Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, Ke Karlovu 455/2, 128 08 Prague 2, Czech Republic; BIOCEV, First Faculty of Medicine, Charles University, Průmyslová 595, 252 50 Vestec, Czech Republic.
Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, Ke Karlovu 455/2, 128 08 Prague 2, Czech Republic; BIOCEV, First Faculty of Medicine, Charles University, Průmyslová 595, 252 50 Vestec, Czech Republic; Department of Analytical Chemistry, Faculty of Chemical Engineering, University of Chemistry and Technology, Technická 5, 166 28 Prague, Czech Republic.
Bioorg Chem. 2022 Jul;124:105793. doi: 10.1016/j.bioorg.2022.105793. Epub 2022 Apr 6.
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 (IC = 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).
非精神类大麻素（例如大麻二酚、大麻醇和大麻萜酚）存在于许多食品和药品中。因此，预测和研究它们可能产生的副作用，如 DNA 甲基化的变化，是评估这些产品安全性的一项重要任务。螯合亚铁离子会干扰 TET 酶，从而导致甲基化模式发生改变。所有测试的大麻素都对 Fe(II)离子表现出很强的亲和力。大麻二酚和大麻醇对 TET1 蛋白表现出很强的抑制活性（IC 分别为 4.8 和 6.27 μM），而大麻萜酚对酶活性没有影响。分子对接研究表明，CBD/CBN 在催化腔中有明显的结合潜力，但也发现 CBG 有一定的亲和力，因此总缺乏活性仍未得到解释。这些结果表明，大麻素可能会影响 TET1 蛋白的活性，不仅是因为它们与 Fe(II)的亲和力，还因为其他类型的相互作用（例如疏水相互作用和氢键）。
