Indole alkaloids of Psychotria as multifunctional cholinesterases and monoamine oxidases inhibitors
2013
Passos, Carolina S. | Simões-Pires, Claudia A. | Nurisso, Alessandra | Soldi, Tatiane C. | Kato, Lucilia | de Oliveira, Cecilia M.A. | de Faria, Emiret O. | Marcourt, Laurence | Gottfried, Carmem | Carrupt, Pierre-Alain | Henriques, Amélia T.
Thirteen Psychotria alkaloids were evaluated regarding their interactions with acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and monoamine oxidases A and B (MAO-A and MAO-B), which are enzymatic targets related with neurodegenerative diseases. Two quaternary β-carboline alkaloids, prunifoleine and 14-oxoprunifoleine, inhibited AChE, BChE and MAO-A with IC50 values corresponding to 10 and 3.39μM for AChE, 100 and 11μM for BChE, and 7.41 and 6.92μM for MAO-A, respectively. Both compounds seem to behave as noncompetitive AChE inhibitors and time-dependent MAO-A inhibitors. In addition, the monoterpene indole alkaloids (MIAs) angustine, vallesiachotamine lactone, E-vallesiachotamine and Z-vallesiachotamine inhibited BChE and MAO-A with IC50 values ranging from 3.47 to 14μM for BChE inhibition and from 0.85 to 2.14μM for MAO-A inhibition. Among the tested MIAs, angustine is able to inhibit MAO-A in a reversible and competitive way while the three vallesiachotamine-like alkaloids display a time-dependent inhibition on this target. Docking calculations were performed in order to understand the binding mode between the most active ligands and the selected targets. Taken together, our findings established molecular details of AChE, BChE and MAO-A inhibition by quaternary β-carboline alkaloids and MIAs from Psychotria, suggesting these secondary metabolites are scaffolds for the development of multifunctional compounds against neurodegeneration.
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