Tacrine - Benzothiazoles: Novel class of potential multitarget anti-Alzheimets drugs dealing with cholinergic, amyloid and mitochondrial systems

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023752%3A_____%2F21%3A43920493" target="_blank" >RIV/00023752:_____/21:43920493 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/60162694:G44__/21:00556798

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S0045206820318940?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0045206820318940?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.bioorg.2020.104596" target="_blank" >10.1016/j.bioorg.2020.104596</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Tacrine - Benzothiazoles: Novel class of potential multitarget anti-Alzheimets drugs dealing with cholinergic, amyloid and mitochondrial systems

Popis výsledku v původním jazyce

A series of tacrine – benzothiazole hybrids incorporate inhibitors of acetylcholinesterase (AChE), amyloid β (Aβ) aggregation and mitochondrial enzyme ABAD, whose interaction with Aβ leads to mitochondrial dysfunction, into a single molecule. In vitro, several of 25 final compounds exerted excellent anti-AChE properties and interesting capabilities to block Aβ aggregation. The best derivative of the series could be considered 10w that was found to be highly potent and selective towards AChE with the IC50 value in nanomolar range. Moreover, the same drug candidate exerted absolutely the best results of the series against ABAD, decreasing its activity by 23% at 100 µM concentration. Regarding the cytotoxicity profile of highlighted compound, it roughly matched that of its parent compound – 6-chlorotacrine. Finally, 10w was forwarded for in vivo scopolamine-induced amnesia experiment consisting of Morris Water Maze test, where it demonstrated mild procognitive effect. Taking into account all in vitro and in vivo data, highlighted derivative 10w could be considered as the lead structure worthy of further investigation.

Název v anglickém jazyce

Tacrine - Benzothiazoles: Novel class of potential multitarget anti-Alzheimets drugs dealing with cholinergic, amyloid and mitochondrial systems

Popis výsledku anglicky

A series of tacrine – benzothiazole hybrids incorporate inhibitors of acetylcholinesterase (AChE), amyloid β (Aβ) aggregation and mitochondrial enzyme ABAD, whose interaction with Aβ leads to mitochondrial dysfunction, into a single molecule. In vitro, several of 25 final compounds exerted excellent anti-AChE properties and interesting capabilities to block Aβ aggregation. The best derivative of the series could be considered 10w that was found to be highly potent and selective towards AChE with the IC50 value in nanomolar range. Moreover, the same drug candidate exerted absolutely the best results of the series against ABAD, decreasing its activity by 23% at 100 µM concentration. Regarding the cytotoxicity profile of highlighted compound, it roughly matched that of its parent compound – 6-chlorotacrine. Finally, 10w was forwarded for in vivo scopolamine-induced amnesia experiment consisting of Morris Water Maze test, where it demonstrated mild procognitive effect. Taking into account all in vitro and in vivo data, highlighted derivative 10w could be considered as the lead structure worthy of further investigation.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30210 - Clinical neurology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2021

Kód důvěrnosti údajů

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

Název periodika

Bioorganic Chemistry

ISSN

0045-2068

e-ISSN

—

Svazek periodika

107

Číslo periodika v rámci svazku

February

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

19

Strana od-do

104596

Kód UT WoS článku

000618104800008

EID výsledku v databázi Scopus

2-s2.0-85099004986