Aromatic Esters of the Crinane Amaryllidaceae Alkaloid Ambelline as Selective Inhibitors of Butyrylcholinesterase.
J Nat Prod
; 83(5): 1359-1367, 2020 05 22.
Article
em En
| MEDLINE
| ID: mdl-32309949
ABSTRACT
A total of 20 derivatives (1-20) of the crinane-type alkaloid ambelline were synthesized. These semisynthetic derivatives were assessed for their potency to inhibit both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). To predict central nervous system (CNS) availability, logBB was calculated, and the data correlated well with those obtained from the parallel artificial membrane permeability assay (PAMPA). All compounds should be able to permeate the blood-brain barrier (BBB) according to the obtained results. A total of 7 aromatic derivatives (5, 6, 7, 9, 10, 12, and 16) with different substitution patterns showed inhibitory potency against human serum BuChE (IC50 < 5 µM), highlighting the three top-ranked compounds as follows 11-O-(1-naphthoyl)ambelline (16), 11-O-(2-methylbenzoyl)ambelline (6), and 11-O-(2-methoxybenzoyl)ambelline (9) with IC50 values of 0.10 ± 0.01, 0.28 ± 0.02, and 0.43 ± 0.04 µM, respectively. Notably, derivatives 6, 7, 9, and 16 displayed selective human BuChE (hBuChE) inhibition profiles with a selectivity index > 100. The in vitro results were supported by computational studies predicting plausible binding modes of the compounds in the active sites of hBuChE.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Butirilcolinesterase
/
Inibidores da Colinesterase
/
Alcaloides de Amaryllidaceae
/
Amaryllidaceae
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
J Nat Prod
Ano de publicação:
2020
Tipo de documento:
Article