Influence of the Structure of New Anthracycline Antibiotics on their Biological Properties

Abstract

In the search for new derivatives of anthracycline antibiotics with advantageous biological properties, particularly with lower toxicity and/or higher activity, a series of new analogs of antibiotics applied in therapy such as daunorubicin, doxorubicin, as well as epidoxorubicin and, for comparison, analogs of epidaunorubicin, have been synthesized. Our results show that the new derivatives have antiproliferative activities similar to or higher than the parent antibiotics. The toxicities of these analogs were significantly lower, with LD₅₀ values from 1.8- to 18.4-fold higher than the referential drugs. Cardiotoxicity determinations, using male mice treated with a single dose of 75% of the LD₅₀ values of all tested compounds, indicated that the cardiotoxicity of the new analogs is significantly lower than that of the parent drugs.