SPECIAL METABOLITES WITH ANTI-Trypanosoma cruzi ACTIVITY ISOLATED FROM Piper truncatum Vell.
The present work aimed to accomplish a phytochemical study of Piper truncatum Vell., in search of special metabolites with activity against Trypanosoma cruzi, the causative agent of Chagas disease. Considering that the n-hexane extract from the plant’s twigs exhibited activity against the trypomastigote forms of the parasite, it was subjected to several chromatographic procedures which resulted in purification of 11 compounds: (+)-sesamin (1), (+)-kobusin (2), (-)-hinokinin (3), cubebin (4), 3’,4’-dimethoxy-3,4-desmethylenedioxycubebin (5), (-)-9α-Omethylcubebin (6), (+)-9β-O-methylcubebin (7), truncatin A (8), truncatin B (9), piplartine (10) and aristolactam BII (11). All eleven compounds are new in the species, while 8 and 9 have not yet been described in literature. The compounds were characterized through spectroscopic and spectrometric methods and
submitted to anti-T. cruzi activity evaluation against trypomastigote forms, as well as cytotoxicity against NCTC cells. Regarding anti-T. cruzi activity, only compounds 4, 7, 9 and 10 were active, with EC50 values of 41.6, 21.0, 39.6 and 4.87 µM, respectively. Among the active compounds, only 7 did not display cytotoxicity against NCTC cells (CC50 > 200 µM) and was considered the most selective (SI > 9.4). It was possible to discuss the pattern of substitution of the aromatic carbons (C-3’ and C-4’), as well as the influence of stereochemistry between H-8 and H-9 for compounds 6 – 9. Finally, it was possible to observe that the presence of the methylenedioxylic system together with the cis stereochemistry between H-8 and H-9, was fundamental to the increase in antiT. cruzi activity and diminished cytotoxicity.