One new aporphine, dicentrine-β-N-oxide (1), together with five related known alkaloids dehydrodicentrine (2), predicentrine (3), N-methyllaurotetanine (4), cassythicine (5), and dicentrine (6) were isolated from the leaves of Ocotea puberula (Lauraceae). Antiprotozoal activity of the isolated compounds was evaluated in vitro against trypomastigote forms of Trypanosoma cruzi. Among the tested compounds, alkaloid 1 exhibited higher potential with EC50 value of 18.2 μM and reduced toxicity against NCTC cells (CC50 >200 μM - SI>11.0), similar to positive control benznidazole (EC50 of 17.7 μM and SI=10.7). Considering the promising results of dicentrine-β-N-oxide (1) against trypomastigotes, the mechanism of parasite death caused by this alkaloid was investigated. As observed, this compound reached the plasma membrane electric potential directly after 2 h of incubation and triggered mitochondrial depolarization, which probably leads to trypomastigote death. Therefore, dicentrine-β-N-oxide (1), reported for the first time in this work, can contribute to future works for the development of new trypanocidal agents.
Keywords: N-oxide; Ocotea puberula; Trypanosoma cruzi; aporphine alkaloids.
© 2021 Wiley-VHCA AG, Zurich, Switzerland.