Discovery of Potent Glucokinase and PPARγ Dual-Target Agonists through an Innovative Scheme for Regioselective Modification of Silybin

[Image: see text] Glucokinase (GK) and PPARγ are important targets for antidiabetic use. Silybin is one of the major active ingredients of Silybum marianum. The regioselective modification of the five hydroxyl groups in the silybin structure has always been a challenge. In this study, we found that...

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Autores principales: Zhang, Zhipeng, Meng, Yanqiu, Wang, Zhan, Mei, Yu, Gao, Shite, Wu, Yuejiao, Du, Shuxian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2022
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8811767/
https://www.ncbi.nlm.nih.gov/pubmed/35128289
http://dx.doi.org/10.1021/acsomega.1c06778
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author Zhang, Zhipeng
Meng, Yanqiu
Wang, Zhan
Mei, Yu
Gao, Shite
Wu, Yuejiao
Du, Shuxian
author_facet Zhang, Zhipeng
Meng, Yanqiu
Wang, Zhan
Mei, Yu
Gao, Shite
Wu, Yuejiao
Du, Shuxian
author_sort Zhang, Zhipeng
collection PubMed
description [Image: see text] Glucokinase (GK) and PPARγ are important targets for antidiabetic use. Silybin is one of the major active ingredients of Silybum marianum. The regioselective modification of the five hydroxyl groups in the silybin structure has always been a challenge. In this study, we found that silybin was an agonist of GK and PPARγ. A novel synthesis scheme of silybin derivatives was designed, and a series of novel silybin derivatives has been synthesized. The derivative 8d showed relatively strong activation activity for GK and PPARγ in enzyme activity and transactivation assays (GK activation fold: 1.86; PPARγ transactivation activation percentage: 90.32%). This research suggests that silybin and its derivatives could be used as novel GK and PPARγ dual-target agonists.
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spelling pubmed-88117672022-02-04 Discovery of Potent Glucokinase and PPARγ Dual-Target Agonists through an Innovative Scheme for Regioselective Modification of Silybin Zhang, Zhipeng Meng, Yanqiu Wang, Zhan Mei, Yu Gao, Shite Wu, Yuejiao Du, Shuxian ACS Omega [Image: see text] Glucokinase (GK) and PPARγ are important targets for antidiabetic use. Silybin is one of the major active ingredients of Silybum marianum. The regioselective modification of the five hydroxyl groups in the silybin structure has always been a challenge. In this study, we found that silybin was an agonist of GK and PPARγ. A novel synthesis scheme of silybin derivatives was designed, and a series of novel silybin derivatives has been synthesized. The derivative 8d showed relatively strong activation activity for GK and PPARγ in enzyme activity and transactivation assays (GK activation fold: 1.86; PPARγ transactivation activation percentage: 90.32%). This research suggests that silybin and its derivatives could be used as novel GK and PPARγ dual-target agonists. American Chemical Society 2022-01-20 /pmc/articles/PMC8811767/ /pubmed/35128289 http://dx.doi.org/10.1021/acsomega.1c06778 Text en © 2022 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by-nc-nd/4.0/Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Zhang, Zhipeng
Meng, Yanqiu
Wang, Zhan
Mei, Yu
Gao, Shite
Wu, Yuejiao
Du, Shuxian
Discovery of Potent Glucokinase and PPARγ Dual-Target Agonists through an Innovative Scheme for Regioselective Modification of Silybin
title Discovery of Potent Glucokinase and PPARγ Dual-Target Agonists through an Innovative Scheme for Regioselective Modification of Silybin
title_full Discovery of Potent Glucokinase and PPARγ Dual-Target Agonists through an Innovative Scheme for Regioselective Modification of Silybin
title_fullStr Discovery of Potent Glucokinase and PPARγ Dual-Target Agonists through an Innovative Scheme for Regioselective Modification of Silybin
title_full_unstemmed Discovery of Potent Glucokinase and PPARγ Dual-Target Agonists through an Innovative Scheme for Regioselective Modification of Silybin
title_short Discovery of Potent Glucokinase and PPARγ Dual-Target Agonists through an Innovative Scheme for Regioselective Modification of Silybin
title_sort discovery of potent glucokinase and pparγ dual-target agonists through an innovative scheme for regioselective modification of silybin
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8811767/
https://www.ncbi.nlm.nih.gov/pubmed/35128289
http://dx.doi.org/10.1021/acsomega.1c06778
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