AChE inhibitory activity of N-substituted natural galanthamine derivatives.
Bioorg Med Chem Lett
; 112: 129937, 2024 Nov 01.
Article
in En
| MEDLINE
| ID: mdl-39218406
ABSTRACT
Galanthamine derivatives are known for their AChE inhibitory activity. Among them, galanthamine has been approved for treatment of Alzheimer's disease. N-Acetylnorgalanthamine (narcisine) and N-(2'-methyl)allylnorgalanthamine (the most potent natural AChE inhibitor of galanthamine type) were synthetized using N-norgalanthamine as a precursor. The NMR data described previously for narcisine were revised by two-dimensional 1H-1H and 1H-13C chemical shift correlation experiments. AChE inhibitory assays showed that N-acetylnorgalanthamine and N-formylnorgalanthamine (with previously unknown activity) are 4- and 43-times, respectively, less potent than galanthamine. In vitro (AChE inhibitory) and in silico (docking, ADME) assays and comparison of N-(2'-methyl)allylnorgalanthamine with galanthamine prove that this molecule is a very promising natural AChE inhibitor (33-times more potent than galanthamine) which further in vivo studies would provide better estimation about its applicability as a drug.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Acetylcholinesterase
/
Cholinesterase Inhibitors
/
Galantamine
Limits:
Humans
Language:
En
Journal:
Bioorg Med Chem Lett
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2024
Document type:
Article
Affiliation country:
Bulgaria
Country of publication:
United kingdom