Tacrine-resveratrol fused hybrids as multi-target-directed ligands against Alzheimer's disease

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023752%3A_____%2F17%3A43915308" target="_blank" >RIV/00023752:_____/17:43915308 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/60162694:G44__/17:43875734 RIV/00216208:11160/17:10368075 RIV/00179906:_____/17:10368075

Výsledek na webu

<a href="http://www.sciencedirect.com/science/article/pii/S0223523416310546" target="_blank" >http://www.sciencedirect.com/science/article/pii/S0223523416310546</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ejmech.2016.12.048" target="_blank" >10.1016/j.ejmech.2016.12.048</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Tacrine-resveratrol fused hybrids as multi-target-directed ligands against Alzheimer's disease

Popis výsledku v původním jazyce

Multi-target drug discovery is one of the most followed approaches in the active central nervous systém (CNS) therapeutic area, especially in the search for new drugs against Alzheimer&apos;s disease (AD). This is because innovative multi-target-directed ligands (MTDLs) could more adequately address the complexity of this pathological condition. In a continuation of our efforts aimed at a new series of anti-AD MTDLs, we combined the structural features of the cholinesterase inhibitor drug tacrine with that of resveratrol, which is known for its purported antioxidant and anti-neuroinflammatory activities. The most interesting hybrid compounds (5, 8, 9 and 12) inhibited human acetylcholinesterase at micromolar concentrations and effectively modulated Ab self-aggregation in vitro. In addition, 12 showed intriguing antiinflammatory and immuno-modulatory properties in neuronal and glial AD cell models. Importantly, the MTDL profile is accompanied by high-predicted blood-brain barrier permeability, and low cytotoxicity on primary neurons.

Název v anglickém jazyce

Tacrine-resveratrol fused hybrids as multi-target-directed ligands against Alzheimer's disease

Popis výsledku anglicky

Multi-target drug discovery is one of the most followed approaches in the active central nervous systém (CNS) therapeutic area, especially in the search for new drugs against Alzheimer&apos;s disease (AD). This is because innovative multi-target-directed ligands (MTDLs) could more adequately address the complexity of this pathological condition. In a continuation of our efforts aimed at a new series of anti-AD MTDLs, we combined the structural features of the cholinesterase inhibitor drug tacrine with that of resveratrol, which is known for its purported antioxidant and anti-neuroinflammatory activities. The most interesting hybrid compounds (5, 8, 9 and 12) inhibited human acetylcholinesterase at micromolar concentrations and effectively modulated Ab self-aggregation in vitro. In addition, 12 showed intriguing antiinflammatory and immuno-modulatory properties in neuronal and glial AD cell models. Importantly, the MTDL profile is accompanied by high-predicted blood-brain barrier permeability, and low cytotoxicity on primary neurons.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

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

2017

Kód důvěrnosti údajů

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

Název periodika

European Journal of Medicinal Chemistry

ISSN

0223-5234

e-ISSN

—

Svazek periodika

127

Číslo periodika v rámci svazku

February

Stát vydavatele periodika

FR - Francouzská republika

Počet stran výsledku

13

Strana od-do

250-262

Kód UT WoS článku

000397172800021

EID výsledku v databázi Scopus

2-s2.0-85008400066