Biochemical parameters of growth inhibition of human leukemia cells by antitumor anthracycline agents.
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.
D000903:Antibiotics, Antineoplastic / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D002460:Cell Line; D004273:DNA, Neoplasm / Q000096:biosynthesis; D003630:Daunorubicin / Q000031:analogs & derivatives; D004317:Doxorubicin / Q000031:analogs & derivatives; D006027:Glycosides / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007945:Leukemia, Lymphoid / Q000188:drug therapy / Q000378:metabolism*; D009279:Naphthacenes / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*
D000903:Antibiotics, Antineoplastic; D004273:DNA, Neoplasm; D006027:Glycosides; D009279:Naphthacenes; D004317:Doxorubicin; D003630:Daunorubicin