isobologram curve of leishmanicidal effects of amiodarone and ketoconazole

Background: leishmaniasis is a zoonotic parasitic infection with aworldwide distribution. ergosterolandstigmasterol, equivalent to mammalian cholesterol, are the key sterols in leishmania species, and thus can be used as proper targets for drugs. objective: because amiodarone (amd) and ketoconazole (ktz) inhibit the sterol biosynthesis in trypanosomatid parasites, the present study aimed at investigating the effects of amd and ktz, acting individually or in combination, against l. infantum promastigotes and axenic amastigotes. methods: for each stage, drugs were added to the growth medium 24 hours after starting the cultures with 106 parasites/ml. replication of l. infantum promastigotes and axenic amastigotes were investigated in the presence and absence of amdand ktz. isobologram construction and calculation of the fic were performed. results: minimum concentration, which produces total death of parasites against promastigotes and axenic amastigotes, was 28 μmand 12μmforamdand 1μmand 0.75μmfor ktz. according to the concave isobologram and fractional inhibitory concentration < 1, antiproliferative synergism of the drugs was confirmed. conclusions: both drugs in synergy could be effective in arresting parasite proliferation at doses lower than those required when used alone, reducing the potential cost (ktz) or toxic effects (amd) involved.