In vitro and in vivo activity of benzo[ c ]phenanthridines against Leishmania amazonensis

Seven benzo[c]phenanthridines, synthetic or isolated from Zanthoxylum rhoifolium root bark, were evaluated against Leishmania amazonensis axenic amastigotes. Five of them were considered leishmanicidal, with IC₅₀ values ranging from 0.03 to 0.54 μM, and were evaluated on intramacrophagic amastigotes of L.amazonensis. Chelerythrine displayed the best activity (IC ₅₀ = 0.5 μM), which was in the same range as the reference compound amphotericin B (IC₅₀ = 0.4 μM). In vivo studies with chelerythrine, avicine, and fagaridine on a model of mice cutaneous leishmaniasis resulted in the identification of fagaridine as the most active compound. Fagaridine decreased the parasitic burden more than 50 at the 3rd and 6th weeks after the end of treatment.