DNA sequence specificity for Topoisomerase II poisoning by the Quinoxaline anticancer drugs XK469

The two known antineoplastic quinoxaline topoisomerase II poisons, XK469 (NSC 697887) and CQS (chloroquinoxaline sulfonamide, NSC 339004), were compared for DNA cleavage site specificity, using purified human topoisomerase II and human topoisomerase II. The DNA cleavage intensity pattern for topoisomerase II poisoning by CQS closely resembled that of VM-26, despite the lack of any apparent common pharma-cophore. In contrast, the topoisomerase II DNA cleavage in-tensity patterns of XK469 and CQS were very different from one another despite the similar overall structures of the two drugs. This suggests that the differences in DNA site specificity of topoisomerase II poisoning by XK469 and CQS may be caused by differences in their geometry, side chains, or electronic structure. The topoisomerase II-mediated DNA cleavage site