A Series of Ferulic Acid Amides Reveals Unexpected Peroxiredoxin 1 Inhibitory Activity with in vivo Antidiabetic and Hypolipidemic Effects
© 2020 Wiley-VCH GmbH..
Insulin resistance is a major pathophysiological feature in the development of type 2 diabetes (T2DM). Ferulic acid is known for attenuating the insulin resistance and reducing the blood glucose in T2DM rats. In this work, we designed and synthesized a library of new ferulic acid amides (FAA), which could be considered as ring opening derivatives of the antidiabetic PPARγ agonists Thiazolidinediones (TZDs). However, since these compounds displayed weak PPAR transactivation capacity, we employed a proteomics approach to unravel their molecular target(s) and identified the peroxiredoxin 1 (PRDX1) as a direct binding target of FAAs. Interestingly, PRDX1, a protein with antioxidant and chaperone activity, has been implied in the development of T2DM by inducing hepatic insulin resistance. SPR, mass spectrometry-based studies, docking experiments and in vitro inhibition assay confirmed that compounds VIe and VIf bound PRDX1 and induced a dose-dependent inhibition. Furthermore, VIe and VIf significantly improved hyperglycemia and hyperlipidemia in streptozotocin-nicotinamide (STZ-NA)-induced diabetic rats as confirmed by histopathological examinations. These results provide guidance for developing the current FAAs as new potential antidiabetic agents.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:16 |
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| Enthalten in: |
ChemMedChem - 16(2021), 3 vom: 04. Feb., Seite 484-498 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yasmin, Sabina [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 10.11.2021 Date Revised 10.11.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/cmdc.202000564 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 2 | |a A Series of Ferulic Acid Amides Reveals Unexpected Peroxiredoxin 1 Inhibitory Activity with in vivo Antidiabetic and Hypolipidemic Effects |
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| 500 | |a Date Revised 10.11.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2020 Wiley-VCH GmbH. | ||
| 520 | |a Insulin resistance is a major pathophysiological feature in the development of type 2 diabetes (T2DM). Ferulic acid is known for attenuating the insulin resistance and reducing the blood glucose in T2DM rats. In this work, we designed and synthesized a library of new ferulic acid amides (FAA), which could be considered as ring opening derivatives of the antidiabetic PPARγ agonists Thiazolidinediones (TZDs). However, since these compounds displayed weak PPAR transactivation capacity, we employed a proteomics approach to unravel their molecular target(s) and identified the peroxiredoxin 1 (PRDX1) as a direct binding target of FAAs. Interestingly, PRDX1, a protein with antioxidant and chaperone activity, has been implied in the development of T2DM by inducing hepatic insulin resistance. SPR, mass spectrometry-based studies, docking experiments and in vitro inhibition assay confirmed that compounds VIe and VIf bound PRDX1 and induced a dose-dependent inhibition. Furthermore, VIe and VIf significantly improved hyperglycemia and hyperlipidemia in streptozotocin-nicotinamide (STZ-NA)-induced diabetic rats as confirmed by histopathological examinations. These results provide guidance for developing the current FAAs as new potential antidiabetic agents | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Ferulic acid amides | |
| 650 | 4 | |a Hyperglycemia | |
| 650 | 4 | |a Hyperlipidemia | |
| 650 | 4 | |a Peroxiredoxin 1 | |
| 650 | 4 | |a Type 2 diabetes | |
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| 700 | 1 | |a Badavath, Vishnu Nayak |e verfasserin |4 aut | |
| 700 | 1 | |a Laghezza, Antonio |e verfasserin |4 aut | |
| 700 | 1 | |a Dal Piaz, Fabrizio |e verfasserin |4 aut | |
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| 700 | 1 | |a Atlı, Özlem |e verfasserin |4 aut | |
| 700 | 1 | |a Baysal, Merve |e verfasserin |4 aut | |
| 700 | 1 | |a Vadivelan, Sankaran |e verfasserin |4 aut | |
| 700 | 1 | |a Shankar, S |e verfasserin |4 aut | |
| 700 | 1 | |a Siddique, Mohd Usman Mohd |e verfasserin |4 aut | |
| 700 | 1 | |a Pattnaik, Ashok Kumar |e verfasserin |4 aut | |
| 700 | 1 | |a Singh, Ravi Pratap |e verfasserin |4 aut | |
| 700 | 1 | |a Loiodice, Fulvio |e verfasserin |4 aut | |
| 700 | 1 | |a Jayaprakash, Venkatesan |e verfasserin |4 aut | |
| 700 | 1 | |a Lavecchia, Antonio |e verfasserin |4 aut | |
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