Inhibitors of acetylcholinesterase derived from 7-Methoxytacrine and their effects on the Choline Transporter CHT1

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023752%3A_____%2F17%3A43915285" target="_blank" >RIV/00023752:_____/17:43915285 - isvavai.cz</a>

Alternative codes found

RIV/00179906:_____/17:10338030

Result on the web

<a href="https://www.karger.com/Article/FullText/453256" target="_blank" >https://www.karger.com/Article/FullText/453256</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1159/000453256" target="_blank" >10.1159/000453256</a>

Result language

angličtina

Original language name

Inhibitors of acetylcholinesterase derived from 7-Methoxytacrine and their effects on the Choline Transporter CHT1

Original language description

Background: Reversible acetylcholinesterase inhibitors are used in Alzheimer disease therapy. However, tacrine and its derivatives have severe side effects. Derivatives of the tacrine analogue 7-methoxytacrine (MEOTA) are less toxic. Methods: We evaluated new derivatives of 7-MEOTA (2 homodimers linked by 2 C4-C5 chains and 5 N-alkylated C4-C8 side chain derivatives) in vitro, using the rat hippocampal choline transporter CHT1. Results: Some derivatives were effective inhibitors of rat acetylcholinesterase and comparable with 7-MEOTA. All derivatives were able to inhibit CHT1, probably via quaternary ammonium, and this interaction could be involved in the enhancement of their detrimental side effects and/or in the attenuation of their promising effects. Under conditions of disrupted lipid rafts, the unfavorable effects of some derivatives were weakened. Only tacrine was probably able to stereospecifically interact with the naturally occurring amyloid-β isoform and to simultaneously stimulate CHT1. Some derivatives, when coincubated with amyloid β, did not influence CHT1. All derivatives also increased the fluidity of the cortical membranes. Conclusion: The N-alkylated derivative of 7-MEOTA bearing from C4 side chains appears to be the most promising compound and should be evaluated in future in vivo research.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30103 - Neurosciences (including psychophysiology)

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

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

Publication year

2017

Confidentiality

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

Name of the periodical

Dementia and Geriatric Cognitive Disorders

ISSN

1420-8008

e-ISSN

—

Volume of the periodical

43

Issue of the periodical within the volume

1-2

Country of publishing house

CH - SWITZERLAND

Number of pages

14

Pages from-to

45-58

UT code for WoS article

000395664800005

EID of the result in the Scopus database

2-s2.0-85008412627