Cytotoxic acridinylthiourea and its platinum conjugate produce enzyme-mediated DNA strand breaks.
The reactions of plasmid DNA modified with the novel acridinylthiourea, 1-[2-(acridin-9-ylamino)ethyl]-1,3-dimethylthiourea (1), and the corresponding intercalator-tethered platinum complex (2) with human type I and type II topoisomerases have been studied. Assays were based on evaluating DNA cleavage products resulting from incubations of drug-modified DNA in cell-free systems. 2 produces double-strand breaks in the presence of topo II while 1 proved to be a dual topo I/topo II poison.
Brow
Jennifer M
JM
Department of Chemistry, Wake Forest University, Winston-Salem, NC 27109, USA.
Pleatman
Cynthia R
CR
Bierbach
Ulrich
U
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D004247:DNA / Q000302:isolation & purification; D004249:DNA Damage / Q000187:drug effects*; D004278:DNA, Superhelical / Q000187:drug effects; D004591:Electrophoresis, Polyacrylamide Gel; D004791:Enzyme Inhibitors / Q000302:isolation & purification / Q000494:pharmacology; D006801:Humans; D009944:Organoplatinum Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D010957:Plasmids / Q000187:drug effects; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D014508:Urea / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology*
C471910:1-(2-(acridin-9-ylamino)ethyl)-1,3-dimethylthiourea; D000970:Antineoplastic Agents; D004278:DNA, Superhelical; D004791:Enzyme Inhibitors; D009944:Organoplatinum Compounds; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D014508:Urea; D004247:DNA