at Google ScholarTitle data
Pinto, Andrea ; El Ali, Zeina ; Moniot, Sébastien ; Tamborini, Lucia ; Steegborn, Clemens ; Foresti, Roberta ; de Micheli, Carlo:
Effects of 3-Bromo-4,5-dihydroisoxazole Derivatives on Nrf2 Activation and Heme Oxygenase-1 Expression.
In: ChemistryOpen.
Vol. 7
(2018)
Issue 11
.
- pp. 858-864.
ISSN 2191-1363
DOI: https://doi.org/10.1002/open.201800185
Abstract in another language
Natural and synthetic electrophilic compounds have been shown to activate the antioxidant protective Nrf2 (nuclear factor erythroid 2-related factor 2)/heme oxygenase-1 (HO-1) axis in cells and tissues. Here, we tested the ability of different isoxazoline-based electrophiles to up-regulate Nrf2/HO-1. The potency of activation is dependent on the leaving group at the 3-position of the isoxazoline nucleus, and an additional ring on the molecule limits the Nrf2/HO-1 activating properties. Among the synthetized compounds, we identified 3-bromo-5-phenyl-4,5-dihydroisoxazole as the derivative with best activating properties in THP-1 human monocytic cells. We have confirmed that the target of our compounds is the Cys151 of the BTB domain of Keap1 by using mass spectrometry analyses and X-ray crystallography. Our findings demonstrate that these compounds affect the Nrf2/HO-1 axis and highlight a positive activity that can be of relevance from a therapeutic perspective in inflammation and infection.
Further data
| Item Type: | Article in a journal |
|---|---|
| Refereed: | Yes |
| Keywords: | 3-bromo-4,5-dihydroisoxazole; Keap1; crystal structure; cycloaddition; mass spectrometry |
| Institutions of the University: | Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Chair Biochemistry > Chair Biochemistry - Univ.-Prof. Dr. Clemens Steegborn Faculties Faculties > Faculty of Biology, Chemistry and Earth Sciences Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Chair Biochemistry |
| Result of work at the UBT: | No |
| DDC Subjects: | 500 Science > 540 Chemistry |
| Date Deposited: | 22 Nov 2018 08:12 |
| Last Modified: | 07 Sep 2023 13:36 |
| URI: | https://eref.uni-bayreuth.de/id/eprint/46369 |