Search for trypanocidal leads from Stevia aristata (Asteraceae)

BORGO J; ELSO O; SANCHEZ ALBERTI A; GROSO C; BIVONA A; CERNY N; ULLOA J; MALCHIODI E; SÜLSEN V

CABA

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

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

American trypanosomiasis or Chagas disease affects 6 to 7 million people worldwide and causes more than 10000 deaths per year (1). This parasitosis is produced by the protozoan Trypanosoma cruzi. Chagas disease occurs principally in Latin America. However, in the last decades and due to migration phenomena, it has been detected in the United States of America, Canada, and many European and some Western Pacific countries. The available drugs for its treatment are benznidazol and nifurtimox, which have a variable efficacy. Side effects are fairly common with both drugs. This situation 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 aristata D. 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. Ten 10 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 10µg/ml. A precipitate was obtained from this fraction and washed with EtOAc (compound A). The purity of compound A was evaluated by chromatographic techniques (TLC and HPLC). The IC50 (50% inhibitory concentration) value of this compound against epimastigote 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 cytotoxicty of this compound on mammalian cells as well as its identification by spectroscopic methods (IR, UV, MS, 1H-RMN, 13C-RMN) is in progress.References1- World Health Organization (WHO), 2018. Fact Sheet Chagas disease (American trypanosomiasis). 1 February 2018. Available at http://www.who.int/en/news-room/fact-sheets/detail/chagas-disease-(american-trypanosomiasis).2- Beer M.F. et al., 2016. Pharm Biol. 54(10):2188-95.