Aporphine Alkaloids from <i>Ocotea puberula</i> with Anti‐<i>Trypanosoma Cruzi</i> Potential – Activity of Dicentrine‐β‐<i>N</i>‐Oxide in the Plasma Membrane Electric Potentials

Abstract

Abstract 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 EC 50 value of 18.2 μM and reduced toxicity against NCTC cells (CC 50 &gt;200 μM – SI&gt;11.0), similar to positive control benznidazole (EC 50 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.