Development of 2,6,9-trisubstituted purines as neuroprotective agents targeting butyrylcholinesterase and cannabinoid CB2 receptor

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389030%3A_____%2F26%3A00645666" target="_blank" >RIV/61389030:_____/26:00645666 - isvavai.cz</a>

Result on the web

<a href="https://doi.org/10.1016/j.ejmech.2025.118217" target="_blank" >https://doi.org/10.1016/j.ejmech.2025.118217</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ejmech.2025.118217" target="_blank" >10.1016/j.ejmech.2025.118217</a>

Result language

angličtina

Original language name

Development of 2,6,9-trisubstituted purines as neuroprotective agents targeting butyrylcholinesterase and cannabinoid CB2 receptor

Original language description

Neurodegenerative diseases (ND) are a diverse group of disorders characterized by the progressive loss of neurons, leading to severe cognitive and physical impairments. Parkinson's, Alzheimer's, and Huntington's diseases are among the most prominent examples, with their prevalence steadily increasing due to the aging global population. In 2009, approximately 50 million people worldwide were affected by ND, and current projections suggest this number will exceed 115 million by 2050. The development of ND is complex and multifactorial, influenced by genetic predispositions, environmental factors, aging, and cellular dysfunction. A significant challenge in addressing these diseases lies in the absence of curative treatments, existing therapies are limited to symptom management and enhancing quality of life. We report the synthesis and biological evaluation of a series of 2,6,9-trisubstituted purine derivatives, some of which exhibited strong neuroprotective effects in cellular models of mitochondrial (3-nitropropionic acidinduced) and oxidative (glutamate-induced) stress. Also, several compounds functioned as selective butyrylcholinesterase (BChE) inhibitors and three of which showed CB2 receptor agonist activity, supporting their potential as multifunctional agents for neurodegenerative disorders. In vitro assays confirmed their protective effects across multiple cellular pathways, including reduction of apoptosis, oxidative stress, and mitochondrial permeability transition. Notably, compound 3e emerged as the most effective derivative, combining strong BChE inhibition, CB2 receptor activation, and cytoprotective effects. These findings identify 2,6,9-trisubstituted purines as promising scaffolds for the development of multi-target-directed ligands in neurodegenerative disease therapy.

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

10608 - Biochemistry and molecular biology

Project

<a href="/en/project/GA23-05389S" target="_blank" >GA23-05389S: Novel CB2 and BChE modulators against Parkinson's disease and related pathologies</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2026

Confidentiality

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

Name of the periodical

European Journal of Medicinal Chemistry

ISSN

0223-5234

e-ISSN

1768-3254

Volume of the periodical

301

Issue of the periodical within the volume

JAN 5

Country of publishing house

FR - FRANCE

Number of pages

21

Pages from-to

118217

UT code for WoS article

001588413300005

EID of the result in the Scopus database

2-s2.0-105017298985