Morphing cholinesterase inhibitor amiridine into multipotent drugs for the treatment of Alzheimer’s disease

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378041%3A_____%2F24%3A00584241" target="_blank" >RIV/68378041:_____/24:00584241 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00179906:_____/24:10480959 RIV/60162694:G44__/25:00563331 RIV/00216208:11310/24:10480959

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S075333222400283X?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S075333222400283X?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.biopha.2024.116399" target="_blank" >10.1016/j.biopha.2024.116399</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Morphing cholinesterase inhibitor amiridine into multipotent drugs for the treatment of Alzheimer’s disease

Popis výsledku v původním jazyce

The search for novel drugs to address the medical needs of Alzheimer’s disease (AD) is an ongoing process relying on the discovery of disease-modifying agents. Given the complexity of the disease, such an aim can be pursued by developing so-called multi-target directed ligands (MTDLs) that will impact the disease pathophysiology more comprehensively. Herewith, we contemplated the therapeutic efficacy of an amiridine drug acting as a cholinesterase inhibitor by converting it into a novel class of novel MTDLs. Applying the linking approach, we have paired amiridine as a core building block with memantine/adamantylamine, trolox, and substituted benzothiazole moieties to generate novel MTDLs endowed with additional properties like N-methyl-D-aspartate (NMDA) receptor affinity, antioxidant capacity, and anti-amyloid properties, respectively. The top-ranked amiridine-based compound 5d was also inspected by in silico to reveal the butyrylcholinesterase binding differences with its close structural analogue 5b. Our study provides insight into the discovery of novel amiridine-based drugs by broadening their target-engaged profile from cholinesterase inhibitors towards MTDLs with potential implications in AD therapy.

Název v anglickém jazyce

Morphing cholinesterase inhibitor amiridine into multipotent drugs for the treatment of Alzheimer’s disease

Popis výsledku anglicky

The search for novel drugs to address the medical needs of Alzheimer’s disease (AD) is an ongoing process relying on the discovery of disease-modifying agents. Given the complexity of the disease, such an aim can be pursued by developing so-called multi-target directed ligands (MTDLs) that will impact the disease pathophysiology more comprehensively. Herewith, we contemplated the therapeutic efficacy of an amiridine drug acting as a cholinesterase inhibitor by converting it into a novel class of novel MTDLs. Applying the linking approach, we have paired amiridine as a core building block with memantine/adamantylamine, trolox, and substituted benzothiazole moieties to generate novel MTDLs endowed with additional properties like N-methyl-D-aspartate (NMDA) receptor affinity, antioxidant capacity, and anti-amyloid properties, respectively. The top-ranked amiridine-based compound 5d was also inspected by in silico to reveal the butyrylcholinesterase binding differences with its close structural analogue 5b. Our study provides insight into the discovery of novel amiridine-based drugs by broadening their target-engaged profile from cholinesterase inhibitors towards MTDLs with potential implications in AD therapy.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30103 - Neurosciences (including psychophysiology)

Projekt

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

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2024

Kód důvěrnosti údajů

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

Název periodika

Biomedicine & Pharmacotherapy

ISSN

0753-3322

e-ISSN

1950-6007

Svazek periodika

173

Číslo periodika v rámci svazku

April

Stát vydavatele periodika

FR - Francouzská republika

Počet stran výsledku

13

Strana od-do

116399

Kód UT WoS článku

001209991700001

EID výsledku v databázi Scopus

2-s2.0-85188014116