Ellagic Acid and Polyhydroxylated Urolithins Are Potent Catalytic Inhibitors of Human Topoisomerase II: An in Vitro Study
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- 作者：Valentina Furlanetto ; Giuseppe Zagotto ; Riccardo Pasquale ; Stefano Moro ; Barbara Gatto
- 刊名：Journal of Agricultural and Food Chemistry
- 出版年：2012
- 出版时间：September 12, 2012
- 年：2012
- 卷：60
- 期：36
- 页码：9162-9170
- 全文大小：447K
- 年卷期：v.60,no.36(September 12, 2012)
- ISSN：1520-5118
文摘
Ellagic acid (EA), a natural polyphenol abundant in fruits and common in our diet, is under intense investigation for its chemopreventive activity resulting from multiple effects. EA inhibits topoisomerase II, but the effects on the human enzyme of urolithins, its monolactone metabolites, are not known. Therefore, the action of several synthetic urolithins toward topoisomerases II was evaluated, showing that polyhydroxylated urolithins, EA, and EA-related compounds are potent inhibitors of the 伪 and 尾 isoforms of human topoisomerase II at submicromolar concentrations. Competition tests demonstrate a dose-dependent relationship between ATP and the inhibition of the enzyme. Docking experiments show that the active compounds bind the ATP pocket of the human enzyme, thus supporting the hypothesis that EA and polyhydroxylated urolithins act as ATP-competitive inhibitors of human topoisomerase II.