RT Journal Article
T1 Synthesis and characterization of a new bivalent ligand combining caffeine and docosahexaenoic acid
A1 Fernández Dueñas, Víctor
A1 Azuaje Guerrero, Jhonny Alberto
A1 Morató, Xavier
A1 Cordobilla, Begoña
A1 Domingo, Joan Carles
A1 Sotelo Pérez, Eddy
A1 Ciruela, Francisco
K1 Adenosine A2A receptor
K1 Caffeine
K1 Docosahexaenoic acid (DHA)
K1 Inverse agonism
AB Caffeine is a promising drug for the management of neurodegenerative diseases such as Parkinson’s disease (PD), demonstrating neuroprotective properties that have been attributed to its interaction with the basal ganglia adenosine A2A receptor (A2AR). However, the doses needed to exert these neuroprotective effects may be too high. Thus, it is important to design novel approaches that selectively deliver this natural compound to the desired target. Docosahexaenoic acid (DHA) is the major omega-3 fatty acid in the brain and can act as a specific carrier of caffeine. Furthermore, DHA displays properties that may lead to its use as a neuroprotective agent. In the present study, we constructed a novel bivalent ligand covalently linking caffeine and DHA and assessed its pharmacological activity and safety profile in a simple cellular model. Interestingly, the new bivalent ligand presented higher potency as an A2AR inverse agonist than caffeine alone. We also determined the range of concentrations inducing toxicity both in a heterologous system and in primary striatal cultures. The novel strategy presented here of attaching DHA to caffeine may enable increased effects of the drug at desired sites, which could be of interest for the treatment of PD
PB MDPI
YR 2017
FD 2017
LK http://hdl.handle.net/10347/22516
UL http://hdl.handle.net/10347/22516
LA eng
NO Fernández-Dueñas, V.; Azuaje, J.; Morató, X.; Cordobilla, B.; Domingo, J.C.; Sotelo, E.; Ciruela, F. Synthesis and Characterization of a New Bivalent Ligand Combining Caffeine and Docosahexaenoic Acid. Molecules 2017, 22, 366.
NO This work was supported by the grant MINECO/ISCIII (SAF2014-55700-P, PCIN-2013-019-C03-03 and PIE14/00034), the Catalan government (2014 SGR 1054), ICREA (ICREA Academia-2010), as well asgrants from the Fundació la Marató de TV3 (grant 20152031) and FWO (SBO-140028) to FC and those from theConcellería de Cultura, Educación e Ordenación Universitaria of the Galician Government (grant GPC2014/03),Centro Singular de Investigación de Galicia (accreditation 2016–2019; ED431G/09) and the European RegionalDevelopment Fund (ERDF) to ES
DS Minerva
RD 24 abr 2026