{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T06:50:39Z","timestamp":1771829439244,"version":"3.50.1"},"reference-count":58,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2020,9,19]],"date-time":"2020-09-19T00:00:00Z","timestamp":1600473600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010801","name":"Xunta de Galicia","doi-asserted-by":"publisher","award":["ED481B 2014\/027-0, ED481B 2014\/086\u20130 and ED481B 2018\/007"],"award-info":[{"award-number":["ED481B 2014\/027-0, ED481B 2014\/086\u20130 and ED481B 2018\/007"]}],"id":[{"id":"10.13039\/501100010801","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","award":["CEECIND\/02423\/2018"],"award-info":[{"award-number":["CEECIND\/02423\/2018"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Adenosine receptors (ARs) play an important role in neurological and psychiatric disorders such as Alzheimer\u2019s disease, Parkinson\u2019s disease, epilepsy and schizophrenia. The different subtypes of ARs and the knowledge on their densities and status are important for understanding the mechanisms underlying the pathogenesis of diseases and for developing new therapeutics. Looking for new scaffolds for selective AR ligands, coumarin\u2013chalcone hybrids were synthesized (compounds 1\u20138) and screened in radioligand binding (hA1, hA2A and hA3) and adenylyl cyclase (hA2B) assays in order to evaluate their affinity for the four human AR subtypes (hARs). Coumarin\u2013chalcone hybrid has been established as a new scaffold suitable for the development of potent and selective ligands for hA1 or hA3 subtypes. In general, hydroxy-substituted hybrids showed some affinity for the hA1, while the methoxy counterparts were selective for the hA3. The most potent hA1 ligand was compound 7 (Ki = 17.7 \u00b5M), whereas compound 4 was the most potent ligand for hA3 (Ki = 2.49 \u00b5M). In addition, docking studies with hA1 and hA3 homology models were established to analyze the structure\u2013function relationships. Results showed that the different residues located on the protein binding pocket could play an important role in ligand selectivity.<\/jats:p>","DOI":"10.3390\/molecules25184306","type":"journal-article","created":{"date-parts":[[2020,9,20]],"date-time":"2020-09-20T21:20:28Z","timestamp":1600636828000},"page":"4306","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Adenosine Receptor Ligands: Coumarin\u2013Chalcone Hybrids as Modulating Agents on the Activity of hARs"],"prefix":"10.3390","volume":"25","author":[{"given":"Saleta","family":"Vazquez-Rodriguez","sequence":"first","affiliation":[{"name":"Departamento de Qu\u00edmica Org\u00e1nica, Facultad de Farmacia, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain"}]},{"given":"Santiago","family":"Vilar","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Org\u00e1nica, Facultad de Farmacia, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain"}]},{"given":"Sonja","family":"Kachler","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Pharmakologie und Toxikologie, Universit\u00e4t W\u00fcrzburg, 97078 W\u00fcrzburg, Germany"}]},{"given":"Karl-Norbert","family":"Klotz","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Pharmakologie und Toxikologie, Universit\u00e4t W\u00fcrzburg, 97078 W\u00fcrzburg, Germany"}]},{"given":"Eugenio","family":"Uriarte","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Org\u00e1nica, Facultad de Farmacia, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain"},{"name":"Instituto de Ciencias Qu\u00edmicas Aplicadas, Universidad Aut\u00f3noma de Chile, 7500912 Santiago, Chile"}]},{"given":"Fernanda","family":"Borges","sequence":"additional","affiliation":[{"name":"CIQUP\/Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Rua Campo Alegre 687, 4169-007 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3470-8299","authenticated-orcid":false,"given":"Maria Jo\u00e3o","family":"Matos","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Org\u00e1nica, Facultad de Farmacia, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain"},{"name":"CIQUP\/Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Rua Campo Alegre 687, 4169-007 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1124\/pr.110.003285","article-title":"International union of basic and clinical pharmacology. 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