Isolation and identification of a diterpenoid from Gymnocoronis spilanthoides with activity on Trypanosoma cruzi and Trypanosoma brucei brucei

SORAIRES SANTACRUZ M. C. ; SANCHEZ ALBERTI, A. ; CATALÁN CÉSAR; SELENER MARIANA; CERNY, NATACHA; MALCHIODI, EMILIO; SÜLSEN, VALERIA; BIVONA, A. ; ULLOA, JERÓNIMO; REDKO, FLAVIA

Buenos Aires

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

IQUIMEFA

Trypanosomiases are a group of parasitic diseases caused by protozoan parasites of the genus Trypanosoma andare spread by bloodsucking insects. Two species of Trypanosoma, T. cruzi and T. brucei, affect humans producingAmerican trypanosomiasis or Chagas´disease and African trypanosomiasis or sleeping sickness, respectively [1,2].The current available drugs used to treat these parasitoses have limitations due to host toxicity, side effects and lowefficacy. Nature has provided useful drugs that are used nowadays to treat different pains. Asteraceae species havebeen a rich source of active compounds and have been attractive for drug discovery.In this context, it is extremely necessary to develop new drugs. In previous work the trypanocidal activity of thedichloromethane extract of Gymnocoronis spilanthoides (Asteraceae) [GSDE] has been demonstrated [3]. The aim ofthis investigation was to isolate and identify the active compounds present in the GSDE.The GSDE was purified by liquid-liquid partition and fractionated by column chromatography using Silicagel-60 and agradient of CH2Cl2 and EtOAc. From fractions eluted with CH2Cl2:EtOAc (2:1) a precipitate was obatined(compound B).The compound was purified by preparative chromatography in reverse phase by a C18 column using HPLC-DAD.The trypanocidal activity of compound B was evaluated on T. cruzi epimastigotes (RA strain) and on T. brucei bruceitrypomastigotes (427 strain). The cytotoxicity of this compound on mammalian cells was performed using mouse splenocytes.Compound B presented a significant trypanocidal activity on T cruzi epimastigotes (IC50= 5.2 µg/ml) and on T. bruceiepimastigotes (IC50= 8.8 µg/ml). This compound showed some toxicity to mammalian cells (CC50 = 7.8 µg/ml). The structure elucidation of the isolated compound was performed by spectroscopic methods. Compound B was identifiedas the (16R)-ent-llα-hydroxy-15-oxokauran-19-oic acid [4].The activity of (16R)-ent-11α-hydroxy-15-oxokauran-19-oic acid on other T. cruzi and T. brucei brucei forms will beevaluated. We will also continue with the isolation and identification of other compounds present in the active extract.