Bimolane: in vitro inhibitor of human topoisomerase II

Bimolane is a member of the bis(2,6-dioxopiperazine) class of drugs and has been widely used in China as an anti-neoplastic agent and for the treatment of psoriasis. Recent case reports indicate that bimolane is leukemogenic and is thought to exert its effects through the inhibition of topoisomerase II. However, there are no data showing the inhibition of topoisomerase II by this agent. In this report bimolane was shown to inhibit the activity of human topoisomerase II in vitro at concentrations of 100 μM and higher when pBR322 was used as the DNA substrate, whereas inhibition was seen at 1.5 mM when using kDNA as a substrate. The results of enzyme and DNA titration assays indicate that inhibition of topoisomerase II by bimolane occurred through interactions with DNA, similar to the mechanism seen with the epipodophyllotoxin-type inhibitors. These results provide evidence that bimolane is an inhibitor of topoisomerase II in vitro.