Turning Donepezil into a Multi-Target-Directed Ligand through a Merging Strategy

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60162694%3AG44__%2F21%3A00557423" target="_blank" >RIV/60162694:G44__/21:00557423 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00179906:_____/21:10421371

Výsledek na webu

<a href="https://chemistry-europe.onlinelibrary.wiley.com/doi/epdf/10.1002/cmdc.202000484" target="_blank" >https://chemistry-europe.onlinelibrary.wiley.com/doi/epdf/10.1002/cmdc.202000484</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/cmdc.202000484" target="_blank" >10.1002/cmdc.202000484</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Turning Donepezil into a Multi-Target-Directed Ligand through a Merging Strategy

Popis výsledku v původním jazyce

Thanks to the widespread use and safety profile of donepezil (1) in the treatment of Alzheimer's disease (AD), one of the most widely adopted multi-target-directed ligand (MTDL) design strategies is to modify its molecular structure by linking a second fragment carrying an additional AD-relevant biological property. Herein, supported by a proposed combination therapy of1and the quinone drug idebenone, we rationally designed novel1-based MTDLs targeting A beta and oxidative pathways. By exploiting a bioisosteric replacement of the indanone core of1with a 1,4-naphthoquinone, we ended up with a series of highly merged derivatives, in principle devoid of the "physicochemical challenge" typical of large hybrid-based MTDLs. A preliminary investigation of their multi-target profile identified9, which showed a potent and selective butyrylcholinesterase inhibitory activity, together with antioxidant and antiaggregating properties. In addition, it displayed a promising drug-like profile.

Název v anglickém jazyce

Turning Donepezil into a Multi-Target-Directed Ligand through a Merging Strategy

Popis výsledku anglicky

Thanks to the widespread use and safety profile of donepezil (1) in the treatment of Alzheimer's disease (AD), one of the most widely adopted multi-target-directed ligand (MTDL) design strategies is to modify its molecular structure by linking a second fragment carrying an additional AD-relevant biological property. Herein, supported by a proposed combination therapy of1and the quinone drug idebenone, we rationally designed novel1-based MTDLs targeting A beta and oxidative pathways. By exploiting a bioisosteric replacement of the indanone core of1with a 1,4-naphthoquinone, we ended up with a series of highly merged derivatives, in principle devoid of the "physicochemical challenge" typical of large hybrid-based MTDLs. A preliminary investigation of their multi-target profile identified9, which showed a potent and selective butyrylcholinesterase inhibitory activity, together with antioxidant and antiaggregating properties. In addition, it displayed a promising drug-like profile.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30107 - Medicinal chemistry

Projekt

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

Návaznosti

S - Specificky vyzkum na vysokych skolach

Rok uplatnění

2021

Kód důvěrnosti údajů

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

Název periodika

ChemMedChem

ISSN

1860-7179

e-ISSN

1860-7187

Svazek periodika

16

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

12

Strana od-do

187-198

Kód UT WoS článku

000564570900001

EID výsledku v databázi Scopus

2-s2.0-85089982454