N-alkylated tacrine derivatives as potential agents in Alzheimer's disease therapy

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00179906%3A_____%2F19%3A10394461" target="_blank" >RIV/00179906:_____/19:10394461 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/60162694:G44__/19:00536742 RIV/62690094:18470/19:50015597 RIV/00216208:11150/19:10394461 RIV/61988987:17110/19:A21026Z2

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=OuJ8bls4jX" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=OuJ8bls4jX</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.2174/1567205016666190314163942" target="_blank" >10.2174/1567205016666190314163942</a>

Jazyk výsledku

angličtina

Název v původním jazyce

N-alkylated tacrine derivatives as potential agents in Alzheimer's disease therapy

Popis výsledku v původním jazyce

Background: Based on the prevalence studies, the number of people suffering from dementia will almost double every 20 years, to 65.7 million in 2030 and 115.4 million in 2050, assuming no changes in mortality, effective preventative measures, definitive diagnostic guidelines or curative treatment. From the above-mentioned epidemiological data, it is obvious that dementia constitutes a major public health problem not only at present, but unfortunately also in the future. Objectives and Methods: Several N-alkylated tacrine (THA) derivatives have already been synthesized by Pomponi et al., in 1997. However, these compounds were tested for their anti-AChE activity using enzyme isolated from Electrophorus electricus. For this reason, we have decided to extend the previously reported series of THA derivatives and consequently test them in the battery of experiments, the results of which have served to more relevant evaluation of these compounds from the perspective of Alzeimer&apos;s disease compared to that published by Pomponi. Results and Conclusion: In summary, all compounds of interest effectively inhibited ChEs in vitro. One of the most promising derivatives 8 bearing an N-octyl chain showed 2.5-fold higher AChE inhibitory activity in relation to tacrine. With respect to blood-brain barrier (BBB) penetration, it can be claimed that synthesized analogues are presumably able to cross the BBB. From the point of view of hepatotoxicity, selected N-alkylated tacrine derivatives exerted worse results compared to tacrine. However, in vitro results are only illustrative, therefore, only in vivo experiments could determine the real value of selected N-alkylated THA derivatives.

Název v anglickém jazyce

N-alkylated tacrine derivatives as potential agents in Alzheimer's disease therapy

Popis výsledku anglicky

Background: Based on the prevalence studies, the number of people suffering from dementia will almost double every 20 years, to 65.7 million in 2030 and 115.4 million in 2050, assuming no changes in mortality, effective preventative measures, definitive diagnostic guidelines or curative treatment. From the above-mentioned epidemiological data, it is obvious that dementia constitutes a major public health problem not only at present, but unfortunately also in the future. Objectives and Methods: Several N-alkylated tacrine (THA) derivatives have already been synthesized by Pomponi et al., in 1997. However, these compounds were tested for their anti-AChE activity using enzyme isolated from Electrophorus electricus. For this reason, we have decided to extend the previously reported series of THA derivatives and consequently test them in the battery of experiments, the results of which have served to more relevant evaluation of these compounds from the perspective of Alzeimer&apos;s disease compared to that published by Pomponi. Results and Conclusion: In summary, all compounds of interest effectively inhibited ChEs in vitro. One of the most promising derivatives 8 bearing an N-octyl chain showed 2.5-fold higher AChE inhibitory activity in relation to tacrine. With respect to blood-brain barrier (BBB) penetration, it can be claimed that synthesized analogues are presumably able to cross the BBB. From the point of view of hepatotoxicity, selected N-alkylated tacrine derivatives exerted worse results compared to tacrine. However, in vitro results are only illustrative, therefore, only in vivo experiments could determine the real value of selected N-alkylated THA derivatives.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30103 - Neurosciences (including psychophysiology)

Projekt

<a href="/cs/project/GA16-08554S" target="_blank" >GA16-08554S: Nové hybridní molekuly v léčbě kognitivních poruch spojených s neurodegenerací</a><br>

Návaznosti

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

Rok uplatnění

2019

Kód důvěrnosti údajů

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

Název periodika

Current Alzheimer Research

ISSN

1567-2050

e-ISSN

—

Svazek periodika

16

Číslo periodika v rámci svazku

4

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

11

Strana od-do

333-343

Kód UT WoS článku

000465506200006

EID výsledku v databázi Scopus

2-s2.0-85066403647