Arylimidamide-Azole Combinations against Leishmaniasis
Technical Report,28 Aug 2015,27 Aug 2016
The Geneva Foundation Tacoma United States
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Arylimidamide compound DB766D was tested in combination with posaconazole in combination based on the premise that the partial efficacy provided by each compound individually would provide cures when the combination was dosed together. At the maximum tolerable dose of the combined treatment, efficacy was observed, however, no cures of L. major lesions were observed. Three additional compounds, DB2342, DB2332, and DB2336 were tested for potency against Leishmania in vitro, and as all 3 were very potent, all 3 were tested in vivo for toxicity to determine the maximum tolerable dose and ultimately efficacy testing was conducted against L. major to suppress lesion formation. The maximum tolerable dose for all 3compounds was determined, and lesion suppression testing was conducted in vivo at the maximum tolerable dose. None of the 3 compounds were shown to suppress lesion formation. Four additional phenoxyalkyl hybrid compounds were tested in vitro, and one compound, AA2-160, demonstrated potency in vitro against Leishmania species. This compound will be selected for further in vivo testing in Q1 Y3.
- Medicine and Medical Research