Derivatives of the beta-Crinane Amaryllidaceae Alkaloid Haemanthamine as Multi-Target Directed Ligands for Alzheimer's Disease

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60162694%3AG44__%2F19%3A00536708" target="_blank" >RIV/60162694:G44__/19:00536708 - isvavai.cz</a>
Alternative codes found
RIV/00179906:_____/19:10400122 RIV/00216208:11150/19:10400122 RIV/00216208:11160/19:10400122 RIV/00216275:25310/19:39914655
Result on the web
<a href="https://www.mdpi.com/1420-3049/24/7/1307" target="_blank" >https://www.mdpi.com/1420-3049/24/7/1307</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.3390/molecules24071307" target="_blank" >10.3390/molecules24071307</a>

Result language
angličtina
Original language name
Derivatives of the beta-Crinane Amaryllidaceae Alkaloid Haemanthamine as Multi-Target Directed Ligands for Alzheimer's Disease
Original language description
Twelve derivatives 1a-1m of the beta-crinane-type alkaloid haemanthamine were developed. All the semisynthetic derivatives were studied for their inhibitory potential against both acetylcholinesterase and butyrylcholinesterase. In addition, glycogen synthase kinase 3 beta (GSK-3 beta) inhibition potency was evaluated in the active derivatives. In order to reveal the availability of the drugs to the CNS, we elucidated the potential of selected derivatives to penetrate through the blood-brain barrier (BBB). Two compounds, namely 11-O-(2-methylbenzoyl)-haemanthamine (1j) and 11-O-(4-nitrobenzoyl)-haemanthamine (1m), revealed the most intriguing profile, both being acetylcholinesterase (hAChE) inhibitors on a micromolar scale, with GSK-3 beta inhibition properties, and predicted permeation through the BBB. In vitro data were further corroborated by detailed inspection of the compounds' plausible binding modes in the active sites of hAChE and hBuChE, which led us to provide the structural determinants responsible for the activity towards these enzymes.
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
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OECD FORD branch
10608 - Biochemistry and molecular biology

Project
<a href="/en/project/EF18_069%2F0010046" target="_blank" >EF18_069/0010046: Pre-application research into innovative medicines and medical technologies</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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