title: Indole alkaloids of Psychotria as multifunctional cholinesterases and monoamine oxidases inhibitors.
abstract: 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 IC(50) values corresponding to 10 and 3.39 μM for AChE, 100 and 11 μM for BChE, and 7.41 and 6.92 μM 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 IC(50) values ranging from 3.47 to 14 μM for BChE inhibition and from 0.85 to 2.14 μM 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.
authors.affiliation: Departamento de Produção de Matéria-Prima, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, UFRGS, Porto Alegre, RS, Brazil. carolinadspassos@yahoo.com.br
authors.forename: Carolina S
authors.initials: CS
authors.lastname: Passos
authors.forename: Claudia A
authors.initials: CA
authors.lastname: Simões-Pires
authors.forename: Alessandra
authors.initials: A
authors.lastname: Nurisso
authors.forename: Tatiane C
authors.initials: TC
authors.lastname: Soldi
authors.forename: Lucilia
authors.initials: L
authors.lastname: Kato
authors.forename: Cecilia M A
authors.initials: CM
authors.lastname: de Oliveira
authors.forename: Emiret O
authors.initials: EO
authors.lastname: de Faria
authors.forename: Laurence
authors.initials: L
authors.lastname: Marcourt
authors.forename: Carmem
authors.initials: C
authors.lastname: Gottfried
authors.forename: Pierre-Alain
authors.initials: PA
authors.lastname: Carrupt
authors.forename: Amélia T
authors.initials: AT
authors.lastname: Henriques
mesh_terms: D000470:Alkaloids / Q000737:chemistry* / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D002802:Cholinesterases / Q000378:metabolism; D007700:Kinetics; D008958:Models, Molecular; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D032069:Psychotria / Q000737:chemistry*
chemical_list: D000470:Alkaloids; D002800:Cholinesterase Inhibitors; D008996:Monoamine Oxidase Inhibitors; D008995:Monoamine Oxidase; D002802:Cholinesterases