Topoisomerase inhibitors

Topoisomerase inhibitors are chemical compounds that block the action of topoisomerases.

Intercalating drugs are used for cancer chemotherapy because they poison cells that are rapidly dividing, like the cells in a growing tumor
- Action of topoisomerase begins by breaking one of DNA strands
- then they induce a topological change in DNA such as relaxing supercoils or untangling strands
- and finally they reconnect the DNA in its proper form.
Intercalating drugs block the reconnection step, freezing the topoisomerase after it has broken the DNA.
This is a problem for a dividing cell: when a replication fork reaches the site, a lethal double-strand break is formed as the replication machinery passes through the damaged DNA.