Does conjugation of quinones with polyamines and amino acids improve their anti-Trypanosoma/-Leishmania potential?

As a common chemical motif, quinones are recurrent among compounds showing useful antiparasitic properties. Numerous derivatives displayed potent activity against Trypanosoma and Leishmania. However, clinical research with these compounds has been hampered by safety concerns. Subsequent efforts to improve their therapeutic properties have been made by modifying the quinone framework. Another rational strategy to improve selectivity is to combine the moiety with a vector selectively recognized by the parasite. Previous studies suggest that polyamines and arginine might act as carriers, which transport cytotoxic agents into parasites exploiting specific permeases. To explore this possibility, naphthoquinones and anthraquinones developed in our laboratory have been conjugated to polyamines and basic amino acids, affording two novel libraries of hybrid compounds. These molecules may show a dual mechanism of action: preventing parasite growth i) by delivery of the toxic moiety and ii) by interference with the polyamine biosynthetic pathway.