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Arylimidamide-Azole Combinations Against Leishmaniasis

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Technical Report,28 Aug 2014,27 Aug 2015

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The Geneva Foundation Tacoma United States

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Arylimidamide compounds DB2002, DB766D, and DB1960A DB766D and DB1960A are the same base compound with different salts demonstrated in vitro potency as sole agents against the amastigote-macrophage form of a variety of Leishmania parasites known to cause cutaneous and visceral leishmaniasis L. major, L. guyanensis, L. panamensis, L. tropica, L. donovoni, and L. infantum yielding IC50 values ranging from 20 150 nM. No synergy was demonstrated with azole compounds in vitro against L. major. Initial in vivo testing of these compounds using an assay to detect inhibition of cutaneous infection induced by L. major showed DB766 and DB1960 merited further in vivo evaluation to assess the ability of these compounds to actually cure an established L. major lesion. The L. major -infected mice in the DB766 group 60 mpk, 10 days of treatment showed a 40 reduction in ulcer size compared to the vehicle control group mean ulcer size. DB766 treated animals did show some evidence of toxicity at the 60 mpk dose, and any further experiments will need to be conducted at the 40 mpk level which will impact efficacy.

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