Antitumor agents. Part 227: Studies on novel 4′-O-demethyl-epipodophyllotoxins as antitumor agents targeting topoisomerase II Original Research Article

Eight novel epipodophyllotoxin derivatives (6–13), which were designed to overcome drug resistance and enhance topoisomerase II inhibition, were synthesized and evaluated. Two of these compounds (7 and 8) showed better preclinical activity profiles, including cell growth inhibition, cell killing, and in vitro topoisomerase II inhibition, as compared to the prototype molecule etoposide (1). They also retained the superior drug-resistance profile of GL-331 (4), an epipodophyllotoxin derivative currently in clinical evaluation.