In vitro antileukemic effect of a new anthracycline analogue, MEN 11079.

The biological activity of MEN 11079, a new daunorubucin analogue with a fluorine atom in C(8) of ring A, was investigated in the human leukemic cell lines K-562 and in mononuclear cells (MNCs) of 40 patients with acute myeloid leukemia (AML) and the activity compared to two well-characterized anthracyclines, idarubicin (IDA) and doxorubicin (DOXO). IDA and MEN 11079 were more active than DOXO in cytotoxicity tests (WST-1 assay). IDA and MEN 11079 ID(50) values were also significantly different from each other (K-562: P=0.038; MNCs: P=0.003). Moreover, the range was 0.002-4.300 microM for IDA and 0.002-0.670 microM for MEN 11079, in the MNCs. Therefore, the latter appeared to assure a smaller variability of response in the AML cells. Apoptosis assays (performed using Annexin-V assay and propidium iodide) and cell cycle studies demonstrated that the MEN 11079 effective concentration was 10-fold lower than the DOXO and IDA ones. MDR (Pgp and MRP1 proteins), as measured by semiquantitative RT-PCR, cytofluorimetric and functional analysis of proteins, was similarly elicited by IDA and MEN 11079. In conclusion, the response of the cells to the new anthracycline indicates that there is greater cytotoxic activity of this molecule than IDA and DOXO. Its narrower ID(50) range may allow for a more predictable response in the clinical setting.