Leishmanicidal activity of sesquiterpene lactones isolated from Argentinean Asteraceae species

ELSO, ORLANDO; LOMBARDO, ELISA; REDKO, FLAVIA; SULSEN, VALERIA; SOSA, A. ; BARROSO, P.

CABA

Congreso; Drug Discovery for Neglected Diseases International Congress 2018; 2018

Instituto de Quimica y Metabolismo del Farmaco (IQUIMEFA) (UBA-CONICET)

Leishmaniasis is a parasitic disease caused by over 20 Leishmania species transmitted by sand flies. It affects mainly poor people in tropical and subtropical regions of the world [1]. Only a few drugs, with an unfavourable adverse effects profile, are available for its treatment [2]. Sesquiterpene lactones (STL) are secondary metabolites mainly present in Asteraceae species with several biological activities reported such as antiparasitic [3]. The aim of this work was to assess the activity of the STLs eupatoriopicrin, estafietin, eupahakonenin B and minimolide isolated from Stevia maimarensis, Stevia alpina, Stevia gilliesii and Mikania minima, respectively against Leishmania (L.) amazonensis promastigotes and amastigotes and to evaluate their cytotoxicity against mammalian cells (macrophages).Dried aerial parts of each species were extracted by maceration with dichloromethane. Extracts were chromatographed on a Silicagel column with a gradient of dichloromethane-ethyl acetate. Elution was monitored by thin layer chromatography and STL rich fractions were put together. The isolation of the compounds was performed by column chromatography. The purity and the identification of the STLs were determined by HPLC and spectroscopic methods. Leishmania (L.) amazonensis promastigotes were treated with different concentrations of each STL and after incubation living parasites were quantified under an optic microscope. For the evaluation of the activity against amastigotes, a cell line of macrophages (RAW 264.7) was infected with promastigotes of L. (L.) amazonensis. After differentiation into amastigotes, cells were treated with different concentrations of each STL and after incubation living parasites were quantified under an optic microscope. Cytotoxicity on murine macrophages was determined using a Cell Counting Kit-8.The results obtained show the leishmanicidal activity of the four STLs, being estafietin and eupatoriopicrin the most active ones (Table 1). Sesquiterpene lactones were able to reduce the survival of both intracellular amastigote and promastigote forms. These findings indicate that the STLs are potential candidates to test in an animal model of cutaneous leishmaniasis.