Discovery of podophyllotoxins

This review deals with the historical discovery of particularly important lignan derivatives used in cancer chemotherapy. From isolation of the naturally occurring podophyllotoxin, an inhibitor of microtubule assembly, to hemisynthesis of the clinically important anticancer drugs etoposide and teniposide, it will be demonstrated how the activities and the ability of this class of compounds to inhibit topoisomerase II were discovered by different research teams. By virtue of these discoveries, new hemisynthetic derivatives, with different mechanisms of action, are bringing improvements in the ability to treat cancer.