Indole alkaloids of Psychotria as multifunctional cholinesterases and monoamine oxidases inhibitors |
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| Institution: | 1. Laboratory of Pharmacognosy, Faculty of Pharmacy, Universidade Federal do Rio Grande do Sul – UFRGS, Porto Alegre, RS, Brazil;2. Graduate Program in Health Sciences, Universidade do Extremo Sul Catarinense - UNESC, Criciúma, SC, Brazil;3. Laboratory of Synthetic and Natural Products Biotechnology, Institute of Biotechnology, Universidade de Caxias do Sul – UCS, Caxias do Sul, RS, Brazil;4. Laboratory of Conservation and Biodiversity Management, Universidade Lasalle – UNILASALLE, Canoas, RS, Brazil;5. Herbarium Dr. Roberto Miguel Klein, Department of Natural Sciences, Universidade Regional de Blumenau - FURB, Blumenau, SC, Brazil;6. Graduate Program in Biological Sciences: Biochemistry, Department of Biochemistry, Universidade Federal do Rio Grande do Sul – UFRGS, Porto Alegre, RS, Brazil;1. School of Life Science and Engineering, Lanzhou University of Technology, Lanzhou, PR China;2. Department of Chemistry, Lanzhou University, Lanzhou, PR China |
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| 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 IC50 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 IC50 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. |
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