Abstract
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.
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