Structure-activity assessment of flavonoids as modulators of copper transport
Flavonoids are polyphenolic small molecules that are abundant in plant products and are largely recognized for their beneficial health effects. Possessing both antioxidant and prooxidant properties, flavonoids have complex behavior in biological systems. The presented work investigates the intersect...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Chemistry |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fchem.2022.972198/full |
| _version_ | 1828255397536858112 |
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| author | Vanessa J. Lee Marie C. Heffern |
| author_facet | Vanessa J. Lee Marie C. Heffern |
| author_sort | Vanessa J. Lee |
| collection | DOAJ |
| description | Flavonoids are polyphenolic small molecules that are abundant in plant products and are largely recognized for their beneficial health effects. Possessing both antioxidant and prooxidant properties, flavonoids have complex behavior in biological systems. The presented work investigates the intersection between the biological activity of flavonoids and their interactions with copper ions. Copper is required for the proper functioning of biological systems. As such, dysregulation of copper is associated with metabolic disease states such as diabetes and Wilson’s disease. There is evidence that flavonoids bind copper ions, but the biological implications of their interactions remain unclear. Better understanding these interactions will provide insight into the mechanisms of flavonoids’ biological behavior and can inform potential therapeutic targets. We employed a variety of spectroscopic techniques to study flavonoid-Cu(II) binding and radical scavenging activities. We identified structural moieties important in flavonoid-copper interactions which relate to ring substitution but not the traditional structural subclassifications. The biological effects of the investigated flavonoids specifically on copper trafficking were assessed in knockout yeast models as well as in human hepatocytes. The copper modulating abilities of strong copper-binding flavonoids were largely influenced by the relative hydrophobicities. Combined, these spectroscopic and biological data help elucidate the intricate nature of flavonoids in affecting copper transport and open avenues to inform dietary recommendations and therapeutic development. |
| first_indexed | 2024-04-13T02:14:53Z |
| format | Article |
| id | doaj.art-6457809469c54cf68e0d3dab413cdb74 |
| institution | Directory Open Access Journal |
| issn | 2296-2646 |
| language | English |
| last_indexed | 2024-04-13T02:14:53Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Chemistry |
| spelling | doaj.art-6457809469c54cf68e0d3dab413cdb742022-12-22T03:07:12ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462022-08-011010.3389/fchem.2022.972198972198Structure-activity assessment of flavonoids as modulators of copper transportVanessa J. LeeMarie C. HeffernFlavonoids are polyphenolic small molecules that are abundant in plant products and are largely recognized for their beneficial health effects. Possessing both antioxidant and prooxidant properties, flavonoids have complex behavior in biological systems. The presented work investigates the intersection between the biological activity of flavonoids and their interactions with copper ions. Copper is required for the proper functioning of biological systems. As such, dysregulation of copper is associated with metabolic disease states such as diabetes and Wilson’s disease. There is evidence that flavonoids bind copper ions, but the biological implications of their interactions remain unclear. Better understanding these interactions will provide insight into the mechanisms of flavonoids’ biological behavior and can inform potential therapeutic targets. We employed a variety of spectroscopic techniques to study flavonoid-Cu(II) binding and radical scavenging activities. We identified structural moieties important in flavonoid-copper interactions which relate to ring substitution but not the traditional structural subclassifications. The biological effects of the investigated flavonoids specifically on copper trafficking were assessed in knockout yeast models as well as in human hepatocytes. The copper modulating abilities of strong copper-binding flavonoids were largely influenced by the relative hydrophobicities. Combined, these spectroscopic and biological data help elucidate the intricate nature of flavonoids in affecting copper transport and open avenues to inform dietary recommendations and therapeutic development.https://www.frontiersin.org/articles/10.3389/fchem.2022.972198/fullflavonoidscopper traffickingantioxidant activityionophorechelator |
| spellingShingle | Vanessa J. Lee Marie C. Heffern Structure-activity assessment of flavonoids as modulators of copper transport Frontiers in Chemistry flavonoids copper trafficking antioxidant activity ionophore chelator |
| title | Structure-activity assessment of flavonoids as modulators of copper transport |
| title_full | Structure-activity assessment of flavonoids as modulators of copper transport |
| title_fullStr | Structure-activity assessment of flavonoids as modulators of copper transport |
| title_full_unstemmed | Structure-activity assessment of flavonoids as modulators of copper transport |
| title_short | Structure-activity assessment of flavonoids as modulators of copper transport |
| title_sort | structure activity assessment of flavonoids as modulators of copper transport |
| topic | flavonoids copper trafficking antioxidant activity ionophore chelator |
| url | https://www.frontiersin.org/articles/10.3389/fchem.2022.972198/full |
| work_keys_str_mv | AT vanessajlee structureactivityassessmentofflavonoidsasmodulatorsofcoppertransport AT mariecheffern structureactivityassessmentofflavonoidsasmodulatorsofcoppertransport |