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Trypanocidal activity of daunorubicin and related compounds

Abstract

The anthracycline antibiotic daunorubicin is, in vitro, one of the most potent trypanocidal agents reported1; it permanently abolishes the infectivity of African trypanosomes at less than nanomolar concentrations. In contrast, other anthracyclines such as doxorubicin and nogalamycin must be present in milli-molar concentrations to achieve the same effect (Table 1). Despite its uniquely high activity in vitro, daunorubicin is totally inactive against trypanosomes in infected rodents1. An investigation of this lack of in vivo activity suggested that uptake into trypanosomes is only transient2. We therefore tried to prolong exposure of trypanosomes to the drug by coupling it to a carrier macromolecule. The use of such a carrier should delay removal of the drug from the blood and simultaneously exploit the endocytotic properties of trypanosomes. Ferritin and albumin were chosen as potential carriers as these proteins are endocytosed by trypanosomes3,4. We report here that when the drug was attached by a stable linkage, activity was not maintained, but when attached by a labile covalent linkage the preparation was active both in vitro and in vivo, indicating the desirability of testing other macromolecules, such as dextran5, as carriers for trypanocidal drugs.

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Williamson, J., Scott-Finnigan, T., Hardman, M. et al. Trypanocidal activity of daunorubicin and related compounds. Nature 292, 466–467 (1981). https://doi.org/10.1038/292466a0

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