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

• Published in: Bioorganic & medicinal chemistry letters Vol. 20; no. 14; pp. 4237 - 4239
• Main Authors: Kim, Eun-Jin, Ryu, Hyung Won, Curtis-Long, Marcus J., Han, Jaehee, Kim, Jun Young, Cho, Jung Keun, Kang, Dawon, Park, Ki Hun
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 15.07.2010
• Subjects: Cell Line; Chalcones - chemistry; Chalcones - pharmacology; Humans; Potassium Channels, Tandem Pore Domain - drug effects; Sulfonamide chalcone; Sulfonamides - chemistry; Sulfonate chalcone; Sulfonic Acids - chemistry; TREK2 channel; Sulfonamide chalcone; TREK2 channel; Sulfonate chalcone
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2010.05.033

The sulfonamide chalcones behaved as inhibitor, whereas the sulfonate analogues activated TREK2. 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 IC50 of 62μM, whereas the sulfonate analogue 11 activated TREK2 with EC50 value of 167μM.