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Cannabinoid agonists showing BuChE inhibition as potential therapeutic agents for Alzheimer's disease.

Abstract：

:Designing drugs with a specific multi-target profile is a promising approach against multifactorial illnesses as Alzheimer's disease. In this work, new indazole ethers that possess dual activity as both cannabinoid agonists CB2 and inhibitors of BuChE have been designed by computational methods. On the basis of this knowledge, the synthesis, pharmacological evaluation and docking studies of a new class of indazoles has been performed. Pharmacological evaluation includes radioligand binding assays with [(3)H]-CP55940 for CB1R and CB2R and functional activity for cannabinoid receptors on isolated tissue. Additionally, in vitro inhibitory assays of AChE/BuChE and the corresponding competition studies have been carried out. The results of pharmacological tests have revealed that three of these derivatives behave as CB2 cannabinoid agonists and simultaneously show BuChE inhibition. In particular, compounds 3 and 24 have emerged as promising candidates as novel cannabinoids that inhibit BuChE by a non-competitive or mixed mechanism, respectively. On the other hand, both molecules show antioxidant properties.

journal_name

Eur J Med Chem

journal_title

European journal of medicinal chemistry

authors

González-Naranjo P,Pérez-Macias N,Campillo NE,Pérez C,Arán VJ,Girón R,Sánchez-Robles E,Martín MI,Gómez-Cañas M,García-Arencibia M,Fernández-Ruiz J,Páez JA

doi

10.1016/j.ejmech.2013.11.026

subject

Has Abstract

pub_date

2014-02-12 00:00:00

pages

56-72

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(13)00768-X

journal_volume

73

pub_type

杂志文章

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