RT Journal Article
T1 Analogues of cannabinoids as multitarget drugs in the treatment of Alzheimer’s disease
A1 Fernandez, María
A1 Villaro, Wilma
A1 Gómez Cañas, María
A1 García-Arencibia, Moisés
A1 Egea, Javier
A1 Fernández Ruiz, José Javier
A1 Martín, María Isabel
A1 Girón, Rocío
A1 Sánchez Montero, José
A1 Agis Torres, Ángel
A1 Solano, David
A1 Sollhuber Kretzer, Mónica
AB Given that neuronal degeneration in Alzheimer's disease (AD) is caused by the combination of multiple neurotoxic insults, current directions in the research of novel therapies to treat this disease attempts to design multitarget strategies that could be more effective than the simply use of acetylcholinesterase inhibitors; currently, the most used therapy for AD. One option, explored recently, is the synthesis of new analogues of cannabinoids that could competitively inhibit the acetylcholinesterase (AChE) enzyme and showing the classic neuroprotective profile of cannabinoid compounds. In this work, molecular docking has been used to design some cannabinoid analogues with such multitarget properties, based on the similarities of donepezil and Δ9-tetrahydrocannabinol. The analogues synthesized, compounds 1 and 2, demonstrated to have two interesting characteristics in different in vitro assays: competitive inhibition of AChE and competitive antagonism at the CB1/CB2 receptors. They are highly lipophilic, highlighting that they could easily reach the CNS, and apparently presented a low toxicity. These results open the door to the synthesis of new compounds for a more effective treatment of AD.
PB Elsevier
SN 0014-2999
YR 2021
FD 2021-01-15
LK https://hdl.handle.net/20.500.14352/92552
UL https://hdl.handle.net/20.500.14352/92552
LA eng
NO Sánchez Montero JM, Agis-Torres A, Solano D, Söllhuber M, Fernandez M, Villaro W, et al. Analogues of cannabinoids as multitarget drugs in the treatment of Alzheimer's disease. Eur J Pharmacol 2021;895:173875.
NO Ministerio de Ciencia, Innovación y Universidades (España)
DS Docta Complutense
RD 11 abr 2025