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Molecules 2018, 23(8), 1846; https://doi.org/10.3390/molecules23081846

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

1
Laboratory of Molecular Virology and Biological Chemistry, Institute of Medical Biology of the Polish Academy of Sciences, 106 Lodowa St., 93-232 Lodz, Poland
2
Laboratory of Experimental Immunology, Institute of Medical Biology, Polish Academy of Sciences, 106 Lodowa St., 93-232 Lodz, Poland
These authors contributed equally to this work.
Current address: Institute of Biostructures and Bioimaging (IBB), National Research Council (CNR), Via Mezzocannone 16, I-80134 Naples, Italy.
*
Author to whom correspondence should be addressed.
Academic Editors: Rebecca Wade and Outi Salo-Ahen
Received: 26 June 2018 / Revised: 16 July 2018 / Accepted: 18 July 2018 / Published: 25 July 2018
(This article belongs to the Special Issue Molecular Modeling in Drug Design)
Full-Text   |   PDF [3979 KB, uploaded 25 July 2018]   |  

Abstract

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. View Full-Text
Keywords: in silico screening; adenosine; boron cluster; adenosine receptors; AR ligands in silico screening; adenosine; boron cluster; adenosine receptors; AR ligands
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Vincenzi, M.; Bednarska, K.; Leśnikowski, Z.J. 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. Molecules 2018, 23, 1846.

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