Nrf2 Activation and Antioxidant Properties of Chromone-Containing MTDLs for Alzheimer’s Disease Treatment
Alzheimer’s disease (AD) is a devastating neurodegenerative disorder affecting millions worldwide and imposing a significant social and economic burden. Despite extensive research, there is still no effective cure for this disease. AD is multifactorial and involves multiple etiopathogenic mechanisms...
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MDPI AG
2025-05-01
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| author | Alexey Simakov Stecy Chhor Lhassane Ismaili Hélène Martin |
| author_facet | Alexey Simakov Stecy Chhor Lhassane Ismaili Hélène Martin |
| author_sort | Alexey Simakov |
| collection | DOAJ |
| description | Alzheimer’s disease (AD) is a devastating neurodegenerative disorder affecting millions worldwide and imposing a significant social and economic burden. Despite extensive research, there is still no effective cure for this disease. AD is multifactorial and involves multiple etiopathogenic mechanisms, one of which is oxidative stress. Consequently, the Nrf2/ARE pathway, which regulates the expression of cellular defense genes, including those for antioxidant enzymes, is considered to be a prospective therapeutic target for AD. Meanwhile, multitarget-directed ligands (MTDLs) are a promising approach for developing effective AD medications. In this regard, we evaluated the antioxidant potential of eight chromone-containing MTDLs in vitro, including Nrf2 transcriptional activation potencies, Nrf2/ARE downstream genes activation, and antioxidant effects in vitro. All tested compounds effectively activated the Nrf2/ARE pathway. Notably, compounds <b>4b</b>, <b>4c</b>, <b>4f</b>, and <b>4h</b> demonstrated the highest Nrf2 activation potencies, while compounds <b>4b</b>, <b>4c</b>, <b>4d</b>, and <b>4g</b> significantly induced the expression of Nrf2-target antioxidant genes, specifically NQO1 and HO1. Additionally, compound <b>4d</b> exhibited a significant antioxidant effect in vitro. These findings encourage further investigation of the studied compounds, with particular emphasis on compound <b>4d</b> as the most promising candidate. |
| format | Article |
| id | doaj-art-90fdb60d60ef4ebab510dd331a08b75e |
| institution | OA Journals |
| issn | 1420-3049 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
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| spelling | doaj-art-90fdb60d60ef4ebab510dd331a08b75e2025-08-20T01:49:14ZengMDPI AGMolecules1420-30492025-05-01309204810.3390/molecules30092048Nrf2 Activation and Antioxidant Properties of Chromone-Containing MTDLs for Alzheimer’s Disease TreatmentAlexey Simakov0Stecy Chhor1Lhassane Ismaili2Hélène Martin3Université Marie et Louis Pasteur, INSERM UMR1322 LINC, F-25000 Besançon, FranceUniversité Marie et Louis Pasteur, EFS, INSERM UMR1098 RIGHT, F-25000 Besançon, FranceUniversité Marie et Louis Pasteur, INSERM UMR1322 LINC, F-25000 Besançon, FranceUniversité Marie et Louis Pasteur, EFS, INSERM UMR1098 RIGHT, F-25000 Besançon, FranceAlzheimer’s disease (AD) is a devastating neurodegenerative disorder affecting millions worldwide and imposing a significant social and economic burden. Despite extensive research, there is still no effective cure for this disease. AD is multifactorial and involves multiple etiopathogenic mechanisms, one of which is oxidative stress. Consequently, the Nrf2/ARE pathway, which regulates the expression of cellular defense genes, including those for antioxidant enzymes, is considered to be a prospective therapeutic target for AD. Meanwhile, multitarget-directed ligands (MTDLs) are a promising approach for developing effective AD medications. In this regard, we evaluated the antioxidant potential of eight chromone-containing MTDLs in vitro, including Nrf2 transcriptional activation potencies, Nrf2/ARE downstream genes activation, and antioxidant effects in vitro. All tested compounds effectively activated the Nrf2/ARE pathway. Notably, compounds <b>4b</b>, <b>4c</b>, <b>4f</b>, and <b>4h</b> demonstrated the highest Nrf2 activation potencies, while compounds <b>4b</b>, <b>4c</b>, <b>4d</b>, and <b>4g</b> significantly induced the expression of Nrf2-target antioxidant genes, specifically NQO1 and HO1. Additionally, compound <b>4d</b> exhibited a significant antioxidant effect in vitro. These findings encourage further investigation of the studied compounds, with particular emphasis on compound <b>4d</b> as the most promising candidate.https://www.mdpi.com/1420-3049/30/9/2048antioxidant effectNrf2chromoneMTDLsAlzheimer’s disease |
| spellingShingle | Alexey Simakov Stecy Chhor Lhassane Ismaili Hélène Martin Nrf2 Activation and Antioxidant Properties of Chromone-Containing MTDLs for Alzheimer’s Disease Treatment Molecules antioxidant effect Nrf2 chromone MTDLs Alzheimer’s disease |
| title | Nrf2 Activation and Antioxidant Properties of Chromone-Containing MTDLs for Alzheimer’s Disease Treatment |
| title_full | Nrf2 Activation and Antioxidant Properties of Chromone-Containing MTDLs for Alzheimer’s Disease Treatment |
| title_fullStr | Nrf2 Activation and Antioxidant Properties of Chromone-Containing MTDLs for Alzheimer’s Disease Treatment |
| title_full_unstemmed | Nrf2 Activation and Antioxidant Properties of Chromone-Containing MTDLs for Alzheimer’s Disease Treatment |
| title_short | Nrf2 Activation and Antioxidant Properties of Chromone-Containing MTDLs for Alzheimer’s Disease Treatment |
| title_sort | nrf2 activation and antioxidant properties of chromone containing mtdls for alzheimer s disease treatment |
| topic | antioxidant effect Nrf2 chromone MTDLs Alzheimer’s disease |
| url | https://www.mdpi.com/1420-3049/30/9/2048 |
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