Title: Hydrolyzable Tannins Are Iron Chelators That Inhibit DNA Repair Enzyme ALKBH2.
Authors: Chen, Fangyi; Tang, Qi; Ma, Hang; Bian, Ke; Seeram, Navindra P; Li, Deyu
Published In Chem Res Toxicol, (2019 06 17)
Abstract: Hydrolyzable tannins are a class of polyphenolic compounds commonly found in natural products. In this work, we studied the in vitro inhibitory mechanism of six molecules in this class on ALKBH2, an Fe(II)/α-ketoglutarate-dependent DNA repair enzyme in the AlkB family. We determined the IC50 values of these compounds on the repair of 3-methylcytosine and 1-methyladenine, the prototypical substrates of ALKBH2. A structure-activity relationship was also observed between the strength of inhibition and the number of galloyl moieties in a molecule. In addition, we found that the inhibition by this class of polyphenolic compounds on ALKBH2 is through an iron-chelating mechanism.
PubMed ID: 31088072
MeSH Terms: AlkB Homolog 2, Alpha-Ketoglutarate-Dependent Dioxygenase/antagonists & inhibitors*; AlkB Homolog 2, Alpha-Ketoglutarate-Dependent Dioxygenase/metabolism; DNA Repair*; Dose-Response Relationship, Drug; Enzyme Inhibitors/chemistry; Enzyme Inhibitors/pharmacology*; Humans; Hydrolyzable Tannins/chemistry; Hydrolyzable Tannins/pharmacology*; Iron Chelating Agents/chemistry; Iron Chelating Agents/pharmacology*; Molecular Structure; Structure-Activity Relationship