Stevia satureiifolia var. satureiifolia: source of compounds with anti-Trypanosoma cruzi activity

BORGO J; CERNY N; SÜLSEN V; ELSO O; BIVONA A; MALCHIODI E; GROSSO C; BEER MF; SANCHEZ ALBERTI A

CABA

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

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

Chagas disease, caused by the protozoan Trypanosoma cruzi, affects approximately 6-7 million people worldwide, mainly in Latin America (1). In Argentina, it is estimated that about 1.6 million people are infected, so this statistics makes it the principal endemic disease of sanitary importance in our country. Drugs available for Chagas´ treatment produce several adverse effects, so their use has some limitations, due to toxicity, serious adverse effects and lack of efficacy. Natural products have an important role in the search and discovery of new drugs, especially if we think that many drugs that are currently used as gold standard therapies have had their origin in nature.In previous studies we have reported the antiprotozoal activity of the dichloromethane extract and the isolated flavonoids of Stevia satureiifolia var. satureiifolia (2). The objective of this study was to continue with the isolation and identification of new molecules with anti-Trypanosoma cruzi activity from the active extract of this plant Aerial parts of S. satureiifolia var. satureiifolia were collected in Tandil, Buenos Aires, in February 2012. Voucher specimens were deposited at the Museo de Farmacobotánica, Facultad de Farmacia y Bioquımica, Universidad de Buenos Aires (BAF 744). For the preparation of the plant extract, 200 g of the dried aerial parts were extracted by maceration with dichloromethane (3L). The extract was filtered and taken to dryness. Then, the dichloromethane (DCM) extract was fractionated by column chromatography (CC) with a gradient of DCM and ethyl acetate (EtOAc), obtaining 7 fractions (SS1-SS7). From fraction SS5, a white solid precipitated (RAMAD10). The isolated compound was evaluated on T. cruzi epimastigotes for 72 h using the thymidine uptake technique. The cytotoxicity was assessed on HEK293 cells by the MTT assay.The analysis by infrared spectroscopy of RAMAD10 evidenced the presence of γ-lactone carbonyl groups. RAMAD10 showed significant trypanocidal activity on T. cruzi epimastigotes (IC50 = 1.75 μg / ml) and low toxicity on mammalian cells (CC50 > 50 μg/ml). The compound isolated from S. satureiifolia var satureiifolia, RAMAD10, showed the IR spectral features of a sesquiterpene lactone and demosntrated in vitro anti-trypanosomal activity. Currently, the evaluation of the activity on other T. cruzi stages is ongoing. The identification of the molecule will be concluded through the analysis of the mass and nuclear magnetic resonance spectra which are in progress.References1.World Health Organization (WHO), 2018. ?Chagas disease (American tripanosomiasis)?. http://www.who.int/es/news-room/fact-sheets/detail/chagas-disease-(american-trypanosomiasis). Accessed in September 2018.2.Beer MF, Frank F, Elso O, Bivona A, Cerny N, Giberti G, Malchiodi E, Martino V, Alonso MR, Sülsen V, Cazorla S, 2016. Pharm Biol, 17:1-8