2026-06-27T23:38:03Zhttps://docta.ucm.es/rest/oai/request
oai:docta.ucm.es:20.500.14352/936402025-02-22T01:09:11Zcom_20.500.14352_14col_20.500.14352_15
Docta Complutense author González-Naranjo, Pedro author Pérez-Macias, Natalia author Campillo, Nuria author Pérez, Concepción author Arán, Vicente author Girón, Rocio author Sánchez-Robles, Eva author Páez, Juan author Gómez Cañas, María author Martín Fontelles, María Isabel author García Arencibia, Moisés author Fernández Ruiz, José Javier 2024-01-17T14:50:36Z 2024-01-17T14:50:36Z 2014 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. Cannabinoid agonists showing BuChE inhibition as potential therapeutic agents for Alzheimer's disease. Eur J MedChem. 2014, 73:56-72. 0223-5234 10.1016/j.ejmech.2013.11.026 https://hdl.handle.net/20.500.14352/93640 https://doi.org/10.1016/j.ejmech.2013.11.026 Designing drugs with a specific multi-target profile is a promising approach against multifactorial ill nesses 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, com pounds 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. eng Attribution-NonCommercial-NoDerivatives 4.0 International Cannabinoid agonists showing BuChE inhibition as potential therapeutic agents for Alzheimer's disease journal article 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URL https://docta.ucm.es/bitstreams/57ff4ee5-e05e-4877-8b07-91ef383093e6/download File MD5 b4903ff1450215bccab9c4037f79f2a1 1518717 application/pdf Cannabinoid_agonists.pdf