Chemoselective regulation of TREK2 channel: Activation by sulfonate chalcones and inhibition by sulfonamide chalcones

Abstract

Although it has not been extensively studied, a significant volume of literature suggests that TREK2 will probably turn out to be an important channel in charge of tuning neuronal transmitter and hormone levels. Thus, pharmacological tools which can manipulate this channel, such as selective agonists are essential both in drug design and to further our understanding of this system. Our investigations have shown that sulfonate ('O') chalcone and sulfonamide ('N') chalcones regulate the TREK2 channel in remarkably different ways: sulfonamide chalcone 5 behaved as an inhibitor with an IC(50) of 62 mu M, whereas the sulfonate analogue 11 activated TREK2 with EC(50) value of 167 mu M. (C) 2010 Elsevier Ltd. All rights reserved.