In Vitro and In Vivo Activity of Benzo[c]phenanthridines against Leishmania amazonensis

Abstract

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 (IC₅₀ = 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.

Key words

leishmaniasis - Leishmania amazonensis - in vitro - in vivo - leishmanicidal - benzo[c]phenanthridines - Zanthoxylum rhoifolium - Rutaceae

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