Aporphine Alkaloids from Ocotea puberula with Anti-Trypanosoma Cruzi Potential - Activity of Dicentrine-β-N-Oxide in the Plasma Membrane Electric Potentials

Chem Biodivers. 2021 Apr;18(4):e2001022. doi: 10.1002/cbdv.202001022. Epub 2021 Mar 1.

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 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.

MeSH terms

  • Animals
  • Aporphines / chemistry
  • Aporphines / isolation & purification
  • Aporphines / pharmacology*
  • Cell Line
  • Cell Membrane / drug effects*
  • Cell Membrane / metabolism
  • Membrane Potential, Mitochondrial / drug effects
  • Mice
  • Molecular Structure
  • Ocotea / chemistry*
  • Plant Extracts / chemistry
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Trypanocidal Agents / chemistry
  • Trypanocidal Agents / isolation & purification
  • Trypanocidal Agents / pharmacology*
  • Trypanosoma cruzi / drug effects*

Substances

  • Aporphines
  • Plant Extracts
  • Trypanocidal Agents