2024-03-29T05:05:40Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/906192022-06-23T10:24:25Zcom_10261_81com_10261_5col_10261_334
2014-02-10T11:55:23Z
urn:hdl:10261/90619
Cannabinoid agonists showing BuChE inhibition as potential therapeutic agents for Alzheimer's disease
González-Naranjo, Pedro
Pérez-Macias, N.
Campillo, Nuria E.
Pérez, C.
Arán, Vicente J.
Girón, Rocío
Sánchez-Robles, E.
Martín, M. Isabel
Gómez-Cañas, María
García-Arencibia, Moisés
Fernández-Ruiz, Javier
Páez, Juan A.
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 [3H]-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. © 2013 Elsevier Masson SAS. All rights reserved.
2014-02-10T11:55:23Z
2014-02-10T11:55:23Z
2014
2014-02-10T11:55:24Z
artículo
European Journal of Medicinal Chemistry 73: 56- 72 (2014)
http://hdl.handle.net/10261/90619
10.1016/j.ejmech.2013.11.026
eng
closedAccess
Elsevier