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

Eun-Jin Kim; Hyung Won Ryu; Marcus J Curtis-Long; Jaehee Han; Jun Young Kim; Jung Keun Cho; Dawon Kang; Ki Hun Park

doi:10.1016/j.bmcl.2010.05.033

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

Bioorg Med Chem Lett. 2010 Jul 15;20(14):4237-9. doi: 10.1016/j.bmcl.2010.05.033. Epub 2010 May 19.

Authors

Eun-Jin Kim¹, Hyung Won Ryu, Marcus J Curtis-Long, Jaehee Han, Jun Young Kim, Jung Keun Cho, Dawon Kang, Ki Hun Park

Affiliation

¹ Medical Research Center for Neural Dysfunction, Department of Physiology, School of Medicine, Gyeongsang National University, Jinju 660-751, Republic of Korea.

PMID: 20570515
DOI: 10.1016/j.bmcl.2010.05.033

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 microM, whereas the sulfonate analogue 11 activated TREK2 with EC(50) value of 167 microM.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line
Chalcones / chemistry
Chalcones / pharmacology*
Humans
Potassium Channels, Tandem Pore Domain / drug effects*
Sulfonamides / chemistry*
Sulfonic Acids / chemistry*

Substances

Chalcones
KCNK10 protein, human
Potassium Channels, Tandem Pore Domain
Sulfonamides
Sulfonic Acids