Structure-Based Optimization of Coumarin hA3 Adenosine Receptor AntagonistsClick to copy article linkArticle link copied!
- Maria João Matos*Maria João Matos*For M.J.M.: phone, +34 881814936; E-mail, [email protected] or [email protected]CIQUP/Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, 4169-007 Porto, PortugalDepartment of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela, 15782 Santiago de Compostela, SpainMore by Maria João Matos
- Santiago VilarSantiago VilarDepartment of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela, 15782 Santiago de Compostela, SpainMore by Santiago Vilar
- Saleta Vazquez-RodriguezSaleta Vazquez-RodriguezDepartment of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela, 15782 Santiago de Compostela, SpainMore by Saleta Vazquez-Rodriguez
- Sonja KachlerSonja KachlerInstitute of Pharmacology and Toxicology, University of Würzburg, 97078 Würzburg, GermanyMore by Sonja Kachler
- Karl-Norbert KlotzKarl-Norbert KlotzInstitute of Pharmacology and Toxicology, University of Würzburg, 97078 Würzburg, GermanyMore by Karl-Norbert Klotz
- Michela BuccioniMichela BuccioniSchool of Pharmacy, Medicinal Chemistry Unit, University of Camerino, 62032 Camerino, ItalyMore by Michela Buccioni
- Giovanna DeloguGiovanna DeloguDepartment of Life Sciences and Environment—Section of Pharmaceutical Sciences, University of Cagliari, 09124 Cagliari, ItalyMore by Giovanna Delogu
- Lourdes SantanaLourdes SantanaDepartment of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela, 15782 Santiago de Compostela, SpainMore by Lourdes Santana
- Eugenio UriarteEugenio UriarteDepartment of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela, 15782 Santiago de Compostela, SpainInstituto de Ciencias Químicas Aplicadas, Universidad Autónoma de Chile, 7500912 Santiago, ChileMore by Eugenio Uriarte
- Fernanda Borges*Fernanda Borges*For F.B.: phone, +351 220402560; E-mail, [email protected]CIQUP/Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, 4169-007 Porto, PortugalMore by Fernanda Borges
Abstract
Adenosine receptors participate in many physiological functions. Molecules that may selectively interact with one of the receptors are favorable multifunctional chemical entities to treat or decelerate the evolution of different diseases. 3-Arylcoumarins have already been studied as neuroprotective agents by our group. Here, differently 8-substituted 3-arylcoumarins are complementarily studied as ligands of adenosine receptors, performing radioligand binding assays. Among the synthesized compounds, selective A3 receptor antagonists were found. 3-(4-Bromophenyl)-8-hydroxycoumarin (compound 4) displayed the highest potency and selectivity as A3 receptor antagonist (Ki = 258 nM). An analysis of its X-ray diffraction provided detailed information on its structure. Further evaluation of a selected series of compounds indicated that it is the nature and position of the substituents that determine their activity and selectivity. Theoretical modeling calculations corroborate and explain the experimental data, suggesting this novel scaffold can be involved in the generation of candidates as multitarget drugs.
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