IQUIMEFA   05518
INSTITUTO QUIMICA Y METABOLISMO DEL FARMACO
Unidad Ejecutora - UE
artículos
Título:
Assessment of sesquiterpene lactones isolated from Mikania plants species for their potential efficacy against Trypanosoma cruzi and Leishmania sp.
Autor/es:
LAURELLA, LAURA C.; SÁNCHEZ ALBERTI, ANDRÉS; CERNY, NATACHA; MARTINO, VIRGINIA S.; GIBERTI, GUSTAVO; CAZORLA, SILVIA I.; CATALAN, CESAR A.; CERNY, NATACHA; SÜLSEN, VALERIA P.; GIBERTI, GUSTAVO; BIVONA, AUGUSTO E.; CATALAN, CESAR A.; MALCHIODI, EMILIO L.; SÜLSEN, VALERIA P.; BIVONA, AUGUSTO E.; ALONSO, MARÍA ROSARIO; MALCHIODI, EMILIO L.; ALONSO, MARÍA ROSARIO; LAURELLA, LAURA C.; SÁNCHEZ ALBERTI, ANDRÉS; MARTINO, VIRGINIA S.; CAZORLA, SILVIA I.
Revista:
PLOS NEGLECTED TROPICAL DISEASES
Editorial:
PUBLIC LIBRARY SCIENCE
Referencias:
Lugar: San Francisco; Año: 2018 vol. 11
ISSN:
1935-2735
Resumen:
Four sesquiterpene lactones, mikanolide, deoxymikanolide, dihydromikanolide and scandenolide, were isolated by a bioassay-guided fractionation of Mikania variifolia and Mikania micrantha dichloromethane extracts. Mikanolide and deoxymikanolide were the major compounds in both extracts (2.2% and 0.4% for Mikania variifolia and 21.0% and 6.4% for Mikania micrantha respectively, calculated on extract dry weight). Mikanolide, deoxymikanolide and dihydromikanolide were active against Trypanosoma cruzi epimastigotes (50% inhibitory concentrations of 0.7, 0.08 and 2.5 μg/mL, for each compound respectively). These sesquiterpene lactones were also active against the bloodstream trypomastigotes (50% inhibitory concentrations for each compound were 2.1, 1.5 and 0.3 μg/mL, respectively) and against amastigotes (50% inhibitory concentrations for each compound were 4.5, 6.3 and8.5 μg/mL, respectively). By contrast, scandenolide was not active on Trypanosoma cruzi. Besides, mikanolide and deoxymikanolide were also active on Leishmania braziliensis promastigotes (50% inhibitory concentrations of 5.1 and 11.5 μg/mL, respectively). The four sesquiterpene lactones were tested for their cytotoxicity on THP 1 cells. Deoxymikanolide presented the highest selectivity index for trypomastigotes (SI = 54) and amastigotes (SI = 12.5). In an in vivo model of Trypanosoma cruzi infection, deoxymikanolide was able to decrease the parasitemia and the weight loss associated to the acute phase of the parasiteinfection. More importantly, while 100% of control mice died by day 22 after receiving a lethalT. cruzi infection, 70% of deoxymikanolide-treated mice survived. We also observed that this compound increased TNF-α and IL-12 production by macrophages, which could contribute to control T. cruzi infection.