Evaluation of hypoxia inducible factor targeting pharmacological drugs as antileishmanial agents

Objective: To evaluate whether hypoxia inducible factor (HIF-1 alpha) targeting pharmacological drugs, echinomycin, resveratrol and CdCl2, which inhibit HIF-1 alpha stimulation, and mimosine, which enhances the stability of HIF-1 alpha 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) mu M and (24.8 +/- 0.95) mu M, respectively]. The IC50 value of echinomycin was (22.7 +/- 7.36) mu M 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 mu M, >100 mu M > 200 mu M and>2 000 mu M, 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-1 alpha targeting pharmacological drugs require further study to more fully determine their anti-Leishmania potential and their role in therapeutic strategies. (AU)