Chemical Constituents from Aerial Parts of Baccharis sphenophylla and Effects against Intracellular Forms of Trypanosoma cruzi

The hexane extract from aerial parts Baccharis sphenophylla Dusen ex Malme (Asteraceae) displayed activity against amastigote forms of Trypanossoma cruzi and was subjected to chromatographic steps to afford one unreported - 7 alpha-hydroxy-ent-abieta-8(14),13(15)-dien-16,12 beta-olide (1) and three known diterpenes - ent-kaur-16-en-19-oic acid, (2), grandifloric acid (3), and 15 beta-tiglinoyloxy-ent-kaur-16-en-19-oic acid (4), two sesquiterpenes - spathulenol (5) and oplopanone (6) - as well as hexacosyl p-coumarate (7). Isolated compounds were characterized by NMR and ESI-HR-MS spectra and were evaluated in vitro for activity against amastigote forms of the parasite T. cruzi - the relevant clinical form in the chronic phase of Chagas disease. In addition, the activity of compounds 1-7 against NCTC cells was evaluated. Compounds 1 and 7 showed effectiveness with EC50 values of 21.3 and 16.9 mu M, respectively. Both compounds also exhibited reduced toxicity against NCTC cells (CC50>200 mu M) with SI values higher than 9.4 and 11.9. Obtained results suggest that the new ent-abietane diterpene 1 and alkyl coumarate 7 could be used as prototypes for the development of novel and selective semisynthetic derivatives against intracellular forms of T. cruzi.

Automated summary

The hexane extract of Baccharis sphenophylla displayed activity against amastigote forms of Trypanosoma cruzi, leading to the isolation of one unreported diterpene (1) and three known diterpenes. Compounds 1 and 7 showed effectiveness against the parasite with low toxicity against NCTC cells, indicating their potential as prototypes for developing novel drugs against intracellular forms of T. cruzi.