Evaluation of hypoxia inducible factor targeting pharmacological drugs as antileishmanial agents.

OBJECTIVE: To evaluate whether hypoxia inducible factor (HIF-1α) targeting pharmacological drugs, echinomycin, resveratrol and CdCl2 which inhibit HIF-1α stimulation, and mimosine, which enhances the stability of HIF-1α present antileishmanial properties. METHODS: The leishmanicidal effect of drugs was evaluated in mouse macrophages and Balb/c mouse model for cutaneous leishmaniosis. RESULTS: Resveratrol and CdCl2 reduced the parasite load [IC50, (27.3 ± 2.25) µM and (24.8 ± 0.95) µM, respectively]. The IC50 value of echinomycin was (22.7 ± 7.36) nM and mimosine did not alter the parasite load in primary macrophages. The macrophage viability IC50 values for resveratrol, echinomycin and CdCl2 and mimosine were >40 µM, >100 nM, >200 µM and>2000 µM, respectively. In vivo no differences between cutaneous lesions from control, resveratrol- and echinomycin-treated Balb/c mice were detected. CONCLUSIONS: Resveratrol, echinomycin and CdCl2 reduce parasite survival in vitro. The HIF-1α targeting pharmacological drugs require further study to more fully determine their anti-Leishmania potential and their role in therapeutic strategies.