BIMOLANE - IN-VITRO INHIBITOR OF HUMAN TOPOISOMERASE-II

Bimolane is a member of the bis(2,6-dioxopiperazine) class of drugs an d has been widely used in China as an antineoplastic agent and for the treatment of psoriasis. Recent case reports indicate that bimolane is leukemogenic and is thought to exert its effects through the inhibiti on of topoisomerase II. However, there are no data showing the inhibit ion of topoisomerase II by this agent. In this report bimolane was sho wn to inhibit the activity of human topoisomerase II in vitro at conce ntrations of 100 mu M and higher when pBR322 was used as the DNA subst rate, whereas inhibition was seen at 1.5 mM when using kDNA as a subst rate. The results of enzyme and DNA titration assays indicate that inh ibition of topoisomerase II by bimolane occurred through interactions with DNA, similar to the mechanism seen with the epipodophyllotoxin-ty pe inhibitors. These results provide evidence that bimolane is an inhi bitor of topoisomerase II in vitro. (C) 1997 Elsevier Science Ireland Ltd.