Non-psychotropic cannabinoids as inhibitors of TET1 protein
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
35462234
DOI
10.1016/j.bioorg.2022.105793
PII: S0045-2068(22)00198-5
Knihovny.cz E-resources
- Keywords
- Cannabinoids, DNA methylation, Epigenetic, Iron chelation, TET1 protein,
- MeSH
- Cannabis * chemistry MeSH
- Cannabidiol * chemistry pharmacology MeSH
- Cannabinoids * pharmacology MeSH
- Cannabinol pharmacology MeSH
- Molecular Docking Simulation MeSH
- Ferrous Compounds MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Cannabidiol * MeSH
- Cannabinoids * MeSH
- Cannabinol MeSH
- Ferrous Compounds MeSH
Non-psychotropic cannabinoids (e.g., cannabidiol, cannabinol and cannabigerol) are contained in numerous alimentary and medicinal products. Therefore, predicting and studying their possible side effects, such as changes in DNA methylation, is an important task for assessing the safety of these products. Interference with TET enzymes by chelating ferrous ions can contribute to the altered methylation pattern. All tested cannabinoids displayed a strong affinity for Fe(II) ions. Cannabidiol and cannabinol exhibited potent inhibitory activities (IC50 = 4.8 and 6.27 μM, respectively) towards the TET1 protein, whereas cannabigerol had no effect on the enzyme activity. An in silico molecular docking study revealed marked binding potential within the catalytic cavity for CBD/CBN, but some affinity was also found for CBG, thus the total lack of activity remains unexplained. These results imply that cannabinoids could affect the activity of the TET1 protein not only due to their affinity for Fe(II) but also due to other types of interactions (e.g., hydrophobic interactions and hydrogen bonding).
References provided by Crossref.org
Targeting of the Mitochondrial TET1 Protein by Pyrrolo[3,2-b]pyrrole Chelators
