Antitumor agents. Part 230: C4′-esters of GL-331 as cytotoxic agents and DNA topoisomerase II inhibitors

Three C4′-acyl derivatives (5–7) of GL-331 (4) were synthesized and evaluated for cytotoxic and DNA topoisomerase II (topo II) inhibitory activity. All three compounds were cytotoxic against KB and KB-7d cells. Compounds 5 and 7, but not 6, were potent inhibitors of the DNA topoisomerase II in vitro and this relative activity ranking was maintained for cytotoxicity, in vitro cell growth inhibition, and ability to induce cellular double-strand DNA breaks. These results provided new information on the structure–activity relationships of the C4′ molecular area of 4-analogues.