Twelve new aryl-substituted naphthalenoids (1-7, 9, 10, and 13-16) together with four known ones (8, and 11-
13) have been designed and synthesized. Their antitumor activities were evaluated by sulforhodamine B assay on human
breast cancer MDA-MB-231, human lung cancer A549 and human cervical cancer HeLa cell lines. Four compounds (2, 4,
10 and 12) showed potent inhibitory activities against the growth of the three cell lines with IC50 between 0.34-3.49 µM,
and were more potent than the reference etoposide (IC50 3.67-13.78 µM). DNA relaxation assay revealed that compound 2
showed potent inhibitory activity against Topo IIα in vitro. The structure-activity relationships of these compounds were
discussed, suggesting that further structural optimizations of aryl-substituted naphthalenoids could lead to the discovery of
potent antitumor agents targeting topoisomerases.