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

Kód výsledku v 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>

Nalezeny alternativní kódy

RIV/00179906:_____/19:10400122 RIV/00216208:11150/19:10400122 RIV/00216208:11160/19:10400122 RIV/00216275:25310/19:39914655

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/EF18_069%2F0010046" target="_blank" >EF18_069/0010046: Předaplikační výzkum inovativních léčiv a medicínských technologií</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Molecules

ISSN

1420-3049

e-ISSN

—

Svazek periodika

24

Číslo periodika v rámci svazku

7

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

18

Strana od-do

1307

Kód UT WoS článku

000464951700025

EID výsledku v databázi Scopus

2-s2.0-85063755990