Leishmania amazonensis response to artemisinin and derivatives

The worldwide presence of Leishmania parasites increases in the poorest regions. Current leishmaniasis treatments are unsatisfactory due to resistance development, side effects and cost. Herein, we describe the in vitro activity of artemisinin (ART), artemether (ATM), artesunate (ATS) and dihydroartemisinin (DHA) against Leishmania amazonensis. Selected compounds were assayed in the animal model of cutaneous leishmaniasis in BALB/c mice. On intracellular amastigotes, similar activity (p > 0.05) was observed for ART, ATM and ATS (IC₅₀ = 15.0-19.2 microM), which were inferior (p < 0.05) respect to reference endoperoxide ascaridole (IC₅₀ = 11.5 ± 1.0 microM) and superior (p < 0.05) compared with reference drug Glucantime® (IC₅₀ = 30.1 ± 9.0 microM). In contrast, DHA (IC₅₀ = 38.5 ± 4.7 microM) showed higher IC₅₀ values (p < 0.05) than other artemisinins and ascaridole, but similar (p > 0.05) than Glucantime®; while deoxyartemisinin caused smaller inhibition (IC₅₀ = 88.9 ± 5.2 microM). Selectivity indexes of >13, 6, 11 and 1 were obtained for ART, ATM, ATS and DHA, respectively. In addition, the potential effect of ART and ATS was also demonstrated in the murine model, causing a significant reduction (p < 0.05) of the lesion size and parasite load regarding untreated animals and treated with vehicle. Effects of both artemisinins were comparable (p > 0.05) with Glucantime® and ascaridole-treated mice. In particular, artemisinin is recommended to further studies, which could be an advantage over the ascaridole endoperoxide and could be useful in endemic areas of parasite resistance to antimonials.