Resveratrol Analogues as Selective Estrogen Signaling Pathway Modulators: Structure–Activity Relationship
Resveratrol is a plant-derived phytoalexin found in grapes, red wine and many other plants used in Asian folk medicine. It is extensively studied for pleiotropic biological activity. The most crucial are anticancer and chemopreventive properties. Resveratrol has also been reported to be an antioxida...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-10-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/27/20/6973 |
| _version_ | 1797470842565689344 |
|---|---|
| author | Paulina Kobylka Malgorzata Kucinska Jacek Kujawski Dawid Lazewski Marcin Wierzchowski Marek Murias |
| author_facet | Paulina Kobylka Malgorzata Kucinska Jacek Kujawski Dawid Lazewski Marcin Wierzchowski Marek Murias |
| author_sort | Paulina Kobylka |
| collection | DOAJ |
| description | Resveratrol is a plant-derived phytoalexin found in grapes, red wine and many other plants used in Asian folk medicine. It is extensively studied for pleiotropic biological activity. The most crucial are anticancer and chemopreventive properties. Resveratrol has also been reported to be an antioxidant and phytoestrogen. The phytoestrogenic activity of resveratrol was assayed in different in vitro and in vivo models. Although these works brought some, on the first look, conflicting results, it is commonly accepted that resveratrol interacts with estrogen receptors and functions as a mixed agonist/antagonist. It is widely accepted that the hydroxyl groups are crucial for resveratrol’s cytotoxic and antioxidative activity and are responsible for binding estrogen receptors. In this work, we assayed 11 resveratrol analogues, seven barring methoxy groups and six hydroxylated analogues in different combinations at positions 3, 4, 5 and 3′,4′,5′. For this purpose, recombined estrogen receptors and estrogen-dependent MCF-7 and Ishikawa cells were used. Our study was supported by in silico docking studies. We have shown that, resveratrol and 3,4,4′5′-tetrahydroxystilbene, 3,3′,4,5,5′-pentahydroxystilbene and 3,3′,4,4′,5,5′-hexahydroxystilbene may act as selective estrogen receptor modulators. |
| first_indexed | 2024-03-09T19:42:40Z |
| format | Article |
| id | doaj.art-ae41fa2712eb49fb9ab9dd98ab8bc0c0 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T19:42:40Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-ae41fa2712eb49fb9ab9dd98ab8bc0c02023-11-24T01:34:52ZengMDPI AGMolecules1420-30492022-10-012720697310.3390/molecules27206973Resveratrol Analogues as Selective Estrogen Signaling Pathway Modulators: Structure–Activity RelationshipPaulina Kobylka0Malgorzata Kucinska1Jacek Kujawski2Dawid Lazewski3Marcin Wierzchowski4Marek Murias5Department of Toxicology, Poznan University of Medical Sciences, 60-631 Poznan, PolandDepartment of Toxicology, Poznan University of Medical Sciences, 60-631 Poznan, PolandChair and Department of Organic Chemistry, Poznan University of Medical Sciences, 60-780 Poznan, PolandChair and Department of Chemical Technology of Drugs, Poznan University of Medical Sciences, 60-780 Poznan, PolandChair and Department of Chemical Technology of Drugs, Poznan University of Medical Sciences, 60-780 Poznan, PolandDepartment of Toxicology, Poznan University of Medical Sciences, 60-631 Poznan, PolandResveratrol is a plant-derived phytoalexin found in grapes, red wine and many other plants used in Asian folk medicine. It is extensively studied for pleiotropic biological activity. The most crucial are anticancer and chemopreventive properties. Resveratrol has also been reported to be an antioxidant and phytoestrogen. The phytoestrogenic activity of resveratrol was assayed in different in vitro and in vivo models. Although these works brought some, on the first look, conflicting results, it is commonly accepted that resveratrol interacts with estrogen receptors and functions as a mixed agonist/antagonist. It is widely accepted that the hydroxyl groups are crucial for resveratrol’s cytotoxic and antioxidative activity and are responsible for binding estrogen receptors. In this work, we assayed 11 resveratrol analogues, seven barring methoxy groups and six hydroxylated analogues in different combinations at positions 3, 4, 5 and 3′,4′,5′. For this purpose, recombined estrogen receptors and estrogen-dependent MCF-7 and Ishikawa cells were used. Our study was supported by in silico docking studies. We have shown that, resveratrol and 3,4,4′5′-tetrahydroxystilbene, 3,3′,4,5,5′-pentahydroxystilbene and 3,3′,4,4′,5,5′-hexahydroxystilbene may act as selective estrogen receptor modulators.https://www.mdpi.com/1420-3049/27/20/6973resveratrolestrogen receptorresveratrol analogues |
| spellingShingle | Paulina Kobylka Malgorzata Kucinska Jacek Kujawski Dawid Lazewski Marcin Wierzchowski Marek Murias Resveratrol Analogues as Selective Estrogen Signaling Pathway Modulators: Structure–Activity Relationship Molecules resveratrol estrogen receptor resveratrol analogues |
| title | Resveratrol Analogues as Selective Estrogen Signaling Pathway Modulators: Structure–Activity Relationship |
| title_full | Resveratrol Analogues as Selective Estrogen Signaling Pathway Modulators: Structure–Activity Relationship |
| title_fullStr | Resveratrol Analogues as Selective Estrogen Signaling Pathway Modulators: Structure–Activity Relationship |
| title_full_unstemmed | Resveratrol Analogues as Selective Estrogen Signaling Pathway Modulators: Structure–Activity Relationship |
| title_short | Resveratrol Analogues as Selective Estrogen Signaling Pathway Modulators: Structure–Activity Relationship |
| title_sort | resveratrol analogues as selective estrogen signaling pathway modulators structure activity relationship |
| topic | resveratrol estrogen receptor resveratrol analogues |
| url | https://www.mdpi.com/1420-3049/27/20/6973 |
| work_keys_str_mv | AT paulinakobylka resveratrolanaloguesasselectiveestrogensignalingpathwaymodulatorsstructureactivityrelationship AT malgorzatakucinska resveratrolanaloguesasselectiveestrogensignalingpathwaymodulatorsstructureactivityrelationship AT jacekkujawski resveratrolanaloguesasselectiveestrogensignalingpathwaymodulatorsstructureactivityrelationship AT dawidlazewski resveratrolanaloguesasselectiveestrogensignalingpathwaymodulatorsstructureactivityrelationship AT marcinwierzchowski resveratrolanaloguesasselectiveestrogensignalingpathwaymodulatorsstructureactivityrelationship AT marekmurias resveratrolanaloguesasselectiveestrogensignalingpathwaymodulatorsstructureactivityrelationship |