Evaluation of hypoxia inducible factor targeting pharmacological drugs as antileishmanial agents

Abstract

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>2 000 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.