Title: Evaluation of hypoxia inducible factor targeting pharmacological drugs as antileishmanial agents
Author: Dal'bó Pelegrini, Marina; Pereira, Juliana Biar; Dos Santos Costa, Solange; Salazar Terreros, Myriam Janeth; Degrossoli, Adriana; Giorgio, Selma
Is part of: Yatai Redai Yiyao Zazhi, v. 9, p. 652 - 657
Citation: Dal'bó Pelegrini, Marina; Pereira, Juliana Biar; Dos Santos Costa, Solange; Salazar Terreros, Myriam Janeth; Degrossoli, Adriana; Giorgio, Selma; Evaluation of hypoxia inducible factor targeting pharmacological drugs as antileishmanial agents. Yatai Redai Yiyao Zazhi, v.9, p. 652-657, 2016
Abstract: 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.
Funding: This study was supported by Fundacao de Amparo a Pesquisa do Estado de Sao Paulo, Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (NO. 2009/10771-9) and Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (NO. 301052/2009-3), Brazil.