C3 amino-substituted chalcone derivative with selective adenosine A receptor affinity in the micromolar range.

ABSTRACT

To identify novel adenosine receptor (AR) ligands based on the chalcone scaffold, herein the synthesis, characterization and in vitro and in silico evaluation of 33 chalcones (- and -) and structurally related compounds (-) are reported. These compounds were characterized by radioligand binding and GTP shift assays to determine the degree and type of binding affinity, respectively, against rat () A and A ARs. The chalcone derivatives , , and possessed selective A affinity below 10 µM, and thus, are the most active compounds of the present series; compound was the most potent selective A AR antagonist ( () = 1.6 µM). The structure-affinity relationships (SAR) revealed that the NH-group at position C3 of ring A of the chalcone scaffold played a key role in affinity, and also, the Br-atom at position C3' on benzylidene ring B. Upon in vitro and in silico evaluation, the novel C3 amino-substituted chalcone derivative -that contains an α,ß-unsaturated carbonyl system and easily allows structural modification-may possibly be a synthon in future drug discovery.

GRAPHIC ABSTRACT

C3 amino-substituted chalcone derivative () with C3' Br substitution on benzylidene ring B possesses selective adenosine A receptor affinity in micromolar range.