Por favor, use este identificador para citar o enlazar este ítem: https://hdl.handle.net/20.500.12530/73650
Título : Anti-Trypanosoma cruzi Activity of Metabolism Modifier Compounds.
Autor : 
Palabras clave : 
Fecha de publicación : 12-ene-2021
Citación : Int J Mol Sci.2021;(22)2:
Resumen : Chagas disease is caused by the protozoan parasite Trypanosoma cruzi and affects over 6 million people worldwide. Development of new drugs to treat this disease remains a priority since those currently available have variable efficacy and frequent adverse effects, especially during the long regimens required for treating the chronic stage of the disease. T. cruzi modulates the host cell-metabolism to accommodate the cell cytosol into a favorable growth environment and acquire nutrients for its multiplication. In this study we evaluated the specific anti-T. cruzi activity of nine bio-energetic modulator compounds. Notably, we identified that 17-DMAG, which targets the ATP-binding site of heat shock protein 90 (Hsp90), has a very high (sub-micromolar range) selective inhibition of the parasite growth. This inhibitory effect was also highly potent (IC50 = 0.27 μmol L-1) against the amastigote intracellular replicative stage of the parasite. Moreover, molecular docking results suggest that 17-DMAG may bind T. cruzi Hsp90 homologue Hsp83 with good affinity. Evaluation in a mouse model of chronic T. cruzi infection did not show parasite growth inhibition, highlighting the difficulties encountered when going from in vitro assays onto preclinical drug developmental stages.
PMID: 33445756
URI : https://hdl.handle.net/20.500.12530/73650
Derechos: openAccess
Aparece en las colecciones: Hospitales > H. U. Severo Ochoa > Artículos

Ficheros en este ítem:
Fichero Tamaño Formato  
PMC7828178.pdf2.88 MBAdobe PDFVisualizar/Abrir

Este ítem está sujeto a una licencia Creative Commons Licencia Creative Commons Creative Commons