Glucosylated isoflavones as DNA topoisomerase II poisons.
Since topoisomerase poisons allow the enzyme to cut and covalently bind to DNA but abort the subsequent rejoining of the molecule after relieving the torsional stress. To study their action we have made use of a supercoiled form of the pRYG plasmid that bears a specific topoisomerase recognition and binding region. The conversion of the supercoiled circular double-stranded DNA to the linear and open circle forms in the presence of a topoisomerase II poison and a denaturation step by proteinase K-SDS is indicative of the efficiency of our test agents to stabilize the cleavable complex. Using this system, three glucosylated isoflavones (6'-methoxy-pseudobaptigenin-7-O-beta-glucoside, genistin, and daidzin) isolated from cytotoxic chloroform and ethyl acetate extracts of Retama sphaerocarpa Boissier, were found to have the ability to stabilize the cleavage complex human DNA topoisomerase II.
Martín-Cordero
C
C
López-Lazaro
M
M
Piñero
J
J
Ortiz
T
T
Cortés
F
F
Ayuso
M J
MJ
D004247:DNA / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004587:Electrophoresis, Agar Gel; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D006031:Glycosylation; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D008956:Models, Chemical; D009690:Nucleic Acid Conformation; D010936:Plant Extracts / Q000633:toxicity; D059005:Topoisomerase II Inhibitors
D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; D004968:Estrogens, Non-Steroidal; D007529:Isoflavones; D010936:Plant Extracts; D059005:Topoisomerase II Inhibitors; C040641:genistin; C013908:daidzin; C060800:psi-baptigenin; D004247:DNA; D004250:DNA Topoisomerases, Type II