IQUIMEFA   05518
INSTITUTO QUIMICA Y METABOLISMO DEL FARMACO
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Estafietin derivatives as potential antiprotozoal agents
Autor/es:
SULSEN, VALERIA; SANCHEZ ALBERTI, A; MACHIOLDI, EMILIO; CERNY, NATACHA; CAZORLA, SILVIA; LIZARRAGA, EMILIO; BIVONA, A. ; CATALÁN, CÉSAR
Lugar:
CABA
Reunión:
Congreso; Drug Discovery for Neglected Diseases International Congress 2018 4th Scientific Meeting of the Research Network Natural Products against Neglected Diseases; 2019
Institución organizadora:
IQUIMEFA UBA-CONICET
Resumen:
The STL estafietin was isolated from Stevia alpina (Asteraceae). Within a series of 12 STLs studied by our group, this compound showed significant activity on T. cruzi epimastigotes. The aim of this work was to synthetize estafietin derivatives and to evaluate the natural compound and its analogueson T. cruzi trypomastigotes and amastigotes as well as on L. braziliensis promastigotes. Estafietin (1) was submitted to epoxidation with m-chloroperbenzoic acid and reduction with sodium borohydride to obtain epoxiestafietin (2) and 11βH,13-dihydroestafietin (3), respectively. The reaction of the natural STL with MeONa and NaCN yielded the Michael adducts (4) and (5) respectively (Figure 1). All these compounds were assayed on T.cruzi and L. braziliensis and on mammalian cells in order to evaluate their selectivity of action. Estafietin was the most active compound on T. cruzi trypomastigotes and amastigotes with IC50 values of 18.7 y 2.0 μg/ml, espectively. This compound was also the more active one on L. braziliensis promastigotes (IC50=1.0 μg/ml), followed by dihydroestafietin (IC50=1.3 μg/ml) and epoxyestafietin (IC50=7.8 μg/mL). Estafietin and dihydroestafietin showed selectivity of action as antiprotozoal. The antiparasitic activities demonstrated by estafietin and some of its derivatives, makes them bioactive lead molecules worth to be further investigated