Hydrazones as novel epigenetic modulators: Correlation between TET 1 protein inhibition activity and their iron(II) binding ability
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
30999246
DOI
10.1016/j.bioorg.2019.02.034
PII: S0045-2068(18)31169-6
Knihovny.cz E-resources
- Keywords
- Epigenetic, Hydrazone, Inhibitor, Iron(II) affinity, TET 1 protein,
- MeSH
- Iron Chelating Agents chemical synthesis chemistry toxicity MeSH
- Dioxygenases antagonists & inhibitors chemistry MeSH
- Enzyme Assays MeSH
- Epigenesis, Genetic drug effects MeSH
- Hydrazones chemical synthesis chemistry toxicity MeSH
- Enzyme Inhibitors chemical synthesis chemistry toxicity MeSH
- Iron chemistry MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Iron Chelating Agents MeSH
- Dioxygenases MeSH
- Hydrazones MeSH
- Enzyme Inhibitors MeSH
- Iron MeSH
Ten-eleven translocation protein (TET) 1 plays a key role in control of DNA demethylation and thereby of gene expression. Dysregulation of these processes leads to serious pathological states such as oncological and neurodegenerative ones and thus TET 1 targeting is highly requested. Therefore, in this work, we examined the ability of hydrazones (acyl-, aroyl- and heterocyclic hydrazones) to inhibit the TET 1 protein and its mechanism of action. Inhibitory activity of hydrazones 1-7 towards TET 1 was measured. The results showed a high affinity of the tested chelators for iron(II). The study clearly showed a significant correlation between the chelator's affinity for iron(II) ions (represented by the binding constant) and TET 1 protein inhibitory activity (represented by IC50 values).
Research and Development Center C2P s r o Jungmannova 101 503 51 Chlumec nad Cidlinou Czech Republic
References provided by Crossref.org
Targeting of the Mitochondrial TET1 Protein by Pyrrolo[3,2-b]pyrrole Chelators
