Isoquinoline Alkaloids from Berberis vulgaris as Potential Lead Compounds for the Treatment of Alzheimer's Disease
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- Acetylcholinesterase metabolism MeSH
- Alkaloids chemistry isolation & purification therapeutic use MeSH
- Alzheimer Disease drug therapy MeSH
- Berberis chemistry MeSH
- Butyrylcholinesterase metabolism MeSH
- Cholinesterase Inhibitors therapeutic use MeSH
- Blood-Brain Barrier drug effects MeSH
- Isoquinolines chemistry isolation & purification therapeutic use MeSH
- Humans MeSH
- Magnetic Resonance Spectroscopy MeSH
- Plant Exudates analysis MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Acetylcholinesterase MeSH
- Alkaloids MeSH
- Butyrylcholinesterase MeSH
- Cholinesterase Inhibitors MeSH
- Isoquinolines MeSH
- Plant Exudates MeSH
Three new alkaloids, bersavine (3), muraricine (4), and berbostrejdine (8), together with seven known isoquinoline alkaloids (1-2, 5-7, 9, and 10) were isolated from an alkaloidal extract of the root bark of Berberis vulgaris. The structures of the isolated compounds were determined by spectroscopic methods, including 1D and 2D NMR techniques, HRMS, and optical rotation, and by comparison of the obtained data with those in the literature. The NMR data of berbamine (5), aromoline (6), and obamegine (7) were completely assigned employing 2D NMR experiments. Alkaloids isolated in sufficient amounts were evaluated for their in vitro acetylcholinesterase, butyrylcholinesterase (BuChE), prolyl oligopeptidase, and glycogen synthase kinase-3β inhibitory activities. Selected compounds were studied for their ability to permeate through the blood-brain barrier. Significant human BuChE ( hBuChE) inhibitory activity was demonstrated by 6 (IC50 = 0.82 ± 0.10 μM). The in vitro data were further supported by computational analysis that showed the accommodation of 6 in the active site of hBuChE.
Centro de Investigaciones Biologicas CSIC Avenida Ramiro de Maeztu 9 28040 Madrid Spain
Department for Life Quality Studies University of Bologna Corso D'Augusto 237 47921 Rimini Italy
Department of Toxicoloxy and Military Pharmacy Trebesska 1575 500 05 Hradec Kralove Czech Republic
References provided by Crossref.org
Natural Alkaloids as Multi-Target Compounds towards Factors Implicated in Alzheimer's Disease
