title: Inhibition of DNA topoisomerases I and II by G3 PAMAM-NH2 dendrimer-modified digoxin and proscillaridin A conjugates in a cell free system.
abstract: Two modified glycosides--digoxin and proscillaridin A conjugated to a generation 3 of polyamidoamine dendrimer (G3 PAMAM-NH2) were evaluated as DNA topoisomerase II inhibitors. The ability of these compounds (PAMAM-Dig and PAMAM-Prosc) to inhibit topoisomerase I and II activity was quantified by measuring the action on supercoiled DNA substrate as a function of increasing concentration of the test compounds by the use of agarose gel electrophoresis. The obtained results suggest that a conjugation of the modified glycosides with G3 PAMAM-NH2 significantly improved the ability of the parent compounds to an inhibition of DNA topoisomerases.
authors.affiliation: Department of Pharmaceutical Technology, Medical University of Białystok, Kilińskiego 1, 15-089 Białystok, Poland. kwin@umwb.edu.pl
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Winnicka
authors.forename: Anna
authors.initials: A
authors.lastname: Bielawska
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Bielawski
mesh_terms: D000951:Antigens, Neoplasm / Q000737:chemistry / Q000378:metabolism; D004264:DNA Topoisomerases, Type I / Q000737:chemistry / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000737:chemistry / Q000378:metabolism; D004278:DNA, Superhelical / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D050091:Dendrimers / Q000737:chemistry / Q000494:pharmacology*; D004077:Digoxin / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004587:Electrophoresis, Agar Gel; D006801:Humans; D015394:Molecular Structure; D011442:Proscillaridin / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D059003:Topoisomerase Inhibitors / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000951:Antigens, Neoplasm; D004278:DNA, Superhelical; D004268:DNA-Binding Proteins; D050091:Dendrimers; C555765:G3 PAMAM-NH2 dendrimer-modified digoxin; C555764:G3 PAMAM-NH2 dendrimer-modified proscillaridin A; D059003:Topoisomerase Inhibitors; D004077:Digoxin; D004264:DNA Topoisomerases, Type I; C528909:TOP1 protein, human; D004250:DNA Topoisomerases, Type II; D011442:Proscillaridin