- Faculty Chemical and Food Technology, Slovak University of Technology, 812 37 Bratislava, Slovakia
- King Saud University (SA)
- Venue
- Molecules
- Publisher
- MDPI AG
- Published
- 2019-11-27
- Volume
- 24
- Issue
- 23
- Pages
- 4335
- ISSN
- 1420-3049 (ISSN-L)
- PMC
- PMC6930463
- OpenAlex
- W2991164219
- Cited by
- 172
- References
- 63
- Citations by year
- 2026: 13 · 2025: 21 · 2024: 35 · 2023: 37 · 2022: 27 · 2021: 23 · 2020: 16
- FWCI
- 6.47
- Type
- journal article
- Language
- en
- Open access
- gold
- dx.doi.org
- Licence
- Locations
- Molecules (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Agentúra na Podporu Výskumu a Vývoja (APVV-15-0079)
- VEGA (1/0686/17)
- Researchers Supporting Project (RSP-2019/59)
- Topics
- Physical Sciences › Chemistry › Organic Chemistry › Free Radicals and Antioxidants
- Health Sciences › Medicine › Biochemistry › Phytochemicals and Antioxidant Activities
- Health Sciences › Medicine › Pharmacology › Flavonoids in Medical Research
- Keywords
- flavonoids, myricetin, morin, taxifolin, 4-hydroxycoumarin, copper(II) complexes, metal chelation, DNA damage, free radical scavenging, singlet oxygen, superoxide, hydroxyl radicals, Fenton reaction, oxidative stress
- MeSH terms
- Antineoplastic Agents, Antioxidants, Chelating Agents, Copper, Coumarins, DNA Damage, Electron Spin Resonance Spectroscopy, Flavonoids, Humans, Ions, Quercetin, Reactive Oxygen Species, Hydroxyl Radical, Flavones, Photoelectron Spectroscopy, Polyphenols
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