The A2A adenosine receptor (A2AAR) is one of the four subtypes activated by nucleoside adenosine, and the molecules able to selectively counteract its action are attractive tools for neurodegenerative disorders. In order to find novel A2AAR ligands, two series of compounds based on purine and triazolotriazine scaffolds were synthesized and tested at ARs. Compound 13 was also tested in an in vitro model of neuroinflammation. Some compounds were found to possess high affinity for A2AAR, and it was observed that compound 13 exerted anti-inflammatory properties in microglial cells. Molecular modeling studies results were in good agreement with the binding affinity data and underlined that triazolotriazine and purine scaffolds are interchangeable only when 5- and 2-positions of the triazolotriazine moiety (corresponding to the purine 2- and 8-positions) are substituted.
A 2A Adenosine Receptor Antagonists: Are Triazolotriazine and Purine Scaffolds Interchangeable? / Spinaci A, Lambertucci C, Buccioni M, Dal Ben D, Graiff C, Barbalace MC, Hrelia S, Angeloni C, Tayebati SK, Ubaldi M, Masi A, Klotz KN, Volpini R, Marucci G.. - In: MOLECULES. - ISSN 1420-3049. - ELETTRONICO. - 27:8(2022), pp. 2386.1-2386.22. [10.3390/molecules27082386]
A 2A Adenosine Receptor Antagonists: Are Triazolotriazine and Purine Scaffolds Interchangeable?
Barbalace MCMethodology
;Hrelia SWriting – Review & Editing
;Angeloni CWriting – Review & Editing
;
2022
Abstract
The A2A adenosine receptor (A2AAR) is one of the four subtypes activated by nucleoside adenosine, and the molecules able to selectively counteract its action are attractive tools for neurodegenerative disorders. In order to find novel A2AAR ligands, two series of compounds based on purine and triazolotriazine scaffolds were synthesized and tested at ARs. Compound 13 was also tested in an in vitro model of neuroinflammation. Some compounds were found to possess high affinity for A2AAR, and it was observed that compound 13 exerted anti-inflammatory properties in microglial cells. Molecular modeling studies results were in good agreement with the binding affinity data and underlined that triazolotriazine and purine scaffolds are interchangeable only when 5- and 2-positions of the triazolotriazine moiety (corresponding to the purine 2- and 8-positions) are substituted.| File | Dimensione | Formato | |
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