An in vitro model for testing the effect of anti-leishmanial drugs of possible use in topical treatment

The effect of 9 antileishmanial compounds against Leishmania major, the local causative agent of cutaneous leishmaniasis, was studied in vitro, in mouse peritoneal macrophages. Paromomycin sulfate and Berberine sulfate at 10 μg/ml were the only drugs that totally eliminated the intracellular amastigotes, with a therapeutic index of 100 and 5, respectively. Amphotericin B, sodium stibogluconate and pentamidine at 0.1 μg/ml, 100 μg/ml and 10 μg/ml eliminated 70%, 91% and 91% of the parasites, respectively, with a therapeutic index of 5, 5 and 1. Emetine hydrochloride (0.1 μg/ml) was active against the parasite only at a concentration close to toxicity to the host cells, with a therapeutic index of 1. At 100 μg/ml, sulfamethoxazole and the dihydrofolate reductase inhibitor - trimethoprim - eliminated 52% and 62% of the intracellular parasites, with a therapeutic index of 10 and 1, respectively. High activity was also obtained with allopurinol at 100 μg/ml which eliminated 86% of the parasites and had a therapeutic index of 5.