Antioxidant and antileishmanial studies of phytochelators as potential candidates for optimization

Some phytochelators resemble iron chelating drugs and present antioxidant activity, potentially preventing conditions involving free radical damage mediated by iron, including iron overload and neurodegeneration. Also, these compounds could act as iron-scavenging molecules in microorganisms, with possible antimicrobial activity. Here we show that the phytochelators tropolone, morine and maltol can prevent iron-mediated oxidant activity (DCDFA/H2O2 assay)3 at ~50 micromolar. Also, tropolone and esculetin presented intracellular antioxidant activity (in HeLa cells) at 125 micromolar, with efficacy similar to deferiprone. In viability assays of Leishmania infantum chagasi we observed for tropolone an EC50 of ~90 micromolar for promastigotes and an EC50 = 64 micromolar for amastigotes. The tested molecules showed LD50 >500 micromolar in HeLa and HepG2 cells. However, tropolone showed LD50 = 50 for THP1 macrophages. These results reinforce the potential of those molecules as adjuvants in treatments for iron overload or leishmaniasis and as candidates for optimization of toxicity andpotency.