Table 1

Cytotoxic potency, DNA binding affinity constants, and in vitro topoisomerase II cleavage of the anthracycline derivatives studied

CompoundCytotoxicity IC50DNA binding-affinity constantsIn vitro DNA cleavage
μm m −1 K app × 106 n
III0.022.40.170+++ 32
V0.05n.d.n.d.+++ 27
IV0.171.00.072+++ 27, 32
II0.204.80.160++ 27
I0.806.50.179++ 32
VI1.370.860.215+ 27
VII2.600.320.149+ 27

The compounds are listed in order of decreasing cytotoxic potency. IC50 values were determined from dose-response curves from at least three independent experiments (see Fig. 2 for other details).K app was determined in 0.1 m NaCl at 25°. n represents the apparent number of drug binding sites per nucleotide. Drug DNA cleavage activity is expressed in a semiquantitative manner as determined previously using an in vitro assay and murine topoisomerase II.

    • n.d., not determined.

    • ++, doxorubicin activity; +, less than doxorubicin activity; +++, greater than doxorubicin activity.