Antitumor Agents. 78. Inhibition of Human DNA Topoisomerase II by Podophyllotoxin and α-Peltatin Analogues

Article abstract of DOI:10.1021/jm00158a042

It has been reported that the action of etoposide (VP-16) (14) as an antitumor agent is mediated through its interaction with DNA topoisomerase II which results in DNA breakage inside the cell.In order to understand the mechanism of action as well as structure-activity relationships of 14, several novel, synthetic and some naturally occurring analogues related to podophyllotoxin were examined for inhibition of the DNA topoisomerase II activity.Compound 2 exhibited enhanced activity and compound 5 slightly diminished activity relative to 14.A 4β-substituted ether at the C ring and O-demethylation at the E ring appear to enhance activity.