Adenosine A2A receptor agonists with potent antiplatelet activity

Platelets
E FuentesChrista E Müller

Abstract

Selected adenosine A2A receptor agonists (PSB-15826, PSB-12404, and PSB-16301) have been evaluated as new antiplatelet agents. In addition, radioligand-binding studies and receptor-docking experiments were performed in order to explain their differential biological effects on a molecular level. Among the tested adenosine derivatives, PSB-15826 was the most potent compound to inhibit platelet aggregation (EC50 0.32 ± 0.05 µmol/L) and platelet P-selectin cell-surface localization (EC50 0.062 ± 0.2 µmol/L), and to increase intraplatelets cAMP levels (EC50 0.24 ± 0.01 µmol/L). The compound was more active than CGS21680 (EC50 0.97±0.07 µmol/L) and equipotent to NECA (EC50 0.31 ± 0.05 µmol/L) in platelet aggregation induced by ADP. In contrast to the results from cAMP assays, Ki values determined in radioligand-binding studies were not predictive of the A2A agonists' antiplatelet activity. Docking studies revealed the key molecular determinants of this new family of adenosine A2A receptor agonists: differences in activities are related to π-stacking interactions between the ligands and the residue His264 in the extracellular loop of the adenosine A2A receptor which may result in increased residence times. In conclusion, these results...Continue Reading

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Citations

Mar 28, 2020·Cells·Wiwin Is EffendiYoshihiro Nishimura
Nov 7, 2019·International Journal of Molecular Sciences·Nina Wolska, Marcin Rozalski
Jan 8, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Nina WolskaMarcin Rozalski
Feb 13, 2021·Frontiers in Pharmacology·P BoknikU Gergs
May 1, 2021·Antioxidants·Lyanne RodríguezEduardo Fuentes
Sep 1, 2021·Journal of Medicinal Food·Sigrid SanzanaIván Palomo

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