Discovery of novel A3 adenosine receptor ligands based on chromone scaffold

Development of novel adenosine receptor ligands based on the 3-amidocoumarin scaffold

“…Compound 4 also establishes hydrogen bond interactions with the residue Asn250. Previous results performed with other scaffolds at the hA 3 AR [32,33] showed similar ligand poses as reported in this study. Although a similar binding mode was found for compound 4 in the hA 2A AR, the compound is placed slightly shifted toward the upper region causing a disruption in the interaction energy with the residue Asn250 ( Fig.…”

“…1a). This hypothetical binding mode agrees with previous results showing the importance of the residue Asn 6.55 (BallesterosÀWeinstein numbering) in ligand recognition [23,32,33]. However, compound 2 does not establish strong interaction in the hA 3 with the corresponding residue Asn250.…”

Insight into the Interactions between Novel Coumarin Derivatives and Human A3 Adenosine Receptors

“…The extracted poses were optimized using Prime MM-GBSA. [32] As reported previously, [10] the calculations showed great variability in the extracted binding modes, particularly in the homology models. The proposed binding modes were selected by considering the number of similar poses extracted from the calculations and geometrical resemblance to co-crystallized compounds in the hA 2A AR (Figure 2 a).…”

“…[28,34] Previous results also showed the importance of residue Asn 6.55 in ligand recognition. [10,35] Compound 10, with good affinity for hA 1 , hA 2A , and hA 3 ARs, displayed the described binding mode in all the three ARs (Figure 2 b-d). However, the pose retrieved for the hA 2A AR was slightly shifted and did not yield hydrogen bonds with the residue Asn 253.…”

“…In the search for non-classical AR ligands, novel structures have recently been proposed, namely with quinolinone ( Figure 1, structures I and II) [8] and chromone (structure III) scaffolds. [9][10][11] These compounds are particularly interesting, as they are analogues of another well-known family of heterocyclic compounds, the coumarins.…”