Search for trypanocidal leads from Stevia aristata (Asteraceae)

SANCHEZ ALBERTI, A.; CERNY, NATACHA; SÜLSEN, VALERIA; ELSO, ORLANDO; BIVONA, A.; MALCHIODI, EMILIO; BORGO, JIMENA; GROSSO, C. ; ULLOA, JERÓNIMO

Buenos Aires

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

IQUIMEFA

American trypanosomiasis or Chagas disease affects 6 to 7 million people worldwide and causes more than 10000deaths per year [1]. This parasitosis is produced by the protozoan Trypanosoma cruzi. Chagas disease occurs principally inLatin America. However, in the last decades and due to migration phenomena, it has been detected in the United Statesof America, Canada, and many European and some Western Pacific countries. The available drugs for its treatmentare benznidazol and nifurtimox, which have a variable efficacy. Side effects are fairly common with both drugs. Thissituation has led to an urgent need for new therapeutic agents to treat this disease.We have already reported the trypanocidal activity of the organic extract (dichloromethane extract) of Stevia aristataD. Don ex Hook. & Arn. (Asteraceae) as a result of our ongoing search on antiparasitic compounds from Stevia species[2]. Based on this result a bioassay- guided fractionation was carried out for the isolation of its active compounds.Column chromatography (CC) of this extract was performed on Silicagel with a gradient of dichloromethane:EtOAc. Ten10 fractions (FA to FJ) were obtained and evaluated against T. cruzi epimastigotes by the 3-H thymidine uptake assay.The most active fraction was FE, with a 37.7 % of growth inhibition at a concentration of 10 µg/ml. A precipitatewas obtained from this fraction and washed with EtOAc (compound A). The purity of compound A was evaluated bychromatographic techniques (TLC and HPLC). The IC50 (50% inhibitory concentration) value of this compound againstepimastigote forms of Trypanosoma cruzi was 23.4 µg/ml. The chromatographic behaviour of compound A on TLC,employing anisaldehyde sulphuric acid as visualization reagent, indicates that this compound could be a terpenoid.The compound A showed in vitro trypanocidal activity. The cytotoxicity of this compound on mammalian cells as wellas its identification by spectroscopic methods (IR, UV, MS, 1H-RMN, 13C-RMN) is in progress.