Aromatic Esters of the Crinane Amaryllidaceae Alkaloid Ambelline as Selective Inhibitors of Butyrylcholinesterase

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60162694%3AG44__%2F20%3A00555854" target="_blank" >RIV/60162694:G44__/20:00555854 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11160/20:10416889 RIV/00179906:_____/20:10416889
Result on the web
<a href="https://pubs.acs.org/doi/10.1021/acs.jnatprod.9b00561" target="_blank" >https://pubs.acs.org/doi/10.1021/acs.jnatprod.9b00561</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acs.jnatprod.9b00561" target="_blank" >10.1021/acs.jnatprod.9b00561</a>

Result language
angličtina
Original language name
Aromatic Esters of the Crinane Amaryllidaceae Alkaloid Ambelline as Selective Inhibitors of Butyrylcholinesterase
Original language description
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 mu M), 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 mu M, 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.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
10611 - Plant sciences, botany

Project
<a href="/en/project/EF16_019%2F0000841" target="_blank" >EF16_019/0000841: Efficiency and safety improvement of current drugs and nutraceuticals: advanced methods - new challenges</a><br>
Continuities
S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2020
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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