Dihydroindenoisoquinolines function as prodrugs of indenoisoquinolines

Dihydroindenoisoquinolines are analogs of cytotoxic indenoisoquinoline topoisomerase 1 (Top1) inhibitors, exhibiting potent cytotoxicity but weak inhibitory activity toward Top 1. Through COMPARE analysis, cytotoxicity studies in Top 1-deficient cells, chemical synthesis and biological evaluation of methylated dihydroindenoisoquinoline 5, we demonstrated that dihydroindenoisoquinolines function as prodrugs of indenoisoquinolines in cancer cells. (c) 2005 Elsevier Ltd. All rights reserved.