Biochemical parameters of growth inhibition of human leukemia cells by antitumor anthracycline agents

Abstract

Ten antitumor anthracycline derivatives used in this study inhibit growth of a human leukemia cell line over a range of potencies exceeding four orders of magnitude. The agents vary from each other at C-4 and C-13, with stereochemical differences at C-4' and substitutions at C-14 and N. Drug retention, DNA damage, and inhibition of DNA synthesia are parameters used to express potency of the agents in a mathematic model. Estimates of DNA damage are sufficient, however, to describe growth inhibition by a single agent (4-demethoxydaunorubicin). It may be possible now to attempt to extend the model to predict therapeutic responses to a number of anthracyclines, thereby enhancing the clinical utility of this important class of agents.