Allosteric Inhibition of ET-1 Binding to ETA Receptors by

Musa Ahmed, Susanna Nencetti, Maria R. Mazzoni, Francesca Porchia, Federica Antonelli, Annalina Lapucci


Endothelin-1 (ET-1), a potent vasoconstrictor peptide, exerts its physiological effects by binding and activating specific G protein-coupled receptors, named ETA and ETB. An unique property of ET-1 is its ability to bind almost irreversibly to its receptors. Aspirin and Salicylic Acid (SA) are allosteric inhibitors of ET-1 binding to ETA receptors (1). Dihalogenated derivatives of SA have been identified as 50 times more potent allosteric inhibitors than aspirin (2). In this study, we replaced carboxylic acid group of salicylate by oxime moiety with disubstitution at 3,5 position and OH group at position 2 was replaced by NH2 or H, synthesized compounds were tested as inhibitors of [125 I]ET-1 binding to ETA receptors in rat embryonic cardiomyocyte (H9c2 cell) membranes. Most oximes synthesized in this study show modest activity as inhibitors of [125 I] ET-1binding to ETA receptors in relation to salicylic acid derivatives reported in literature (2)


Allosteric, ETA, Aldoxime

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