Chagas disease, a vector-borne illness caused by the parasite Trypanosoma cruzi, is considered a global public health issue. About 6 to 7 million people are estimated to be infected with T. cruzi worldwide1. The synthetic drugs traditionally used for the treatment of Chagas disease have limited efficacy in the chronic phase of the disease, in addition to causing systemic toxicity and adverse side effects. Plant extracts have thus emerged as a promising source of naturally derived trypanocidal agents. In our continuing research on potential trypanocidal constituents from species occurring in the ‘‘Cerrado’’ of the West-Central region of Brazil, we found that the ethanol extract of the xylopodium of Aiouea trinervis Meisn. (Lauraceae) showed activity in vitro against epimastigotes of T. cruzi (IC50 = 7.4 µg/mL). The bioactive EtOH extract was subsequently partitioned between MeOH/H2O 9:1 and hexane; MeOH/H2O 1:1 and CH2Cl2; and MeOH/H2O 1:1 and EtOAc, the activity residing in the hexane and CH2Cl2 solubles (IC50 values of 3.4 and 6.6 µg/mL, respectively). A combination of column chromatography on silica gel, gel filtration on Sephadex LH-20, and reversed phase HPLC separations of the hexane phase led to the isolation of three butanolides, namely, isoobtusilactone A (1), (-)-epilitsenolide C1 (2) and (-)-epilitsenolide C2 (3). The structures of these compounds were established by analyses of 1D- and 2D-NMR and HRESIMS data. Following isolation, compounds 1-3 were further assayed in vitro against epimastigotes of T. cruzi, using the MTS colorimetric assay, in which isoobtusilactone A and (-)-epilitsenolide C1 proved active (IC50 values of 3.4 and 4.1 µg/mL, respectively), while (-)-epilitsenolide C2 was shown to be inactive. Even though the genus Aiouea belongs to a widely studied plant family known for providing a number of bioactive secondary metabolites, it had not been previously investigated for its potential trypanocidal activity. Likewise, although the occurrence of butanolides 1-3 was previously described in A. trinervis2 and in other Lauraceae species, this is the first report of in vitro trypanocidal activities of compounds 1 and 2.

References:1WHO. Neglected Tropical Diseases – a Statistical Update, 2017.2Garcez, F.R.; Garcez, W. S.; Martins, M.; Matos, M. F. C.; Guterres, Z. R.; Mantovani, M. S.; Misu, C. K.; Nakashita, S. T. Planta Medica 2005, 71, 923.