Novel lignan derivatives as selective inhibitors of DNA topoisomerase II

Rabdosiin (1) and its isomer (2), isolated from Arnebia euchroma, were potent non-selective inhibitors of mammalian DNA topoisomerases in vitro. Evaluation of synthetic analogs led to the discovery of 3 – 5 as selective inhibitors of topoisomerase II. Unlike etoposide, which inhibits by preventing the DNA rejoining process, compounds 1 – 5 did not induce DNA breakage in either cellular or in vitro assay systems.