Alkaloids Purified from Aristotelia chilensis Inhibit the Human α3β4 Nicotinic Acetylcholine Receptor with Higher Potencies Compared with the Human α4β2 and α7 Subtypes

Abstract

The alkaloids aristoteline (1), aristoquinoline (2), and aristone (3) were purified from the leaves of the Maqui tree Aristotelia chilensis and chemically characterized by NMR spectroscopy. The pharmacological activity of these natural compounds was evaluated on human (h) α3β4, α4β2, and α7 nicotinic acetylcholine receptors (AChRs) by Ca2+ influx measurements. The results suggest that these alkaloids do not have agonistic, but inhibitory, activity on each receptor subtype. The obtained IC50 values indicate the following receptor selectivity: hα3β4 > hα4β2 ≫ hα7. In the particular case of hα3β4 AChRs, 1 (0.40 ± 0.20 μM) and 2 (0.96 ± 0.38 μM) show higher potencies compared with 3 (167 ± 3 μM). Molecular docking and structure–activity relationship results indicate that ligand lipophilicity is important for the interaction with the luminal site located close to the cytoplasmic side of the hα3β4 ion channel between positions -2′ and -4′. Compound 1 could be used as a molecular scaffold for the development of more potent noncompetitive inhibitors with higher selectivity for the hα3β4 AChR that could serve for novel addiction and depression therapies.

Beneficial Effect of Alkaloids From Sophora alopecuroides L. on CUMS-Induced Depression Model Mice via Modulating Gut Microbiota

“…Its main ingredient is alkaloids, which have antitumor, antibacterial, anti-inflammatory, and other biological activities (Zhang et al, 2017). Previous studies have shown that alkaloids from other plants have good antidepressant effects (Coetzee et al, 2016;Hamid et al, 2017;Jia et al, 2017;Wu et al, 2018;Arias et al, 2019;Chen et al, 2019;Khan et al, 2019), while the effect of alkaloids from S. alopecuroides on depression and gut microbes has not been investigated. In the current study, we used chronic unpredictable mild stress (CUMS) to establish a depression mouse model and assess the changes in depression-like behaviors and depression-related indicators to evaluate the beneficial effect of alkaloids on CUMS depression-like mice.…”

Comparative Study of Metabolomic Profile and Antioxidant Content of Adult and In Vitro Leaves of Aristotelia chilensis

“…According to the results of HPLC-DAD-ESI-MS n , the expression of phenolics compounds was more related to the type of leaf than to the season of the year. It is well-known that phenols are a distinctive feature of A. chilensis , and some of its nutritional and pharmacological effects can be attributed to their presence in the plant [ 17 , 41 ].…”

Syntheses of Aristotelia Alkaloids: Reflections in the Chiral Pool

“…Both (–)- 5 and (+)- 5 possessed identical 1 H and 13 C NMR spectra to the compound isolated from A. chilensis , indicating we had synthesized the natural product and its enantiomer. Furthermore, an X-ray crystal structure of the hydrochloride salt of (–)- 5 provided unambiguous proof of the relative configuration of the C9 stereocenter, which was previously misreported by Arias et al 28…”