Table 1.
Cytotoxicity in rat cardiomyocytes, cellular and nuclear uptake of anthracycline derivatives, and their DNA binding constant values
| Compound | Cytotoxicity IC50 (nM) |
P | Cellular uptake nmoles/106 cells |
% of drug localized in the nucleus | Kapp × 105 [M-1] | logP* |
|---|---|---|---|---|---|---|
| DOX | 35 ± 4 | 890 ± 42 | 80.2 ± 3.1 | 18.1 ± 0.41 | -0.644 | |
| DOXM | 138 ± 18 | < 0.001 | 690 ± 21 | 23.7 ± 1.0 | 0.90 ± 0.12 | -0.995 |
| DOXH | 87 ± 7 | < 0.001 | 1330 ± 120 | 54.2 ± 6.2 | 7.30 ± 0.14 | 1.459 |
| DRB | 76 ± 7 | 3230 ± 153 | 35.8 ± 4.1 | 11.7 ± 0.22 | -1.344 | |
| DRBM | 626 ± 18 | < 0.001 | 618 ± 51 | 19.9 ± 1.4 | 0.64 ± 0.03 | -0.791 |
| DRBH | 172 ± 14 | < 0.001 | 5640 ± 168 | 21.9 ± 2.1 | 4.1 ± 0.08 | 0.758 |
Cytotoxicity was determined by MTT assay. All IC50 values are the means of six independent experiments ± S.D. P values refer to the significances of differences between parent compounds and their analogs as analyzed by Student’s t-test. The data for cellular uptake are the means of 7 independent experiments ± S.D. The data presenting the % of drug in the nucleus are the means of 25 estimations for individual cells ± S.D. The DNA binding constant values are presented as the means of three independent estimations ± S.D. */logP is the partition coefficient calculated by Chem3D Ultra v. 6 software (Cambridge Soft).