Comparative Study of Carborane- and Phenyl-Modified Adenosine Derivatives as Ligands for the A2A and A3 Adenosine Receptors Based on a Rigid in Silico Docking and Radioligand Replacement Assay.
Adenosine receptors are involved in many physiological processes and pathological conditions and are therefore attractive therapeutic targets. To identify new types of effective ligands for these receptors, a library of adenosine derivatives bearing a boron cluster or phenyl group in the same position was designed. The ligands were screened in silico to determine their calculated affinities for the A2A and A3 adenosine receptors. An virtual screening protocol based on the PatchDock web server was developed. In the first screening phase, the effects of the functional group (organic or inorganic modulator) on the adenosine ligand affinity for the receptors were determined. Then, the lead compounds were identified for each receptor in the second virtual screening phase. Two pairs of the most promising ligands, compounds 3 and 4, and two ligands with lower affinity scores (compounds 11 and 12, one with a boron cluster and one with a phenyl group) were synthesized and tested in a radioligand replacement assay for affinity to the A2A and A3 receptors. A reasonable correlation of in silico and biological assay results was observed. In addition, the effects of a phenyl group and boron cluster, which is new adenosine modifiers, on the adenosine ligand binding were compared.
['Vincenzi|Marian|M|0000-0003-1692-5908', 'Bednarska|Katarzyna|K|0000-0001-6675-0670', 'Leśnikowski|Zbigniew J|ZJ|0000-0003-3158-5796']
D000241:Adenosine D001665:Binding Sites D001880:Boranes D003198:Computer Simulation D006367:HeLa Cells D006801:Humans D008024:Ligands D062105:Molecular Docking Simulation D015394:Molecular Structure D011485:Protein Binding D011487:Protein Conformation D011869:Radioligand Assay D043684:Receptor, Adenosine A3 D043683:Receptors, Adenosine A2 D013329:Structure-Activity Relationship
adenosine adenosine receptors boron cluster AR ligands in silico screening