title: Ellagic acid and polyhydroxylated urolithins are potent catalytic inhibitors of human topoisomerase II: an in vitro study.
abstract: 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 α and β 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.
authors.affiliation: Dipartimento di Scienze del Farmaco, Università di Padova, via Marzolo 5, 35131 Padova, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Furlanetto
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Zagotto
authors.forename: Riccardo
authors.initials: R
authors.lastname: Pasquale
authors.forename: Stefano
authors.initials: S
authors.lastname: Moro
authors.forename: Barbara
authors.initials: B
authors.lastname: Gatto
mesh_terms: D001665:Binding Sites; D002384:Catalysis; D003374:Coumarins / Q000737:chemistry / Q000494:pharmacology*; D004250:DNA Topoisomerases, Type II / Q000737:chemistry; D004610:Ellagic Acid / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry; D059005:Topoisomerase II Inhibitors / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D003374:Coumarins; D007527:Isoenzymes; D059005:Topoisomerase II Inhibitors; C026423:3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one; D004610:Ellagic Acid; D004250:DNA Topoisomerases, Type II