Alkaloids of Zephyranthes citrina (Amaryllidaceae) and their implication to Alzheimer's disease: Isolation, structural elucidation and biological activity
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
33387730
DOI
10.1016/j.bioorg.2020.104567
PII: S0045-2068(20)31865-4
Knihovny.cz E-resources
- Keywords
- Alkaloids, Alzheimer's disease, Amaryllidaceae, Docking studies, Narcieliine, Zephyranthes citrina,
- MeSH
- Acetylcholinesterase chemistry metabolism MeSH
- Alkaloids chemistry isolation & purification pharmacology therapeutic use MeSH
- Alzheimer Disease drug therapy pathology MeSH
- Amaryllidaceae chemistry metabolism MeSH
- Butyrylcholinesterase chemistry metabolism MeSH
- Cholinesterase Inhibitors chemistry metabolism pharmacology therapeutic use MeSH
- Blood-Brain Barrier drug effects metabolism MeSH
- Catalytic Domain MeSH
- Kinetics MeSH
- Humans MeSH
- Magnetic Resonance Spectroscopy MeSH
- Molecular Conformation MeSH
- Molecular Docking Simulation MeSH
- Binding Sites MeSH
- Structure-Activity Relationship 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
Twenty known Amaryllidaceae alkaloids of various structural types, and one undescribed alkaloid of narcikachnine-type, named narcieliine (3), have been isolated from fresh bulbs of Zephyranthes citrina. The chemical structures of the isolated alkaloids were elucidated by a combination of MS, HRMS, 1D and 2D NMR, and CD spectroscopic techniques, and by comparison with literature data. The absolute configuration of narcieliine (3) has also been determined. Compounds isolated in a sufficient quantity were evaluated for their in vitro acetylcholinesterase (AChE; E.C. 3.1.1.7), butyrylcholinesterase (BuChE; E.C. 3.1.1.8), and prolyl oligopeptidase (POP; E.C. 3.4.21.26) inhibition activities. Significant human AChE/BuChE (hAChE/hBuChE) inhibitory activity was demonstrated by the newly described alkaloid narcieliine (3), with IC50 values of 18.7 ± 2.3 µM and 1.34 ± 0.31 µM, respectively. This compound is also predicted to cross the blood-brain barrier (BBB) through passive diffusion. The in vitro data were further supported by in silico studies of 3 in the active site of hAChE/hBuChE.
References provided by Crossref.org
Undescribed Amaryllidaceae Alkaloids from Zephyranthes citrina and Their Cytotoxicity
