THE ONE-RING OPEN HYDROLYSIS INTERMEDIATES OF THE CARDIOPROTECTIVE AGENT DEXRAZOXANE (ICRF-187) DO NOT INHIBIT THE GROWTH OF CHINESE-HAMSTER OVARY CELLS OR THE CATALYTIC ACTIVITY OF DNA TOPOISOMERASE-II

Dexrazoxane (ICRF-187), which is clinically used to reduce doxorubicin -induced cardiotoxicity, has growth inhibitory properties through its ability to inhibit the catalytic activity of DNA topoisomerase II. Bec ause the bisdioxopiperazine dexrazoxane undergoes significant ring-ope ning hydrolysis under physiological conditions to form two one-ring op en hydrolysis intermediates, a study was undertaken to determine if th ese two intermediates had either any growth inhibitory or topoisomeras e II inhibitory effects. Neither of the one-ring open intermediates ex hibited growth inhibitory effects towards Chinese hamster ovary cells nor were they able to inhibit topoisomerase II. Thus, it was concluded that only intact dexrazoxane is able to inhibit the catalytic activit y of topoisomerase II. [(C) 1998 Lippincott-Raven Publishers.].