دورية أكاديمية
Targeting of the Mitochondrial TET1 Protein by Pyrrolo[3,2-b]pyrrole Chelators
| العنوان: | Targeting of the Mitochondrial TET1 Protein by Pyrrolo[3,2-b]pyrrole Chelators |
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| المؤلفون: | Veronika Antonyová, Ameneh Tatar, Tereza Brogyányi, Zdeněk Kejík, Robert Kaplánek, Fréderic Vellieux, Nikita Abramenko, Alla Sinica, Jan Hajduch, Petr Novotný, Bettie Sue Masters, Pavel Martásek, Milan Jakubek |
| المصدر: | International Journal of Molecular Sciences, Vol 23, Iss 18, p 10850 (2022) |
| بيانات النشر: | MDPI AG, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Biology (General) LCC:Chemistry |
| مصطلحات موضوعية: | TET1 protein inhibitor, pyrrolo[3,2-b]pyrrole, hydrazone, mitochondria, Biology (General), QH301-705.5, Chemistry, QD1-999 |
| الوصف: | Targeting of epigenetic mechanisms, such as the hydroxymethylation of DNA, has been intensively studied, with respect to the treatment of many serious pathologies, including oncological disorders. Recent studies demonstrated that promising therapeutic strategies could potentially be based on the inhibition of the TET1 protein (ten-eleven translocation methylcytosine dioxygenase 1) by specific iron chelators. Therefore, in the present work, we prepared a series of pyrrolopyrrole derivatives with hydrazide (1) or hydrazone (2–6) iron-binding groups. As a result, we determined that the basic pyrrolo[3,2-b]pyrrole derivative 1 was a strong inhibitor of the TET1 protein (IC50 = 1.33 μM), supported by microscale thermophoresis and molecular docking. Pyrrolo[3,2-b]pyrroles 2–6, bearing substituted 2-hydroxybenzylidene moieties, displayed no significant inhibitory activity. In addition, in vitro studies demonstrated that derivative 1 exhibits potent anticancer activity and an exclusive mitochondrial localization, confirmed by Pearson’s correlation coefficient of 0.92. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1422-0067 1661-6596 |
| Relation: | https://www.mdpi.com/1422-0067/23/18/10850; https://doaj.org/toc/1661-6596; https://doaj.org/toc/1422-0067 |
| DOI: | 10.3390/ijms231810850 |
| URL الوصول: | https://doaj.org/article/c484fc82904b4b44ac4591198eb9a57e |
| رقم الأكسشن: | edsdoj.484fc82904b4b44ac4591198eb9a57e |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 14220067 16616596 |
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| DOI: | 10.3390/ijms231810850 |